bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy
Authors: Gong Chunai , Yu Xiaoyan , You Benming , Wu Yan , Wang Rong , Han Lu , Wang Yujie , Gao Shen , Yuan Yongfang 
Published: June 2020

AbstractCell membrane- covered drug-delivery nanoplatforms have been garnering attention because of their enhanced bio-interfacing capabilities that originate from source cells. In this top-down technique, nanoparticles (NPs) are covered by various membrane coatings, including membranes from specialized cells or hybrid membranes that combine the capacities of different types of cell membranes. Here, hybrid membrane-coated doxorubicin (Dox)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (DPLGA@[RAW-4T1] NPs) were fabricated by fusing membrane components derived from RAW264.7(RAW) and 4T1 cells (4T1). These NPs were used to treat lung metastases originating from breast cancer. This study indicates that the coupling of NPs with a hybrid membrane derived from macrophage and cancer cells has several advantages, such as the tendency to accumulate at sites of inflammation, ability to target specific metastasis, homogenous tumor targeting abilities in vitro, and markedly enhanced multi-target capability in a lung metastasis model in vivo. The DPLGA@[RAW-4T1] NPs exhibited excellent chemotherapeutic potential with approximately 88.9% anti-metastasis efficacy following treatment of breast cancer-derived lung metastases. These NPs were robust and displayed the multi-targeting abilities of hybrid membranes. This study provides a promising biomimetic nanoplatform for effective treatment of breast cancer metastasis.
Patient reported symptoms, coping and quality of life during somatostatin analogue treatment for metastatic small- intestinal neuroendocrine tumours
Authors: Sorbye Halfdan , Meyer Liv Sylvi , Mordal Kjersti Elisabeth , Myhre Simen , Thiis-Evensen Espen 
Published: June 2020

Abstract
Background
Patients with metastatic small-intestinal neuroendocrine tumours (NET) have been shown to have a reduced quality of life compared to the general population and many have disabling symptoms during somatostatin analogue (SSA) treatment. The aim of this prospective study was to document the patient-reported symptoms, coping and quality of life during SSA treatment and to measure patients’ fat-soluble vitamin levels.

Methods
Patients with metastatic small-intestinal NET on treatment with long-acting SSA were included. Data on patient characteristics, blood samples, questionnaires (EORTC-QLQ-C30 and GI.NET-21) and structured patient interviews were collected at inclusion and after 1 year.

Results
Eighty-eight patients were included, 77 (88%) attended 1 year follow-up. Approximately 50% of patients reported symptoms, the most common symptoms at baseline and after 1 year follow-up were diarrhoea, flatulence, fatigue, abdominal discomfort and sore injection lumps. Diarrhoea and fatigue were reported as their main complaint, 23% had > 5 daily episodes of diarrhoea and 59% reported fatigue. However, patients reported a high perceived quality of life, high daily activity, coped with their symptoms and managed their daily life well. Deficiency of vitamin D (27%) and A (13%) were observed.

Conclusions
Patients with metastatic small-intestinal NET on SSA treatment reported a high frequency of symptoms. Minor improvements were seen after 1-year of follow-up, illustrating that many symptoms might be difficult to improve, or may not be recognised by the health service. Patients, however, generally reported a high quality of life. Care for NET patients on SSA treatment should include a regular systematic symptom registration and vitamin measurements.
β-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes
Authors: Robinson KaReisha F. , Narasipura Srinivas D. , Wallace Jennillee , Ritz Ethan M. , Al-Harthi Lena 
Published: June 2020

