bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures and Deformation in Glaciers and Ice Sheets
Authors: Jennings Stephen J. A. , Hambrey Michael J. 
Published: July 2021

AbstractThe aims of this review are to: (a) describe and interpret structures in valley glaciers in relation to strain history; and (b) to explore how these structures inform our understanding of the kinematics of large ice masses, and a wide range of other aspects of glaciology. Structures in glaciers give insight as to how ice deforms at the macroscopic and larger scale. Structures also provide information concerning the deformation history of ice masses over centuries and millennia. From a geological perspective, glaciers can be considered to be models of rock deformation, but with rates of change that are measurable on a human time‐scale. However, structural assemblages in glaciers are commonly complex, and unraveling them to determine the deformation history is challenging; it thus requires the approach of the structural geologist. A wide range of structures are present in valley glaciers: (a) primary structures include sedimentary stratification and various veins; (b) secondary structures that are the result of brittle and ductile deformation include crevasses, faults, crevasse traces, foliation, folds, and boudinage structures. Some of these structures, notably crevasses, relate well to measured strain‐rates, but to explain ductile structures analysis of cumulative strain is required. Some structures occur in all glaciers irrespective of size, and they are therefore recognizable in ice streams and ice shelves. Structural approaches have wide (but as yet under‐developed potential) application to other sub‐disciplines of glaciology, notably glacier hydrology, debris entrainment and transfer, landform development, microbiological investigations, and in the interpretation of glacier‐like features on Mars.
Improved Regional Scale Dynamic Evapotranspiration Estimation Under Changing Vegetation and Climate
Authors: Giles‐Hansen Krysta , Wei Xiaohua 
Published: July 2021

AbstractVegetation change can significantly alter evapotranspiration (ET), an important component of the terrestrial water balance, and consequently influences other hydrological processes. With no direct measurement techniques available at large spatial scales, the accurate estimation of ET under changing forest landscapes and climate is challenging. In this study, we used an improved method based on Fuh's equation (a functional form of the Budyko framework) to investigate ET responses to cumulative forest disturbance and climate in the snow‐dominated interior of British Columbia, Canada. First, we divided the study region into three distinct climate groups, and then related the watershed parameter m in Fuh's equation to vegetation change (represented by cumulative equivalent clearcut area (CECA)) and watershed properties, with independent calibration and validation watersheds. The validated relationships were used to examine regional ET variations (∼380,000 km2). Our results showed that ET in moderate climates had the highest sensitivity to CECA, characterized by wetness index between 1 and 2 (the ratio of precipitation to potential evapotranspiration). ET in dry climates (wetness index <1) was also significantly related to CECA, but with reduced sensitivity compared to the moderate climates. Wetter climates (wetness index >2) did not show a significant relationship with CECA, suggesting an insensitivity of ET to forest change. Simulations under future climate and vegetation disturbance scenarios demonstrated that ET would be further decreased in most of the study region. Forest management should consider reducing disturbance in the dry to moderate climate areas to mitigate negative impacts on hydrological processes and functions.
B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2
Authors: Fan Xiaoyan , Wang Yitao , Jiang Tinghui , Liu Tao , Jin Yuelei , Du Kailong , Niu Yulong , Zhang Chunxue , Liu Zhongyu , Lei Yunlong , Bu Youquan 
Published: July 2021

AbstractB-Myb is an important transcription factor that plays a critical role in gene expression regulation and tumorigenesis. However, its functional implication in colorectal cancer remains elusive. In this study, we found that B-Myb was significantly upregulated at both mRNA and protein levels in colorectal cancer samples compared to non-tumor counterparts. B-Myb overexpression accelerated cell proliferation, cell cycle progression and cell motility in colorectal cancer cells, and promoted tumor growth in orthotopic nude mouse models in vivo. In contrast, B-Myb depletion inhibited these malignant phenotypes. Mechanistic investigations revealed that E2F2 was a novel transcriptional target of B-Myb and is essential to B-Myb-induced malignant phenotypes. Notably, B-Myb and E2F2 exhibited positive expression correlation, and interacted with each other in colorectal cancer cells. In addition to their autoregulatory mechanisms, B-Myb and E2F2 can also directly transactivate each other, thus constituting consolidated reciprocal feed-forward transactivation loops. Moreover, both B-Myb and E2F2 are required for the activation of ERK and AKT signaling pathways in colorectal cancer cells. Taken together, our data clarified a critical role for B-Myb in colorectal cancer and unraveled an exquisite mutual collaboration and reciprocal cross regulation between B-Myb and E2F2 that contribute to the malignant progression of human colorectal cancer.
Bruton’s tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma
Authors: Yeh Chi-Tai , Chen Tzu-Tao , Satriyo Pamungkas Bagus , Wang Chun-Hua , Wu Alexander T. H. , Chao Tsu-Yi , Lee Kang-Yun , Hsiao Michael , Wang Liang-Shun , Kuo Kuang-Tai 
Published: July 2021

AbstractEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are current standard of care for patients with EGFR mutation and metastatic non-small-cell lung carcinoma (NSCLC), but most patients using EGFR TKIs acquire resistance later. So, overcoming resistance of EGFR TKIs has become an important issue in the treatment of NSCLC. Previously, therapeutics targeting Bruton’s tyrosine kinase (BTK) have been successful in treating several hematologic malignancies. However, the role of BTK in NSCLC is still unknown. In this study, by examining surgical specimens from 80 NSCLC patients and their clinicopathologic parameters, we found significant correlation between high BTK expression and tumor differentiation, p-stage, lymph node metastatic status, maximum tumor size, and poor prognosis of patients. Using two NSCLC cell lines A540 and PC9, we demonstrated that BTKpos cells exhibited more stemness (OCT4, SOX2) and EMT (E-Cadherin, Slug) markers than BTKneg cells. Knockdown of BTK sensitized the NSCLC cells to Gefitinib. Meanwhile, the second-generation BTK inhibitor Acalabrutinib effectively suppressed SOX2, STAT3/JAK2/Akt axis and potentiated the anti-proliferative effect of Gefitinib and Osimertinib in NSCLC cells, including the T790M H1975 cells. Furthermore, Acalabrutinib and Osimertinib combination exhibited significant tumor growth inhibition of H1975-derived tumors in vivo. Our findings suggested that BTK mediates stemness and EMT properties, and inhibition of BTK potentiates the effect of Gefitinib and Osimertinib in NSCLC cells resistant to TKI. This implies a new approach to treat the NSCLC patients with resistance to previous TKI treatment.
Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells
Authors: Zou Zhigeng , Zheng Wei , Fan Hongjun , Deng Guodong , Lu Shih-Hsin , Jiang Wei , Yu Xiying 
Published: July 2021

Abstract
Background
Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood.

Methods
We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells.

Results
ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model.

Conclusions
ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.
The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging
Authors: Jiang Zhong-xin , Wang Yi-ning , Li Zi-yuan , Dai Zhi-hui , He Yi , Chu Kun , Gu Jia-yi , Ji Yi-Xuan , Sun Ning-xia , Yang Fu , Li Wen 
Published: July 2021

AbstractMultifunctional N6-methyladenosine (m6A) has been revealed to be an important epigenetic component in various physiological and pathological processes, but its role in female ovarian aging remains unclear. Thus, we demonstrated m6A demethylase FTO downregulation and the ensuing increased m6A in granulosa cells (GCs) of human aged ovaries, while FTO-knockdown GCs showed faster aging-related phenotypes mediated. Using the m6A-RNA-sequence technique (m6A-seq), increased m6A was found in the FOS-mRNA-3′UTR, which is suggested to be an erasing target of FTO that slows the degradation of FOS-mRNA to upregulate FOS expression in GCs, eventually resulting in GC-mediated ovarian aging. FTO acts as a senescence-retarding protein via m6A, and FOS knockdown significantly alleviates the aging of FTO-knockdown GCs. Altogether, the abovementioned results indicate that FTO in GCs retards FOS-dependent ovarian aging, which is a potential diagnostic and therapeutic target against ovarian aging and age-related reproductive diseases.
TRIB2 desensitizes ferroptosis via βTrCP-mediated TFRC ubiquitiantion in liver cancer cells
Authors: Guo Susu , Chen Yuxin , Xue Xiangfei , Yang Yueyue , Wang Yikun , Qiu Shiyu , Cui Jiangtao , Zhang Xiao , Ma Lifang , Qiao Yongxia , Wang Jiayi 
Published: July 2021

