bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer health disparities in racial/ethnic minorities in the United States
Authors: Zavala Valentina A. , Bracci Paige M. , Carethers John M. , Carvajal-Carmona Luis , Coggins Nicole B. , Cruz-Correa Marcia R. , Davis Melissa , de Smith Adam J. , Dutil Julie , Figueiredo Jane C. , Fox Rena , Graves Kristi D. , Gomez Scarlett Lin , Llera Andrea , Neuhausen Susan L. , Newman Lisa , Nguyen Tung , Palmer Julie R. , Palmer Nynikka R. , Pérez-Stable Eliseo J. , Piawah Sorbarikor , Rodriquez Erik J. , Sanabria-Salas María Carolina , Schmit Stephanie L. , Serrano-Gomez Silvia J. , Stern Mariana C. , Weitzel Jeffrey , Yang Jun J. , Zabaleta Jovanny , Ziv Elad , Fejerman Laura 
Published: September 2020

AbstractThere are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA—African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.
Bisphosphonates and risk of cancers: a systematic review and meta-analysis
Authors: Li Yuan-Yuan , Gao Li-Jie , Zhang Yu-Xue , Liu Shu-Juan , Cheng Shuo , Liu Yu-Peng , Jia Cun-Xian 
Published: September 2020

Abstract
Background
It is unclear whether bisphosphonates are associated with risk of cancers. Therefore, this meta-analysis aimed to evaluate the effect of bisphosphonates on overall cancers.

Methods
A search in Pubmed, Embase, Cochrane Library and Web of Science databases was conducted, from the inception date of each resource to September 26, 2019. The summarised effect estimates with 95% CIs were calculated using a random-effect model. Heterogeneity and publication bias were explored.

Results
Thirty-four articles were included in this study (4,508,261 participants; 403,196 cases). The results revealed that bisphosphonates significantly decreased the risk of colorectal cancer (RR = 0.89, 95% CI: 0.81–0.98), breast cancer (RR = 0.87, 95% CI: 0.82–0.93) and endometrial cancer (RR = 0.75, 95% CI: 0.61–0.94), but no significant association was observed in all-cause cancer. Furthermore, nitrogen-containing bisphosphonates only had protective effects both on breast cancer (RR = 0.94, 95% CI: 0.90–0.99) and endometrial cancer (RR = 0.70, 95% CI: 0.54–0.92). Non-nitrogen-containing bisphosphonates tended to increase the risk of liver cancer (RR = 2.14, 95% CI: 1.23–3.72) and pancreas cancer (RR = 1.75, 95% CI: 1.32–2.33).

Conclusion
Bisphosphonates are significantly associated with risk reduction of colorectal, breast and endometrial cancer, especially nitrogen-containing bisphosphonates. It should be noted that non-nitrogen-containing bisphosphonates might increase the risk of liver and pancreas cancer. Large prospective cohort studies are needed to find the causal association between bisphosphonates and risk of cancers.
CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage
Authors: Albert Marie-Christine , Brinkmann Kerstin , Pokrzywa Wojciech , Günther Saskia Diana , Krönke Martin , Hoppe Thorsten , Kashkar Hamid 
Published: September 2020

AbstractThe BH3-only protein NOXA is a regulator of mitochondrial apoptosis by specifically antagonizing the anti-apoptotic protein MCL-1. Here we show that the E3 ubiquitin ligase CHIP controls NOXA stability after DNA damage. Our findings reveal that CHIP and MCL-1 are binding partners of NOXA and differentially define the fate of NOXA. Whereas NOXA is initially targeted to mitochondria upon MCL-1-binding, CHIP mediates ubiquitylation of cytosolic NOXA and promotes lysosomal degradation of NOXA, which is not bound by MCL-1. Our data indicate that MCL-1 defines NOXA abundance and its pro-apoptotic activity. Increased NOXA levels beyond this threshold are effectively removed by lysosomal protein degradation triggered via CHIP-mediated ubiquitylation. Together, these results shed new light on regulatory circuits controlling DNA damage response and identified the E3 ligase CHIP as a new molecular guardian, which restricts the cytosolic accumulation of NOXA upon genotoxic stress.
UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis
Authors: Gu Chaohui , Zhao Keyuan , Zhou Naichun , Liu Feng , Xie Fei , Yu Shunli , Feng Yongjie , Chen Long , Yang Jinjian , Tian Fengyan , Jiang Guosong 
Published: September 2020

AbstractEmerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan–Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3′UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.
Upregulation of CPT1A is essential for the tumor-promoting effect of adipocytes in colon cancer
Authors: Xiong Xiaopeng , Wen Yang-An , Fairchild Rachelle , Zaytseva Yekaterina Y. , Weiss Heidi L. , Evers B. Mark , Gao Tianyan 
Published: September 2020

AbstractColon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient deprivation and reduced tumor organoid formation in 3D culture and the expression of genes associated with cancer stem cells downstream of Wnt/β-catenin. Mechanistically, CPT1A-dependent FAO promoted the acetylation and nuclear translocation of β-catenin. Furthermore, knockdown of CPT1A blocked the tumor-promoting effect of adipocytes in vivo and inhibited xenograft tumor initiation. Taken together, our findings identify CPT1A-depedent FAO as an essential metabolic pathway that enables the interaction between adipocytes and colon cancer cells.
Bromodomain-containing protein 9 promotes the growth and metastasis of human hepatocellular carcinoma by activating the TUFT1/AKT pathway
Authors: Dou Changwei , Sun Liankang , Wang Liang , Cheng Jian , Wu Weiding , Zhang Chengwu , Xu Qiuran , Tu Kangsheng , Liu Jie 
Published: September 2020

AbstractBromodomain-containing protein 9 (BRD9) has a critical role in human squamous cell lung cancer, acute myeloid leukemia, and malignant rhabdoid tumors. However, the expression and biological role of BRD9 in hepatocellular carcinoma (HCC) is poorly understood. In this study, BRD9 expression was found to be elevated in HCC through data mining of public databases. Next, we confirmed that the expression of BRD9 was increased in HCC tissues compared with that in adjacent non-tumor tissues. The upregulated level of BRD9 was also observed in HCC cells in comparison to LO2 cells. The increased BRD9 expression was correlated with unfavorable clinicopathological features. A high level of BRD9 predicted a poorer overall survival and disease-free survival of HCC patients. Functionally, BRD9 overexpression facilitated the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of Hep3B cells. Conversely, either BRD9 depletion or pharmacological inhibition of BRD9 resulted in the reduced proliferation and invasiveness of HCCLM3 cells. In addition, the BRD9 knockdown restrained the growth and metastasis of HCCLM3 cells in vivo. Mechanistically, BRD9 positively regulated TUFT1 expression and AKT activation in HCC cells. ChIP-qPCR analysis indicated that BRD9 promoted the binding of P300 acetyltransferase to the TUFT1 promoter and epigenetically regulated TUFT1 expression by increasing H3K27Ac in the promoter. Notably, either TUFT1 knockdown or AKT inhibitor (MK2206) abrogated the promoting effects of BRD9 on the proliferation, migration, invasion, and EMT of Hep3B cells. The forced expression of TUFT1 abolished the effects of BRD9 knockdown on the growth and metastasis of HCCLM3 cells. Altogether, these data indicate that BRD9 promotes the growth and metastasis of HCC cells by activating the TUFT1/AKT pathway and may serve as a promising biomarker and therapeutic target for HCC.
MFG-E8 accelerates wound healing in diabetes by regulating “NLRP3 inflammasome-neutrophil extracellular traps” axis
Authors: Huang Wei , Jiao Jinyu , Liu Ju , Huang Meng , Hu Yanyan , Ran Wenzhuo , Yan Li , Xiong Yin , Li Mei , Quan Ziyao , Rao Yahua , Chen Jiayi , Huang Yan , Zhang Dongxin 
Published: September 2020

