bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetic information in Swiss drug labels – a systematic analysis
Authors: Jeiziner C. , Suter K. , Wernli U. , Barbarino J. M. , Gong L. , Whirl-Carrillo M. , Klein T. E. , Szucs T. D. , Hersberger K. E. , Meyer zu Schwabedissen H. E. 
Published: October 2020

AbstractImplementation of pharmacogenetics (PGx) and individualization of drug therapy is supposed to obviate adverse drug reactions or therapy failure. Health care professionals (HCPs) use drug labels (DLs) as reliable information about drugs. We analyzed the Swiss DLs to give an overview on the currently available PGx instructions. We screened 4306 DLs applying natural language processing focusing on drug metabolism (pharmacokinetics) and we assigned PGx levels following the classification system of PharmGKB. From 5979 hits, 2564 were classified as PGx-relevant affecting 167 substances. 55% (n = 93) were classified as “actionable PGx”. Frequently, PGx information appeared in the pharmacokinetics section and in DLs of the anatomic group “nervous system”. Unstandardized wording, appearance of PGx information in different sections and unclear instructions challenge HCPs to identify and interpret PGx information and translate it into practice. HCPs need harmonization and standardization of PGx information in DLs to personalize drug therapies and tailor pharmaceutical care.
Polycyclic polyprenylated acylphloroglucinols fromGarcinia xanthochymusfruits exhibit antitumor effects through inhibition of the STAT3 signaling pathway
Authors: Xu Jing , Jin Shan , Gan Fei , Xiong Hui , Mei Zhinan , Chen Yu , Yang Guangzhong 
Published: October 2020

PPAPs from Garcinia xanthochymus fruits exhibit antitumor effects through STAT3 pathway.
In vitro evolution of antibody affinity via insertional scanning mutagenesis of an entire antibody variable region
Authors: Skamaki Kalliopi , Emond Stephane , Chodorge Matthieu , Andrews John , Rees D. Gareth , Cannon Daniel , Popovic Bojana , Buchanan Andrew , Minter Ralph R. , Hollfelder Florian 
Published: October 2020

Significance
Insertion/deletion (InDel) mutations play key roles in genome and protein evolution. Despite their prominence in evolutionary history, the potential of InDels for changing function in protein engineering by directed evolution remains unexplored. Instead point mutagenesis is widely used. Here we create antibody libraries containing InDels and demonstrate that affinity maturation can be achieved in this way, establishing an alternative to the point mutation strategies employed in all previous in vitro selections. These InDels mirror the observation of considerable length variation in loops of natural antibodies originating from the same germline genes and be combined with point mutations, making both natural sources of functional innovation available for artificial evolution in the test tube.
Prediction and prevention of disproportionally dominant agents in complex networks
Authors: Lera Sandro Claudio , Pentland Alex , Sornette Didier 
Published: October 2020

Significance
Proportional growth is the driver behind the dynamics of a large class of complex networks. However, if left uncontrolled a few agents may become so dominant that their actions compromise the entire system. We present a framework that monitors the system’s distance from such imbalanced states. When the system approaches an imbalanced state, we show how to structure an optimal, cost-efficient intervention policy. Focusing only on either helping the least-fit agents or punishing the most dominant ones in isolation turns out to be inefficient. Instead, our results call for a more wholistic approach, with important implications for the structure of regulatory matters such as antitrust policies, taxation law, subsidies, or development aid.
Desmosome architecture derived from molecular dynamics simulations and cryo-electron tomography
Authors: Sikora Mateusz , Ermel Utz H. , Seybold Anna , Kunz Michael , Calloni Giulia , Reitz Julian , Vabulas R. Martin , Hummer Gerhard , Frangakis Achilleas S. 
Published: October 2020

Significance
The desmosome is a major cell–cell junction connecting cells in tissues under high mechanical load. Currently, while structures of the constituent cadherins are known, the desmosome architecture has remained elusive. The primary reason is the high plasticity of the cadherins. As many other cellular structures, their high flexibility cannot be easily addressed by conventional structural techniques that rely on averaging many identical structures. For this, we combine high-end cryo-electron tomography with large-scale molecular dynamics simulations to produce a molecular model of the desmosome that integrates new with decades-old observations, accounts for the remarkable biophysical properties, and maps the intermolecular interactions.
Voluntary leadership and the emergence of institutions for self-governance
Authors: Andersson Krister P. , Chang Kimberlee , Molina-Garzón Adriana 
Published: October 2020

