bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing a High Water Abundance in the Upper Mesosphere of Mars With ACS Onboard TGO
Authors: Belyaev Denis A. , Fedorova Anna A. , Trokhimovskiy Alexander , Alday Juan , Montmessin Franck , Korablev Oleg I. , Lefèvre Franck , Patrakeev Andrey S. , Olsen Kevin S. , Shakun Alexey V. 
Published: May 2021

AbstractWe present the first water vapor profiles encompassing the upper mesosphere of Mars, 100–120 km, far exceeding the maximum altitudes where remote sensing has been able to observe water to date. Our results are based on solar occultation measurements by Atmospheric Chemistry Suite (ACS) onboard the ExoMars Trace Gas Orbiter (TGO). The observed wavelength range around 2.7 μm possesses strong CO2 and H2O absorption lines allowing sensitive temperature and density retrievals. We report a maximum H2O mixing ratio varying from 10 to 50 ppmv at 100–120 km during the global dust storm (GDS) of Martian Year (MY) 34 and around southern summer solstice of MY 34 and 35. During other seasons water remains persistently below ∼2 ppmv. We claim that contributions of the MY34 GDS and perihelion periods into the projected hydrogen escape from Mars are nearly equivalent.
Mixing Efficiency for Breaking Internal Solitary Waves
Authors: la Forgia Giovanni , Cavaliere Davide , Adduce Claudia , Falcini Federico 
Published: May 2021

AbstractWe propose a semi‐analytic approach to estimate mixing induced by internal solitary waves (ISWs) breaking over a sloping boundary. The theoretical framework we develop describes the energetics of a stratified fluid flow during the interaction of ISWs with a slope. In particular, through both Ozmidov and Thorpe lengthscales we derive a heuristic expression for mixing efficiency, valid for plunging and plunging‐collapsing breakers. On the other hand, we perform laboratory experiments that also provide mixing efficiency by estimating both changes of the background potential energy and the incident and reflected ISWs energy. We then compare those results with the ones derived by our theoretical model, obtaining a power law that relates the two quantities. This function allows to estimate mixing efficiency when the change in the background potential energy due to the ISWs breaking is unknown. We finally successfully apply our model to estimate the mixing efficiency under real field conditions.
Barrier Breaching Versus Overwash Deposition: Predicting the Morphologic Impact of Storms on Coastal Barriers
Authors: Nienhuis Jaap H. , Heijkers Leoni G. H. , Ruessink Gerben 
Published: May 2021

AbstractWaves and water level setup during storms can create overwashing flows across barrier islands. Overwashing flows can cause erosion, barrier breaching, and inlet formation, but their sediments can also be deposited and form washover fans. These widely different outcomes remain difficult to predict. Here we suggest that a breach develops when the sediment volume transported by overwashing flows exceeds the barrier subaerial volume. We form a simple analytical theory that estimates overwashing flows from storm characteristics, barrier morphology, and dune vegetation, and which can be used to assess washover deposition and breaching likelihood. Our theory suggests that barrier width and storm surge height are two important controls on barrier breaching. We test our theory with the hydrodynamic and morphodynamic model Delft3D as well as with field observations of 21 washover fans and 6 breaches that formed during Hurricane Sandy. There is reasonable correspondence for natural but not for developed barrier coasts, where traditional sediment transport equations do not readily apply. Our analytical formulations for breach formation and overwash deposition can be used to improve long‐term barrier island models.
Family environment and development in children adopted from institutionalized care
Authors: Keil Margaret F. , Leahu Adela , Rescigno Megan , Myles Jennifer , Stratakis Constantine A. 
Published: May 2021

Abstract
Background
After adoption, children exposed to institutionalized care show significant improvement, but incomplete recovery of growth and developmental milestones. There is a paucity of data regarding risk and protective factors in children adopted from institutionalized care. This prospective study followed children recently adopted from institutionalized care to investigate the relationship between family environment, executive function, and behavioral outcomes.

Methods
Anthropometric measurements, physical examination, endocrine and bone age evaluations, neurocognitive testing, and behavioral questionnaires were evaluated over a 2-year period with children adopted from institutionalized care and non-adopted controls.

