bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper Atmosphere Radiance Data Assimilation: A Feasibility Study for GOLD Far Ultraviolet Observations
Authors: Cantrall Clayton E. , Matsuo Tomoko , Solomon Stanley C. 
Published: October 2019

AbstractFar ultraviolet observations of Earth's dayglow from the National Aeronautics and Space Administration (NASA) Global‐scale Observations of the Limb and Disk (GOLD) mission presents an unparalleled opportunity for upper atmosphere radiance data assimilation. Assimilation of the Lyman‐Birge‐Hopfield (LBH) band emissions can be formulated in a similar fashion to lower atmosphere radiance data assimilation approaches. To provide a proof‐of‐concept for such an approach, this paper presents assimilation experiments of simulated LBH emission data using an ensemble filter measurement update step implemented with National Oceanic and Atmospheric Administration (NOAA)'s Whole Atmosphere Model (WAM) and National Center for Atmospheric Research (NCAR)'s Global Airglow (GLOW) model. Primary findings from observing system simulation experiments (OSSEs), wherein “truth” atmospheric conditions simulated by NCAR's Thermosphere Ionosphere Electrodynamic General Circulation Model (TIEGCM) are used to generate synthetic GOLD data, are as follows: (1) Assimilation of GOLD LBH disk emission data can reduce the bias in model temperature specification (ensemble mean) by 60% under both geomagnetically quiet conditions and disturbed conditions. (2) The reduction in model uncertainty (ensemble spread) as a result of assimilation is about 20% in the lower thermosphere and 30% in the upper thermosphere for both conditions. These OSSEs demonstrate the potential for far ultraviolet radiance data assimilation to dramatically reduce the model biases in thermospheric temperature specification and to extend the utility of GOLD observations by helping to resolve the altitude‐dependent global‐scale response of the thermosphere to geomagnetic storms.
Substorm Energy Transport From the Magnetotail to the Nightside Ionosphere
Authors: Ohtani Shinichi 
Published: October 2019

AbstractThe present study addresses the transport of energy from the nightside magnetosphere to the ionosphere during the substorm expansion phase. From the cross‐examination of the estimates of various ionospheric and magnetospheric processes, it is inferred that (1) Poynting flux from the tail lobes to the plasma sheet accounts for the ionospheric energy dissipation during the substorm expansion phase, suggesting that the lobe reconnection is the primary driver of the substorm energy transport to the ionosphere; (2) the area around the duskside poleward boundary of the auroral bulge, where auroral emission is intense throughout the expansion phase, accounts for >10%, likely a few tens of percent, of the ionospheric substorm energy dissipation, suggesting that the area is a crucial energy sink; and (3) kinetic energy carried by the bursty bulk flows is comparable to the energy deposited in association with the auroral streamers, and each bursty bulk flow accounts for ~1% of the total substorm energy deposition, which may sum up to 10% throughout the expansion phase. Points 2 and 3 imply that energy deposited to the ionosphere is transported mostly along, rather than across, the magnetic field lines in the plasma sheet. The responsible field‐aligned plasma flows may be generated as the perpendicular plasma motion creates field‐aligned pressure gradient in the presence of field line curvature. Energy flux associated with enhanced convection in the plasma sheet is statistically examined with the Geotail data set, which confirms that more energy is carried earthward by the field‐aligned flows than by the convection flows.
Comparison of IRI‐2016 F2 Layer Model Parameters with Ionosonde Measurements
Authors: Arıkan Feza , Sezen Umut , Gulyaeva Tamara L. 
Published: October 2019

AbstractInternational Reference Ionosphere (IRI) is the international standard ionospheric climatic model. Since the original formation of the international task force in 1970s, the IRI model has been continuously improved by ingesting developments in research in ionosphere. The most current version, namely, IRI‐2016, is offered with International Radio Consultative Committee (CCIR) and International Union of Radio Science (URSI) model choices with “STORM” option for the F2 layer critical plasma frequency (foF2) and BSE‐1979, AMTB‐2013, and SHU‐2015 options for maximum ionization height, hmF2. Since these two parameters are the determining values for the other model outputs, the evaluation of the options offered by IRI‐2016 is critical for various applications. In this study, all foF2 and hmF2 model options offered online at irimodel.org are computed for winter and summer solstice and equinox seasons of 2011 and 2015 at the locations of all available ionosondes and for all measurement intervals. The ionosondes are grouped into northern and southern midlatitude, northern and southern high‐latitude and equatorial regions. Individual, regional and global model output foF2 and hmF2 values are compared with those of ionosondes in both root‐mean‐square (RMS) and normalized RMS (NRMS) senses. For foF2, “STORM ON” can be used any time and in any region. Equatorial and high‐latitude regions have larger RMS values due to the sparse ionosondes. In northern midlatitude and high‐latitude regions URSI, in all other regions CCIR is the better option. For hmF2, SHU‐2015 and BSE‐1979 options provide a better fit for all regions, seasons, and years.
Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and a perspective on resistance mechanisms
Authors: Sahin Ibrahim Halil , Akce Mehmet , Alese Olatunji , Shaib Walid , Lesinski Gregory B. , El-Rayes Bassel , Wu Christina 
Published: October 2019

