bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cloud Factory II: gravoturbulent kinematics of resolved molecular clouds in a galactic potential
Authors: Izquierdo Andrés F , Smith Rowan J , Glover Simon C O , Klessen Ralf S , Treß Robin G , Sormani Mattia C , Clark Paul C , Duarte-Cabral Ana , Zucker Catherine 
Published: November 2020

ABSTRACTWe present a statistical analysis of the gravoturbulent velocity fluctuations in molecular cloud complexes extracted from our ‘Cloud Factory’ Galactic-scale interstellar medium (ISM) simulation suite. For this purpose, we produce non-local thermodynamic equilibrium 12CO J = 1 − 0 synthetic observations and apply the principal component analysis (PCA) reduction technique on a representative sample of cloud complexes. The velocity fluctuations are self-consistently generated by different physical mechanisms at play in our simulations, which include Galactic-scale forces, gas self-gravity, and supernova feedback. The statistical analysis suggests that, even though purely gravitational effects are necessary to reproduce standard observational laws, they are not sufficient in most cases. We show that the extra injection of energy from supernova explosions plays a key role in establishing the global turbulent field and the local dynamics and morphology of molecular clouds. Additionally, we characterize structure function scaling parameters as a result of cloud environmental conditions: some of the complexes are immersed in diffuse (interarm) or dense (spiral-arm) environments, and others are influenced by embedded or external supernovae. In quiescent regions, we obtain time-evolving trajectories of scaling parameters driven by gravitational collapse and supersonic turbulent flows. Our findings suggest that a PCA-based statistical study is a robust method to diagnose the physical mechanisms that drive the gravoturbulent properties of molecular clouds. Also, we present a new open source module, the pcafactory, which smartly performs PCA to extract velocity structure functions from simulated or real data of the ISM in a user-friendly way.
On rare core collapse supernovae inside planetary nebulae
Authors: Bear Ealeal , Soker Noam 
Published: November 2020

ABSTRACT
We conduct simulations using mesa of the reverse formation of a white dwarf (WD)–neutron star (NS) binary system in which the WD forms before the NS. We conclude that a core collapse supernova (CCSN) explosion might occur inside a planetary nebula (PN) only if a third star forms the PN. In this WD–NS reverse binary evolution, the primary star evolves and transfers mass to the secondary star, forms a PN, and leaves a WD remnant. If the mass-transfer brings the secondary star to have a mass of $\gtrsim 8\, \mathrm{ M}_\odot$ before it develops a helium core, and if the secondary does not suffer an enhanced mass-loss before it develops a massive helium core, e.g. by mass-transfer, it explodes as a CCSN and leaves an NS remnant. The time period from the formation of the PN by the primary to the explosion of the secondary is $\gtrsim 10^6 {~\rm yr}$. By that time, the PN has long dispersed into the interstellar medium. In a binary system with nearly equal-mass components, the first mass-transfer episode takes place after the secondary star has developed a helium core and it ends its life forming a PN and a WD. The formation of a CCSN inside a PN (CCSNIP) requires the presence of a third star. The third star should be less massive than the secondary star but by no more than few ×0.01 M⊙. We estimate that the rate of CCSNIP is ≈10−4 times the rate of all CCSNe.
Exploring the origin of low-metallicity stars in Milky-Way-like galaxies with the NIHAO-UHD simulations
Authors: Sestito Federico , Buck Tobias , Starkenburg Else , Martin Nicolas F , Navarro Julio F , Venn Kim A , Obreja Aura , Jablonka Pascale , Macciò Andrea V 
Published: November 2020

ABSTRACT
The kinematics of the most metal-poor stars provide a window into the early formation and accretion history of the Milky Way (MW). Here, we use five high-resolution cosmological zoom-in simulations (∼ 5 × 106 star particles) of MW-like galaxies taken from the NIHAO-UHD project, to investigate the origin of low-metallicity stars ([Fe/H] ≤ −2.5). The simulations show a prominent population of low-metallicity stars confined to the disc plane, as recently discovered in the MW. The ubiquity of this finding suggests that the MW is not unique in this respect. Independently of the accretion history, we find that ≳90 per cent of the retrograde stars in this population are brought in during the initial build-up of the galaxies during the first few Gyr after the Big Bang. Our results therefore highlight the great potential of the retrograde population as a tracer of the early build-up of the MW. The prograde planar population, on the other hand, is accreted during the later assembly phase and samples the full galactic accretion history. In case of a quiet accretion history, this prograde population is mainly brought in during the first half of cosmic evolution (t ≲ 7 Gyr), while, in the case of an ongoing active accretion history, later mergers on prograde orbits are also able to contribute to this population. Finally, we note that the MW shows a rather large population of eccentric, very metal-poor planar stars. This is a feature not seen in most of our simulations, with the exception of one simulation with an exceptionally active early building phase.
LIN 358: a symbiotic binary accreting above the steady hydrogen fusion limit
Authors: Kuuttila J , Gilfanov M , Woods T E , Seitenzahl I R , Ruiter A J 
Published: November 2020

