bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetric evaluation of VMAT treatment plans for patients with stage IIB or III non-small cell lung carcinomas
Authors: Shaaer Amani , Osei Ernest , Darko Johnson , Gopaul Darin 
Published: May 2023

Abstract

Introduction:
Volumetric-modulated arc therapy (VMAT) has emerged as a promising radiation treatment technique. One of the challenges in VMAT planning for lung carcinoma is the lack of consistency among different institutions with respect to what is considered an acceptable treatment plan in terms of target coverage and doses to the organs at risk (OAR). Additionally, the accuracy of dose calculations in the presence of heterogeneous medium (i.e. air) is another challenge in lung VMAT planning. Our objective is to develop an institutional criteria for non-stereotactic body radiotherapy (non-SBRT) lung treatment plans by evaluating the dosimetric impact of plan normalisation and dose calculation algorithms, including the Anisotropic Analytical Algorithm (AAA), AcurosXB (AXB) and Monte Carlo (MC) simulation, on VMAT plans for non-small cell lung cancer (NSCLC).

Methods:
The CT dataset of 20 patients with NSCLC was randomly selected to ensure a spectrum of target sizes and locations. All treatment planning was accomplished with 2–3 VMAT arcs and a prescription of 60 Gy in 30 fractions. Two plan normalisation methods were employed: (i) planning target volume (PTV) V100% = 95% and (ii) PTV V95% = 95%.

Results:
All three dose calculation algorithms revealed heterogeneous and conformal plans irrespective of plan normalisations. The PTV and OARs dose–volume constraints were met using both normalisation methods. However, we observed that AAA overestimated the minimum PTV doses by 2–5% regardless of plan normalisation. The mean PTV-V100% was lower for AAA in comparison with AXB and MC algorithms.

Conclusions:
VMAT is an effective radiotherapy technique for achieving greater target dose conformity, heterogeneity and dose fall-off from the PTV for the treatment of NSCLC. The results of this study can provide the basis for the development of local plan acceptability criteria for NSCLC VMAT plans, and the clinical implementation can be achieved with minimal or no imposition on resources and time constraints. Occasionally, plan normalisation of PTV-V95% = 95% may be required to ensure that the OAR dose tolerances are not exceeded.
The Intrinsic 150‐Day Periodicity of the Southern Hemisphere Extratropical Large‐Scale Atmospheric Circulation
Authors: Lubis Sandro W. , Hassanzadeh Pedram 
Published: May 2023

AbstractThe variability of the Southern Hemisphere (SH) extratropical large‐scale circulation is dominated by the Southern Annular Mode (SAM), whose timescale is extensively used as a key metric in evaluating state‐of‐the‐art climate models. Past observational and theoretical studies suggest that the SAM lacks any internally generated (intrinsic) periodicity. Here, we show, using observations and a climate model hierarchy, that the SAM has an intrinsic 150‐day periodicity. This periodicity is robustly detectable in the power spectra and principal oscillation patterns (aka dynamical mode decomposition) of the zonal‐mean circulation, and in hemispheric‐scale precipitation and ocean surface wind stress. The 150‐day period is consistent with the predictions of a new reduced‐order model for the SAM, which suggests that this periodicity is associated with a complex interaction of turbulent eddies and zonal wind anomalies, as the latter propagate from low to high latitudes. These findings present a rare example of periodic oscillations arising from the internal dynamics of the extratropical turbulent circulations. Based on these findings, we further propose a new metric for evaluating climate models, and show that some of the previously reported shortcomings and improvements in simulating SAM's variability connect to the models' ability in reproducing this periodicity. We argue that this periodicity should be considered in evaluating climate models and understanding the past, current, and projected Southern Hemisphere climate variability.
Investigating Surface Deformation and Its Intrinsic Mechanism in Shenzhen, China Using Sentinel‐1A SAR Imagery
Authors: Zhou Lv , Liu Suoge , Li Jiahao , Pan Yuanjin , Wang Cheng , Huang Liangke , Huang Ling 
Published: May 2023

