bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Breast Cancer Using CRISPR-Cas9–Mediated Engineering of Human Breast Organoids
Authors: Dekkers Johanna F , Whittle James R , Vaillant François , Chen Huei-Rong , Dawson Caleb , Liu Kevin , Geurts Maarten H , Herold Marco J , Clevers Hans , Lindeman Geoffrey J , Visvader Jane E 
Published: September 2019

Abstract
Breast cancer is characterized by histological and functional heterogeneity, posing a clinical challenge for patient treatment. Emerging evidence suggests that the distinct subtypes reflect the repertoire of genetic alterations and the target cell. However, the precise initiating events that predispose normal epithelium to neoplasia are poorly understood. Here, we demonstrate that breast epithelial organoids can be generated from human reduction mammoplasties (12 out of 12 donors), thus creating a tool to study the clonal evolution of breast cancer. To recapitulate de novo oncogenesis, we exploited clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 for targeted knockout of four breast cancer–associated tumor suppressor genes (P53, PTEN, RB1, NF1) in mammary progenitor cells from six donors. Mutant organoids gained long-term culturing capacity and formed estrogen-receptor positive luminal tumors on transplantation into mice for one out of six P53/PTEN/RB1–mutated and three out of six P53/PTEN/RB1/NF1–mutated lines. These organoids responded to endocrine therapy or chemotherapy, supporting the potential utility of this model to enhance our understanding of the molecular events that culminate in specific subtypes of breast cancer.
Prenatal Biochemical Screening and a Woman’s Long-Term Risk of Cancer: A Population-Based Cohort Study
Authors: Park Alison L , Huang Tianhua , Meschino Wendy S , Iqbal Javaid , Ray Joel G 
Published: September 2019

Abstract

Background
Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman’s subsequent risk of hormone-sensitive cancer.

Methods
This population-based cohort study included women aged 12–55 years who underwent prenatal screening between 11 weeks + 0 days of gestation to 20 weeks + 6 days of gestation in Ontario, Canada, 1993–2011, where universal health care is available. The hazard ratio of newly diagnosed breast, ovarian, endometrial, and thyroid cancer—arising at 21 weeks + 0 days of gestation or thereafter—was estimated in association with an abnormally low (≤5th) or high (&gt;95th) percentile multiple of the median (MoM) for alpha-fetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol, pregnancy-associated plasma protein A, and dimeric inhibin A.

Results
Among 677 247 pregnant women followed for a median of 11.0 years (interquartile range = 7.5–16.1), 7231 (1.07%) developed breast cancer, 515 (0.08%) ovarian cancer, 508 (0.08%) endometrial cancer, and 4105 (0.61%) thyroid cancer. In multivariable adjusted models, abnormally high hCG greater than the 95th percentile MoM was associated with a doubling in the risk of endometrial cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.33 to 2.95), and abnormally low AFP at the fifth percentile or less MoM conferred a moderately greater risk of thyroid cancer (aHR = 1.21, 95% CI = 1.07 to 1.38). Abnormally low pregnancy-associated plasma protein A at the fifth percentile or less MoM was not statistically significantly associated with breast cancer after multivariable adjustment (aHR = 1.19, 95% CI = 0.98 to 1.36).

Conclusions
Women with abnormally high levels of serum hCG or low AFP in early pregnancy may be at a greater future risk of certain types of hormone-sensitive cancers.
Desmoplastic Infantile Ganglioglioma: A MAPK Pathway-Driven and Microglia/Macrophage-Rich Neuroepithelial Tumor
Authors: Blessing Melissa M , Blackburn Patrick R , Krishnan Chandra , Harrod Virginia L , Barr Fritcher Emily G , Zysk Christopher D , Jackson Rory A , Milosevic Dragana , Nair Asha A , Davila Jaime I , Balcom Jessica R , Jenkins Robert B , Halling Kevin C , Kipp Benjamin R , Nageswara Rao Amulya A , Laack Nadia N , Daniels David J , Macon William R , Ida Cristiane M 
Published: September 2019

