bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of a nucleus pulposus‐derived cartilage analog scaffold for chondral repair and regeneration
Authors: Thomas Vishal Joseph , Buchweitz Nathan Foster , Baek Jay John , Wu Yongren , Mercuri Jeremy John 
Published: November 2023

AbstractFocal chondral defects (FCDs) significantly impede quality of life for patients and impose severe economic costs on society. One of the most promising treatment options—autologous matrix‐induced chondrogenesis (AMIC)—could benefit from a scaffold that contains both of the primary cartilage matrix components—sulfated glycosaminoglycans (sGAGs) and collagen type II. Here, 17 different protocols were evaluated to determine the most optimum strategy for decellularizing (decelling) the bovine nucleus pulposus (bNP) to yield a natural biomaterial with a cartilaginous constituency. The resulting scaffold was then characterized with respect to its biochemistry, biomechanics and cytocompatibility. Results indicated that the optimal decell protocol involved pre‐crosslinking the tissue prior to undergoing decell with trypsin and Triton X‐100. The residual DNA content of the scaffold was found to be 32.64 ± 9.26 ng/mg dry wt. of tissue with sGAG and hydroxyproline (HYP) contents of 72.53 ± 16.43. and 78.38 ± 8.46 μg/mg dry wt. respectively. The dynamic viscoelastic properties were found to be preserved (complex modulus: 17.92–16.62 kPa across a range of frequencies) while the equilibrium properties were found to have significantly decreased (aggregate modulus: 11.51 ± 9.19 kPa) compared to the non‐decelled fresh bNP tissue. Furthermore, the construct was also found to be cytocompatible with bone marrow stem cells (BMSCs). While it was not permissive of cellular infiltration, the BMSCs were still found to have lined the laser drilled channels in the scaffold. Taken together, the biomaterial developed herein could be a valuable addition to the AMIC family of scaffolds or serve as an off‐the‐shelf standalone option for cartilage repair.
A Q‐learning method based on coarse‐to‐fine potential energy surface for locating transition state and reaction pathway
Authors: Xu Wenjun , Zhao Yanling , Chen Jialu , Wan Zhongyu , Yan Dadong , Zhang Xinghua , Zhang Ruiqin 
Published: November 2023

AbstractTransition state (TS) on the potential energy surface (PES) plays a key role in determining the kinetics and thermodynamics of chemical reactions. Inspired by the fact that the dynamics of complex systems are always driven by rare but significant transition events, we herein propose a TS search method in accordance with the Q‐learning algorithm. Appropriate reward functions are set for a given PES to optimize the reaction pathway through continuous trial and error, and then the TS can be obtained from the optimized reaction pathway. The validity of this Q‐learning method with reasonable settings of Q‐value table including actions, states, learning rate, greedy rate, discount rate, and so on, is exemplified in 2 two‐dimensional potential functions. In the applications of the Q‐learning method to two chemical reactions, it is demonstrated that the Q‐learning method can predict consistent TS and reaction pathway with those by ab initio calculations. Notably, the PES must be well prepared before using the Q‐learning method, and a coarse‐to‐fine PES scanning scheme is thus introduced to save the computational time while maintaining the accuracy of the Q‐learning prediction. This work offers a simple and reliable Q‐learning method to search for all possible TS and reaction pathway of a chemical reaction, which may be a new option for effectively exploring the PES in an extensive search manner.
SPANA: Spatial decomposition analysis for cellular‐scale molecular dynamics simulations
Authors: Yu Isseki , Mori Takaharu , Matsuoka Daisuke , Surblys Donatas , Sugita Yuji 
Published: November 2023

