bluuebunny/crossref_metadata_2025_split huggingface dataset:
UMOD and you! Explaining a rare disease diagnosis
Authors: Mabillard Holly , Olinger Eric , Sayer John A. 
Published: December 2022

AbstractThe precise molecular genetic diagnosis of a rare inherited disease is nearly always a prolonged odyssey. Fortunately, modern molecular testing strategies are allowing more diagnoses to be made. There are many different rare inherited kidney diseases and both the genetic heterogeneity of these conditions and the clinical diversity often leads to confusing nomenclature. Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an example of this. ADTKD, an inherited kidney disease that leads to worsening of kidney function over time, often culminating in end stage kidney disease, accounting for around 2% of this cohort. UMOD is the most common gene implicated in this disorder but there are at least 6 subtypes. At present, there are no specific treatments for ADTKD. Here, we review the current understanding of this condition and provide patient-centred information to allow conceptual understanding of this disease to allow better recognition, diagnosis and management.
Using a multicultural and multilingual awareness-raising strategy to enhance enrollment of racially underrepresented minoritized communities – the PassITON trial
Authors: Bell Jasmine , Cook Sarah , Edwards Terri L. , Rice Todd W. , Self Wesley H. , Wheeler Allison , Rhoads Jillian , Stewart Thomas G. , Pulley Jill M. , Benhoff Katelyn , Harris Paul A. , Wilkins Consuelo 
Published: December 2022

Abstract
Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.
Sixty years of ice form and flow at Camp Century, Greenland
Authors: Colgan William , Jakobsen Jakob , Solgaard Anne , Løkkegaard Anja , Abermann Jakob , Khan Shfaqat A. , Csatho Beata , MacGregor Joseph A. , Fausto Robert S. , Karlsson Nanna , Pedersen Allan Ø. , Andersen Signe B. , Sonntag John , Hvidberg Christine S. , Ahlstrøm Andreas P. 
Published: December 2022

AbstractThe magnitude and azimuth of horizontal ice flow at Camp Century, Greenland have been measured several times since 1963. Here, we provide a further two independent measurements over the 2017–21 period. Our consensus estimate of horizontal ice flow from four independent satellite-positioning solutions is 3.65 ± 0.13 m a−1at an azimuth of 236 ± 2°. A portion of the small, but significant, differences in ice velocity and azimuth reported between studies likely results from spatial gradients in ice flow. This highlights the importance of restricting inter-study comparisons of ice flow estimates to measurements surveyed within a horizontal distance of one ice thickness from each other. We suggest that ice flow at Camp Century is stable on seasonal to multi-decadal timescales. The airborne and satellite laser altimetry record indicates an ice thickening trend of 1.1 ± 0.3 cm a−1since 1994. This thickening trend is qualitatively consistent with previously inferred ongoing millennial-scale ice thickening at Camp Century. The ice flow divide immediately north of Camp Century may now be migrating southward, although the reasons for this divide migration are poorly understood. The Camp Century flowlines presently terminate in the vicinity of Innaqqissorsuup Oqquani Sermeq (Gade Gletsjer) on the Melville Bay coast.
On intersection probabilities of four lines inside a planar convex domain
Authors: Martirosyan Davit , Ohanyan Victor 
Published: December 2022

AbstractLet
$n\geq 2$
random lines intersect a planar convex domain D. Consider the probabilities
$p_{nk}$
,
$k=0,1, \ldots, {n(n-1)}/{2}$
that the lines produce exactly k intersection points inside D. The objective is finding
$p_{nk}$
through geometric invariants of D. Using Ambartzumian’s combinatorial algorithm, the known results are instantly reestablished for
$n=2, 3$
. When
$n=4$
, these probabilities are expressed by new invariants of D. When D is a disc of radius r, the simplest forms of all invariants are found. The exact values of
$p_{3k}$
and
$p_{4k}$
are established.
Contracting Welfare Services to Social Organizations in China: Multiple Logics
Authors: Qu Yuanyuan , Howell Jude , Enjuto Martinez Regina 
Published: December 2022

