bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of breast density and key demographics of radiographers on mammography reporting performance – a pilot study
Authors: Alakhras Maram , Al‐Mousa Dana S. , Alqadi Alaa K. , Sabaneh Haneen A. , Karasneh Ruba M. , Spuur Kelly M.
Published: May 2021

Introduction

A high demand has been placed on radiologists to perform screen reads due to higher number of women undergoing mammography. This study aims to examine radiographer performance in reporting low compared with high‐mammographic density (MD) images; and to assess the influence of key demographics of Jordanian radiographers on their performance.

Methods

Thirty mammograms with varied MD were reported by 12 radiographers using the Breast Imaging‐Reporting and Data System (BI‐RADS). Radiographer performance was measured using sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and area under the receiver operating characteristic curve (ROC AUC). Performance measures were compared between cases with low‐ and high‐MD and between subgroups of radiographers according to key demographics.

Results

All performance measures were significantly higher in low‐ compared to high‐MD cases (P value < 0.0). The mean sensitivity, specificity, PPV, NPV and ROC AUC were 0.58, 0.68, 0.67, 0.63 and 0.69 respectively. PPV was significantly different for readers who had different years of experience in mammography, hours and cases per week P value = 0.023, 0.01, 0.017 respectively. ROC AUC was significantly different for radiographers with different number of hours and cases performed per week (P value = 0.001 and 0.004 respectively).

Conclusions

The results of this pilot study are encouraging however a more extensive study is required to determine if Jordanian radiographers are capable of successfully taking part in breast screen reading. The lack of skills and knowledge required for correct and consistent reporting of high‐MD images highlights the need for any formal training in mammographic interpretation to focus on the dense breast.
Present‐day and future climate over central and South America according to CMIP5/CMIP6 models
Authors: Ortega Geusep , Arias Paola A. , Villegas Juan Camilo , Marquet Pablo A. , Nobre Paulo
Published: May 2021

In tropical regions, particularly in Central and South America (CSA), the projections of climate seasonality under climate change are still uncertain. This is especially true for ecologically‐relevant variables such as precipitation and temperature. However, assessments of model‐based projections of seasonal climate for this region are scarce. We analyzed the simulation of seasonal precipitation and air surface temperature in CSA and six sub‐regions within from 49 models included in the Coupled Intercomparison Project Phase 5 (CMIP5) and 33 models from CMIP6. In general, continental patterns and seasonality of both variables are moderately well resembled, while most models show systematic biases over the oceans, producing unrealistic spatial patterns. To quantify how well CMIP5/CMIP6 models simulate these variables, we used Taylor diagrams with respect to TRMM for precipitation and ERA5 for temperature. Precipitation shows the largest spread among models. Conversely, temperature shows a better simulation. CMIP5/CMIP6 models exhibit a better performance simulating both variables during December–January–February and March–April–May than during the other seasons. This is partly due to the reduced model biases in representing the Intertropical Convergence Zone during these two seasons. In general, biases are reduced in the CMIP6 models with respect to CMIP5. Regarding regional evaluations, precipitation patterns for Mesoamerica, Cerrado and Chaco regions are better reproduced compared to TRMM, while the annual cycles for the Andes hotspot, Central Chile and Guianas are not well simulated, mainly during their wet seasons. However, these biases are reduced in CMIP6 models. In regard to precipitation projections, models only agree over most of the regions with decreasing precipitation. Conversely, temperature exhibits a general consensus on persistent warming even during the historical period, with an average increase of 6°C by the end of the century, according to the CMIP6 models.
Investigating the urban heat and cool island effects during extreme heat events in high‐density cities: A case study of Hong Kong from 2000 to 2018
Authors: Ren Chao , Wang Kai , Shi Yuan , Kwok Yu Ting , Morakinyo Tobi Eniolu , Lee Tsz‐cheung , Li Yuguo
Published: May 2021