Results
Adopted children had significant deficits in growth, cognitive, and developmental measurements compared to controls that improved; however, residual deficits remained. Family cohesiveness and expressiveness were protective influences, associated with less behavioral problems, while family conflict and greater emphasis on rules were associated with greater risk for executive dysfunction.

Conclusions
Our data suggest that a cohesive and expressive family environment moderated the effect of pre-adoption adversity on cognitive and behavioral development in toddlers, while family conflict and greater emphasis on rules were associated with greater risk for executive dysfunction. Early assessment of child temperament and parenting context may serve to optimize the fit between parenting style, family environment, and the child’s development.

Impact

Children who experience institutionalized care are at increased risk for significant deficits in developmental, cognitive, and social functioning associated with a disruption in the development of the prefrontal cortex. Aspects of the family caregiving environment moderate the effect of early life social deprivation in children.

Family cohesiveness and expressiveness were protective influences, while family conflict and greater emphasis on rules were associated with a greater risk for executive dysfunction problems.

This study should be viewed as preliminary data to be referenced by larger studies investigating developmental and behavioral outcomes of children adopted from institutional care.
Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing
Authors: Gebauer Niklas , Künstner Axel , Ketzer Julius , Witte Hanno M. , Rausch Tobias , Benes Vladimir , Zimmermann Jürgen , Gebauer Judith , Merz Hartmut , Bernard Veronica , Harder Lana , Ratjen Katharina , Gesk Stefan , Peter Wolfgang , Busch Yannik , Trojok Peter , von Bubnoff Nikolas , Biersack Harald , Busch Hauke , Feller Alfred C. 
Published: May 2021

AbstractEpstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitute a distinct clinicopathological entity in the current World Health Organization (WHO) classification. However, its genomic features remain sparsely characterized. Here, we combine whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS), and fluorescence in situ hybridization (FISH) from 47 EBV + DLBCL (NOS) cases to delineate the genomic landscape of this rare disease. Integrated WGS and tNGS analysis clearly distinguished this tumor type from EBV-negative DLBCL due to frequent mutations in ARID1A (45%), KMT2A/KMT2D (32/30%), ANKRD11 (32%), or NOTCH2 (32%). WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%), and YY1 (6%). Lastly, functional annotation of the mutational landscape by sequential gene set enrichment and network propagation predicted an effect on the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL6/JAK/STAT (SOCS1/3, STAT3), and WNT signaling (FRAT1, SFRP5) alongside aberrations in immunological processes, such as interferon response. This first comprehensive description of EBV + DLBCL (NOS) tumors substantiates the evidence of its pathobiological independence and helps stratify the molecular taxonomy of aggressive lymphomas in the effort for future therapeutic strategies.
Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM)
Authors: Lonial Sagar , Nooka Ajay K. , Thulasi Praneetha , Badros Ashraf Z. , Jeng Bennie H. , Callander Natalie S. , Potter Heather A. , Sborov Douglas , Zaugg Brian E. , Popat Rakesh , Degli Esposti Simona , Byrne Julie , Opalinska Joanna , Baron January , Piontek Trisha , Gupta Ira , Dana Reza , Farooq Asim V. , Colby Kathryn , Jakubowiak Andrzej 
Published: May 2021

AbstractBelantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody–drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit–risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.
Ethnicity and the tumour characteristics of invasive breast cancer in over 116,500 women in England
Authors: Gathani Toral , Reeves Gillian , Broggio John , Barnes Isobel 
Published: May 2021

Abstract
Background
Ethnic minority women are commonly reported to have more aggressive breast cancer than White women, but there is little contemporary national evidence available.

Methods
We analysed data from the National Cancer Registration and Analysis Service on women diagnosed with invasive breast cancer during 2013–2018. Multivariable logistic regression yielded adjusted odds ratios (and 95% confidence intervals) of less favourable tumour characteristics (high stage, high grade, ER negative, Her2 positive) by ethnicity (black African, black Caribbean, Indian, Pakistani and white) in younger (30–46 years) and older (53–70 years) women.

Results
In 24,022 women aged 30–46 at diagnosis, all ethnic minority groups apart from Indian women had a significantly greater odds of certain less favourable tumour characteristics compared to white women in fully adjusted models. In 92,555 women aged 53–70, all ethnic minorities had a significantly greater adjusted odds of several of the less favourable tumour characteristics. These differences were most marked in black African and black Caribbean women.