AbstractAs part of a broader direction of welfare and governance reforms, China has launched a policy to contract welfare services out to social organizations. Scholars have explored the implementation of the policy in a few socioeconomically advanced cities such as Guangzhou, Shenzhen and Shanghai. In this article, we examine how local governments lacking nongovernmental services suppliers or resources for contracting respond to the policy. We developed a framework of multiple logics to analyse services contracting in a county-level city in eastern China. We found that local officials follow three logics in implementing the policy: to meet the central state's targets, to balance policy outcomes and risks, and to stimulate a more participatory society. This generates a mix of policy behaviour, including entrepreneurialism, welfarism, innovation, risk-sharing and collaboration. We thus argue the interplay of the logics determines the local policy process of services contracting in China.
The Roman Republican castellum of Puig Castellar (Biosca): the earliest evidence for military headquarters in Hispania Citerior (180–120 BCE)
Authors: Rodrigo Esther , Romaní Núria , Carreras Cesar , Pera Joaquim , Catarineu Laia 
Published: December 2022

AbstractThis paper illustrates the results of research carried out at the archaeological site of Puig Castellar de Biosca (Catalonia, Spain), located in the northeast of the Iberian Peninsula. This Republican military fortress, a castellum, is exceptional due both to its early chronology, which ranges between 180 and 120 BCE, and to the fact that it acted as a long-lasting military installation situated in a pacified area on the periphery of the Celtiberian conflict zone. Work at the site has uncovered a central building on the top of a hill, which due to its Italian features has been identified as the headquarters of the military fortress. If this interpretation is correct, this might be one of the first examples of a Republican military headquarters building documented to date. It could then be considered a predecessor of later praetoria and principia, which have been recorded in the Numantine camps and on the Roman westernlimes.
Sea Level and Socioeconomic Uncertainty Drives High‐End Coastal Adaptation Costs
Authors: Wong T. E. , Ledna C. , Rennels L. , Sheets H. , Errickson F. C. , Diaz D. , Anthoff D. 
Published: December 2022

AbstractSea‐level rise and associated flood hazards pose severe risks to the millions of people globally living in coastal zones. Models representing coastal adaptation and impacts are important tools to inform the design of strategies to manage these risks. Representing the often deep uncertainties influencing these risks poses nontrivial challenges. A common uncertainty characterization approach is to use a few benchmark cases to represent the range and relative probabilities of the set of possible outcomes. This has been done in coastal adaptation studies, for example, by using low, moderate, and high percentiles of an input of interest, like sea‐level changes. A key consideration is how this simplified characterization of uncertainty influences the distributions of estimated coastal impacts. Here, we show that using only a few benchmark percentiles to represent uncertainty in future sea‐level change can lead to overconfident projections and underestimate high‐end risks as compared to using full ensembles for sea‐level change and socioeconomic parametric uncertainties. When uncertainty in future sea level is characterized by low, moderate, and high percentiles of global mean sea‐level rise, estimates of high‐end (95th percentile) damages are underestimated by between 18% (SSP1‐2.6) and 46% (SSP5‐8.5). Additionally, using the 5th and 95th percentiles of sea‐level scenarios underestimates the 5%–95% width of the distribution of adaptation costs by a factor ranging from about two to four, depending on SSP‐RCP pathway. The resulting underestimation of the uncertainty range in adaptation costs can bias adaptation and mitigation decision‐making.
Investigation of the ΣO/N2 Depletion With Latitudinally Tilted Equatorward Boundary Observed by GOLD During the Geomagnetic Storm on April 20, 2020
Authors: Yu Tingting , Cai Xuguang , Ren Zhipeng , Li Shaoyang , Pedatella Nicholas , He Maosheng 
Published: December 2022

