bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial
Authors: Chaft Jamie E. , Oezkan Filiz , Kris Mark G. , Bunn Paul A. , Wistuba Ignacio I. , Kwiatkowski David J. , Owen Dwight H. , Tang Yan , Johnson Bruce E. , Lee Jay M. , Lozanski Gerard , Pietrzak Maciej , Seweryn Michal , Byun Woo Yul , Schulze Katja , Nicholas Alan , Johnson Ann , Grindheim Jessica , Hilz Stephanie , Shames David S. , Rivard Chris , Toloza Eric , Haura Eric B. , McNamee Ciaran J. , Patterson G. Alexander , Waqar Saiama N. , Rusch Valerie W. , Carbone David P. ,   LCMC study investigators, Waqar Saiama N. , Shum Elaine , Nagasaka Misako , Koczywas Marianna , Garon Edward B. , Finley David J. , Camidge David R. , Carlisle Jennifer W. , Blasberg Justin D. 
Published: September 2022

AbstractIn an ongoing, open-label, single-arm phase II study (NCT02927301), 181 patients with untreated, resectable, stage IB–IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14–28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.
Patient-derived head and neck tumor slice cultures: a versatile tool to study oncolytic virus action
Authors: Runge Annette , Mayr Melissa , Schwaiger Theresa , Sprung Susanne , Chetta Paolo , Gottfried Timo , Dudas Jozsef , Greier Maria C. , Glatz Marlies C. , Haybaeck Johannes , Elbers Knut , Riechelmann Herbert , Erlmann Patrik , Petersson Monika 
Published: September 2022

AbstractHead and neck cancer etiology and architecture is quite diverse and complex, impeding the prediction whether a patient could respond to a particular cancer immunotherapy or combination treatment. A concomitantly arising caveat is obviously the translation from pre-clinical, cell based in vitro systems as well as syngeneic murine tumor models towards the heterogeneous architecture of the human tumor ecosystems. To bridge this gap, we have established and employed a patient-derived HNSCC (head and neck squamous cell carcinoma) slice culturing system to assess immunomodulatory effects as well as permissivity and oncolytic virus (OV) action. The heterogeneous contexture of the human tumor ecosystem including tumor cells, cancer-associated fibroblasts and immune cells was preserved in our HNSCC slice culturing approach. Importantly, the immune cell compartment remained to be functional and cytotoxic T-cells could be activated by immunostimulatory antibodies. In addition, we uncovered that a high proportion of the patient-derived HNSCC slice cultures were susceptible to the OV VSV-GP. More specifically, VSV-GP infects a broad spectrum of tumor-associated lineages including epithelial and stromal cells and can induce apoptosis. In sum, this human tumor ex vivo platform might complement pre-clinical studies to eventually propel cancer immune-related drug discovery and ease the translation to the clinics.
Heart rate and blood lactate responses during the volleyball match
Authors: Akarçeşme Cengiz , Cengizel Elif , Şenel Ömer , Yıldıran İbrahim , Akyildiz Zeki , Nobari Hadi 
Published: September 2022

AbstractThis study aimed to examine the heart rate and blood lactate responses of female volleyball players during the match according to the player positions. A total of 24 senior female volleyball players (middle blocker (n = 6), setter (n = 6), spiker (n = 6), and libero (n = 6)) were monitored for heart rate and blood lactate before, during and after a volleyball match. The mean heart rate and blood lactate level of volleyball players were determined 117.2 ± 13.9 bpm, 2.7 ± 1.2 mmol/L during the match. Heart rate was statistically different between all playing positions except middle blockers vs. spikers (p < 0.05). The blood lactate levels between the groups were not statistically different. The setters have the lowest heart rate and the libero players have the highest during the match. All subjects have a heart rate 50–60% and below 50% of their heart rate maximum during more than half of the match duration. These current results can be used by coaches to determine a specific training load based on the heart rate and blood lactate differences between playing positions.
Transmembrane helices mediate the formation of a stable ternary complex of b5R, cyt b5, and SCD1
Authors: Shen Jiemin , Wu Gang , Tsai Ah-Lim , Zhou Ming 
Published: September 2022