AbstractTribbles homolog 2 (TRIB2) is known to boost liver tumorigenesis via regulating Ubiquitin (Ub) proteasome system (UPS). At least two ways are involved, i.e., acts as an adaptor protein to modulate ubiquitination functions of certain ubiquitin E3 ligases (E3s) and reduces global Ub levels via increasing the proteolysis activity of proteasome. Recently, we have identified the role of TRIB2 to relieve oxidative damage via reducing the availability of Ub that is essential for the ubiquitination and subsequent degradation of Glutathione peroxidase 4 (GPX4). Although GPX4 is a critical antioxidant factor to protect against ferroptosis, the exact evidence showing that TRIB2 desensitizes ferroptosis is lacking. Also, whether such function is via E3 remains unclear. Here, we demonstrated that deletion of TRIB2 sensitized ferroptosis via lifting labile iron in liver cancer cells. By contrast, overexpression of TRIB2 led to the opposite outcome. We further demonstrated that transferrin receptor (TFRC) was required for TRIB2 to desensitize the cells to ferroptosis. Without TFRC, the labile iron pool could not be reduced by overexpressing TRIB2. We also found that beta-transducin repeat containing E3 ubiqutin protein ligase (βTrCP) was a genuine E3 for the ubiquitination of TFRC, and TRIB2 was unable to decline labile iron level once upon βTrCP was knocked out. In addition, we confirmed that the opposite effects on ferroptosis and ferroptosis-associated lipid reactive oxygen species (ROS) generation resulted from knockout and overexpression of TRIB2 were all indispensible of TFRC and βTrCP. Finally, we demonstrated that TRIB2 exclusively manipulated RSL3- and erastin-induced-ferroptosis independent of GPX4 and glutathione (GSH). In conclusion, we elucidated a novel role of TRIB2 to desensitize ferroptosis via E3 βTrCP, by which facilitates TFRC ubiquitiation and finally decreases labile iron in liver cancer cells.
The therapeutic implications of immunosuppressive tumor aerobic glycolysis
Authors: Reinfeld Bradley I. , Rathmell W. Kimryn , Kim Tae Kon , Rathmell Jeffrey C. 
Published: July 2021

AbstractIn 2011, Hanahan and Weinberg added “Deregulating Cellular Energetics” and “Avoiding Immune Destruction” to the six previous hallmarks of cancer. Since this seminal paper, there has been a growing consensus that these new hallmarks are not mutually exclusive but rather interdependent. The following review summarizes how founding genetic events for tumorigenesis ultimately increase tumor cell glycolysis, which not only supports the metabolic demands of malignancy but also provides an immunoprotective niche, promoting malignant cell proliferation, maintenance and progression. The mechanisms by which altered metabolism contributes to immune impairment are multifactorial: (1) the metabolic demands of proliferating tumor cells and activated immune cells are similar, thus creating a situation where immune cells may be in competition for key nutrients; (2) the metabolic byproducts of aerobic glycolysis directly inhibit antitumor immunity while promoting a regulatory immune phenotype; and (3) the gene programs associated with the upregulation of glycolysis also result in the generation of immunosuppressive cytokines and metabolites. From this perspective, we shed light on important considerations for the development of new classes of agents targeting cancer metabolism. These types of therapies can impair tumor growth but also pose a significant risk of stifling antitumor immunity.
Treatment-related amenorrhea in a modern, prospective cohort study of young women with breast cancer
Authors: Poorvu Philip D. , Hu Jiani , Zheng Yue , Gelber Shari I. , Ruddy Kathryn J. , Tamimi Rulla M. , Peppercorn Jeffrey M. , Schapira Lidia , Borges Virginia F. , Come Steven E. , Warner Ellen , Lambertini Matteo , Rosenberg Shoshana M. , Partridge Ann H. 
Published: July 2021

AbstractYoung women with breast cancer experience unique treatment and survivorship issues centering on treatment-related amenorrhea (TRA), including fertility preservation and management of ovarian function as endocrine therapy. The Young Women’s Breast Cancer Study (YWS) is a multi-center, prospective cohort study of women diagnosed at age ≤40, enrolled from 2006 to 2016. Menstrual outcomes were self-reported on serial surveys. We evaluated factors associated with TRA using logistic regression. One year post-diagnosis, 286/789 (36.2%) experienced TRA, yet most resumed menses (2-year TRA: 120/699; 17.2%). Features associated with 1-year TRA included older age (OR≤30vs36-40 = 0.29 (0.17–0.48), OR31-35vs36-40 = 0.67 (0.46–0.94), p = 0.02); normal body mass index (BMI) (OR≥25vs18.5-24. =0.59 (0.41–0.83), p < 0.01); chemotherapy (ORchemo vs no chemo = 5.55 (3.60–8.82), p < 0.01); and tamoxifen (OR = 1.55 (1.11–2.16), p = 0.01). TRA rates were similar across most standard regimens (docetaxel/carboplatin/trastuzumab +/− pertuzumab: 55.6%; docetaxel/cyclophosphamide +/− trastuzumab/pertuzumab: 41.8%; doxorubicin/cyclophosphamide/paclitaxel +/− trastuzumab/pertuzumab: 44.1%; but numerically lower with AC alone (25%) or paclitaxel/trastuzumab (11.1%). Among young women with breast cancer, lower BMI appears to be an independent predictor of TRA. This finding has important implications for interpretation of prior studies, future research, and patient care in our increasingly obese population. Additionally, these data describe TRA associated with use of docetaxel/cyclophosphamide, which is increasingly being used in lieu of anthracycline-containing regimens. Collectively, these data can be used to inform use of fertility preservation strategies for women who need to undergo treatment as well as the potential need for ovarian suppression following modern chemotherapy for young women with estrogen-receptor-positive breast cancer.Clinical trial registration: www.clinicaltrials.gov, NCT01468246.
Association between genes regulating neural pathways for quantitative traits of speech and language disorders
Authors: Benchek Penelope , Igo Robert P. , Voss-Hoynes Heather , Wren Yvonne , Miller Gabrielle , Truitt Barbara , Zhang Wen , Osterman Michael , Freebairn Lisa , Tag Jessica , Taylor H. Gerry , Chan E. Ricky , Roussos Panos , Lewis Barbara , Stein Catherine M. , Iyengar Sudha K. 
Published: July 2021