AbstractBackgroundThe Wnt/β-catenin signaling pathway is a prolific regulator of cell-to-cell communication and gene expression. Canonical Wnt/β-catenin signaling involves partnering of β-catenin with members of the TCF/LEF family of transcription factors (TCF1, TCF3, TCF4, LEF1) to regulate gene expression. IL-6 is a key cytokine involved in inflammation and is particularly a hallmark of inflammation in the brain. Astrocytes, specialized glial cells in the brain, secrete IL-6. How astrocytes regulate IL-6 expression is not entirely clear, although in other cells NFκB and C/EBP pathways play a role. We evaluated here the interface between β-catenin, TCFs/LEF and C/EBP and NF-κB in relation to IL-6 gene regulation in astrocytes.MethodsWe performed molecular loss and/or gain of function studies of β-catenin, TCF/LEF, NFκB, and C/EBP to assess IL-6 regulation in human astrocytes. Specifically, siRNA mediated target gene knockdown, cDNA over expression of target gene, and pharmacological agents for regulation of target proteins were used. IL-6 levels was evaluated by real time quantitative PCR and ELISA. We also cloned the IL-6 promoter under a firefly luciferase reporter and used bioinformatics, site directed mutagenesis, and chromatin immunoprecipitation to probe the interaction between β-catenin/TCFs/LEFs and IL-6 promoter activity.Resultsβ-catenin binds to TCF/LEF to inhibits IL-6 while TCFs/LEF induce IL-6 transcription through interaction with ATF-2/SMADs. β-catenin independent of TCFs/LEF positively regulates C/EBP and NF-κB, which in turn activate IL-6 expression. The IL-6 promoter has two putative regions for TCFs/LEF binding, a proximal site located at -91 nt and a distal site at -948 nt from the transcription start site, both required for TCF/LEF induction of IL-6 independent of β-catenin.ConclusionIL-6 regulation in human astrocytes engages a discordant interaction between β-catenin and TCF/LEF. These findings are intriguing given that no role for β-catenin nor TCFs/LEF to date is associated with IL-6 regulation and suggest that β-catenin expression in astrocytes is a critical regulator of anti-inflammatory responses and its disruption can potentially mediate persistent neuroinflammation.Graphical abstract
Mesenchymal stem cells activate Notch signaling to induce regulatory dendritic cells in LPS-induced acute lung injury
Authors: Lu Zhonghua , Meng Shanshan , Chang Wei , Fan Shanwen , Xie Jianfeng , Guo Fengmei , Yang Yi , Qiu Haibo , Liu Ling 
Published: June 2020

Abstract
Background
Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) and induce the production of regulatory dendritic cells (DCregs), but the potential link between these two cell types remains unclear. The goal of this study was to investigate the effect and mechanism of MSC-induced regulatory dendritic cells in ALI mice.

Material/methods
In vivo experiments, C57BL/6 wild-type male mice were sacrificed at different times after intratracheal injection of LPS to observe changes in lung DC maturation and pathological damage. MSCs, DCregs or/and carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled DCs were administered to the mice by tail vein, and flow cytometry was performed to measure the phenotype of lung DCs and T cells. Lung injury was estimated by the lung wet weight/body weight ratio and histopathological analysis. In vitro, Western blotting or flow cytometry was used to detect the expression of Notch ligand or receptor in MSCs or DCs after coculture or LPS stimulation. Finally, in vivo and in vitro, we used the Notch signaling inhibitor DAPT to verify the effect of the Notch pathway on MSC-induced DCregs and their pulmonary protection.

Results
We showed significant accumulation and maturation of lung DCs 2 h after intratracheal injection of LPS, which were positively correlated with the lung pathological injury score. MSC treatment alleviated ALI lung injury, accompanied by a decrease in the number and maturity of classical DCs in the lungs. CFSE-labeled DCs migrated to the lungs of ALI mice more than those of the normal group, and the elimination of CFSE-labeled DCs in the blood was slower. MSCs inhibited the migration of CFSE-labeled DCs to the lung and promoted their elimination in the blood. DCregs, which are obtained by contact coculture of mDCs with MSCs, expressed reduced levels of MHCII, CD86, CD40 and increased levels of PD-L1, and had a reduced ability to stimulate lymphocyte proliferation and activation (expression of CD44 and CD69). mDCs expressing Notch2 significantly increased after coculture with MSCs or rhJagged1, and MSCs expressed more Jagged1 after LPS stimulation. After stimulation of mDCs with recombinant Jagged1, DCs with low expression of MHCII, CD86 and CD40 were also induced, and the effects of both rhJagged1 and MSCs on DCs were blocked by the Notch inhibitor DAPT. Intra-airway DAPT reversed the inhibitory effect of mesenchymal stem cells on DC recruitment to the lungs and its maturation.

