bluuebunny/crossref_metadata_2025_split huggingface dataset:
The p97 Inhibitor CB-5083 Is a Unique Disrupter of Protein Homeostasis in Models of Multiple Myeloma
Authors: Le Moigne Ronan , Aftab Blake T. , Djakovic Stevan , Dhimolea Eugen , Valle Eduardo , Murnane Megan , King Emily M. , Soriano Ferdie , Menon Mary-Kamala , Wu Zhi Yong , Wong Stephen T. , Lee Grace J. , Yao Bing , Wiita Arun P. , Lam Christine , Rice Julie , Wang Jinhai , Chesi Marta , Bergsagel P. Leif , Kraus Marianne , Driessen Christoph , Kiss Von Soly Szerenke , Yakes F. Michael , Wustrow David , Shawver Laura , Zhou Han-Jie , Martin Thomas G. , Wolf Jeffrey L. , Mitsiades Constantine S. , Anderson Daniel J. , Rolfe Mark 
Published: September 2017

Abstract
Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system, and CB-5083, a first-in-class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematologic and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma cell lines and a number of in vivo multiple myeloma models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response, and apoptosis. CB-5083 decreases viability in multiple myeloma cell lines and patient-derived multiple myeloma cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs, which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. In vivo studies using clinically relevant multiple myeloma models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with multiple myeloma standard-of-care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several multiple myeloma disease models and provide the rationale for clinical evaluation as monotherapy and in combination in multiple myeloma. Mol Cancer Ther; 16(11); 2375–86. ©2017 AACR.
Scaling Analysis of Temperature and Liquid Water Content in the Marine Boundary Layer Clouds during POST
Authors: Ma Yong-Feng , Malinowski Szymon P. , Karpińska Katarzyna , Gerber Hermann E. , Kumala Wojciech 
Published: September 2017

AbstractThe authors have analyzed the scaling behavior of marine boundary layer (MBL) clouds using high-resolution temperature (T) and liquid water content (LWC) fluctuations from aircraft measurements collected over the Pacific Ocean during the Physics of Stratocumulus Top (POST) research campaign in summer of 2008. As an extension of the past studies for scale-invariant properties of MBL clouds, the authors studied the variability of scaling exponents with height. The results showed that both LWC and T have two distinct scaling regimes: the first one displays scale invariance over a range from about 1–5 m to at least 7 km, and the second one goes from about 0.1–1 to 1–5 m. For the large-scale regime (r &gt; 1–5 m), turbulence in MBL clouds is multifractal, while scale break and scaling exponents vary with height, most significantly in the cloud-top region. For example, LWC spectral exponent β increases from 1.42 at cloud base to 1.58 at cloud top, while scale break decreases from ~5 m at cloud base to 0.8 m at cloud top. The bifractal parameters (H1, C1) for LWC increase from (0.14, 0.02) at cloud base to (0.33, 0.1) at cloud top while maintaining a statistically significant linear relationship C1 ≈ 0.4H1 − 0.04 in MBL clouds. From near surface to cloud top, (H1, C1) for T also increase with height, but above cloud top H1 increases and C1 decreases with height. The results suggest the existence of three turbulence regimes: near the surface, in the middle of the boundary layer, and in the cloud-top region, which need to be distinguished.
On the Forcing of the Summertime Great Plains Low-Level Jet
Authors: Parish Thomas R. 
Published: September 2017

AbstractThe low-level jet (LLJ) is a ubiquitous feature of the lower atmosphere over the Great Plains during summer. The LLJ is a nocturnal phenomenon, developing during the 6–9-h period after sunset. Forcing of the LLJ has been debated for over 60 years, the focus being on two processes: decoupling of the residual layer from the surface owing to nighttime cooling and diurnal heating and cooling of the sloping Great Plains topography.To examine characteristics and forcing mechanisms for the LLJ, composite grids were compiled from the North American Mesoscale Forecast System for the summertime months of June and July over a 5-yr period (2008–12). One composite set was assembled from well-developed LLJ episodes during which the maximum nocturnal jet magnitude at 0900 UTC over northwestern Oklahoma exceeded 20 m s−1. A second set consists of nonjet conditions for which the maximum nighttime wind magnitude in the lowest 3 km did not exceed 10 m s−1.The intensity of the horizontal pressure gradient and hence background geostrophic flow at jet level was the dominant difference between composite cases. The horizontal pressure gradient forms in response to the thermal wind above jet level that results primarily from seasonal heating of the sloping Great Plains. Thermal wind forcing is thus the key link between the Great Plains and the high frequency of LLJ occurrence. The nocturnal wind maximum develops primarily because of the inertial oscillation of the ageostrophic wind occurring after decoupling of the lower atmosphere from the surface owing to radiational cooling in the early evening.
Dysphagia screening after intracerebral hemorrhage
Authors: Joundi Raed A , Martino Rosemary , Saposnik Gustavo , Giannakeas Vasily , Fang Jiming , Kapral Moira K 
Published: September 2017

