bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antigen‐binding moiety in the driver's seat of CARs
Authors: Hanssens Heleen , Meeus Fien , De Veirman Kim , Breckpot Karine , Devoogdt Nick 
Published: May 2021

AbstractImmuno‐oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)‐T cell therapy have achieved spectacular results. Over the years, CAR‐T cell development has followed a steady evolutionary path, focusing on increasing T cell potency and sustainability, which has given rise to different CAR generations. However, there was less focus on the mode of interaction between the CAR‐T cell and the cancer cell; more specifically on the targeting moiety used in the CAR and its specific properties. Recently, the importance of optimizing this domain has been recognized and the possibilities have been exploited. Over the last 10 years—in addition to the classical scFv‐based CARs—single domain CARs, natural receptor‐ligand CARs, universal CARs and CARs targeting more than one antigen have emerged. In addition, the specific parameters of the targeting domain and their influence on T cell activation are being examined. In this review, we concisely present the history of CAR‐T cell therapy, and then expand on various developments in the CAR ectodomain. We discuss different formats, each with their own advantages and disadvantages, as well as the developments in affinity tuning, avidity effects, epitope location, and influence of the extracellular spacer.
Cone beam CT based validation of neural network generated synthetic CTs for radiotherapy in the head region
Authors: Irmak Sinan , Zimmermann Lukas , Georg Dietmar , Kuess Peter , Lechner Wolfgang 
Published: May 2021

PurposeIn the past years, many different neural network‐based conversion techniques for synthesizing computed tomographys (sCTs) from MR images have been published. While the model's performance can be checked during the training against the test set, test datasets can never represent the whole population. Conversion errors can still occur for special cases, for example, for unusual anatomical situations. Therefore, the performance of sCT conversion needs to be verified on a patient specific level, especially in the absence of a planning CT (pCT). In this study, the capability of cone‐beam CTs (CBCTs) for the validation of sCTs generated by a neural network was investigated.Methods41 patients with tumors in the head region were selected. 20 of them were used for model training and 10 for validation. Different implementations of CycleGAN (with/without identity and feature loss) were used to generate sCTs. The pixel (MAE, RMSE, PSNR) and geometric error (DICE, Sensitivity, Specificity) values were reported to identify the best model. VMAT plans were created for the remaining 11 patients on the pCTs. These plans were re‐calculated on sCTs and CBCTs. An automatic density overriding method () and a population‐based dose calculation method () were employed for CBCT‐based dose calculation. The dose distributions were analysed using 3D global gamma analysis, applying a threshold of 10% with respect to the prescribed dose. Differences in DVH metrics for the PTV and the organs‐at‐risk were compared among the dose distributions based on pCTs, sCTs, and CBCTs.ResultsThe best model was the CycleGAN without identity and feature matching loss. Including the identity loss led to a metric decrease of 10% for DICE and a metric increase of 20–60 HU for MAE. Using the 2%/2 mm gamma criterion and pCT as reference, the mean gamma pass rates were 99.0 0.4% for sCTs. Mean gamma pass rate values comparing pCT and CBCT were 99.0 0.8% and 99.1 0.8% for the and , respectively. The mean gamma pass rates comparing sCT and CBCT resulted in 98.4 1.6% and 99.2 0.6% for and , respectively. The differences between the gamma‐pass‐rates of the sCT and two CBCT‐based methods were not significant. The majority of deviations of the investigated DVH metrices between sCTs and CBCTs were within 2%.ConclusionThe dosimetric results demonstrate good agreement between sCT, CBCT, and pCT based calculations. A properly applied CBCT conversion method can serve as a tool for quality assurance procedures in an MR only radiotherapy workflow for head patients. Dosimetric deviations of DVH metrics between sCT and CBCTs of larger than 2% should be followed up. A systematic shift of approximately 1% should be taken into account when using the approach in an MR only workflow.
Multiecho complex total field inversion method (mcTFI) for improved signal modeling in quantitative susceptibility mapping
Authors: Wen Yan , Spincemaille Pascal , Nguyen Thanh , Cho Junghun , Kovanlikaya Ilhami , Anderson Julie , Wu Gaohong , Yang Baolian , Fung Maggie , Li Ke , Kelley Douglas , Benhamo Nissim , Wang Yi 
Published: May 2021

