bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comet C/2018 V1 (Machholz–Fujikawa–Iwamoto): dislodged from the Oort Cloud or coming from interstellar space?
Authors: de la Fuente Marcos C , de la Fuente Marcos R 
Published: August 2019

ABSTRACT
The chance discovery of the first interstellar minor body, 1I/2017 U1 (‘Oumuamua), indicates that we may have been visited by such objects in the past and that these events may repeat in the future. Unfortunately, minor bodies following nearly parabolic or hyperbolic paths tend to receive little attention: over 3/4 of those known have data-arcs shorter than 30 d and, consistently, rather uncertain orbit determinations. This fact suggests that we may have observed interstellar interlopers in the past, but failed to recognize them as such due to insufficient data. Early identification of promising candidates by using N-body simulations may help in improving this situation, triggering follow-up observations before they leave the Solar system. Here, we use this technique to investigate the pre- and post-perihelion dynamical evolution of the slightly hyperbolic comet C/2018 V1 (Machholz–Fujikawa–Iwamoto) to understand its origin and relevance within the context of known parabolic and hyperbolic minor bodies. Based on the available data, our calculations suggest that although C/2018 V1 may be a former member of the Oort Cloud, an origin beyond the Solar system cannot be excluded. If extrasolar, it might have entered the Solar system from interstellar space at low relative velocity with respect to the Sun. The practical feasibility of this alternative scenario has been assessed within the kinematic context of the stellar neighbourhood of the Sun, using data from Gaia second data release, and two robust solar sibling candidates have been identified. Our results suggest that comets coming from interstellar space at low heliocentric velocities may not be rare.
Lack of close-in, massive planets of main-sequence A-type stars from Kepler
Authors: Sabotta Silvia , Kabath Petr , Korth Judith , Guenther Eike W , Dupkala Daniel , Grziwa Sascha , Klocova Tereza , Skarka Marek 
Published: August 2019

ABSTRACT
Some theories of planet formation and evolution predict that intermediate-mass stars host more hot Jupiters than Sun-like stars, others reach the conclusion that such objects are very rare. By determining the frequencies of those planets we can test those theories.
Based on the analysis of Kepler light curves it has been suggested that about 8 per cent of the intermediate-mass stars could have a close-in substellar companion. This would indicate a very high frequency of such objects. Up to now, there was no satisfactory proof or test of this hypothesis.
We studied a previously reported sample of 166 planet candidates around main-sequence A-type stars in the Kepler field. We selected six of them for which we obtained extensive long-term radial velocity measurements with the Alfred Jensch 2-m telescope in Tautenburg and the Perek 2-m telescope in Ondřejov. We derive upper limits of the masses of the planet candidates. We show that we are able to detect this kind of planet with our telescopes and their instrumentation using the example of MASCARA-1 b.
With the transit finding pipeline Extrans we confirm that there is no single transit event from a Jupiter-like planet in the light curves of those 166 stars. We furthermore determine that the upper limit for the occurrence rate of close-in, massive planets for A-type stars in the Kepler sample is around 0.75 per cent.
We argue that there is currently little evidence for a very high frequency of close-in, massive planets of intermediate-mass stars.
On the nature of radio filaments near the Galactic Centre
Authors: Barkov Maxim V , Lyutikov Maxim 
Published: August 2019

ABSTRACT
We suggest that narrow, long radio filaments near the Galactic Centre arise as kinetic jets – streams of high-energy particles escaping from ram pressure confined pulsar wind nebulae (PWNe). The reconnection between the PWN and interstellar magnetic field allows pulsar wind particles to escape, creating long narrow features. They are the low-frequency analogues of kinetic jets seen around some fast-moving pulsars, such as The Guitar and The Lighthouse PWNe. The radio filaments trace a population of pulsars also responsible for the Fermi GeV excess produced by the Inverse Compton scattering by the pulsar wind particles. The magnetic flux tubes are stretched radially by the large-scale Galactic winds. In addition to PWNe accelerated particles can be injected at supernovae remnants. The model predicts variations of the structure of the largest filaments on scales of ∼dozens of years – smaller variations can occur on shorter time-scales. We also encourage targeted observations of the brightest sections of the filaments and of the related unresolved point sources in search of the powering PWNe and pulsars.
Unexpected behavior of DNA polymerase Mu opposite template 8-oxo-7,8-dihydro-2′-guanosine
Authors: Kaminski Andrea M , Chiruvella Kishore K , Ramsden Dale A , Kunkel Thomas A , Bebenek Katarzyna , Pedersen Lars C 
Published: August 2019

