bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hMTR4‐PDIA3P1‐miR‐125/124‐TRAF6 Regulatory Axis and Its Function in NF kappa B Signaling and Chemoresistance
Authors: Xie Chen , Zhang Li‐Zhen , Chen Zhan‐Li , Zhong Wang‐Jing , Fang Jian‐Hong , Zhu Ying , Xiao Man‐Huan , Guo Zhi‐Wei , Zhao Na , He Xionglei , Zhuang Shi‐Mei 
Published: September 2019

Background and Aims
DNA damage‐induced NF‐κB activation is a major obstacle to effective antitumour chemotherapy. Long noncoding RNAs (lncRNAs) that regulate chemoresistance of cancer cells remain largely unknown. This study aimed to characterize the lncRNAs that may affect chemotherapy sensitivity.

Approach and Results
We found that lncRNA PDIA3P1 (protein disulfide isomerase family A member 3 pseudogene 1) was up‐regulated in multiple cancer types and following treatment with DNA‐damaging chemotherapeutic agents, like doxorubicin (Dox). Higher PDIA3P1 level was associated with poorer recurrence‐free survival of human hepatocellular carcinoma (HCC). Both gain‐of‐function and loss‐of‐function studies revealed that PDIA3P1 protected cancer cells from Dox‐induced apoptosis and allowed tumor xenografts to grow faster and to be more resistant to Dox treatment. Mechanistically, miR‐125a/b and miR‐124 suppressed the expression of tumor necrosis factor receptor‐associated factor 6 (TRAF6), but PDIA3P1 bound to miR‐125a/b/miR‐124 and relieved their repression on TRAF6, leading to activation of the nuclear factor kappa B (NF‐κB) pathway. Consistently, the effect of PDIA3P1 inhibition in promoting Dox‐triggered apoptosis was antagonized by silencing the inhibitor of κBα (IκBα) or overexpressing TRAF6. Administration of BAY 11‐7085, an NF‐κB inhibitor attenuated PDIA3P1‐induced resistance to Dox treatment in mouse xenografts. Moreover, up‐regulation of PDIA3P1 was significantly correlated with elevation of TRAF6, phosphorylated p65, or NF‐κB downstream anti‐apoptosis genes in human HCC tissues. These data indicate that enhanced PDIA3P1 expression may confer chemoresistance by acting as a microRNA sponge to increase TRAF6 expression and augment NF‐κB signaling. Subsequent investigations into the mechanisms of PDIA3P1 up‐regulation revealed that human homologue of mRNA transport mutant 4 (hMTR4), which promotes RNA degradation, could bind to PDIA3P1, and this interaction was disrupted by Dox treatment. Overexpression of hMTR4 attenuated Dox‐induced elevation of PDIA3P1, whereas silencing hMTR4 increased PDIA3P1 level, suggesting that Dox may up‐regulate PDIA3P1 by abrogating the hMTR4‐mediated PDIA3P1 degradation.

Conclusion
There exists a hMTR4‐PDIA3P1‐miR‐125/124‐TRAF6 regulatory axis that regulates NF‐κB signaling and chemoresistance, which may be exploited for anticancer therapy.
SESTET: A spatially explicit stream temperature model based on equilibrium temperature
Authors: Carraro Luca , Toffolon Marco , Rinaldo Andrea , Bertuzzo Enrico 
Published: September 2019

