bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Alternative Pasteurization Techniques on Human Milk's Bioactive Proteins
Authors: Aceti Arianna , Cavallarin Laura , Martini Silvia , Giribaldi Marzia , Vitali Francesca , Ambretti Simone , Zambrini Vittorio , Corvaglia Luigi 
Published: December 2019

ABSTRACTObjectives:Human milk (HM) feeding leads to improved outcome for preterm infants. When mother's milk is unavailable, pasteurized donor HM (DHM) is the recommended alternative over formula. The Holder pasteurization (HoP) method is universally performed in HM banks; however, it is known to impair several functional HM components. The aim of this study was to compare the efficacy of HoP with 2 innovative processing methods (high‐temperature short‐time [HTST] pasteurization and high‐pressure processing [HPP]) in preserving some bioactive HM protein components.Methods:HM samples from donors of the Bologna HM bank were collected and divided into 4 subsamples: 1 was kept raw, and each of the others was processed using a different technique (HoP, HTST, and HPP at 600 MPa for 3 minutes). Total protein content, secretory immunoglobulin A (sIgA), and lactoferrin contents were compared.Results:Both HM lactoferrin and sIgA content were negatively affected, but to a different extent, by each method: sIgA was preserved by HTST, with only HPP leading to a significant reduction (−38.8%); lactoferrin content was strongly reduced by HoP (−87.5%) and HTST (‐83.5%), and preserved by HPP. Variations in protein profile were seen for all processing methods, being more relevant for HoP, followed by HTST and, finally, by HPP. All the 3 methods lowered the untreated HM microbial counts to undetectable levels, in accordance with national guidelines.Conclusions:Both HTST and HPP better preserved the original HM protein profile, compared to HoP. They, however, affected differently some bioactive HM components involved in immune response and antibacterial activity.
Effect of Mild Hypothermia on the Diaphragmatic Microcirculation and Function in A Murine Cardiopulmonary Resuscitated Model
Authors: Li Shao-Ping , Zhou Xian-Long , Li Qi , Zhao Yu-Qian , Zhao Zhi-Gang , Zhao Yan 
Published: December 2019

ABSTRACT

Objective:
Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA); however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model.

Methods:
Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intraresuscitation hypothermia group (IRH), a postresuscitation hypothermia group (PRH), or a sham control group. CA was induced by airway occlusion, and resuscitation was implemented by precordial compression and MV. The diaphragmatic microvascular blood flow velocity, diaphragmatic microcirculation flow index (MFI), and perfused vascular density (PVD) were measured. The diaphragm was then removed for in vitro contractile property examination and cross-sectional area measurement. The lipid peroxidation and superoxide dismutase (SOD) levels in the diaphragm were also assayed.

Results:
Either early or delayed MHT intervention did not improve the diaphragmatic microvascular blood flow velocity, MFI, and PVD, which were significantly decreased during prolonged MV after resuscitation. Compared with the RNT group, treatment with MHT increased the diaphragm contractility, fiber dimensions, and SOD levels and decreased diaphragm lipid peroxidation. A more significant change in these indices was observed in the IRH group compared with that in the PRH group.

Conclusion:
MHT preserves the diaphragm contractility and fiber dimensions and decreases oxidative stress but does not improve the microcirculatory blood supply during prolonged MV after resuscitation. Early MHT intervention is more efficient in preventing diaphragm dysfunction than delayed intervention after CA.
Five-year Outcomes of Pulmonary Hypertension With and Without Elevated Left Atrial Pressure in Patients Evaluated for Kidney Transplantation
Authors: Caughey Melissa C. , Detwiler Randal K. , Sivak Joseph A. , Rose-Jones Lisa J. , Kshirsagar Abhijit V. , Hinderliter Alan L. 
Published: December 2019

Background.
Pulmonary hypertension (PH) is frequently reported in patients with advanced chronic kidney disease and is associated with early allograft failure and death. However, the causes of PH are heterogeneous, and patient prognosis may vary by etiologic subtype.