Background Dysphagia screening is recommended after acute stroke to identify patients at risk of aspiration and implement appropriate care. However, little is known about the frequency and outcomes of patients undergoing dysphagia screening after intracerebral hemorrhage (ICH). Methods We used the Ontario Stroke Registry from 1 April 2010 to 31 March 2013 to identify patients hospitalized with acute stroke and to compare dysphagia screening rates in those with ICH and ischemic stroke. In patients with ICH we assessed predictors of receiving dysphagia screening, predictors of failing screening, and outcomes after failing screening. Results Among 1091 eligible patients with ICH, 354 (32.4%) patients did not have documented dysphagia screening. Patients with mild ICH were less likely to receive screening (40.4% of patients were omitted, adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI) 0.26–0.63). Older age, greater stroke severity, speech deficits, lower initial level of consciousness, and admission to intensive care unit were predictive of failing the screening test. Failing screening was associated with poor outcomes, including pneumonia (aOR 5.3, 95% CI 2.36–11.88), severe disability (aOR 4.78, 95% CI 3.08–7.41), and 1-year mortality (adjusted hazard ratio 2.1, 95% CI 1.38–3.17). When compared to patients with ischemic stroke, patients with ICH were less likely to receive dysphagia screening (aOR 0.64, 95% CI 0.54–0.76) and more likely to fail screening (aOR 1.98, 95% 1.62–2.42). Conclusion One-third of patients with ICH did not have documented dysphagia screening, increasing to 40% in patients with mild clinical severity. Failing screening was associated with poor outcomes. Patients with ICH were less like to receive screening and twice as likely to fail compared to patients with ischemic stroke, and thus efforts should be made to include ICH patients in dysphagia screening protocols whenever possible.
Autobiographical memory: A candidate latent vulnerability mechanism for psychiatric disorder following childhood maltreatment
Authors: McCrory Eamon J. , Puetz Vanessa B. , Maguire Eleanor A. , Mechelli Andrea , Palmer Amy , Gerin Mattia I. , Kelly Philip A. , Koutoufa Iakovina , Viding Essi 
Published: September 2017

BackgroundAltered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and posttraumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk.AimsTo investigate the impact of childhood maltreatment on ABM functioning.MethodThirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally valenced cue words during functional magnetic resonance imaging.ResultsChildren with maltreatment experience showed reduced hippocampal and increased middle temporal and parahippocampal activation during positive ABM recall compared with peers. During negative ABM recall they exhibited increased amygdala activation, and greater amygdala connectivity with the salience network.ConclusionsChildhood maltreatment is associated with altered ABM functioning, specifically reduced activation in areas encoding specification of positive memories, and greater activation of the salience network for negative memories. This pattern may confer latent vulnerability to future depression and posttraumatic stress disorder.
Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project
Authors: Mincer Joshua S. , Baxter Mark G. , McCormick Patrick J. , Sano Mary , Schwartz Arthur E. , Brallier Jess W. , Allore Heather G. , Delman Bradley N. , Sewell Margaret C. , Kundu Prantik , Tang Cheuk Ying , Sanchez Angela , Deiner Stacie G. 
Published: September 2017

BACKGROUND:
Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia.

METHODS:
The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40–80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia.

RESULTS:
The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia.

CONCLUSIONS:
The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs.
Mitochondrial dynamics in Parkinson's disease: a role for α-synuclein?
Authors: Pozo Devoto Victorio M. , Falzone Tomas L. 
Published: September 2017

ABSTRACT
The distinctive pathological hallmarks of Parkinson's disease are the progressive death of dopaminergic neurons and the intracellular accumulation of Lewy bodies enriched in α-synuclein protein. Several lines of evidence from the study of sporadic, familial and pharmacologically induced forms of human Parkinson's disease also suggest that mitochondrial dysfunction plays an important role in disease progression. Although many functions have been proposed for α-synuclein, emerging data from human and animal models of Parkinson's disease highlight a role for α-synuclein in the control of neuronal mitochondrial dynamics. Here, we review the α-synuclein structural, biophysical and biochemical properties that influence relevant mitochondrial dynamic processes such as fusion-fission, transport and clearance. Drawing on current evidence, we propose that α-synuclein contributes to the mitochondrial defects that are associated with the pathology of this common and progressive neurodegenerative disease.
NFκB signaling in alveolar rhabdomyosarcoma
Authors: Cleary Megan M. , Mansoor Atiya , Settelmeyer Teagan , Ijiri Yuichi , Ladner Katherine J. , Svalina Matthew N. , Rubin Brian P. , Guttridge Denis C. , Keller Charles 
Published: September 2017