AbstractTo avoid disasters caused by surface deformation in urban areas, monitoring and analyzing the mechanism of surface deformation in urban areas on a large scale and in long‐term series is mandatory. Based on PS‐InSAR technology and using 157 Sentinel‐1A images, the surface deformation in Shenzhen was monitored from 2015 to 2022, and the obtained deformation rate ranged from −22.8 to +23.2 mm/year. In this paper, analysis is presented by integrating urbanization, climate, and geology data from Shenzhen. The analysis indicates that surface deformation caused by natural factors is typically observed in regions with unique geological characteristics, such as seasonal deformation in sedimentary areas and uplift along reverse fault zones. Human factors chiefly cause subsidence, and the areas with greater subsidence are generally urbanized areas (∼10 mm/year), industrial areas (∼20 mm/year), and reclamation areas (∼15 mm/year). The deformation of the reservoir dam is subject to multiple factors. The differential subsidence of 2–8 mm/year at both ends is due to the engineering geological conditions. In comparison, the weak rotation with a linear velocity of 18 mm/year is due to hydrostatic pressure and its structural characteristics. The research results of this paper systematically explore the phenomena and the intrinsic mechanism of surface deformation in Shenzhen, providing a safety basis for urban development and emergency disaster prevention in Shenzhen.
Micromechanical interlocking structure at the filler/resin interface for dental composites: a review
Authors: Zhang Shuning , Wang Xiao , Yang Jiawei , Chen Hongyan , Jiang Xinquan 
Published: May 2023

AbstractDental resin composites (DRCs) are popular materials for repairing caries or dental defect, requiring excellent properties to cope with the complex oral environment. Filler/resin interface interaction has a significant impact on the physicochemical/biological properties and service life of DRCs. Various chemical and physical modification methods on filler/resin interface have been introduced and studied, and the physical micromechanical interlocking caused by the modification of fillers morphology and structure is a promising method. This paper firstly introduces the composition and development of DRCs, then reviews the chemical and physical modification methods of the filler/resin interface, mainly discusses the interface micromechanical interlocking structures and their enhancement mechanism for DRCs, finally give a summary on the existing problems and development potential.
Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants
Authors: Straumann Isabelle , Ley Laura , Holze Friederike , Becker Anna M. , Klaiber Aaron , Wey Kathrin , Duthaler Urs , Varghese Nimmy , Eckert Anne , Liechti Matthias E. 
Published: May 2023

Abstract
There is renewed interest in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. Although acute subjective effects of LSD are mostly positive, negative subjective effects, including anxiety, may occur. The induction of overall positive acute subjective effects is desired in psychedelic-assisted therapy because positive acute experiences are associated with greater therapeutic long-term benefits. 3,4-Methylenedioxymethamphetamine (MDMA) produces marked positive subjective effects and is used recreationally with LSD, known as “candyflipping.” The present study investigated whether the co-administration of MDMA can be used to augment acute subjective effects of LSD. We used a double-blind, randomized, placebo-controlled, crossover design with 24 healthy subjects (12 women, 12 men) to compare the co-administration of MDMA (100 mg) and LSD (100 µg) with MDMA and LSD administration alone and placebo. Outcome measures included subjective, autonomic, and endocrine effects and pharmacokinetics. MDMA co-administration with LSD did not change the quality of acute subjective effects compared with LSD alone. However, acute subjective effects lasted longer after LSD + MDMA co-administration compared with LSD and MDMA alone, consistent with higher plasma concentrations of LSD (Cmax and area under the curve) and a longer plasma elimination half-life of LSD when MDMA was co-administered. The LSD + MDMA combination increased blood pressure, heart rate, and pupil size more than LSD alone. Both MDMA alone and the LSD + MDMA combination increased oxytocin levels more than LSD alone. Overall, the co-administration of MDMA (100 mg) did not improve acute effects or the safety profile of LSD (100 µg). The combined use of MDMA and LSD is unlikely to provide relevant benefits over LSD alone in psychedelic-assisted therapy. Trial registration: ClinicalTrials.gov identifier: NCT04516902.
Structure and transport mechanism of the human calcium pump SPCA1
Authors: Wu Mengqi , Wu Cang , Song Tiefeng , Pan Kewu , Wang Yong , Liu Zhongmin 
Published: May 2023