AbstractThe rapid increase in computational power with the latest supercomputers has enabled atomistic molecular dynamics (MDs) simulations of biomolecules in biological membrane, cytoplasm, and other cellular environments. These environments often contain a million or more atoms to be simulated simultaneously. Therefore, their trajectory analyses involve heavy computations that can become a bottleneck in the computational studies. Spatial decomposition analysis (SPANA) is a set of analysis tools in the Generalized‐Ensemble Simulation System (GENESIS) software package that can carry out MD trajectory analyses of large‐scale biological simulations using multiple CPU cores in parallel. SPANA applies the spatial decomposition of a large biological system to distribute structural and dynamical analyses into individual CPU cores, which reduces the computational time and the memory size, significantly. SPANA opens new possibilities for detailed atomistic analyses of biomacromolecules as well as solvent water molecules, ions, and metabolites in MD simulation trajectories of very large biological systems containing more than millions of atoms in cellular environments.
A cross‐professional competency framework for communicating genomic results
Authors: Pichini Amanda , Tatton‐Brown Kate , Thomas Ellen , Bishop Michelle 
Published: November 2023

AbstractTo ensure genomic medicine is delivered safely and effectively, it is crucial that healthcare professionals are able to understand and communicate genomic results. This Education Innovation describes a nationally agreed, cross‐professional competency framework outlining the knowledge, skills and behaviors required to communicate genomic results. Using principles of the nominal group technique, consensus meetings with clinical, scientific and educational experts identified six stages in the return of results process, drafted and iterated competencies. Competencies were then mapped across three levels to acknowledge different degrees of experiences and scopes of practice. The framework was open for consultation with healthcare professionals and patient communities before being published. The finalized framework includes six core competency statements required to communicate genomic results. This framework is designed to be a guide for best practice and a developmental tool to support individuals and organizations. It can be used by healthcare professionals, such as genetic counselors, to identify individual learning needs or to structure the development of training for other healthcare professionals who are increasingly involved in requesting and returning results for genomic tests.
Mindfulness and yoga therapy for acute pain in sickle cell disease
Authors: Dev Pallavi , Bavli Natalie , Sims Brittney , Foster Jenny , Moscowitz Anna , Makris Una E. , Rambally Siayareh 
Published: November 2023

AbstractThere is a paucity of data regarding the use of non‐pharmacologic therapies for pain in sickle cell disease. The purpose of this pilot study was to assess the acceptability and feasibility of video‐guided mindfulness meditation, breathing exercises, and yoga, in addition to standard of care, during admission for painful vaso‐occlusive crisis. Feasibility was demonstrated by the enrollment rate of > 90% and high level of participant engagement in the intervention. Acceptability was demonstrated by positive feedback obtained in post‐intervention surveys and the majority of subjects who expressed interest in participating in future mindfulness and yoga therapy sessions.
ENSO and IOD contributions to seasonal meteorological droughts over the Yangtze River basin
Authors: Yin Hao , Fowler Hayley J. , Blenkinsop Stephen , Wu Zhiyong , He Hai , Li Yuan 
Published: November 2023

AbstractThe Yangtze River basin (YRB) has experienced frequent extreme drought events in recent years. Many studies have explored the impact of anomalous tropical sea surface temperatures on seasonal meteorological droughts over the YRB, yet two critical issues remain: (1) the regimes of the El Niño–Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD) causing YRB droughts; (2) the timing and spatial pattern of YRB droughts caused by ENSO and IOD. To address these knowledge gaps, we employed a comprehensive investigation. First, the Severity–Area–Density (SAD) method is applied to identify seasonal drought events over the YRB during 1971–2022. Second, we utilize composite analysis to specify the effects of ENSO and IOD. Our findings indicate that YRB droughts are significantly increased in the August of combined Eastern Pacific (EP) El Niño and positive IOD developing years, October of Central Pacific (CP) El Niño developing years, January of EP La Niña years, and April of CP El Niño decaying years. Third, we conduct numerical simulations and conclude that ENSO and IOD events contribute to the YRB droughts by modulating large‐scale circulation patterns, triggering the formation of cyclones and anticyclones over the Western North Pacific (WNP) and the Tibetan Plateau, and affecting the westerlies and other water vapour transport processes. These results on the physical mechanisms causing seasonal drought in the YRB can guide drought monitoring and prediction in the region.
Increased anoxia following species invasion of a eutrophic lake
Authors: Rohwer Robin R. , Ladwig Robert , Hanson Paul C. , Walsh Jake R. , Vander Zanden M. Jake , Dugan Hilary A. 
Published: November 2023