ABSTRACT
Alveolar rhabdomyosarcoma (aRMS) is a pediatric soft tissue cancer commonly associated with a chromosomal translocation that leads to the expression of a Pax3:Foxo1 or Pax7:Foxo1 fusion protein, the developmental underpinnings of which may give clues to its therapeutic approaches. In aRMS, the NFκB–YY1–miR-29 regulatory circuit is dysregulated, resulting in repression of miR-29 and loss of the associated tumor suppressor activity. To further elucidate the role of NFκB in aRMS, we first tested 55 unique sarcoma cell lines and primary cell cultures in a large-scale chemical screen targeting diverse molecular pathways. We found that pharmacological inhibition of NFκB activity resulted in decreased cell proliferation of many of the aRMS tumor cultures. Surprisingly, mice that were orthotopically allografted with aRMS tumor cells exhibited no difference in tumor growth when administered an NFκB inhibitor, compared to control. Furthermore, inhibition of NFκB by genetically ablating its activating kinase inhibitor, IKKβ, by conditional deletion in a mouse model harboring the Pax3:Foxo1 chimeric oncogene failed to abrogate spontaneous tumor growth. Genetically engineered mice with conditionally deleted IKKβ exhibited a paradoxical decrease in tumor latency compared with those with active NFκB. However, using a synthetic-lethal approach, primary cell cultures derived from tumors with inactivated NFκB showed sensitivity to the BCL-2 inhibitor navitoclax. When used in combination with an NFκB inhibitor, navitoclax was synergistic in decreasing the growth of both human and IKKβ wild-type mouse aRMS cells, indicating that inactivation of NFκB alone may not be sufficient for reducing tumor growth, but, when combined with another targeted therapeutic, may be clinically beneficial.
A Demonstration of Physician-Generated Health Care Costs in an Initial Orthopaedic Visit
Authors: Schwartz Andrew , Levin Paul , Lovy Andrew , Koenig Jonathan 
Published: September 2017

Background: The cost of health care in the United States continues to grow faster than any other sector of the economy. A small portion of the health care costs is attributed to physician reimbursement, but orthopaedic surgeons have an abundance of costly diagnostic and therapeutic modalities for patient care. Providers must be aware of the health care costs they generate in their practice in order to become stewards of cost control. Identifying the costs associated with an ambulatory orthopaedic practice is an important foundation in understanding and controlling the costs that the practice generates. Questions: What is the average cost of an initial encounter with an orthopaedic surgeon? What are the most costly elements in a management plan? How can we financially optimize resource utilization? Methods: We conducted a retrospective review of the records of 23 orthopaedic surgeons that span the main orthopaedic subspecialties at an urban academic medical center. All physician-generated orders were obtained and valuated by their cost to the institution’s health care management organization. Results: A total patient of 822 encounters were reviewed with a total cost of $403,235 (an average of $490 per patient). The most prevalent order was an x-ray (68.1% of patients). The majority of the financial burden was from physical therapy prescriptions (43.1% of total costs). The most expensive diagnostic modalities were advanced imaging studies, particularly magnetic resonance imaging and computed tomography (20.8% of costs). Conclusion: This health care burden exposé is not designed to discourage technology utilization. The authors aim to encourage stewardship through judicious use of diagnostic and therapeutic modalities. Most common musculoskeletal conditions presenting for evaluation can be appropriately diagnosed with a thorough history and physical examination followed by initial non-operative management. Diagnostic workups are only necessary during an initial visit when the initial evaluation suggests life or limb threatening conditions that need to be identified in an expeditious fashion. Diagnostic imaging may become necessary during future visits if the patient has not responded to the initial management and the patient is ready to undergo a surgical intervention based on the imaging. Obtaining imaging to identify a surgical lesion is an unnecessary expense if the patient is not ready to undergo surgery. Understanding the cost of clinical decisions can promote adherence to evidence-based diagnostic indications to more efficiently use health care funds.
The lectotypification of two names referred by Linnaeus to the genus Illecebrum (Caryophyllales): Illecebrum benghalense and Iresine javanica , with comments on Aerva tomentosa
Authors: Iamonico Duilio , Friis Ib 
Published: September 2017