AbstractStream‐water temperature is a key variable controlling chemical, biological, and ecological processes in freshwater environments. Most models focus on a single river cross‐section; however, temperature gradients along stretches and tributaries of a river network are crucial to assess ecohydrological features such as aquatic species suitability, growth and feeding rates, or disease transmission. We propose SESTET, a deterministic, spatially explicit stream temperature model for a whole river network, based on water and energy budgets at a reach scale and requiring only commonly available spatially distributed datasets, such as morphology and air temperature, as input. Heat exchange processes at the air–water interface are modelled via the widely used equilibrium temperature concept, whereas the effects of network structure are accounted for through advective heat fluxes. A case study was conducted on the prealpine Wigger river (Switzerland), where water temperatures have been measured in the period 2014–2018 at 11 spatially distributed locations. The results show the advantages of accounting for water and energy budgets at the reach scale for the entire river network, compared with simpler, lumped formulations. Because our approach fundamentally relies on spatially distributed air temperature fields, adequate spatial interpolation techniques that account for the effects of both elevation and thermal inversion in air temperature are key to a successful application of the model. SESTET allows the assessment of the magnitude of the various components of the heat budget at the reach scale and the derivation of reliable estimates of spatial gradients of mean daily stream temperatures for the whole catchment based on a limited number of conveniently located (viz., spanning the largest possible elevation range) measuring stations. Moreover, accounting for mixing processes and advective fluxes through the river network allows one to trust regionalized values of the parameters controlling the relationship between equilibrium and air temperature, a key feature to generalize the model to data‐scarce catchments.
Human amnion‐derived mesenchymal stem cells enhance the osteogenic differentiation of human adipose‐derived stem cells by promoting adiponectin excretion via the APPL1‐ERK1/2 signaling pathway
Authors: Wang Yuli , Du Yifei , Yuan Hua , Pan Yongchu , Wu Jun , Du Xin , Hao Shushu , Yan Zixin , Li Xuan , Liu Keyue , Xu Fan 
Published: September 2019

AbstractHuman adipose‐derived stem cells (HASCs) represent pluripotent cells capable of differentiating into the bone tissue. Meanwhile, human amnion‐derived mesenchymal stem cells (HAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. This work assessed the osteogenic effects exerted by HAMSCs on the potential of HASCs to form bone cells. Cell growth was evaluated flow‐cytometrically. Differentiation into osteoblasts and mineral formation were assessed by chromogenic alkaline phosphatase activity substrate assay and Alizarin red S staining. Adiponectin (APN), the adipocytokine secreted by adipocytes, was evaluated by enzyme‐linked immunosorbent assay. In this study, HAMSCs concentration‐dependently induced growth, osteoblastic differentiation, and APN excretion in HASCs. Mechanistically, immunofluorescence and immunoblot revealed HAMSCs promoted cytosolic translocation of leucine zipper motif (APPL1) from the nucleus and induced extracellular signaling‐regulated kinase 1/2 (ERK1/2) phosphorylation in HASCs. Furthermore, HAMSC effects were markedly blunted by pretreatment with APPL1 siRNA and U0126, an ERK1/2 signaling inhibitor with high selectivity. These results suggested that APN excretion is not suppressed by APPL1 knockdown in HASCs, but by ERK1/2 inhibition. These findings collectively indicate that HAMSCs induce the osteogenesis of HASCs by promoting APN excretion through APPL1‐ERK1/2 activation.
Chitosan‐laponite nanocomposite scaffolds for wound dressing application
Authors: Gonzaga Virgínia de A. M. , Poli Alessandra L. , Gabriel Juliana S. , Tezuka Daiane Y. , Valdes Talita A. , Leitão Andrei , Rodero Camila F. , Bauab Taís M. , Chorilli Marlus , Schmitt Carla C. 
Published: September 2019

AbstractThe pivotal issue of skin regeneration research is the development of effective biomaterials that exhibit biological activities as fungicide and bactericide, combining simple and low cost manufacturing technologies. In this context, nanocomposite scaffolds based on chitosan (Ch)/Laponite (Lap) were produced by using different concentrations of Lap via freeze‐drying process for potential application in skin regeneration. The influence of Lap concentration on the scaffold properties was evaluated. The prepared scaffolds were characterized by x‐ray diffraction (XRD), scanning electron microscopy (SEM), porosity, swelling capacity, and mechanical analyses. The results revealed that the scaffolds exhibited a porous architecture, besides the increase in the clay content, leads to an increase in the porosity, an improvement of mechanical strength, and a decrease of swelling capacity. In vitro tests were also carried out to evaluate the biocompatibility of the materials, such as bioadhesion, antibacterial activity, viability, and cell adhesion. Viability and cell adhesion demonstrated that all scaffolds were not cytotoxic and the fibroblast cells readily attached on the surface of the scaffolds. Thereby, the results suggested that the nanocomposite scaffolds are biomaterials potentially useful as wound dressings.
New approaches to diversity in clinical work
Authors: Rosa Dinelia 
Published: September 2019