Abstract
DNA double-strand breaks (DSBs) resulting from reactive oxygen species generated by exposure to UV and ionizing radiation are characterized by clusters of lesions near break sites. Such complex DSBs are repaired slowly, and their persistence can have severe consequences for human health. We have therefore probed DNA break repair containing a template 8-oxo-7,8-dihydro-2′-guanosine (8OG) by Family X Polymerase μ (Pol μ) in steady-state kinetics and cell-based assays. Pol μ tolerates 8OG-containing template DNA substrates, and the filled products can be subsequently ligated by DNA Ligase IV during Nonhomologous end-joining. Furthermore, Pol μ exhibits a strong preference for mutagenic bypass of 8OG by insertion of adenine. Crystal structures reveal that the template 8OG is accommodated in the Pol μ active site with none of the DNA substrate distortions observed for Family X siblings Pols β or λ. Kinetic characterization of template 8OG bypass indicates that Pol μ inserts adenosine nucleotides with weak sugar selectivity and, given the high cellular concentration of ATP, likely performs its role in repair of complex 8OG-containing DSBs using ribonucleotides.
Specificity of MYB interactions relies on motifs in ordered and disordered contexts
Authors: Millard Peter S , Weber Konrad , Kragelund Birthe B , Burow Meike 
Published: August 2019

AbstractPhysical interactions between members of the MYB and bHLH transcription factor (TF) families regulate many important biological processes in plants. Not all reported MYB–bHLH interactions can be explained by the known binding sites in the R3 repeat of the MYB DNA-binding domain. Noteworthy, most of the sequence diversity of MYB TFs lies in their non-MYB regions, which contain orphan small subgroup-defining motifs not yet linked to molecular functions. Here, we identified the motif mediating interaction between MYB TFs from subgroup 12 and their bHLH partners. Unlike other known MYB–bHLH interactions, the motif locates to the centre of the predicted disordered non-MYB region. We characterised the core motif, which enabled accurate prediction of previously unknown bHLH-interacting MYB TFs in Arabidopsis thaliana, and we confirmed its functional importance in planta. Our results indicate a correlation between the MYB–bHLH interaction affinity and the phenotypic output controlled by the TF complex. The identification of an interaction motif outside R3 indicates that MYB–bHLH interactions must have arisen multiple times, independently and suggests many more motifs of functional relevance to be harvested from subgroup-specific studies.
Post-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin
Authors: Kong Ka-Yiu Edwin , Hung Ting-Ngai Felix , Man Pui-Hei Marcus , Wong Tin-Ning , Cheng Tao , Jin Dong-Yan 
Published: August 2019

Abstract
When proteostasis is disrupted by stresses such as heat shock, the heat stress response will be stimulated, leading to up-regulation of molecular chaperones by transcriptional activation and mRNA stabilization for restoring proteostasis. Although the mechanisms for their transcriptional activation have been clearly defined, how chaperone mRNAs are stabilized remains largely unknown. Starting by exploring the coupling between the apparently unrelated RNA degradation and protein quality control (PQC) systems, we show that the Dis3 ribonuclease, catalytic subunit of the RNA exosome required for RNA degradation, suppresses PQC activity in unstressed cells by degrading mRNAs encoding the Hsp70 cofactors Sis1, Ydj1 and Fes1, as well as some other chaperones or PQC factors, thereby limiting their protein expression. Dis3 is stabilized through its binding to Sis1 and the Hsp70s Ssa1/2. Upon heat stress, loss of Sis1 and Ssa1/2 availability triggers Dis3 ubiquitination and degradation, leading to stabilization of those chaperone mRNAs originally targeted by Dis3. We further demonstrate that polyQ-expanded huntingtin delays Dis3 degradation during heat stress and thus hinders chaperone mRNA stabilization. Our findings not only reveal a post-transcriptional negative feedback loop for maintaining proteostasis, but also uncover a mechanism that contributes to the impaired heat stress response in Huntington's disease.
Neural substrates for anticipation and consumption of social and monetary incentives in depression
Authors: He Zhenhong , Zhang Dandan , Muhlert Nils , Elliott Rebecca 
Published: August 2019