AbstractMAPK pathway activation has been recurrently observed in desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) with reported disproportionally low mutation allele frequencies relative to the apparent high tumor content, suggesting that MAPK pathway alterations may be subclonal. We sought to expand the number of molecularly profiled cases and investigate if tumor cell composition could account for the observed low mutation allele frequencies. Molecular (targeted neuro-oncology next-generation sequencing/RNA sequencing and OncoScan microarray) and immunohistochemical (CD68-PGM1/CD163/CD14/CD11c/lysozyme/CD3/CD20/CD34/PD-L1) studies were performed in 7 DIG. Activating MAPK pathway alterations were identified in 4 (57%) cases: 3 had a BRAF mutation (V600E/V600D/V600_W604delinsDQTDG, at 8%–27% variant allele frequency) and 1 showed a TPM3-NTRK1 fusion. Copy number changes were infrequent and nonrecurrent. All tumors had at least 30% of cells morphologically and immunophenotypically consistent with microglial/macrophage lineage. Two subtotally resected tumors regrew; 1 was re-excised and received adjuvant treatment (chemotherapy/targeted therapy), with clinical response to targeted therapy only. Even with residual tumor, all patients are alive (median follow-up, 83 months; 19–139). This study further supports DIG as another MAPK pathway-driven neuroepithelial tumor, thus expanding potential treatment options for tumors not amenable to surgical cure, and suggests that DIG is a microglia/macrophage-rich neuroepithelial tumor with frequent low driver mutation allele frequencies.
Meningococcal Serogroup B Disease in Vaccinated Children
Authors: Soler-Garcia Aleix , Fernández de Sevilla Mariona , Abad Raquel , Esteva Cristina , Alsina Laia , Vázquez Julio , Muñoz-Almagro Carmen , Noguera-Julian Antoni 
Published: September 2019

Abstract

Background
Neisseria meningitidis serogroup B (MenB) is the most frequent cause of invasive meningococcal disease (IMD) in Spain. The multicomponent vaccine against MenB (4CMenB) was approved in Spain in January 2014.

Methods
We present 4 cases of children who developed MenB-associated IMD despite previous vaccination with 4CMenB. Extensive immunologic diagnostic work-up was performed in order to rule out any immunodeficiency. Also, molecular characterization of the MenB strain was conducted to determine whether bacterial antigens matched vaccine antigens.

Results
Among the 4 patients (2 girls), 2 had previous risk factors for IMD (recurrent bacterial meningitis of unknown origin and treatment with eculizumab). All patients developed meningitis, but only 2 developed septic shock; they were all cured without sequelae. No other primary or secondary immunodeficiencies were detected. MenB sequence type 213 was identified in 3 cases. With the exception of neisserial heparin-binding antigen peptide 465 present in 1 isolate, the rest of the isolated strains harbored vaccine antigen variants that did not match antigen variants included in the vaccine.

Conclusions
We present 4 children who developed MenB-associated IMD despite previous vaccination with 4CMenB. In 2 cases, the antibodies induced by 4CMenB likely were not effective against the isolated strains. A high level of suspicion for IMD seems advisable regardless of the patient’s vaccination history.
Prepositions and the Grammaticalization of Ancient Hebrew Bipartite Reciprocal Markers
Authors: Staps Camil 
Published: October 2019

Abstract
Besides using the verbal niphal and hitpael stems, ancient Hebrew can indicate semantic reciprocity with bipartite reciprocal markers such as , literally ‘someone with his brother’. In contrast to the Western European counter-parts of these constructions (e.g. English each other), the ancient Hebrew variants are not fully grammaticalized into a single morphological unit like . This article considers one type of bipartite reciprocal marker (the one using ‘someone’ and a term denoting kinship or fellowship) in detail, to see whether the preposition in the construction (e.g., ‘with’) may have prevented further grammaticalization. Since no bleaching of the preposition can be observed in the corpus of Biblical and Qumran Hebrew, we conclude that prepositions continued to have a significant semantic value, which indeed suggests that their near-obligatory presence has prevented further grammaticalization.
An improved test of the binary black hole hypothesis for quasars with double-peaked broad Balmer lines
Authors: Doan Anh , Eracleous Michael , Runnoe Jessie C , Liu Jia , Mathes Gavin , Flohic Helene M L G 
Published: September 2019

