bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blame it on the injury: Trauma is a risk factor for pancreatic fistula following distal pancreatectomy compared with elective resection
Authors: Rozich Noah S. , Morris Katherine T. , Garwe Tabitha , Sarwar Zoona , Landmann Alessandra , Siems Chesney B. , Jones Alexandra , Butler Casey S. , McGaha Paul K. , Axtman Benjamin C. , Edil Barish H. , Lees Jason S. 
Published: August 2019

BACKGROUND
Postoperative pancreatic fistula (POPF) remains a significant source of morbidity following distal pancreatectomy (DP). There is a lack of information regarding the impact of trauma on POPF rates when compared with elective resection. We hypothesize that trauma will be a significant risk factor for the development of POPF following DP.

METHODS
A retrospective, single-institution review of all patients undergoing DP from 1999 to 2017 was performed. Outcomes were compared between patients undergoing DP for traumatic injury to those undergoing elective resection. Univariate and multivariable analyses were performed using SAS (version 9.4).

RESULTS
Of the 372 patients who underwent DP during the study period, 298 met inclusion criteria: 38 DPs for trauma (TDP), 260 elective DPs (EDP). Clinically significant grade B or C POPFs occurred in 17 (44.7%) of 38 TDPs compared with 41 (15.8%) of 260 EDPs (p < 0.0001). On multivariable analysis, traumatic injury was found to be independently predictive of developing a grade B or C POPF (odds ratio, 4.3; 95% confidence interval, 2.10–8.89). Age, sex, and wound infection were highly correlated with traumatic etiology and therefore were not retained in the multivariable model. When analyzing risk factors for each group (trauma vs. elective) separately, we found that TDP patients who developed POPFs had less sutured closure of their duct, higher infectious complications, and longer hospital stays, while EDP patients that suffered POPFs were more likely to be male, younger in age, and at a greater risk for infectious complications. Lastly, in a subgroup analysis involving only patients with drains left postoperatively, trauma was an independent predictor of any grade of fistula (A, B, or C) compared with elective DP (odds ratio, 8.6; 95% confidence interval, 3.09–24.15), suggesting that traumatic injury is risk factor for pancreatic stump closure disruption following DP.

CONCLUSION
To our knowledge, this study represents the largest cohort of patients comparing pancreatic leak rates in traumatic versus elective DP, and demonstrates that traumatic injury is an independent risk factor for developing an ISGPF grade B or C pancreatic fistula following DP.

LEVEL OF EVIDENCE
Prognostic study, Therapeutic, level III.
Diagnosis of Rapidly Progressive Dementia in a Referral Center in Argentina
Authors: Acosta Julián N. , Ricciardi Mario E. , Alessandro Lucas , Carnevale Martin , Farez Mauricio F. , Nagel Vanesa , Allegri Ricardo F. , Varela Francisco 
Published: August 2019

Introduction:
Rapidly progressive dementia (RPD) is a broadly defined clinical syndrome. Our aim was to describe clinical and ancillary study findings in patients with RPD and evaluate their diagnostic performance for the identification of nonchronic neurodegenerative rapidly progressive dementia (ncnRPD).

Methods:
We reviewed clinical records and ancillary methods of patients evaluated for RPD at our institution in Buenos Aires, Argentina from 2011 to 2017. We compared findings between chronic neurodegenerative RPD and ncnRPD and evaluated the diagnostic metrics using receiver operating characteristic curves.

Results:
We included 104 patients with RPD, 29 of whom were chronic neurodegenerative RPD and 75 of whom were ncnRPD. The 6-month time to dementia cutpoint had a sensitivity of 89% and specificity of 100% for ncnRPD, with an area under the receiver operating characteristic curve of 0.965 (95% confidence interval=0.935-0.99; P<0.001). A decision tree that included time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis identified ncnRPD patients with a sensitivity of 100%, specificity of 79%, positive predictive value of 93%, and negative predictive value of 100% overall.

