bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multicenter, Phase II study
Authors: Cheng Yu , Teng Zan , Zhang Yanqiao , Jin Bo , Zheng Zhendong , Man Li , Wang Zhenghua , Teng Yuee , Yu Ping , Shi Jing , Luo Ying , Wang Ying , Zhang Jingdong , Zhang Huijuan , Liu Jiwei , Chen Hao , Xiao Jiawen , Zhao Lei , Zhang Lingyun , Jiang Yu , Chen Ying , Zhang Jian , Wang Chang , Liu Sa , Qu Jinglei , Qu Xiujuan , Liu Yunpeng 
Published: February 2024

Abstract

Background
Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size.
Methods
This is a prospective open-label, single-arm, multicenter, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety.
Results
A total of 108 patients were enrolled between October 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1–5.7) and median overall survival was 13.1 months (95% CI 12.2–15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths.
Conclusions
Raltitrexed is strongly recommended as second-line treatment after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients).
Trial registration
ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.
WITHDRAWN: Creating Highly Efficient Stretchable OLEDs with Nanowavy Structures for Angle-Independent Narrow Band Emission
Authors: Suh Min Chul , Nimbalkar Ajay , Irfan Aqsa 
Published: February 2024

Abstract

Stretchable organic light-emitting diodes (SOLEDs) have been the challenging class of OLED as they have limited processability to fabricate a design that can withstand external deformation. Herein, we demonstrated the first highly efficient geometrical stretchable top-emitting OLED by incorporating the prestretched optical adhesive film. Compared to a reference glass substrate, an optical adhesive substrate facilitates more extraction of light that would trap inside the device due to various light trapping modes. The experimental and theoretical characterizations verified the enhancement of device efficiencies with the light extraction phenomenon brought by the nanowavy corrugated structures. In addition, GSOLED shows stability in stretchable conditions and displayed a narrower emission spectrum with improved color purity by controlling the thickness of electrodes and organic layers. The full width at half maximum (FWHM) of 21 nm shows narrowband emission with a high current efficiency and EQE of 221 cd A− 1 and 51.30% respectively. This work marks a significant step forward, providing unprecedented insights into the factors influencing device performance in current and future material systems for stretchable organic light-emitting diodes.
Predicting humoral responses to primary and booster SARS-CoV-2 mRNA vaccination in people living with HIV: a Machine Learning approach
Authors: Montesi Giorgio , Augello Matteo , Polvere Jacopo , Marchetti Giulia , Medaglini Donata , Ciabattini Annalisa 
Published: February 2024

Abstract

Background
SARS-CoV-2 mRNA vaccines are highly immunogenic in people living with HIV (PLWH) on effective antiretroviral therapy (ART). However, whether viro-immunologic parameters or other factors affect immune responses to vaccination is debated. This study aimed to develop a Machine Learning (ML)-based model able to predict the humoral response to mRNA vaccines in PLWH and to assess the impact of demographic and clinical variables on antibody production overtime.
Methods
Different ML-algorithms have been compared in the setting of a longitudinal observational study involving 497 PLWH, after primary and booster vaccination. Both Generalized Linear Models and non-linear Models (Tree Regression and Random Forest [RF]) were trained and tested.
Results
Non-linear algorithms showed better ability to predict vaccine-elicited humoral responses. The best-performing RF model identified few variables as more influential, within 40 clinical, demographic, and immunological factors. In particular, previous SARS-CoV-2 infection, BMI, CD4 T-cell count and CD4/CD8 ratio were positively associated with the primary cycle immunogenicity, yet their predictive value diminished with the administration of booster doses.
Conclusions
RF ML-algorithm accurately predicted humoral responses to SARS-CoV-2 mRNA vaccination in PLWH, highlighting that who are underweight, those with poor immune recovery on ART, and those without previous SARS-CoV-2 infection have reduced humoral responses to SARS-CoV-2 mRNA primary vaccination. The administration of booster doses overcomes the influence of these factors, suggesting that further vaccine doses could be offered to PLWH as the humoral immunity wanes over time.
First insight into the whole-genome sequence variations in clarithromycin- resistant Helicobacter pylori clinical isolates in Russia
Authors: Starkova Daria , Gladyshev Nikita , Polev Dmitrii , Saitova Alina , Egorova Svetlana , Svarval Alena 
Published: February 2024