AbstractA long‐lived (>10 hr) O/N2 column density ratio (∑O/N2) depletion at middle latitudes was observed by the Global‐scale Observations of the Limb and Disk (GOLD) during the 20 April 2020 geomagnetic storm. The observed ∑O/N2 depletion tilts latitudinally at equatorward boundary with the lowest latitude of ∼20°N at ∼75°W, and changes orientation near 75°W, with a north‐westward tilt to the west of ∼75W and a north‐eastward tilt to the east of ∼75W. The National Center for Atmospheric Research Thermosphere Ionosphere Electrodynamics General Circulation Model shows the similar ∑O/N2 depletion patterns and magnitudes, but the longitudes with the most equatorward were ∼100°W and moved westward from ∼100°W to ∼140°W during the storm recovery period. Horizontal winds play major role in forming this middle‐latitude ∑O/N2 depletion structure. The strongest equatorward winds in the longitude sector near the magnetic pole resulted in the most equatorward expansion of all longitudes, generating the depletion with latitudinally tilted equatorward boundary. In addition, the high‐latitude westward zonal wind and the middle‐latitude eastward zonal wind maintained the long existence of this depletion in the GOLD Field of View. The further analysis on neutral winds shows that storm‐time meridional winds at middle latitudes in the mid‐low thermosphere are mainly dominated by pressure gradient force, while zonal winds are determined primarily by horizontal momentum advection.
Composition of Mars's Dayside Ionosphere Under Changing Solar Irradiance Conditions
Authors: Hensley K. , Withers P. , Thiemann E. 
Published: December 2022

AbstractThe response of the Mars ionosphere to changes in solar irradiance is an important aspect of how conditions on Mars are shaped by our dynamic Sun. Changes in the composition of ionospheric plasma with changes in solar irradiance will affect how the ionosphere mediates the interaction of the neutral atmosphere with the surrounding space environment. Here we use MAVEN ion and neutral density measurements acquired at low (Deep Dip 8) and high (Deep Dip 2) solar irradiance conditions to determine how ion and neutral densities change when the ionizing solar irradiance doubles. We find that the neutral composition does not change significantly when examined at fixed total neutral number density. Furthermore, we find that and O+ densities increase by a factor of 2, but densities increase by a factor of 1.5. The relative abundance of decreases as solar irradiance increases. These results are explained by straightforward theoretical considerations of changes in ion production and loss rates. However, a photochemical model fails to reproduce these results with its default set of inputs. Consistent with previous modeling efforts, densities are over‐predicted. Acceptable model–data agreement requires significant adjustments to important model inputs, such as reduction in irradiance by 15%, reduction in CO2 density by a factor of 2, and increase in O density by a factor of 2. These large adjustments are suggestive of the need for improvements to the state of Mars ionosphere models based on MAVEN inputs rather than issues with the underlying data.
Submesoscale Frontal Instabilities Modulate Large‐Scale Distribution of the Winter Deep Mixed Layer in the Kuroshio‐Oyashio Extension
Authors: Ding Yang , Xu Lixiao , Xie Shang‐Ping , Sasaki Hideharu , Zhang Zhengguang , Cao Haijin , Zhang Yang 
Published: December 2022