ABSTRACT
Symbiotic binaries are long-period interacting binaries consisting of a white dwarf (WD) accreting material from a cool evolved giant star via stellar winds. In this paper, we study the symbiotic binary LIN 358 located in the Small Magellanic Cloud. We have observed LIN 358 with the integral field spectrograph WiFeS and obtained its line emission spectrum. With the help of the plasma simulation and spectral synthesis code cloudy, we have constructed a 2D photoionization model of LIN 358. From comparison with the observations, we have determined the colour temperature of the WD in LIN 358 to be 19 eV, its bolometric luminosity L = (1.02 ± 0.15) × 1038 erg s−1, and the mass-loss rate from the donor star to be 1.2 × 10−6 M⊙ yr−1. Assuming a solar H to He ratio in the wind material, a lower limit to the accreted mass fraction in LIN 358 is 0.31. The high mass accretion efficiency of a wind Roche lobe overflow implies that the WD is accreting above the upper boundary of stable hydrogen fusion and thus growing in mass with the maximal rate of ≈4 × 10−7 M⊙ yr−1. This causes the WD photosphere to expand, which explains its low colour temperature. Our calculations show that the circumstellar material in LIN 358 is nearly completely ionized except for a narrow cone around the donor star, and that the WD emission is freely escaping the system. However, due to its low colour temperature, this emission can be easily attenuated by even moderate amounts of neutral interstellar medium. We speculate that other symbiotic systems may be operating in a similar regime, thus explaining the paucity of observed systems.
The chemotherapeutic agent CX-5461 irreversibly blocks RNA polymerase I initiation and promoter release to cause nucleolar disruption, DNA damage and cell inviability
Authors: Mars Jean-Clément , Tremblay Michel G , Valere Mélissa , Sibai Dany S , Sabourin-Felix Marianne , Lessard Frédéric , Moss Tom 
Published: November 2020

Abstract
In the search for drugs to effectively treat cancer, the last 10 years have seen a resurgence of interest in targeting ribosome biogenesis. CX-5461 is a potential inhibitor of ribosomal RNA synthesis that is now showing promise in phase I trials as a chemotherapeutic agent for a range of malignancies. Here, we show that CX-5461 irreversibly inhibits ribosomal RNA transcription by arresting RNA polymerase I (RPI/Pol1/PolR1) in a transcription initiation complex. CX-5461 does not achieve this by preventing formation of the pre-initiation complex nor does it affect the promoter recruitment of the SL1 TBP complex or the HMGB-box upstream binding factor (UBF/UBTF). CX-5461 also does not prevent the subsequent recruitment of the initiation-competent RPI–Rrn3 complex. Rather, CX-5461 blocks promoter release of RPI–Rrn3, which remains irreversibly locked in the pre-initiation complex even after extensive drug removal. Unexpectedly, this results in an unproductive mode of RPI recruitment that correlates with the onset of nucleolar stress, inhibition of DNA replication, genome-wide DNA damage and cellular senescence. Our data demonstrate that the cytotoxicity of CX-5461 is at least in part the result of an irreversible inhibition of RPI transcription initiation and hence are of direct relevance to the design of improved strategies of chemotherapy.
Sequence variation, common tissue expression patterns and learning models: a genome-wide survey of vertebrate ribosomal proteins
Authors: Kyritsis Konstantinos A , Ouzounis Christos A , Angelis Lefteris , Vizirianakis Ioannis S 
Published: November 2020