Urban heat island (UHI) and cool island (UCI) effects are well‐known and prevalent in cities worldwide. An increasing trend of extreme heat events has been observed over the last few decades and is expected to continue in the foreseeable future. In this study, warm periods (May to September) of 2000–2018 were examined to acquire a comprehensive understanding of the UHI and UCI characteristics for the case study of Hong Kong, China. Twenty‐two weather stations in Hong Kong were classified into four categories, namely urban, urban oasis, suburban, and rural, with reference to the local climate zone (LCZ) scheme, to analyze UHI and UCI phenomena during extreme heat and non‐extreme heat situations. One representative type of extreme heat events was considered in this study: three consecutive hot nights with two very hot days in between (2D3N). Results show that both the UHI and UCI effects are exacerbated during extreme heat events. Using the concept of the UHI degree hours (UHIdh) and UCI degree hours (UCIdh), their spatial patterns in Hong Kong during extreme heat and non‐extreme heat situations were mapped based on multiple linear regression models. It is found that the predictor variable – windward/leeward index is a significant influential factor of both UHIdh and UCIdh during extreme heat events. The resulting UHIdh and UCIdh maps not only enhance our understanding on the spatial pattern and characteristics of the UHI and UCI during extreme heat events, but could also serve as a useful reference in climate change adaptation, heat‐health risk detection, cooling‐energy estimation and policy making.
Flavor impartment of mushroom on egg whites and sensory properties of egg whites with mushroom topping using quantitative descriptive analysis
Authors: Muniz Adriana , Du Xiaofen , Shanks Marcus
Published: May 2021

BACKGROUND

Mushroom possesses desirable aroma, taste, texture, health‐promoting and disease‐preventing dietary components, making it an ideal ingredient, especially for animal‐based food substitution. Nevertheless, no study has replaced egg whites partially with mushrooms and investigated their sensory quality. This study aimed to investigate flavor impartment of mushroom on egg whites and the sensory quality of roasting and steaming egg whites replaced by white and crimini mushrooms at 0%, 10%, 20% and 30%, respectively, using a panel trained with aroma chemical references for 31 sensory attributes with 0–10 line scales.

RESULTS

Roasted and steamed egg whites possessed major sensory attributes of sulfury and egg‐like aroma and flavor (intensities > 3). After mushroom topping was added, the dominant sensory attributes shifted to mushroom‐based flavor characteristics, including mushroom‐like, earthy, dark meat, roasted, hay, soybean, potato, woody, umami, bitter, astringent and firmness texture. Mushroom variety showed significant (P ≤ 0.05) impacts on egg white sensory quality, with crimini introducing more intense flavor. The higher the mushroom proportion with egg whites, the more intense was the flavor associated with mushroom. Mushroom could enhance egg‐like flavor in multiple dimensions, including aroma, taste and texture, according to partial least square regression.

CONCLUSION

White and crimini mushrooms enriched roasted and steamed egg white sensory quality with introduction of characteristic sensory attributes from mushrooms. Mushroom variety and proportion with egg whites displayed significant impacts on egg white sensory properties. The study contributed to understanding the impact of mushrooms on egg white sensory profile and served as a guide in incorporating mushroom in product development. © 2021 Society of Chemical Industry.
Inadequate prediction of postoperative complications in breast cancer surgery: An evaluation of the ACS Surgical Risk Calculator
Authors: Gonzalez‐Woge Miguel A. , Martin‐Tellez Karla S. , Gonzalez‐Woge Ricardo , Teran‐De‐la‐Sancha Kevin , de la Rosa‐Abaroa Marco , Garcia‐Cardenas Francisco J. , Munguia‐Garza Paulina , Cervantes‐Delgado Paloma , Garcia‐Tapia Prandiz Luis R. , Mangwani‐Mordani Simran , Esparza‐Arias Nereida , Bargallo‐Rocha Juan E.
Published: May 2021

Background

The American College of Surgeon (ACS) Surgical Risk Calculator is an online tool that helps surgeons estimate the risk of postoperative complications for numerous surgical procedures across several surgical specialties.