Discussion:
RPD is a clinical syndrome that comprises different diagnoses, many of them for treatable diseases. Using the time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis when triaging these patients could help identify those diseases that need to be studied more aggressively.
Lipid-derived electrophiles induce covalent modification and aggregation of Cu,Zn-superoxide dismutase in a hydrophobicity-dependent manner
Authors: Dantas Lucas S. , Viviani Lucas G. , Inague Alex , Piccirillo Erika , de Rezende Leandro , Ronsein Graziella E. , Augusto Ohara , de Medeiros Marisa H. G. , Amaral Antonia T.-do , Miyamoto Sayuri 
Published: August 2019

ABSTRACTLipid peroxidation generates a huge number of reactive electrophilic aldehyde products. These reactive aldehydes can modify macromolecules such as proteins, resulting in loss of function and/or aggregation. The accumulation of Cu,Zn-superoxide dismutase (SOD1) aggregates is associated with familial cases of amyotrophic lateral sclerosis (ALS). Recent studies have shown that lipid and its oxidized derivatives may play a role in this process. Here we aimed to compare and characterize the ability of lipid-derived electrophiles with different hydrophobicities to induce SOD1 modification and aggregationin vitro. SOD1 was incubated with 4-hydroxy-2-hexenal (HHE), 4-hydroxy- 2-nonenal (HNE), 2-hexen-1-al (HEX), 2,4-nonadienal (NON), 2,4-decadienal (DEC) or secosterol aldehydes (Seco-A or Seco-B) at 37°C for 24 h. Size exclusion chromatography analysis showed that hydrophobic aldehydes smarkedly enhances apo- SOD1 aggregation. More importantly, aggregation level was positively correlated to calculated aldehyde hydrophobicities (LogP). Protein sequencing by LC-MS/MS showed that aldehydes covalently modifies SOD1 at aggregation prone regions. For instance, specific lysine residues located mainly nearby the dimer interface (K3, K9) and at the electrostatic loop (K122, K128, K136) were ubiquitously modified by all aldehydes. The α,β-unsaturated aldehydes also promoted modifications on histidine and cysteine residues, with H120 and C6 being the most commonly modified residues. Overall, our data suggest that electrophile’s hydrophobicity is a critical factor that strongly influences protein aggregation propensity.Graphical abstractHighlights- Aldehyde hydrophobicity is positively correlated to SOD1 aggregation;- Lys residues located nearby the SOD1 dimer interface and electrostatic loop are ubiquitously modified by all aldehydes;- Hydrophobic aldehydes increase the lipophilic potential surface of the region where they bind;
Enhanced cytokine responsiveness in natural killer cells from a pilot cohort of uninfected seronegative women exposed to hepatitis C virus contaminated anti-D immunoglobulin
Authors: Robinson M. W. , Keane C. , Needham M. , Roche G. , Wallace E. , Connell J. , de Gascun C. F. , Naik A. , Fanning L. J. , Gardiner C. , Houlihan D. D. , O’Farrelly C. 
Published: August 2019

AbstractBackgroundSome people exposed to hepatitis C virus (HCV) appear to be capable of preventing infection in the absence of detectable antibody responses. These ‘exposed seronegative (ESN)’ people appear naturally resistant to HCV infection. Here, we aimed to examine innate immune mechanisms in ESN individuals amongst rhesus negative Irish women exposed to HCV via contaminated anti-D immunoglobulin between 1977-79 and 1991-94.MethodsA total of 16 ESN individuals were recruited, along with 9 age- and gender-matched healthy controls. All tested negative for HCV-specific antibodies using conventional diagnostic assays. Peripheral blood cells were analysed for presence of adaptive immune response markers, innate immune responsiveness and natural killer cell phenotype and function.ResultsThe innate immune cell profile of ESN women in the present study was characterised by a significant decrease in monocyte frequency and elevated levels of interleukin-8 and -18 compared to age- and gender-matched healthy controls. NK cells from ESN women had normal expression of NK cell receptors but increased IFNγ-production upon cytokine and target cell stimulation as well as enhanced natural killer (NK) cell STAT3 phosphorylation in response to Type I IFN.ConclusionsWe describe for the first time ESN individuals amongst Irish women with past exposure to HCV via contaminated anti-D immunoglobulin. NK cells from these ESN individuals are more responsive to cytokine signalling compared with age- and gender-matched controls. Human ESN cohorts can provide unique insights into the biological mechanisms associated with antigen-independent natural resistance to viral infection.
The oldest freshwater crabs: claws on dinosaur bones
Authors: Robin Ninon , Bakel Barry W.M. van , Hyžný Matúš , Cincotta Aude , Garcia Géraldine , Charbonnier Sylvain , Godefroit Pascal , Valentin Xavier 
Published: August 2019

