bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bifidobacterium adolescentis improves lifespan and healthspan by regulating catalase activity and oxidative stress-associated metabolites
Authors: Chen Shujie , Chen Luyi , Qi Yadong , Xu Jilei , Ge Qiwei , Fan Yuedan , Chen Du , Zhang Yawen , Wang Lan , Hou Tongyao , Yang Xiaohang , Xi Yongmei , Si Jianmin , Kang Lijun , Wang Liangjing 
Published: October 2020

Abstract
Microbiota-host interaction was involved in aging, while the specific bacterium was undetermined. To identify candidate bacterium with aging, we performed fecal microbiota sequencing. Less richness of gut microbial community, and a reduction of B.adolescentis abundance was observed in elderly individuals. B. adolescentis supplement improved osteoporosis and neurodegeneration in telomerase RNA component deletion (Terc−/−) aged mice. B.adolescentis induced prolongevity and healthspan improvement in Drosophila melanogaster and C. elegans. Transgenic deletion of ctl-2 in C. elegans abolished the effect on lifespan and healthspan by B. adolescentis. The catalase activity was decreased in skeletal muscle and brain tissues of Terc−/− mice, as well as cellular senescence in mouse embryonic fibroblasts. B. adolescentis alleviated ROS accumulation by regulation of oxidative stress-associated metabolites. These results suggest a role for B. adolescentis in improving lifespan and healthspan by regulating catalase activity and host metabolism. Supplement with commensal bacteria is a promising strategy against age related diseases.
Microscale diffusiophoresis of proteins
Authors: Peter Quentin , Jacquat Raphaël , Herling Therese , Challa Pavan , Kartanas Tadas , Knowles Tuomas 
Published: October 2020

Abstract
Living systems are characterised by their spatially highly inhomogeneous nature which is susceptible to modify fundamentally the behaviour of biomolecular species, including the proteins that underpin biological functionality in cells. Spatial gradients in chemical potential are known to lead to strong transport effects for colloidal particles, but their effect on molecular scale species such as proteins has remained largely unexplored. Here we demonstrate with microfluidic measurements that individual proteins can undergo strong diffusiophoretic motion in salt gradients in a manner which is sufficient to overcome diffusion and lead to dramatic changes in their spatial organisation on the scale of a cell. Moreover, we demonstrate that this phenomenon can be used to control the motion of proteins in microfluidics devices. These results open up a path towards a physical understanding of the role of gradients in living systems in the spatial organisation of macromolecules and highlight novel routes towards protein sorting applications on device.
Most cancers carry a substantial deleterious load due to Hill-Robertson interference
Authors: McFarland Christopher , Tilk Susanne , Curtis Christina , Petrov Dmitri 
Published: October 2020