Methods

We evaluated the predictive performance of the calculator in 385 cancer patients undergoing breast surgery. Calculator‐predicted complication rates were compared with observed complication rates; calculator performance was evaluated using calibration and discrimination analyses.

Results

The mean calculator‐predicted rates for any complication (4.1%) and serious complication (3.2%) were significantly lower than the observed rates (11.2% and 5.2%, respectively). The area under the curve was 0.617 for any complication and 0.682 for serious complications. p Values for the Hosmer–Lemeshow test were significant (<.05) for both outcomes. Brier scores were 0.102 for any complication and 0.048 for serious complication.

Conclusions

The ACS risk calculator is not an ideal tool for predicting individual risk of complications following breast surgery in a Mexican cohort. The most valuable use of the calculator may reside in its role as an aid for patient‐led surgery planning. The possibility of introducing breast surgery‐specific data could improve the performance of the calculator. Furthermore, a disease‐specific calculator could provide more accurate predictions and include complications more frequently found in breast cancer surgery.
Soil physicochemical property and arbuscular mycorrhizal fungi resilience to degradation and deforestation of a dry evergreen Afromontane forest in central Ethiopia
Authors: Asmelash Fisseha , Bekele Tamrat , Belay Zerihun , Kebede Fassil
Published: May 2021

We investigated the soil physicochemical property and arbuscular mycorrhizal fungi (AMF) resilience to the degradation and deforestation of a dry evergreen Afromontane forest, the Chilimo Forest (CF). Topsoil (1‐10 cm) physicochemical property, AMF spore abundance (SA), and AMF infectivity were determined across four land uses, viz., natural forest (NF), shrubland (ShL), cropland (CrL), and grazing land (GrL). According to the permutational multivariate analysis of variance and nonmetric multidimensional scaling results, soil physicochemical property was resilient to degradation (NF‐ShL conversion) but not deforestation (NF‐CrL or NF‐GrL conversions) of CF. The one‐way ANOVA results indicated that most soil physicochemical variables were significantly (p < 0.05) affected by land‐use change. Soil organic matter and total nitrogen, in particular, reduced significantly (p < 0.05) by up to 48% and 57% due to NF‐CrL and NF‐GrL conversions, respectively. Whereas SA was found to be resilient to both CF degradation and deforestation, AMF infectivity was resilient only to NF‐CrL conversion. Generally, our results did not show a similar pattern in soil physicochemical property, SA, and AMF infectivity resilience to degradation and deforestation. However, in the case of NF‐GrL conversion, both soil physicochemical property and AMF infectivity exhibited significantly (p < 0.05) low resilience. Based on our results, we conclude that soil physicochemical property and AMF are important factors to consider in CF restoration planning. When planting sites are either the croplands or grazing lands, soil amendment could be recommended. AMF inoculation, however, could be recommended when the planting sites are grazing lands. These recommendations may also apply widely to dry evergreen Afromontane forests restoration but additional studies are required.
Observation of “Frozen‐Phase” Propagation of THz Pulses in a Dispersive Optical System
Authors: Lu Yao , Wu Qiang , Xiong Hao , Huang Song , Pan Chongpei , Zhang Bin , Qi Jiwei , Chen Zhigang , Xu Jingjun
Published: May 2021

