bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between frailty syndrome and survival in patients with pancreatic adenocarcinoma
Authors: Ngo‐Huang An , Holmes Holly M. , des Bordes Jude K. A. , Parker Nathan H. , Fogelman David , Petzel Maria Q. B. , Song Juhee , Bruera Eduardo , Katz Matthew H. G. 
Published: April 2019

AbstractBackgroundFrailty is a syndrome characterized by weakness, slow gait, weight loss, exhaustion, and low activity. We sought to determine whether frailty was associated with age or stage in newly diagnosed patients with pancreatic ductal adenocarcinoma (PDAC), and determine its association with survival.MethodsConsecutive patients with newly diagnosed PDAC of all stages underwent baseline assessment. Frailty (per Fried criteria) was defined as having three or more abnormalities in: grip strength, gait speed, weight loss, self‐reported exhaustion, or self‐reported physical activity. Baseline clinicodemographic characteristics, anatomic stage, performance status, and laboratory markers of prognosis were included. The association between baseline characteristics, frailty, and survival was determined. The associations of individual frailty measures with age, stage, comorbidities, and performance status were examined. Body composition was measured from computed tomographic images using SliceOMatic software.ResultsOf 150 patients enrolled, 8 were excluded because they did not have PDAC on final diagnosis. The median age was 65 years (range, 32‐89). Seventy‐nine patients (55.6%) were sarcopenic, and 36 (25.4%) were frail. Frailty was associated with increasing comorbidities (P = 0.03) and worse performance status (P < 0.01). During follow‐up, 79 patients (56%) died. Frailty was significantly associated with death during the follow‐up period (P < 0.001) for the entire cohort, including patients with curative (P = 0.038) and palliative (P = 0.003) treatment plans.ConclusionsFrailty was seen frequently in patients with newly diagnosed PDAC and was not associated with increasing age or more advanced stage. Frailty was a predictor of survival, including patients treated with curative intent.
RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway
Authors: Yan Xueqi , Chen Jie , Meng You , He Chao , Zou Shitao , Li Peng , Chen Ming , Wu Jinchang , Ding Wei‐Qun , Zhou Jundong 
Published: April 2019

AbstractNeoadjuvant chemoradiotherapy (nCRT) has been widely applied to improve the local control rate and survival rate in patients with locally advanced rectal cancer (LARC), yet only part of LARC patients would benefit from nCRT. Therefore, it is imperative to predict the therapeutic outcome of nCRT. Here, we showed that RAD18, an E3 ubiquitin‐linked enzyme, played a fundamental role in predicting the response of LARC patients to nCRT. According to clinical data, patients with low RAD18 expression level in their pre‐nCRT biopsies had a superior response to nCRT compared to those with high RAD18 expression. Inhibition of RAD18 expression in rectal cancer cells pronouncedly attenuated the proliferation and promoted apoptosis after exposing to irradiation or/and 5‐fluorouracil (5‐Fu). Downregulated RAD18 levels increased cell apoptosis by activating caspase‐9‐caspase‐3‐mediated apoptotic pathway, thus resulting in the enhancement of cell radiosensitivity and 5‐Fu susceptibility. Furthermore, a xenograft nude mouse model showed that silencing RAD18 significantly slowed tumor growth after irradiation or/and 5‐Fu in vivo. Collectively, these results implied that RAD18 could be a new biomarker to predict LARC patients who might benefit from nCRT and provide new strategies for clinical treatment of LARC.
Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: A retrospective cooperative Central‐Eastern European study
Authors: Yarema Roman , Mielko Jerzy , Fetsych Taras , Ohorchak Myron , Skorzewska Magdalena , Rawicz‐Pruszyński Karol , Mashukov Artem , Maksimovsky Viatcheslav , Jastrzębski Tomasz , Polkowski Wojciech , Gyrya Petro , Kovalchuk Yuriy , Safiyan Victor , Karelin Ivan , Kopetskiy Viatcheslav , Kolesnik Olena , Kondratskiy Yuriy , Paskonis Marius 
Published: April 2019