Abstract
Cancer genomes exhibit surprisingly weak signatures of negative selection. This may be because tumors evolve under weak selective pressures (‘weak selection’) or because genome-wide linkage in cancer prevents most deleterious mutations from being removed due to Hill-Robertson interference3 (‘inefficient selection’). The weak selection model argues that most genes are only important for multicellular function and that selection acts only on a subset of essential genes. In contrast, the inefficient selection model predicts that only cancers with low mutational burdens, where linkage effects are minimal, will exhibit strong signals of negative selection against deleterious passengers and positive selection for beneficial drivers. We leverage the 10,000-fold variation in mutational burden across cancer subtypes to stratify tumors by their genome-wide mutational burden and used a normalized ratio of nonsynonymous to synonymous substitutions (dN/dS) to quantify the extent that selection varies with mutation rate. We find that appreciable negative selection (dN/dS ~ 0.4) is present in tumors with a low mutational burden, while the remaining cancers (96%) exhibit dN/dS ratios approaching 1, suggesting that the majority of tumors do not remove deleterious passengers. A parallel pattern is seen in drivers, where positive selection attenuates as the mutational burden of cancers increases. Both trends persist across tumor-types, are not exclusive to essential or housekeeping genes, are present in clonal and subclonal mutations, and persist in Copy Number Alterations. A consequence of this inability to remove deleterious passengers is that tumors with elevated mutational burdens, which are expected to harbor substantial protein folding stress, upregulate heat shock pathways. Finally, using evolutionary modeling, we find that Hill-Robertson interference alone can reproduce the patterns of attenuated selection observed in both drivers and passengers if the average fitness cost of passengers is 1.0% and the average fitness benefit of drivers is 19%. As a result, despite the weak individual fitness effects of passengers, most cancers harbor a large mutational load (median ~40% total fitness cost). Collectively, our findings suggest that the lack of observed negative selection in most tumors is not due to relaxed selective pressures, but rather the inability of selection to remove individual deleterious mutations in the presence of genome-wide linkage.
Combined Pars Plana Glaucoma Drainage Device Placement and Vitrectomy Using a Vitrectomy Sclerotomy Site for Tube Placement: A Case Series
Authors: Chang Enchi Kristina , Gupta Sanchay , Chachanidze Marika , Miller John B. , Chang Ta Chen , Valle David A. Solá-Del 
Published: October 2020

Abstract
Background: The purpose of this study is to report the safety and efficacy of pars plana (PP) glaucoma drainage devices (GDDs) with pars plana vitrectomy (PPV) using one of the vitrectomy sclerotomy sites for tube placement in patients with refractory glaucoma.Methods: Retrospective case series of 28 eyes of 28 patients who underwent combined PP GDD and PPV between November 2016 and September 2019 at Massachusetts Eye and Ear. Main outcome measures were intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity (BCVA), and complications. Statistical tests were performed with R and included Kaplan-Meier analyses, Wilcoxon paired signed-rank tests, and Fisher tests.Results: Mean IOP decreased from 22.8 mmHg to 11.4 mmHg at 1.5 years (p = 0.009), and mean medication burden decreased from 4.3 to 1.7 at 1.5 years (p = 0.009). Both IOP and medication burden were significantly lower at all follow-up time points. The probability of achieving 5 ≤ IOP ≤ 18 mmHg with at least 20% IOP reduction from preoperative levels was 77.7% at 1 year and 45.8% at 1.5 years. At their last visit, four eyes (14.3%) achieved complete success with IOP reduction as above without medications, and 13 eyes (46.2%) achieved qualified success with medications. Visual acuity was unchanged or improved in 23 eyes (82.1%) at their last follow-up. Two patients had a visual acuity decrease of >2 lines. Two eyes required subsequent PPV for tube obstruction, and one eye had transient hypotony.Conclusions: The results of pars plana GDD and vitrectomy using one of the vitrectomy sclerotomy sites for tube placement are promising, resulting in significant IOP and medication-burden reductions through postoperative year 1.5 without additional risk of postoperative complications. Inserting GDDs into an existing vitrectomy sclerotomy site may potentially save surgical time by obviating the need to create another sclerotomy for tube placement and suture one of the vitrectomy ports.
Combined Vaccine-Immune-Checkpoint Inhibition Constitutes a Promising Strategy for Treatment of dMMR Tumors
Authors: Salewski Inken , Kuntoff Steffen , Kuemmel Andreas , Feldtmann Rico , Felix Stephan , Henze Larissa , Junghanss Christian , Maletzki Claudia 
Published: October 2020