AbstractSpecies invasions can disrupt aquatic ecosystems by re‐wiring food webs. A trophic cascade triggered by the invasion of the predatory zooplankter spiny water flea (Bythotrephes cederströmii) resulted in increased phytoplankton due to decreased zooplankton grazing. Here, we show that increased phytoplankton biomass led to an increase in lake anoxia. The temporal and spatial extent of anoxia experienced a step change increase coincident with the invasion, and anoxic factor increased by 11 d. Post‐invasion, anoxia established more quickly following spring stratification, driven by an increase in phytoplankton biomass. A shift in spring phytoplankton phenology encompassed both abundance and community composition. Diatoms (Bacillaryophyta) drove the increase in spring phytoplankton biomass, but not all phytoplankton community members increased, shifting the community composition. We infer that increased phytoplankton biomass increased labile organic matter and drove hypolimnetic oxygen consumption. These results demonstrate how a species invasion can shift lake phenology and biogeochemistry.
Temperature effects on the passivity breakdown of copper in chloride‐containing borate buffer solution
Authors: Zhou Yuting , Mao Feixiong , Yu Jingkun , Assellin Edouard 
Published: November 2023

AbstractPassivity and passivity breakdown of pure copper were studied in alkaline chloride‐containing borate buffer solution from 25°C to 80°C by electrochemical measurements and scanning electron microscopy. The corresponding E–pH diagrams were also calculated. Increased temperatures make the open circuit potential and formation potential for cuprous oxide (Cu2O) shift in a negative direction. The mean breakdown potential shifts in a positive direction and the distribution of breakdown potential has a wider width, while the minimum breakdown potential decreases slightly at higher temperature. The anodic passive film formed at 0.4 V versus Ag/AgCl for 6 h in a chloride‐free solution at T ≥ 40°C can maintain passivity after the addition of 0.1 M NaCl, but cannot maintain passivity at 25°C at the same concentration. High temperature benefits the growth of copper oxide over the formation of copper chloride species. Cu2O and CuO have excellent corrosion resistance to 0.1 M NaCl and passivity can be maintained well above the CuO/Cu2O equilibrium at pH > 8.
Effects of compressive damage on the corrosion protection performance of offshore wind power coating systems
Authors: Momber Andreas W. , Marquardt Tom , Irmer Michael , Kelm Daniel 
Published: November 2023

AbstractDamage to multilayer organic coating systems due to compressive loads can deteriorate the corrosion protection performance of the coatings under offshore exposure. The contribution is concerned with statistical investigations into the effects of load‐based and coating‐based factors on the protection performance of different coating systems. Accelerated cyclic laboratory tests (ISO 12944‐9) were performed on four multilayer coating systems, and the results were statistically analyzed. Results of analysis of variance investigations revealed that the effects on the anticorrosive performance of the coatings (anticorrosive effect [AE]) were dominated by coating‐based factors, namely coating system and total dry film thickness. These factors could explain 86% of all effects. Coating system was the only extremely significant factor. Load‐based factors did not deliver notable effects (5%). Except for the contact stiffness, these factors were insignificant. The load intensity was insignificant for all target parameters (blistering, delamination, AE). Coating regions, plastically deformed during the compression tests, did not lead to a reduction in the protection performance.
Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design
Authors: Tolonen Jussi Pekka , Parolin Schnekenberg Ricardo , McGowan Simon , Sims David , McEntagart Meriel , Elmslie Frances , Shears Debbie , Stewart Helen , Tofaris George K. , Dabir Tabib , Morrison Patrick J. , Johnson Diana , Hadjivassiliou Marios , Ellard Sian , Shaw‐Smith Charles , Znaczko Anna , Dixit Abhijit , Suri Mohnish , Sarkar Ajoy , Harrison Rachel E. , Jones Gabriela , Houlden Henry , Ceravolo Giorgia , Jarvis Joanna , Williams Jonathan , Shanks Morag E. , Clouston Penny , Rankin Julia , Blumkin Lubov , Lerman‐Sagie Tally , Ponger Penina , Raskin Salmo , Granath Katariina , Uusimaa Johanna , Conti Hector , McCann Emma , Joss Shelagh , Blakes Alexander J.M. , Metcalfe Kay , Kingston Helen , Bertoli Marta , Kneen Rachel , Lynch Sally Ann , Martínez Albaladejo Inmaculada , Moore Austen Peter , Jones Wendy D. ,   Genomics England Research Consortium, Becker Esther B.E. , Németh Andrea H. 
Published: November 2023