Abstract

Clarithromycin (CLR) is a key drug to treat Helicobacter pylori infection, however the data on CLR resistance patterns in Russia are missing. Here, we applied next-generation sequencing (NGS)-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variations, identify putative markers of CLR resistance and correlate them with phenotypic drug susceptibility testing (DST). The phenotypic susceptibility of 44 H. pylori isolates (2014–2022) to CLR was determined by disc diffusion method. All isolates were undergone whole-genome sequencing and submitted to GenBank. Twenty-three H. pylori isolates were phenotypically CLR-resistant and 21- were CLR-susceptible. Based on complete sequence analysis, we showed that among all genetic variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic DST. For the first time, the average number of nucleotide variants in 108 virulence-associated genes between resistant and susceptible groups were compared. Moreover, this study presents the first WGS insight into genetic diversity of H. pylori in Russia with a particular focus on the molecular basis of drug resistance: the novel mutations were described as potential markers for the resistance development. Of these, the most prominent was frameshift deletion in HP0820 coding region, which is a good candidate for further investigation.
Partner quality matters - overyielding in a maize/soybean mixture depends on the initiator of common mycorrhizal networks
Authors: Liu Yalin , Kuyper Thomas W. , Zhang Lin , Li Chunjie 
Published: February 2024

Abstract

Aims
Cereal/legume intercropping has advantages in yield and nutrient uptake. However, how common mycorrhizal networks (CMNs), formed by arbuscular mycorrhizal fungi (AMF) play a role in those benefits has not been fully clarified. This study aimed to explore how CMNs initiated by different host plants affected plant performance and nutrient acquisition in a maize/soybean mixture.
Methods
Microcosms with three compartments were used; these were separated by 30-µm nylon mesh. Two compartments were root compartments (RCs), and the third compartment was a hyphal compartment (HC). One RC was inoculated with the AMF Rhizophagus irregularis and the plant in this compartment was referred to as CMNs donor, and the plant in the other RC compartment as CMNs receiver.
Results
Maize biomass was twice that of soybean. Nitrogen (N) and phosphorus (P) content of both maize and soybean were higher in the presence of CMNs compared with the treatment without AMF. When maize was the CMNs donor, shoot biomass, N and P content of the mixture were higher than the expected biomass, N and P content based on monocultures, and effect not seen when soybean was the CMNs donor. Overyielding in biomass but not in N and P content, suggesting a disconnect between an AMF-induced increase in N, P acquisition and biomass increases.
Conclusion
CMNs asymmetrically increased biomass, N and P content of the larger-biomass species in this crop mixture compared with monocultures.
Factors Influencing Covid-19 Vaccination Uptake Among Nurses and Midwives Students in Select Ghanaian Multi-Training Settings Using the Theory of Reasoned Action.
Authors: Owusu Lydia Boampong , Zakaria Abdul-Fatawu Suglo , Collins Anita , Nukpezah Ruth Nimota , Mensah Olivia Nyarko 
Published: February 2024