AbstractMetastatic colorectal cancer (CRC) with a mismatch repair-deficiency (MMR-D)/microsatellite instability-high (MSI-H) phenotype carries unique characteristics such as increased tumour mutational burden and tumour-infiltrating lymphocytes. Studies have shown a sustained clinical response to immune checkpoint inhibitors with dramatic clinical improvement in patients with MSI-H/MMR-D CRC. However, the observed response rates range between 30% and 50% suggesting the existence of intrinsic resistance mechanisms. Moreover, disease progression after an initial positive response to immune checkpoint inhibitor treatment points to acquired resistance mechanisms. In this review article, we discuss the clinical trials that established the efficacy of immune checkpoint inhibitors in patients with MSI-H/MMR-D CRC, consider biomarkers of the immune response and elaborate on potential mechanisms related to intrinsic and acquired resistance. We also provide a perspective on possible future therapeutic approaches that might improve clinical outcomes, particularly in patients with actionable resistance mechanisms.
How to Save a Life From Macroscopic Fat Embolism: A Narrative Review of Treatment Options
Authors: Lari Aqeel , Abdulshakoor Abeer , Zogheib Elie , Assaf Nizar , Mojallal Ali , Lari Abdul-Reda , Bauer Christian , Sinna Raphael 
Published: October 2019

AbstractMacroscopic fat embolism (MAFE) has grabbed the attention of the plastic surgery community in recent years because of its high mortality rate. Many articles on preventing MAFE during gluteal fat grafting are available in the literature. However, total prevention is difficult: a number of factors, both technical and human, mean that MAFE remains a potential complication. This review was written with the main goal of providing a treatment plan. MAFE shares many similar pathophysiologic and hemodynamic features with massive thrombotic pulmonary embolism (PE), especially the associated cardiopulmonary decompensation. Lessons learned from PE management were used to devise a management algorithm for MAFE. The use of extracorporeal membrane oxygenation and its potential application as a main modality of treatment for MAFE was explored. The lack of evidence in the literature for the treatment of MAFE, and its high mortality, lent urgency to the need to write an article on the management aspect in the form of a narrative review, to ensure that every plastic surgeon practicing gluteal fat grafting is knowledgeable about the treatment aspect of this deadly complication.
The Pursuit and Advancement of Knowledge as a Justification for the Use of Animals in Research
Authors: Tannenbaum Jerrold 
Published: October 2019

AbstractIt is commonly said that animal research is sometimes ethically appropriate because it can lead to knowledge, irrespective of benefits this knowledge might bring to humans or animals. Proponents of this view, which I call the “knowledge justification,” have been unclear about what they mean by the term “knowledge.” They also omit from the justification other features of animal research that are intimately connected with the pursuit and advancement of knowledge. This article identifies and includes in a modified knowledge justification 5 general elements of the pursuit and advancement of knowledge in animal research: “knowledge” in the sense of facts, information, or explanations; “knowledge” in the sense of the experience of having knowledge; contemplation; the exercise of intellectual faculties and skills; and pleasures, frustrations, and challenges in the pursuit and advancement of knowledge. The article explains why these elements are valuable and must be given weight in assessing the ethical appropriateness of curiosity-driven animal research. The discussion critiques defenses and applications of current expressions of the knowledge justification. The article offers a preliminary defense of curiosity-driven animal research by arguing that using animals to obtain scientific knowledge and the pleasures of scientific inquiry can be far more valuable for humans and no more harmful to some animals than the use of these animals to produce meat for human consumption. The article presents 2 examples of curiosity-driven animal research to further establish the plausibility of the knowledge justification and suggests questions and guidelines for developing the justification.
Production and Clinical Evaluation of Norwalk GI.1 Virus Lot 001-09NV in Norovirus Vaccine Development
Authors: Mateo Roberto , Lindesmith Lisa C , Garg Shaily J , Gottlieb Keith , Lin Karen , Said Sara , Leon Juan S , Sims Amy C , Weber David J , Baric Ralph S , Tucker Sean N , Taylor David N 
Published: October 2019

Abstract

Background
Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM).

Methods
A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses.

Results
Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells.