AbstractBackgroundThe ITPR1 gene encodes the inositol 1,4,5‐trisphosphate (IP3) receptor type 1 (IP3R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.ObjectivesWe aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy.MethodsCases were identified using next‐generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction.ResultsWe report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N‐terminal IP3‐binding domain, the carbonic anhydrase 8 (CA8)‐binding region, and the C‐terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype–phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression.ConclusionsThis dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Studying carrier frequency of spinal muscular atrophy in the State of Qatar and comparison to other ethnic groups: Pilot study
Authors: Ibrahim Faisal , Velayutham Dinesh , Alsharshani Mohamed , AlAlami Usama , AlDewik Manar , Abuarja Tala , Al Rifai Hilal , Al‐Dewik Nader I. 
Published: November 2023

AbstractBackgroundSpinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations and deletions in SMN1 at exon 7. The carrier frequency for SMN1 mutations ranges from 2 to 4% in the general population.MethodsWe examined allelic, genotypic relatedness and copy number (CN) variations and frequencies of SMN1 and SMN2, in 13,426 samples from Qatar biobank (QBB) to provide a precise estimation of SMA carrier frequency in Qatar in comparison to other populations.ResultsThe SMA carrier frequency was found to be (2.8%) and the rs143838139 was found in 491/13426 (3.66%) of individuals. The SNP rs121909192, which is a pathogenic risk factor, was found in 321/13500 (2.38%). In Addition 242/11379 (2.13%) had two copies of SMN1 and the rs143838139, which may explain the (2 + 0) silent carrier. Additionally, two participants were found to be SMA type 4 with 0 and 4 copy numbers in SMN1 and SMN2, respectively.ConclusionThe SMA carrier frequency in Qatar was found to be comparable to Saudi Arabia and Caucasians. The likely pathogenic variant, rs121909192, was found to be significantly higher when compering with other in our study. The rs143838139 variant, which has a strong association with the silent carrier genotype, has been found. Consequently, testing for this SNP may enhance the precision of evaluating the likelihood of a patient having an affected child. We conclude that the frequency of SMA carriers varies within the Qatar population and other ethnic groups.
Machine learning based on SPECT/CT to differentiate bone metastasis and benign bone lesions in lung malignancy patients
Authors: Wang Huili , Chen Yiru , Qiu Jianfeng , Xie Jindong , Lu Weizhao , Ma Junchi , Jia Mingsheng 
Published: November 2023

AbstractBackgroundBone metastasis is a common event in lung cancer progression. Early diagnosis of lung malignant tumor with bone metastasis is crucial for selecting effective treatment strategies. However, 14.3% of patients are still difficult to diagnose after SPECT/CT examination.PurposeMachine learning analysis of [99mTc]‐methylene diphosphate (99mTc‐MDP) SPECT/CT scans to distinguish bone metastases from benign bone lesions in patients with lung cancer.MethodsOne hundred forty‐one patients (69 with bone metastases and 72 with benign bone lesions) were randomly assigned to the training group or testing group in a 7:3 ratio. Lesions were manually delineated using ITK‐SNAP, and 944 radiomics features were extracted from SPECT and CT images. The least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomics features in the training set, and the single/bimodal radiomics models were established based on support vector machine (SVM). To further optimize the model, the best bimodal radiomics features were combined with clinical features to establish an integrated Radiomics‐clinical model. The diagnostic performance of models was evaluated using receiver operating characteristic (ROC) curve and confusion matrix, and performance differences between models were evaluated using the Delong test.ResultsThe optimal radiomics model comprised of structural modality (CT) and metabolic modality (SPECT), with an area under curve (AUC) of 0.919 and 0.907 for the training and testing set, respectively. The integrated model, which combined SPECT, CT, and two clinical features, exhibited satisfactory differentiation in the training and testing set, with AUC of 0.939 and 0.925, respectively.ConclusionsThe machine learning can effectively differentiate between bone metastases and benign bone lesions. The Radiomics‐clinical integrated model demonstrated the best performance.
Integrin α6: a potential target for cancer molecular imaging and targeting therapy
Authors: Li Xin‐Ling , Shen Zhuo‐Lun , Wang Qiao‐Li , Ye Jia‐Cong , Zhang Wen‐Biao , Li Ying‐He , Feng Guo‐Kai , Zeng Mu‐Sheng 
Published: November 2023

