bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple‐negative breast cancer who received at least two prior treatments
Authors: Xu Binghe , Ma Fei , Wang Tao , Wang Shusen , Tong Zhongsheng , Li Wei , Wu Xinhong , Wang Xiaojia , Sun Tao , Pan Yueyin , Yao Herui , Wang Xian , Luo Ting , Yang Jin , Zeng Xiaohua , Zhao Weihong , Cong Xiuyu Julie , Chen Jiongjie 
Published: January 2023

AbstractRefractory or relapsing metastatic triple‐negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody‐drug conjugate, targeting human trophoblast cell‐surface antigen 2 (Trop‐2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER‐132‐001 (NCT04454437) was a multicenter, single‐arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21‐day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression‐free survival (PFS), overall survival (OS) and safety. Eighty female Chinese patients (median age 47.6 years; range 24‐69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0‐8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06‐50.30) and 43.8% (95% CI, 32.68‐55.30) of patients, respectively. The median PFS was 5.55 months (95% CI, 4.14‐N/A). SG‐related Grade ≥3 treatment‐emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%) and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pretreated Chinese patients with mTNBC. The observed safety profile was generally manageable.
Transcriptomic analyses reveal three distinct molecular subgroups of Merkel cell carcinoma with differing prognoses
Authors: Sundqvist Benjamin Z. , Kilpinen Sami K. , Böhling Tom O. , Koljonen Virve S. K. , Sihto Harri J. 
Published: January 2023

AbstractMerkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a poor prognosis and an unknown cell of origin. Proffered cells of origin include epithelial stem cells of the hair follicle or interfollicular epidermis, dermal stem cells and pro/pre‐ or pre‐B cells. MCC has also been proposed to have more than one cell of origin and indeed to represent more than one type of carcinoma, currently grouped together due to phenotypic similarities. We explored the heterogeneous nature of MCC by studying the most variably expressed genes with the goal of identifying gene expression patterns that are either clinically relevant or have implications regarding the cell(s) of origin. We performed RNA sequencing on primary tumor samples from 102 patients and identified the top 200 most variably expressed genes. These genes and the tumor samples were hierarchically clustered based on their expression. The functions of three gene clusters exhibiting clearly divergent expression between samples were studied by cross‐referencing the lists of genes with online databases. High expression of a gene cluster related to embryonic developmental processes and low expression of a gene cluster related to neuroendocrine processes distinguished Merkel cell polyomavirus (MCPyV)‐negative tumors from MCPyV‐positive tumors. Furthermore, two prognostically relevant subgroups of MCPyV‐positive MCC were identified based on dichotomic expression of genes related to epidermal structures and processes. We identified three distinct molecular subgroups of MCC with prognostic relevance. We propose that the dichotomic expression of epidermis‐related genes might reflect both an epidermal and a nonepidermal origin for MCPyV‐positive MCC.
COVID‐19 vaccination in pregnancy: Need for global pharmaco‐vigilance
Authors: Sarwal Yamini , Sarwal Rakesh 
Published: January 2023

AbstractCoronavirus infectious disease has been around for more than 2 years as a pandemic, but now appears to have taken the form of an endemic. COVID‐19 vaccination in pregnant women is presently being recommended and followed in most countries. However, robust scientific evidence on safety of the vaccine in the medium or long term, or regarding any adverse effects, is lacking. We searched the PubMed and gray literature for evidence on medium‐ or long‐term effects of COVID‐19 vaccination during pregnancy on the mother or her fetus/newborn and found limited data on this subject. Moreover, available evidence comes almost exclusively from the Western world. Any adverse effects of COVID‐19 vaccination during or after pregnancy may take time to manifest. Therefore, there is a need to keep the cohort of vaccinated women and their children under scrutiny for any possible adverse effects. This is also needed to build confidence in the long term in the vaccines. A global pharmaco‐vigilance or post‐marketing surveillance network covering pregnant recipients of COVID‐19 vaccines can identify and help to address any medium‐ or long‐term adverse effects of the COVID‐19 vaccines on pregnancy and the newborn.
Strategies and tools in illumina and nanopore‐integrated metagenomic analysis of microbiome data
Authors: Xia Yu , Li Xiang , Wu Ziqi , Nie Cailong , Cheng Zhanwen , Sun Yuhong , Liu Lei , Zhang Tong 
Published: January 2023

