bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine-learning based investigation of prognostic indicators for oncological outcome of pancreatic ductal adenocarcinoma
Authors: Chang Jeremy , Liu Yanan , Saey Stephanie A. , Chang Kevin C. , Shrader Hannah R. , Steckly Kelsey L. , Rajput Maheen , Sonka Milan , Chan Carlos H. F. 
Published: December 2022

IntroductionPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Surgical resection remains the only potential curative treatment option for early-stage resectable PDAC. Patients with locally advanced or micrometastatic disease should ideally undergo neoadjuvant therapy prior to surgical resection for an optimal treatment outcome. Computerized tomography (CT) scan is the most common imaging modality obtained prior to surgery. However, the ability of CT scans to assess the nodal status and resectability remains suboptimal and depends heavily on physician experience. Improved preoperative radiographic tumor staging with the prediction of postoperative margin and the lymph node status could have important implications in treatment sequencing. This paper proposes a novel machine learning predictive model, utilizing a three-dimensional convoluted neural network (3D-CNN), to reliably predict the presence of lymph node metastasis and the postoperative positive margin status based on preoperative CT scans.MethodsA total of 881 CT scans were obtained from 110 patients with PDAC. Patients and images were separated into training and validation groups for both lymph node and margin prediction studies. Per-scan analysis and per-patient analysis (utilizing majority voting method) were performed.ResultsFor a lymph node prediction 3D-CNN model, accuracy was 90% for per-patient analysis and 75% for per-scan analysis. For a postoperative margin prediction 3D-CNN model, accuracy was 81% for per-patient analysis and 76% for per-scan analysis.DiscussionThis paper provides a proof of concept that utilizing radiomics and the 3D-CNN deep learning framework may be used preoperatively to improve the prediction of positive resection margins as well as the presence of lymph node metastatic disease. Further investigations should be performed with larger cohorts to increase the generalizability of this model; however, there is a great promise in the use of convoluted neural networks to assist clinicians with treatment selection for patients with PDAC.
Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer
Authors: Spira Alexander , Awada Ahmad , Isambert Nicolas , Lorente David , Penel Nicolas , Zhang Yue , Ojalvo Laureen S. , Hicking Christine , Rolfe P. Alexander , Ihling Christian , Dussault Isabelle , Locke George , Borel Christian 
Published: December 2022

BackgroundWe report the clinical activity, safety, and identification of a predictive biomarker for bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβRII (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1, in patients with advanced triple-negative breast cancer (TNBC).MethodsIn this expansion cohort of a global phase 1 study, patients with pretreated, advanced TNBC received bintrafusp alfa 1200 mg every 2 weeks intravenously until disease progression, unacceptable toxicity, or withdrawal. The primary objective was confirmed best overall response by RECIST 1.1 assessed per independent review committee (IRC).ResultsAs of May 15, 2020, a total of 33 patients had received bintrafusp alfa, for a median of 6.0 (range, 2.0-48.1) weeks. The objective response rate was 9.1% (95% CI, 1.9%-24.3%) by IRC and investigator assessment. The median progression-free survival per IRC was 1.3 (95% CI, 1.2-1.4) months, and median overall survival was 7.7 (95% CI, 2.1-10.9) months. Twenty-five patients (75.8%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 patients (15.2%); no patients had a grade 4 TRAE. There was 1 treatment-related death (dyspnea, hemolysis, and thrombocytopenia in a patient with extensive disease at trial entry). Responses occurred independently of PD-L1 expression, and tumor RNAseq data identified HMGA2 as a potential biomarker of response.ConclusionsBintrafusp alfa showed clinical activity and manageable safety in patients with heavily pretreated advanced TNBC. HMGA2 was identified as a potential predictive biomarker of response.ClinicalTrials.gov identifierNCT02517398
Necrotizing pneumonia and purulent meningitis caused by bloodstream infection of CA-MRSA in a child: A rare case report
Authors: Li Peng , Dai Lizhong , Yuan Ke , Song Chunlan , Cheng Yibing , Jing Yu , Chen Na , Cui Junhao , Wang Yangji , Fu Shuqin 
Published: December 2022