Methods.
Data from the University of North Carolina Cardiorenal Registry were examined to determine associations between PH, with or without elevated left atrial pressure (eLAP), and mortality in candidates for kidney transplantation. PH and eLAP were determined by Doppler echocardiography and by tissue Doppler imaging, respectively.

Results.
From 2006 to 2013, 778 registry patients were screened preoperatively by echocardiography. Most patients were black (64%) and men (56%); the mean age was 56 years. PH was identified in 97 (12%) patients; of these, eLAP was prevalent in half. During a median follow-up of 4.4 years, 179 (23%) received a kidney transplant, and 195 (25%) died. After adjustments for demographics, comorbidities, dialysis vintage, and kidney transplantation, PH was associated with twice the 5-year mortality (hazard ratio [HR] = 2.11; 95% confidence interval [CI]: 1.48-3.03), with stronger associations in the absence of eLAP (HR = 2.87; 95% CI: 1.83-4.49) than with eLAP (HR = 1.11; 95% CI: 0.57-2.17), P for interaction = 0.01.

Conclusions.
The mortality risk associated with PH among patients with advanced chronic kidney disease appears to differ by etiology. Patients with PH in the absence of eLAP are at high risk of death and in need of focused attention. Future research efforts should investigate potential strategies to improve outcomes for these patients.
Bilateral Proximal Forearm Transplantation: Case Report at 7 Years
Authors: Iglesias Martín , Villanueva-Castro Eliezer , Macias-Gallardo Julio , Alberú-Gómez Josefina , Leal-Villalpando Rafael P. , Zamudio-Bautista Jorge , Acosta Victor , Butrón Patricia , Sierra-Madero Juan G. , Cuellar-Rodriguez Jennifer , Espinosa-Cruz Verónica , Gómez-Camargo Claudia , Mayorquín-Ruiz Mariana , Vázquez-Lamadrid Jorge , Toussaint-Caire Sonia , Domínguez-Cherit Judith , Dorantes-García Joel , Furuzawa-Carballeda Janette , Hernandez-Castillo Carlos R. , Guzmán González Juan M. , Castelan-Carmona Natalia , López-Mártinez Mayra , González-Tableros Norma , Arvizu-Hernández Adriana , De Santiago-Zárate Adrián 
Published: December 2019

Background.
Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT.

Case Presentation.
A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force.

Results.
Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year.

Conclusions.
Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.
High Content Screening, a reliable system forCoxiella burnetiiisolation from clinical samples
Authors: Francis Rania , Mioulane Maxime , Bideau Marion Le , Mati Marie-Charlotte , Fournier Pierre-Edouard , Raoult Didier , Khalil Jacques Yaacoub Bou , Scola Bernard La 
Published: December 2019

AbstractQ fever, caused byCoxiella burnetii, is a worldwide zoonotic disease that may cause severe forms in humans and requires a specific and prolonged antibiotic treatment. Although the current serological and molecular detection tools enable a reliable diagnosis of the disease, culture ofC. burnetiistrains is mandatory to evaluate their antibiotic susceptibility and sequence their genome in order to optimize patient management and epidemiological studies. However, cultivating this fastidious microorganism is difficult and restricted to reference centers as it requires biosafety-level 3 laboratories and relies on cell culture performed by experienced technicians. In addition, the culture yield is low, which results in a small number of isolates being available. In this work, we developed a novel high content screening (HCS) isolation strategy based on optimized high-throughput cell culture and automated microscopic detection of infected cells with specifically-designed algorithms targeting cytopathic effects. This method was more efficient than the shell-vial assay when applied to both frozen specimens (7 isolates recovered by HCS only, sensitivity 91%vs78% for shell-vial) and fresh samples (1 additional isolate using HCS, sensitivity 7%vs5% for shell-vial). In addition, detecting positive cultures by an automated microscope reduced the need for expertise and saved 24% of technician working time. Application of HCS to antibiotic susceptibility testing of 12 strains demonstrated that it was as efficient as the standard procedure that combines shell-vial culture and quantitative PCR. Overall, this high-throughput HCS system paves the way to the development of improved cell culture isolation of human viruses.
The Two Amino Acids Proximate to the Renin Cleavage Site of Human Angiotensinogen Do Not Affect Angiotensin II-mediated Functions in Mice
Authors: Wu Chia-Hua , Wu Congqing , Howatt Deborah A. , Moorleghen Jessica J. , Cassis Lisa A. , Daugherty Alan , Lu Hong S. 
Published: December 2019

