bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent progress on combining geomorphological and geochronological data with ice sheet modelling, demonstrated using the last British–Irish Ice Sheet
Authors: Ely Jeremy C. , Clark Chris D. , Hindmarsh Richard C. A. , Hughes Anna L. C. , Greenwood Sarah L. , Bradley Sarah L. , Gasson Edward , Gregoire Lauren , Gandy Niall , Stokes Chris R. , Small David 
Published: July 2019

ABSTRACTPalaeo‐ice sheets are important analogues for understanding contemporary ice sheets, offering a record of ice sheet behaviour that spans millennia. There are two main approaches to reconstructing palaeo‐ice sheets. Empirical reconstructions use the available glacial geological and chronological evidence to estimate ice sheet extent and dynamics but lack direct consideration of ice physics. In contrast, numerically modelled simulations implement ice physics, but often lack direct quantitative comparison with empirical evidence. Despite being long identified as a fruitful scientific endeavour, few ice sheet reconstructions attempt to reconcile the empirical and model‐based approaches. To achieve this goal, model‐data comparison procedures are required. Here, we compare three numerically modelled simulations of the former British–Irish Ice Sheet with the following lines of evidence: (a) position and shape of former margin positions, recorded by moraines; (b) former ice‐flow direction and flow‐switching, recorded by flowsets of subglacial bedforms; and (c) the timing of ice‐free conditions, recorded by geochronological data. These model–data comparisons provide a useful framework for quantifying the degree of fit between numerical model simulations and empirical constraints. Such tools are vital for reconciling numerical modelling and empirical evidence, the combination of which will lead to more robust palaeo‐ice sheet reconstructions with greater explicative and ultimately predictive power.
Late Pleistocene climate of the northern Iberian Peninsula: New insights from palaeoglaciers at Fuentes Carrionas (Cantabrian Mountains)
Authors: Pellitero Ramón , Fernández‐Fernández José M. , Campos Néstor , Serrano Enrique , Pisabarro Alfonso 
Published: July 2019

ABSTRACTNew 10Be dates for glacial landforms in the Fuentes Carrionas area (Cantabrian Mountains, nothern Spain) are presented. Mapped and dated landforms in Fuentes Carrionas made possible a palaeoglacier reconstruction for four glacial stages. Results were compared to other nearby palaeoenvironmental proxies, so a final approximation on the mean annual temperature and annual precipitation that caused the four glacial advance stages is proposed. Glaciers reached their maximum extension at 36 ka, in a cold and dry environment. A second advance stage took place between 18.5 and 19.5 ka, during the Last Glacial Maximum (LGM), when glaciers advanced in a wet environment, with positive rainfall anomalies. A third glacial advance was dated during the Oldest Dryas, in which climate shifted to extremely cold and dry conditions. Finally, a last stage has been identified and proposed to the Younger Dryas, in which precipitation anomalies are negligible. Our results confirm some of the previously made palaeoglacial and palaeoenvironmental inferences for the Iberian Peninsula, as well as provide valuable and accurate anomalies, which are useful for climate modelling.
Frequent rectal gastrointestinal stromal tumor recurrences in the imatinib era: Retrospective analysis of an International Patient Registry
Authors: Stuart Emelia , Banerjee Sudeep , de la Torre Jorge , Wang Yu , Scherzer Norman , Burgoyne Adam M. , Parry Lisa , Fanta Paul T. , Ramamoorthy Sonia , Sicklick Jason K. 
Published: July 2019

AbstractIntroductionRectal gastrointestinal stromal tumor (GIST) is rare and comprises about 3% of GIST.MethodsRegistry data was collected by the Life Raft Group June 1976 to November 2017. All patients had a histologic GIST diagnosis. Demographic, clinicopathologic, and clinical outcome data were patient reported. Recurrence‐free survival (RFS) was analyzed using the Kaplan‐Meier method and Cox regression analysis.ResultsOf 1798 patients in the database, 48 had localized rectal GIST (2.7%). Patients were frequently male (58.3%) and non‐Hispanic whites (58.3%). Median age at diagnosis was 52 years. Most patients (77%) were diagnosed in the imatinib era (2001 to current). Over half (54.2%) of the cohort had mutation testing and all profiled tumors possessed KIT mutations (exon 9: 7.7%, exon 11: 88.5%, and exon 13: 3.8%). Most evaluable patients (26/28; 92.9%) had high‐risk disease (modified NIH criteria) and nearly all patients (95.8%) received imatinib. Median follow‐up was 8.8 years (range, 0.3‐30.7) and overall RFS was 8.0 years (95% CI, 2.9‐13.1). Thirty‐two percent (12/37) of patients in the post‐imatinib era developed recurrent disease. Diagnosis in the imatinib era was associated with improved RFS (HR = 0.22, 95% CI, 0.08‐0.62; P = .004) in the multivariable model.ConclusionWe find that disease recurrence remains prevalent in one‐third of patients treated during the imatinib‐era.
Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
Authors: Varden Lara J. , Nguyen Duc T. , Michalek Arthur J. 
Published: July 2019