Conclusions
Ethnic minority women are at greater risk of breast cancers with less favourable characteristics, even after allowing for age and other potential confounders. These differences are greater in older than younger women, and in the Black rather than South Asian ethnic groups.
Tumor-derived exosomal components: the multifaceted roles and mechanisms in breast cancer metastasis
Authors: Tan Yufang , Luo Xiao , Lv Wenchang , Hu Weijie , Zhao Chongru , Xiong Mingchen , Yi Yi , Wang Dawei , Wang Yichen , Wang Haiping , Wu Yiping , Zhang Qi 
Published: May 2021

AbstractBreast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.
Biodegradation of bio-sourced and synthetic organic electronic materials towards green organic electronics
Authors: Di Mauro Eduardo , Rho Denis , Santato Clara 
Published: May 2021

AbstractUbiquitous use of electronic devices has led to an unprecedented increase in related waste as well as the worldwide depletion of reserves of key chemical elements required in their manufacturing. The use of biodegradable and abundant organic (carbon-based) electronic materials can contribute to alleviate the environmental impact of the electronic industry. The pigment eumelanin is a bio-sourced candidate for environmentally benign (green) organic electronics. The biodegradation of eumelanin extracted from cuttlefish ink is studied both at 25 °C (mesophilic conditions) and 58 °C (thermophilic conditions) following ASTM D5338 and comparatively evaluated with the biodegradation of two synthetic organic electronic materials, namely copper (II) phthalocyanine (Cu–Pc) and polyphenylene sulfide (PPS). Eumelanin biodegradation reaches 4.1% (25 °C) in 97 days and 37% (58 °C) in 98 days, and residual material is found to be without phytotoxic effects. The two synthetic materials, Cu–Pc and PPS, do not biodegrade; Cu–Pc brings about the inhibition of microbial respiration in the compost. PPS appears to be potentially phytotoxic. Finally, some considerations regarding the biodegradation test as well as the disambiguation of “biodegradability” and “bioresorbability” are highlighted.
Interfacial piezoelectric polarization locking in printable Ti3C2Tx MXene-fluoropolymer composites
Authors: Shepelin Nick A. , Sherrell Peter C. , Skountzos Emmanuel N. , Goudeli Eirini , Zhang Jizhen , Lussini Vanessa C. , Imtiaz Beenish , Usman Ken Aldren S. , Dicinoski Greg W. , Shapter Joseph G. , Razal Joselito M. , Ellis Amanda V. 
Published: May 2021

AbstractPiezoelectric fluoropolymers convert mechanical energy to electricity and are ideal for sustainably providing power to electronic devices. To convert mechanical energy, a net polarization must be induced in the fluoropolymer, which is currently achieved via an energy-intensive electrical poling process. Eliminating this process will enable the low-energy production of efficient energy harvesters. Here, by combining molecular dynamics simulations, piezoresponse force microscopy, and electrodynamic measurements, we reveal a hitherto unseen polarization locking phenomena of poly(vinylidene fluoride–co–trifluoroethylene) (PVDF-TrFE) perpendicular to the basal plane of two-dimensional (2D) Ti3C2Tx MXene nanosheets. This polarization locking, driven by strong electrostatic interactions enabled exceptional energy harvesting performance, with a measured piezoelectric charge coefficient, d33, of −52.0 picocoulombs per newton, significantly higher than electrically poled PVDF-TrFE (approximately −38 picocoulombs per newton). This study provides a new fundamental and low-energy input mechanism of poling fluoropolymers, which enables new levels of performance in electromechanical technologies.
Live-cell imaging reveals the spatiotemporal organization of endogenous RNA polymerase II phosphorylation at a single gene
Authors: Forero-Quintero Linda S. , Raymond William , Handa Tetsuya , Saxton Matthew N. , Morisaki Tatsuya , Kimura Hiroshi , Bertrand Edouard , Munsky Brian , Stasevich Timothy J. 
Published: May 2021

