bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of clinical trials of new oncology drugs approved in China
Authors: Yang Jing , Yang Ji , Hu Yuan‐Jia 
Published: November 2023

AbstractBackgroundSince reforms were introduced to incentivize drug innovation in 2015, the Chinese pharmaceutical market has experienced unprecedented prosperity, with more new drugs than ever before, especially anticancer treatments. In 2021, Chinese regulatory agencies issued the new guideline for clinical research and development of antitumor drugs, triggering a series of responses on the drug market. Limited research has outlined the nature of the original new drugs in China to understand the dynamic response of the market.MethodsThe objective of this article was to map the clinical development of approved new oncology drugs in China from 2015 to 2021 and differed from previous studies by focusing on original new drugs, using the United States as a benchmark, and elaborating the endogenous features of clinical trials.ResultsClinical trials conducted in China have risen to a level similar to that of the United States in many aspects of trial design, but there is still distance between the implementation and operational details of clinical trials. In the meantime, China has made significant breakthroughs in drug approval. Greater than 60% of novel anticancer drugs in China received accelerated approved for their first listing. Approximately 90% of the pivotal clinical trials supporting initial drug approval used surrogate measures as end points, and one half were nonrandomized or did not have a control group. However, duplicate development without evidence of a clinical advantage compared with current therapies was widely observed.ConclusionsBy presenting a multidimensional landscape of clinical trials and approvals in the real world, this review allows interested researchers, developers, and even regulators to understand what has been done and what should be done next in anticancer drug development in China.
Puzzling Structure of the Key Intermediates in Gold(I)‐catalyzed Cyclization Reactions of Enynes and Allenenes
Authors: García‐Padilla Eduardo , Escofet Imma , Maseras Feliu , Echavarren Antonio M. 
Published: November 2023

AbstractWe identify the dominant structures of the intermediates of gold(I)‐catalyzed cyclizations of 1,5‐enynes and 1,5‐allenenes through computational analysis as gold(I) cyclopropylcarbenes, endocyclic vinylgold complexes and previously unreported non‐classical carbocationic minima. In contrast to 1,6‐enynes, the exocyclic carbocations are found to be less stable. Cyclopropylcarbene structures are consistently favoured as the most stable intermediates for all studied substitution patterns. We validate the computational methods used by using DLPNO‐CCSD(T) energies as a benchmark, indicating that the B3LYP‐D3 and M06‐D3 functionals are most accurate for energy determination, while NPA charges are mostly insensitive to functional. The evolution of a 1,6‐enyne in a single‐cleavage or double‐cleavage rearrangement is attributed to the barrierless evolution of a common cyclopropyl–gold(I) carbocation non‐stationary geometry. Our findings provide insights into reaction pathways and substrate dependence of the cycloisomerization processes.
Mechanistic Insight into how β‐Ketoacyl ACP Synthase I (KasA) Recognizes the Fatty Acid Chain Length of its Substrate
Authors: Lee Wook 
Published: November 2023

Abstractβ‐ketoacyl ACP synthase I (KasA) has been considered as a promising drug target against Tuberculosis because it is known to play a pivotal role in the survival of Mycobacterium Tuberculosis, a causative agent of Tuberculosis. KasA catalyzes the reaction elongating only the acyl chain that is 16 carbon atoms in length or longer, but the molecular details of how KasA selectively recognizes only the substrate longer than a certain length still remain unknown. In the present study, this challenging subject is addressed, and to this end, molecular dynamics (MD) simulations and free energy calculations for actual substrate binding process are carried out. The results illustrate that the substrate specificity of KasA is highly linked to its cooperativity and this cooperativity is realized through the activation of catalytic residues. Through these results, the mechanistic details of how KasA can be selectively activated only by the substrate with a proper length are suggested.
Complementary Tumor Diagnosis by Single Cell–Based Cytogenetics Using Multi‐marker Fluorescence In Situ Hybridization (mFISH)
Authors: Brockhoff Gero 
Published: November 2023