Significance
We offer evidence on the role of local, voluntary leaders during the initial stages of the self-governance process. Our findings, which show that unselfish leadership actions can foster self-governance under conditions that are unfavorable for collective action, provide hope for efforts to address creeping environmental degradation problems, such as climate change and biodiversity loss. The significance of these findings goes beyond environmental policy and speaks to the potential role of voluntary leaders in the formulation of policy responses to new, emerging threats to human well-being for which there are no established governance institutions.
Mapping glycan-mediated galectin-3 interactions by live cell proximity labeling
Authors: Joeh Eugene , O’Leary Timothy , Li Weichao , Hawkins Richard , Hung Jonathan R. , Parker Christopher G. , Huang Mia L. 
Published: October 2020

Significance
Because of the weak interactions between individual glycan-binding proteins (GBPs), such as galectin-3, and glycans, strategies that enable the direct interrogation of these interactions in living cells remain limited. Thus, the glycan and glycoprotein ligands that are physiologically relevant for galectin-3 binding are insufficiently described. Here we used a proximity labeling approach that catalytically tags interactors for galectin-3 and identified its pertinent glycan and glycoprotein counter-receptors in live cells. This study demonstrates that proximity labeling is a powerful tool for mapping GBP complexes in living cells, and when coupled with chemical inhibitors, it can discriminate between protein–protein and protein–glycan interactions.
Diatom modulation of select bacteria through use of two unique secondary metabolites
Authors: Shibl Ahmed A. , Isaac Ashley , Ochsenkühn Michael A. , Cárdenas Anny , Fei Cong , Behringer Gregory , Arnoux Marc , Drou Nizar , Santos Miraflor P. , Gunsalus Kristin C. , Voolstra Christian R. , Amin Shady A. 
Published: October 2020

Significance
Phytoplankton are major primary producers in the marine environment that excrete a wide range of metabolites. These exudates support the growth of surrounding bacteria that in turn provide phytoplankton cells with resources and growth cofactors to proliferate. Unlike multicellular eukaryotes with dedicated structures housing microbiomes, mechanisms enabling unicellular eukaryotic phytoplankton hosts to modulate potential symbionts and opportunists within a natural microbial community are unknown. Exposure of a host phytoplankton cell to its natural microbial community triggers major transcriptional and metabolic reprogramming to release unique secondary metabolites that selectively enable growth and attachment of symbiotic taxa while simultaneously suppressing the colonization of nonsymbiont bacteria. These results suggest strong and highly selective microbiome-modulating strategies shared across the unicellular and multicellular eukaryotic lineages.
Application of portal dosimetry and Dolphin in clinical machine and patient-specific quality assurance
Authors: Cai M , Archibald-Heeren B , Wang Y 
Published: October 2020

Abstract
This paper introduces Varian portal dosimetry and IBA dolphin detector. Clinical machine QA examples were presented including DLG measurement and monthly beam constancy check. For patient-specific QA, both detectors generated similar passing rates to film and were able to identify an erroneous delivery with 3mm MLC offset.
Test of innovative silicon detectors for the monitoring of a therapeutic proton beam
Authors: Sacchi R , Ahmadi Ganjeh Z , Arcidiacono R , Attili A , Cartiglia N , Donetti M , Fausti F , Ferrero M , Giordanengo S , Hammad Ali O , Mandurrino M , Manganaro L , Mazza G , Monaco V , Sola V , Staiano A , Vignati A , Cirio R 
Published: October 2020