AbstractBackground and ObjectivesClinical experience in Western Europe suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are promising methods in the management of gastric cancer (GC) with peritoneal metastases. However, there are almost no data on such treatment results in patient from Central‐Eastern European population.MethodsA retrospective cooperative study was performed at 6 Central‐Eastern European HIPEC centers. HIPEC was used in 117 patients for the following indications: treatment of GC with limited overt peritoneal metastases (n = 70), adjuvant setting after radical gastrectomy (n = 37) and palliative approach for elimination of severe ascites without gastrectomy (n = 10).ResultsPostoperative morbidity and mortality rates were 29.1% and 5.1%, respectively. Median overall survival in the groups with therapeutic, adjuvant, and palliative indications was 12.6, 34, and 3.5 months. The only long‐term survivors occurred in the group with peritoneal cancer index (PCI) of 0‐6 points without survival difference in groups with PCI 7‐12 vs PCI 13 or more points.ConclusionsGC patients with limited peritoneal metastases can benefit from CRS + HIPEC. Hyperthermic intraperitoneal chemotherapy could be an effective method of adjuvant treatment of GC with a high risk of intraperitoneal progression. No long‐term survival may be expected after palliative approach to HIPEC.
Design of and Stability Studies on Trefoil Knots Featuring RhCp* Building Blocks
Authors: Guo Bei‐Bei , Lin Yue‐Jian , Jin Guo‐Xin 
Published: April 2019

AbstractFour flexible ligands with different lengths, degrees of flexibility, and steric bulk were synthesized and used to prepare metal‐directed assemblies. Interestingly, minor differences among the ligands led to products with dramatically different topologies: a binuclear D‐shaped macrocycle, tetranuclear rectangles, and hexanuclear trefoil knots. The interconversion of the trefoil‐shaped complexes was also investigated. This contribution introduces a rare ligand‐controlled trefoil–rectangle shape transformation in solution.
Peptide:MHCII Tetramer‐Based Cell Enrichment for the Study of Epitope‐Specific CD4+ T Cells
Authors: Kotov Dmitri I. , Jenkins Marc K. 
Published: April 2019

AbstractEpitope‐specific CD4+ T cells can be labeled in complex cell mixtures from secondary lymphoid organs with fluorophore‐labeled peptide:major histocompatibility complex class II (p:MHCII) tetramers and then detected by flow cytometry. Magnetic enrichment of tetramer‐bound cells before flow cytometry increases the sensitivity of detection to the point where epitope‐specific cells can be studied even when very rare at early and late times after the host has been exposed to the epitope. This method is very useful for studying polyclonal epitope‐specific CD4+ T cells under physiological conditions. © 2019 by John Wiley & Sons, Inc.
Semi‐polar root exudates in natural grassland communities
Authors: Dietz Sophie , Herz Katharina , Döll Stefanie , Haider Sylvia , Jandt Ute , Bruelheide Helge , Scheel Dierk 
Published: April 2019

AbstractIn the rhizosphere, plants are exposed to a multitude of different biotic and abiotic factors, to which they respond by exuding a wide range of secondary root metabolites. So far, it has been unknown to which degree root exudate composition is species‐specific and is affected by land use, the local impact and local neighborhood under field conditions. In this study, root exudates of 10 common grassland species were analyzed, each five of forbs and grasses, in the German Biodiversity Exploratories using a combined phytometer and untargeted liquid chromatography‐mass spectrometry (LC‐MS) approach. Redundancy analysis and hierarchical clustering revealed a large set of semi‐polar metabolites common to all species in addition to species‐specific metabolites. Chemical richness and exudate composition revealed that forbs, such as Plantago lanceolata and Galium species, exuded more species‐specific metabolites than grasses. Grasses instead were primarily affected by environmental conditions. In both forbs and grasses, plant functional traits had only a minor impact on plant root exudation patterns. Overall, our results demonstrate the feasibility of obtaining and untargeted profiling of semi‐polar metabolites under field condition and allow a deeper view in the exudation of plants in a natural grassland community.
Translational repression of Ccl5 and Cxcl10 by 4E‐BP1 and 4E‐BP2 restrains the ability of mouse macrophages to induce migration of activated T cells
Authors: William Mirtha , Leroux Louis‐Philippe , Chaparro Visnu , Graber Tyson E. , Alain Tommy , Jaramillo Maritza 
Published: April 2019