AbstractMammalian cytochrome b5 (cyt b5) and cytochrome b5 reductase (b5R) are electron carrier proteins for membrane-embedded oxidoreductases. Both b5R and cyt b5 have a cytosolic domain and a single transmembrane (TM) helix. The cytosolic domains of b5R and cyt b5 contain cofactors required for electron transfer, but it is not clear if the TM helix has function beyond being an anchor to the membrane. Here we show that b5R and cyt b5 form a stable binary complex, and so do cyt b5 and stearoyl-CoA desaturase-1 (SCD1). We also show that b5R, cyt b5 and SCD1 form a stable ternary complex. We demonstrate that the TM helices are required for the assembly of stable binary and ternary complexes where electron transfer rates are greatly enhanced. These results reveal a role of the TM helix in cyt b5 and b5R, and suggest that an electron transport chain composed of a stable ternary complex may be a general feature in membrane-embedded oxidoreductases that require cyt b5 and b5R.
Analysis of genome and methylation changes in Chinese indigenous chickens over time provides insight into species conservation
Authors: Zeng Tao , Yin Jianmei , Feng Peishi , Han Feiran , Tian Yong , Wang Yuntong , Gu Tiantian , Xu Yuhui , Liu Yali , Li Guohui , Qu Liang , Chen Li , Gu Lihong , Xu Wenwu , Xue Qian , Wei Qingyu , Cao Yongqing , Li Peifeng , Zhang Huiyong , Li Guoqin , Liu Lijun , Zhou Chenghao , Tao Zhengrong , Shen Junda , Han Wei , Lu Lizhi 
Published: September 2022

AbstractConservation of natural resources is a vital and challenging task. Numerous animal genetic resources have been effectively conserved worldwide. However, the effectiveness of conservation programmes and the variation information of species have rarely been evaluated. Here, we performed whole-genome and whole-genome bisulfite sequencing of 90 Chinese indigenous chickens, which belonged to the Tibetan, Wenchang and Bian chicken breeds, and have been conserved under different conservation programmes. We observed that low genetic diversity and high DNA methylation variation occurs during ex situ in vivo conservation, while higher genetic diversity and differentiation occurs during in situ conservation. Further analyses revealed that most DNA methylation signatures are unique within ex situ in vivo conservation. Moreover, a high proportion of differentially methylated regions is found in genomic selection regions, suggesting a link between the effects of genomic variation and DNA methylation. Altogether our findings provide valuable information about genetic and DNA methylation variations during different conservation programmes, and hold practical relevance for species conservation.
Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERRα deficiency
Authors: Dufour Catherine R. , Xia Hui , B’chir Wafa , Perry Marie-Claude , Kuzmanov Uros , Gainullina Anastasiia , Dejgaard Kurt , Scholtes Charlotte , Ouellet Carlo , Zuo Dongmei , Sanguin-Gendreau Virginie , Guluzian Christina , Smith Harvey W. , Muller William J. , Audet-Walsh Etienne , Sergushichev Alexey A. , Emili Andrew , Giguère Vincent 
Published: September 2022

AbstractFunctional oncogenic links between ErbB2 and ERRα in HER2+ breast cancer patients support a therapeutic benefit of co-targeted therapies. However, ErbB2 and ERRα also play key roles in heart physiology, and this approach could pose a potential liability to cardiovascular health. Herein, using integrated phosphoproteomic, transcriptomic and metabolic profiling, we uncovered molecular mechanisms associated with the adverse remodeling of cardiac functions in mice with combined attenuation of ErbB2 and ERRα activity. Genetic disruption of both effectors results in profound effects on cardiomyocyte architecture, inflammatory response and metabolism, the latter leading to a decrease in fatty acyl-carnitine species further increasing the reliance on glucose as a metabolic fuel, a hallmark of failing hearts. Furthermore, integrated omics signatures of ERRα loss-of-function and doxorubicin treatment exhibit common features of chemotherapeutic cardiotoxicity. These findings thus reveal potential cardiovascular risks in discrete combination therapies in the treatment of breast and other cancers.
Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients
Authors: Svanberg Rebecka , MacPherson Cameron , Zucco Adrian , Agius Rudi , Faitova Tereza , Andersen Michael Asger , da Cunha-Bang Caspar , Gjærde Lars Klingen , Møller Maria Elizabeth Engel , Brooks Patrick Terrence , Lindegaard Birgitte , Sejdic Adin , Harboe Zitta Barrella , Gang Anne Ortved , Hersby Ditte Stampe , Brieghel Christian , Nielsen Susanne Dam , Podlekareva Daria , Hald Annemette , Bay Jakob Thaning , Marquart Hanne , Lundgren Jens , Lebech Anne-Mette , Helleberg Marie , Niemann Carsten Utoft , Ostrowski Sisse Rye 
Published: September 2022

Abstract
Background
The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease.

Methods
We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients.

Results
Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1β, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts.