AbstractNeedle injection has been indicated as the most practical method of delivering therapeutic agents to the intervertebral disc due to the disc's largely avascular nature. As the disc is characterized by both high stiffness and low permeability, injection requires substantial pressure, which may not relax on practical time scales. Additionally, needle puncture results in a localized disruption to the annulus fibrosus that can provide a leakage pathway for pressurized injectate. We hypothesized that intradiscal injection would result in slow relaxation of injectate pressure, followed by leakage upon needle retraction. This hypothesis was tested via controlled injection of fluorescently labeled saline into bovine caudal discs via a 21 gauge needle. Injections were performed with 10% of total disc volume injected at 3%/s followed by a 4‐minute dwell. An analytical poroelastic model was calibrated to the experimental data and used to estimate injectate delivery with time. Experimental results confirmed both pressurization (with a peak of 199 ± 45 kPa) and slow recovery (final pressure of 81 ± 23 kPa). Injectate leakage through the needle puncture was verified following needle retraction in all samples. Histological sections of the discs displayed a clear defect at each disc's injection site with strong fluorescent labeling indicating a leakage pathway. The modeling results suggest that less than one‐fourth of the injected volume was absorbed by the tissue in 4 minutes. Taken together these results suggest that needle injection is a feasible, albeit inefficient method for delivery of therapeutic agents into the intervertebral disc. Particular care should be taken to aspirate un‐absorbed injectate prior to needle retraction to prevent leakage and exposure of surrounding tissues.
Maximizing dissemination and engaging readers: The other 50% of an author's day: A case study
Authors: Green Toby 
Published: July 2019

Key points
Dissemination should be the other 50% of what authors do: being read and having impact will not happen by itself.
Authors can influence discovery and readership through owned media – i.e. their own communication activities.
Earned media – i.e. when influencers write about your work – is key to reaching larger and more diverse audiences.
There is plenty of data for tracking engagement and use of articles, but it is scattered across multiple tools and providers and can be misleading or even incorrect.
Listservs can have higher engagement than modern, ‘cool’, social networking tools.
Older Donor Age Is a Risk Factor for Negative Outcomes After Adult Living Donor Liver Transplantation Using Small‐for‐Size Grafts
Authors: Macshut Mahmoud , Kaido Toshimi , Yao Siyuan , Yagi Shintaro , Ito Takashi , Kamo Naoko , Nagai Kazuyuki , Sharshar Mohamed , Uemoto Shinji 
Published: July 2019

Adult‐to‐adult living donor liver transplantation (ALDLT) using small‐for‐size grafts (SFSGs), ie, a graft with a graft‐to‐recipient weight ratio (GRWR) <0.8%, has been a challenge that should be carefully dealt with, and risk factors in this category are unclear. Therefore, we aimed to examine the risk factors and outcomes of ALDLT using SFSGs over a 13‐year period in 121 patients who had undergone their first ALDLT using SFSGs. Small‐for‐size syndrome (SFSS), early graft loss, and 1‐year mortality were encountered in 21.6%, 14.9%, and 18.4% of patients, respectively. By multivariate analysis, older donor age (≥45 years) was an independent risk factor for SFSS (odds ratio [OR], 4.46; P = 0.004), early graft loss (OR, 4.11; P = 0.02), and 1‐year mortality (OR, 3.76; P = 0.02). Child‐Pugh C class recipients were associated with a higher risk of SFSS development (P = 0.013; OR, 7.44). Despite no significant difference between GRWR categories in the multivariate outcome analysis of the whole population, in the survival analysis of the 2 donor age groups, GRWR <0.6% was associated with significantly lower 1‐year survival than the other GRWR categories in the younger donor group. Moreover, in the high final portal venous pressure (PVP) group (>15 mm Hg), younger ABO‐compatible donors showed 100% 1‐year survival with a significant difference from the group of other donors. Older donor age was an independent risk factor for SFSS, early graft loss, and 1‐year mortality after ALDLT using SFSGs. GRWR should not be <0.6%, and PVP modulation is indicated when grafts from older or ABO‐incompatible donors are used.
A Comprehensive Outlook of Synthetic Strategies and Applications of Redox‐Responsive Nanogels in Drug Delivery
Authors: Kumar Parveen , Liu Bo , Behl Gautam 
Published: July 2019