AbstractSpeech sound disorders (SSD) manifest as difficulties in phonological memory and awareness, oral motor function, language, vocabulary, reading, and spelling. Families enriched for SSD are rare, and typically display a cluster of deficits. We conducted a genome-wide association study (GWAS) in 435 children from 148 families in the Cleveland Family Speech and Reading study (CFSRS), examining 16 variables representing 6 domains. Replication was conducted using the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 18 significant loci (combined p < 10−8) that we pursued bioinformatically. We prioritized 5 novel gene regions with likely functional repercussions on neural pathways, including those which colocalized with differentially methylated regions in our sample. Polygenic risk scores for receptive language, expressive vocabulary, phonological awareness, phonological memory, spelling, and reading decoding associated with increasing clinical severity. In summary, neural-genetic influence on SSD is primarily multigenic and acts on genomic regulatory elements, similar to other neurodevelopmental disorders.
Zero gravity induced by parabolic flight enhances automatic capture and weakens voluntary maintenance of visuospatial attention
Authors: Salatino Adriana , Iacono Claudio , Gammeri Roberto , Chiadò Stefano T. , Lambert Julien , Sulcova Dominika , Mouraux André , George Mark S. , Roberts Donna R. , Berti Anna , Ricci Raffaella 
Published: July 2021

AbstractOrienting attention in the space around us is a fundamental prerequisite for willed actions. On Earth, at 1 g, orienting attention requires the integration of vestibular signals and vision, although the specific vestibular contribution to voluntary and automatic components of visuospatial attention remains largely unknown. Here, we show that unweighting of the otolith organ in zero gravity during parabolic flight, selectively enhances stimulus-driven capture of automatic visuospatial attention, while weakening voluntary maintenance of covert attention. These findings, besides advancing our comprehension of the basic influence of the vestibular function on voluntary and automatic components of visuospatial attention, may have operational implications for the identification of effective countermeasures to be applied in forthcoming human deep space exploration and habitation, and on Earth, for patients’ rehabilitation.
Factors influencing SARS-CoV-2 transmission and outbreak control measures in densely populated settings
Authors: Pung Rachael , Lin Bernard , Maurer-Stroh Sebastian , Sirota Fernanda L. , Mak Tze Minn , Octavia Sophie , Pang Junxiong , Tan Iain Beehuat , Tan Clive , Ong Biauw Chi , Cook Alex R. ,   The Singapore COVID-19 Outbreak Research Team, Tan Doreen , Chua Qin Xuan , Chong Samuel Zeng Rong , Koh Han Fang , Yap Elena , Sia Priscilla , Tan Ze Ren , Lee Fong Sin , Goh Jun Kang Enan , Suor Peou Socheata Monica , Ang Julian Xiao Li , Lee Vernon J. 
Published: July 2021

AbstractStarting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid transmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories in Singapore. The aim of the study is to identify combination of factors facilitating SARS-CoV-2 transmission and the impact of control measures in a dormitory through extensive epidemiological, serological and phylogenetic investigations, supported by simulation models. Our findings showed that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak. Furthermore, each resident had about 30 close contacts and each infected resident spread to 4.4 (IQR 3.5–5.3) others at the start of the outbreak. The final attack rate of the current outbreak was 76.2% (IQR 70.6–98.0%) and could be reduced by further 10% under a modified dormitory housing condition. These findings are important when designing living environments in a post COVID-19 future to reduce disease spread and facilitate rapid implementation of outbreak control measures.
Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
Authors: AuYeung Amanda W. K. , Mould Robert C. , Stegelmeier Ashley A. , van Vloten Jacob P. , Karimi Khalil , Woods J. Paul , Petrik James J. , Wood Geoffrey A. , Bridle Byram W. 
Published: July 2021

AbstractVaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.