Abstract
Background: Mlh1-knock-out-driven mismatch-repair-deficient (dMMR) tumors can be targeted immunologically. By applying therapeutic tumor vaccination, tumor growth is delayed but escape mechanisms evolve, characterized by the upregulation of immune-checkpoint molecules (LAG-3, PD-L1). To counteract immune escape, we investigated the therapeutic activity of a combined tumor vaccine-immune checkpoint inhibitor therapy using α-PD-L1 monoclonal antibody clone 6E11.Design: In this trial, Mlh1-knock-out mice with established gastrointestinal tumors received single or thrice injections of α-PD-L1 monoclonal antibody clone 6E11 (2.5 mg/kg bw, q2w, i.v.) either alone or in combination with the vaccine. Longitudinal flow cytometry and PET/CT imaging studies were followed by ex vivo functional immunological and gene expression assays.Results: 6E11 monotherapy slightly increased median overall survival (mOS: 6.0 weeks vs. control 4.0 weeks). Increasing the number of injections (n=3) improved therapy outcome (mOS: 9.2 weeks) and was significantly boosted by combining 6E11 with the vaccine (mOS: 19.4 weeks vs. 10.2 weeks vaccine monotherapy). Accompanying PET/CT imaging confirmed treatment-induced tumor growth control, with the strongest inhibition in the combination group. Three mice (30%) achieved a complete remission and showed long-term survival. Decreased levels of circulating splenic and intratumoral myeloid-derived suppressor cells (MDSC) and decreased numbers of immune-checkpoint-expressing splenic T cells (LAG-3, CTLA-4) accompanied therapeutic effects. Gene expression and protein analysis of residual tumors revealed downregulation of PI3K/Akt/Wnt and TGF-signaling, leading to T cell infiltration and reduced numbers of macrophages, neutrophils, and MDSC.Conclusions: By successful uncoupling of the PD-1/PD-L1 axis, we provide further evidence for the safe and successful application of immunotherapies to combat dMMR-driven malignancies that warrants further investigation.
GRP75-upregulated HMGA1 Expression Promotes Stage I Lung Adenocarcinoma Progression by Activating the JNK/c-JUN Signaling Pathway
Authors: Qiao Guo-Bing , Wang Ren-Tao , Wang Shu-Nan , Tao Shaolin , Tan Qun-You , Jin Hua 
Published: October 2020

Abstract
Background: Recurrence is a major challenge in early-stage lung adenocarcinoma (LUAD) treatment. However, the recurrence mechanism is still unclear, and no biomarkers can predict recurrence in early-stage LUAD. Here, we investigated the role and mechanism of high-mobility group AT-hook 1 (HMGA1) and glucose-regulated protein 75-kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD.Methods: A TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early-stage LUAD. Western blotting and immunohistochemistry were used to measure protein expression levels. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA-sequencing analysis.Results: High expression of HMGA1 and GRP75 was associated with recurrence and a poor prognosis in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor. Overexpression of GRP75 or HMGA1 promoted LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis. In vitro and clinical data showed that the expression level of GRP75 positively regulated HMGA1 in LUAD and that GRP75 played an HMGA1-dependent role. In addition, GRP75 prolonged the half-life of HMGA1 by inhibiting HMGA1 ubiquitination via direct binding to HMGA1. Finally, we demonstrated that the GRP75/HMGA1 axis played a role by activating JNK/c-JUN signaling in LUAD.Conclusions: The activation of GRP75/HMGA1/JNK/c-JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and prognosis in patients with stage I LUAD.
Mechanical Power During Extracorporeal Membrane Oxygenation and Hospital Mortality in Patients With Acute Respiratory Distress Syndrome
Authors: Chiu Li-Chung , Lin Shih-Wei , Chuang Li-Pang , Li Hsin-Hsien , Liu Pi-Hua , Tsai Feng-Chun , Chang Chih-Hao , Hung Chen-Yiu , Lee Chung-Shu , Leu Shaw-Woei , Hu Han-Chung , Huang Chung-Chi , Wu Huang-Pin , Kao Kuo-Chin 
Published: October 2020