AbstractMetagenomic strategy serves as the foundation for the ecological exploration of novel bioresources (e.g., industrial enzymes and bioactive molecules) and biohazards (e.g., pathogens and antibiotic resistance genes) in natural and engineered microbial systems across multiple disciplines. Recent advancements in sequencing technology have fostered rapid development in the field of microbiome research where an increasing number of studies have applied both illumina short reads (SRs) and nanopore long reads (LRs) sequencing in their metagenomic workflow. However, given the high complexity of an environmental microbiome data set and the bioinformatic challenges caused by the unique features of these sequencing technologies, integrating SRs and LRs is not as straightforward as one might assume. The fast renewal of existing tools and growing diversity of new algorithms make access to this field even more difficult. Therefore, here we systematically summarized the complete workflow from DNA extraction to data processing strategies for applying illumina and nanopore‐integrated metagenomics in the investigation in environmental microbiomes. Overall, this review aims to provide a timely knowledge framework for researchers that are interested in or are struggling with the SRs and LRs integration in their metagenomic analysis. The discussions presented will facilitate improved ecological understanding of community functionalities and assembly of natural, engineered, and human microbiomes, benefiting researchers from multiple disciplines.
Destabilized microbial networks with distinct performances of abundant and rare biospheres in maintaining networks under increasing salinity stress
Authors: Li Changchao , Jin Ling , Zhang Chao , Li Shuzhen , Zhou Tong , Hua Zhongyi , Wang Lifei , Ji Shuping , Wang Yanfei , Gan Yandong , Liu Jian 
Published: January 2023

AbstractGlobal changes such as seawater intrusion and freshwater resource salinization increase environmental stress imposed on the aquatic microbiome. A strong predictive understanding of the responses of the aquatic microbiome to environmental stress will help in coping with the “gray rhino” events in the environment, thereby contributing to an ecologically sustainable future. Considering that microbial ecological networks are tied to the stability of ecosystem functioning and that abundant and rare biospheres with different biogeographic patterns are important drivers of ecosystem functioning, the roles of abundant and rare biospheres in maintaining ecological networks need to be clarified. Here we showed that, with the increasing salinity stress induced by the freshwater‐to‐seawater transition, the microbial diversity reduced significantly and the taxonomic structure experienced a strong succession. The complexity and stability of microbial ecological networks were diminished by the increasing stress. The composition of the microorganisms supporting the networks underwent sharp turnovers during the freshwater‐to‐seawater transition, with the abundant biosphere behaving more robustly than the rare biosphere. Notably, the abundant biosphere played a much more important role than the rare biosphere in stabilizing ecological networks under low‐stress environments, but the difference between their relative importance narrowed significantly with the increasing stress, suggesting that the environmental stress weakened the “Matthew effect” in the microbial world. With in‐depth insights into the aquatic microbial ecology under stress, our findings highlight the importance of adjusting conservation strategies for the abundant and rare biospheres to maintain ecosystem functions and services in response to rising environmental stress.
Prevalence of veterinary antibiotics in natural and organic fertilizers from animal food production and assessment of their potential ecological risk
Authors: Patyra Ewelina , Nebot Carolina , Gavilán Rosa Elvira , Kwiatek Krzysztof , Cepeda Alberto 
Published: January 2023

AbstractBACKGROUNDVeterinary antibiotics are emerging contaminants and enter into soil principally by agricultural application of organic fertilizers. This article presents the results of the research obtained for the analyzed 70 samples of fertilizers (pig and poultry manure and slurry and digestate) for various classes of antibiotics.RESULTSDoxycycline, oxytetracycline, tetracycline, lincomycin, tiamulin and enrofloxacin were found in tested samples. Doxycycline was found as a dominant compound, and its highest concentration was 175 mg/kg in pig manure. This investigation indicated that fertilization with manure, especially animal feces, might be the primary source of antibiotics. Additionally, a risk assessment based on a risk quotient was carried out, which showed that the determined concentrations of antibiotics in fertilizers may pose a threat to soil microorganisms.CONCLUSIONSResults suggested that the ecological risk effects of antibiotic contamination on soil bases and their potential adverse risk on human health needs special attention. © 2023 Society of Chemical Industry.
Environmental and ecological drivers of harmful algal blooms revealed by automated underwater microscopy
Authors: Kenitz Kasia M. , Anderson Clarissa R. , Carter Melissa L. , Eggleston Emily , Seech Kristi , Shipe Rebecca , Smith Jayme , Orenstein Eric C. , Franks Peter J. S. , Jaffe Jules S. , Barton Andrew D. 
Published: January 2023