AbstractIncreasing recognition of the role of oxidative stress in the pathogenesis of many clinical conditions and the existence of defined redox potential in healthy tissues has led to extensive research in the development of redox‐responsive materials for biomedical applications. Especially, considerable growth has been seen in the fabrication of polymeric nanogel–based drug delivery carriers utilizing redox‐responsive cross‐linkers bearing a variety of functional groups via various synthetic strategies. Redox‐responsive polymeric nanogels provide an advantage of facile chemical modification post synthesis and exhibit a remarkable response to biological redox stimuli. Due to the interdisciplinary nature of the subject, a more profound combined conceptual knowledge from a chemical and biological point of view is imperative for the rational design of redox‐responsive nanogels. The present review provides an insight into the design and fabrication of redox‐responsive nanogels with particular emphasis on synthetic strategies utilized for the development of redox‐responsive cross‐linkers, polymerization techniques being followed for nanogel development and biomedical applications. Cooperative effect of redox trigger with other stimuli such as pH and temperature in the evolution of dual and triple stimuli‐responsive nanogels is also discussed.
Comprehensive mismatch repair gene panel identifies variants in patients with Lynch‐like syndrome
Authors: Xavier Alexandre , Olsen Maren Fridtjofsen , Lavik Liss A. , Johansen Jostein , Singh Ashish Kumar , Sjursen Wenche , Scott Rodney J. , Talseth‐Palmer Bente A. 
Published: July 2019

AbstractBackgroundLynch‐like syndrome (LLS) represents around 50% of the patients fulfilling the Amsterdam Criteria II/revised Bethesda Guidelines, characterized by a strong family history of Lynch Syndrome (LS) associated cancer, where a causative variant was not identified during genetic testing for LS.MethodsUsing data extracted from a larger gene panel, we have analyzed next‐generation sequencing data from 22 mismatch repair (MMR) genes (MSH3, PMS1, MLH3, EXO1, POLD1, POLD3 RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, LIG1, RPA1, RPA2, RPA3, POLD2, POLD4, MLH1, MSH2, MSH6, and PMS2) in 274 LLS patients. Detected variants were annotated and filtered using ANNOVAR and FILTUS software.ResultsThirteen variants were revealed in MLH1, MSH2, and MSH6, all genes previously linked to LS. Five additional genes (EXO1, POLD1, RFC1, RPA1, and MLH3) were found to harbor 11 variants of unknown significance in our sample cohort, two of them being frameshift variants.ConclusionWe have shown that other genes associated with the process of DNA MMR have a high probability of being associated with LLS families. These findings indicate that the spectrum of genes that should be tested when considering an entity like Lynch‐like syndrome should be expanded so that a more inclusive definition of this entity can be developed.
Choline Supplementation Ameliorates Behavioral Deficits and Alzheimer's Disease‐Like Pathology in Transgenic APP/PS1 Mice
Authors: Wang Yanyan , Guan Xingying , Chen Xuedan , Cai Yulong , Ma Yuanyuan , Ma Jiming , Zhang Qiming , Dai Limeng , Fan Xiaotang , Bai Yun 
Published: July 2019

ScopeAlzheimer's disease (AD) is a detrimental neurodegenerative disease and has no known effective treatment. The essential nutrient choline potentially plays an important role in cognition. Perinatal choline supplementation (CS) is critical for memory performance. Findings have shown that postnatal choline‐containing compounds enhance memory functions in populations with memory impairments. However, whether CS can be targeted to decelerate the progression of AD remains unknown.Methods and resultsAPP/PS1 mice and their wild‐type littermates are fed either a control or CS diet from 2 to 11 months of age. As compared to WT mice, APP/PS1 mice on the control diet are characterized by the reduction in the number of cholinergic neurons in the basal forebrain, reduced cholinergic fiber staining intensity in the amygdala, and reduced hippocampal and cerebral cortical levels of choline and acetylcholine. CS partially prevents these changes and ameliorates cognitive deficits and anxiety. Furthermore, amyloid‐β deposition and microgliosis are decreased in the APP/PS1 mice fed a CS diet. These effects may have been due to inhibition of NLRP3 inflammasome activation and restoration of synapse membrane formation.ConclusionThese findings reveal a beneficial effect of CS on AD progression during adulthood and provide a likely therapeutic intervention for AD patients.
Effect of Synbiotic Supplementation in a Very‐Low‐Calorie Ketogenic Diet on Weight Loss Achievement and Gut Microbiota: A Randomized Controlled Pilot Study
Authors: Gutiérrez‐Repiso Carolina , Hernández‐García Carmen , García‐Almeida José Manuel , Bellido Diego , Martín‐Núñez Gracia María , Sánchez‐Alcoholado Lidia , Alcaide‐Torres Juan , Sajoux Ignacio , Tinahones Francisco J. , Moreno‐Indias Isabel 
Published: July 2019