Abstract
Background
The investigation into the adoption of the COVID-19 vaccine within diverse populations has undergone rigorous examination. A thorough analysis has illuminated that 48% of healthcare professionals and 34% of healthcare students have embraced the vaccination. However, a noticeable dearth of research exists regarding the vaccination uptake among Ghanaian nursing and midwifery students. Consequently, this study seeks to elucidate the landscape of COVID-19 vaccine acceptance among Ghanaian student nurses and midwives across various settings.
Methods
A descriptive cross-sectional convenient sample design was adopted. An adapted Vaccination Attitude scale questionnaire was administered online to 557 nurses and midwives’ students at two diploma and two bachelor's degree-granting nursing and midwifery educational institutions in southern and northern Ghana. The data were analysed using SPSS 25.
Results
Eighty percent of the nurses and midwives were vaccinated. According to the TRA, unknown COVID-19 vaccine adverse effects, the notion that natural immunity lasts longer than immunisation and the chance that the vaccine may create future difficulties affect students' vaccine uptake. Risk perception led to COVID-19 vaccine uptake. Age and vaccination perception were weakly correlated with COVID-19 vaccination uptake. Age: Spearman's rank correlation, rs = .12, p = .005; perception: -0.14, p = .001).
Conclusion
Using the TRA to analyse the factors influencing COVID-19 vaccination, students who desired the vaccination strongly thought it would protect them and others, suggesting that they would follow the suggestion. Students were vaccinated because they believed that COVID-19 was important and dangerous, felt responsible for their health, and followed the authorities' advice. This study revealed that age and vaccination perception impact COVID-19 vaccine uptake.
LARP7 liquid-liquid phase separation restrains HIV replication
Authors: Li Weihua , Li Zhuoxin , Fang Xiya , Zhao Bing , Li Tingting , Liu Ran , shen Yezhuang , Guo Zenglin , Wang Wen , Zhang Biyu , Han Qiu-Ying , Xu Xin , Wang Kai , Yin Libing , Gong Wei-Li , Li Ai-Ling , Zhou Tao , Li Teng 
Published: February 2024

Abstract
HIV-1 initiates replication by hijacking host transcription factor P-TEFb through transactivator Tat. The majority of P-TEFb is kept inactive by 7sk snRNP until brought to transcription initiation complex by cellular or viral transactivators that dramatically accelerate transcription and enable full-length transcripts. Understanding the mechanism behind the release of P-TEFb from 7sk snRNP is key in blocking the initial step of HIV-1 replication. Here, we report that HIV-1 infection triggers liquid-liquid phase separation (LLPS) of LARP7, the core component of the 7sk snRNP, in T cells. We demonstrated that LARP7 is capable of forming condensates with Tat, and the conserved lysine residues in the intrinsically disordered region (IDR) of LARP7 are crucial for its phase separation and inhibition of Tat-mediated transcription. Our findings unravel a new mechanism that P-TEFb and Tat are retained in LARP7 condensates and HIV-1 transcription is restrained until accumulated Tat breaks the balance, which offer novel insights into the host protein's defense against HIV-1 infection through LLPS, highlighting the potential of targeting the phase separation of LARP7 as a new strategy for fighting HIV-1/AIDS.
Research on alkali-carbonate reaction (ACR) and damage of freeze-thaw for pure dolomite as concrete coarse aggregate
Authors: Chen Yulin , Xiong Xuefei , Wang Ding , Zhou Xianliang , Liu Changwu , Xu Zhipeng 
Published: February 2024

Abstract
Alkali-carbonate reaction (ACR) is one of the important components of alkali aggregate reaction (AAR) in concrete structures, which may lead to a serious damage for the concrete construction and effect on the durability of concrete projects adversely. Previous research has systematically investigated the possibility of ACR in dolomitic limestone. However, there is limited literature available for ACR in pure dolomite aggregate specifically. Therefore, this paper aims to investigates whether pure dolomite occur ACR and the freeze-thaw resistance of pure dolomite coarse aggregate concrete (PDCAC) due to the raw materials produced in the southwest of China, which is cold in winter. To determine the alkali activity of pure dolomite, three methods were employed: lithofacies method (LM), rock-cylinder method (RCM), and rapid preliminary screening test for carbonate aggregates (AAR-5). Lithofacies method confirmed that the dolomite used in this paper was pure almost, and no SiO2 content, ruling out the possibility of alkali-silica reaction (ASR). The rock-cylinder method indicated a reduction in length during the 84-day test period, which indicates the absence of ACR. Subsequently, the AAR-5 method was used to test ACR, and the samples exhibited a length expansion rate of far less than 0.1% within 28 days, which further confirmed the absence of alkali activity in pure dolomite. Finally, the freeze-thaw cycles test was carried out on the concrete with pure dolomite as concrete coarse aggregate. The results revealed no significant spalling on the concrete surface after 200 freeze-thaw cycles, and pure dolomite coarse aggregate concrete can withstand freeze-thaw damage to a certain extent.
Genetic Diversity Between and Within Opuntia Spp. Species Revealed by Molecular Marker Issr.
Authors: DE ARAÚJO JOSEILSON MOREIRA , Rêgo Maílson Monteiro do , Rêgo Elizanilda Ramalho do 
Published: February 2024