AbstractIn recent years, harmful algal blooms (HABs) have increased in their severity and extent in many parts of the world and pose serious threats to local aquaculture, fisheries, and public health. In many cases, the mechanisms triggering and regulating HAB events remain poorly understood. Using underwater microscopy and Residual Neural Network (ResNet‐18) to taxonomically classify imaged organisms, we developed a daily abundance record of four potentially harmful algae (Akashiwo sanguinea, Chattonella spp., Dinophysis spp., and Lingulodinium polyedra) and major grazer groups (ciliates, copepod nauplii, and copepods) from August 2017 to November 2020 at Scripps Institution of Oceanography pier, a coastal location in the Southern California Bight. Random Forest algorithms were used to identify the optimal combination of environmental and ecological variables that produced the most accurate abundance predictions for each taxon. We developed models with high prediction accuracy for A. sanguinea (), Chattonella spp. (), and L. polyedra (), whereas models for Dinophysis spp. showed lower prediction accuracy (). Offshore nutricline depth and indices describing climate variability, including El Niño Southern Oscillation, Pacific Decadal Oscillation, and North Pacific Gyre Oscillation, that influence regional‐scale ocean circulation patterns and environmental conditions, were key predictor variables for these HAB taxa. These metrics of regional‐scale processes were generally better predictors of HAB taxa abundances at this coastal location than the in situ environmental measurements. Ciliate abundance was an important predictor of Chattonella and Dinophysis spp., but not of A. sanguinea and L. polyedra. Our findings indicate that combining regional and local environmental factors with microzooplankton populations dynamics can improve real‐time HAB abundance forecasts.
Loss of CBX2 causes genomic instability and Wnt activation in high grade serous ovarian carcinoma cells
Authors: Ma Yujia , Liu Lin , Wei Zheng , Zhu Mengna , Huang Lin , Wang Shan , Yi Xiaoqing , Ying Feiquan , Zhao Simei , Cai Jing , Wang Zehua , Sun Si 
Published: January 2023

AbstractHigh grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis‐associated PRC1 components were identified through data‐mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3. Complete loss of CBX2 by CRISPR‐cas9 editing (CBX2KO) destabilized genome stability with increased spontaneous chromosomal breaks and tendency to polyploidy accompanied by disrupted cell cycle especially stalled G2/M transition and caused severe cell death. Wnt/β‐catenin/LEF1/TCF7L1 was activated in surviving OVCAR4‐CBX2KO clones to bypass the crisis caused by loss of CBX2. The relieve of TCF7L1 core‐promoter region occupied by CBX2 might be one of the possible explanations to TCF7L1 increase in OVCAR4‐CBX2KO clones. Subcutaneous tumor model further validated that depletion of CBX2 repressed HGSOC cell line derived tumor growth. High immunohistochemistry score of CBX2 in primary ovarian cancer tissue associated with advanced clinical stage (p = 0.033), poor overall survival (HR = 3.056, 95% CI: 1.024−9.123), and progression free survival (HR = 4.455, 95% CI: 1.513−13.118) in HGSOC. Overall, our results suggested that CBX2 was a promising prognostic factor and therapeutic target in HGSOC.
Using Movement Disorder Society Unified Parkinson's Disease Rating Scale Parts 2 and 3 Simultaneously: Combining the Patient Voice with Clinician Ratings
Authors: Guo Yuanyuan , Goetz Christopher G. , Stebbins Glenn T. , Mestre Tiago A. , Luo Sheng 
Published: January 2023

AbstractBackgroundRegulatory recommendations favor outcomes combining objective and patient input. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), the most commonly used scale in Parkinson's disease (PD), includes patient and investigator ratings in distinct parts, but original clinimetric analyses failed to confirm the validity of combining parts by simple summing.ObjectivesThe aim was to develop clinimetrically valid constructs for combining patient‐reported Part 2 and investigator‐rated Part 3 MDS‐UPDRS scores.MethodsUsing 7888 MDS‐UPDRS scores, we assessed construct validity of combined Part 2 and Part 3 items using exploratory factor analysis (EFA) and graded item response theory (IRT) with threshold criteria: comparative fit index ≥0.9 (EFA) and discrimination parameters ≥0.65 (IRT).ResultsThe direct sum of Parts 2 + 3 failed to meet the threshold for a valid outcome of PD severity (comparative fit index, CFI = 0.855). However, a two‐domain construct combining item scores for tremor and non‐tremor domains from Parts 2 and 3 confirmed validity, meeting both EFA and IRT criteria as distinct but correlated indices of disease severity (CFI = 0.923; discrimination mean 2.197 ± 0.480 [tremor] and 1.737 ± 0.344 [non‐tremor] domains).ConclusionsThe sum of Parts 2 + 3 is not clinimetrically sound. However, considering tremor and non‐tremor items of both Parts 2 and 3 as two outcomes results in a valid summary of PD motor severity that leverages simultaneous patient‐ and investigator‐derived measures. This analytic application addresses regulatory prioritizations and retains the well‐validated MDS‐UPDRS items. In future interventional trials, we suggest that tremor and non‐tremor components of PD motor severity from Parts 2 + 3 be monitored and analyzed to accurately detect objective changes that integrate the patient's voice. © 2023 International Parkinson and Movement Disorder Society.
Quantification of blood–brain barrier water exchange and permeability with multidelay diffusion‐weighted pseudo‐continuous arterial spin labeling
Authors: Shao Xingfeng , Zhao Chenyang , Shou Qinyang , St Lawrence Keith S. , Wang Danny J. J. 
Published: January 2023

PurposeTo present a pulse sequence and mathematical models for quantification of blood–brain barrier water exchange and permeability.MethodsMotion‐compensated diffusion‐weighted (MCDW) gradient‐and‐spin echo (GRASE) pseudo‐continuous arterial spin labeling (pCASL) sequence was proposed to acquire intravascular/extravascular perfusion signals from five postlabeling delays (PLDs, 1590–2790 ms). Experiments were performed on 11 healthy subjects at 3 T. A comprehensive set of perfusion and permeability parameters including cerebral blood flow (CBF), capillary transit time (τc), and water exchange rate (kw) were quantified, and permeability surface area product (PSw), total extraction fraction (Ew), and capillary volume (Vc) were derived simultaneously by a three‐compartment single‐pass approximation (SPA) model on group‐averaged data. With information (i.e., Vc and τc) obtained from three‐compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual kw quantification, and Ew and PSw can be estimated from long PLD (2490/2790 ms) signals. MCDW‐pCASL was compared with a previously developed diffusion‐prepared (DP) pCASL sequence, which calculates kw by a two‐compartment SPA model from PLD = 1800 ms signals, to evaluate the improvements.ResultsUsing three‐compartment SPA modeling, group‐averaged CBF = 51.5/36.8 ml/100 g/min, kw = 126.3/106.7 min−1, PSw = 151.6/93.8 ml/100 g/min, Ew = 94.7/92.2%, τc = 1409.2/1431.8 ms, and Vc = 1.2/0.9 ml/100 g in gray/white matter, respectively. Temporal SNR of MCDW‐pCASL perfusion signals increased 3‐fold, and individual kw maps calculated by the LRL method achieved higher spatial resolution (3.5 mm3 isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm3).ConclusionMCDW‐pCASL allows visualization of intravascular/extravascular ASL signals across multiple PLDs. The three‐compartment SPA model provides a comprehensive measurement of blood–brain barrier water dynamics from group‐averaged data, and a simplified LRL method was proposed for individual kw quantification.
Discrete empirical interpolation for hyper‐reduction of hydro‐mechanical problems in groundwater flow through soil
Authors: Nasika Christina , Díez Pedro , Gerard Pierre , Massart Thierry J. , Zlotnik Sergio 
Published: January 2023

AbstractThe recent surge in the availability of sensor data and computational resources has fostered the development of technologies for optimization, control, and monitoring of large infrastructures, integrating data and numerical modeling. The major bottleneck in this type of technologies is the model response time, since repetitive solutions are typically required. To reduce the computational time, reduced order models (ROMs) are used as surrogates for expensive finite element (FE) simulations enabling the use of complex models in this type of applications. In this work, ROMs are explored for the solution of the fully coupled hydro‐mechanical system of equations that governs the water flow through partially saturated soil. The POD‐based Reduced Basis Method and the Discrete Empirical Interpolation Method (DEIM), as well as its localized version (LDEIM), are examined in solving a parametrized problem simulating the mechanical loading of an embankment dam. Hydraulic and mechanical soil properties are considered as parameters. It is shown that the combination of these methods results in simulations that require 1/10 to 1/100 of the FE response time. Moreover, the method is shown to yield scaling efficiency gains with increasing problem size.
Maximizing the weighted number of just‐in‐time jobs in a distributed flow‐shop scheduling system
Authors: Shabtay Dvir 
Published: January 2023

AbstractWe study a set of scheduling problems in a distributed flow‐shop scheduling system consisting of several flow‐shop production systems (factories) working in parallel. Our objective is to assign the jobs to the factories, and to devise a job schedule for each of the factories such that the weighted number of jobs completed in just‐in‐time mode is maximized. We classify computational complexity of the problems, including the special cases of unit weights and job‐ or machine‐independent processing times.
Automatic generation of interpretable hyperelastic material models by symbolic regression
Authors: Abdusalamov Rasul , Hillgärtner Markus , Itskov Mikhail 
Published: January 2023

AbstractIn this article, we present a new procedure to automatically generate interpretable hyperelastic material models. This approach is based on symbolic regression which represents an evolutionary algorithm searching for a mathematical model in the form of an algebraic expression. This results in a relatively simple model with good agreement to experimental data. By expressing the strain energy function in terms of its invariants or other parameters, it is possible to interpret the resulting algebraic formulation in a physical context. In addition, a direct implementation of the obtained algebraic equation for example into a finite element procedure is possible. For the validation of the proposed approach, benchmark tests on the basis of the generalized Mooney–Rivlin model are presented. In all these tests, the chosen ansatz can find the predefined models. Additionally, this method is applied to the multi‐axial loading data set of vulcanized rubber. Finally, a data set for a temperature‐dependent thermoplastic polyester elastomer is evaluated. In latter cases, good agreement with the experimental data is obtained.