Dispersion occurs naturally in many wave systems. So far, a variety of techniques have been proposed and demonstrated to compensate the second‐order (group‐velocity) dispersion, such as dispersion management and nonlinear soliton formation, yet it is commonly believed that the first‐order dispersion (FOD) is less amenable and cannot be eliminated. In this work, it is shown that a phase‐invariant propagation of THz pulses, namely the “frozen‐phase” propagation, can be realized by a complete cancellation of the FOD, achieved by implementing a synchronized THz moving source with a locked initial phase. The dynamic generation and propagation process of the THz pulses is examined directly by a time‐resolved imaging system. To the best of authors' knowledge, this represents the first demonstration of the “frozen‐phase” propagation of a light pulse in dispersive optical systems.
Fluoride‐Triggered Self‐Degradation of Poly(2,4‐disubstitued 4‐hydroxybutyric acid) Derivatives
Authors: Kan Xiao‐Wei , Zhang Li‐Jing , Li Zhao‐Yue , Du Fu‐Sheng , Li Zi‐Chen
Published: May 2021

Self‐immolative polymers are a special kind of degradable polymers that depolymerize into small molecules through a cascade of reactions upon stimuli‐triggered cleavage of the polymer chain ends. This work reports the design and synthesis of a fluoride‐triggered self‐immolative polyester. A 2,4‐disubstitued 4‐hydroxy butyrate is first confirmed to quickly cyclize in solution to form a γ−butyrolactone derivative. Then, the Passerini three component reaction (P‐3CR) of an AB dimer (A: aldehyde, B: carboxylic acid) with tert‐butyl isocyanide or oligo(ethylene glycol) isocyanide affords two poly(2,4‐disubstitued 4‐hydroxybutyrate) derivatives (P2 and P3). Two silyl ether end‐capped polymers (P4 and P5) are abtained from P2 and P3, and their degradation in solution is examined by NMR spectrum and size exclusion chromatography. Polymers P4 and P5 are stable in the absence of tetrabutylammonium fluoride (TBAF), while in the presence of TBAF, the molar masses of P4 and P5 gradually decrease with time together with the increase of the amount of formed 2,4‐disubstitued γ‐butyrolactone. The depolymerization mechanism is proposed. The first step is the fast removal of the silyl ether by fluoride. Then, the released hydroxyl group initiates the quick head‐to‐tail depolymerization of the polyester via intramolecular cyclization.
Kinetically Interlocking Multiple‐Units Polymerization of DNA Double Crossover and Its Application in Hydrogel Formation
Authors: Shi Jiezhong , Zhu Chenyou , Li Qian , Li Yujie , Chen Liangxiao , Yang Bo , Xu Jiang‐Fei , Dong Yuanchen , Mao Chengde , Liu Dongsheng
Published: May 2021

A novel kinetically interlocking multiple‐units (KIMU) supramolecular polymerization system with DNA double crossover backbone is designed. The rigidity of DX endows the polymer with high molecular weight and stability. The observed concentration of the formed polymers is insensitive and stable under ultralow monomer concentration owing to the KIMU interactions, in which multiple noncovalent interactions are connected by the phosphodiester bonds. Furthermore, a pH‐responsive DNA supramolecular hydrogel is constructed by introducing a halfi‐motif domain into the DNA monomer. The rigidity of DNA polymer endows the hydrogel with high mechanical strength and low gelation concentration. This study enriches the KIMU strategy and offers a simple but effective way to fabricate long and stable supramolecular polymers by balancing the reversibility and stability. It also shows great potentials to construct next generation of smart materials, such as DNA nanostructures, DNA motors, and DNA hydrogels.
The development and application of matrix assisted laser desorption electrospray ionization: The teenage years
Authors: Caleb Bagley Michael , Garrard Kenneth P. , Muddiman David C.
Published: May 2021

In the past 15 years, ambient ionization techniques have witnessed a significant incursion into the field of mass spectrometry imaging, demonstrating their ability to provide complementary information to matrix‐assisted laser desorption ionization. Matrix‐assisted laser desorption electrospray ionization is one such technique that has evolved since its first demonstrations with ultraviolet lasers coupled to Fourier transform‐ion cyclotron resonance mass spectrometers to extensive use with infrared lasers coupled to orbitrap‐based mass spectrometers. Concurrently, there have been transformative developments of this imaging platform due to the high level of control the principal group has retained over the laser technology, data acquisition software (RastirX), instrument communication, and image processing software (MSiReader). This review will discuss the developments of MALDESI since its first laboratory demonstration in 2005 to the most recent advances in 2021.
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

Immuno‐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

Purpose

In 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.