Conclusions
Our results suggested that the recruitment and maturation of lung DCs is an important process in early ALI, MSCs attenuate LPS-induced ALI by inducing the production of DCregs by activating Notch signaling.
Serum IgG-induced microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma
Authors: Ding Xu , Yang Wei , Ren Qinghua , Hu Jiajian , Yang Shen , Han Wei , Wang Jing , Wang Xu , Wang Huanmin 
Published: June 2020

Abstract
Background
Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis and activates several signaling pathways. However, the mechanisms underlying OMS remain unclear. Here, we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS.

Methods
The activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines, and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia-conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated.

Results
Incubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells. Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB. Furthermore, the expression of NO, sGC, and PKG was increased. Neuronal cytolysis was relieved by the inhibitors of NO signaling, while neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. The cytolysis of neurons was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG.

Conclusions
Serum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate.
A comparison of two personalization and adaptive cognitive rehabilitation approaches: a randomized controlled trial with chronic stroke patients
Authors: Faria Ana Lúcia , Pinho Maria Salomé , Bermúdez i Badia Sergi 
Published: June 2020

Abstract
Background
Paper-and-pencil tasks are still widely used for cognitive rehabilitation despite the proliferation of new computer-based methods, like VR-based simulations of ADL’s. Studies have established construct validity of VR assessment tools with their paper-and-pencil version by demonstrating significant associations with their traditional construct-driven measures. However, VR rehabilitation intervention tools are mostly developed to include mechanisms such as personalization and adaptation, elements that are disregarded in their paper-and-pencil counterparts, which is a strong limitation of comparison studies. Here we compare the clinical impact of a personalized and adapted paper-and-pencil training and a content equivalent and more ecologically valid VR-based ADL’s simulation.

Methods
We have performed a trial with 36 stroke patients comparing Reh@City v2.0 (adaptive cognitive training through everyday tasks VR simulations) with Task Generator (TG: content equivalent and adaptive paper-and-pencil training). The intervention comprised 12 sessions, with a neuropsychological assessment pre, post-intervention and follow-up, having as primary outcomes: general cognitive functioning (assessed by the Montreal Cognitive Assessment - MoCA), attention, memory, executive functions and language specific domains.

Results
A within-group analysis revealed that the Reh@City v2.0 improved general cognitive functioning, attention, visuospatial ability and executive functions. These improvements generalized to verbal memory, processing speed and self-perceived cognitive deficits specific assessments. TG only improved in orientation domain on the MoCA, and specific processing speed and verbal memory outcomes. However, at follow-up, processing speed and verbal memory improvements were maintained, and a new one was revealed in language. A between-groups analysis revealed Reh@City v2.0 superiority in general cognitive functioning, visuospatial ability, and executive functions on the MoCA.

Conclusions
The Reh@City v2.0 intervention with higher ecological validity revealed higher effectiveness with improvements in different cognitive domains and self-perceived cognitive deficits in everyday life, and the TG intervention retained fewer cognitive gains for longer.

Trial registration
The trial is registered at ClinicalTrials.gov, number NCT02857803. Registered 5 August 2016, .
Performance of commercially available anti-HDV enzyme-linked immunosorbent assays in Taiwan
Authors: Lin Guan-Yu , Wu Yi-Le , Wang Cheng-Si , Ko Chia-Yun , Chen Chien-Hung , Chen Pei-Jer , Peng Po-Hsin , Hsu Chao-Wei 
Published: June 2020

Abstract
Background
Hepatitis D virus (HDV) infection is a major global health issue around the world. There are approximately 15–20 million individuals infected with HDV worldwide. HDV infection usually causes increased mortality compared with infection with hepatitis B virus (HBV) alone. However, testing for the detection of HDV is not widely available in Taiwan. Therefore, the General Biologicals Corporation (GB) HDV Ab kit was developed for detecting anti-HDV antibodies.

