bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redefining the age of the lower Colorado River, southwestern United States
Authors: Crow R.S. , Schwing J. , Karlstrom K.E. , Heizler M. , Pearthree P.A. , House P.K. , Dulin S. , Jänecke S.U. , Stelten M. , Crossey L.J. 
Published: February 2021

Abstract
Sanidine dating and magnetostratigraphy constrain the timing of integration of the lower Colorado River (southwestern United States and northern Mexico) with the evolving Gulf of California. The Colorado River arrived at Cottonwood Valley (Nevada and Arizona) after 5.24 Ma (during or after the Thvera subchron). The river reached the proto–Gulf of California once between 4.80 and 4.63 Ma (during the C3n.2r subchron), not at 5.3 Ma and 5.0 Ma as previously proposed. Duplication of section across newly identified strands of the Earthquake Valley fault zone (California) probably explains the discrepancy. The data also imply the start of focused plate motion and basin development in the Salton Trough (California) at 6–6.5 Ma and relative tectonic stability of the southernmost part of the lower Colorado River corridor after its integration. After integration, the Colorado River quickly incised through sediment-filled basins and divides between them as it also likely excavated Grand Canyon (Arizona). The liberated sediment from throughout the system led to deposition of hundreds of meters of Bullhead Alluvium downstream of Grand Canyon after 4.6 Ma as the river adjusted to its lower base level.
External signal preservation in halokinetic stratigraphy: A discrete element modeling approach
Authors: Cumberpatch Zoë A. , Finch Emma , Kane Ian A. 
Published: February 2021

Abstract
Subsurface salt movement in the absence of external tectonic forces can affect contemporaneous sediment deposition, mask allocyclic signals, and deform older strata. We used a discrete element model (DEM) to better understand salt-related modification of a sedimentary sequence with an increasing sedimentation rate. This permitted quantification of thinning rates and analysis of the lateral extent of synkinematic layers. Results show realistic evolution of salt-related faults, defining two salt-withdrawal basins, beyond which strata are undeformed. Thinning of stratigraphy is four times greater between the salt flank and crest than between the undeformed zone and flank, confirming an intense zone of halokinetic modulation adjacent to the diapir. Early, slowly aggrading layers are isolated within the salt-withdrawal basin and strongly influenced by salt growth, whereas later, quickly aggrading layers are more laterally extensive, matching inferences made from subsurface and outcrop data. Halokinetic modulation reduces up the stratigraphic section, mirroring observations around the Pierce diapirs, in the North Sea, offshore UK. Our DEM provides quantitative insights into the dynamic interplay between halokinetic and allocyclic controls on salt-stratigraphic relationships.
Consultant-led triage of paediatric hospital referrals: a service evaluation
Authors: Hodgson Heather Sharon , Webb Nicholas , Diskin Lynn 
Published: February 2021

ObjectiveWe established a paediatric demand management (PDM) service in our paediatric department in 2017. The aim of this consultant-delivered service is to manage referrals more efficiently by providing active triage of all referrals, daily rapid access clinics and easily accessible advice for primary healthcare professionals. This study presents an evaluation of this service.DesignMixed-methods service evaluation with analysis of data for every contact with the PDM service over a 2-year period. For each patient, the method of contact, reason for contact, presenting complaint and triage outcome were recorded. Feedback from general practitioners (GPs) and patients was gathered.ResultsData were analysed for 7162 patients. More than a quarter (2034; 28%) of all referrals were managed with advice only. Of the 4703 outpatient clinic referrals, 1285 (27%) were managed without a clinic appointment. More than half (54%) of the requests for paediatric assessment unit (PAU) admission were managed alternatively, typically with advice only or a rapid access clinic appointment. This has reversed the increasing trend of PAU admissions from primary care of preceding years. Financial analysis suggested the avoidance of these clinic appointments, and PAU admissions provided a substantial cost saving.ConclusionsOur results indicate that the PDM service has succeeded in reducing unnecessary hospital attendances by managing patients more effectively and strengthening partnerships with primary care. The service has received overwhelmingly positive feedback from GPs. This service could be replicated in other Trusts and developed in the future to facilitate further management of paediatric cases in a primary care setting.
Risks of post-colonoscopic polypectomy bleeding and thromboembolism with warfarin and direct oral anticoagulants: a population-based analysis
Authors: Lau Louis HS , Guo Cosmos LT , Yip Terry CF , Mak Joyce WY , Wong Sunny H , Lam Kelvin LY , Wong Grace LH , Ng Siew C , Chan Francis KL 
Published: February 2021

