bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty Acid-Saturated Albumin Reduces High Mortality and Fluid Requirements in a Rat Model of Hemorrhagic Shock Plus Tourniquet and Hypotensive Resuscitation
Authors: Penn Alexander H. , Williams Charnae E. , Walters Thomas J. , Dubick Michael A. , Torres Filho Ivo P. 
Published: March 2019

ABSTRACT
Military prehospital care for hemorrhage is often characterized by use of tourniquets (TQ) and permissive hypotensive resuscitation (PHR) with crystalloids or colloids, but these treatments have not been previously combined in an animal model. Although albumin resuscitation solutions have been tested, the potential effects of nonesterified fatty acids (NEFAs) bound to albumin have not been evaluated in vivo, and few studies have investigated concentrated albumin solutions to reduce fluid requirements. We created a militarily relevant rat model of trauma and hemorrhagic shock (T/HS) (27 mL/kg hemorrhage) with TQ and PHR. We investigated the ability of resuscitation with concentrated (250 mg/mL) albumin, followed by Plasmalyte as needed to maintain PHR, to reduce fluid volumes (vs. Plasmalyte alone, N = 17). Albumin was free of nonesterified fatty acids (N = 15) or saturated with oleic acid (OA; N = 13). The model resulted in high (53%) mortality within 3 h of injury. Only OA-saturated albumin was able to significantly reduce mortality (from 47% to 8%) and fluid requirements (from 56 to 6 mL/kg) compared to Plasmalyte alone. Plasma NEFA-binding capacity was saturated earliest in the OA-saturated albumin group. Likewise, OA-saturated albumin tended to increase cell-free hemoglobin in the broncheoalveolar lavage fluid, which was significantly associated with survival. Our findings suggest incorporating TQ and PHR in T/HS models may result in high mortality and fluid requirements and that OA-saturated albumin, but not NEFA-free albumin or Plasmalyte alone, may provide a benefit to early survival and resuscitation volume, though a hemolytic mechanism may have later consequences, so caution is advised.
Trends in Surgical Exposure and Experience in Female Pelvic Medicine and Reconstructive Surgery Fellowship Programs
Authors: Andiman Sarah E. , Fantl John A. 
Published: March 2019

Objectives
This study aimed to characterize variations in female pelvic medicine and reconstructive surgery (FPMRS) fellows’ surgical experiences, concurrence with Accreditation Council for Graduate Medical Education (ACGME) proposed procedural volume guidelines, and to explore how these factors affect self-assessed preparedness to practice independently upon graduation.

Methods
An electronic survey was sent to 166 fellows enrolled in ACGME-approved FPMRS fellowship programs during the 2017–2018 academic year. The survey included questions on demographics, program specifics, desires for future practice, case volume, and self-assessed ability to independently perform selected procedures.

Results
A total of 99 fellows responded, yielding a 59.6% (99/166) response rate. Procedures assessed as “core” urogynecologic surgeries were midurethral sling, sacral nerve stimulator placement, abdominal sacrocolpopexy, laparoscopic sacrocolpopexy, extraperitoneal colpopexy, intraperitoneal colpopexy, anterior colporrhaphy, posterior colporrhaphy, colpocleisis, rectovaginal fistula repair, vesicovaginal fistula repair, and urethral diverticulectomy. The percentage of third-year respondents meeting proposed ACGME guidelines varied from 56.3% (18/32; sling procedures) to 96.9% (31/32; intraperitoneal colpopexy and rectovaginal fistula repair). Although 67.7% (67/99) of all respondents reported that they did not expect to feel qualified to perform at least one of these procedures independently upon graduation from fellowship, 99.0% (98/99) predicted that they would be adequately trained overall to practice independently upon graduation.

Conclusions
Surgical experience varied among FMPRS surgical fellows. Case volume was somewhat but not completely associated with self-perceived ability to practice a procedure independently.
Superior Outcomes and Reduced Wait Times in Pediatric Recipients of Living Donor Liver Transplantation
Authors: Kehar Mohit , Parekh Rulan S. , Stunguris Jennifer , De Angelis Maria , Van Roestel Krista , Ghanekar Anand , Cattral Mark , Fecteau Annie , Ling Simon , Kamath Binita M. , Jones Nicola , Avitzur Yaron , Grant David , Ng Vicky Lee 
Published: March 2019

Background
Living donor liver transplantation (LDLT) is increasingly used to bridge the gap between the current supply and demand imbalance for deceased donor organs to provide lifesaving liver transplantation.