ABSTRACTObjectiveRenin cleavage of angiotensinogen (AGT) has species specificity. Since the residues at positions 11 and 12 of AGT are different between human and mouse AGT, we determined whether these two residues in AGT affect renin cleavage and angiotensin II-mediated functions using an adeno-associated viral (AAV) approach for manipulating AGT in vivo.Approach and ResultsHepatocyte-specific AGT deficient (hepAGT-/-) mice in an LDL receptor -/- background were infected with AAVs containing a null insert, human AGT, or mouse AGT expressing the same residues of the human protein at positions 11 and 12 [mouse AGT (L11V;Y12I)]. Expression of human AGT in hepAGT-/- mice led to high plasma human AGT concentrations without changes in plasma mouse endogenous AGT, plasma renin concentrations, blood pressure, or atherosclerosis. This is consistent with human AGT not being cleaved by mouse renin. To determine whether the residues at positions 11 and 12 in human AGT lead to the inability of mouse renin to cleave human AGT, hepAGT-/- mice were injected with AAV encoding mouse AGT (L11V;Y12I). Expression of mouse AGT (L11V;Y12I) resulted in increased plasma mouse AGT concentrations, reduced renin concentrations, and increased renal AngII concentrations that were comparable to their concentrations in hepAGT+/+ mice. This mouse AGT variant increased blood pressure and atherosclerosis in hepAGT-/- mice to the magnitude of hepAGT+/+ mice.ConclusionReplacement of L11 and Y12 to V11 and I12, respectively, in mouse AGT does not affect renin cleavage and AngII-mediated functions in mice.HIGHLIGHTSHuman AGT is not cleaved by mouse renin and does not change AngII-mediated functions in hepatocyte-specific AGT -/- mice.Replacement of the N-terminal amino acids at 11 and 12 positions from mouse to human AGT does not affect renin cleavage and AngII-mediated functions in hepatocyte-specific AGT -/- mice.
Stroke Volume Reserve Is an Independent Predictor of Survival and Need for Advanced Therapies in Systolic Heart Failure Patients
Authors: Selevany Ibrahim , Vaida Florin , Adler Eric D. , Kim Paul J. , Morris Timothy 
Published: December 2019

BackgroundCurrent predictors of clinical deterioration in patients with heart-failure with reduced ejection fraction (HFrEF) have limited accuracy. We investigated whether stroke volume reserve index (SVRI) would predict 1-year mortality and need for advanced therapies in HFrEF patients.MethodsWe retrospectively studied a consecutive series of 104 ambulatory HFrEF patients (59±11 years, 89% men) at our center who underwent cardiopulmonary exercise testing (CPET) from January 2017 to September 2018. The primary outcome was defined as heart-transplantation, urgent left ventricular assist device (LVAD) implantation or death within 1 year of evaluation. SVRI was estimated at rest and at anaerobic threshold (AT) by VO2 (oxygen consumption)/pulse and previously validated estimates of C[a-v]O2 (arteriovenous difference in oxygen content). Multivariate regression selected the optimal predictors from clinical, CPET and right heart catheterization data.ResultsAmong HFrEF patients studied, 39 (37.5%) deteriorated: 16 required heart-transplantation, 8 required LVADs and 15 died. SVRI 128% or less was the best predictor (OR 6.69, p=0.001), followed by an invasively determined resting cardiac index 2 L/min/m2 or less (OR 3.18, p=0.02), and peak VO2 below the International Society for Heart and Lung Transplantation (ISHLT) cut-off (OR 4.15, p=0.01). A scoring system derived from the SVRI (less than 128%: 2 points), peak VO2 (below the ISHLT cut-off: 1 point), and cardiac index (less than 2 L/min/m2: 1 point) predicted clinical deterioration with a sensitivity of 64% and specificity of 81%.ConclusionsSVRI is a non-invasive measurement that may predict deterioration in HFrEF patients more accurately than currently recommended predictors.
Recellularization of bronchial extracellular matrix with primary bronchial smooth muscle cells
Authors: Hamouda Selma Ben , Vargas Amandine , Boivin Roxane , Miglino Maria Angelica , da Palma Renata Kelly , Lavoie Jean-Pierre 
Published: December 2019