ABSTRACT
Velocity offsets in the broad Balmer lines of quasars and their temporal variations serve as indirect evidence for bound supermassive black hole binaries (SBHBs) at sub-parsec separations. In this work, we test the SBHB hypothesis for 14 quasars with double-peaked broad emission lines using their long-term (14–41 yr) radial velocity curves. We improve on the previous work by (i) using elliptical instead of circular orbits for the SBHBs, (ii) adopting a statistical model for radial velocity jitter, (iii) employing a Markov chain Monte Carlo method to explore the orbital parameter space efficiently and build posterior distributions of physical parameters, and (iv) incorporating new observations. We determine empirically that jitter comprises approximately Gaussian distributed fluctuations about the smooth radial velocity curves that are larger than the measurement errors by factors of a few. We initially treat jitter by enlarging the effective error bars and then verify this approach via a variety of Gaussian process models for it. We find lower mass limits for the hypothesized SBHBs in the range 108–1011 M⊙. For seven objects, the SBHB scenario appears unlikely based on goodness-of-fit tests. For two additional objects, the minimum SBHB masses are unreasonably large (&gt;1010 M⊙), strongly disfavouring the SBHB scenario. Using constraints on the orbital inclination angle (which requires some assumptions) makes the minimum masses of four more objects unreasonably large. We also cite physical and observational arguments against the SBHB hypothesis for nine objects. We conclude that the SBHB explanation is not the favoured explanation of double-peaked broad emission lines.
Synthetic 26Al emission from galactic-scale superbubble simulations
Authors: Rodgers-Lee D , Krause M G H , Dale J , Diehl R 
Published: October 2019

ABSTRACT
Emission from the radioactive trace element 26Al has been observed throughout the Milky Way with the COMPTEL and INTEGRAL satellites. In particular, the Doppler shifts measured with INTEGRAL connect 26Al with superbubbles, which may guide 26Al flows off spiral arms in the direction of Galactic rotation. In order to test this paradigm, we have performed galaxy-scale simulations of superbubbles with 26Al injection in a Milky Way-type galaxy. We produce all-sky synthetic γ-ray emission maps of the simulated galaxies. We find that the 1809 keV emission from the radioactive decay of 26Al is highly variable with time and the observer’s position. This allows us to estimate an additional systematic variability of 0.2 dex for a star formation rate derived from 26Al for different times and measurement locations in Milky Way-type galaxies. High-latitude morphological features indicate nearby emission with correspondingly high-integrated γ-ray intensities. We demonstrate that the 26Al scale height from our simulated galaxies depends on the assumed halo gas density. We present the first synthetic 1809 keV longitude-velocity diagrams from 3D hydrodynamic simulations. The line-of-sight velocities for 26Al can be significantly different from the line-of-sight velocities associated with the cold gas. Over time, 26Al velocities consistent with the INTEGRAL observations, within uncertainties, appear at any given longitude, broadly supporting previous suggestions that 26Al injected into expanding superbubbles by massive stars may be responsible for the high velocities found in the INTEGRAL observations. We discuss the effect of systematically varying the location of the superbubbles relative to the spiral arms.
The ASAS-SN catalogue of variable stars – V. Variables in the Southern hemisphere
Authors: Jayasinghe T , Stanek K Z , Kochanek C S , Shappee B J , Holoien T W-S , Thompson T A , Prieto J L , Dong S , Pawlak M , Pejcha O , Shields J V , Pojmanski G , Otero S , Hurst N , Britt C A , Will D 
Published: September 2019