Methods
Outcomes of 135 children who underwent LDLT were compared with 158 recipients of deceased donor liver transplantation (DDLT) at the largest pediatric liver transplant program in Canada.

Results
Recipients of LDLT were significantly younger than deceased donor recipients (P ≤ 0.001), less likely to require dialysis pretransplant (P < 0.002) and had shorter wait time duration when the primary indication was cholestatic liver disease (P = 0.003). The LDLT donors were either related genetically or emotionally (79%), or unrelated (21%) to the pediatric recipients. One-, 5-, and 10-year patient survival rates were significantly higher in LDLT (97%, 94%, and 94%) compared with DDLT (92%, 87%, and 80%; log-rank P = 0.02) recipients, as were graft survival rates (96%, 93%, and 93% for LDLT versus 89%, 81.4%, and 70%, respectively, for DDLT; log-rank P = 0.001). Medical and surgical complications were not statistically different between groups. Graft failure was higher in recipients of DDLT (odds ratio, 2.60; 95% confidence interval, 1.02, 6.58) than in the LDLT group after adjustment for clinical characteristics and propensity score.

Conclusions
Living donor liver transplantation provides superior outcomes for children and is an excellent and effective strategy to increase the chances of receiving a liver transplant.
Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema
Authors: Mallery Robert M. , Rehmani Obeidurahman F. , Woo John H. , Chen Yin Jie , Reddi Sudama , Salzman Karen L. , Pinho Marco C. , Ledbetter Luke , Tamhankar Madhura A. , Shindler Kenneth S. , Digre Kathleen B. , Friedman Deborah I. , Liu Grant T. 
Published: March 2019

Objective:
Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP.

Methods:
Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension.

Results:
Reduced pituitary gland height was moderately sensitive for IIH WP (80%) but had low specificity (64%). Increased optic nerve sheath diameter was less sensitive (51%) and only moderately specific (83%). Flattening of the posterior globe was highly specific (97%) but had low sensitivity (57%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100% specific, while maintaining a sensitivity of 64%. Of patients with CH + EOP, 30% had 3 or more MRI features, suggesting IIH WOP in those patients.

Conclusion:
A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.
Epithelial retinoic acid receptor β regulates serum amyloid A expression and vitamin A-dependent intestinal immunity
Authors: Gattu Sureka , Bang Ye-Ji , Pendse Mihir , Dende Chaitanya , Chara Andrew L. , Harris Tamia A. , Wang Yuhao , Ruhn Kelly A. , Kuang Zheng , Sockanathan Shanthini , Hooper Lora V. 
Published: March 2019

AbstractVitamin A is a dietary component that is essential for the development of intestinal immunity. Vitamin A is absorbed and converted to its bioactive derivatives retinol and retinoic acid by the intestinal epithelium, yet little is known about how epithelial cells regulate vitamin A-dependent intestinal immunity. Here we show that epithelial cell expression of the transcription factor retinoic acid receptor β (RARβ) is essential for vitamin A-dependent intestinal immunity. Epithelial RARβ activated vitamin A-dependent expression of serum amyloid A (SAA) proteins by binding directly to Saa promoters. In accordance with the known role of SAAs in regulating Th17 cell effector function, epithelial RARβ promoted IL-17 production by intestinal Th17 cells. More broadly, epithelial RARβ was required for the development of key vitamin A-dependent adaptive immune responses, including CD4+ T cell homing to the intestine and the development of immunoglobulin A-producing intestinal B cells. Our findings provide insight into how the intestinal epithelium senses dietary vitamin A status to regulate adaptive immunity and highlight the role of epithelial cells in regulating intestinal immunity in response to diet.Significance StatementVitamin A is a nutrient that is essential for the development of intestinal immunity. It is absorbed by gut epithelial cells which convert it to retinol and retinoic acid. Here we show that the transcription factor retinoic acid receptor β (RARβ) allows epithelial cells to sense vitamin A in the diet and regulate vitamin A-dependent immunity in the intestine. We find that epithelial RARβ regulates several intestinal immune responses, including production of the immunomodulatory protein serum amyloid A, T cell homing to the intestine, and B cell production of immunoglobulin A. Our findings provide new insight into how epithelial cells sense vitamin A to regulate intestinal immunity and highlight why vitamin A is so important for immunity to infection.
Global transcriptome analysis of theMyxococcus xanthusmulticellular developmental program
Authors: Muñoz-Dorado J. , Moraleda-Muñoz A. , Marcos-Torres F.J. , Contreras-Moreno F.J. , Martin-Cuadrado A.B. , Schrader J.M. , Higgs P.I. , Pérez J. 
Published: March 2019