Conclusions
GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates.
Suprapubic penetrating abdominal trauma - defining peritoneal breach and choices in operative intervention
Authors: Papanikolas Michael J , Sarkar Anik , Kandiah Shivanthi , Niles Navin 
Published: October 2019

Abstract
Penetrating abdominal trauma is an uncommon cause of presentation to emergency departments in Australia and is frequently associated with the clinical need for emergent operative intervention. Advances in imaging modalities, improved laparoscopic techniques and structured approaches to resuscitation in trauma have now allowed potential minimally invasive management of such injuries, avoiding laparotomy and therefore defining peritoneal breach; the major determinant of intra-abdominal organ injury in this setting is critical. We present the case of a self-inflicted stab injury to the suprapubic region in an otherwise healthy man and describe the combination of imaging and operative modalities used to define peritoneal breach in this case which successfully reduced the patient’s morbidity by avoiding non-therapeutic laparotomy.
Cloud–cloud collisions in the common foot point of molecular loops 1 and 2 in the Galactic Center
Authors: Enokiya Rei , Torii Kazufumi , Fukui Yasuo 
Published: October 2019

AbstractRecent large-area, deep CO surveys in the Galactic disk have revealed the formation of ~50 high-mass stars or clusters triggered by cloud–cloud collisions (CCCs). Although the Galactic Center (GC)—which contains the highest volume density of molecular gas—is the most favorable place for cloud collisions, systematic studies of CCCs in that region are still untouched. Here we report for the first time evidence of CCCs in the common foot point of molecular loops 1 and 2 in the GC. We have investigated the distribution of molecular gas toward the foot point by using a methodology for identifying CCCs, and we have discovered clear signatures of CCCs. Using the estimated displacements and relative velocities of the clouds, we find the elapsed time since the beginnings of the collisions to be 105–106yr. We consider possible origins for previously reported peculiar velocity features in the foot point and discuss star formation triggered by CCCs in the GC.
Stress induces dynamic, cytotoxicity-antagonizing TDP-43 nuclear bodies via paraspeckle lncRNA NEAT1-mediated liquid-liquid phase separation
Authors: Wang Chen , Duan Yongjia , Duan Gang , Wang Qiangqiang , Zhang Kai , Deng Xue , Qian Beituo , Gu Jinge , Ma Zhiwei , Zhang Shuang , Guo Lin , Liu Cong , Fang Yanshan 
Published: October 2019

Graphic AbstractHighlights(Up to four bullet points. The length of each highlight cannot exceed 85 characters, including spaces)Stress induces phase-separated TDP-43 NBs to alleviate cytotoxicityThe two RRMs interact with different RNAs and act distinctly in the assembly of TDP-43 NBsLncRNA NEAT1 promotes TDP-43 LLPS and is upregulated in stressed neuronsThe ALS-causing D169G mutation is NB-defective and forms pTDP-43 cytoplasmic fociSummaryDespite the prominent role of TDP-43 in neurodegeneration, its physiological and pathological functions are not fully understood. Here, we report an unexpected function of TDP-43 in the formation of dynamic, reversible, liquid droplet-like nuclear bodies (NBs) in response to stress. Formation of NBs alleviates TDP-43-mediated cytotoxicity in mammalian cells and fly neurons. Super-resolution microscopy reveals a “core-shell” organization of TDP-43 NBs, antagonistically maintained by the two RRMs. TDP-43 NBs are partially colocalized with nuclear paraspeckles, whose scaffolding lncRNA NEAT1 is dramatically upregulated in stressed neurons. Moreover, increase of NEAT1 promotes TDP-43 liquid-liquid phase separation (LLPS) in vitro. Finally, we uncover that the ALS-associated mutation D169G impairs the NEAT1-mediated TDP-43 LLPS and NB assembly, causing excessive cytoplasmic translocation of TDP-43 to form stress granules that become phosphorylated TDP-43 cytoplasmic foci upon prolonged stress. Together, our findings suggest a stress-mitigating role and mechanism of TDP-43 NBs, whose dysfunction may be involved in ALS pathogenesis.
MICU1 regulates mitochondrial cristae structure and function independent of the mitochondrial calcium uniporter channel
Authors: Tomar Dhanendra , Thomas Manfred , Garbincius Joanne F. , Kolmetzky Devin W. , Salik Oniel , Jadiya Pooja , Carpenter April C. , Elrod John W. 
Published: October 2019

AbstractMICU1 is an EF-hand-containing mitochondrial protein that is essential for gating of the mitochondrial Ca2+ uniporter channel (mtCU) and is reported to interact directly with the pore-forming subunit, MCU and scaffold EMRE. However, using size-exclusion proteomics, we found that MICU1 exists in mitochondrial complexes lacking MCU. This suggests that MICU1 may have additional cellular functions independent of regulating mitochondrial Ca2+ uptake. To discern mtCU-independent MICU1 functions, we employed a proteomic discovery approach using BioID2-mediated proximity-based (<10nm) biotinylation and subsequent LC-MS detection. The expression of a MICU1-BioID2 fusion protein in MICU1-/- and MCU-/- cells allowed the identification of total vs. mtCU-independent MICU1 interactors. Bioinformatics identified the Mitochondrial Contact Site and Cristae Organizing System (MICOS) components MIC60 (encoded by the IMMT gene) and Coiled-coil-helix-coiled-coil helix domain containing 2 (CHCHD2) as novel MICU1 interactors, independent of the mtCU. We demonstrate that MICU1 is essential for proper proteomic organization of the MICOS complex and that MICU1 ablation results in altered cristae organization and mitochondrial ultrastructure. We hypothesize that MICU1 serves as a MICOS calcium sensor, since perturbing MICU1 is sufficient to modulate cytochrome c release independent of mitochondrial Ca2+ uptake across the inner mitochondrial membrane (IMM). Here, we provide the first experimental evidence suggesting that MICU1 regulates cellular functions independent of mitochondrial calcium uptake and may serve as a critical mediator of Ca2+-dependent signaling to modulate mitochondrial membrane dynamics and cristae organization.
Improved longevity and efficacy of sacral nerve stimulation by simple adjustments at follow‐up
Authors: Duelund‐Jakobsen J. , Buntzen S. , Laurberg S. , Lundby L. 
Published: October 2019

AbstractAimSacral nerve stimulation (SNS) for faecal incontinence (FI) at subsensory amplitudes as low as 50% of the sensory threshold has been found to be effective at 3 months’ follow‐up. Furthermore, alternative pacemaker settings may improve functional outcome in patients with suboptimal treatment efficacy. In this work we aim to explore if sub‐sensory stimulation as low as 50% of sensory threshold is effective at 1‐year follow‐up. We also aimed to investigate if 31 Hz (frequency) or 90 µs (pulse width) stimulation improved treatment efficacy in dissatisfied patients.MethodAll patients in whom the stimulation was effective in controlling FI (satisfied group) were encouraged to have the stimulation amplitude reduced. Those in whom the device was less effective (dissatisfied group) were offered alternative frequency settings or pulse width (31 Hz or 90 µs). Patients were follow‐up after 12 months and evaluated by a visual analogue scale (VAS) for patient satisfaction, the Cleveland Clinic Continence Score (CCCS), Rockwood Faecal Incontinence Quality of Life Scale (QoL) and a bowel habit diary.ResultsTwo hundred and nineteen patients were contacted, with a response rate of 71% (n = 155). Those who were successfully contacted comprised 110 (71%) patients classed as satisfied and 45 (29%) as dissatisfied. Seventy‐five (68%) of the satisfied patients agreed to have their stimulation amplitude reduced. At 1‐year follow‐up the median amplitude had reduced from 1.5 V [interquartile range (IQR) 0.85–2.0 V] to 0.75 V (IQR 0.45–1.4 V) (P‐value < 0.001) representing an overall reduction of 39% (6.6–62.5%). There were no significant differences in VAS, CCCS or QoL despite subsensory stimulation at 1‐year follow‐up. In 28% of the dissatisfied patients alternative pacemaker settings improved VAS to satisfactory levels.ConclusionSubsensory stimulation is as effective as stimulation at or above the sensory threshold. High‐frequency stimulation (31 Hz) can improve functional outcome in patients with loss of efficacy.
Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE trial
Authors: McBane Robert D. , Loprinzi Charles L. , Ashrani Aneel , Lenz Charles J. , Houghton Damon , Zemla Tyler , Le‐Rademacher Jennifer G. , Wysokinski Waldemar E. 
Published: October 2019

AbstractBackgroundCancer‐associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA‐approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double‐blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883).Methods/DesignThe primary study objective is to estimate differences in the combined rate of major plus clinically relevant non‐major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium.ConclusionWe anticipate these trial results to provide evidence supporting low‐dose apixaban as a safe agent for secondary prevention of cancer‐associated VTE for patients who have already completed 6‐12 months of anticoagulation.
Pavlovian‐to‐instrumental transfer in Anorexia Nervosa: A pilot study on conditioned learning and instrumental responding to low‐ and high‐calorie food stimuli
Authors: Vogel Verena , Dittrich Marie , Horndasch Stefanie , Kratz Oliver , Moll Gunther H. , Erim Yesim , Paslakis Georgios , Rauh Elisabeth , Steins‐Loeber Sabine 
Published: October 2019

AbstractAnorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder‐compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food‐related conditioned responses and the influence of conditioned low‐calorie and high‐calorie food stimuli on instrumental responding for different foods. A Pavlovian‐to‐instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE‐Q, EDI‐2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low‐ and high‐calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low‐calorie food increased with increasing severity of eating disorder psychopathology suggesting weight‐loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward‐associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.