PurposeTypical quantitative susceptibility mapping (QSM) reconstruction steps consist of first estimating the magnetization field from the gradient‐echo images, and then reconstructing the susceptibility map from the estimated field. The errors from the field‐estimation steps may propagate into the final QSM map, and the noise in the estimated field map may no longer be zero‐mean Gaussian noise, thus, causing streaking artifacts in the resulting QSM. A multiecho complex total field inversion (mcTFI) method was developed to compute the susceptibility map directly from the multiecho gradient echo images using an improved signal model that retains the Gaussian noise property in the complex domain. It showed improvements in QSM reconstruction over the conventional field‐to‐source inversion.MethodsThe proposed mcTFI method was compared with the nonlinear total field inversion (nTFI) method in a numerical brain with hemorrhage and calcification, the numerical brains provided by the QSM Challenge 2.0, 18 brains with intracerebral hemorrhage scanned at 3T, and 6 healthy brains scanned at 7T.ResultsCompared with nTFI, the proposed mcTFI showed more accurate QSM reconstruction around the lesions in the numerical simulations. The mcTFI reconstructed QSM also showed the best image quality with the least artifacts in the brains with intracerebral hemorrhage scanned at 3T and healthy brains scanned at 7T.ConclusionThe proposed multiecho complex total field inversion improved QSM reconstruction over traditional field‐to‐source inversion through better signal modeling.
Eating and Exercise‐Related Correlates of Weight Stigma: A Multinational Investigation
Authors: Lessard Leah M. , Puhl Rebecca M. , Himmelstein Mary S. , Pearl Rebecca L. , Foster Gary D. 
Published: May 2021

ObjectiveWeight stigma is prevalent across the world. However, little is known about whether and how the harmful health consequences of weight stigma may vary across countries. The current study examined the association between experiences of weight stigma and multiple eating and exercise‐related indicators among a large, multinational sample of adults.MethodsAdults enrolled in an international weight management program residing in Australia, Canada, France, Germany, the United Kingdom, and the United States completed identical Web‐based surveys in the dominant language for their country. Participants (N = 13,996) reported on their personal experiences of weight stigma and health, including eating behaviors, attitudes toward exercise, and perceived stress.ResultsMore than half of all participants in each country reported experiencing weight stigma. Participants who had experienced weight stigma reported engaging in more eating to cope, gym avoidance, and self‐monitoring behaviors, as well as higher levels of stress and reduced eating self‐efficacy. These associations were documented over and above sociodemographic characteristics and BMI and did not vary across countries.ConclusionsStudy findings document uniform health‐related correlates of weight stigma within a multinational context and underscore the need for global initiatives to curtail weight stigma in order to support population health.
Epicardial fat inflammation response to COVID‐19 therapies
Authors: Iacobellis Gianluca , Malavazos Alexis Elias , Basilico Sara , Tresoldi Silvia , Rinaldo Rocco Francesco , Dubini Carola , Capitanio Gloria , Serpi Francesca , Schiaffino Simone , Oliva Omar Alessandro , Cariati Maurizio , Morricone Lelio , Centanni Stefano , Sardanelli Francesco , Carruba Michele , Corsi Romanelli Massimiliano Marco , Secchi Francesco 
Published: May 2021