AbstractSignaling through the mechanistic target of rapamycin complex 1 (mTORC1) is a major regulatory node of pro‐inflammatory mediator production by macrophages (MΦs). However, it is still unclear whether such regulation relies on selective translational control by two of the main mTORC1 effectors, the eIF4E‐binding proteins 1 and 2 (4E‐BP1/2). By comparing translational efficiencies of immune‐related transcripts of MΦs from WT and 4E‐BP1/2 double‐KO (DKO) mice, we found that translation of mRNAs encoding the pro‐inflammatory chemokines CCL5 and CXCL10 is controlled by 4E‐BP1/2. Macrophages deficient in 4E‐BP1/2 produced higher levels of CCL5 and CXCL10 upon LPS stimulation, which enhanced chemoattraction of activated T cells. Consistent with this, treatment of WT cells with mTORC1 inhibitors promoted the activation of 4E‐BP1/2 and reduced CCL5 and CXCL10 secretion. In contrast, the phosphorylation status of eIF4E did not affect the synthesis of these chemokines since MΦs derived from mice harboring a non‐phosphorylatable form of the protein produced similar levels of CCL5 and CXCL10 to WT counterparts. These data provide evidence that the mTORC1‐4E‐BP1/2 axis contributes to regulate the production of chemoattractants by MΦs by limiting translation efficiency of Ccl5 and Cxcl10 mRNAs, and suggest that 4E‐BP1/2 act as immunological safeguards by fine‐tuning inflammatory responses in MΦs.
Capsule optoacoustic endoscopy for esophageal imaging
Authors: He Hailong , Stylogiannis Antonios , Afshari Parastoo , Wiedemann Tobias , Steiger Katja , Buehler Andreas , Zakian Christian , Ntziachristos Vasilis 
Published: April 2019

AbstractDetection and monitoring of esophageal cancer severity require an imaging technique sensitive enough to detect early pathological changes in the esophagus and capable of analyzing the esophagus over 360 °in a non‐invasive manner. Optoacoustic endoscopy (COE) has been shown to resolve superficial vascular structure of the esophageal lumen in rats and rabbits using catheter‐type probes. Although these systems can work well in small animals, they are unsuitable for larger lumens with thicker walls as required for human esophageal screening, due to their lack of position stability along the full organ circumference, sub‐optimal acoustic coupling and limited signal‐to‐noise ratio (SNR). In this work, we introduce a novel capsule COE system that provides high‐quality 360° images of the entire lumen, specifically designed for typical dimensions of human esophagus. The pill‐shaped encapsulated probe consists of a novel and highly sensitive ultrasound transducer fitted with an integrated miniature pre‐amplifier, which increases SNR of 10 dB by minimizing artifacts during signal transmission compared to the configuration without the preamplifier. The scanner rotates helically around the central axis of the probe to capture three‐dimensional images with uniform quality. We demonstrate for the first time ex vivo volumetric vascular network images to a depth of 2 mm in swine esophageal lining using COE. Vascular information can be resolved within the mucosa and submucosa layers as confirmed by histology of samples stained with hematoxylin and eosin and with antibody against vascular marker CD31. COE creates new opportunities for optoacoustic screening of esophageal cancer in humans.
Lipofectamine 2000/siRNA complexes cause endoplasmic reticulum unfolded protein response in human endothelial cells
Authors: Li Zhengzheng , Zhang Chi , Wang Zhiting , Shen Jian , Xiang Pingping , Chen Xiao , Nan Jinliang , Lin Yinuo 
Published: April 2019

AbstractLipofectamine 2000 (Lipo2000) delivery system is commonly used for short interfering RNA (siRNA) transfection, whereas the cellular responses have attracted little attention. The purpose of this study is to evaluate the effect of siRNA transfection using Lipo2000 on cellular functions and the possible underlying mechanism. Primary human umbilical vein endothelial cells (HUVECs) and adult human coronary artery endothelial cell line (HCAECs) were treated with different concentrations of a Lipo2000/negative control siRNA (NC siRNA) complex or Lipo2000 for specific durations. The cell proliferation, apoptosis rate, and protein expression of claudin5 (CLDN5) and ETS‐related gene (ERG) were analyzed as indicators of cellular function. The effects of the Lipo2000/NC siRNA complex on cellular autophagy and endoplasmic reticulum (ER) unfolded protein response (UPR) were investigated by western blot and real‐time polymerase chain reaction analyses; autophagy was also evaluated by transmission electron microscopy. The Lipo2000/NC siRNA complex inhibited proliferation, downregulated various proteins, and increased the apoptosis in both HUVECs and HCAECs. Both autophagy and UPR were observed in HUVECs treated with the Lipo2000/NC siRNA complex, ER stress‐induced autophagy acted as a cellular protective factor against apoptosis, as inhibition of autophagy by chemical inhibitors increased the cell apoptosis rate. Chemical chaperones failed to prevent the Lipo2000/siRNA complex‐induced UPR. However, knockdown of protein kinase RNA‐like ER kinase and inositol‐requiring protein 1, instead of activating transcription factor‐6, partially ameliorated the UPR and reversed the protein level of CLDN5 and ERG downregulated by Lipo2000/NC siRNA complex. This study provides the first evidence that the Lipo2000‐mediated transport of siRNA leads to an increase in UPR and ER stress‐related apoptosis in endothelial cells.
Acute exposure to triphenyl phosphate inhibits the proliferation and cardiac differentiation of mouse embryonic stem cells and zebrafish embryos
Authors: Qi Zenghua , Chen Min , Song Yuanyuan , Wang Xiya , Li Bingkun , Chen Zhi‐Feng , Tsang Suk Ying , Cai Zongwei 
Published: April 2019