ScopeLittle is known about the changes that a very‐low‐calorie ketogenic diet (VLCKD) produces in gut microbiota or the effect of synbiotics during the diet. The aim of this study is to evaluate changes in gut microbiota produced by a VLCKD and synbiotic supplementation.Methods and resultsA randomized, single‐blind, parallel‐design trial is conducted in 33 obese patients who follow a weight‐loss program (PnK‐Method) that include a VLCKD followed by a low‐calorie diet (LCD). Subjects are randomly allocated to three groups: one supplemented with synbiotics, a second group supplemented with a placebo during the VLCKD and synbiotics during the LCD phase, and a control group given a placebo.Although symbiotic administration do not produce an effect on microbial diversity, an increase in short‐chain fatty aciding producing bacteria and anti‐inflammatory mediator signals such as Odoribacter and Lachnospira is shown. The administration of Bifidobacterium animalis subsp. lactis and prebiotics fiber during the LCD is significantly associated with the percentage of weight loss and change in glucose, C‐reactive protein and lipopolysaccharide‐binding protein.ConclusionsVLCKD produces important changes in gut microbiota. The administration of synbiotics during VLCKD can improve weight loss through the amelioration of inflammation, which may be mediated by the gut microbiota.
Epidemiology, progression, and predictive factors of urinary incontinence in older community‐dwelling Mexican adults: Longitudinal data from the Mexican Health and Aging Study
Authors: Giraldo‐Rodríguez Liliana , Agudelo‐Botero Marcela , Mino‐León Dolores , Álvarez‐Cisneros Teresa 
Published: July 2019

AbstractAimsTo understand the epidemiology, progression, and predictive factors of urinary incontinence (UI) in community‐dwelling Mexican adults aged ≥ 50 by sex and UI subtypes (stress, urge, and mixed).MethodsWe analyzed longitudinal UI data in community‐dwelling adults aged ≥ 50 (7783 women and 5843 men) for the 2012 to 2015 period of the Mexican Health and Aging Study. We estimated mixed, stress, and urgency incontinence prevalence (2012); 2‐year cumulative incidence and remissions (2015); and progression (2012‐2015). A multivariate analysis was undertaken to evaluate the predictive factors for UI and its subtypes by sex.ResultsThe prevalence of UI was higher (27.7%) for women (average age 65.9 ± 9.5) than 12.5% men (average age 67.4 ± 9.3) and increased with age in both sexes (26.7% in women 50 to 59, to 48.5% in ≥ 90; and 6.8% in men 50 to 59, to 26.2% ≥ 90). The most frequent UI subtypes were mixed in women and urge in men. The cumulative incidence of UI was higher in women (22.9%) than men (12.3%) while its remission was higher in men than women. Predictive factors for UI in both sexes were depressive symptoms, a higher number of concomitant diseases and a history of falls; while advanced age was a factor only for men.ConclusionsUI is a common health problem and its prevalence and severity increase with age. Addressing modifiable risk factors such as depression and falls could decrease the prevalence and incidence of UI and its subtypes. Further studies should also focus on the relationship between mixed UI and male mortality.
The solvatochromic response of benzo[a]fluorenone in aprotic solvents compared with benzo[b]fluorenone and 9‐fluorenone
Authors: Kopkalli Yasemin , Celius Tevye C. , Dickson‐Karn Nicole M. , Davenport Lesley , Williams Brian Wesley 
Published: July 2019