AbstractMulti‐color (or multi‐marker) fluorescence in situ hybridization (mFISH) is a well‐established, valuable, complementary tool for prenatal and pathological (tumor) diagnosis. A variety of chromosomal abnormalities, such as partial or total chromosomal gains, losses, inversions, or translocations, which are considered to cause genetic syndromes, can relatively easily be detected on a cell‐by‐cell basis. Individual cells either in suspension (e.g., in the form of a cytological specimen derived from body fluids) or within a tissue (e.g., a solid tumor specimen or biopsy) can be quantitatively evaluated with respect to the chromosomal hybridization markers of interest (e.g., a gene or centromeric region) and with due consideration of cellular heterogeneity. FISH is helpful or even essential for the (sub‐)classification, stratification, and unambiguous diagnosis of a number of malignant diseases and contributes to treatment decision in many cases. Here, the diagnostic power and limitations of typical FISH and mFISH approaches (except chromosome painting and RNA hybridization) are discussed, with special emphasis on tumor and single‐cell diagnostics. Well‐established and novel FISH protocols, the latter addressed to accelerate and flexibilize the preparation and hybridization of formalin‐fixed and paraffin‐embedded tissues, are provided. Moreover, guidelines and molecular aspects important for data interpretation are discussed. Finally, sophisticated multiplexed approaches and those that analyze very rare single‐cell events, which are not yet implemented in diagnostic procedures, will be touched upon. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.This article was corrected on 21 December 2023. See the end of the full text for details.Basic Protocol 1: (m)FISH applied to formaldehyde‐fixed paraffin‐embedded tissuesBasic Protocol 2: (m)FISH applied to cytological specimens
Asynchrony is more important than genetic distance in driving yield stability in wheat variety mixtures
Authors: Stefan Laura , Fossati Dario , Camp Karl‐Heinz , Pellet Didier , Foiada Flavio , Levy Lilia 
Published: November 2023

AbstractIn the face of climate change, improving yield stability is critical for food production systems. Increasing diversity in agricultural systems can be a way to stabilize yield across time and/or space. This can be done with mixtures of varieties, which represent a practical way to introduce diversity at the genotype level in agricultural fields. However, in Switzerland, wheat variety mixtures are still rarely used, due to a lack of understanding of the processes driving yield benefits and, consequently, no clear rules as to which varieties to combine. In this study, we used results from a Swiss wheat variety mixture trial to investigate the drivers of mixture productivity and stability. We hypothesized that mixtures composed of more different varieties—in terms of genetic distance but also of morphological, agronomic, or synchronicity aspects—would be more productive and/or stable. We did not find any effects of genetic distance on mixture productivity or stability, but we did observe an increase in mixture stability with reduced synchrony of the components, that is, when the components reacted differently to environmental conditions. This result was only significant in the first year of the trial, which was less productive due to more stressful conditions. This study shows that when combining asynchronous varieties, wheat variety mixtures have the potential to buffer possible yield losses due to external stressors during suboptimal years. While more research is needed to confirm this result, variety mixtures nonetheless represent a promising solution to sustainably increase the stability of wheat production in Switzerland.
Can external and internal corporate social responsibility contribute to green customer behaviour? The mediating role of green trust in hotels
Authors: Jaaron Ayham A. M. , Javaid Mudaser , Garcia R. L. Fernando 
Published: November 2023