AbstractIn the mid‐latitude North Pacific, the wintertime ocean heat loss reaches the maximum in the Kuroshio‐Oyashio Extension (KOE) region. However, the mixed layer depth (MLD) there is shallow (<50 m), flanked by a zonal band of deep MLD (>100 m) on either side. Such an observed mixed layer pattern is not reproduced by coarse‐resolution or mesoscale eddy‐resolving (1/10°) models. What causes the observed MLD shoaling along the KOE frontal region? Here we show that the mixed layer shoaling in the front is well reproduced by a 1/30°, submesoscale‐permitting ocean general circulation model, indicating that it is closely related to the submesoscale frontal dynamics. The geostrophic strain rate is strong along the sharp KOE front, favoring submesoscale frontal instabilities. The surface buoyancy loss during winter reduces stratification and enhances the fronts (i.e., with steeper, northward rising isopycnals). The available potential energy stored in the narrow fronts can be released in the form of eddy kinetic energy by the mixed layer baroclinic instabilities (MLI). The associated vigorous ageostrophic motions associated with MLI efficiently slump the vertically oriented isopycnals and restratify the mixed layer. Thus, the MLD is shallow in the KOE frontal region despite the strong surface heat loss and wind stirring during winter. The submesoscale processes revealed here have important implications for improving climate models.
Secular Evolution of Continents and the Earth System
Authors: Cawood Peter A. , Chowdhury Priyadarshi , Mulder Jacob A. , Hawkesworth Chris J. , Capitanio Fabio A. , Gunawardana Prasanna M. , Nebel Oliver 
Published: December 2022

AbstractUnderstanding of secular evolution of the Earth system is based largely on the rock and mineral archive preserved in the continental lithosphere. Based on the frequency and range of accessible data preserved in this record, we divide the secular evolution into seven phases: (a) “Proto‐Earth” (ca. 4.57–4.45 Ga); (b) “Primordial Earth” (ca. 4.45–3.80 Ga); (c) “Primitive Earth” (ca. 3.8–3.2 Ga); (d) “Juvenile Earth” (ca. 3.2–2.5 Ga); (e) “Youthful Earth” (ca. 2.5–1.8 Ga); (f) “Middle Earth” (ca. 1.8–0.8 Ga); and (g) “Contemporary Earth” (since ca. 0.8 Ga). Integrating this record with knowledge of secular cooling of the mantle and lithospheric rheology constrains the changes in the tectonic modes that operated through Earth history. Initial accretion and the Moon forming impact during the Proto‐Earth phase likely resulted in a magma ocean. The solidification of this magma ocean produced the Primordial Earth lithosphere, which preserves evidence for intra‐lithospheric reworking of a rigid lid, but which also likely experienced partial recycling through mantle overturn and meteorite impacts. Evidence for craton formation and stabilization from ca. 3.8 to 2.5 Ga, during the Primitive and Juvenile Earth phases, likely reflects some degree of coupling between the convecting mantle and a lithosphere initially weak enough to favor an internally deformable, squishy‐lid behavior, which led to a transition to more rigid, plate like, behavior by the end of the early Earth phases. The Youthful to Contemporary phases of Earth, all occurred within a plate tectonic framework with changes between phases linked to lithospheric behavior and the supercontinent cycle.
Multi‐Scale Geomagnetic Forcing Derived From High‐Resolution Observations and Their Impacts on the Upper Atmosphere
Authors: Sheng Cheng , Deng Yue , Bristow William A. , Nishimura Yukitoshi , Heelis Roderick A. , Gabrielse Christine 
Published: December 2022

AbstractTechniques developed in the past few years enable the derivation of high‐resolution regional ion convection and particle precipitation patterns from the Super Dual Auroral Radar Network (SuperDARN) and Time History of Events and Macroscale Interactions during Substorms All‐Sky Imager (ASI) observations, respectively. For the first time in this study, a global ionosphere‐thermosphere model (GITM) is driven by such high‐resolution patterns to simulate the I‐T response to the multi‐scale geomagnetic forcing during a real event. Specifically, GITM simulations have been conducted for the 26 March 2014 event with different ways to specify the high‐latitude forcing, including empirical models, high‐resolution SuperDARN convection patterns, and high‐resolution ASI particle precipitation maps. Multi‐scale ion convection forcing estimated from high‐resolution SuperDARN observations is found to have a very strong meso‐scale component. Multi‐scale convection forcing increases the regional Joule heating (integrated over the high‐resolution SuperDARN observation domain) by ∼30% on average, which is mostly contributed by the meso‐scale component. Meso‐scale electron precipitation derived from ASI measurements contributes on average about 30% to the total electron energy flux, and its impact on the I‐T system is comparable to the meso‐scale convection forcing estimated from SuperDARN observations. Both meso‐scale convection and precipitation forcing are found to enhance ionospheric and thermospheric disturbances with prominent structures and magnitudes of a few tens of meters per second in the horizontal neutral winds at 270 km and a few percent in the neutral density at 400 km through comparisons between simulations driven by the original and smoothed high‐resolution forcing patterns.
Lipid desaturation regulates the balance between self-renewal and differentiation in mouse blastocyst-derived stem cells
Authors: Mannully Chanchal Thomas , Bruck-Haimson Reut , Zacharia Anish , Orih Paul , Shehadeh Alaa , Saidemberg Daniel , Kogan Natalya M. , Alfandary Sivan , Serruya Raphael , Dagan Arie , Petit Isabelle , Moussaieff Arieh 
Published: December 2022