ABSTRACTThe bacteriaMyxococcus xanthusexhibit a complex multicellular life cycle. In the presence of nutrients, cells prey cooperatively. Upon starvation, they enter a developmental cycle wherein cells aggregate to produce macroscopic fruiting bodies filled with resistant myxospores. We used RNA-Seq technology to examine the global transcriptome of the 96 h developmental program. This data revealed that many genes were sequentially expressed in discrete modules, with expression peaking during aggregation, in the transition from aggregation to sporulation, or during sporulation. Analysis of genes expressed at each specific time point provided a global framework integrating regulatory factors coordinating motility and differentiation in the developmental program. These data provided insights as to how starving cells obtain energy and precursors necessary for assembly of fruiting bodies and into developmental production of secondary metabolites. This study offers the first global view of developmental transcriptional profiles and provides an important scaffold for future studies.IMPACT STATEMENTInvestigation of global gene expression profiles during formation of theMyxococcus xanthusspecialized biofilm reveals a genetic regulatory network that coordinates cell motility, differentiation, and secondary metabolite production.
Signatures of divergent antimalarial treatment responses in peripheral blood from infants and adults in Malawi
Authors: Maurizio Paul L. , Fuseini Hubaida , Tegha Gerald , Hosseinipour Mina , Paris Kristina De 
Published: March 2019

AbstractBackgroundHeterogeneity in the immune response to parasite infection is mediated in part by differences in host genetics, sex, and age group. In neonates and infants, ongoing immunological maturation often results in increased susceptibility to infection and variable responses to drug treatment, increasing the risk of complications. Even though significant age-specific effects on host cytokine responses to Plasmodium falciparum infection have been identified, age effects on uncomplicated malaria infection and antimalarial treatment remain poorly understood.MethodsIn samples of whole blood from a cohort of naturally infected malaria-positive individuals in Malawi (n=63 total; 34 infants <2 years old, 29 adults >18 years old), we assessed blood cytokine levels and characterized monocyte and dendritic cell frequencies at two timepoints: acute infection, and four weeks post antimalarial treatment. We modeled the effects of age group, sex, and timepoint, and evaluated the role of these factors on infection and treatment outcomes.ResultsRegardless of treatment timepoint, in our population age was significantly associated with overall blood hemoglobin, which was higher in adults, and plasma nitric oxide, IL-10, and TNF-α levels, which were higher in infants. We found a significant effect of age on the hemoglobin treatment response, whereby after treatment, levels increased in infants and decreased in adults. Furthermore, we observed significant age-specific effects on treatment response for overall parasite load, IFN-γ and IL-12(p40), and these effects were sex-dependent. We uncovered significant age effects on the overall levels and treatment response of myeloid dendritic cell frequencies. In addition, within each age group, we found continuous age effects on gametocyte levels (Pfs16), TNF-α, and nitric oxide.ConclusionsIn a clinical study of infants and adults experiencing natural malaria infection and receiving antimalarial treatment, we identified age-specific signatures of infection and treatment responses in peripheral blood. We describe host markers that may indicate, and potentially mediate, differential post-treatment outcomes for malaria in infants versus adults.
Evolutionary analyses unveil the molecular mechanism of fast inactivation in calcium-permeable TRP channels
Authors: Flores-Aldama Lisandra , Vandewege Michael W. , Zavala Kattina , Colenso Charlotte K. , Bustos Daniel , Gonzalez Wendy , Brauchi Sebastian E. , Opazo Juan C. 
Published: March 2019