Methods
A total of 913 serum and 462 EDTA-treated plasma samples were obtained from HBsAg-positive individuals in three hospitals in Taiwan from June 2014 to November 2017. We used three commercially available ELISA kits, DiaPro HDV Ab, DiaSorin ETI-AB-DELTAK-2 and GB HDV Ab, which were utilized strictly according to the instructions of the manufacturers.

Results
A comparative study of the results from the GB HDV Ab kit and the other commercial ELISA kits (DiaPro and DiaSorin) was performed to determine their efficacy for anti-HDV detection. The results indicated that the sensitivity of the GB HDV Ab kit for serum and EDTA samples was 100% compared to that of the DiaPro and DiaSorin kits, whereas the specificity for serum and EDTA samples was 99.3 and 98.1%, respectively. In addition, the overall agreement of the results of the GB HDV Ab kit for the serum and EDTA samples was 99.3 and 98.3%, respectively. It is worth noting that the performance of the GB HDV Ab kit was not affected by interference from triglyceride, bilirubin, hemoglobin, or human anti-mouse antibody. The limit of detection of the GB HDV Ab kit is approximately 100-fold lower than that of the other two commercial kits.

Conclusions
The GB HDV Ab kit, which presented equivalent sensitivity and specificity compared to both certified anti-HDV kits, would be a suitable kit for HDV diagnosis in Taiwan.
Minimally invasive far lateral debridement combined with posterior instrumentation for thoracic and lumbar tuberculosis without severe kyphosis
Authors: Xiong Wei , Yu Bing , Zhang Yao , Wang Chunxiao , Tang Xiaojie , Cao Haifei , Zhang Xibing , Song Qinyong , Tan Fang , Tan Jiangwei 
Published: June 2020

Abstract
Background
Anti-tuberculous therapy (ATT) alone cannot easily cure spine tuberculosis (STB) though it is the most essential treatment. Many studies have confirmed the efficacy of the surgical treatment of STB through anterior, anterolateral, posterior debridement, and intervertebral fusion or combined with internal fixation. However, the conventional surgical approach requires extensive exposure of the affected areas with high rates of morbidity and mortality. Recently, minimally invasive surgery has come into use to reduce iatrogenic trauma and relevant complications. Here, we introduced a novel technique for the treatment of thoracic and lumbar spine tuberculosis: minimally invasive far lateral debridement and posterior instrumentation (MI-FLDPI). In this study, we evaluated the technical feasibility, the clinical outcomes, and the postoperative complications.

Methods
We did a prospective, non-randomized study on this new technique. Twenty three patients (13 males) with thoracic or lumbar spine tuberculosis who underwent minimally invasive far lateral debridement and posterior instrumentation were included in the study. The preoperative comorbidities, operation duration, intra-operative hemorrhage, Cobb’s angles, and postoperative complications were recorded and analyzed. Clinical outcomes were evaluated by Visual Analog Scale (VAS), Oswestry Disability Index (ODI), neurological recovery, and eradication of tuberculosis. Radiological outcomes were evaluated by changes in Cobb’s angle and fusion status of the affected segments.

Results
The patients were followed for an average of 19 months (ranging from 12 to 36 months). At the final follow-up, CRP and ESR of all patients were normal. The VAS and ODI were significantly improved compared with preoperative values (P < 0.05). No evident progression of the kyphotic deformity was found after surgery. Twenty two patients showed spontaneous peripheral interbody fusion 1 year after surgery. There were no failure of the instrumentation even though a young female with drug-resistant tuberculosis showed no sign of interbody fusion at the third year follow-up. All the patients with preoperative neurological deficit showed complete recovery at the final follow-up.

Conclusions
MI-FLDPI using expandable tubular retractor could be recommended to treat thoracic and lumbar spine tuberculosis for the advantages of less trauma, earlier recovery, and less complications. Spontaneous peripheral interbody fusion was observed in nearly all the cases even without bone grafting.
Repeat-induced point mutation in Neurospora crassa causes the highest known mutation rate and mutational burden of any cellular life
Authors: Wang Long , Sun Yingying , Sun Xiaoguang , Yu Luyao , Xue Lan , He Zhen , Huang Ju , Tian Dacheng , Hurst Laurence D. , Yang Sihai 
Published: June 2020

Abstract
Background
Repeat-induced point (RIP) mutation in Neurospora crassa degrades transposable elements by targeting repeats with C→T mutations. Whether RIP affects core genomic sequence in important ways is unknown.