AbstractThe solvatochromism and possible excited state deactivation pathways of benzo[a]fluorenone were investigated and compared with the related aromatic compounds 9‐fluorenone and benzo[b]fluorenone. These molecules can serve as molecular building blocks with application in light emitting diodes, catalysts, and dye‐sensitized solar cells. A study of the effect changes in aromatic structure might have on their relative photophysical responses is therefore of interest. Steady‐state absorption and emission spectra, Lippert‐Mataga plots, fluorescence lifetimes, and absolute quantum yields were used in tandem with time dependent density functional theory (TD‐DFT) calculations to investigate solvatochromism, excited state decay, and the relative energies of singlet and triplet excited states. It was found that changes in aromaticity affect the energetic order and character of the excited singlet and triplet states differently among these fluorenones as solvent polarity is varied. The observed fluorescence emission from all these molecules can be understood in terms of their relative ability to undergo intersystem crossing. Additional calculations on the related benzo[c]fluorenone predict that its solvatochromic behavior should resemble that of benzo[a]fluorenone.
Dynamic Aha1 co‐chaperone binding to human Hsp90
Authors: Oroz Javier , Blair Laura J. , Zweckstetter Markus 
Published: July 2019

AbstractHsp90 is an essential chaperone that requires large allosteric changes to determine its ATPase activity and client binding. The co‐chaperone Aha1, which is the major ATPase stimulator in eukaryotes, is important for regulation of Hsp90's allosteric timing. Little is known, however, about the structure of the Hsp90/Aha1 complex. Here, we characterize the solution structure of unmodified human Hsp90/Aha1 complex using NMR spectroscopy. We show that the 214‐kDa complex forms by a two‐step binding mechanism and adopts multiple conformations in the absence of nucleotide. Aha1 induces structural changes near Hsp90's nucleotide‐binding site, providing a basis for its ATPase‐enhancing activity. Our data reveal important aspects of this pivotal chaperone/co‐chaperone interaction and emphasize the relevance of characterizing dynamic chaperone structures in solution.
Leveraging technology to minimize operational error and hazards—Rise of the Operator 2.0
Authors: Thompson Michael , Falco Jenna 
Published: July 2019

AbstractWe are living in a time where operations and reliability are being impacted by the limits of our own humanity. Decades of research in the field of human factors engineering has shown that, often, we as humans are in fact the weakest link in the successful operation of a plant or facility. Complex systems coupled with the human element give rise to a new class of problem, the socio‐technical problem. Fortunately, we now have proven technology to mitigate some of our inherent shortcomings. The use of this technology can radically alter the way we operate and will give rise to what I call the Operator 2.0. Imagine automated work procedures that appear in the operators work environment that guide them through an activity, instant access to remote expertise that guide them through troubleshooting from anywhere in the world, and a technology that can reduce training time for operators and technicians from years, down to months. Imagine sending a drone to perform an inspection in the process, as opposed to sending an operator into harm's way. Think of the implications of not having people in the actual process. This opportunity exists today.
Beta-Cell Dedifferentiation in Type 2 Diabetes: Concise Review
Authors: Efrat Shimon 
Published: July 2019

Abstract
Type 2 diabetes (T2D) is caused by an inherited predisposition to pancreatic islet β-cell failure, which is manifested under cellular stress induced by metabolic overload. The decrease in the functional β-cell mass associated with T2D has been attributed primarily to β-cell death; however, studies in recent years suggested that β-cell dedifferentiation may contribute to this decline. The mechanisms linking genetic factors and cellular stress to β-cell dedifferentiation remain largely unknown. This study evaluated the evidence for β-cell dedifferentiation in T2D, and T2D and examined experimental systems in which its mechanisms may be studied. Understanding these mechanisms may allow prevention of β-cell dedifferentiation or induction of cell redifferentiation for restoration of the functional β-cell mass. Stem Cells 2019;37:1267–1272
Effective gauge theories of superfluidity with topological order
Authors: Hirono Yuji , Tanizaki Yuya 
Published: July 2019

AbstractWe discuss the low-energy dynamics of superfluidity with topological order in (3 + 1) spacetime dimensions. We generalize a topologicalBFtheory by introducing a non-squareKmatrix, and this generalizedBFtheory can describe massless Nambu-Goldstone bosons and anyonic statistics between vortices and quasiparticles. We discuss the general structure of discrete and continuous higher-form symmetries in this theory, which can be used to classify quantum phases. We describe how to identify the appearance of topological order in such systems and discuss its relation to a mixed ’t Hooft anomaly between discrete higher-form symmetries. We apply this framework to the color-flavor locked phase of dense QCD, which shows anyonic particle-vortex statistics while no topological order appears. An explicit example of superfluidity with topological order is discussed.