AbstractAttention has recently paid to the interaction of triphenyl phosphate (TPHP) and body tissues, particularly within the reproductive and development systems, due to its endocrine‐disrupting properties. However, the acute effects of TPHP on early embryonic development remain unclear. Here, we used mouse embryonic stem cells (mESC) and zebrafish embryos to investigate whether TPHP is an embryo toxicant. First, we found that continuous exposure of TPHP decreased the proliferation and increased the apoptotic populations of mESCs in a concentration‐dependent manner. Results of mass spectrometry showed that the intracellular concentration of TPHP reached 39.45 ± 7.72 µg/g w/w after 3 hr of acute exposure with TPHP (38.35 μM) but gradually decreased from 3 hr to 48 hr. Additionally, DNA damage was detected in mESCs after a short‐term treatment with TPHP, which in turn, activated DNA damage responses, leading to cell cycle arrest by changing the expression levels of p53, proliferating cell nuclear antigen, and Y15‐phosphorylated Cdk I. Furthermore, our results revealed that short‐term treatment with TPHP disturbed cardiac differentiation by decreasing the expression levels of Oct4, Sox2, and Nanog and transiently reduced the glycolysis capacity in mESCs. In zebrafish embryos, exposure to TPHP resulted in broad, concentration‐dependent developmental defects and coupled with heart malformation and reduced heart rate. In conclusion, the two models demonstrate that acute exposure to TPHP affects early embryonic development and disturbs the cardiomyogenic differentiation.
Influence of temperature variation on incubation period, hatching success, sex ratio, and phenotypes in Caiman latirostris
Authors: Simoncini Melina S. , Leiva Pamela M.L. , Piña Carlos I. , Cruz Felix B. 
Published: April 2019

AbstractTemperature is crucial for reptiles, also during embryonic development, particularly for species with temperature‐dependent sex determination. Under natural conditions, Broad‐snouted caiman (Caiman latirostris) eggs are influenced by thermal changes in the interior of the nest related to the external environmental temperature. As nests are subject to variations in temperature and most lab studies on crocodilian incubation have been carried out at constant temperatures, we were interested in determining how temperature fluctuations may affect the development of caiman embryos. We investigated the effects of incubation at constant temperatures (31°C, 32°C, and 33°C) and fluctuating temperatures (31 ± 2, 32 ± 1, and 32 ± 2°C) on the following aspects: incubation period duration, hatching success, sex ratio, total length, and body mass of C. latirostris hatchlings. Eggs incubated at 31°C produced 100% females, those at 32°C produced 71.6% females (however, the sex ratio was nest related), and at 33°C produced 100% males. We found a masculinizing effect when incubation was at 31 ± 2°C compared with a constant 31°C; and temperature fluctuations at 32°C (32 ± 1 and 32 ± 2°C) had a negative effect on hatchlings size and mass, and hatching success compared with constant incubation temperatures of 32°C and 33°C. Finally, the effect of temperature variation during the incubation period on sex ratio, hatching success, and phenotype depends on the mean temperature, as the fluctuation around 31°C affected the sex ratios and incubation period, and the fluctuation around 32°C affected hatchling success and size.
Vernonia amygdalina inhibited osteoarthritis development by anti‐inflammatory and anticollagenase pathways in cartilage explant and osteoarthritis‐induced rat model
Authors: Madzuki Iffah Nadhira , Lau Seng Fong , Abdullah Rasedee , Mohd Ishak Nur Iliyani , Mohamed Suhaila 
Published: April 2019