AbstractRibosomal genes produce the constituents of the ribosome, one of the most conserved subcellular structures of all cells, from bacteria to eukaryotes, including animals. There are notions that some protein-coding ribosomal genes vary in their roles across species, particularly vertebrates, through the involvement of some in a number of genetic diseases. Based on extensive sequence comparisons and systematic curation, we establish a reference set for ribosomal proteins (RPs) in eleven vertebrate species and quantify their sequence conservation levels. Moreover, we correlate their coordinated gene expression patterns within up to 33 tissues and assess the exceptional role of paralogs in tissue specificity. Importantly, our analysis supported by the development and use of machine learning models strongly proposes that the variation in the observed tissue-specific gene expression of RPs is rather species-related and not due to tissue-based evolutionary processes. The data obtained suggest that RPs exhibit a complex relationship between their structure and function that broadly maintains a consistent expression landscape across tissues, while most of the variation arises from species idiosyncrasies. The latter may be due to evolutionary change and adaptation, rather than functional constraints at the tissue level throughout the vertebrate lineage.
Prevalence of Sleep Disordered Breathing in Children With Myelomeningocele
Authors: Rocque Brandon G , Maddox Mary Halsey , Hopson Betsy D , Shamblin Isaac C , Aban Inmaculada , Arynchyna Anastasia A , Blount Jeffrey P 
Published: November 2020

Abstract

BACKGROUND
Retrospective studies have shown high rates of sleep disordered breathing in children with myelomeningocele. However, most patients included in those studies underwent polysomnography because of symptoms, so the prevalence of sleep disordered breathing in this population is unknown.

OBJECTIVE
To determine the prevalence of sleep disordered breathing in children with myelomeningocele using screening polysomnography.

METHODS
In this cross-sectional study, all children with myelomeningocele seen in a multi-disciplinary spina bifida clinic between 2016 and 2020 were referred for polysomnography regardless of clinical symptoms. Included children had not previously undergone polysomnography. The primary outcome for this study was presence of sleep disordered breathing, defined as Apnea-Hypopnea Index (AHI, number of apnea or hypopnea events per hour of sleep) greater than 2.5. Clinical and demographic variables relevant to myelomeningocele were also prospectively collected and tested for association with presence of sleep apnea.

RESULTS
A total of 117 participants underwent polysomnography (age 1 mo to 21 yr, 49% male). The majority were white, non-Hispanic. Median AHI was 1.9 (interquartile range 0.6-4.2). A total of 49 children had AHI 2.5 or greater, yielding a sleep disordered breathing prevalence of 42% (95% CI 33%-51%). In multivariable logistic regression analysis, children with more rostral neurological lesion levels had higher odds of sleep disordered breathing (OR for thoracic, mid-lumbar, and low-lumbar: 7.34, 3.70, 4.04, respectively, compared to sacral level, P = .043).

CONCLUSION
Over 40% of a sample of children with myelomeningocele, who underwent screening polysomnography, had significant sleep disordered breathing. Routine screening polysomnography may be indicated in this population.
Data-driven prioritization and preclinical evaluation of therapeutic targets in glioblastoma
Authors: Brahm Cyrillo G , Abdul U Kulsoom , Houweling Megan , van Linde Myra E , Lagerweij Tonny , Verheul Henk M W , Westerman Bart A , Walenkamp Annemiek M E , Fehrmann Rudolf S N 
Published: November 2020

AbstractBackgroundPatients with glioblastoma (GBM) have a dismal prognosis, and there is an unmet need for new therapeutic options. This study aims to identify new therapeutic targets in GBM.MethodsmRNA expression data of patient-derived GBM (n = 1279) and normal brain tissue (n = 46) samples were collected from Gene Expression Omnibus and The Cancer Genome Atlas. Functional genomic mRNA profiling was applied to capture the downstream effects of genomic alterations on gene expression levels. Next, a class comparison between GBM and normal brain tissue was performed. Significantly upregulated genes in GBM were further prioritized based on (1) known interactions with antineoplastic drugs, (2) current drug development status in humans, and (3) association with biologic pathways known to be involved in GBM. Antineoplastic agents against prioritized targets were validated in vitro and in vivo.ResultsWe identified 712 significantly upregulated genes in GBM compared to normal brain tissue, of which 27 have a known interaction with antineoplastic agents. Seventeen of the 27 genes, including EGFR and VEGFA, have been clinically evaluated in GBM with limited efficacy. For the remaining 10 genes, RRM2, MAPK9 (JNK2, SAPK1a), and XIAP play a role in GBM development. We demonstrated for the MAPK9 inhibitor RGB-286638 a viability loss in multiple GBM cell culture models. Although no overall survival benefit was observed in vivo, there were indications that RGB-286638 may delay tumor growth.ConclusionsThe MAPK9 inhibitor RGB-286638 showed promising in vitro results. Furthermore, in vivo target engagement studies and combination therapies with this compound warrant further exploration.
“Living Well with Chronic Pain”: Integrative Pain Management via Shared Medical Appointments
Authors: Znidarsic Josie , Kirksey Kellie N , Dombrowski Stephen M , Tang Anne , Lopez Rocio , Blonsky Heather , Todorov Irina , Schneeberger Dana , Doyle Jonathan , Libertini Linda , Jamie Starkey , Segall Tracy , Bang Andrew , Barringer Kathy , Judi Bar , Ehrman Jane Pernotto , Roizen Michael F , Golubić Mladen 
Published: November 2020