Abstract
Opuntia fodder palm spp., constitutes a viable solution for animal feeding in arid and semi-arid regions due to its easy adaptation to this type of environment, its physiological characteristics and low production cost. Given its importance, it is essential to know more about its genetic characteristics. One of the most used techniques is molecular markers. Within this context, the objective of this work was to evaluate the genetic diversity of 40 Opuntia genotypes spp. from the Active Germplasm Bank-BAG of the National Semiarid Institute-INSA, using Inter Simple molecular markers Sequence Repeats - ISSR. Extraction of Deoxyribonucleic Acid - DNA from the accessions was carried out using the DNeasy Plant Mini® Kit ( Qiagen ). 11 ISSR oligonucleotide primers ( primers ) were used. With this technique, 839 fragments were amplified, distributed across 91 loci. From the genetic distances of the 40 accessions, nine groups were constructed. It was found that there is high genetic diversity between and within the species evaluated, contributing to expanding the genetic base of segregating populations. It is suggested intraspecific crossing between accessions 87 and 117 and interspecific crossing with accessions 1 x 119, 86 x ? (101), 86 x 135, 88 x 135, ?(101) x 135.
Lymphovascular invasion affects prognosis of colorectal cancer liver metastasis underwent primary resection: a propensity score matching analysis
Authors: li wei , Liu Bo , Xiang Xingxing , Zhang Qun , Yang QingLin , Cao Yinghao , Liu Tao 
Published: February 2024

Abstract
Background: Lymphovascular invasion (LVI) is associated with poor prognosis in a variety of malignancies; however, its prognostic value has not been fully defined in patients with colorectal cancer with liver metastases (CRCLM). The aim of this study was to investigate the impact of lymphovascular invasion on long-term postoperative recurrence and survival in patients with CRCLM.
Methods：Clinicopathologic data were retrospectively collected from patients who underwent primary resection for CRCLM at Wuhan Union Hospital from 2013 to 2018. To reduce potential confounders and selection bias, we used propensity score matching (PSM) to compare the clinicopathologic characteristics and long-term prognostic outcomes of patients in the LVI(+) and LVI(-) groups. Cox unifactorial and multifactorial analyses were used to screen relevant factors affecting patient prognosis, and Kaplan-Meier curves were plotted to compare differences in patient OS and DFS. The predictive power of independent factors on patients' long-term prognosis was assessed using receiver operating characteristic ROC) curves and area under the curve (AUC).
Results: After PSM, 230 patients were enrolled in the study (n=115 per group). Multifactorial analysis revealed that LVI was an independent prognostic factor for OS and DFS (hazard ratio [HR], 1.424; 95% confidence interval [CI], 1.004–2.022; P=0.048 and HR, 1.452; 95% CI, 1.020–2.069; p=0.039, respectively). In the LVI(-) group, postoperative chemotherapy did not significantly improve OS or DFS; however, in the LVI(+) group, those who received chemotherapy had significantly improved OS (HR: 2.424 , 95% CI: 1.471−3.992; P=0.00034) and DFS (HR: 2.164, 95% CI. 1.328−3.525; P=0.0014) compared with patients not treated with chemotherapy. In the LVI(+) group, the AUC for the OS AUROC curves was more favorable compared with after PSM (AUC at 3 years: 0.786 vs 0.903; AUC at 5 years: 0.744 vs 0.889). For DFS, the area under the AUROC curve was also better in the LVI(+) subgroup compared with after PSM (AUC at 3 years: 0.874 vs 0.786; AUC at 5 years: 0.863 vs 0.744).
Conclusions: LVI significantly impacts long-term survival and prognosis in patients with CRLM undergoing primary resection and is an independent prognostic factor for OS and DFS. Postoperative chemotherapy significantly improved the long-term prognosis of patients with LVI(+).
ABA-activated nanomolar Ca2+-CPK signalling controls root cap cycle plasticity and stress adaptation
Authors: Liu Kun-Hsiang , Lin Ziwei , Guo ying , Zhang Ruiyuan , Li Yiming , Wu Yue , Sheen Jen 
Published: February 2024