AbstractWith approximately 1,500 extant species, freshwater crabs (Decapoda: Brachyura) are among the most diverse decapod crustaceans. Nevertheless, their fossil record is extremely limited: only Potamidae, Potamonautidae and Trichodactylidae are reported up to the Eocene of the Neotropics so far. This work documents unusually large decapod claws from the Upper Cretaceous (Campanian) continental deposits of Velaux and vicinity (southern France), in close association with large vertebrate remains. In addition to (1) the systematic assignment of these claws, the study addresses (2) the salinity trends in the deposit environment from its faunal assemblage and the elementary chemical patterns of fossils, and (3) the likely scenario for their auto/allochtony in the Velaux fluvial system. These claws belong to a new taxon,Dinocarcinus velauciensisn. gen. n. sp., referred to as Portunoidea sensu lato, a group of “true” crabs nowadays linked to marine systems. However, the faunal assemblage, the claw taphonomy and the carbonates Y/Ho signatures support their ancient freshwater/terrestrial ecology, making them the oldest reported continental brachyurans and extending the presence of crabs in freshwater environments by 40 Ma. Either as primary or as secondary freshwater crabs, the occurrence of these portunoids in Velaux is an evidence for the independent colonizations of continental environments by multiple brachyuran clades over time, as early as the Campanian.
Integrating When and What Information in the Left Parietal Lobe Allows Language Rule Generalization
Authors: Orpella J , Ripollés P , Ruzzoli M , Amengual JL , Callejas A , Martinez-Alvarez A , Soto-Faraco S , de Diego-Balaguer R 
Published: August 2019

AbstractA crucial aspect when learning a language is discovering the rules that govern how words are combined in order to convey meanings. Since rules are characterized by sequential co-occurrences between elements (e.g. ‘These cupcakes are unbelievable’), tracking the statistical relationships between these elements is fundamental. However, statistical learning alone cannot fully account for the ability to create abstract rule representations that can be generalized, a paramount requirement of linguistic rules. Here, we provide evidence that, after the statistical relations between words have been extracted, the engagement of goal-directed attention is key to enable rule generalization. Incidental learning performance during a rule-learning task on an artificial language revealed a progressive shift from statistical learning to goal-directed attention. In addition, and consistent with the recruitment of attention, fMRI analyses of late learning stages showed left parietal activity within a broad bilateral dorsal fronto-parietal network. Critically, rTMS on participants’ peak of activation within the left parietal cortex impaired their ability to generalize learned rules to a structurally analogous new language. No stimulation or rTMS on a non-relevant brain region did not have the same interfering effect on generalization. Performance on an additional attentional task showed that rTMS on the same parietal site hindered participants’ ability to integrate what (stimulus identity) and when (stimulus timing) information about an expected target. The present findings suggest that learning rules from speech is a two-stage process: following statistical learning, goal-directed attention –involving left parietal regions– integrates what and when stimulus information to facilitate rapid rule generalization.
Antisense inhibition of accA in E. coli suppressed luxS expression and increased antibiotic susceptibility
Authors: Hillman Tatiana 
Published: August 2019

ABSTRACTBacterial multiple drug resistance is a significant issue for the medical community. Gram-negative bacteria exhibit higher rates of multi-drug resistance, partly due to the impermeability of the Gram-negative bacterial cell wall and double-membrane cell envelope, which limits the internal accumulation of antibiotic agents. The outer lipopolysaccharide membrane regulates the transport of hydrophobic molecules, while the inner phospholipid membrane controls influx of hydrophilic particles. In Escherichia coli, the gene accA produces the acetyl-CoA carboxylase transferase enzyme required for catalyzing synthesis of fatty acids and phospholipids that compose the inner membrane. To increase antibiotic susceptibility and decrease growth, this study interrupted fatty acid synthesis and disrupted the composition of the inner membrane through inhibiting the gene accA with antisense RNA. This inhibition suppressed expression of luxS, a vital virulence factor that regulates cell growth, transfers intercellular quorum-sensing signals mediated by autoinducer-2, and is necessary for biofilm formation. Bacterial cells in which accA was inhibited also displayed a greater magnitude of antibiotic susceptibility. These findings confirm accA as a potent target for developing novel antibiotics such as antimicrobial gene therapies.
BISON: Brain tISue segmentatiON pipeline using T1-weighted magnetic resonance images and a random forests classifier
Authors: Dadar Mahsa , Collins D. Louis 
Published: August 2019