AbstractFundamental for calcium homeostasis in vertebrates, TRPV5 and TRPV6 are calcium-selective ion channels belonging to the Transient Receptor Potential (TRP) gene family. Detailed phylogenetic analysis suggests that duplications from which TRPV5 and TRPV6 originated occurred independently in the ancestors of mammals, sauropsids, amphibians, and chondrichthyans. Coincident with the conquest of land and the physiological changes needed to maintain calcium homeostasis, our expression analyses suggest a change in the expression pattern from gills to kidney. Within amniotes, we identified a traceable sequence signature of three amino acids at the amino-terminal intracellular region that correlates well with both of the duplication events and the phenotype of fast inactivation observed in TRPV6 channels. Electrophysiological recordings and mutagenesis suggest that calcium-induced fast inactivation is an evolutionary innovation that emerged independently from each duplication event. Simulations of molecular dynamics suggest that calcium-induced channel rearrangements are important modulatory regions of TRP channels.
Shotgun proteomics analysis of nanoparticle-synthesisingDesulfovibrio alaskensisin response to platinum and palladium
Authors: Capeness Michael J. , Imrie Lisa , Mühlbauer Lukas F. , Bihan Thierry Le , Horsfall Louise E. 
Published: March 2019

AbstractPlatinum and palladium are much sought-after metals of global critical importance in terms of abundance and availability. At the nano-scale these metals are of even higher value due to their catalytic abilities for industrial applications.Desulfovibrio alaskensisis able to capture ionic forms of both of these metals, reduce them, and synthesize elemental nanoparticles. Despite this ability very little is known about the biological pathways involved in the formation of these nanoparticles. Proteomic analysis ofD. alaskensisin response to platinum and palladium has highlighted those proteins involved in both the reductive pathways and the wider stress-response system. A core set of 13 proteins was found in both treatments and consisted of proteins involved in metal transport and reduction. There were also 7 proteins specific to either platinum or palladium. Over-expression of one of these platinum-specific genes, a NiFe hydrogenase small subunit (Dde_2137), resulted in the formation of larger nanoparticles. This study improves our understanding of the pathways involved in the metal resistance mechanism ofDesulfovibrioand informs how we can tailor the bacterium for nanoparticle production, enhancing its application as a bioremediation tool and as way to capture contaminant metals from the environment.ImportanceBacteria, in particularlyD. alaskensis, represent a biological and greener way to capture high value metals such as platinum group metals from environmental and industrial waste streams. The recovery of these metals in nanoparticle forms adds extra value to this process as they can be used in a variety of different industrial applications as they have exceptional catalytic capabilities.D. alaskensisability to do this, has been widely reported, though very little is understood about the underlying protein and genetic components. It is by understanding the biological basis of this capability that we can further improve and adapt this bacterium to be better at bioremediation and to control its ability to do so.
Learning what is irrelevant or relevant: Expectations facilitate distractor inhibition and target facilitation through distinct neural mechanisms
Authors: van Moorselaar Dirk , Slagter Heleen A. 
Published: March 2019