Conclusions
We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.
Transient surface charging of tri‐post insulator in SF6‐filled direct current gas‐insulated transmission lines: Effects of electric conductivity, gas pressure, and voltage amplitude
Authors: Li Xiaolong , Zhang Guangkuo , Cao Chen , Shi Yan , Lin Ying , Chang Wenzhi 
Published: September 2022

AbstractThe transient surface charging characteristics of a tri‐post insulator in a ± 500 kV direct current gas‐insulated transmission lines (DC‐GIL) filled with sulfur hexafluoride (SF)6 gas are investigated. An improved method is introduced to calculate the surface charge distribution with satisfactory efficiency and accuracy, which involves applying weak form partial differential equation (PDE), simplifying ion transport equation and geometric model. The influence of volume and surface conductivity, gas pressure, voltage amplitude on the transient surface charging is discussed with the method. The charge density shows non‐synchronously increasing pace in different regions. The transient surface charging shows non‐monotonic tendency in some regions. With increasing volume conductivity, the transient surface charging is accelerated obviously. With increasing surface conductivity, the charge density near the enclosure increases. With varying electric conductivity, the dominant conduction changes. Thus, the volume and surface conductivity should be concerned in the design of DC‐GIL tri‐post insulators. With increasing gas pressure, slight acceleration in surface charging is observed. The acceleration in charging with high voltage amplitude cannot be employed to improve the efficiency in measurement. The result indicates that the simulation of transient surface charging is beneficial in evaluating the insulating characteristics of tri‐post insulators with flexibility and reasonability.
A novel approach for securing data against adversary attacks in UAV embedded HetNet using identity based authentication scheme
Authors: Wani Aabid Rashid , Gupta Sachin Kumar , Khanam Zeba , Rashid Mamoon , Alshamrani Sultan S. , Baz Mohammed 
Published: September 2022

AbstractUnmanned Aerial Vehicle (UAV) integrated Heterogeneous Network (HetNet) is currently considered as one of the promising technologies. This technology helps in fulfilling high demands of bandwidth, volume, and range as per user needs. In this paper, the work is carried out by authors to assure high security for the users in such a network by incorporating an authentication‐based security known as Identity based Scheme (IBA). The IBA based implemented networks improve the confidentiality of data and the authenticity of the users. Privacy and reliability come through the entity's capacity to authenticate, sign and transact authenticated data without central directory interference. Therefore,the primary scope of this research project is to create an identity‐based authentication mechanism in HetNets that are assisted by UAVs and to secure communication against potential intruder threats. In this way, the security assurance is increased and dreadful intruder attacks are minimized. Moreover, in this research work, the implementing zones would be areas of defence for observation of a region to locate an enemy or as certain strategic features. The security rules are formulated in the coded language known as High Level Protocol Specification Language (HLPSL) and outcomes are verified through Automated Validation Internet Security Protocols and Applications (AVISPA).
Heart rate monitoring of physical fitness training load based on wavelet transform
Authors: Zhao Feng , Sharma Ashutosh , Samori Issah Abubakari 
Published: September 2022

AbstractThe detection of fluctuations is a crucial step in the process of isolating heart rate oscillation signals. This is necessary to circumvent the issue wherein a variety of auditory signals will invariably interfere with the collection of centre velocity signals during physical activity, which has a significant impact on the detection efficiency of automated testing. To obtain heart rate fluctuation signals that are more precise, the paper proposes a method of R‐wave identification that is based on heartbeat conversion while the athlete is exercising. The proposed model relies heavily on the technique of wave analysis to filter out the background noise of the heartbeat when the athlete exercises and isolates the R‐wave signal of the heartbeat from the background noise. The proposed algorithm is evaluated in terms of noise interference that removes approximately 90% of noise, the heart rate data which is obtained after the noise is normally distributed, the average detection rate of the R‐wave algorithm is 98.65%. It has been demonstrated that the detection accuracy of the proposed algorithm is sufficient to meet the requirements of generating heart rate oscillatory signals.
Improving the accuracy of estimators for the two-point correlation function
Authors: Kerscher Martin 
Published: September 2022

Aims.We show how to increase the accuracy of estimates of the two-point correlation function without sacrificing efficiency.Methods.We quantify the error of the pair-counts and of the Landy & Szalay estimator by comparing them with exact reference values. The standard method, using random point sets, is compared to geometrically motivated estimators and estimators using quasi-Monte Carlo integration.Results.In the standard method, the error scales proportionally to 1/√Nr, withNrbeing the number of random points. In our improved methods, the error scales almost proportionally to 1/Nq, whereNqis the number of points from a low-discrepancy sequence. We study the run times of the new estimator in comparison to those of the standard estimator, keeping the same level of accuracy. For the considered case, we always see a speedup ranging from 50% up to a factor of several thousand. We also discuss how to apply these improved estimators to incompletely sampled galaxy catalogues.
A bubble size distribution model for the Epoch of Reionization
Authors: Doussot Aristide , Semelin Benoît 
Published: September 2022