AbstractThe inclusion of diversity issues in clinical work has risen in the last years. With APA's multicultural guidelines and diversity courses becoming a requirement in doctoral programs, we see a concerted effort to increase awareness, knowledge, and understanding of diversity issues in clinical work. Yet, there is still much to do. In this issue of Journal of Clinical Psychology: In Session, seven authors conceptualize diversity from various therapeutic approaches, including relational cognitive behavior therapy, couples therapy, multicultural counseling, and psychodynamic psychotherapy. We learn how diversity and clinical work are not mutually exclusive regardless of the therapeutic approach used as long as the therapist is culturally sensitive and competent, and motivated to pursue such integration. We also learn that regardless of their commitment to social justice, and their understanding of the consequences of inequality and oppression on individuals’ mental health, clinicians vary considerably in the extent to which they actively integrate diversity considerations in the treatment room. The authors in this issue present clinical vignettes describing how they have integrated diversity into their therapeutic work. Furthermore, they discuss how the process of addressing issues of diversity has impacted their work. Lastly, the authors offer recommendations from their experiences as clinicians.
Reconsidering culture, attachment, and inequality in the treatment of a Puerto Rican migrant: Toward structural competence in psychotherapy
Authors: Gaztambide Daniel J. 
Published: September 2019

AbstractCultural competence refers to our ability to understand, engage, and treat patients from diverse backgrounds or belief systems different from our own. Although addressing culture and cultural difference as part of diversity is important, it is also critical to consider how systemic and economic forces influence the patient's presenting problem and clinical interactions. Summarizing research on cultural competence, attachment, and inequality, this paper reconsiders diversity considerations by discussing how structural inequities disrupt one's ability to trust others interpersonally and across cultural difference. Psychotherapy from this point of view is a relationship that attempts to address the effects of inequality at an individual level by repairing trust and using that trust to work toward change. To illustrate this perspective, the author presents a case of a Puerto Rican migrant whose developmental and family history was impacted by colonial, racial, cultural, and socioeconomic inequality.
MicroRNA‐448 overexpression inhibits fibroblast proliferation and collagen synthesis and promotes cell apoptosis via targeting ABCC3 through the JNK signaling pathway
Authors: Xu Feihong , Xu Fei , Xie Shiguang , Zuo Wei , Wen Guilan , Zhao Tiantian , Wan Xuan 
Published: September 2019