AbstractLinnaeus had a broad concept of Illecebrum and, based on the current circumscription wherein the genus is considered monotypic, only one out of the seventeen names Linnaeus treated in combination with Illecebrum – I. verticillatum – remains in the genus. The other sixteen names are now referred to other genera of both Caryophyllaceae (Chaetonychia , Paronychia , Polycarpon ), and Amaranthaceae (Achyranthes ,Aerva ,Althernanthera ,Blutaparon ,Nothosaerva ). Two of the species referred to Illecebrum by Linnaeus have remained to be investigated from a nomenclatural point of view, I. bengalense and I. javanicum. Illecebrum bengalense is here lectotypified with a specimen preserved at LINN and is placed in synonymy withNothosaerva brachiata. Illecebrum javanicum , based onIresine javanica , is lectotypified with a Burman illustration. The name Aerva tomentosa is placed in synonymy ofIresine javanica.
Potential correlation of wound bed score and biomarkers in chronic lower leg wounds: an exploratory study
Authors: Dini V. , Papadia F. , Francesco F. Di , Salvo P. , Paolicchi A. , Janowska A. , Chiricozzi A. , Oranges T. 
Published: September 2017

Objective: The wound bed score is a validated tool to monitor wound healing in chronic wounds, and depends on visual examination by trained personnel. This study describes the feasibility of adding some biochemical and immunohistochemical parameters to increase the objectivity and specificity of the wound bed score Method: Patients with chronic wounds on the lower leg with different durations were enrolled to assess the correlation between the wound bed score and specific wound-related biomarkers, namely MMP-9, MMP-2, NGAL, albumin, integrin α2/β1, and other histochemical (CD68, PK1, CD32, fractalkine, periostin) and immunocytochemical markers from biopsies and smears taken from wound edges and bed. Results: The study examined samples from 10 patients. Patients with an unfavourable wound bed score had a low expression of periostin and fractalkine in the wound bed tissue. CD68 PK1 showed a low or negative expression in the majority of the samples. Patients negative for CD68 PK1 were also negative for CD32. Principal component analysis revealed that the albumin level and the amount of proteins were associated with a high wound bed score. Two different subsets of patients could be discriminated either by integrin α2/β1 and albumin percentages or the MMP-9 and MMP-2 activities Conclusion: These preliminary results pave the way towards an improved wound status diagnosis and an advanced quality of wound care and management. These findings need confirming with a large number of patients and at different time points.
PARTISIPASI KELUARGA ANGGOTA BINA KELUARGA BALITA (BKB) DALAM PENGASUHAN DAN TUMBUH KEMBANG ANAK USIA 0-6 TAHUN
Authors: Oktriyanto NFN 
Published: September 2017

The age of 0-6 years is the most critical period in determining the quality of life in the future. By participating in the activities of Bina Keluarga Balita (BKB), families are expected to be able to provide the best care for the growth and development of the children. The purpose of this analysis is to determine: 1) The differences between families member of BKB and families are not member BKB on their participation in growth and development of children age 0- 6 years. 2) Factors that affect the family's participation in growth and development of children age 0- 6 years. This analysis used secondary data from Performance Indicator Survey of The National Medium Term Development Plan in Population and Family Planning Proram Year 2015. The survey was conducted in 34 provinces throughout Indonesia. Respondents used are families with children age 0-6 years, with the total number of respondents 16 172 families. The results showed that the family’s participation in the growth and development of children age 0-6 years is better in the family members of BKB than families who do not participate in BKB from all aspects (physical, mental and social). The results of logistic regression analysis showed that the level of family welfare, maternal age, maternal education, maternal work status, family who have children aged 0-6 years, and family participation in BKB group has significant effect on family participation in growth and development of children age 0- 6 years
STEED
Authors: Wang Zhiyi , Zhou Dongyan , Chen Shimin 
Published: September 2017

Tree-structured data formats, such as JSON and Protocol Buffers, are capable of expressing sophisticated data types, including nested, repeated, and missing values. While such expressing power contributes to their popularity in real-world applications, it presents a significant challenge for systems supporting tree-structured data. Existing systems have focused on general-purpose solutions either extending RDBMSs or designing native systems. However, the general-purpose approach often results in sophisticated data structures and algorithms, which may not reflect and optimize for the actual structure patterns in the real world.
In this demonstration, we showcase Steed, an analytical database <u>Sy</u>stem for <u>t</u>r<u>ee</u>-structured <u>d</u>ata. We use the insights gained by analyzing representative real-world tree structured data as guidelines in the design of Steed. Steed learns and extracts a schema tree for a data set and uses the schema tree to reduce the storage space and improve the efficiency of data field accesses. We observe that sub-structures in real world data are often simple, while the tree-structured data types can support very sophisticated structures. We optimize the storage structure, the column assembling algorithm, and the in-memory layout for the simple sub-structures (a.k.a. simple paths). Compared to representative state-of-the-art systems (i.e. PostgreSQL/JSON, MongoDB, and Hive+Parquet), Steed achieves orders of magnitude better performance for data analysis queries.