AbstractTo date, hospitality literature has mainly used an aggregated measure of corporate social responsibility (CSR) to assess hotels' green trust (GT) and green customer behaviour (GCB). The differential impact of internal and external CSR on GT and GCB is crucial as this may lead to different levels of impacts on hotels' environmental performance. This study investigates how internal and external CSR impact customers' GT and GCB. It also investigates how GT mediates the relationship between internal and external CSR and GCB. Using survey data from 304 customers from eight green hotels in Manila and employing the PLS‐SEM technique for analysis, the results show that internal and external CSR positively impact GT and GCB. Moreover, GT mediates the relationship between internal CSR and GCB, but not between external CSR and GCB. This study extends stakeholder theory and the theory of planned behaviour by providing novel insights into how customers' GT and GCB may differ in relation to internal and external dimensions of CSR.
A Comprehensive Review on Modification of Titanium Dioxide‐Based Catalysts in Advanced Oxidation Processes for Water Treatment
Authors: Tanos Fida , Razzouk Antonio , Lesage Geoffroy , Cretin Marc , Bechelany Mikhael 
Published: November 2023

AbstractIt has become necessary to develop effective strategies to prevent and reduce water pollution as a result of the increase in dangerous pollutants in water reservoirs. Consequently, there is a need to design new catalyst materials to promote the efficiency of advanced oxidation processes (AOPs) in the field of wastewater treatment plant to ensure the mineralization of trace organic contaminants. A notable approach gaining attention involves the coupling of sulfate radicals‐based AOPs to photocatalysis or electrocatalysis processes, aiming to achieve the complete removal of refractory contaminants into water and carbon dioxide. Titanium dioxide as metal oxide has received great attention for its catalytic application in water purification. TiO2catalysts offer a multitude of advantages in AOPs. They are characterized by their high photocatalytic activity under both ultraviolet and visible light, making them environmentally friendly due to the absence of toxic byproducts during oxidation. Their versatility is remarkable, finding utility in various AOPs, from photocatalysis to photo‐Fenton processes. TiO2′s durability ensures long‐lasting catalytic activity, which is crucial for continuous treatment processes, and their cost‐effectiveness is particularly advantageous. Furthermore, their chemical stability allows it to withstand varying pH conditions. However, the large band gap energy and low electrical conductivity hinder the catalytic reaction effectiveness. This review aims to examine various approaches to enhance the catalytic performance of titanium dioxide, with the objective of enabling more efficient water purification methods.
Magnetic tile fault detection of high‐voltage electric machines: A multiview feature selection method via consistent soft label
Authors: Chen Junhang , Yang Zunyuan , Liu Mingyang , Li Daoyuan 
Published: November 2023

AbstractImage‐based scheme has attracted wide attention in the fault detection of high‐voltage permanent magnet motors, but it often suffers from the shooting conditions. Multiview feature selection allows multisource information to be fused, which can improve the accuracy and robustness of image detection. Therefore, we propose multiview unsupervised consistency via soft‐label feature selection (MUCSFS). This method constructs consistent pseudo labels through soft labels from clustering affinity of each view sample and builds the model by integrating selection constraints into the graph model. This model filters the fault data set to obtain the feature subset, which is used for clustering. We verify the method's effectiveness by simulating multiview data. The fault clustering experiment on the high‐voltage motors' magnetic tile fault data set confirm that our method can effectively cluster the fault categories.
Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives
Authors: Zou Chentao , Zan Xinquan , Jia Zhenyu , Zheng Lu , Gu Yijie , Liu Fei , Han Ye , Xu Chunfang , Wu Airong , Zhi Qiaoming 
Published: November 2023

AbstractBackgroundAlternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD).MethodsOur review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next‐generation sequencing (NGS) for AS events in IBD have been also discussed.ResultsAvailable evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis‐associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro‐fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third‐generation sequencing (TGS), single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST), will be desired with great expectations.ConclusionsTo our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.
Binomial distribution based grey wolf optimization algorithm for channel estimation in wireless communication system
Authors: Selvaraj Dhanasekaran , Shanmugam Ramalingam , Thangarajan Thamaraimanalan 
Published: November 2023