AbstractSevere asthma is associated with an increased airway smooth muscle (ASM) mass and an altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment. Our goal was to obtain acellular bronchial matrices and then develop a recellularization protocol with ASM cells. We studied equine bronchi as horses spontaneously develop a human asthma-like disease. The bronchi were decellularized using Triton/Sodium Deoxycholate. The obtained scaffolds retained their anatomical and histological properties. Using immunohistochemistry and a semi-quantitative score to compare native bronchi to scaffolds revealed no significant variation for matrixial proteins. A DNA quantification and electrophoresis indicated that most of DNA was 29.6 ng/mg of tissue ± 5.6 with remaining fragments of less than 100 bp. Primary ASM cells were seeded on the scaffolds. Histological analysis after recellularization showed that ASM cells migrated and proliferated primarily in the decellularized smooth muscle matrix, suggesting a chemotactic effect of the scaffolds. This is the first report of primary ASM cells preferentially repopulating the smooth muscle matrix layer in bronchial matrices. This protocol is now being used to study the molecular interactions occurring between the asthmatic ECMs and ASM to identify effectors of asthmatic bronchial remodeling.
Sources of predictive information in dynamical neural networks
Authors: Candadai Madhavun , Izquierdo Eduardo J. 
Published: December 2019

Behavior involves the ongoing interaction between an organism and its environment. One of the prevailing theories of adaptive behavior is that organisms are constantly making predictions about their future environmental stimuli. However, how they acquire that predictive information is still poorly understood. Two complementary mechanisms have been proposed: predictions are generated from an agent’s internal model of the world or predictions are extracted directly from the environmental stimulus. In this work, we demonstrate that predictive information, measured using mutual information, cannot distinguish between these two kinds of systems. Furthermore, we show that predictive information cannot distinguish between organisms that are adapted to their environments and random dynamical systems exposed to the same environment. To understand the role of predictive information in adaptive behavior, we need to be able to identify where it is generated. To do this, we decompose information transfer across the different components of the organism-environment system and track the flow of information in the system over time. To validate the proposed framework, we examined it on a set of computational models of idealized agent-environment systems. Analysis of the systems revealed three key insights. First, predictive information, when sourced from the environment, can be reflected in any agent irrespective of its ability to perform a task. Second, predictive information, when sourced from the nervous system, requires special dynamics acquired during the process of adapting to the environment. Third, the magnitude of predictive information in a system can be different for the same task if the environmental structure changes.Significance StatementAn organism’s ability to predict the consequences of its actions on future stimuli is considered a strong indicator of its environmental adaptation. However, in highly structured natural environments, to what extent does an agent have to develop specialized mechanisms to generate predictions? To study this, we present an information theoretic framework to infer the source of predictive information in an organism: extrinsically from the environment or intrinsically from the agent. We find that predictive information extracted from the environment can be reflected in any agent and is therefore not a good indicator of behavioral performance. Studying the flow of predictive information over time across the organism-environment system enables us to better understand its role in behavior.
Deciphering the many maps of the Xingu – an assessment of land cover classifications at multiple scales
Authors: Kalacska M , Arroyo-Mora J.P , Lucanus O , Sousa L , Pereira T , Vieira T 
Published: December 2019