AbstractSustained activation of NLRP3 inflammasome and release of neutrophil extracellular traps (NETs) impair wound healing of diabetic foot ulcers (DFUs). Our previous study reported that milk fat globule epidermal growth factor VIII (MFG-E8) attenuates tissue damage in systemic lupus erythematosus. However, the functional effect of MFG-E8 on “NLRP3 inflammasome-NETs” inflammatory loop in wound healing of diabetes is not completely elucidated. In this study, neutrophils from DFU patients are susceptible to undergo NETosis, releasing more NETs. The circulating levels of NET components neutrophil elastase and proteinase 3 and inflammatory cytokines IL-1β and IL-18 were significantly elevated in DFU patients compared with healthy controls or diabetic patients, in spite of higher levels of MFG-E8 in DFU patients. In Mfge8−/− diabetic mice, skin wound displayed exaggerated inflammatory response, including leukocyte infiltration, excessive activation of NLRP3 inflammasome (release of higher IL-1β, IL-18, and TNF-α), largely lodged NETs, resulting in poor angiogenesis and wound closure. When stimulated with high-dose glucose or IL-18, MFG-E8-deficient neutrophils release more NETs than WT neutrophils. After administration of recombinant MFG-E8, IL-18-primed NETosis of WT or Mfge8−/− neutrophils was significantly inhibited. Furthermore, NET and mCRAMP (component of NETs, the murine equivalent of cathelicidin LL-37 in human)-mediated activation of NLRP3 inflammasome and production of IL-1β/IL-18 were significantly elevated in Mfge8−/− macrophages compared with WT macrophages, which were also significantly dampened by the administration of rmMFG-E8. Therefore, our study demonstrated that as inhibitor of the “NLRP3 inflammasome-NETs” inflammatory loop, exogenous rMFG-E8 improves angiogenesis and accelerates wound healing, highlighting possible therapeutic potential for DFUs.
Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance
Authors: Eagle Andrew L. , Manning Claire E. , Williams Elizabeth S. , Bastle Ryan M. , Gajewski Paula A. , Garrison Amber , Wirtz Alexis J. , Akguen Seda , Brandel-Ankrapp Katie , Endege Wilson , Boyce Frederick M. , Ohnishi Yoshinori N. , Mazei-Robison Michelle , Maze Ian , Neve Rachel L. , Robison Alfred J. 
Published: September 2020

AbstractChronic stress is a key risk factor for mood disorders like depression, but the stress-induced changes in brain circuit function and gene expression underlying depression symptoms are not completely understood, hindering development of novel treatments. Because of its projections to brain regions regulating reward and anxiety, the ventral hippocampus is uniquely poised to translate the experience of stress into altered brain function and pathological mood, though the cellular and molecular mechanisms of this process are not fully understood. Here, we use a novel method of circuit-specific gene editing to show that the transcription factor ΔFosB drives projection-specific activity of ventral hippocampus glutamatergic neurons causing behaviorally diverse responses to stress. We establish molecular, cellular, and circuit-level mechanisms for depression- and anxiety-like behavior in response to stress and use circuit-specific gene expression profiling to uncover novel downstream targets as potential sites of therapeutic intervention in depression.
Low dimensional nanostructures of fast ion conducting lithium nitride
Authors: Tapia-Ruiz Nuria , Gordon Alexandra G. , Jewell Catherine M. , Edwards Hannah K. , Dunnill Charles W. , Blackman James M. , Snape Colin P. , Brown Paul D. , MacLaren Ian , Baldoni Matteo , Besley Elena , Titman Jeremy J. , Gregory Duncan H. 
Published: September 2020

AbstractAs the only stable binary compound formed between an alkali metal and nitrogen, lithium nitride possesses remarkable properties and is a model material for energy applications involving the transport of lithium ions. Following a materials design principle drawn from broad structural analogies to hexagonal graphene and boron nitride, we demonstrate that such low dimensional structures can also be formed from an s-block element and nitrogen. Both one- and two-dimensional nanostructures of lithium nitride, Li3N, can be grown despite the absence of an equivalent van der Waals gap. Lithium-ion diffusion is enhanced compared to the bulk compound, yielding materials with exceptional ionic mobility. Li3N demonstrates the conceptual assembly of ionic inorganic nanostructures from monolayers without the requirement of a van der Waals gap. Computational studies reveal an electronic structure mediated by the number of Li-N layers, with a transition from a bulk narrow-bandgap semiconductor to a metal at the nanoscale.
Femtosecond laser programmed artificial musculoskeletal systems
Authors: Ma Zhuo-Chen , Zhang Yong-Lai , Han Bing , Hu Xin-Yu , Li Chun-He , Chen Qi-Dai , Sun Hong-Bo 
Published: September 2020

AbstractNatural musculoskeletal systems have been widely recognized as an advanced robotic model for designing robust yet flexible microbots. However, the development of artificial musculoskeletal systems at micro-nanoscale currently remains a big challenge, since it requires precise assembly of two or more materials of distinct properties into complex 3D micro/nanostructures. In this study, we report femtosecond laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive protein (bovine serum albumin, BSA) as the smart muscle. To realize the programmable integration of the two materials into a 3D configuration, a successive on-chip two-photon polymerization (TPP) strategy that enables structuring two photosensitive materials sequentially within a predesigned configuration was proposed. As a proof-of-concept, we demonstrate a pH-responsive spider microbot and a 3D smart micro-gripper that enables controllable grabbing and releasing. Our strategy provides a universal protocol for directly printing 3D microbots composed of multiple materials.
Computational screen-out strategy for electrically pumped organic laser materials
Authors: Ou Qi , Peng Qian , Shuai Zhigang 
Published: September 2020