SummarySeveral input high‐data‐rate transmissions over broadband wireless channels are possible using multiple input multiple output (MIMO) systems paired with orthogonal frequency division multiplexing (OFDM) technology. Channel estimation is an essential technique and a necessary component of MIMO‐OFDM systems. However, the noise will be there in MIMO‐OFDM due to the environment. As a result, the wireless system performs degrades in terms of bit error rate (BER). The suggested method offers a better pilot pattern strategy for MIMO‐OFDM and an efficient power allocation to address this issue. The binomial distribution‐based grey wolf optimization (BDGWO) algorithm is proposed to identify the optimal pilot patterns. The power is then adaptively distributed to each transmit antenna to increase the spectral efficiency and maximum channel capacity through an adaptive neuro‐fuzzy inference system with a sigmoid membership function (SMFANFIS). The best pilot patterns in PDGSIP (pilot design with generalized shift invariant property) were determined using the BDGWO algorithm based on the binomial distribution. According to the simulation results, the proposed BDGWO established pilot design with generalized shift invariant property (BDGWO‐DGSIP) achieves higher performance compared other existing approaches such as PDGSIP, TPDGSIP, and LS in terms of NMSE, BER, and SER. Compared to the PDGSIP technique, the proposed PDGSIP‐BDGWO system minimizes NMSE at 10%, BER at about 12%, and SER at 15%.
Veni, vidi, vici? Future spread and ecological impacts of a rapidly expanding invasive predator population
Authors: Nelsen David R. , Corbit Aaron G. , Chuang Angela , Deitsch John F. , Sitvarin Michael I. , Coyle David R. 
Published: November 2023

AbstractEconomic and ecological consequences of invasive species make biological invasions an influential driver of global change. Monitoring the spread and impacts of non‐native species is essential, but often difficult, especially during the initial stages of invasion. The Jorō spider, Trichonephila clavata (L. Koch, 1878, Araneae: Nephilidae), is a large‐bodied orb weaver native to Asia, likely introduced to northern Georgia, U.S. around 2010. We investigated the nascent invasion of T. clavata by constructing species distribution models (SDMs) from crowd‐sourced data to compare the climate T. clavata experiences in its native range to its introduced range. We found evidence that the climate of T. clavata's native range differs significantly from its introduced range. Species distribution models trained with observations from its native range predict that the most suitable habitats in North America occur north of its current introduced range. Consistent with SDM predictions, T. clavata appears to be spreading faster to the north than to the south. Lastly, we conducted surveys to investigate potential ecological impacts of T. clavata on the diversity of native orb weaving spiders. Importantly, Trichonephila clavata was the most common and abundant species observed in the survey, and was numerically dominant at half of the sites it was present in. Our models also suggest that there is lower native orb weaver species richness and diversity closer to where T. clavata was initially found and where it has been established the longest, though human population density complicates this finding. This early study is the first to forecast how widely this spider may spread in its introduced range and explore its potential ecological impacts. Our results add evidence that T. clavata is an invasive species and deserves much more ecological scrutiny.
Density‐dependent within‐patch movement behavior of two competing species
Authors: Cronin James T. , Goddard Jerome , Krivchenia Aaron , Shivaji Ratnasingham 
Published: November 2023