Abstract
Background: Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP normalized to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of normalized MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).Methods: We performed a secondary analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. Results: A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3 %. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that MP alone, MP normalized to PBW, and MP normalized to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP normalized to compliance (HR 2.289 [95% CI 1.214-4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018-1.104], p = 0.005) or MP normalized to PBW (HR 1.004 [95% CI 1.002-1.007], p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7 % versus 46.8 %, p = 0.004), and the 90-day hospital mortality of patients with high MP normalized to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP normalized to compliance (≦ 0.53 J/min/ml/cm H2O) (63.1 % versus 29.5 %, p < 0.001).Conclusions: MP during the first 3 days of ECMO was the only ventilator setting independently associated with 90-day hospital mortality, and MP normalized to compliance during ECMO was more predictive for mortality than was MP alone.
BiVO4/Fe3O4@polydopamine Superparticles for Tumor Multimodal Imaging and Synergistic Therapy
Authors: Wang Ze , Wang Guan , Kang Tingting , Liu Shuwei , Wang Lu , Zou Haoyang , Chong Yu , Liu Yi 
Published: October 2020

Abstract
Background: Despite tremendous progress has been achieved in tumor theranostic over the past decade, accurate identification and complete eradication of tumor cells remain a great challenge owing to the limitation of single imaging modality and therapeutic strategy. Results: Herein, we successfully design and construct BiVO4/Fe3O4@polydopamine (PDA) superparticles (SPs) for computed tomography (CT)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging and radiotherapy (RT)/photothermal therapy (PTT) synergistic therapy toward oral epithelial carcinoma. On the one hand, BiVO4 NPs endow BiVO4/Fe3O4@PDA SPs with impressive X-ray absorption capability due to the high X-ray attenuation coefficient of Bi, which is beneficial for their utilization as radiosensitizers for CT imaging and RT. On the other hand, Fe3O4 NPs impart BiVO4/Fe3O4@PDA SPs with the superparamagnetic property as a T2-weighted contrast agent for MR imaging. Importantly, the aggregation of Fe3O4 NPs in SPs and the presence of PDA shell greatly improve the photothermal conversion capability of SPs, making BiVO4/Fe3O4@PDA SPs as an ideal photothermal transducer for PA imaging and PTT. By integrating advantages of various imaging modalities (CT/PA/MR) and therapeutic strategies (RT/PTT), our BiVO4/Fe3O4@PDA SPs exhibit the sensitive multimodal imaging feature and superior synergistic therapeutic efficacy on tumors. Conclusion: Since there are many kinds of building blocks with unique properties appropriating for self-assembly, our work may largely enrich the library of nanomateirals for tumor diagnosis and treatment.
Protective Effects of Erythronium Japonicum and Corylopsis Coreana Uyeki Extracts Against 1,3-dichloro-2-propanol-induced Hepatotoxicity in Rats
Authors: Bae Chun-Sik , Kim Seunghyun , Boo Hee-Ock , Ahn Taeho 
Published: October 2020

Abstract
Erythronium japonicum (E. japonicum) and Corylopsis coreana Uyeki (C. coreana Uyeki, Korean winter hazel) have been shown to significantly decrease 1,3-dichloro-2-propanol (1,3-DCP)-induced generation of reactive oxygen species and CYP2E1 activity in HuH7, human hepatocytes. In this study, we expanded upon the previous study and investigated the effects of E. japonicum and C. coreana Uyeki extracts on 1,3-DCP-induced liver damage in rats. The pre-treatment of rats with these extracts alleviated a decrease in body weight and reduced 1,3-DCP-induced increase in catalytic activities of hepatic enzymes, such as aspartate aminotransferase and alanine aminotransferase, in the serum. Moreover, treatment with the extracts restored the 1,3-DCP-induced decreases in anti-oxidant enzyme activities, such as the activities of superoxide dismutase and catalase, in the rat liver. Histopathological studies also strongly supported the results of enzyme activities.
A Bimodal Burst Energy Distribution of a Repeating Fast Radio Burst Source
Authors: Li Di , Wang P. , Zhu Weiwei , Zhang Bing , Zhang Xinxin , Duan Ran , Zhang Yongkun , Feng Yi , Tang Ningyu , Chatterjee Shami , Cordes James , Cruces Marylin , Gajjar Vishal , Hobbs George , Jin Chengjin , Kramer Michael , Lorimer Duncan , Miao C.C. , Niu Chenhui , Niu J.R. , Pan Zhichen , Qian Lei , Dai Shi , Spitler Laura , Werthimer Dan , Xie Xiaoyao , Yue Youling , Zhang Lei , Zhi Qijun , Zhu Yan 
Published: October 2020