Methods

41 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.

Results

The 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%.

Conclusion

The 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

Purpose

Typical 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.

Methods

The 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.

Results

Compared 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.

Conclusion

The 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

Objective

Weight 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.

Methods

Adults 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.

Results

More 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.

Conclusions

Study 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

Objective

Adipose 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.

Methods

The 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.

Results

At 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).

Conclusions

Dexamethasone 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

Background

Neratinib 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 Methods

NALA 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.

Results

Of 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.

Conclusion

These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC.

Implications for Practice

In 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

We 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 Practice

This 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

This 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

Introduction

131I‐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.

Methods

Patients 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.

Results

Fifty‐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%).

Conclusion

This 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

The 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

We 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.
E‐cigarettes: informing the conversation with patients
Authors: Barton Anna Kate
Published: May 2021

The stance of different authorities on the relative harms of e‐cigarettes and their role in smoking cessation is currently variable. This article examines the evidence for the benefits and risks associated with e‐cigarettes in order to help healthcare professionals discuss these issues with patients.
Pleiotropic nature of curcumin in targeting multiple apoptotic‐mediated factors and related strategies to treat gastric cancer: A review
Authors: Shetty Nandini P. , Prabhakaran Manoj , Srivastava Akhileshwar Kumar
Published: May 2021

Gastric cancer (GC) is one of the major reasons for cancer‐associated death and exhibits the second‐highest mortality rate worldwide. Several advanced approaches have been designed to treat GC; however, these strategies possess many innate complications. In view of this, the upcoming research relying on natural products could result in designing potential anticancer agents with fewer side effects. Curcumin, isolated from the rhizomes of Curcuma longa L. has several medicinal properties like antiinflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic. Such pleiotropic nature of curcumin impedes the invasion and proliferation of GC by targeting several oncogenic factors like p23, human epidermal factor receptor2 including Helicobacter pylori. The side effect of chemotherapy, that is, chemotherapeutic resistance and radiotherapy could be reduced combination therapy of curcumin. Moreover, the photodynamic therapy of curcumin destroys the cancer cells without affecting normal cells. However, further more potential studies are required to establish the potent efficacy of curcumin in the treatment of GC. The current review details the anticancer activities of curcumin and related strategies which could be employed to treat GC with additional focus on its inhibitory properties against viability, proliferation, and migration of GC cells through cell cycle arrest and stimulation by apoptosis‐mediated factors.
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

Background

Safety, 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.

Methods

This 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).

Results

All 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.

Conclusion

While 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.
A discussion of approaches for fitting asymmetric signals in X‐ray photoelectron spectroscopy (XPS), noting the importance of Voigt‐like peak shapes
Authors: Major George H. , Avval Tahereh G. , Patel Dhananjay I. , Shah Dhruv , Roychowdhury Tuhin , Barlow Anders J. , Pigram Paul J. , Greiner Mark , Fernandez Vincent , Herrera‐Gomez Alberto , Linford Matthew R.
Published: May 2021