Abstract

Objective
To evaluate the effectiveness of a multidisciplinary, nonpharmacological, integrative approach that uses shared medical appointments to improve health-related quality of life and reduce opioid medication use in patients with chronic pain.

Design
This is a retrospective, pre–post review of “Living Well with Chronic Pain” shared medical appointments (August 2016 through May 2018).

Setting
The appointments included eight 3-hour-long visits held once per week at an outpatient wellness facility.

Subjects
Patients with chronic, non–cancer-related pain.

Methods
Patients received evaluation and evidence-based therapies from a team of integrative and lifestyle medicine professionals, as well as education about nonpharmacological therapeutic approaches, the etiology of pain, and the relationship of pain to lifestyle factors. Experiential elements focused on the relaxation techniques of meditation, yoga, breathing, and hypnotherapy, while patients also received acupuncture, acupressure, massage, cognitive behavioral therapy, and chiropractic education. Patients self-reported data via the Patient-Reported Outcomes Measurement Information System (PROMIS-57) standardized questionnaire. Use of opioid medications was evaluated in morphine milligram equivalents.

Results
A total of 178 participants completed the PROMIS-57 questionnaire at the first and the last visits. Statistically significant improvements in all domains (Physical Functioning, Anxiety, Depression, Fatigue, Social Roles, Pain Interference, and Sleep Disturbance) were observed (P &lt; 0.001) between the pre-intervention (visit 1) and post-intervention (visit 8) scores. Average opioid use decreased nonsignificantly over the 8-week intervention, but the lower rate of opioid use was not sustained at 6 and 12 months’ follow-up.

Conclusions
Patients suffering from chronic pain who participated in a multidisciplinary, nonpharmacological treatment approach delivered via shared medical appointments experienced reduced pain and improved measures of physical, mental, and social health without increased use of opioid pain medications.
Construct Validity and Reliability of the Japanese Version of the Lumbar Stiffness Disability Index
Authors: Furuya Hidetaka , Ito Takashi , Hirohata Kenji , Mitomo Sho , Yamasaki Koji , Igarashi Hidetoshi , Omori Keita , Hoshino Masahiro , Hart Robert A. 
Published: November 2020

Study Design.
Outcome study to determine the construct validity and reliability of the Japanese version of the Lumbar Stiffness Disability Index.

Objective.
The aim of this study was to evaluate the psychometric measurement properties of the Japanese version of the Lumbar Stiffness Disability Index (J-LSDI) following lumbar spinal surgery in order to assess its construct validity and reliability.

Summary of Background Data.
The LSDI was designed and validated as a tool to assess functional impacts of lumbar spine stiffness and diminished spinal flexibility. A Japanese version has been developed, but its construct validity and reliability have not been evaluated.

Methods.
A Pearson correlation coefficient was calculated using flexion and extension range of motion, Oswestry Disability Index (ODI) and Tampa Scale for Kinesiophobia (TSK) as external standards to evaluate construct validity. An intraclass correlation coefficient (ICC) and a Bland-Altman analysis were used to evaluate test–retest reliability.

Results.
A total of 244 patients following lumbar spinal surgery participated in the study. Fifty one of the 244 patients participated in the reliability study. The ICC of the J-LSDI for test–retest reliability was 0.89 (95% confidence interval, 0.79–0.93). There was no systematic error found in the results of the Bland-Altman analysis. One hundred ninety-three of the 244 patients participated in the validity study. There were significant correlations between the J-LSDI and trunk flexion range of motion (r = −0.66), extension (r = −0.51), ODI (r = 0.62), and TSK (r = 0.38).

Conclusion.
The construct validity and reliability of the Japanese version of the LSDI were confirmed. The J-LSDI can be used to evaluate lumbar stiffness and associated disability in Japanese patients following lumbar spinal surgery.