Abstract
Beam monitoring in particle therapy is a critical task that, because of the high flux and the time structure of the beam, can be challenging for the instrumentation. Recent developments in thin silicon detectors with moderate internal gain, optimized for timing applications (Ultra Fast Silicon Detectors, UFSD), offer a favourable technological option to conventional ionization chambers. Thanks to their fast collection time and good signal-to-noise ratio, properly segmented sensors allow discriminating and counting single protons up to the high fluxes of a therapeutic beam, while the excellent time resolution can be exploited for measuring the proton beam energy using time-of-flight techniques. We report here the results of the first tests performed with UFSD detector pads on a therapeutic beam. It is found that the signal of protons can be easily discriminated from the noise, and that the very good time resolution is confirmed. However, a careful design is necessary to limit large pile-up inefficiencies and early performance degradation due to radiation damage.
Evaluation of RBE-weighted doses for various radiotherapy beams based on a microdosimetric function implemented in PHITS
Authors: Takada Kenta , Sato Tatsuhiko , Kumada Hiroaki , Sakurai Hideyuki , Sakae Takeji 
Published: October 2020

Abstract
University of Tsukuba is developing a new TPS for boron neutron capture therapy (BNCT) equipped with Monte Carlo dose-calculation engine based on Particle and Heavy Ion Transport code System PHITS. It is currently in the process of extending its adaptation to other radiotherapy beams. For this extension, not only physical doses but also their relative biological effectiveness (RBE) must be evaluated for various radiotherapy in the same framework. Frequent and dose probability densities of lineal energy, y, are the key quantities in the RBE estimation, and they must be precisely evaluated for various locations in a patient. In this study, the probability densities of y for a site diameter of 0.564 µm were calculated for X-ray, proton, carbon-ion, and BNCT beams with appropriate geometry settings using the microdosimetric function implemented in PHITS, and they were converted to the corresponding RBE-weighted doses using the microdosimetric kinetic model. The accuracy of the calculated data were well verified by several experimental data, indicating the adequacy of the use of PHITS and microdosimetric kinetic model in the dose-calculation engine for TPS applicable to various radiotherapy.
Carbon Ion Radiotherapy for Prostate Cancer: Current Status in Japan
Authors: Tsuji H 
Published: October 2020

Abstract
Clinical trials on carbon ion radiotherapy (C-ion RT) for the prostate cancer were conducted at the NIRS for over 20 years. The results so far have been quite satisfactory in both toxicity and tumour control. In addition, advancement of hypofractionation has been successfully progressed and 12-fraction C-ion RT could be established. To obtain the outcomes of multi-institutional clinical trials, a study group, J-CROS, was organized and conducts several multicenter clinical trials including the prospective study for the high-risk prostate cancer. It is expected that the outcomes of these clinical studies would result in widening the coverage of National Health Insurance for the C-ion RT. Technical progression has been also achieved at the NIRS. The scanning irradiation became available in 2011 and all the prostate cancers are treated with scanning at present. A new clinical trial of 4-fraction C-ion RT for the locally recurrent prostate cancer has been started using dose painting of scanning beam. The rotating gantry of heavy ion beam was also installed. These technical progressions enable to perform the intensity modulated ion therapy with carbon beam alone or with various ion species.
Microdosimetry at the 62 MeV Proton Beam of CATANA: preliminary comparison of three detectors
Authors: Bianchi A , Colautti P , Conte V , Selva A , Agosteo S , Bortot D , Mazzucconi D , Pola A , Reniers B , Parisi A , Struelens L , Vanhavere F , Tran Linh , Rosenfeld A B , Cirrone G A P , Petringa G 
Published: October 2020

Abstract
A microdosimetric characterization of the 62 MeV proton beam line of CATANA has been performed all along the Spread Out Bragg Peak with three different detectors. Two silicon detectors and a Tissue Equivalent Proportional Counter measured at approximately the same depths of the SOBP. The TEPC is a new miniaturized gas counter developed at the Legnaro National Laboratories of INFN, modified to work without gas flow. The first silicon detector has been developed at the Politecnico of Milano and it is a monolithic telescope composed by a matrix of 2 µm thick cylindrical diodes with a diameter 9 µm. that compose the ΔE layer. The E and ΔE layers are fabricated on a single substrate of silicon. The third detector is the MicroPlus probe developed at the CMRP - University of Wollongong, it is an array of 3D sensitive volumes each with dimension 30x30 µm and 10 µm thick fabricated on SOI. Measurements performed with the three detectors are presented and discussed.
The use of a new 2D array of diodes for small-field dosimetry of a CyberKnife equipped with a novel multi-leaf collimator
Authors: Biasi G , Munoz L , Hug B , Ebert M A , Petasecca M , Bucci J , Jackson M , Rosenfeld A B 
Published: October 2020