Vernonia amygdalina (VA) is a medicinal tropical herb for diabetes and malaria and believed to be beneficial for joint pains. The antiosteorthritis effects of VA leaf in cartilage explant assays and on postmenopausal osteoarthritis (OA) rat model were investigated. The VA reduced the proteoglycan and nitric oxide release from the cartilage explants with interleukin 1β (IL‐1β) stimulation. For the preclinical investigation, ovariectomized (OVX) female rats were grouped (n = 8) into nontreated OA, OA + diclofenac (5 mg/kg), OA + VA extract (150 and 300 mg/kg), and healthy sham control. Monosodium iodoacetate was injected into the knee joints to accelerate OA development. After 8 weeks, the macroscopic, microscopic, and histological images showed that the OA rats treated with VA 300 mg/kg and diclofenac had significantly reduced cartilage erosions and osteophytes unlike the control OA rats. The extract significantly down‐regulated the inflammatory prostaglandin E2, nuclear factor κβ, IL‐1β, ADAMTS‐5, collagen type 10α1, and caspase3 in the OVX‐OA rats. It up‐regulated the anti‐inflammatory IL‐10 and collagen type 2α1 mRNA expressions, besides reducing serum collagenases (MMP‐3 and MMP‐13) and collagen type II degradation biomarker (CTX‐II) levels in these rats. The VA (containing various caffeoyl‐quinic acids, flavanone‐O‐rutinoside, luteolin, apigenin derivative and vernonioside D) suppressed inflammation, pain, collagenases as well as cartilage degradation, and improved cartilage matrix synthesis to prevent OA.
What do implicit measures measure?
Authors: Brownstein Michael , Madva Alex , Gawronski Bertram 
Published: April 2019

AbstractWe identify several ongoing debates related to implicit measures, surveying prominent views and considerations in each. First, we summarize the debate regarding whether performance on implicit measures is explained by conscious or unconscious representations. Second, we discuss the cognitive structure of the operative constructs: are they associatively or propositionally structured? Third, we review debates about whether performance on implicit measures reflects traits or states. Fourth, we discuss the question of whether a person's performance on an implicit measure reflects characteristics of the person who is taking the test or characteristics of the situation in which the person is taking the test. Finally, we survey the debate about the relationship between implicit measures and (other kinds of) behavior.This article is categorized under:
Philosophy > Representation
Psychology > Theory and Methods
Psychology > Prediction
Philosophy > Psychological Capacities
Enabling Emergent Workplace Design
Authors: Oppl Stefan , Stary Christian 
Published: April 2019

AbstractThis chapter offers a synthesis of the conceptual and methodological considerations of the previously presented frameworks and instruments. It adjusts the methodological concepts for eliciting, representing, and processing work knowledge for practical use. Based on elementary modeling constructs we provide a unifying framework that guides the design of organizational interventions when enabling the emergence of novel digital workplace designs and work practices. According to the architecture, support systems for organizational learning enable augmenting processes with work-relevant knowledge, including the execution of specified behavior representations. Overall goal is developing consensually shared workflow designs—developed for and by the actual set of people executing a workflow. The structured procedure allows a generalized architecture based on a common organizational memory and dedicated components for articulation, informed alignment through organizational learning support, and process prototyping.
Putting the Framework to Operation: Enabling Organizational Development Through Learning
Authors: Oppl Stefan , Stary Christian 
Published: April 2019

AbstractThis chapter instantiates the proposed framework for developing consensually shared workflow designs. It shows how the framework can be put to operation using instruments that have been successfully deployed in practice. These instruments enable articulation and alignment of work process knowledge, allow its representation and transfer within organizations, and facilitate acting on these representations for validation and implementation in diverse organizational settings. We here adopt an organizational learning perspective and situate the presented socio-technical instruments along a multi-perspective learning chain informed by the components of the framework. It thus offers instruments supporting the articulation and alignment of work process knowledge, its multi-faceted representation and flexible manipulation, as well as support for processing the resulting models for validation and refinement. Using the framework as a coherent lens on the requirements on support and the respective features of the instruments allows to offer an integrated view, which demonstrates digital work design support in organizational practice.