AbstractIt is well known that attention can facilitate performance by top-down biasing processing of task-relevant information in advance. Recent findings from behavioral studies suggest that distractor inhibition is not under similar direct control, but strongly dependent on expectations derived from previous experience. Yet, how expectations about distracting information influence distractor inhibition at the neural level remains unclear. The current study addressed this outstanding question in three experiments in which search displays with repeating distractor or target locations across trials allowed observers to learn which location to selectively suppress or boost. Behavioral findings demonstrated that both distractor and target location learning resulted in more efficient search, as indexed by faster response times. Crucially, benefits of distractor learning were observed without target location foreknowledge, unaffected by the number of possible target locations, and could not be explained by priming alone. To determine how distractor location expectations facilitated performance, we applied a spatial encoding model to EEG data to reconstruct activity in neural populations tuned to the distractor or target location. Target location learning increased neural tuning to the target location in advance, indicative of preparatory biasing. This sensitivity increased after target presentation. By contrast, distractor expectations did not change preparatory spatial tuning. Instead, distractor expectations reduced distractor-specific processing, as reflected in the disappearance of the Pd ERP component, a neural marker of distractor inhibition, and decreased decoding accuracy. These findings suggest that the brain may no longer process expected distractors as distractors, once it has learned they can safely be ignored.Significance statementWe constantly try hard to ignore conspicuous events that distract us from our current goals. Surprisingly, and in contrast to dominant attention theories, ignoring distracting, but irrelevant events does not seem to be as flexible as is focusing our attention on those same aspects. Instead, distractor suppression appears to strongly rely on learned, context-dependent expectations. Here, we investigated how learning about upcoming distractors changes distractor processing and directly contrasted the underlying neural dynamics to target learning. We show that while target learning enhanced anticipatory sensory tuning, distractor learning only modulated reactive suppressive processing. These results suggest that expected distractors may no longer be considered distractors by the brain once it has learned that they can safely be ignored.
A smooth muscle-like niche facilitates lung epithelial regeneration
Authors: Moiseenko Alena , Vazquez-Armendariz Ana Ivonne , Chu Xuran , Günther Stefan , Lebrigand Kevin , Kheirollahi Vahid , Herold Susanne , Braun Thomas , Mari Bernard , De Langhe Stijn , Chen Chengshui , Li Xiaokun , Seeger Werner , Zhang Jin-San , Bellusci Saverio , Agha Elie El 
Published: March 2019

AbstractThe mammalian lung is a highly complex organ due to its branched, tree-like structure and diverse cellular composition. Recent efforts using state-of-the-art genetic lineage tracing and single-cell transcriptomics have helped reduce this complexity and delineate the ancestry and fate of various cell subpopulations during organogenesis, homeostasis and repair after injury. However, mesenchymal cell heterogeneity and function in development and disease remain a longstanding issue in the lung field. In this study, we break down smooth muscle heterogeneity into the constituent subpopulations by combiningin vivolineage tracing, single-cell RNA sequencing andin vitroorganoid cultures. We identify a repair-supportive mesenchymal cell (RSMC) population that is distinct from pre-existing airway smooth muscle cells (ASMC) and is critical for regenerating the conducting airway epithelium. Progenitors of RSMCs are intertwined with airway smooth muscle, undergo active WNT signaling, transiently acquire the expression of the smooth muscle marker ACTA2 in response to epithelial injury and are marked by PDGFRα expression. Our data simplify the cellular complexity of the peribronchiolar domain of the adult lung and represent a forward step towards unraveling the role of mesenchymal cell subpopulations in instructing epithelial behavior during repair processes.
A state-dependent mean-field formalism to model different activity states in conductance based networks of spiking neurons
Authors: Capone Cristiano , Volo Matteo di , Romagnoni Alberto , Mattia Maurizio , Destexhe Alain 
Published: March 2019

AbstractHigher and higher interest has been shown in the recent years to large scale spiking simulations of cerebral neuronal networks, coming both from the presence of high performance computers and increasing details in the experimental observations. In this context it is important to understand how population dynamics are generated by the designed parameters of the networks, that is the question addressed by mean field theories. Despite analytic solutions for the mean field dynamics has already been proposed generally for current based neurons (CUBA), the same for more realistic neural properties, such as conductance based (COBA) network of adaptive exponential neurons (AdEx), a complete analytic model has not been achieved yet. Here, we propose a novel principled approach to map a COBA on a CUBA. Such approach provides a state-dependent approximation capable to reliably predict the firing rate properties of an AdEx neuron with non-instantaneous COBA integration. We also applied our theory to population dynamics, predicting the dynamical properties of the network in very different regimes, such as asynchronous irregular (AI) and synchronous irregular (SI) (slow oscillations, SO).This results show that a state-dependent approximation can be successfully introduced in order to take into account the subtle effects of COBA integration and to deal with a theory capable to correctly predicts the activity in regimes of alternating states like slow oscillations.