BackgroundThere were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.MethodsWe performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.ResultsApixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, p<0.001). Dabigatran (aHR 2.23, 95% CI 1.04 to 4.77, adjusted p (ap)=0.035) and rivaroxaban (aHR 2.72, 95% CI 1.35 to 5.48, ap=0.002) were associated with higher PPB risk than apixaban. In subgroup analysis, apixaban was associated with lower PPB risk in patients aged ≥70 years and patients with right-sided colonic polyps.For thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, p<0.001). Dabigatran (aHR 2.60, 95% CI 1.06 to 6.41, ap=0.033) and rivaroxaban (aHR 2.96, 95% CI 1.19 to 7.37, ap =0.013) were associated with higher thromboembolic risk than apixaban.ConclusionsApixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.
The reduced Dijkgraaf–Witten invariant of twist knots in the Bloch group of a finite field
Authors: Karuo Hiroaki 
Published: February 2021

Let [Formula: see text] be a closed oriented 3-manifold and let [Formula: see text] be a discrete group. We consider a representation [Formula: see text]. For a 3-cocycle [Formula: see text], the Dijkgraaf–Witten invariant is given by [Formula: see text], where [Formula: see text] is the map induced by [Formula: see text], and [Formula: see text] denotes the fundamental class of [Formula: see text]. Note that [Formula: see text], where [Formula: see text] is the map induced by [Formula: see text], we consider an equivalent invariant [Formula: see text], and we also regard it as the Dijkgraaf–Witten invariant. In 2004, Neumann described the complex hyperbolic volume of [Formula: see text] in terms of the image of the Dijkgraaf–Witten invariant for [Formula: see text] by the Bloch–Wigner map from [Formula: see text] to the Bloch group of [Formula: see text]. In this paper, by replacing [Formula: see text] with a finite field [Formula: see text], we calculate the reduced Dijkgraaf–Witten invariants of the complements of twist knots, where the reduced Dijkgraaf–Witten invariant is the image of the Dijkgraaf–Witten invariant for SL[Formula: see text] by the Bloch–Wigner map from [Formula: see text] to the Bloch group of [Formula: see text].
Marie Byrd Land lithospheric mantle: a review of the xenolith record
Authors: Handler Monica R. , Wysoczanski Richard J. , Gamble John A. 
Published: February 2021

Abstract
The Marie Byrd Land (MBL) lithospheric mantle xenolith record comprises over 100 samples from a range of localities spanning both major crustal terranes that comprise MBL: Ross and Amundsen provinces. Coarse granular to porphyroclastic in texture, the xenoliths are predominantly Type I spinel-bearing lherzolites to harburgites, but include rare dunite and pyroxenite examples. Garnet is absent and no hydrous phases, such as amphibole or mica, have been reported to date, although traces of apatite may be present. Characterisation of the lithospheric mantle composition and its evolution however, is hampered by patchy and uneven geochemical analyses across the xenolith suite. Nonetheless, a picture emerges of a heterogeneous lithosphere beneath both Ross and Amundsen Provinces. Previously published and new data reported here are consistent with samples ranging from variably cryptically metasomatized residua from variable (10–25%) degrees of partial melt extraction to refertilized compositions. Limited isotopic data point to a complex history, providing evidence for both ancient Proterozoic lithospheric mantle and preservation of Ordovician events. The Sr–Nd–Pb composition of the sampled lithospheric mantle overlaps the common low-µ isotopic endmember identified in Cenozoic magmatism from MBL and the wider West Antarctic Rift System.
NPM–ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation
Authors: Pawlicki Jan M. , Cookmeyer David L. , Maseda Damian , Everett John K. , Wei Fang , Kong Hong , Zhang Qian , Wang Hong Y. , Tobias John W. , Walter David M. , Zullo Kelly M. , Javaid Sarah , Watkins Amanda , Wasik Mariusz A. , Bushman Frederic D. , Riley James L. 
Published: February 2021