AbstractIdiopathic pulmonary fibrosis (IPF) is a condition that results in the progressive deterioration of lung function with poor prognosis. The current study is aimed at exploring how microRNA‐448 (miR‐448) targeting ABCC3 affects fibroblast proliferation, apoptosis, and collagen synthesis of mice with IPF via the Jun N‐terminal kinase (JNK) signaling pathway. Bioinformatics and dual‐luciferase polymerase chain reaction were used to predict the relationship of miR‐448 and ABCC3. The expression of miR‐448 and ABCC3 was detected in IPF tissues. Using IPF mouse models, lung fibroblasts for the experiments were treated with miR‐448 mimic, miR‐448 inhibitor, si‐ABCC3, or SP600125 (inhibitor of JNK) to evaluate the cell proliferation and apoptosis in response to miR‐448. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to identify the expression of miR‐448, ABCC3, and the activation of the JNK signaling pathway. ABCC3 was targeted and downregulated by miR‐448 based on bioinformatics prediction and dual‐luciferase reporter gene assay. Additionally, miR‐448 was found to be highly expressed in IPF lung tissues with low expression levels of ABCC3. In response to the treatment of miR‐448 mimic or si‐ABCC3, lung fibroblasts exhibited decreased cell proliferation and increased apoptotic rates, whereas the miR‐448 inhibitor reversed the conditions. Notably, we also found that miR‐448 mimic inhibited the JNK signaling pathway. In conclusion, by using miR‐448 to target and downregulate ABCC3 to block the JNK signaling pathway in mice with IPF, we found an increase in fibroblast apoptosis, inhibited cell proliferation, and decreased collagen synthesis of fibroblasts.
Autophagy inhibition via Becn1 downregulation improves the mesenchymal stem cells antifibrotic potential in experimental liver fibrosis
Authors: Wang Hang Yu , Li Can , Liu Wei Hua , Deng Feng Mei , Ma Yan , Guo Li Na , Kong De Hua , Hu Kang An , Liu Qin , Wu Jiang , Sun Jing , Liu Yi Lun 
Published: September 2019

AbstractLiver fibrosis (LF) is the result of a vicious cycle between inflammation‐induced chronic hepatocyte injury and persistent activation of hepatic stellate cells (HSCs). Mesenchymal stem cell (MSC)‐based therapy may represent a potential remedy for treatment of LF. However, the fate of transplanted MSCs in LF remains largely unknown. In the present study, the fate and antifibrotic effect of MSCs were explored in a LF model induced by CCl4 in mouse. Additionally, MSCs were stimulated in vitro with LF‐associated factors, tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), and transforming growth factor‐β1 (TGF‐β1), to mimic the LF microenvironment. We unveiled that MSCs exhibited autophagy in response to the LF microenvironment through Becn1 upregulation both in vivo and in vitro. However, autophagy suppression induced by Becn1 knockdown in MSCs resulted in enhanced antifibrotic effects on LF. The improved antifibrotic potential of MSCs may be attributable to their inhibitory effects on T lymphocyte infiltration, HSCs proliferation, as well as production of TNF‐α, IFN‐γ, and TGF‐β1, which may be partially mediated by elevated paracrine secretion of PTGS2/PGE2. Thus, autophagy manipulation in MSCs may be a novel strategy to promote their antifibrotic efficacy.
α‐Chymotrypsin–catalyzed direct C (Sp3)–H functionalization reactions for synthesis of azaarene derivatives in water
Authors: Le Zhang‐Gao , Lu Yue , Jiang Guo‐Fang , Liu Yi‐Shuai , Liu Jia , Xie Zong‐Bo 
Published: September 2019

Abstractα‐Chymotrypsin from the bovine pancreas has been shown for the first time to display catalytic nonnatural catalytic ability toward the C (sp3)–H functionalization reaction of 2‐methylquinoline and aromatic aldehydes in water. α‐Chymotrypsin exhibited favorable catalytic activity with good adaptability to different substrates. The activity of the enzyme could be improved by adjusting the solvent, temperature, molar ratio of substrates, and protein loading. The products were obtained in moderate to excellent yields (51%‐93%) in 24 samples. This process afforded a potential biocatalytic approach as an alternative to chemical synthesis for azaarene derivatives.
Synthesis of novel hexahydroquinolines and 6‐amino‐2‐oxopyridine‐3,5‐dicarbonitriles incorporating sulfamethoxazole via [3 + 3] annulation
Authors: Abdelmoniem Amr M. , Abdelrahman Mohamed Gamal Mohamed , Ghozlan Said Ahmed Soliman , Abdelhamid Ismail A. 
Published: September 2019