Abstract
Depression has been reliably associated with abnormalities in the neural representation of reward and loss. However, most studies have focused on monetary incentives; fewer studies have considered neural representation of social incentives. A direct comparison of non-social and social incentives within the same study would establish whether responses to the different incentives are differentially affected in depression. The functional magnetic resonance imaging study presented here investigated the neural activity of individuals with subthreshold depression (SD) and healthy controls (HCs) while they participated in an incentive delay task offering two types of reward (monetary gain vs social approval) and loss (monetary loss vs social disapproval). Compared to HCs, individuals with SD showed increased subgenual anterior cingulate cortex (sgACC) activity during anticipation of social loss, whereas the response in the putamen was decreased during consumption of social gain. Individuals with SD also exhibited diminished insula responses in consuming social loss. Furthermore, positive connectivity between the insula and ventral lateral pre-frontal cortex (VLPFC) was observed in individuals with SD while negative connectivity was found in HCs when consuming social loss. These results demonstrate neural alterations in individuals with depression, specific to the processing of social incentives, mainly characterised by dysfunction within the ‘social pain network’ (sgACC, insula and VLPFC).
Ozone-Induced Dysregulation of Neuroendocrine Axes Requires Adrenal-Derived Stress Hormones
Authors: Henriquez Andres R , House John S , Snow Samantha J , Miller Colette N , Schladweiler Mette C , Fisher Anna , Ren Hongzu , Valdez Matthew , Kodavanti Prasada R , Kodavanti Urmila P 
Published: August 2019

Abstract
Acute ozone inhalation increases circulating stress hormones through activation of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes. Rats with adrenalectomy (AD) have attenuated ozone-induced lung responses. We hypothesized that ozone exposure will induce changes in circulating pituitary-derived hormones and global gene expression in the brainstem and hypothalamus, and that AD will ameliorate these effects. Male Wistar-Kyoto rats (13 weeks) that underwent sham surgery (SHAM) or AD were exposed to ozone (0.8 ppm) or filtered-air for 4 h. In SHAM rats, ozone exposure decreased circulating thyroid-stimulating hormone (TSH), prolactin (PRL), and luteinizing hormone (LH). AD prevented reductions in TSH and PRL, but not LH. AD increased adrenocorticotropic hormone approximately 5-fold in both air- and ozone-exposed rats. AD in air-exposed rats resulted in few significant transcriptional differences in the brainstem and hypothalamus (approximately 20 genes per tissue). In contrast, ozone-exposure in SHAM rats resulted in either increases or decreases in expression of hundreds of genes in the brainstem and hypothalamus relative to air-exposed SHAM rats (303 and 568 genes, respectively). Differentially expressed genes from ozone exposure were enriched for pathways involving hedgehog signaling, responses to alpha-interferon, hypoxia, and mTORC1, among others. Gene changes in both brain areas were analogous to those altered by corticosteroids and L-3,4-dihydroxyphenylalanine, suggesting a role for endogenous glucocorticoids and catecholamines. AD completely prevented this ozone-induced transcriptional response. These findings show that short-term ozone inhalation promotes a shift in brainstem and hypothalamic gene expression that is dependent upon the presence of circulating adrenal-derived stress hormones. This is likely to have profound downstream influence on systemic effects of ozone.
Health-related Quality of Life With Ulipristal Acetate for Treatment of Uterine Leiomyomas: A Randomized Controlled Trial
Authors: Lukes Andrea S. , Soper David , Harrington Amanda , Sniukiene Vilma , Mo Yifan , Gillard Patrick , Shulman Lee 
Published: August 2019

(Abstracted from Obstet Gynecol 2019;133:869–878)
A significant health issue for women in the United States is the occurrence of uterine leiomyomas. The estimated cumulative incidence of uterine leiomyomas by age 50 years is more than 80% in black women and nearly 70% in white women.
Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism
Authors: van der Pol Liselotte M. , Tromeur Cecile , Bistervels Ingrid M. , Ni Ainle Fionnuala , van Bemmel Thomas , Bertoletti Laurent , Couturaud Francis , van Dooren Yordi P. A. , Elias Antoine , Faber Laura M. , Hofstee Herman M. A. , van der Hulle Tom , Kruip Marieke J. H. A. , Maignan Maxime , Mairuhu Albert T. A. , Middeldorp Saskia , Nijkeuter Mathilde , Roy Pierre-Marie , Sanchez Olivier , Schmidt Jeannot , ten Wolde Marije , Klok Frederikus A. , Huisman Menno V. 
Published: August 2019

(Abstracted from N Engl J Med 2019;380:1139–1149)
Acute pulmonary embolism is one of the leading causes of maternal death, with the overall incidence reported to be 1.72 cases per 1000 deliveries, accounting for approximately 1 death in every 100,000 deliveries. Since the d-dimer test has low specificity and sensitivity, it is common for pregnant women with suspected pulmonary embolism to undergo computed tomography (CT) pulmonary angiography or ventilation-perfusion (V/Q) scanning, both of which involve radiation exposure to the mother and fetus.
A Randomized Trial of Progesterone in Women With Bleeding in Early Pregnancy
Authors: Coomarasamy Arri , Devall Adam J. , Cheed Versha , Harb Hoda , Middleton Lee J. , Gallos Ioannis D. , Williams Helen , Eapen Abey K. , Roberts Tracy , Ogwulu Chriscasimir C. , Goranitis Ilias , Daniels Jane P. , Ahmed Amna , Bender-Atik Ruth , Bhatia Kalsang , Bottomley Cecilia , Brewin Jane , Choudhary Meenakshi , Crosfill Fiona , Deb Shilpa , Duncan W. Colin , Ewer Andrew , Hinshaw Kim , Holland Tom , Izzat Feras , Johns Jemma , Kriedt Kathiuska , Lumsden Mary-Ann , Manda Padma , Norman Jane E. , Nunes Natalie , Overton Caroline E. , Quenby Siobhan , Rao Sandhya , Ross Jackie , Shahid Anupama , Underwood Martyn , Vaithilingam Nirmala , Watkins Linda , Wykes Catherine , Horne Andrew , Jurkovic Davor 
Published: August 2019

(Abstracted from N Engl J Med 2019;380:1815–1824)
The hormone progesterone plays a critical role in preparing the endometrium for implantation of the embryo and continues to be produced throughout pregnancy. Historically, progesterone supplementation has been initiated during early pregnancies to prevent miscarriages in asymptomatic women who have a history of recurrent miscarriages or to rescue a pregnancy in women who have started to bleed during early pregnancy.
Development of a Peer Support Model Using Experience-Based Co-Design to Improve Critical Care Recovery
Authors: Haines Kimberley J. , Holdsworth Clare , Cranwell Kathryn , Skinner Elizabeth H , Holton Sara , MacLeod-Smith Belinda , Bates Samantha , Iwashyna Theodore J. , French Craig , Booth Sarah , Carmody Jacki , Henningham Lucy , Searle Grey , Shackell Melina , Maher Lynne 
Published: August 2019

Objectives:
To use experience-based co-design to identify the key design requirements of a peer support model for critical care survivors; understand the use of the experience-based co-design method from clinician, patients, and family perspectives.

Design:
Using experience-based co-design, qualitative data about participants’ preferences for a peer support model were generated via workshops. Participants’ perspectives of experience-based co-design were evaluated with focus groups.

Setting:
University-affiliated hospital in Melbourne, Australia.

Subjects:
Snowball sampling was used to recruit clinicians from across the care spectrum (ICU-community); critical care survivors and nominated family members were recruited using convenience sampling.

Measurements and Main Results:
Consensus on a peer support model was reached through the experience-based co-design process, with the following key themes: 1) socialization and group cohesion; 2) management of potential risks; and 3) individualized needs of patients and families. Evaluation of participants’ perspectives of the experience-based co-design method identified five key themes: 1) participation as a positive experience; 2) emotional engagement in the process; 3) learning from patients and family members; 4) feeling heard; and 5) practical challenges of experience-based co-design and readiness to participate.

Conclusions:
Experience-based co-design was a feasible approach to developing a peer support model for use with critical care survivors and was well received by participants. Future testing of the co-designed peer support model in a pilot randomized controlled trial will enhance understanding of peer support in critical care and the use of experience-based co-design as a design methodology.
Transitions, Suicidality, and Underappreciated Autism Spectrum Disorder in a High School Student
Authors: Ignaszewski Martha J. , Munshi Kaizad , Fogler Jason , Augustyn Marilyn 
Published: August 2019

CASE:

Alex is a 14-year-old Portuguese-American boy with a psychiatric history starting at age 5 who presents to your primary care practice after an insurance change.
He was delivered prematurely at 32 weeks and diagnosed with congenital hypothyroidism at the age of 6 weeks and growth hormone deficiency at the age of 2 years; he is in active treatment for both. He otherwise met developmental milestones on time yet continues to have significant fatigue despite adequate sleep and vitamin D supplementation.
His family history is remarkable for maternal anxiety, depression, suicidal thoughts, and previous attempted suicide, as well as anxiety, alcoholism, depression, and attention-deficit/hyperactivity disorder (ADHD) in the extended family.
Alex has had multiple psychiatric diagnoses by sequential providers. He was diagnosed with generalized anxiety disorder and ADHD by 5 years of age, major depressive disorder by 11 years of age, persistent depressive disorder by 12 years of age, and ultimately disruptive mood dysregulation disorder because of severe and persistent temper outbursts associated with negative mood and behavioral dysregulation, leading to recurrent crisis evaluations. He has been psychiatrically hospitalized twice, in the fifth and seventh grade, for suicidal ideation (SI) and elopement from home, respectively. He recently completed a 2-week acute residential placement, during which no medication changes were made. Current medications include escitalopram 20 mg daily, guanfacine 1 mg 3 times daily, sustained release bupropion 100 mg twice daily, levothyroxine, vitamin D, and a weekly somatropin injection. He has not been able to tolerate psychostimulants or nonstimulant agents because of treatment-emergent SI.
Now in the ninth grade, he continues to be easily distracted by peers, with impulsive behaviors and reduced self-regulation. Despite receiving special education services since the fifth grade, his academic performance has been poor, and he has limited motivation. Previous testing indicated average in an intelligence quotient test, with relative deficits in working memory compared with above average strength in fluid reasoning. He dislikes school and has few friends. He has always been noted to be “immature.” He displays temper tantrums at home and school around transitions and behavioral expectations and has complained of feeling “different” and misunderstood by peers in addition to having difficulty reading social cues. His interests include acting and playing Fortnite and other video/computer games. His screen time is limited to 1 to 2 hr/d by the family.
As the new clinician, you raise the possibility of undiagnosed autism spectrum disorder as a unifying/underlying diagnosis with his mother, who disagrees and does not consent to additional workup despite your recommendations. How would you proceed with next steps to best support your patient and his family in obtaining further clarifying evaluation?
Management of Malignant Large-Bowel Obstruction
Authors: Hsu June , Sevak Shruti 
Published: August 2019

CASE SUMMARY:
An otherwise healthy 59-year-old man presented to the emergency department with 2 weeks of narrowed stools, 5 days of obstipation, and 1 day of abdominal pain, nausea, and vomiting. Computed tomography revealed an obstructing sigmoid mass without evidence of metastatic disease, and the CEA was 1.2 ng/mL. Flexible sigmoidoscopy confirmed a circumferentially obstructing distal sigmoid neoplasm. Endoscopic stent placement was immediately followed by a firm distended abdomen. An upright radiograph obtained following the procedure demonstrated free intraperitoneal air. An emergent Hartmann procedure was performed for iatrogenic colon perforation in a patient with malignant obstruction and chronic dilation of the proximal colon.
Safety of Combination Laser or Intense Pulsed Light Therapies and Doxycycline for the Treatment of Rosacea
Authors: Schilling Laura M. , Halvorson Christian R. , Weiss Robert A. , Weiss Margaret A. , Beasley Karen L. 
Published: August 2019

BACKGROUND
Current treatment options for rosacea include topical agents, oral therapies, phototherapy using lasers, or intense pulsed light (IPL). Combination therapy for rosacea often yields better results than monotherapy. The safety of laser/light treatments in combination with systemic doxycycline has been questioned because of the theoretical risk of photosensitivity.

OBJECTIVE
The purpose of this study was to assess the incidence of phototoxicity or photosensitivity in rosacea patients receiving concomitant laser or light treatments and systemic doxycycline.

METHODS
Treatment records of 36 patients receiving laser/light treatments while also being treated with standard dose or anti-inflammatory dose of doxycycline were retrospectively reviewed.

RESULTS
No adverse reactions related to doxycycline combined with laser/light therapy were reported. Specifically, no photosensitivity or sensitivity to wavelengths in the pulsed dye laser (PDL), or IPL range was observed in this cohort. All patients achieved some degree of clearance.

CONCLUSION
The results of this retrospective study demonstrate that doxycycline used in conjunction with laser or nonlaser light therapy is a valid combination therapy for improving signs and symptoms of rosacea. No photosensitivity reactions were observed to commonly used IPL or PDL devices.