Abstract

Abscisic acid (ABA) regulates plant stress adaptation, growth, and reproduction. Despite extensive ABA-Ca2+ signaling links, imaging ABA-induced Ca2+ concentration increase was challenging, except in guard cells. Here, we visualize ABA-triggered [Ca2+] dynamics in diverse organs and cell types using a genetically-encoded Ca2+ ratiometric sensor (CRS) with nanomolar affinity and large dynamic range. Subcellular-targeted CRS reveals time-resolved and unique spatiotemporal Ca2+ signatures from the initial plasma-membrane nanodomain, cytosol, to nuclear oscillation. Via receptors and sucrose-non-fermenting1-related protein kinases (SNRK2.2,2.3,2.6), ABA activates nanomolar Ca2+ waves and Ca2+-sensor protein kinase (CPK10,30,32) signalling in the root cap cycle from stem cells to cell detachment. Surprisingly, unlike the prevailing NaCl-stimulated micromolar Ca2+ spike, salt stress induces a nanomolar Ca2+ wave through ABA signaling, repressing key transcription factors dictating cell fate and enzymes crucial to root cap maturation and slough. Our findings uncover ultrasensitive ABA-Ca2+-CPK signalling in modulating root cap cycle plasticity in adaptation to adverse environments.
Fenofibrate positively affects gene expression profiles and metabolic pathway of high-fat diet-treated hamsters gut microbiota
Authors: Liu Qifeng 
Published: February 2024

Abstract
Background: Fenofibrate is a compound with diverse biological properties that can be utilized to lower blood lipids. Understanding the impact of the gut microbiota in hyperlipidemia is vital for controlling systemic inflammation and improving serum lipid control. Nevertheless, the specific effects of fenofibrate on the phenotype and gene expression of resident gut bacteria, as well as its influence on the transformation of microbial metabolism into functional networks, remain unclear. In this study, our aimed to examine the gene expression profile and metabolic pathways of the gut microbiota in a hamster model fed a high-fat diet (HFD) and administered fenofibrate.
Results: The results indicated that the group treated with fenofibrate exhibited higher levels of beneficial bacterial species associated with health, including Bacteroides ovatus, Bifidobacterium animalis, Bacteroides intestinalis, Allobaculum stercoricanis, Lactobacillus reuteri, and Bacteroides acidifaciens, in comparison to the HFD group. Additionally, analysis of metabolic pathways demonstrated that dietary fenofibrate significantly enhanced the biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and pyrimidine metabolism, while reducing glyoxylate and dicarboxylate metabolism, tyrosine metabolism, tryptophan metabolism, and nonribosomal peptide structures. Furthermore, these metabolic pathway changes were associated with relative alterations in the abundance of genes from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, namely K01667, K11358, K13953, K04072, K06131, K00655, K04567, K02864, K06409, K05366, K01867, K21071, and K13292. Moreover, significant changes were observed in the expression of enzymes and genes related to carbohydrate and antibiotic resistance, such as glycosyltransferase family 51 (GT51) as well as adeC, carA, and MexT.
Conclusions: Dietary fenofibrate exerted significant effects on genes and pathways related to lipid, energy, and amino acid metabolism, ultimately promoting a healthier colonic environment for the host. And these findings contribute to a better understanding of the mechanism of action of fenofibrate and provide a valuable foundation for future experimental and clinical studies, aiming to explore its practical applications.