Although the fundamental, theoretical peak shape in X‐ray photoelectron spectroscopy (XPS) is Lorentzian, some Gaussian character is observed in most XPS signals. Additional complexity in the form of asymmetry is also found in many XPS signals, which requires more advanced peak shapes than the traditional, symmetric Voigt and Gaussian‐Lorentzian sum and product (pseudo‐Voigt) functions. Here, we discuss the merits and disadvantages of four approaches that have been used to introduce asymmetry into XPS peak shapes: addition of a decaying exponential tail to a symmetric peak shape, the Doniach‐Sunjic peak shape, the double‐Lorentzian, DL, function, and the LX peak shapes, which include the asymmetric Lorentzian (LA), finite Lorentzian (LF), and square Lorentzian (LS) functions. The Doniach‐Sunjic peak shape is the only asymmetric, synthetic peak that has a theoretical basis. However, it has an infinite integral, which makes it problematic in quantitative work. The mathematical bases for the LX and DL peak shapes are discussed, and practical examples of their use in peak fitting are presented. The case is made for the Voigt function being the most appropriate function for XPS peak fitting, in general, which suggests that a modified Voigt function may be the most reasonable for fitting asymmetric XPS signals. The LX and DL functions include convolution with a Guassian, which, with the exception of the LS function, makes them Voigt‐like functions. The sources of asymmetry and its complexity are discussed. It is emphasized that not every asymmetric spectrum should be fit with an asymmetric peak shape.
Electrochemical and Spectrometric Study of Reactivity of Orthophthalaldehyde with Hydroxylamine: Mechanistic Considerations
Authors: Donkeng‐Dazie Joël , Urban Jiří , Ludvík Jiří
Published: May 2021

Orthophthalaldehyde (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).
Facile Preparation of a Porous Nanosheet PX‐Doped Fe Bi‐Functional Catalyst with Excellent OER and HER Electrocatalytic Activity
Authors: Ju Yan , Feng Suyang , Wang Xuanbing , Li Min , Wang Li , Xu Ruidong , Wang Junli
Published: May 2021

The principal factor restricting large‐scale hydrogen production via water electrolysis is the development of inexpensive and efficient catalysts that attain high current densities to produces hydrogen at low potentials. In this study, a series of iron‐based phosphide catalysts (denoted as: PX‐doped Fe/NF) were prepared via one‐step electrodeposition from a eutectic solvent to examine their oxygen evolution reaction (OER) or hydrogen evolution reaction (HER) performance. Notably, P30‐doped Fe/NF forms a porous interconnected nanosheet structure, providing a large active surface areas, abundant active sites and low charge transfer resistance. P30‐doped Fe/NF attained the lowest OER (284.15 mV) and HER (158.17 mV) overpotentials at 10 mA cm−2 in 1.0 M KOH of all the tested catalysts. When used in overall water splitting, the catalyst displayed outstanding adaptability to a range of potentials and current densities. This study provides a facile route for the synthesis of bifunctional transition‐metal phosphide catalysts for the electrolysis of water.
Trifunctional Electrocatalytic Activities of Nitrogen‐Doped Graphitic Carbon Nanofibers Synthesized by Chemical Vapor Deposition
Authors: Todankar Bhagyashri , Desai Pradeep , Ranade Ajinkya K. , Narayanan Tharangattu N. , Tanemura Masaki , Kalita Golap
Published: May 2021

High performance multifunctional electrocatalysts are attracting significant importance for application in energy storage, energy conversion and various other electrochemical reactions. In this prospect, we report on the effective trifunctional electrocatalytic properties of nitrogen (N) doped graphitic carbon nanofibers (CNFs). The CNFs were synthesized on a nichrome (NiCr) foil by chemical vapor deposition (CVD) process. Incorporation of Ni and Cr was observed in the N doped CNFs sample from microscopic and spectroscopic analysis. The metal nanoparticles can be significant in boosting the trifunctional electrocatalytic behavior. The effective oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) activities were obtained for the CNFs sample with relatively good overpotential values. The electron transfer number per O2 molecule calculated from Koutecky‐Levich (K‐L) plot was found to be 2e− for the ORR reaction. The OER activity of the CNFs is comparable to commercially available iridium oxide (IrO2), signifying the effectiveness of the developed catalyst. Our study revealed that N doped CNFs with incorporation of metal particles synthesized on a binary metal substrate can be significant as ORR, OER, HER trifunctional electrocatalyst.