AbstractIntroductionAccurate differentiation of brain tissue types from T1-weighted magnetic resonance images (MRIs) is a critical requirement in many neuroscience and clinical applications. Accurate automated tissue segmentation is challenging due to the variabilities in the tissue intensity profiles caused by differences in scanner models and acquisition protocols, in addition to the varying age of the subjects and potential presence of pathology. In this paper, we present BISON (Brain tISue segmentatiON), a new pipeline for tissue segmentation.MethodsBISON performs tissue segmentation using a random forests classifier and a set of intensity and location priors obtained based on T1-weighted images. The proposed method has been developed and cross-validated based on multi-center and multi-scanner manual labels of 72 subjects aging from 5-96 years old, ensuring the generalizability of the results to new data from various age ranges. In addition, we assessed the test-retest reliability of BISON on 2 datasets; a. using 20 subjects that had scan/re-scan MRIs and manual segmentations available, and b. using a human phantom dataset including 90 scans from a single individual acquired across 10 years.ResultsThe results of the proposed method were compared against Atropos, a commonly used tissue classification method from ANTs. The proposed method yielded cross-validation Dice Kappa values of κGM= 0.88 ± 0.03, κWM= 0.85 ± 0.03, κCSF= 0.77 ± 0.11, outperforming ANTs Atropos (κGM= 0.79 ± 0.05, κWM= 0.84 ± 0.05, κCSF= 0.64 ± 0.22) as well as test-retest Dice Kappa values of κGM= 0.94 ± 0.006, κWM= 0.92 ± 0.006, κCSF= 0.77 ± 0.11 outperforming both manual (κGM= 0.92 ± 0.01, κWM= 0.91 ± 0.01, κCSF= 0.74 ± 0.03) and ANTs Atropos (κGM= 0.87 ± 0.001, κWM= 0.92 ± 0.001, κCSF= 0.79 ± 0.05). The human phantom dataset validations showed high generalizability for both Atropos (κGM= 0.97 ± 0.01, κWM= 0.96 ± 0.01, κCSF= 0.93 ± 0.02) and BISON (κGM= 0.95 ± 0.01, κWM= 0.94 ± 0.01, κCSF= 0.85 ± 0.03), while Atropos tended to consistently under-segment the cortical CSF. Finally, our assessment of BISON, Atropos, FAST from FSL, and SPM12 segmentations in presence of white matter hyperintensities (WMHs) showed that BISON outperforms the other three methods, correctly detecting WMHs as WM.ConclusionOur results show that BISON can provide accurate and robust segmentations in data from different age ranges and various scanner models, making it ideal for performing tissue classification in large multi-center and multi-scanner databases.
Chromosome-level hybrid de novo genome assemblies as an attainable option for non-model organisms
Authors: Jaworski Coline C. , Allan Carson W. , Matzkin Luciano M. 
Published: August 2019

AbstractThe emergence of third generation sequencing (3GS; long-reads) is making closer the goal of chromosome-size fragments in de novo genome assemblies. This allows the exploration of new and broader questions on genome evolution for a number of non-model organisms. However, long-read technologies result in higher sequencing error rates and therefore impose an elevated cost of sufficient coverage to achieve high enough quality. In this context, hybrid assemblies, combining short-reads and long-reads provide an alternative efficient and cost-effective approach to generate de novo, chromosome-level genome assemblies. The array of available software programs for hybrid genome assembly, sequence correction and manipulation is constantly being expanded and improved. This makes it difficult for non-experts to find efficient, fast and tractable computational solutions for genome assembly, especially in the case of non-model organisms lacking a reference genome or one from a closely related species. In this study, we review and test the most recent pipelines for hybrid assemblies, comparing the model organism Drosophila melanogaster to a non-model cactophilic Drosophila, D. mojavensis. We show that it is possible to achieve excellent contiguity on this non-model organism using the DBG2OLC pipeline.
Harnessing natural modularity of cellular metabolism to design a modular chassis cell for a diverse class of products by using goal attainment optimization
Authors: Garcia Sergio , Trinh Cong T. 
Published: August 2019