AbstractThe carboxyl-terminal domain of RNA polymerase II (RNAP2) is phosphorylated during transcription in eukaryotic cells. While residue-specific phosphorylation has been mapped with exquisite spatial resolution along the 1D genome in a population of fixed cells using immunoprecipitation-based assays, the timing, kinetics, and spatial organization of phosphorylation along a single-copy gene have not yet been measured in living cells. Here, we achieve this by combining multi-color, single-molecule microscopy with fluorescent antibody-based probes that specifically bind to different phosphorylated forms of endogenous RNAP2 in living cells. Applying this methodology to a single-copy HIV-1 reporter gene provides live-cell evidence for heterogeneity in the distribution of RNAP2 along the length of the gene as well as Serine 5 phosphorylated RNAP2 clusters that remain separated in both space and time from nascent mRNA synthesis. Computational models determine that 5 to 40 RNAP2 cluster around the promoter during a typical transcriptional burst, with most phosphorylated at Serine 5 within 6 seconds of arrival and roughly half escaping the promoter in ~1.5 minutes. Taken together, our data provide live-cell support for the notion of efficient transcription clusters that transiently form around promoters and contain high concentrations of RNAP2 phosphorylated at Serine 5.
The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing
Authors: Goulielmaki Evi , Tsekrekou Maria , Batsiotos Nikos , Ascensão-Ferreira Mariana , Ledaki Eleftheria , Stratigi Kalliopi , Chatzinikolaou Georgia , Topalis Pantelis , Kosteas Theodore , Altmüller Janine , Demmers Jeroen A. , Barbosa-Morais Nuno L. , Garinis George A. 
Published: May 2021

AbstractRNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csbm/m developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for transcription-coupled DNA repair disorders.
A tighter constraint on Earth-system sensitivity from long-term temperature and carbon-cycle observations
Authors: Wong Tony E. , Cui Ying , Royer Dana L. , Keller Klaus 
Published: May 2021

AbstractThe long-term temperature response to a given change in CO2 forcing, or Earth-system sensitivity (ESS), is a key parameter quantifying our understanding about the relationship between changes in Earth’s radiative forcing and the resulting long-term Earth-system response. Current ESS estimates are subject to sizable uncertainties. Long-term carbon cycle models can provide a useful avenue to constrain ESS, but previous efforts either use rather informal statistical approaches or focus on discrete paleoevents. Here, we improve on previous ESS estimates by using a Bayesian approach to fuse deep-time CO2 and temperature data over the last 420 Myrs with a long-term carbon cycle model. Our median ESS estimate of 3.4 °C (2.6-4.7 °C; 5-95% range) shows a narrower range than previous assessments. We show that weaker chemical weathering relative to the a priori model configuration via reduced weatherable land area yields better agreement with temperature records during the Cretaceous. Research into improving the understanding about these weathering mechanisms hence provides potentially powerful avenues to further constrain this fundamental Earth-system property.
Early constipation predicts faster dementia onset in Parkinson’s disease
Authors: Camacho M. , Macleod A. D. , Maple-Grødem J. , Evans J. R. , Breen D. P. , Cummins G. , Wijeyekoon R. S. , Greenland J. C. , Alves G. , Tysnes O. B. , Lawson R. A. , Barker R. A. , Williams-Gray C. H. 
Published: May 2021

AbstractConstipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson’s Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan–Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.
Quantum enhanced measurement of an optical frequency comb
Authors: Cai Y. , Roslund J. , Thiel V. , Fabre C. , Treps N. 
Published: May 2021

AbstractMeasuring the spectral properties of an optical frequency comb is among the most fundamental tasks of precision metrology. In contrast to general single-parameter measurement schemes, we demonstrate here single shot multi-parameter estimation of an optical frequency comb at and beyond the standard quantum limit. The mean energy and the central frequency as well as the spectral bandwidth of ultrafast pulses are simultaneously determined with a multi-pixel spectrally resolved (MPSR) apparatus, without changing the photonics architecture. Moreover, using a quantum frequency comb that intrinsically consists of multiple squeezed states in a family of Hermite–Gaussian spectral/temporal modes, the signal-to-noise ratios of the multiple spectral parameters estimation can surpass the standard quantum limit. Combining our multi-pixel detection scheme and the multimode entangled resource could find applications in ultrafast quantum metrology and multimode quantum information processing.