AbstractCyclic enaminone and cyanoacetamide derivative with incorporated sulfamethoxazole moiety were prepared. Their reactions with arylidenemalononitrile derivatives in ethanol or pyridine/piperidine at reflux yielded the corresponding hexahydroquinoline and 6‐amino‐2‐oxopyridine‐3,5‐dicarbonitrile derivatives incorporating sulfamethoxazole. The mechanism and structural elucidation of products were discussed.
Integrated provision of topical pre‐exposure prophylaxis in routine family planning services in South Africa: a non‐inferiority randomized controlled trial
Authors: Mansoor Leila E , Yende‐Zuma Nonhlanhla , Baxter Cheryl , Mngadi Kathryn T , Dawood Halima , Gengiah Tanuja N , Samsunder Natasha , Schwartz Jill L , Doncel Gustavo F , Abdool Karim Quarraisha 
Published: September 2019

AbstractIntroductionTenofovir‐containing oral pre‐exposure prophylaxis (PrEP) is recommended for those at substantial risk as part of combination HIV prevention. However, there are limited data, beyond clinical trial settings, to guide the introduction of PrEP in healthcare services with adequate levels of adherence. Since young women in Africa are at high risk of HIV and likely to utilize family planning (FP) services, the feasibility, acceptability and effectiveness of integrating topical PrEP provision into routine FP services was assessed.MethodsThis two‐arm, randomized controlled, non‐inferiority, open‐label extension trial was undertaken in urban and rural KwaZulu‐Natal, South Africa. HIV‐negative eligible women (n = 372) from the parent trial (Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004) were randomized to receive tenofovir gel either through intervention (FP clinics, n = 189) or control clinics (CAPRISA research clinics, n = 183). Non‐inferiority was predefined as gel use in the intervention clinics would be no more than 20% lower than in the control clinics. Adherence, retention and HIV incidence rates were assessed.ResultsWomen were enrolled between November 2012 and October 2014, and followed up for 682.3 women‐years (mean = 22 months). Baseline characteristics of women in intervention and control clinics were comparable and retention rates were 92.1% and 92.3% respectively. Women in intervention clinics and control clinics returned on average 5.2 (95% confidence interval (CI): 4.7 to 5.7) and 5.7 (CI: 5.2 to 6.2) used gel applicators per month respectively, with a mean difference of −0.47 (CI: −1.16 to 0.21). Per‐protocol estimates were on average 5.5 (CI: 5.0 to 6.1) and 5.8 (CI: 5.3 to 6.3) respectively, with a mean difference of −0.25 (CI: −0.98 to 0.48), meeting the non‐inferiority criteria. Adherence, based on proportion of reported sex acts covered by two gel doses, was 79.9% (CI: 76.7 to 83.2) in intervention compared with 73.9% (CI: 70.7 to 77.1) in control clinics; mean difference:6.0% (CI: 1.5 to 10.6) (p = 0.009). HIV incidence rates were 3.5 (CI: 1.8 to 6.0) and 3.6 (CI: 1.9 to 6.3) per 100 women‐years in intervention and control clinics respectively. Both these incidence rates were lower than the age‐standardized rate of 6.2 per 100 women‐years (n = 444) in the placebo arm of the parent trial (p = 0.019).ConclusionsProvision of topical PrEP as part of an integrated FP service achieved higher adherence, and was as feasible, acceptable and effective in preventing HIV as provision through a research setting. This provides useful evidence for scale‐up of oral PrEP in urban and rural high burden communities.
Comparison of pulsed and oscillating gradient diffusion‐weighted MRI for characterizing hepatocellular nodules in liver cirrhosis: ex vivo study in a rat model
Authors: Wagner Mathilde , Doblas Sabrina , Poté Nicolas , Lambert Simon A. , Ronot Maxime , Garteiser Philippe , Paradis Valérie , Vilgrain Valérie , Van Beers Bernard E. 
Published: September 2019