AbstractLiving cells optimize their fitness against constantly changing environments to survive. Goal attainment optimization is a mathematical framework to describe the simultaneous optimization of multiple conflicting objectives that must all reach a performance above a threshold or goal. In this study, we applied goal attainment optimization to harness natural modularity of cellular metabolism to design a modular chassis cell for optimal production of a diverse class of products, where each goal corresponds to the minimum biosynthesis requirements (e.g., yields and rates) of a target product. This modular cell design approach enables rapid generation of optimal production strains that can be assembled from a modular cell and various exchangeable production modules and hence accelerates the prohibitively slow and costly strain design process. We formulated the modular cell design problem as a blended or goal attainment mixed integer linear program, using mass-balance metabolic models as biological constraints. By applying the modular cell design framework for a genome-scale metabolic model of Escherichia coli, we demonstrated that a library of biochemically diverse products could be effectively synthesized at high yields and rates from a modular (chassis) cell with only a few genetic manipulations. Flux analysis revealed this broad modularity phenotype is supported by the natural modularity and flexible flux capacity of core metabolic pathways. Overall, we envision the developed modular cell design framework provides a powerful tool for synthetic biology and metabolic engineering applications such as industrial biocatalysis to effectively produce fuels, chemicals, and therapeutics from renewable and sustainable feedstocks, bioremediation, and biosensing.
The NanoZoomer Connectomics Pipeline for Tracer Injection Studies of the Marmoset Brain
Authors: Woodward Alexander , Gong Rui , Abe Hiroshi , Nakae Ken , Hata Junichi , Skibbe Henrik , Yamaguchi Yoko , Ishii Shin , Okano Hideyuki , Yamamori Tetsuo , Ichinohe Noritaka 
Published: August 2019

AbstractWe describe our connectomics pipeline for processing tracer injection data for the brain of the common marmoset (Callithrix jacchus). Brain sections were imaged using a batch slide scanner (NanoZoomer 2.0-HT) and we used artificial intelligence to precisely segment the anterograde tracer signal from the background in the fluorescence images. The shape of each brain was reconstructed by reference to a block-face and all data was mapped into a common 3D brain space with atlas and 2D cortical flat map. To overcome the effect of using a single template atlas to specify cortical boundaries, each brain was cytoarchitectonically annotated and used for making an individual 3D atlas. Registration between the individual and common brain cortical boundaries in the flat map space was done to absorb the variation of each brain and precisely map all tracer injection data into one cortical brain space. We describe the methodology of our pipeline and analyze tracer segmentation and brain registration accuracy. Results show our pipeline can successfully process and normalize tracer injection experiments into a common space, making it suitable for large-scale connectomics studies with a focus on the cerebral cortex.
Oral administration of an anti-CfaE secretory IgA antibody protects against EnterotoxigenicEscherichia colidiarrheal disease in a non-human primate model
Authors: Stoppato Matteo , Gaspar Carlos , Regeimbal James , Nunez Gladys , Giuntini Serena , Gawron Melissa A. , Pondish Jessica R. , Martin Joseph C. , Schneider Matthew , Schiller Zachary A. , Klempner Mark S. , Cavacini Lisa A. , Wang Yang 
Published: August 2019

ABSTACTEnterotoxigenicEscherichia coli(ETEC) is a leading cause of diarrhea-associated illness in developing countries. There is currently no vaccine licensed to prevent ETEC and the development of an efficacious prophylaxis would provide an intervention with significant impact. Recent studies suggested that effective protection could be achieved by inducing immunity to block colonization of ETEC. Here, we evaluated the efficacy of secretory (s) IgA2 and dimeric (d) IgA2 of an anti-colonization factor antigen antibody, 68-61, in theAotus nancymaaenon-human primate (NHP) ETEC challenge model via oral and parental delivery. Thirty-nine animals were distributed across 3 groups of 13, and challenged with 5.0×1011cfu of H10407 on Day 0. Group 1 received a dIgA2 68-61 subcutaneously on day 0. Group 2 received a SIgA2 68-61 orally on days −1, 0, and +1, and Group 3 received an irrelevant SIgA2 antibody orally on days −1, 0, and +1. All animals were observed for symptoms of diarrhea, and stools were collected for ETEC colony counts. SIgA2 treatment significantly lowered the attack rate, resulting in a protective efficacy of 71.4% (p=0.025) in Group 2 as compared to Group 3. Anti-CfaE dIgA2 treatment group reduced the diarrheal attack rate, although the reduction did not reach significance (57.1%; P=0.072) as compared to the irrelevant SIgA2 Group 3. Our results demonstrated the feasibility of oral administration of SIgA as a potential immunoprophylaxis against enteric infections. To our knowledge, this is the first study to demonstrate the efficacy of administrated SIgA in a non-human primate model.