ABSTRACT
The All-Sky Automated Survey for Supernovae (ASAS-SN) provides long baseline (∼4 yr) light curves for sources brighter than V ≲ 17 mag across the whole sky. As part of our effort to characterize the variability of all the stellar sources visible in ASAS-SN, we have produced ∼30.1 million V-band light curves for sources in the Southern hemisphere using the APASS DR9 (AAVSO Photometric All-Sky Survey Data Release) catalogue as our input source list. We have systematically searched these sources for variability using a pipeline based on random forest classifiers. We have identified ${\sim } 220\, 000$ variables, including ${\sim } 88\, 300$ new discoveries. In particular, we have discovered ${\sim }48\, 000$ red pulsating variables, ${\sim }23\, 000$ eclipsing binaries, ∼2200 δ-Scuti variables, and ${\sim }10\, 200$ rotational variables. The light curves and characteristics of the variables are all available through the ASAS-SN variable stars data base (https://asas-sn.osu.edu/variables). The pre-computed ASAS-SN V-band light curves for all the ∼30.1 million sources are available through the ASAS-SN photometry data base (https://asas-sn.osu.edu/photometry). This effort will be extended to provide ASAS-SN light curves for sources in the Northern hemisphere and for V ≲ 17 mag sources across the whole sky that are not included in APASS DR9.
WASP-South hot Jupiters: WASP-178b, WASP-184b, WASP-185b, and WASP-192b
Authors: Hellier Coel , Anderson D R , Barkaoui K , Benkhaldoun Z , Bouchy F , Burdanov A , Cameron A Collier , Delrez L , Gillon M , Jehin E , Nielsen L D , Maxted P F L , Pepe F , Pollacco D , Pozuelos F J , Queloz D , Ségransan D , Smalley B , Triaud A H M J , Turner O D , Udry S , West R G 
Published: September 2019

ABSTRACTWe report on four new transiting hot Jupiters discovered by the WASP-South survey. WASP-178b transits a V = 9.9, A1V star with Teff = 9350 ± 150 K, the second-hottest transit host known. It has a highly bloated radius of 1.81 ± 0.09 RJup, in line with the known correlation between high irradiation and large size. With an estimated temperature of 2470 ± 60 K, the planet is one of the best targets for studying ultrahot Jupiters that is visible from the Southern hemisphere. The three host stars WASP-184, WASP-185, and WASP-192 are all post-main-sequence G0 stars of ages 4–8 Gyr. The larger stellar radii (1.3–1.7 M⊙) mean that the transits are relatively shallow (0.7–0.9 per cent) even though the planets have moderately inflated radii of 1.2–1.3 RJup. WASP-185b has an eccentric orbit (e = 0.24) and a relatively long orbital period of 9.4 d. A star that is 4.6 arcsec from WASP-185 and 4.4 mag fainter might be physically associated.
Continuous gravitational wave from magnetized white dwarfs and neutron stars: possible missions for LISA, DECIGO, BBO, ET detectors
Authors: Kalita Surajit , Mukhopadhyay Banibrata 
Published: October 2019

ABSTRACT
Recent detection of gravitational wave from nine black hole merger events and one neutron star merger event by LIGO and VIRGO shed a new light in the field of astrophysics. On the other hand, in the past decade, a few super-Chandrasekhar white dwarf candidates have been inferred through the peak luminosity of the light curves of a few peculiar Type Ia supernovae, though there is no direct detection of these objects so far. Similarly, a number of neutron stars with mass $>\! 2\, \mathrm{M}_\odot$ have also been observed. Continuous gravitational wave can be one of the alternate ways to detect these compact objects directly. It was already argued that magnetic field is one of the prominent physics to form super-Chandrasekhar white dwarfs and massive neutron stars. If such compact objects are rotating with certain angular frequency, then they can efficiently emit gravitational radiation, provided their magnetic field and rotation axes are not aligned, and these gravitational waves can be detected by some of the upcoming detectors, e.g. LISA, BBO, DECIGO, Einstein Telescope, etc. This will certainly be a direct detection of rotating magnetized white dwarfs as well as massive neutron stars.
Prevalent externally driven protoplanetary disc dispersal as a function of the galactic environment
Authors: Winter Andrew J , Kruijssen J M Diederik , Chevance Mélanie , Keller Benjamin W , Longmore Steven N 
Published: October 2019