AbstractFusion genes including NPM–ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM–ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM–ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Finally, T-cell receptor (TCR)–generated signals were required to achieve T-cell transformation, explaining how healthy individuals can harbor T cells with NPM–ALK translocations. These findings describe the fundamental mechanisms of NPM–ALK-mediated oncogenesis and may serve as a model to better understand factors that regulate tumor formation.Significance:This investigation into malignant transformation of T cells uncovers a requirement for TCR triggering, elucidates integral signaling complexes nucleated by NPM–ALK, and delineates dynamic transcriptional changes as a T cell transforms.See related commentary by Spasevska and Myklebust, p. 3160
Chr20q Amplification Defines a Distinct Molecular Subtype of Microsatellite Stable Colorectal Cancer
Authors: Zhang Baoyi , Yao Kevin , Zhou Emily , Zhang Lanjing , Cheng Chao 
Published: February 2021

Abstract

Colorectal cancer is the third leading cause of cancer-related death in the United States. About 15% of colorectal cancers are associated with microsatellite instability (MSI) due to loss of function in the DNA mismatch repair pathway. This subgroup of patients has better survival rates and is more sensitive to immunotherapy. However, it remains unclear whether microsatellite stable (MSS) patients with colorectal cancer can be further stratified into subgroups with differential clinical characteristics. In this study, we analyzed The Cancer Genome Atlas data and found that Chr20q amplification is the most frequent copy number alteration that occurs specifically in colon (46%) and rectum (61%) cancer and is mutually exclusive with MSI. Importantly, MSS patients with Chr20q amplification (MSS-A) were associated with better recurrence-free survival compared with MSS patients without Chr20q amplification (MSS-N; P = 0.03). MSS-A tumors were associated with high level of chromosome instability and low immune infiltrations. In addition, MSS-A and MSS-N tumors were associated with somatic mutations in different driver genes, with high frequencies of mutated TP53 in MSS-A and mutated KRAS and BRAF in MSS-N. Our results suggest that MSS-A and MSS-N represent two subtypes of MSS colorectal cancer, and such stratification may be used to improve therapeutic treatment in an individualized manner.

Significance:
This study shows that chromosome 20q amplification occurs predominately in microsatellite-stable colorectal cancer and defines a distinct subtype with good prognosis, high chromosomal instability, distinct mutation profiles, and low immune infiltrations.
Depot-Medroxyprogesterone Acetate Use Is Associated with Decreased Risk of Ovarian Cancer: The Mounting Evidence of a Protective Role of Progestins
Authors: Phung Minh Tung , Lee Alice W. , Wu Anna H. , Berchuck Andrew , Cho Kathleen R. , Cramer Daniel W. , Doherty Jennifer Anne , Goodman Marc T. , Hanley Gillian E. , Harris Holly R. , McLean Karen , Modugno Francesmary , Moysich Kirsten B. , Mukherjee Bhramar , Schildkraut Joellen M. , Terry Kathryn L. , Titus Linda J. , Jordan Susan J. , Webb Penelope M. , Pike Malcolm C. , Pearce Celeste Leigh 
Published: February 2021

AbstractBackground:Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered.Methods:The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case–control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted.Results:Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50–0.85). There was a statistically significant trend of decreasing risk with increasing duration of use (Ptrend &lt; 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk.Conclusions:DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted.Impact:The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect.
Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans
Authors: Tang Li , Zhu Qianqian , Wang Zinian , Shanahan Clayton M. , Bensen Jeannette T. , Fontham Elizabeth T.H. , Smith Gary J. , Pop Elena A. , Azabdaftari Gissou , Mohler James L. , Wu Yue 
Published: February 2021

Abstract

Background:
Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA).

Methods:
SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina–Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and in situ RNA hybridization in independent sets of prostate cancer cases.

Results:
Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (Pinteraction &lt; 0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively.

Conclusions:
SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs.

Impact:
The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.
Lifestyle, Behavioral, and Dietary Risk Factors in Relation to Mammographic Breast Density in Women at High Risk for Breast Cancer
Authors: Ahern Thomas P. , Sprague Brian L. , Farina Nicholas H. , Tsai Erin , Cuke Melissa , Kontos Despina , Wood Marie E. 
Published: February 2021