AbstractObjectiveAdipose tissue plays a role in the novel coronavirus disease 2019 (COVID‐19). Epicardial adipose tissue (EAT), a unique visceral fat, presents with a high degree of inflammation in severe COVID‐19. Whether and how adipose tissue may respond to the COVID‐19 therapies is unknown.MethodsThe difference in computed tomography‐measured EAT and subcutaneous (SAT) attenuation, defined as mean attenuation expressed in Hounsfield units (HU), was retrospectively analyzed in 72 patients (mean [SD] age was 59.6 [12.4] years, 50 patients [69%] were men) at the hospital admission for COVID‐19 and 99 days (interquartile range = 71‐129) after discharge.ResultsAt the admission, EAT‐HU was significantly correlated with blood glucose levels, interleukin 6, troponin T levels, and waist circumference. EAT‐HU decreased from −87.21 (16.18) to −100.0 (11) (p < 0.001), whereas SAT‐HU did not change (−110.21 [12.1] to −111.11 [27.82]; p = 0.78) after therapy. Changes in EAT‐HU (expressed as ∆) significantly correlated with dexamethasone therapy (r = −0.46, p = 0.006) and when dexamethasone was combined with tocilizumab (r = −0.24, p = 0.04).ConclusionsDexamethasone therapy was associated with significant reduction of EAT inflammation in COVID‐19 patients, whereas SAT showed no changes. Anti‐inflammatory therapies targeting visceral fat may be helpful in COVID‐19.
Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial
Authors: Hurvitz Sara A. , Saura Cristina , Oliveira Mafalda , Trudeau Maureen E. , Moy Beverly , Delaloge Suzette , Gradishar William , Kim Sung-Bae , Haley Barbara , Ryvo Larisa , Dai Ming-Shen , Milovanov Vladimir , Alarcón Jesús , Kalmadi Sujith , Cronemberger Eduardo , Souza Cristiano , Landeiro Luciana , Bose Ron , Bebchuk Judith , Kabbinavar Fairooz , Bryce Richard , Keyvanjah Kiana , Brufsky Adam M. 
Published: May 2021

AbstractBackgroundNeratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C).Materials and MethodsNALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered.ResultsOf 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41–1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59–1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed.ConclusionThese analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC.Implications for PracticeIn a subgroup of patients with central nervous system (CNS) metastases from HER2-positive breast cancer after two or more previous HER2-directed regimens, the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2-positive brain metastases following antibody-based HER2-directed therapies.
COVID-19 in Patients with Cancer: A Retrospective Study of 212 Cases from a FrenchSARS-CoV-2 Cluster During the First Wave of theCOVID-19 Pandemic
Authors: Martin Sophie , Kaeuffer Charlotte , Leyendecker Pierre , Tuzin Nicolas , Tazi Youssef , Schaff-Wendling Frédérique , Kleinheny Tiffanie , Husson-Wetzel Stéphanie , Pamart Guillaume , Limacher Jean-Marc , Clerc Olivier , Dicop Elise , Kurtz Jean-Emmanuel , Barthélémy Philippe , Gantzer Justine 
Published: May 2021

AbstractWe describe a large series of patients with solid tumors in an early COVID-19 cluster in the eastern part of France. From February to May 2020, this multicenter retrospective study enrolled 212 patients with cancer under treatment or on follow-up for any type of malignant solid tumor and positive for SARS-CoV-2. The mortality rate was 30%. Patients with gastrointestinal cancers were identified as a subset of more vulnerable patients; immunotherapy and radiotherapy within 3 months from COVID-19 diagnosis were risk factors for death. The reported data support the essential need to be proactive and weigh the risks of morbidity from COVID-19 against the magnitude of benefits of intended cancer therapies during this pandemic.Implications for PracticeThis article supports the essential need to be proactive (treatment delay or modification) in oncology in the setting of pandemic. This study identified patients with gastrointestinal cancers as a more vulnerable subset of patients with cancer and found that immunotherapy and radiotherapy within 3 months from COVID-19 diagnosis to be risk factors for death. The reported data indicate the necessity of weighing the risks of morbidity from COVID-19 against the magnitude of benefits of intended cancer therapies in any future wave of COVID-19.
Chitosan/Agarose‐g‐poly (methacrylate) pH responsive polymeric blend: A dais for controlled delivery of Capecitabine
Authors: Rehman Umaira , Sarfraz Rai Muhammad , Mahmood Asif , Zafar Nadiah , Ashraf Muhammad Umar 
Published: May 2021