BackgroundIn contrast to classical pulsed gradient diffusion‐weighted MRI, oscillating gradient diffusion‐weighted MR imaging (DWI) is sensitive to short distance diffusion changes at the intracellular level.PurposeTo compare the diagnostic performance of pulsed and oscillating DWI for characterizing hepatocellular nodules in a rat model of hepatic cirrhosis.Study TypeProspective, experimental study.Animal ModelCirrhosis was induced by weekly intraperitoneal injection of diethylnitrosamine in Wistar rats.Field Strength/SequenceEx vivo liver MRI was performed at 7T with T1‐weighted, T2‐weighted, pulsed, and oscillating gradient diffusion‐weighted sequences.AssessmentApparent diffusion coefficient from pulsed (ADCpulsed) and oscillating gradient (ADCoscillating) sequences was calculated in 82 nodules identified on the T1/T2‐weighted images and on pathological examination. Two pathologists classified the nodules in three categories: benign (regenerative and low‐grade dysplastic nodules), with intermediate malignancy (high‐grade dysplastic nodules and early hepatocellular carcinomas) and overtly malignant (progressed hepatocellular carcinomas).Statistical TestsDifferences between groups were assessed with Kruskal–Wallis and Mann–Whitney tests.ResultsADC, mainly ADCoscillating, increased in the group of nodules with intermediate malignancy (ADCpulsed: 0.75 ± 0.25 × 10‐3 mm2/s vs. 0.64 ± 0.07 × 10‐3 mm2/s in benign nodules, P = 0.025; ADCoscillating: 0.81 ± 0.20 × 10‐3 mm2/s vs. 0.65 ± 0.13 × 10‐3 mm2/s, P = 0.0008) and ADCpulsed decreased in the group of progressed hepatocellular carcinomas (ADCpulsed: 0.60 ± 0.08 × 10‐3 mm2/s, P = 0.042; ADCoscillating: 0.68 ± 0.08 × 10‐3 mm2/s, P = 0.1).Data ConclusionADC during hepatocarcinogenesis in rats increased in nodules with intermediate malignancy and decreased in progressed hepatocellular carcinomas. Our results suggest that oscillating gradient DWI is more sensitive to the early steps of hepatocarcinogenesis and might be useful for differentiating between high‐grade dysplastic nodules / early hepatocellular carcinomas and regenerating nodules / low‐grade dysplastic nodules.Level of Evidence: 2Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2020;51:1065–1074.
Relative Magnetic Force Measures and Their Potential Role in MRI Safety Practice
Authors: Panych Lawrence P. , Kimbrell Vera K. , Mukundan Srinivasan , Madore Bruno 
Published: September 2019

BackgroundMagnetic field markings are occasionally used at MRI sites to provide visual feedback of magnetic field strength at locations within the MRI scan room for safety purposes. In addition to magnetic field line markings, relative magnetic force, or ratio of magnetic to gravitational forces on an object, may be considered a useful complementary metric to quantify the risk associated with bringing objects containing ferromagnetic material into the magnetic field.PurposeTo develop and validate methods for deriving useful relative magnetic‐force measures including a simple force index for application to MRI safety.Study TypePhantom.PhantomA special‐purpose rig was built to experimentally measure relative magnetic forces on small ferromagnetic objects.Field StrengthRanging from 1.5T to 7T.AssessmentQuantitative comparisons were made between theoretical and measured relative magnetic forces on six objects containing ferromagnetic material: a piece of iron, a paper clip, a Kelly clamp, nail clippers, a cell phone, and a small permanent magnet.Statistical TestsAn analysis based on the Bland–Altman method was employed.ResultsAfter correction of the 1.5T data to account for assumed positioning errors of the test rig, limits of agreement between measured and estimated relative forces in the four MRI systems were ±0.16, where a relative force of 1.0 indicates that the magnetic force is equal to gravitation force. There was no significant bias in the data (P <  = 0.05).Data ConclusionAccurate measures of relative magnetic forces on ferromagnetic objects can be derived for MRI safety purposes.Level of Evidence: 1Technical Efficacy Stage: 1J. Magn. Reson. Imaging 2020;51:1260–1271.