Results
By parent-offspring whole genome sequencing, we estimate a mutation rate (3.38 ×  10−6 per bp per generation) that is two orders of magnitude higher than reported for any non-viral organism, with 93–98% of mutations being RIP-associated. RIP mutations are, however, relatively rare in coding sequence, in part because RIP preferentially attacks GC-poor long duplicates that interact in three dimensional space, while coding sequence duplicates are rare, GC-rich, short, and tend not to interact. Despite this, with over 5 coding sequence mutations per genome per generation, the mutational burden is an order of magnitude higher than the previously highest observed. Unexpectedly, the majority of these coding sequence mutations appear not to be the direct product of RIP being mostly in non-duplicate sequence and predominantly not C→T mutations. Nonetheless, RIP-deficient strains have over an order of magnitude fewer coding sequence mutations outside of duplicated domains than RIP-proficient strains.

Conclusions
Neurospora crassa has the highest mutation rate and mutational burden of any non-viral life. While the high rate is largely due to the action of RIP, the mutational burden appears to be RIP-associated but not directly caused by RIP.
Study protocol for daiobotanpito combined with antibiotic therapy for treatment of acute diverticulitis: a study protocol for a randomized controlled trial
Authors: Ogawa-Ochiai Keiko , Yoshimura Kenichi , Shirai Akiko , Sakai Seisho , Moriyama Hideki , Nakamura Keishi , Murayama Toshinori , Ishikawa Hideki 
Published: June 2020

Abstract
Background
Colonic diverticular disease has been increasing in prevalence due to the rapidly aging global population, but standard treatment has not changed dramatically in recent years. Daiobotanpito (DBT; Da Huang Mu Dan Tang in Chinese) has been used in medical treatment of acute abdominal abscesses, such as appendicitis or diverticulitis in traditional Japanese (Kampo) medicine for many years, based on more than 3000 years of experience. Prior to this study, a retrospective open-label trial was conducted to compare patients with acute diverticulitis who received oral DBT combined with intravenous antibiotics with those who received intravenous antibiotic alone; it showed a positive effect of DBT on acute diverticulitis. We aim to investigate whether moderate to severe acute diverticulitis shows greater improvement with intravenous antibiotics plus orally administered DBT compared with intravenous antibiotics plus placebo.

Methods
This is a two-group, randomized, double-blind, placebo-controlled, multi-center trial, which is designed to evaluate the efficacy and safety of DBT in patients with moderate to severe diverticulitis treated with intravenous antibiotics. Eligible participants will be randomized to either a treatment group receiving a 10-day oral DBT regimen plus conventional therapy or a control group receiving a 10-day placebo regimen plus conventional therapy. The primary outcome will be success in treating diverticulitis: the success rate will be defined as elimination of abdominal pain within 4 days in all patients, and in patients with fever (body temperature ≧ 37.5 °C) on inclusion into this study, fever relief with reduction in body temperature to < 37.5 °C within 3 days. Secondary endpoints will include the number of hospitalization days, changes in inflammatory response (C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts), fever type, number of days before beginning food intake, recurrence rate (observation for 1 year after registration), and adverse event expression rate. Assessments will be performed at baseline and on the day of discharge. The recurrence rate will be recorded at 1 year after registration.

Discussion
This study is expected to provide evidence to support the clinical benefits of DBT in the treatment of acute diverticulitis. It may also provide evidence on the efficacy and safety of DBT in the recurrence of acute diverticulitis.

Trial registration
UMIN-CTR: UMIN000027381. Registered on 27 April 2017.
https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000031377, and changed to jRCTs041180063, registered on 30 July 2019; as a result of the revision of the domestic law in 2018 in Japan.