AbstractThis project was designed to develop pH responsive smart chitosan/agarose‐g‐poly (methacrylate) hydrogels using free radical polymerization for targeted delivery of Capecitabine (a prodrug of 5‐fluorouracil) for the treatment of colorectal cancer. Developed hydrogels were evaluated for drug loading efficiency, thermal stability, compatibility of components, morphology, swelling behavior, release kinetics and acute oral toxicity studies in rabbits. Moreover, pharmacokinetic parameters were also measured in healthy rabbits. Structural entanglement was confirmed via FTIR providing evidence of hydrogel formation. Loading of Capecitabine was in range from 60.35% to 62.57%. Hydrogels showed pH‐responsive behavior by providing maximum swelling of 93.84% at pH 7.4 identical to colon. Release of Capecitabine from hydrogels was in controlled pattern over a period of 36 h. Toxicity studies revealed no signs of ocular, dermal and oral toxicity providing safety evidence of hydrogels. In addition, pharmacokinetic evaluations of Capecitabine loaded hydrogels showed significant increase in plasma half‐life of 17 h and AUC of 57.65 μg.h/ml in comparison to pure Capecitabine solution. Therefore, these results strongly suggest that newly formed hydrogels are biocompatible, capable of providing sustained release at specific pH and can be employed as a cargo for colorectal delivery.
A safety and feasibility trial of 131I‐MIBG in newly diagnosed high‐risk neuroblastoma: A Children's Oncology Group study
Authors: Weiss Brian D. , Yanik Gregory , Naranjo Arlene , Zhang Fan F. , Fitzgerald Wendy , Shulkin Barry L. , Parisi Marguerite T. , Russell Heidi , Grupp Stephan , Pater Luke , Mattei Peter , Mosse Yael , Lai Hollie A. , Jarzembowski Jason A. , Shimada Hiroyuki , Villablanca Judith G. , Giller Roger , Bagatell Rochelle , Park Julie R. , Matthay Katherine K. 
Published: May 2021

AbstractIntroduction131I‐meta‐iodobenzylguanidine (131I‐MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131I−MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high‐risk neuroblastoma.MethodsPatients with MIBG‐avid high‐risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re‐designed to include an 131I‐MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10‐week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131I‐MIBG feasibility; those who completed 131I‐MIBG therapy were evaluable for assessment of 131I‐MIBG + Bu/Mel feasibility.ResultsFifty‐nine of 68 patients (86.8%) who completed induction chemotherapy received 131I‐MIBG. Thirty‐seven of 45 patients (82.2%) evaluable for 131I‐MIBG + Bu/Mel received this combination. Among those who received 131I‐MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131I‐MIBG and 131I‐MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%‐99.4%) and 81.0% (95% CI: 60.0%‐92.3%).ConclusionThis pilot trial demonstrated feasibility and tolerability of administering 131I‐MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high‐risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131I‐MIBG during induction therapy.
Density functional estimation of hydride and proton affinities of substituted allenes and heteroallenes
Authors: Saeidian Hamid , Malekian Hadi , Vessally Esmail 
Published: May 2021

AbstractThe hydride affinity (HA) of 20 allene and heteroallene derivatives containing unsaturated rings such as cyclopentadiene (CP) ring has been computationally investigated using the B3LYP/6‐311++G(3df, 2p) method. The interaction of hydride ion (H−) with the central sp1 carbon of the designed molecules containing electron‐withdrawing groups on the CP ring has been highly desirable, and their HA values were obtained in the range of 369–788 kJ/mol. The aromaticity of CP anion has the key role in the HA increasing and its stability. The harmonic oscillator model of aromaticity (HOMA) and nucleus‐independent chemical shifts (NICS) values associated with the CP ring were calculated and compared before and after the interaction with H−. The calculated data indicated a sharp increase in HOMA and NICS indices for the anions. In the following, the protonation of three designated allenes containing a cyclopropene or cycloheptatriene and a CP ring was also investigated using the density functional theory calculations. Electrostatic potential maps for some key structures were also used for charge distribution analysis.
Line Bundle Hidden Sectors for Strongly Coupled Heterotic Standard Models
Authors: Ashmore Anthony , Dumitru Sebastian , Ovrut Burt A. 
Published: May 2021