Abstract
Fast radio bursts (FRBs) are cosmic sources that emit millisecond-duration radio pulses with a wide range of luminosities and yet unknown origin(s) (Petroff et al. 2019; cordes et al. 2019). A subset of FRBs were found to repeat, the prototype of which is the first precisely-located FRB 121102 (Spitler et al. 2016), residing in a dwarf galaxy at redshift z=0.193 (Chatterjee 2017; Tendulkar et al. 2017). The source has been observed by most major telescopes and shows non-Poisson clustering of bursts over time, the hitherto highest burst rate, and a burst isotropic equivalent energy largely consistent with a power-law (Law et al. 2017; zhang et al. 2018; Gourdji et al. 2019), all of which are crucial characteristics to be compared to non-repeating sources. However, due to sensitivity limits, no true energy distribution of any FRB is known. Here we report the detection of 1652 independent bursts, more than quadruple the total of all previously published ones combined, in a total of 59.5 observing hours spanning 47 days using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). The peak burst rate of 122 hr-1is by far the highest ever observed of any FRB. A characteristic peak in the isotropic equivalent energy distribution is found to be ~4.8×1037 erg at 1.25 GHz, suggesting a possible threshold for producing abundant coherent radio bursts from FRBs. The burst energy distribution is optimally described by a bimodal distribution consisting of a log-normal function plus a Cauchy function. While no periodicity was found between 1 ms and 1000 s, and the majority of the burst arrival times are consistent with being random, there exists a visible peak in the waiting time distribution at about 3.4 ms, corresponding to significant clustering. Our results start to reveal the stochastic nature of abundant weaker bursts, which could be present in other FRB sources, apparently repeating or not. FRB generation mechanisms must be efficient and economical. Expensive triggers and/or contrived conditions for burst production seem unlikely.
Breast Cancer Screening Strategies and Indicators in Iran, A Systematic Review
Authors: Omidi Zahra , Koosha Maryam , Nazeri Najmeh , Khosravi Nasim , Haghighat Shahpar 
Published: October 2020

Abstract
BackgroundA lot of individual health behaviors and multi-faceted approached have been introduced for breast cancer early diagnosis and prevention. This systematic review aimed to investigate the status of Breast cancer preventive behaviors and screening indicators among Iranian women.MethodsIn this study, two reviewers included English and Persian articles about breast cancer screening modalities and its indicators in Iran from January 2005 to 2020. English electronic databases of Web of Science, PubMed and Scopus and Persian databases of SID and IranMedex were used. The critical information of articles was extracted and classified to different categories according to the studied outcomes. ResultsA total of 246 articles were assessed which 129 of them were excluded and 114 studies were processed for further evaluation. Performing BSE, CBE, and Mammo in Iranian women had been reported 0- 79.4%, 4.1%-41.1%, and 1.3%-45%, respectively. All of the educational interventions had increased the knowledge, attitude and practice of participants in performing the screening behaviors. The most important screening indicators included participation rate (3.8% to 16.8%), detection rate (0.23 to 8.5 per 1000), abnormal call rate (28.77% to 33%), and recall rate (24.7%).ConclusionThis systematic review demonstrated a lot of heterogeneity in population and design of researches about breast cancer early detection in Iran. The necessity of a cost-effective screening program, presenting a proper educational method for increasing women's awareness and estimating screening indices can be the priorities of future researches. Establishing big studies at the national level in a standard framework are advised