Case presentationWe report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.Symptoms and signsThe patient experienced a rapid onset of symptoms with fever, vomiting, and convulsions. Upon physical examination on admission, she presented with the following: temperature 38.6°C; pulse 185 beats/min; respiration 49 beats/min; blood pressure 89/51 mmHg; drowsiness; piebald skin all over her body; rice-grain-sized pustular rashes scattered on the front chest and both lower limbs, protruding from the surface of the skin; bilateral pupils that were equal in size and a circle with a diameter of about 3.0 mm, and slow light reflex; cyanotic lips; shortness of breath; positive for the three-concave sign; a small amount of phlegm that could be heard in both lungs; capillary refill time of 5 s; cold extremities; and a positive Babinski sign.Diagnostic methodA chest computed tomography scan showed multiple nodular and flake-like high-density shadows of varying sizes in each lobe in bilateral lungs, and a cavity with blurred edges could be seen in some nodules. A cranial magnetic resonance imaging examination demonstrated that the hyperintensity of diffusion-weighted imaging could be observed on the left cerebellar hemisphere and left parietal blade. Blood cultures, sputum, cerebrospinal fluid, and bronchoalveolar lavage fluid (BALF) by fiberoptic bronchoscopy all indicated the growth of methicillin-resistant Staphylococcus aureus (MRSA).Treatment methodsAfter admission, the child was given meropenem combined with vancomycin, cefoperazone sulbactam combined with rifamycin, linezolid (oral) for anti-infection successively, and other adjuvant therapies.Clinical outcomesThe patient recovered clinically and was discharged from our hospital.Recommended readersNeurology; Respiratory Medicine; Infectious Diseases Department.
Induction of whole-body gene deletion via R26-regulated tamoxifen-inducible Cre recombinase activity
Authors: Kumar Rahul , Mao Yun , Patial Sonika , Saini Yogesh 
Published: December 2022

Germline deletion of certain genes causes embryonic lethality, therefore, understanding the effect of deletion of such genes on mammalian pathophysiology remains challenging. Tamoxifen (TAM)-inducible Cre recombinase is widely used for tissue-specific and temporal induction of gene deletion in mice. However, the tamoxifen treatment regimen for the generation of whole-body deletion of a gene is not yet fully standardized for the majority of organs/tissues. Accordingly, we employed GtROSA26 (R26) promoter-regulated Cre and a reporter gene expression strategy. GtROSA26 (R26) is an ubiquitous promoter and mice carrying the R26Cre−ERT2 transgene express Cre-ERT2 in all the cells. Similarly, mice carrying the R26mTOM-mEGFP transgene express mTOM (membrane-targeted tdTomato), in the absence of Cre or mEGFP (membrane-targeted enhanced green fluorescent protein), in the presence of Cre, in all the cells. The progeny carrying one allele of both transgenes were subjected to different TAM regimens, i.e., IP injections (4 injections; 1.35 mg/injection), diet (400 mg TAM-citrate/kg food), or diet (400 mg TAM-citrate/kg food) combined with either TAM-oral gavage (4 gavages; 1.35 mg/gavage) or TAM IP injections (4 injections; 1.35 mg/injection) for 2-weeks beginning at postnatal day (PND) 21 and the extent of Cre recombination in different tissues was determined at PND35. Tamoxifen administration resulted in a transient loss of body weight in all the treatment regimens with a relatively slower rate of weight gain in the TAM-diet plus TAM-oral gavage group compared to other groups. While the efficiency of Cre recombination, as determined by the expression of mEGFP protein, was variable among tissues, major tissues such as the liver, heart, lungs, spleen, and thymus—showed almost complete recombination. No recombination was evident in any of the tissues examined from the control mice. In general, the efficiency of Cre recombination was better with a combined regimen of TAM-diet with either TAM-injections or TAM-oral gavage compared to TAM-diet alone or TAM-injections alone. Our results demonstrate that a combination of TAM-diet with either TAM-injections or TAM-oral gavage can be employed for the efficient deletion of a gene in the whole body. Our findings will provide technical expertise to the researchers employing TAM-inducible Cre for the deletion of floxed genes in varied tissues.
Atorvastatin attenuates ferroptosis-dependent myocardial injury and inflammation following coronary microembolization via the Hif1a/Ptgs2 pathway
Authors: Liu Tao , Shu Jin , Liu Yangchun , Xie Jian , Li Tao , Li Haoliang , Li Lang 
Published: December 2022