AbstractMovement behavior is central to understanding species distributions, population dynamics and coexistence with other species. Although the relationship between conspecific density and emigration has been well studied, little attention has been paid to how interspecific competitor density affects another species' movement behavior. We conducted releases of two species of competing Tribolium flour beetles at different densities, alone and together in homogeneous microcosms, and tested whether their recaptures‐with‐distance were well described by a random‐diffusion model. We also determined whether mean displacement distances varied with the release density of conspecific and heterospecific beetles. A diffusion model provided a good fit to the redistribution of T. castaneum and T. confusum at all release densities, explaining an average of >60% of the variation in recaptures. For both species, mean displacement (directly proportional to the diffusion rate) exhibited a humped‐shaped relationship with conspecific density. Finally, we found that both species of beetle impacted the within‐patch movement rates of the other species, but the effect depended on density. For T. castaneum in the highest density treatment, the addition of equal numbers of T. castaneum or T. confusum had the same effect, with mean displacements reduced by approximately one half. The same result occurred for T. confusum released at an intermediate density. In both cases, it was total beetle abundance, not species identity that mattered to mean displacement. We suggest that displacement or diffusion rates that exhibit a nonlinear relationship with density or depend on the presence or abundance of interacting species should be considered when attempting to predict the spatial spread of populations or scaling up to heterogeneous landscapes.
Accelerometer vs. other activity measures in heart failure with preserved ejection fraction: the VITALITY‐HFpEF trial
Authors: Butler Javed , Khan Muhammad Shahzeb , Gasior Tomasz , Erickson Tyler R. , Vlajnic Vanja , Kramer Frank , Blaustein Robert O. , Goldsbury David , Roessig Lothar , Lam Carolyn S.P. , Anstrom Kevin J. , Armstrong Paul W. ,   for the VITALITY Study Group
Published: November 2023

AbstractAimsThe relationship between accelerometry data and changes in Kansas City Cardiomyopathy Questionnaire‐Physical Limitation Score (KCCQ‐PLS) or 6 min walk test (6MWT) is not well understood.Methods and resultsVITALITY‐HFpEF accelerometry substudy (n = 69) data were assessed at baseline and 24 weeks. Ordinal logistic regression models were used to assess the association between accelerometry activity and deterioration, improved, or unchanged KCCQ‐PLS (≥8.33 and ≤ −4.17 points) and 6MWT (≥32 vs. ≤ −32 m). KCCQ‐PLS score deteriorated in 16 patients, improved in 34, and was unchanged in 19. 6MWT deteriorated in 8 patients, improved in 21, and was unchanged in 19. Mean accelerometer wear was 21.4 (±2.1) h/day. Changes in hours active from baseline to 24 weeks were not significantly different among patients who exhibited deterioration, improvement, or no change in KCCQ‐PLS [odds ratio (OR) 0.91, 95% confidence interval (CI) 0.71–1.18; P = 0.48] or 6MWT (OR 1.21, 95% CI 0.91–1.60; P = 0.18). Similar lack of association was observed for other accelerometry metrics and change in KCCQ and 6MWT. These findings were unaffected when KCCQ and 6MWT were examined as continuous variables.ConclusionsAccelerometer‐based activity measures did not correlate with subjective or objective standard measures of health status and functional capacity in heart failure with preserved ejection fraction. Further investigation of their relationships to clinical outcomes is required.
Tissue niches and immunopathology through the lens of spatial tissue profiling techniques
Authors: Pascual‐Reguant Anna , Kroh Sandy , Hauser Anja E. 
Published: November 2023

AbstractSpatial organization plays a fundamental role in biology, influencing the function of biological structures at various levels. The immune system, in particular, relies on the orchestrated interactions of immune cells with their microenvironment to mount protective or pathogenic immune responses. The COVID‐19 pandemic has underscored the significance of studying immunity within target organs to understand disease progression and severity. To achieve this, multiplex histology and spatial transcriptomics have proven indispensable in providing a spatial context to protein and gene expression patterns. By combining these techniques, researchers gain a more comprehensive understanding of the complex interactions at the cellular and molecular level in distinct tissue niches, key functional units modulating health and disease. In this review, we discuss recent advances in spatial tissue profiling techniques, highlighting their advantages over traditional histopathology studies. The insights gained from these approaches have the potential to revolutionize the diagnosis and treatment of various diseases including cancer, autoimmune disorders, and infectious diseases. However, we also acknowledge their challenges and limitations. Despite these, spatial tissue profiling offers promising opportunities to improve our understanding of how tissue niches direct regional immunity, and their relevance in tissue immunopathology, as a basis for novel therapeutic strategies and personalized medicine.