Abstract
In the present work, we reported on the use of a new 2D array of diodes, the Duo, for dosimetry of small beams produced with a CyberKnife system, and shaped with a novel multi-leaf collimator, the InCise 2.
Experimental measurements confirm decreased supralinearity in the thermoluminescence of beta/gamma irradiated LiF:Mg,Ti (TLD-100) following 3.6 eV and 5 eV optical excitation
Authors: Ginzburg D , Oster L , Eliyahu I , Reshes G , Biderman S , Horowitz Y S 
Published: October 2020

Abstract
Photon excitation at selected energies following beta/gamma irradiation is found to significantly reduce the supralinearity of the thermoluminescence dose response of composite peak 5 in LiF:Mg,Ti (TLD-100). Following a dose of 100 Gy, photon excitation at an energy of 5 eV and fluence of 1.3 × 1018 ph cm−2 reduces the normalized TL efficiency from 2.8 to 1.9 and at 400 Gy from 3.5 to 2.7. Excitation by photons of energy 3.65 eV (1019 ph cm−2) reduces the normalized efficiency of glow peak 5a (a low temperature satellite of peak 5) at 100 Gy from 2.9 to a value of 0.95 thereby resulting in a linear dose response. The high values of dose of 100 Gy and 400 Gy well beyond the normal dose range of clinical radiation therapy were chosen for demonstrative purposes in order to evaluate the likelihood of success of the proposed technique. Additional experiments are underway to determine the photon levels of fluence, which will result in a linear dose response for both glow peaks 5, and 5a in the range of doses 1-30 Gy of interest to radiotherapy and intraoperative electron therapy.
The black box problem of AI in oncology
Authors: Hagenbuchner Markus 
Published: October 2020

Abstract
The rapidly increasing amount and complexity of data in healthcare, the pace of published research, drug development, biomarker discovery, and clinical trial enrolment in oncology renders AI an approach of choice in the development of machine assisted methods for data analysis and machine assisted decision making.
Machine learning algorithms, and artificial neural networks in particular, drive recent successes of AI in oncology. Performances of AI driven methods continue to improve with respect to both speed and precision thus leading to a great potential for AI to improve clinical practice. But the acceptance and a lasting breakthrough of AI in clinical practice is hampered by the black box problem. The black box problem refers to limits in the interpretability of results and to limits in explanatory functionality. Addressing the black box problem has become a major focus of research [1]. This talk describes recent attempts to addressing the black box problem in AI, offers a discussion on the suitability of those attempts for applications to oncology, and provides some future directions.
Monte Carlo based corrections for the dosimetry of x-ray microbeams with diamond detectors
Authors: Hugtenburg Richard P. , Reynard Dimitri D. H. 
Published: October 2020

Abstract
X-ray microbeams are a potential, novel mode of radiation therapy and dosimetry methods are under development that require micrometric spatial precision. The microDiamond detector has the requisite resolution and is composed of diamond which is closely tissue-equivalent. The high density of diamond however perturbs of secondary electrons and Monte Carlo methods are needed to determine corrections to accurately measure clinical parameters. The PENELOPE Monte Carlo code has been used to calculate corrections for the output factor (OF) and peak-to-valley dose ratio (PVDR). A high-performance computing (HPC) system was found to be necessary and the calculation took 72 hours when performed on a cluster of 100 CPUs. The correction for the output factor was found to be 1.009±0.016 (2 s.d.). The correction factor for the peak-to-valley ratio was found to be 1.144±0.013 (2 s.d.) and was larger due to Compton scattering of the microbeam in the extracameral components of the detector, in particular the 300 micron bulk diamond crystal. It was found that considerable improvements in efficiency could be achieved without loss of precision by switching off electron transport for electrons that are generated far from the sensitive element of the detector.
Development of wide-bandgap semiconductor-based dosimeter for LET distribution measurement in carbon therapy filed
Authors: Kada W , Ohsaki K , Ohki Y , Yamazaki Y , Makino T , Ohshima T , Mattsumura A , Sakai M 
Published: October 2020