AbstractAs a major kind of cell surface adhesion molecules with signal transduction function, integrins play a major role in tumorigenesis and tumor progression. The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed. Among the integrin family, integrin αvβ3 is the most studied integrin in the past 20 years. Plenty of preclinical and clinical studies have been conducted, which showed clinical benefits of targeting integrin αvβ3 in tumor imaging and treatment. Currently, the focus of interest is gradually shifting from integrin αvβ3 toward other integrin subtypes. Integrin α6 is expressed in many malignant tumors, such as colorectal cancer, head and neck squamous cell carcinoma, breast cancer, pancreatic cancer, and liver cancer, and its expression is correlated with poor survival of the patients. Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrin α6 have excellent safety and efficacy in preclinical mouse models, encouraging clinical translation of this promising target. In this review, we briefly overview the physiological and pathological function of integrin α6 and highlight the recent advances in integrin α6‐targeted imaging and therapeutics in tumors.
A novel design of three‐dimensional/unidirectional hybrid composites to balance in‐plane and interlaminar mechanical properties
Authors: Zha Yibin , Li Zherui , Cai Zhixiang , Qin Cheng , Fan Yi , Li Yongfeng , Ma Qihua , Zhang Hui , Gan Xuehui 
Published: November 2023

AbstractThe working condition of the rail transit components such as bogies is complicated, so the high comprehensive performance of composite parts is desperately required. However, existing pure three‐dimensional braided or laminated composites have been unable to satisfy the cooperative demand of in‐plane and interlaminar properties. In this paper, a novel design of three‐dimensional braided/unidirectional (3D/UD) hybrid composite is proposed to balance the in‐plane (tensile, compression, bending), interlaminar (interlaminar shear, low‐speed impact) properties of the composite. The effects of different 3D/UD mixing ratio and layup sequence on the mechanical properties and damage mechanism of hybrid composites were studied by the parametric analysis of the experimental test results, and the comprehensive mechanical properties of the hybrid structure were optimized by COPRAS evaluation method. The results show that the larger the proportion of unidirectional layer, the better the mechanical property in‐plane, but the worse interlayer property. In addition, the change of layup sequence induces a complex nonlinear relationship between 3D/UD mixing ratio and mechanical properties. Combined with microscopic failure characterization results, it is found that the sandwich structure and the addition of uniformly distributed interfacial layer can improve the mechanical properties of the hybrid composite. The optimization results show that the sandwich structure hybrid composite UD6/3D/UD6 with the best balance between in‐plane and interlaminar properties was selected by COPRAS. Compared with pure 3D composites, the comprehensive mechanical properties of UD6/3D/UD6 are increased by 53.9%, which provides a reference for the structural design of hybrid composites in the future.Highlights
A novel design of 3D/UD hybrid composite is proposed to balance the in‐plane and interlaminar properties.
The influence regularity of 3D/UD mixing ratio and layup sequence on properties of hybrid composites were obtained.
The mixing failure mechanism of interlayer and in‐plane was revealed.
The optimal structure UD6/3D/UD6 under complex working conditions was obtained by COPRAS.