AbstractStem cells are defined by their ability to self-renew and differentiate, both shown in multiple studies to be regulated by metabolic processes. To decipher metabolic signatures of self-renewal in blastocyst-derived stem cells, we compared early differentiating embryonic stem cells (ESCs) and their extra-embryonic counterparts, trophoblast (T)SCs to their self-renewing counterparts. A metabolomics analysis pointed to the desaturation of fatty acyl chains as a metabolic signature of differentiating blastocyst-derived SCs via the upregulation of delta-6 desaturase (D6D; FADS2) and delta-5 desaturase (D5D; FADS1), key enzymes in the biosynthesis of polyunsaturated fatty acids (PUFAs). The inhibition of D6D or D5D by specific inhibitors or SiRNA retained stemness in ESCs and TSCs, and attenuated endoplasmic reticulum (ER) stress-related apoptosis. D6D inhibition in ESCs upregulated stearoyl-CoA desaturase-1 (Scd1), essential to maintain ER homeostasis. In TSCs, however, D6D inhibition downregulated Scd1. TSCs show higher Scd1 mRNA expression and high levels of monounsaturated fatty acyl chain products in comparison to ESCs. The addition of oleic acid, the product of Scd1 (essential for ESCs), to culture medium, was detrimental to TSCs. Interestingly, TSCs express a high molecular mass variant of Scd1 protein, hardly expressed by ESCs. Taken together, our data suggest that lipid desaturation is a metabolic regulator of the balance between differentiation and self-renewal of ESCs and TSCs. They point to lipid polydesaturation as a driver of differentiation in both cell types. Monounsaturated fatty acids (MUFAs), essential for ESCs are detrimental to TSCs.
The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling
Authors: Laham Blake J. , Murthy Sahana S. , Hanani Monica , Clappier Mona , Boyer Sydney , Vasquez Betsy , Gould Elizabeth 
Published: December 2022

AbstractEarly-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice.
Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features
Authors: Flanagan Dustin J. , Amirkhah Raheleh , Vincent David F. , Gunduz Nuray , Gentaz Pauline , Cammareri Patrizia , McCooey Aoife J. , McCorry Amy M. B. , Fisher Natalie C. , Davis Hayley L. , Ridgway Rachel A. , Lohuis Jeroen , Leach Joshua D. G. , Jackstadt Rene , Gilroy Kathryn , Mariella Elisa , Nixon Colin , Clark William , Hedley Ann , Markert Elke K. , Strathdee Douglas , Bartholin Laurent , Redmond Keara L. , Kerr Emma M. , Longley Daniel B. , Ginty Fiona , Cho Sanghee , Coleman Helen G. , Loughrey Maurice B. , Bardelli Alberto , Maughan Timothy S. , Campbell Andrew D. , Lawler Mark , Leedham Simon J. , Barry Simon T. , Inman Gareth J. , van Rheenen Jacco , Dunne Philip D. , Sansom Owen J. 
Published: December 2022

AbstractThe pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFβ signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFβ signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFβ signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC’s with born to be bad traits.