Abstract
This paper presents a proof of concept of silicon carbide (SiC), a type of wideband semiconductor, based dosimeter for linear energy transfer (LET) distribution measurement at clinical carbon beam therapy field. SiC Schottky barrier diode (SBD), which has been designed for ionization detector, was utilized for spectroscopy of pristine 290 MeV/u 12C heavy ion therapy beams at Gunma University Heavy Ion Medical Centre (GHMC) facility, Japan. Measurement of LET distribution was successfully demonstrated at different depth with developed SiC SBD dosimeter. Also SiC SBD was exposed with clinical carbon beam with high intensity condition. Through CCE and deep level defect evaluation, sufficient radiation tolerance was examined for SiC SBD for futuristic usage in clinical carbons. Those results suggested that preliminary evaluation of SiC SBD was successful as energy-dispersive dosimeter for heavy ion therapy field.
Training and validation of a commercial deep learning contouring platform
Authors: Koo J , Caudell J , Feygelman V , Moros E , Latifi K 
Published: October 2020

Abstract
We present our experience with training and validation of a commercially available deep learning algorithm for organs at risk(OAR) auto-contouring. Computed tomography(CTs) with OARs from a cohort of 213 head and neck(H&N) patients were used for training the deep learning model. A separate cohort of 85 CTs and structure sets was used for validation. All OARs (13) were contoured by a single physician. Metrics such as the DICE similarity coefficient (DSC), Jaccard similarity coefficient (JSC), and volumetric difference (VD) were used to analyze contouring variation. Mean DSC and JSC values ranged 0.48-0.89 and 0.32-0.8, respectively, depending on OAR. A DSC value ≥0.7 indicated low inter-observer variability. In our study, all but one of the contours were above this threshold. DSC for the middle pharyngeal constrictor had the lowest value of all the contours. This may be due to the small volume of this structure. Qualitative assessment of auto-segmented structure samples confirmed the reliability of DSC by demonstrating the compatibility between the expert’s evaluation and DSC values. Overall, we found that deep learning auto contouring is a useful tool to speed up the process of contouring in radiotherapy treatment planning.
FASTRACK II magnetic resonance imaging sub-study Diffusion and perfusion biomarkers for renal SABR response
Authors: Korte J C , Reynolds H , Lasocki A , Vanneste B G L , Miclea R , Backes W H , Sridharan S , Sidhom M , Rai R , Kron T , Hardcastle N , Siva S 
Published: October 2020

Abstract
Stereotactic ablative body radiotherapy (SABR) is demonstrating good local control for patients with inoperable primary renal cell carcinoma. In a previous pilot study we identified magnetic resonance imaging (MRI) early response biomarkers that correlate with later morphological changes in computed tomography (CT) images. These early functional changes in diffusion and perfusion following radiotherapy were observed on MRI and have the potential to identify non-responders who may benefit from adjuvant or salvage therapies. Here we detail the imaging protocol for an MRI sub-study of the Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney (FASTRACK II) trial. A preliminary patient case demonstrates the high quality of the imaging data, with discussion of the improvements made from the pilot protocol for improved motion management and correction. We aim to validate the previously identified early response MRI biomarkers with this rich prospective multi-centre dataset.
Multimodal Monte Carlo treatment system capable of microdosimetry with PHITS
Authors: Kumada H , Takada K , Sato T , Sakurai H , Sakae T 
Published: October 2020

Abstract
Boron neutron capture therapy (BNCT) is a radiation therapy that combines neutrons and boron drugs. An industry-academia-government collaboration team is currently developing the linac-based treatment device and several peripheral devices to establish this therapy. In the project, a demonstration device, “iBNCT001”, for a linac-based neutron source applicable to BNCT treatment is being developed. We are developing Tsukuba Plan, a multimodal Monte Carlo-based treatment planning system, in addition to the linac-based neutron source device. Tsukuba-Plan has adopted a Particle and Heavy Ion Transport code System (PHITS) as the Monte Carlo-based dose calculation engine. PHITS has a microdosimetric function that can compute a lineal energy distribution and determine relative biological effectiveness through combination with the stochastic microdosimetric kinetic model parameters. By utilising these functions, Tsukuba-Plan is expected to estimate the weighted doses administered to the tumour region and normal tissues in the irradiation field more accurately.