AbstractElectrically pumped organic lasing is one of the most challenging issues in organic optoelectronics. We present a systematic theoretical investigation to screen out electrical pumping lasing molecules over a wide range of organic materials. With the electronic structure information obtained from time-dependent density functional theory, we calculate multiple photophysical parameters of a set of optical pumping organic laser molecules in our self-developed molecular material property prediction package (MOMAP) to judge whether the electrically pumped lasing conditions can be satisfied, namely, to avoid reabsorption from excitons and/or polarons, and the accumulation of triplet excitons. In addition, a large oscillator strength of S1 and weak intermolecular π–π interaction are preferred. With these criteria, we are able to conclude that BP3T, BSBCz, and CzPVSBF compounds are promising candidates for electrically pumped lasing, and the proposed computational strategy could serve as a general protocol for molecular design of organic lasing materials.
Integration of molecular profiles in a longitudinal wellness profiling cohort
Authors: Tebani Abdellah , Gummesson Anders , Zhong Wen , Koistinen Ina Schuppe , Lakshmikanth Tadepally , Olsson Lisa M. , Boulund Fredrik , Neiman Maja , Stenlund Hans , Hellström Cecilia , Karlsson Max J. , Arif Muhammad , Dodig-Crnković Tea , Mardinoglu Adil , Lee Sunjae , Zhang Cheng , Chen Yang , Olin Axel , Mikes Jaromir , Danielsson Hanna , von Feilitzen Kalle , Jansson Per-Anders , Angerås Oskar , Huss Mikael , Kjellqvist Sanela , Odeberg Jacob , Edfors Fredrik , Tremaroli Valentina , Forsström Björn , Schwenk Jochen M. , Nilsson Peter , Moritz Thomas , Bäckhed Fredrik , Engstrand Lars , Brodin Petter , Bergström Göran , Uhlen Mathias , Fagerberg Linn 
Published: September 2020

AbstractAn important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
Chiroptical spectroscopy of a freely diffusing single nanoparticle
Authors: Sachs Johannes , Günther Jan-Philipp , Mark Andrew G. , Fischer Peer 
Published: September 2020

AbstractChiral plasmonic nanoparticles can exhibit strong chiroptical signals compared to the corresponding molecular response. Observations are, however, generally restricted to measurements on stationary single particles with a fixed orientation, which complicates the spectral analysis. Here, we report the spectroscopic observation of a freely diffusing single chiral nanoparticle in solution. By acquiring time-resolved circular differential scattering signals we show that the spectral interpretation is significantly simplified. We experimentally demonstrate the equivalence between time-averaged chiral spectra observed for an individual nanostructure and the corresponding ensemble spectra, and thereby demonstrate the ergodic principle for chiroptical spectroscopy. We also show how it is possible for an achiral particle to yield an instantaneous chiroptical response, whereas the time-averaged signals are an unequivocal measure of chirality. Time-resolved chiroptical spectroscopy on a freely moving chiral nanoparticle advances the field of single-particle spectroscopy, and is a means to obtain the true signature of the nanoparticle’s chirality.
Collectively stabilizing and orienting posterior migratory forces disperses cell clusters in vivo
Authors: Lin B. , Luo J. , Lehmann R. 
Published: September 2020

AbstractIndividual cells detach from cohesive ensembles during development and can inappropriately separate in disease. Although much is known about how cells separate from epithelia, it remains unclear how cells disperse from clusters lacking apical–basal polarity, a hallmark of advanced epithelial cancers. Here, using live imaging of the developmental migration program of Drosophila primordial germ cells (PGCs), we show that cluster dispersal is accomplished by stabilizing and orienting migratory forces. PGCs utilize a G protein coupled receptor (GPCR), Tre1, to guide front-back migratory polarity radially from the cluster toward the endoderm. Posteriorly positioned myosin-dependent contractile forces pull on cell–cell contacts until cells release. Tre1 mutant cells migrate randomly with transient enrichment of the force machinery but fail to separate, indicating a temporal contractile force threshold for detachment. E-cadherin is retained on the cell surface during cell separation and augmenting cell–cell adhesion does not impede detachment. Notably, coordinated migration improves cluster dispersal efficiency by stabilizing cell–cell interfaces and facilitating symmetric pulling. We demonstrate that guidance of inherent migratory forces is sufficient to disperse cell clusters under physiological settings and present a paradigm for how such events could occur across development and disease.