Objectives: Coronary microembolization (CME) represents a serious periprocedural complication after percutaneous coronary intervention. Ferroptosis has been identified in multiple cardiovascular diseases. In this study, we aimed to investigate the effects of atorvastatin (ATV) on ferroptosis and inflammation following CME and elucidate the underlying mechanism.Methods: We established a rat model of CME by injecting microspheres into the left ventricle. Deferoxamine (DFO), a selective ferroptosis inhibitor, or ATV was pretreated before modeling. Cardiac function and cardiac troponin T (cTnT) levels were detected. Levels of ferroptosis-associated genes, malondialdehyde (MDA), glutathione (GSH), and ferrous iron (Fe2+) were measured to validate ferroptosis. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) were assayed to determine the inflammation. Chromatin immunoprecipitation was performed to determine the binding of hypoxia-inducible factor 1 subunit alpha (Hif1a) to the promoter of prostaglandin-endoperoxide synthase-2 (Ptgs2).Results: Ferroptosis and inflammation were induced following CME with increased levels of MDA (∼2.5 fold, p &lt; 0.01), Fe2+ (∼1.5 fold, p &lt; 0.01), TNF-α, and IL-1β and decreased GSH levels (∼42%, p &lt; 0.01). Meanwhile, the level of Ptgs2 was significantly increased, while those of glutathione peroxidase 4 (Gpx4) and solute carrier family 7 member 11 (Slc7a11) were decreased. The level of cTnT was increased by 7-fold (p &lt; 0.01). Left ventricular ejection fraction (LVEF) was significantly reduced (∼85% in the sham group versus ∼45% in the CME group, p &lt; 0.01). DFO or Ptgs2 silencing inhibited the increase of MDA, Ptgs2, TNF-α, and IL-1β, and induced the levels of GSH and Gpx4, followed by reduction in cTnT levels by approximately 50% (p &lt; 0.01). LVEF was improved by approximately 2 fold (p &lt; 0.01). Mechanistically, the transcription factor Hif1a bound to the promoter of Ptgs2 and upregulated its expression. In addition, ATV inhibited the activation of the Hif1a/Ptgs2 axis and attenuated cardiac ferroptosis and inflammation, thus ameliorating CME-induced myocardial injury (LVEF, ∼34% elevation; cTnT, ∼1.8 fold decrease, p &lt; 0.01).Conclusion: Atorvastatin ameliorates ferroptosis-mediated myocardial injury and inflammation following CME via the Hif1a/Ptgs2 pathway.
Phytohustil® and root extract of Althaea officinalis L. exert anti-inflammatory and anti-oxidative properties and improve the migratory capacity of endothelial cells in vitro
Authors: Bonaterra Gabriel A. , Schmitt Johanna , Schneider Kim , Schwarzbach Hans , Aziz-Kalbhenn Heba , Kelber Olaf , Müller Jürgen , Kinscherf Ralf 
Published: December 2022

Introduction:Althaea officinalis L.'s root extract (REA) has been used as a medicinal plant since ancient times to treat a cough. Applying REA leads to a protective film that induces a faster regeneration of the lesioned laryngopharyngeal mucosa caused by dry coughs. The buccopharyngeal mucosa is a highly vascularized tissue. In this regard, anti-inflammatory/-oxidant phytochemicals that improve the repair of the lesion site, e.g., neovascularization in the wound, are critical for promoting healing. For this reason, it is essential to investigate the effects of Phytohustil® and REA on different cellular components of the mucosa under conditions similar to those found in the injured mucosa. Thus, this in vitro study investigated the anti-inflammatory/oxidative and pro-migratory properties of Phytohustil® cough syrup on vascular endothelial cells.Methods: Human umbilical vein endothelial cells (HUVEC) were pretreated (24 h) with Phytohustil®, its excipients, or REA, followed by incubation with hydrogen peroxide (H2O2; 1 h; pro-oxidative) or with lipopolysaccharides (LPS; 3 h; pro-inflammatory). Viability and cytotoxicity were measured by PrestoBlue® assay. Intracellular reactive oxygen species (ROS) were quantified with 20-70-dichlorofluorescein diacetate (DCFDA). The release of interleukin 6 (IL6) was determined by enzyme-linked immunosorbent assay (ELISA). The migratory capacity of HUVEC was measured using a scratch assay.Results: Our results show that Phytohustil®, its excipients and REA were not cytotoxic. Pretreatment of HUVEC (24 h) with Phytohustil® or REA inhibited the LPS-activated IL6 release. Phytohustil® or REA inhibited the H2O2-induced cytotoxicity and intracellular ROS production. Phytohustil® and REA significantly stimulated wound closure compared to the control.Conclusion: Our data show that Phytohustil® and REA have anti-inflammatory/-oxidant properties and improve the migratory capacity of vascular endothelial cells. These properties may contribute to the healing characteristics of Phytohustil® and support the benefit of Phytohustil® in patient’s treatment of irritated oral mucosa.
Quasi-continuous time-stretched photon Doppler velocimetry
Authors: Lv Linjie , Yang Yongjun , Wu Tengfei , Han Jibo , Ma Pengmou , Chen Xiangmiao , Khan Abdul Qayyum 
Published: December 2022