AbstractWe review the compactification to five‐dimensional heterotic M‐theory on a Schoen Calabi–Yau threefold and the specific vector bundle leading to the “heterotic standard model” in the observable sector. Within strongly coupled heterotic M‐theory, a formalism for consistent hidden‐sector bundles associated with a single line bundle is presented, and a specific line bundle is introduced as a concrete example. Anomaly cancellation and the associated bulk space five‐branes are discussed in this context, as is slope‐stability of both the observable and hidden sector bundles. The further compactification to a four‐dimensional effective theory on a linearized BPS double domain wall is then presented to order . Specifically, the generic constraints required for anomaly cancellation and the restrictions imposed by positive squared gauge couplings to order are presented in detail. Three additional constraints are imposed, one guaranteeing that the orbifold length is sufficiently larger than the average Calabi–Yau radius, and two enforcing that the hidden sector be compatible with both the unification mass scale and unified gauge coupling of the group in the observable sector. Finally, the expression for the Fayet–Iliopoulos term associated with an anomalous U(1) symmetry is presented and its role in supersymmetry in the low‐energy effective theory is discussed. It is shown that supersymmetry can be preserved by cancelling the tree‐level and genus‐one contributions against each another. As a check on our results, we calculate several quantities to order and show that they remain physically acceptable, and even improve, when computed to higher order.
Framed and non‐framed robotics in neurosurgery: A 10‐year single‐center experience
Authors: Naros Georgios , Machetanz Kathrin , Grimm Florian , Roser Florian , Gharabaghi Alireza , Tatagiba Marcos 
Published: May 2021

AbstractBackgroundSafety, efficacy and efficiency of neurosurgical robots are defined by their design (i.e., framed and non‐framed) and procedural workflow (PW) (from image to surgery). The present study describes the quality indicators of three different robots in brain and spine surgery.MethodsThis single‐centre study enrolled 252 patients over a 10‐year period. Safety (complication rate) and efficacy (diagnostic yield, pedicle screw placement) were determined. Predictors of workflow efficiency (e.g., skin‐to‐skin) were evaluated and compared to conventional techniques (neuronavigation, stereotaxy).ResultsAll robots showed excellent reliability (97.5%–100%) with low complication rates (4.5%–5.3%) and high efficacy (94.7%–97.7%). Robotics demonstrated a better time‐efficiency than neuronavigation. However, there was no shortening of surgery time compared to conventional stereotaxy. Time‐efficiency differed significantly between framed and non‐framed workflows.ConclusionWhile all neurosurgical robots were reliable, safe and efficacious, there were significant differences in time‐efficiency. PWs should be improved to increase the acceptance of robotics in neurosurgery.
Electrochemical and Spectrometric Study of Reactivity of Orthophthalaldehyde with Hydroxylamine: Mechanistic Considerations
Authors: Donkeng‐Dazie Joël , Urban Jiří , Ludvík Jiří 
Published: May 2021

AbstractOrthophthalaldehyde (o‐phthalaldehyde, OPA) is a broadly used biologically, synthetically and analytically significant compound. Its properties are connected with its reactivity towards nucleophiles, namely amines in aqueous – mostly basic – solutions. Since the reaction mechanisms of OPA and amine condensation are complicated, strongly depending on the amine structure and, therefore, a systematic study of this kind of reaction is presented. Structure activity relationships based on amine structure and their application in reaction optimization are reported. The present paper deals with reaction of OPA with hydroxylamine which is monitored electrochemically and spectrometrically. The mechanism was formulated on the basis of detailed analysis of electrochemical behavior, of the interception of the intermediate (phthalaldehyde mono‐oxime) and of the isolation and identification of the main product (1H‐2,3‐benzoxazin‐1‐ol).