AbstractRemote sensing is an invaluable tool to objectively illustrate the rapid decline in habitat extents worldwide. The many operational Earth Observation platforms provide options for the generation of land cover maps, each with unique characteristics, as well as considerable semantic differences in the definition of classes. As a result, differences in baseline estimates are inevitable. Here we compare forest cover and surface water estimates over four time periods spanning three decades (1989–2018) for ∼1.3 million km2encompassing the Xingu river basin, Brazil, from published, freely accessible remotely sensed classifications. While all datasets showed a decrease in forest extent over time, we found a large range in the total area reported by each product for all time periods. The greatest differences ranged from 9% (year 2000) to 17% of the total area (2014-2018 period). We also show the high sensitivity of forest fragmentation metrics (entropy and foreground area density) to data quality and spatial resolution, with cloud cover and sensor artefacts resulting in errors. We further show the importance of choosing surface water datasets carefully because they differ greatly in location and amount of surface water mapped between sources. In several of the datasets illustrating the land cover following operationalization of the Belo Monte dam, the large reservoirs are notably absent. Freshwater ecosystem health is influenced by the land cover surrounding water bodies (e.g. Riparian zones). Understanding differences between the many remotely sensed baselines is fundamentally important to avoid information misuse, and to objectively choose the most appropriate dataset for conservation, taxonomy or policy-making. The differences in forest cover between the datasets examined here are not a failure of the technology, but due to different interpretations of ‘forest’ and characteristics of the input data (e.g. spatial resolution). Our findings demonstrate the importance of transparency in the generation of remotely sensed datasets and the need for users to familiarize themselves with the characteristics and limitations of each chosen data set.
Cytoplasmic streaming drifts the polarity cue and specifies the cell polarity inCaenorhabditis eleganszygotes
Authors: Kimura Kenji , Kimura Akatsuki 
Published: December 2019

AbstractCell polarisation is required to define body axes during development. The position of spatial cues for polarisation is critical to direct the body axes. InCaenorhabditis eleganszygotes, the sperm-derived pronucleus/centrosome complex (SPCC) serves as the spatial cue to specify the anterior–posterior axis. Approximately 30 minutes after fertilisation, the contractility of the cell cortex is relaxed near the SPCC, which is the earliest sign of polarisation and called symmetry breaking (SB). It is unclear how the position of SPCC at SB is determined after fertilisation. Here, we show that SPCC drifts dynamically through the cell-wide flow of the cytoplasm, called meiotic cytoplasmic streaming. This flow occasionally brings SPCC to the opposite side of the sperm entry site before SB. Our results demonstrate that cytoplasmic flow determines stochastically the position of the spatial cue of the body axis, even in an organism likeC. elegansfor which development is stereotyped.
Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein
Authors: Kobayashi Kazuhiro , Shihoya Wataru , Nishizawa Tomohiro , Kadji Francois Marie Ngako , Aoki Junken , Inoue Asuka , Nureki Osamu 
Published: December 2019

AbstractPituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide hormone functioning in the central nervous system and peripheral tissues. The PACAP receptor PAC1R, which belongs to the class B G-protein-coupled receptors (GPCRs), is a drug target for mental disorders and dry eye syndrome. Here we present a cryo-electron microscopy structure of human PAC1R bound to PACAP and an engineered Gs heterotrimer. The structure revealed that TM1 plays an essential role in PACAP recognition. The ECD (extracellular domain) of PAC1R tilts by ~40° as compared to that of the glucagon-like peptide-1 receptor (GLP1R), and thus does not cover the peptide ligand. A functional analysis demonstrated that the PAC1R-ECD functions as an affinity trap and is not required for receptor activation, whereas the GLP1R-ECD plays an indispensable role in receptor activation, illuminating the functional diversity of the ECDs in the class B GPCRs. Our structural information will facilitate the design and improvement of better PAC1R agonists for clinical applications.This article is a preprint version and has not been certified by peer review.