AbstractBackground:Women at high risk for breast cancer due to genetics or risk factor profiles are counseled to adopt lifestyle, behavioral, and dietary changes to help reduce their risk. These recommendations are based on studies of women at average risk, so their effectiveness in high-risk women is unclear.Methods:We evaluated the impact of physical activity, smoking, alcohol consumption, and intake of folate and carotenoids on mammographic breast density—a proxy for breast cancer risk—among 387 high-risk women. Exposures were self-reported on questionnaires. Breast dense area, nondense area, and percent dense area were measured from screening mammograms with Library for Breast Radiodensity Assessment software. Cross-sectional associations were estimated with multivariable quantile regression models.Results:After adjusting for age, adiposity, reproductive history, and use of postmenopausal hormones, no breast density measure was associated with physical activity level, smoking status, alcohol consumption, or estimated intake of folate, alpha-carotene, beta-carotene, lutein/zeaxanthin, and beta-cryptoxanthin. Lycopene intake was associated with lower dense area when comparing the highest and lowest intake categories (adjusted difference in median = −14 cm2, 95% confidence interval: −29 to 1.3 cm2). This association may be explained by incomplete adjustment for adiposity.Conclusions:Recommended lifestyle, behavioral, and dietary changes to mitigate personal risk of breast cancer do not substantially impact mammographic breast density measures.Impact:Alternative strategies, such as increased uptake of chemoprevention, may better serve risk reduction efforts in women at high risk for breast cancer.
Beta-Blockers Use and Risk of Breast Cancer in Women with Hypertension
Authors: Zheng Guoqiao , Sundquist Jan , Sundquist Kristina , Ji Jianguang 
Published: February 2021

Abstract

Background:
The risk of breast cancer among hypertensive patients who use beta-blockers has attracted attention. However, the evidence is inconsistent and investigation of the dose-specific associations for subtypes of beta-blockers is limited.

Methods:
By incorporating Swedish national registers, breast cancer risk was estimated in women with hypertension who used nonselective beta-blockers and beta-1 selective blockers compared with propensity score–matched nonusers. The cumulative defined daily dose was used to study the dose–response association. Test of interaction between beta-blocker use and other antihypertensive medications was performed.

Results:
Hypertensive patients taking beta-1 selective blockers (metoprolol, atenolol, bisoprolol) had an increased risk of breast cancer with a HR and 95% confidence interval (CI) of 2.39 (1.95–2.94), 2.31 (1.46–3.64), and 3.02 (2.09–4.36), respectively. All of the observed associations were dose-dependent (Ptrend &lt; 0.0001). No significant association was found for the nonselective beta-blocker (propranolol) except that among users of agents acting on the renin–angiotensin system, those who used propranolol had increased breast cancer risk. Modification of agents acting on the renin–angiotensin system on breast cancer risk was also observed for atenolol.

Conclusions:
The increased risk of breast cancer associates with the use of beta-1 selective blockers in a dose–response manner.

Impact:
Breast cancer surveillance is recommended for hypertensive female patients using beta-1 selective blockers.
Hysterectomy and Risk of Breast, Colorectal, Thyroid, and Kidney Cancer – an Australian Data Linkage Study
Authors: Wilson Louise F. , Tuesley Karen M. , Webb Penelope M. , Dixon-Suen Suzanne C. , Stewart Louise M. , Jordan Susan J. 
Published: February 2021

Abstract

Background:
This study aimed to investigate the associations between hysterectomy for benign indications and risk of breast, colorectal, kidney, and thyroid cancer, and to explore whether these associations are modified by removal of ovaries at the time of surgery or by age at surgery.

Methods:
We conducted a retrospective cohort study of the female population of Western Australia (n = 839,332) linking data from electoral, hospital, births, deaths, and cancer records. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the associations between hysterectomy and diagnosis of breast, colorectal, kidney, and thyroid cancers.

Results:
Compared with no surgery, hysterectomy without oophorectomy (hysterectomy) and hysterectomy with bilateral salpingo-oophorectomy (hysterectomy-BSO) were associated with higher risk of kidney cancer (HR, 1.32; 95% CI, 1.11–1.56 and HR, 1.29; 95% CI, 0.96–1.73, respectively). Hysterectomy, but not hysterectomy-BSO, was related to higher risk of thyroid cancer (HR, 1.38; 95% CI, 1.19–1.60). In contrast, hysterectomy (HR, 0.94; 95% CI, 0.90–0.98) and hysterectomy-BSO (HR, 0.92; 95% CI, 0.85–1.00) were associated with lower risk of breast cancer. We found no association between hysterectomy status and colorectal cancer.

Conclusions:
The associations between hysterectomy and cancer varied by cancer type with increased risks for thyroid and kidney cancer, decreased risk for breast cancer, and no association for colorectal cancer.

Impact:
As breast, colorectal, and gynecologic cancers comprise a sizeable proportion of all cancers in women, our results suggest that hysterectomy is unlikely to increase overall cancer risk; however, further research to understand the higher risk of thyroid and kidney cancer is warranted.