ABSTRACT
The stellar birth environment can significantly shorten protoplanetary disc (PPD) lifetimes due to the influence of stellar feedback mechanisms. The degree to which these mechanisms suppress the time and mass available for planet formation is dependent on the local far-ultraviolet (FUV) field strength, stellar density, and ISM properties. In this work, we present the first theoretical framework quantifying the distribution of PPD dispersal time-scales as a function of parameters that describe the galactic environment. We calculate the probability density function for FUV flux and stellar density in the solar neighbourhood. In agreement with previous studies, we find that external photoevaporation is the dominant environment-related factor influencing local stellar populations after the embedded phase. Applying our general prescription to the Central Molecular Zone of the Milky Way (i.e. the central $\sim 250~\mbox{${\rm pc}$}$), we predict that $90{{\ \rm per\ cent}}$ of PPDs in the region are destroyed within 1 Myr of the dispersal of the parent molecular cloud. Even in such dense environments, we find that external photoevaporation is the dominant disc depletion mechanism over dynamical encounters between stars. PPDs around low-mass stars are particularly sensitive to FUV-induced mass-loss, due to a shallower gravitational potential. For stars of mass ∼1 M⊙, the solar neighbourhood lies at approximately the highest gas surface density for which PPD dispersal is still relatively unaffected by external FUV photons, with a median PPD dispersal time-scale of ∼4 Myr. We highlight the key questions to be addressed to further contextualize the significance of the local galactic environment for planet formation.
DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives?
Authors: Czarny Piotr , Bialek Katarzyna , Ziolkowska Sylwia , Strycharz Justyna , Sliwinski Tomasz 
Published: September 2019

AbstractOver the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.
SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia
Authors: Bon Carlotta , Luffarelli Riccardo , Russo Roberta , Fortuni Silvia , Pierattini Bianca , Santulli Chiara , Fimiani Cristina , Persichetti Francesca , Cotella Diego , Mallamaci Antonello , Santoro Claudio , Carninci Piero , Espinoza Stefano , Testi Roberto , Zucchelli Silvia , Condò Ivano , Gustincich Stefano 
Published: September 2019

Abstract
Friedreich's ataxia (FRDA) is an untreatable disorder with neuro- and cardio-degenerative progression. This monogenic disease is caused by the hyper-expansion of naturally occurring GAA repeats in the first intron of the FXN gene, encoding for frataxin, a protein implicated in the biogenesis of iron-sulfur clusters. As the genetic defect interferes with FXN transcription, FRDA patients express a normal frataxin protein but at insufficient levels. Thus, current therapeutic strategies are mostly aimed to restore physiological FXN expression. We have previously described SINEUPs, natural and synthetic antisense long non-coding RNAs, which promote translation of partially overlapping mRNAs through the activity of an embedded SINEB2 domain. Here, by in vitro screening, we have identified a number of SINEUPs targeting human FXN mRNA and capable to up-regulate frataxin protein to physiological amounts acting at the post-transcriptional level. Furthermore, FXN-specific SINEUPs promote the recovery of disease-associated mitochondrial aconitase defects in FRDA-derived cells. In summary, we provide evidence that SINEUPs may be the first gene-specific therapeutic approach to activate FXN translation in FRDA and, more broadly, a novel scalable platform to develop new RNA-based therapies for haploinsufficient diseases.
A pilot randomized controlled trial of exercise to improve cognitive performance in patients with stable glioma: a proof of concept
Authors: Gehring Karin , Stuiver Martijn M , Visser Eva , Kloek Corelien , van den Bent Martin , Hanse Monique , Tijssen Cees , Rutten Geert-Jan , Taphoorn Martin J B , Aaronson Neil K , Sitskoorn Margriet M 
Published: September 2019

Abstract

Background
Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs).

Methods
Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20–45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months.

Results
The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health–related quality of life.

Conclusions
This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients.