bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent insights on indirect mechanisms in developmental toxicity of nanomaterials
Authors: Dugershaw Battuja Batbajar , Aengenheister Leonie , Hansen Signe Schmidt Kjølner , Hougaard Karin Sørig , Buerki-Thurnherr Tina 
Published: July 2020

Abstract
Background
Epidemiological and animal studies provide compelling indications that environmental and engineered nanomaterials (NMs) pose a risk for pregnancy, fetal development and offspring health later in life. Understanding the origin and mechanisms underlying NM-induced developmental toxicity will be a cornerstone in the protection of sensitive populations and the design of safe and sustainable nanotechnology applications.

Main body
Direct toxicity originating from NMs crossing the placental barrier is frequently assumed to be the key pathway in developmental toxicity. However, placental transfer of particles is often highly limited, and evidence is growing that NMs can also indirectly interfere with fetal development. Here, we outline current knowledge on potential indirect mechanisms in developmental toxicity of NMs.

Short conclusion
Until now, research on developmental toxicity has mainly focused on the biodistribution and placental translocation of NMs to the fetus to delineate underlying processes. Systematic research addressing NM impact on maternal and placental tissues as potential contributors to mechanistic pathways in developmental toxicity is only slowly gathering momentum. So far, maternal and placental oxidative stress and inflammation, activation of placental toll-like receptors (TLRs), impairment of placental growth and secretion of placental hormones, and vascular factors have been suggested to mediate indirect developmental toxicity of NMs. Therefore, NM effects on maternal and placental tissue function ought to be comprehensively evaluated in addition to placental transfer in the design of future studies of developmental toxicity and risk assessment of NM exposure during pregnancy.
Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia
Authors: Wu Tianshu , Liang Xue , Liu Xi , Li Yimeng , Wang Yutong , Kong Lu , Tang Meng 
Published: July 2020

Abstract
Background
Graphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation.

Results
The cytosolic iron overload, glutathione (GSH) depletion, excessive reactive oxygen species (ROS) production and lipid peroxidation (LPO) were observed in microglial BV2 cells treated with N-GQDs, which indicated that N-GQDs could damage the iron metabolism and redox balance in microglia. The pre-treatments of a specific ferroptosis inhibitor Ferrostatin-1 (Fer-1) and an iron chelater Deferoxamine mesylate (DFO) not only inhibited cell death, but also alleviated iron overload, LPO and alternations in ferroptosis biomarkers in microglia, which were caused by N-GQDs. When assessing the potential mechanisms of N-GQDs causing ferroptosis in microglia, we found that the iron content, ROS generation and LPO level in mitochondria of BV2 cells all enhanced after N-GQDs exposure. When the antioxidant ability of mitochondria was increased by the pre-treatment of a mitochondria targeted ROS scavenger MitoTEMPO, the ferroptotic biological changes were effectively reversed in BV2 cells treated with N-GQDs, which indicated that the N-GQDs-induced ferroptosis in microglia could be attributed to the mitochondrial oxidative stress. Additionally, amino functionalized GQDs (A-GQDs) elicited milder redox imbalance in mitochondria and resulted in less ferroptotic effects than N-GQDs in microglia, which suggested a slight protection of amino group functionalization in GQDs causing ferroptosis.

Conclusion
N-GQDs exposure caused ferroptosis in microglia via inducing mitochondrial oxidative stress, and the ferroptotic effects induced by A-GQDs were milder than N-GQDs when the exposure method is same. This study will not only provide new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs.
Intraoperative ultrasonography assistance for minimally invasive repair of the acute Achilles tendon rupture
Authors: Yongliang Yang , Honglei Jia , Wupeng Zhang , Shihong Xu , Fu Wang , Bomin Wang , Qinghu Li , Yonghui Wang , Shumei Han 
Published: July 2020

Abstract
Background
Minimally invasive repair is a better option for Achilles tendon rupture with low re-rupture and wound-related complications than conservative treatment or traditional open repair. The major problem is sural nerve injury. The purpose of this study was to evaluate the effect and advantage of the intraoperative ultrasonography assistance for minimally invasive repair of the acute Achilles tendon rupture.

Methods
A retrospective study was performed on 36 cases of acute Achilles tendon rupture treated with minimally invasive repair assisted with intraoperative ultrasonography from January 2015 to December 2017. The relationship of the sural nerve and small saphenous vein was confirmed on the preoperative MRI. The course of the small saphenous vein and the sural nerve was identified and marked by intraoperative ultrasonography. The ruptured Achilles tendon was repaired with minimally invasive Bunnell suture on the medial side of the small saphenous vein (SSV).

Results
All patients were followed up for at least 12 months. No sural nerve injury or other complications was found intraoperatively and postoperatively. All the patients returned to work and light sporting activities at a mean of 12.78 ± 1.40 weeks and 17.28 ± 2.34 weeks, respectively. The Mean American Orthopaedic Foot & Ankle Society (AOFAS) scores improved from 59.17 ± 5.31 preoperatively to 98.92 ± 1.63 at the time of 12 months follow-up. There was a statistically significant difference (P < 0.001). No patient complained of a negative effect on their life.

Conclusions
The minimally invasive repair assisted with intraoperative ultrasonography can yield good clinical outcomes, less surgical time, and less complications, especially sural nerve injury. It is an efficient, reliable, and safe method for acute Achilles tendon (AT) rupture.
Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy
Authors: Marchica Valentina , Franceschi Valentina , Vescovini Rosanna , Storti Paola , Vicario Emanuela , Toscani Denise , Zorzoli Alessia , Airoldi Irma , Dalla Palma Benedetta , Campanini Nicoletta , Martella Eugenia , Mancini Cristina , Costa Federica , Donofrio Gaetano , Giuliani Nicola 
Published: July 2020

Abstract
Background
The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients’ antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46.

Methods
We treated several human myeloma cell lines and non-myeloma cell lines with BVDV to evaluate the expression of CD46 and to study the effect on cell viability by flow cytometry. The possible synergistic effect of bortezomib in combination with BVDV was also tested. Moreover, we infected the bone marrow mononuclear cells obtained from myeloma patients and we checked the BVDV effect on different cell populations, defined by CD138, CD14, CD3, CD19, and CD56 expression evaluated by flow cytometry. Finally, the in vivo BVDV effect was tested in NOD-SCID mice injected subcutaneously with myeloma cell lines.

Results
Human myeloma cells were selectively sensitive to BVDV treatment with an increase of cell death and, consequently, of apoptotic markers. Consistently, bone marrow mononuclear cells isolated from myeloma patients treated with BVDV, showed a significant selective decrease of the percentage of viable CD138+ cells. Interestingly, bortezomib pre-treatment significantly increased the cytotoxic effect of BVDV in myeloma cell lines with a synergistic effect. Finally, the in vitro data were confirmed in an in vivo myeloma mouse model showing that BVDV treatment significantly reduced the tumoral burden compared to the vehicle.

Conclusions
Overall, our data indicate, for the first time, a direct oncolytic effect of the BVDV in human myeloma cells suggesting its possible use as novel alternative anti-myeloma virotherapy strategy.
RNA-binding proteins in tumor progression
Authors: Qin Hai , Ni Haiwei , Liu Yichen , Yuan Yaqin , Xi Tao , Li Xiaoman , Zheng Lufeng 
Published: July 2020

AbstractRNA-binding protein (RBP) has a highly dynamic spatiotemporal regulation process and important biological functions. They are critical to maintain the transcriptome through post-transcriptionally controlling the processing and transportation of RNA, including regulating RNA splicing, polyadenylation, mRNA stability, mRNA localization, and translation. Alteration of each process will affect the RNA life cycle, produce abnormal protein phenotypes, and thus lead to the occurrence and development of tumors. Here, we summarize RBPs involved in tumor progression and the underlying molecular mechanisms whereby they are regulated and exert their effects. This analysis is an important step towards the comprehensive characterization of post-transcriptional gene regulation involved in tumor progression.
LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells
Authors: Zhang Shuyao , Zheng Fuchun , Zhang Liqun , Huang Zuojun , Huang Xiaoshan , Pan Zhen , Chen Shuang , Xu Chenchen , Jiang Yi , Gu Shuyi , Zhao Chengkuan , Zhang Qiuzhen , Shi Ganggang 
Published: July 2020

Abstract
Background
Esophageal cancer (EC) represents one of the most aggressive digestive neoplasms globally, with marked geographical variations in morbidity and mortality. Chemoprevention is a promising approach for cancer therapy, while acquired chemoresistance is a major obstacle impeding the success of 5-fluorouracil (5-FU)-based chemotherapy in EC, with the mechanisms underlying resistance not well-understood. In the present study, we focus on exploring the role of long non-coding RNA (lncRNA) HOTAIR in EC progression and sensitivity of EC cells to 5-FU.

Methods
Paired cancerous and pre-cancerous tissues surgically resected from EC patients were collected in this study. Promoter methylation of the MTHFR was assessed by methylation-specific PCR. RIP and ChIP assays were adopted to examine the interaction of DNA methyltransferases (DNMTs) with lncRNA HOTAIR and MTHFR, respectively. EC cells resistant to 5-FU were induced by step-wise continuous increasing concentrations of 5-FU. The sensitivity of EC cells to 5-FU in vivo was evaluated in nude mice treated with xenografts of EC cells followed by injection with 5-FU (i.p.).

Results
We found reciprocal expression patterns of lncRNA HOTAIR and MTHFR in EC tissues and human EC cells. Interference with lncRNA HOTAIR enhanced 5-FU-induced apoptosis, exhibited anti-proliferative activity, and reduced promoter methylation of the MTHFR in EC cells. Besides, overexpression of MTHFR attenuated the acquired chemoresistance induced by overexpression of lncRNA HOTAIR in EC cells. At last, enhanced chemosensitivity was observed in vivo once nude mice xenografted with lncRNA HOTAIR-depleted EC cells.

Conclusion
Together, our study proposes that pharmacologic targeting of lncRNA HOTAIR sensitizes EC cells to 5-FU-based chemotherapy by attenuating the promoter hypermethylation of the MTHFR in EC.
CPEB3 inhibits epithelial-mesenchymal transition by disrupting the crosstalk between colorectal cancer cells and tumor-associated macrophages via IL-6R/STAT3 signaling
Authors: Zhong Qian , Fang Yuxin , Lai Qiuhua , Wang Shanci , He Chengcheng , Li Aimin , Liu Side , Yan Qun 
Published: July 2020

Abstract
Background
Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been shown to exhibit tumor-suppressive role in CRC.

Methods
The expression of CPEB3, CD68, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells overexpressing CPEB3 and LoVo or RKO cells with CPEB3 knockdown were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, macrophage polarization, and secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice.

Results
Decreased CPEB3 expression in CRC was associated with fewer CD86+ TAMs and more CD163+ TAMs. CPEB3 knockdown in CRC cells increased the number of CD163+ TAMs and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAM supernatants. TAMs enhanced CRC cell proliferation and invasion via IL-6, and then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein levels by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in CPEB3 knockdown cells, while CCL2 antibody treatment rescued the effect of CPEB3 knockdown in promoting CD163+ TAM polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAM polarization in vivo.

Conclusions
CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.
Higher plasma cystatin C is associated with mortality after acute respiratory distress syndrome: findings from a Fluid and Catheter Treatment Trial (FACTT) substudy
Authors: Hendrickson Carolyn M. , Kwong Yuenting D. , Belzer Annika G. , Shlipak Michael G. , Matthay Michael A. , Liu Kathleen D. 
Published: July 2020

Abstract
Background
Cystatin C is a well-validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous populations of critically ill patients and may be superior to creatinine in identifying kidney injury in critically ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with acute respiratory distress syndrome (ARDS) would be associated with mortality risk.

Methods
In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

Results
Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9–1.9) mg/L vs. 0.8 (0.6–1.2) mg/L, p < 0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2–2.6), p = 0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0–2.4), p = 0.048] and those without AKI [OR 2.4 (1.2–5.0), p = 0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality.

Conclusions
Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60 days in patients with ARDS with and without AKI identified by creatinine-based definitions. Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.
Bedside calculation of mechanical power during volume- and pressure-controlled mechanical ventilation
Authors: Chiumello Davide , Gotti Miriam , Guanziroli Mariateresa , Formenti Paolo , Umbrello Michele , Pasticci Iacopo , Mistraletti Giovanni , Busana Mattia 
Published: July 2020

Abstract
Background
Mechanical power (MP) is the energy delivered to the respiratory system over time during mechanical ventilation. Our aim was to compare the currently available methods to calculate MP during volume- and pressure-controlled ventilation, comparing different equations with the geometric reference method, to understand whether the easier to use surrogate formulas were suitable for the everyday clinical practice. This would warrant a more widespread use of mechanical power to promote lung protection.

Methods
Forty respiratory failure patients, sedated and paralyzed for clinical reasons, were ventilated in volume-controlled ventilation, at two inspiratory flows (30 and 60 L/min), and pressure-controlled ventilation with a similar tidal volume. Mechanical power was computed both with the geometric method, as the area between the inspiratory limb of the airway pressure and the volume, and with two algebraic methods, a comprehensive and a surrogate formula.

Results
The bias between the MP computed by the geometric method and by the comprehensive algebraic method during volume-controlled ventilation was respectively 0.053 (0.77, − 0.81) J/min and − 0.4 (0.70, − 1.50) J/min at low and high flows (r2 = 0.96 and 0.97, p < 0.01). The MP measured and computed by the two methods were highly correlated (r2 = 0.95 and 0.94, p < 0.01) with a bias of − 0.0074 (0.91, − 0.93) and − 1.0 (0.45, − 2.52) J/min at high-low flows. During pressure-controlled ventilation, the bias between the MP measured and the one calculated with the comprehensive and simplified methods was correlated (r2 = 0.81, 0.94, p < 0.01) with mean differences of − 0.001 (2.05, − 2.05) and − 0.81 (2.11, − 0.48) J/min.

Conclusions
Both for volume-controlled and pressure-controlled ventilation, the surrogate formulas approximate the reference method well enough to warrant their use in the everyday clinical practice. Given that these formulas require nothing more than the variables already displayed by the intensive care ventilator, a more widespread use of mechanical power should be encouraged to promote lung protection against ventilator-induced lung injury.
Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
Authors: Lecronier Marie , Beurton Alexandra , Burrel Sonia , Haudebourg Luc , Deleris Robin , Le Marec Julien , Virolle Sara , Nemlaghi Safaa , Bureau Côme , Mora Pierre , De Sarcus Martin , Clovet Olivier , Duceau Baptiste , Grisot Paul Henri , Pari Marie Hélène , Arzoine Jérémy , Clarac Ulrich , Boutolleau David , Raux Mathieu , Delemazure Julie , Faure Morgane , Decavele Maxens , Morawiec Elise , Mayaux Julien , Demoule Alexandre , Dres Martin 
Published: July 2020

Abstract
Background
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.

Methods
The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.

Results
Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.

Conclusion
In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.