Level of Evidence: 2
Does a Multidisciplinary Triage Pathway Facilitate Better Outcomes After Spine Surgery?
Authors: Wu Adam , Liu Lucy , Fourney Daryl R. 
Published: November 2020

Study Design.
Single-center prospective non-randomized matched cohort comparison.

Objective.
To compare elective lumbar spine surgery outcomes for cases triaged through a multidisciplinary spine pathway versus conventional referral processes.

Summary of Background Data.
Many health care systems have facilitated low back pain (LBP) guidelines into primary care practice by creating local or regional “pathways” with the goal of enhanced quality of care, improved patient satisfaction and optimal resource utilization, particularly for imaging and surgery. Few comparative outcomes exist for LBP pathways, particularly for surgical outcomes.

Methods.
One-hundred-fifty patients (SSP group n = 75; conventional group n = 75) undergoing elective lumbar surgery for degenerative conditions between 2011 and 2016 were analyzed with 1-year follow-up. Patient self-reported outcomes included the Oswestry disability index (ODI), visual analogue pain scores (VAS) for back and leg, and EuroQol Group 5—Dimension self-report (EQ-5D). We also assessed baseline clinical features, indications for surgery, therapies received prior to surgery, type of surgery, wait times, and overall patient satisfaction.

Results.
The groups had equivalent baseline demographics, body mass index, Saskatchewan Spine Pathway (SSP) classification of pain pattern, pain scores, functional scores, quality of life scores, indication for surgery, and type of surgery (instrumented or non-instrumented). There was no difference with respect to wait times to see the surgeon or for surgery. Wait time for magnetic resonance imaging (MRI) was significantly shorter for the SSP group (16.8 vs. 63.0 days, P < 0.001). Patients triaged through the SSP were significantly more likely to utilize multiple nonoperative treatment strategies prior to seeing the surgeon (P < 0.04). Patient satisfaction was significantly higher for SSP patients prior to surgical assessment (P = 0.03) but did not differ between groups after surgery.

Conclusion.
The SSP facilitates significantly shorter wait times for MRI and promotes nonoperative treatment strategies. Preoperative patient satisfaction is significantly higher among SSP patients, but there were no significant differences in surgical outcomes.

Level of Evidence: 3
Time Course of Physical and Mental Well-being Improvements After Cervical Surgery
Authors: Tamai Koji , Suzuki Akinobu , Terai Hidetomi , Hoshino Masatoshi , Toyoda Hiromitsu , Takahashi Shinji , Hori Yusuke , Yabu Akito , Nakamura Hiroaki 
Published: November 2020

Study Design.
Retrospective cohort study.

Objective.
To elucidate the postoperative time course of improvements in physical and mental well-being in patients with cervical spondylotic myelopathy (CSM).

Summary of Background Data.
Spinal surgeons should understand the postoperative course in detail. However, data are still needed regarding the time course of improvements in well-being, a fundamental aspect of human life, after cervical surgery for CSM.

Methods.
One hundred consecutive patients who underwent laminoplasty for CSM, with complete clinical data preoperatively and 3 months and 2 years postoperatively, were enrolled. The Short Form-36 physical component summary (PCS) and mental component summary (MCS) scores were used as parameters of physical and mental well-being, respectively, and 4.0 was defined as the minimal clinically important difference (MCID) for both parameters.

Results.
On average, PCS and MCS scores were significantly improved after surgery (P < 0.001, P=0.004, respectively). Moreover, 64 and 48 patients achieved meaningful improvement (>MCID) in PCS and MCS scores at 3 months postoperatively, with maintained improvement (to 2 yr) in 46/64 (71.9%) and 34/48 patients (70.8%), respectively (PCS vs. MCS: P = 0.912). Additionally, 15 of 36 patients (41.7%) and 8 of 52 patients (15.4%) achieved late improvement (meaningful improvement at 2 yr but not at 3 months) in PCS and MCS scores, respectively (PCS vs. MCS: P = 0.007). In multivariate regression analysis, improvement in cJOA score was significantly associated with PCS improvement, but not MCS improvement, at both 3 months and 2 years (P = 0.001, P > 0.001, respectively).

Conclusion.
The overall outcome of physical well-being improvement is decided within 3 months postoperatively, in proportion to the recovery in myelopathy, with a relatively high chance of meaningful improvement over the next 21 months. The outcome of improvement in mental well-being is decided within 3 months postoperatively, independently from the recovery in myelopathy, with a low chance of meaningful improvement over the next 21 months.

Level of Evidence: 3