Aims. The bubble size distribution is a summary statistics that can be computed from the observed 21-cm signal from the Epoch of Reionization. As it depends only on the ionization field and is not limited to Gaussian information, it is an interesting probe that is complementary to the power spectrum of the full 21-cm signal. Devising a flexible and reliable theoretical model for the bubble size distribution paves the way for its use in astrophysical parameter inference.
Methods. The proposed model was built from the excursion set theory and a functional relation between the bubble volume and the collapsed mass in the bubble. Unlike previous models, it can accommodate any functional relation or distribution. The use of parameterized relations allows us to test the predictive power of the model by performing a minimization best-fit to the bubble size distribution obtained from a high-resolution, fully coupled radiative hydrodynamics simulation known as HIRRAH-21.
Results. Our model is able to provide a better fit to the numerical bubble size distribution at an ionization fraction of xH II ∼ 1% and 3%, as compared to other existing models. Moreover, we compare the relation between the bubble volume and the collapsed mass corresponding to the best-fit parameters, which is not an observable, to the numerical simulation data. A good match is obtained, confirming the possibility of inferring this relation from an observed bubble size distribution using our model. Finally, we present a simple algorithm that empirically implements the process of percolation. We show that it extends the usability of our bubble size distribution model up to xH II ∼ 30%.
Gaia–TESS synergy: improving the identification of transit candidates
Authors: Panahi Aviad , Mazeh Tsevi , Zucker Shay , Latham David W. , Collins Karen A. , Rimoldini Lorenzo , Evans Dafydd Wyn , Eyer Laurent 
Published: September 2022

Context. The TESS team periodically issues a new list of transiting exoplanet candidates based on the analysis of the accumulating light curves obtained by the satellite. The list includes the estimated epochs, periods, and durations of the potential transits. As the point spread function (PSF) of TESS is relatively wide, follow-up photometric observations at higher spatial resolution are required in order to exclude apparent transits that are actually blended background eclipsing binaries (BEBs).
Aims. The Gaia space mission, with its growing database of epoch photometry and high angular resolution, enables the production of distinct light curves for all sources included in the TESS PSF, up to the limiting magnitude of Gaia. This paper reports the results of an ongoing Gaia-TESS collaboration that uses the Gaia photometry to facilitate the identification of BEB candidates and even to confirm on-target candidates in some cases.
Methods. We inspected the Gaia photometry of the individual sources included in the TESS PSF, searching for periodic dimming events compatible with their ephemerides and uncertainties, as published by TESS. The performance of the search depends mainly on the number of Gaia measurements during transit and their precision.
Results. Since February 2021, the collaboration has been able to confirm 126 on-target candidates and exclude 124 as BEBs. Since June 2021, when our search methodology matured, we have been able to identify on the order of 5% as on-target candidates and another 5% as BEBs.
Conclusions. This synergistic approach is combining the complementary capabilities of two of the astronomical space missions of NASA and ESA. It serves to optimize the process of detecting new planets by making better use of the resources of the astronomical community.
CBP/p300 bromodomain: new promising epigenetic target
Authors: Xiang Qiuping , Zhou Yang , Zhang Yan , Xu Yong 
Published: September 2022

CREB (cAMP responsive element binding protein) binding protein (CBP) and adenovirus E1A-associated 300 kDa protein (p300) are histone acetyltransferases, which are necessary for multiple cellular processes. Thus, CBP/p300 are promising potential antitumor targets. To date, despite various small molecule inhibitors of CBP/p300 bromodomain (BRD) having been reported, no specific inhibitor was approved by U.S. Food and Drug Administration (FDA). In this review, we described the discovery, optimization, binding mode evaluation, selectivity and potency evaluation, and therapeutic opportunities of our CBP/p300 bromodomain inhibitors, aiming to inspire new inhibitor design and advance drug discovery research in this field. One video presents the development of CBP/p300 bromodomain inhibitors.
Endo-Praxis
Authors: Beilenhoff Ulrike 
Published: September 2022

Liebe Leserinnen und Leser,Der Herbst steht vor der Tür und die Corona-Krise bestimmt auch weiterhin
unseren Alltag, auch wenn Feste wieder möglich sind und die Maskenpflicht
nur noch in Gesundheitseinrichtungen und im öffentlichen Verkehr besteht.
Wegen der steigenden Infektionen leiden viele Endoskopieabteilungen an
Personalmangel und arbeiten auch weiterhin unter verschärften
Arbeitsbedingungen. Die Situation bleibt weiterhin fragil und alle schauen mit etwas
Skepsis in den Herbst und Winter.
Improvements in Efficiency and Selectivity for C–F Bond Halogen-Exchange Reactions by Using Boron Reagents
Authors: Ćorković Andrej , Dorian Andreas , Williams Florence J. 
Published: September 2022

AbstractThe use of boron Lewis acids as instigators of bond cleavage offers a number of synthetic possibilities. A unique feature of this class of reagents is the ability to functionalize otherwise inert C–F bonds. We summarize notable developments in C–F bond halogen exchange using Lewis acidic boron reagents and we conclude by featuring our group’s advances in activating CF3 groups by using boron trihalides.1	Introduction2	Boron-Mediated Halogen Exchange3	Mono-Selective C–F Activation4	Conclusions