In transient high-speed scenes such as chemical explosions, magnetic compression, electric explosion, and laser-driven flyer, the target object can accelerate from 0 to tens of km/s in a few nanoseconds. The time-stretched photon Doppler velocimetry uses the time-stretched interferometry to downscale the frequency of the Doppler shift signal in the optical domain, which breaks through the bandwidth limitations of photoelectric detectors and electrical digital to analog converters. A quasi-continuous time-stretched photon Doppler velocimetry (QT-PDV) is proposed in this paper, for the measurement of microsecond high-speed movement events. On the principle of hardware optical path, the velocity signal of the target object is encoded on multiple stretched chirp pulses, avoiding sampling interruptions and trigger condition limitations; in the signal demodulation methods, the error compensation algorithm is used to compensate for the frequency shift signal, which reduces the system error caused by the displacement and increases the effective recording time. This paper adopts the high-power nanosecond laser to drive the metal film to produce a high-speed target, where beat frequency was downscaled to 2.2 GHz from 4.4 GHz.
Sprint and upper limbs power field tests for the screening of low bone mineral density in children
Authors: Mello Júlio B. , Pedretti Augusto , Bergmann Gabriel G. , Gaya Anelise R. , Ubago-Guisado Esther , Gaya Adroaldo C. A. 
Published: December 2022

Background: The possibility of carrying out screening, with acceptable accuracy, of a child’s bone mass status based on a physical fitness test can advance the concept of health-related physical fitness. In addition, the relevance of the applicability of this type of screening in educational environments is mainly due to the difficulty of direct assessments of bone health indicators. This study aimed to propose cut-off points for physical fitness tests based on children’s bone health indicators.Methods: This is a two-phase cross-sectional study. Phase-1: 160 children (6–11 years-old) performed the 20-m sprint test (20-mST) and the 2 kg medicine ball throw test (2 kgMBTT). Areal bone mineral density (aBMD) and content was assessed by DXA. The area under the ROC curve greater than 70% was considered valid. Phase-2: It was carried out a secondary analysis in a sample with 8,750 Brazilians (6–11 years-old). The percentile values (identified in phase-1) were used to identify the values of the cut-off points in the unit of measurement of the tests. The validation of the cut-off points found was by odds ratio values and p ≤ 0.05.Results: Phase 1: The areas under the ROC curve were 0.710, 0.712 (boys and girls–20-mST), 0.703, and 0.806 (boys and girls–2 kgMBTT) with total spine and pelvis aBMD as the outcome. Phase 2: From percentile values, we find valid cut-off points in the Brazilian sample (OR &gt; 3.00; p &lt; 0.001) for boys and girls. Values ranged between 5.22 s–4.00 s to 20-mST and between 125.0 cm–160.0 cm to 2 kgMBTT. Conclusion. The 20-mST and the 2 kgMBTT presented sufficient accuracy for the screening of children aged between 6 and 11 years with greater chances of having low aBMD in the total spine and pelvis, with valid cut-off points.
Integrated bioinformatics analysis of the transcription factor-mediated gene regulatory networks in the formation of spermatogonial stem cells
Authors: Shi Kesong , Wang Baoluri , Dou Le , Wang Shu , Fu Xinrui , Yu Haiquan 
Published: December 2022