AbstractSecretory-pathway Ca2+-ATPases (SPCAs) play critical roles in maintaining Ca2+ homeostasis, but the exact mechanism of SPCAs-mediated Ca2+ transport remains unclear. Here, we determined six cryo-electron microscopy (cryo-EM) structures of human SPCA1 (hSPCA1) in a series of intermediate states, revealing a near-complete conformational cycle. With the aid of molecular dynamics simulations, these structures offer a clear structural basis for Ca2+ entry and release in hSPCA1. We found that hSPCA1 undergoes unique conformational changes during ATP binding and phosphorylation compared to other well-studied P-type II ATPases. In addition, we observed a conformational distortion of the Ca2+-binding site induced by the separation of transmembrane helices 4L and 6, unveiling a distinct Ca2+ release mechanism. Particularly, we determined a structure of the long-sought CaE2P state of P-type IIA ATPases, providing valuable insights into the Ca2+ transport cycle. Together, these findings enhance our understanding of Ca2+ transport by hSPCA1 and broaden our knowledge of P-type ATPases.
An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment
Authors: Li Guoqing , Liu Su , Chen Yixiao , Zhao Jin , Xu Huihui , Weng Jian , Yu Fei , Xiong Ao , Udduttula Anjaneyulu , Wang Deli , Liu Peng , Chen Yingqi , Zeng Hui 
Published: May 2023

AbstractIntra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.
In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer
Authors: Dervovic Dzana , Malik Ahmad A. , Chen Edward L. Y. , Narimatsu Masahiro , Adler Nina , Afiuni-Zadeh Somaieh , Krenbek Dagmar , Martinez Sebastien , Tsai Ricky , Boucher Jonathan , Berman Jacob M. , Teng Katie , Ayyaz Arshad , Lü YiQing , Mbamalu Geraldine , Loganathan Sampath K. , Lee Jongbok , Zhang Li , Guidos Cynthia , Wrana Jeffrey , Valipour Arschang , Roux Philippe P. , Reimand Jüri , Jackson Hartland W. , Schramek Daniel 
Published: May 2023

AbstractHow the genetic landscape governs a tumor’s response to immunotherapy remains poorly understood. To assess the immune-modulatory capabilities of 573 genes associated with altered cytotoxicity in human cancers, here we perform CRISPR/Cas9 screens directly in mouse lung cancer models. We recover the known immune evasion factors Stat1 and Serpinb9 and identify the cancer testis antigen Adam2 as an immune modulator, whose expression is induced by KrasG12D and further elevated by immunotherapy. Using loss- and gain-of-function experiments, we show that ADAM2 functions as an oncogene by restraining interferon and TNF cytokine signaling causing reduced presentation of tumor-associated antigens. ADAM2 also restricts expression of the immune checkpoint inhibitors PDL1, LAG3, TIGIT and TIM3 in the tumor microenvironment, which might explain why ex vivo expanded and adoptively transferred cytotoxic T-cells show enhanced cytotoxic efficacy in ADAM2 overexpressing tumors. Together, direct in vivo CRISPR/Cas9 screens can uncover genetic alterations that control responses to immunotherapies.
Data-driven design of new chiral carboxylic acid for construction of indoles with C-central and C–N axial chirality via cobalt catalysis
Authors: Zhang Zi-Jing , Li Shu-Wen , Oliveira João C. A. , Li Yanjun , Chen Xinran , Zhang Shuo-Qing , Xu Li-Cheng , Rogge Torben , Hong Xin , Ackermann Lutz 
Published: May 2023

AbstractChallenging enantio- and diastereoselective cobalt-catalyzed C–H alkylation has been realized by an innovative data-driven knowledge transfer strategy. Harnessing the statistics of a related transformation as the knowledge source, the designed machine learning (ML) model took advantage of delta learning and enabled accurate and extrapolative enantioselectivity predictions. Powered by the knowledge transfer model, the virtual screening of a broad scope of 360 chiral carboxylic acids led to the discovery of a new catalyst featuring an intriguing furyl moiety. Further experiments verified that the predicted chiral carboxylic acid can achieve excellent stereochemical control for the target C–H alkylation, which supported the expedient synthesis for a large library of substituted indoles withC-central and C–N axial chirality. The reported machine learning approach provides a powerful data engine to accelerate the discovery of molecular catalysis by harnessing the hidden value of the available structure-performance statistics.
Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
Authors: M. Naeini Marjan , Newell Felicity , Aoude Lauren G. , Bonazzi Vanessa F. , Patel Kalpana , Lampe Guy , Koufariotis Lambros T. , Lakis Vanessa , Addala Venkateswar , Kondrashova Olga , Johnston Rebecca L. , Sharma Sowmya , Brosda Sandra , Holmes Oliver , Leonard Conrad , Wood Scott , Xu Qinying , Thomas Janine , Walpole Euan , Tao Mai G. , Ackland Stephen P. , Martin Jarad , Burge Matthew , Finch Robert , Karapetis Christos S. , Shannon Jenny , Nott Louise , Bohmer Robert , Wilson Kate , Barnes Elizabeth , Zalcberg John R. , Mark Smithers B. , Simes John , Price Timothy , Gebski Val , Nones Katia , Watson David I. , Pearson John V. , Barbour Andrew P. , Waddell Nicola 
Published: May 2023

AbstractOesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.
The largest prehistoric mound in Europe is the Bronze-Age Hill of Udine (Italy) and legend linked its origin to Attila the Hun
Authors: Fontana A. , Vinci G. , Ronchi L. , Mocchiutti A. , Muscio G. , Visentini P. , Bassetti M. , Novellino M. D. , Badino F. , Musina G. , Bonomi S. 
Published: May 2023

AbstractPrehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun’s soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age.
Visualization of the relationship between electrogustometry and whole mouth test using multidimensional scaling
Authors: Ha Jong-Gyun , Kim Bo-ra , Cho Ara , Jeong Yeonsu , Rha Min-Seok , Kang Ju-Wan , Cho Hyung-Ju , Yoon Joo-Heon , Kim Chang-Hoon 
Published: May 2023

AbstractInterpreting the relationship between different taste function tests of different stimuli, such as chemical and electrical stimulation, is still poorly understood. This study aims to analyze visually as well as quantitatively how to interpret the relationship of results between taste function tests using different stimuli. Patients who underwent the whole mouth test and Electrogustometry (EGM) at a tertiary medical center between August 2018 and December 2018 were reviewed retrospectively with electronic medical records. Of the 110 patients, a total of 86 adults who self-reported that their taste function was normal through a questionnaire were enrolled. EGM measured the thresholds of the chorda tympani (CT) and glossopharyngeal nerve (GL) area of the tongue. The whole mouth test measured detection and recognition thresholds for sweet, salty, bitter, sour, and umami taste. Statistical analyses of Pearson’s, Spearman’s rank and polyserial correlation and multidimensional scaling (MDS) was performed. The EGM threshold for the average value of both CT regions and the recognition threshold of the whole mouth test were significantly correlated in sweet, salty, bitter, and sour taste (r = 0.244–0.398, P < 0.05), and the detection threshold was correlated only significant in sweet (r = 0.360, P = 0.007). In the MDS analysis results, the three-dimensional (D) solution was chosen over the 2-D solution because of the lower stress. Detection-, recognition threshold of whole mouth test and EGM thresholds of CT and GL area, those were standardized by Z-score, formed well-distinguished sections in the MDS analyses. The EGM threshold of the CT area was closer to the detection and recognition thresholds than the EGM threshold of the GL area. In general, the EGM threshold was closer to the recognition threshold than the detection threshold for each taste. Overall, visualization of the relationship of whole mouth test and EGM by MDS was in good agreement with quantitative analysis. EGM and whole mouth test seem to reflect different aspects of taste. However, when interpreting the EGM results, the EGM threshold of the CT area will show more similarity to the recognition threshold than the detection threshold for the whole mouth test.
Ensemble-based multi-tissue classification approach of colorectal cancer histology images using a novel hybrid deep learning framework
Authors: Khazaee Fadafen Masoud , Rezaee Khosro 
Published: May 2023

AbstractColorectal cancer (CRC) is the second leading cause of cancer death in the world, so digital pathology is essential for assessing prognosis. Due to the increasing resolution and quantity of whole slide images (WSIs), as well as the lack of annotated information, previous methodologies cannot be generalized as effective decision-making systems. Since deep learning (DL) methods can handle large-scale applications, they can provide a viable alternative to histopathology image (HI) analysis. DL architectures, however, may not be sufficient to classify CRC tissues based on anatomical histopathology data. A dilated ResNet (dResNet) structure and attention module are used to generate deep feature maps in order to classify multiple tissues in HIs. In addition, neighborhood component analysis (NCA) overcomes the constraint of computational complexity. Data is fed into a deep support vector machine (SVM) based on an ensemble learning algorithm called DeepSVM after the features have been selected. CRC-5000 and NCT-CRC-HE-100 K datasets were analyzed to validate and test the hybrid procedure. We demonstrate that the hybrid model achieves 98.75% and 99.76% accuracy on CRC datasets. The results showed that only pathologists' labels could successfully classify unseen WSIs. Furthermore, the hybrid deep learning method outperforms state-of-the-art approaches in terms of computational efficiency and time. Using the proposed mechanism for tissue analysis, it will be possible to correctly predict CRC based on accurate pathology image classification.