Background:In vitro induction of spermatogonial stem cells (SSCs) from embryonic stem cells (ESCs) provides a promising tool for the treatment of male infertility. A variety of molecules are involved in this complex process, which needs to be further clarified. Undoubtedly, the increased knowledge of SSC formation will be beneficial to facilitate the currently complex induction process.Methods: Based on ATAC-seq, DNase-seq, RNA-seq, and microarray data from GEO datasets, chromatin property data (ATAC-seq, DNase-seq) and gene expression data (RNA-seq, microarray data) were combined to search for SSC-specific transcription factors (TFs) and hub SSC-specific genes by using the WGCNA method. Then, we applied RNA-seq and microarray data screening for key SSC-specific TFs and constructed key SSC-specific TF-mediated gene regulatory networks (GRNs) using ChIP-seq data.Results: First, after analysis of the ATAC-seq and DNase-seq data of mouse ESCs, primordial germ cells (PGCs), and SSCs, 33 SSC-specific TFs and 958 targeting genes were obtained. RNA-seq and WGCNA revealed that the key modules (turquoise and red) were the most significantly related to 958 SSC-specific genes, and a total of 10 hub SSC-specific genes were identified. Next, when compared with the cell-specific TFs in human ESCs, PGCs, and SSCs, we obtained five overlapping SSC-specific TF motifs, including the NF1 family TF motifs (NFIA, NFIB, NFIC, and NFIX), GRE, Fox:Ebox, PGR, and ARE. Among these, Nfib and Nfix exhibited abnormally high expression levels relative to mouse ESCs and PGCs. Moreover, Nfib and Nfix were upregulated in the testis sample with impaired spermatogenesis when compared with the normal group. Finally, the ChIP-seq data results showed that NFIB most likely targeted the hub SSC-specific genes of the turquoise module (Rpl36al, Rps27, Rps21, Nedd8, and Sec61b) and the red module (Vcam1 and Ccl2).Conclusion: Our findings preliminarily revealed cell-specific TFs and cell-specific TF-mediated GRNs in the process of SSC formation. The hub SSC-specific genes and the key SSC-specific TFs were identified and suggested complex network regulation, which may play key roles in optimizing the induction efficiency of the differentiation of ESCs into SSCs in vitro.
Analysis of the response regulatory network of pepper genes under hydrogen peroxide stress
Authors: Tang Bingqian , Yang Guangbin , Du Juan , Xie Lingling , Wang Jin , Pan Luzhao , Luo Yin , Shan Qingyun , Zou Xuexiao , Xiong Cheng , Liu Feng 
Published: December 2022

Hydrogen peroxide (H2O2) is a regulatory component related to plant signal transduction. To better understand the genome-wide gene expression response to H2O2 stress in pepper plants, a regulatory network of H2O2 stress-gene expression in pepper leaves and roots was constructed in the present study. We collected the normal tissues of leaves and roots of pepper plants after 40 days of H2O2 treatment and obtained the RNA-seq data of leaves and roots exposed to H2O2 for 0.5–24 h. By comparing the gene responses of pepper leaves and roots exposed to H2O2 stress for different time periods, we found that the response in roots reached the peak at 3 h, whereas the response in leaves reached the peak at 24 h after treatment, and the response degree in the roots was higher than that in the leaves. We used all datasets for K-means analysis and network analysis identified the clusters related to stress response and related genes. In addition, CaEBS1, CaRAP2, and CabHLH029 were identified through a co-expression analysis and were found to be strongly related to several reactive oxygen species-scavenging enzyme genes; their homologous genes in Arabidopsis showed important functions in response to hypoxia or iron uptake. This study provides a theoretical basis for determining the dynamic response process of pepper plants to H2O2 stress in leaves and roots, as well as for determining the critical time and the molecular mechanism of H2O2 stress response in leaves and roots. The candidate transcription factors identified in this study can be used as a reference for further experimental verification.
Effect of long term application of super absorbent polymer on soil structure, soil enzyme activity, photosynthetic characteristics, water and nitrogen use of winter wheat
Authors: Yang Yonghui , Zhang Sensen , Wu Jicheng , Gao Cuimin , Lu Defu , Tang Darrell W. S. 
Published: December 2022

IntroductionWater scarcity and seasonal drought are major constraints on agricultural development globally. Super absorbent polymer (SAP) is a good amendment that can improve soil structure, increase soil water retention, and promote crop growth even with less soil moisture. We hypothesize that long term application of SAP has a better effect on soil organic carbon, soil enzyme activity, photosynthetic characteristics, yield, and water and nitrogen use than short term application. MethodsA long term field experiment with different application rates (0 (CK), 15 (L), 30 (M), 45 (H) kg ha-1) of SAP was conducted at the Yuzhou water conservation agriculture base of the Henan Academy of Agricultural Sciences from 2011 to 2019.Results and DiscussionThe results indicate that applying SAP increases &gt; 0.25 mm aggregates and decreased&lt;0.25 mm aggregates in the soil after one year (2011) and 9 years (2019) of application. In addition, soil organic carbon, soil microbial biomass carbon, soil sucrase and cellulase activities, soil water consumption, water consumption, net photosynthetic rate (Pn), leaf water use efficiency (LWUE) of wheat and yield, all increased after SAP application. SAP also boosts water use efficiency and nitrogen use efficiency. Correlation analyses show that SAP promotes the growth of wheat, and improves the utilization rate of soil water and nutrients by improving the soil structure and increasing soil organic carbon and microbial enzyme activity.ConclusionBased on our research, SAP treatment at a dosage of 45 kg ha-1 is most effective and is thus recommended.