bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xenin-25 induces anion secretion by activating noncholinergic secretomotor neurons in the rat ileum
Authors: Kuwahara Atsukazu , Kuwahara Yuko , Kato Ikuo , Kawaguchi Kotoku , Harata Daiki , Asano Shinji , Inui Toshio , Marunaka Yoshinori 
Published: April 2019

Xenin-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine. Xenin-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the xenin-25-induced anion secretion were characterized using the Ussing-chambered, mucosa-submucosa preparation from the rat ileum. Serosal application of xenin-25 increased the short-circuit current in a concentration-dependent manner. The responses were abolished by the combination of Cl−-free and [Formula: see text]-free solutions. The responses were almost completely blocked by TTX (10−6M) but not by atropine (10−5M) or hexamethonium (10−4M). The selective antagonists for neurotensin receptor 1 (NTSR1), neurokinin 1 (NK1), vasoactive intestinal polypeptide (VIP) receptors 1 and 2 (VPAC1 and VPAC2, respectively), and capsaicin, but not 5-hydroxyltryptamine receptors 3 and 4 (5-HT3and 5-HT4), NTSR2, and A803467, inhibited the responses to xenin-25. The expression of VIP receptors ( Vipr) in rat ileum was examined using RT-PCR. The Vipr1 PCR products were detected in the submucosal plexus and mucosa. Immunohistochemical staining showed the colocalization of NTSR1 and NK1 with substance P (SP)- and calbindin-immunoreactive neurons in the submucosal plexus, respectively. In addition, NK1 was colocalized with noncholinergic VIP secretomotor neurons. Based on the results from the present study, xenin-25-induced Cl−/[Formula: see text] secretion is involved in NTSR1 activation on intrinsic and extrinsic afferent neurons, followed by the release of SP and subsequent activation of NK1 expressed on noncholinergic VIP secretomotor neurons. Finally, the secreted VIP may activate VPAC1 on epithelial cells to induce Cl−/[Formula: see text] secretion in the rat ileum. Activation of noncholinergic VIP secretomotor neurons by intrinsic primary afferent neurons and extrinsic afferent neurons by postprandially released xenin-25 may account for most of the neurogenic secretory response induced by xenin-25.NEW & NOTEWORTHY This study is the first to investigate the intrinsic neuronal circuit responsible for xenin-25-induced anion secretion in the rat small intestine. We have found that nutrient-stimulated xenin-25 release may activate noncholinergic vasoactive intestinal polypeptide (VIP) secretomotor neurons to promote Cl−/[Formula: see text] secretion through the activation of VIP receptor 1 on epithelial cells. Moreover, the xenin-25-induced secretory responses are mainly linked with intrinsic primary afferent neurons, which are involved in the activation of neurotensin receptor 1 and neurokinin 1 receptor.
Inhibition of jejunal protein synthesis and breakdown in Pseudomonas aeruginosa-induced sepsis pig model
Authors: Ten Have Gabriëlla A. M. , Engelen Mariëlle P. K. J. , Wolfe Robert R. , Deutz Nicolaas E. P. 
Published: April 2019

Maintenance of gut integrity has long been recognized as crucial for survival in sepsis, but alterations in protein metabolism have not previously been documented. Therefore, in the present study, we measured in a Pseudomonas aeruginosa-induced porcine sepsis model fractional protein synthesis (FSR) and breakdown rates (FBR) in jejunal mucosa in a fasted, conscious state. FSR was measured by the incorporation rate of stable tracer amino acid (l-[ ring-13C6]phenylalanine) into tissue protein. FBR was determined using the relation between blood arterial enrichment and intracellular enrichment of phenylalanine in consecutive mucosal biopsies after a pulse of l-[15N]phenylalanine. Additionally, we determined the FSR in jejunum, ileum, liver, muscle, and lung tissue. We found in this sham-controlled acute sepsis pig model (control: n = 9; sepsis: n = 13) that jejunal mucosal protein turnover is reduced with both decreased FSR (control: 3.29 ± 0.22; sepsis: 2.32 ± 0.12%/h, P = 0.0008) and FBR (control: 0.72 ± 0.12; sepsis: 0.34 ± 0.04%/h, P = 0.006). We also found that FSR was unchanged in ileum and muscle, whereas it was higher in the liver (control: 0.87 ± 0.05; sepsis: 1.05 ± 0.06%/h, P = 0.041). Our data, obtained with a translational acute sepsis model, suggest that jejunal mucosal protein metabolism is diminished in acute sepsis. Comparison with other tissues indicates that the most serious acute metabolic changes in sepsis occur in the jejunum rather than the muscle. NEW & NOTEWORTHY In a highly translational acute sepsis model, presented data suggest that jejunal mucosal protein metabolism is diminished in acute sepsis, even if the origin of the sepsis is not located in the gut. Comparison with other tissues indicates that the most serious acute changes in the protein synthesis rates in sepsis occur in the gut rather than the muscle. Therefore, we hypothesize that preventing a compromised gut is critical to maintain gut function during sepsis.
Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci
Authors: Xu Maria M. , Ménoret Antoine , Nicholas Sarah-Anne E. , Günther Sebastian , Sundberg Eric J. , Zhou Beiyan , Rodriguez Annabelle , Murphy Patrick A. , Vella Anthony T. 
Published: April 2019

Effector CD8 T cells infiltrate atherosclerotic lesions and are correlated with cardiovascular events, but the mechanisms regulating their recruitment and retention are not well understood. CD137 (4–1BB) is a costimulatory receptor induced on immune cells and expressed at sites of human atherosclerotic plaque. Genetic variants associated with decreased CD137 expression correlate with carotid-intimal thickness and its deficiency in animal models attenuates atherosclerosis. These effects have been attributed in part to endothelial responses to low and disturbed flow (LDF), but CD137 also generates robust effector CD8 T cells as a costimulatory signal. Thus, we asked whether CD8 T cell-specific CD137 stimulation contributes to their infiltration, retention, and IFNγ production in early atherogenesis. We tested this through adoptive transfer of CD8 T cells into recipient C57BL/6J mice that were then antigen primed and CD137 costimulated. We analyzed atherogenic LDF vessels in normolipidemic and PCSK9-mediated hyperlipidemic models and utilized a digestion protocol that allowed for lesional T-cell characterization via flow cytometry and in vitro stimulation. We found that CD137 activation, specifically of effector CD8 T cells, triggers their intimal infiltration into LDF vessels and promotes a persistent innate-like proinflammatory program. Residence of CD137+ effector CD8 T cells further promoted infiltration of endogenous CD8 T cells with IFNγ-producing potential, whereas CD137-deficient CD8 T cells exhibited impaired vessel infiltration, minimal IFNγ production, and reduced infiltration of endogenous CD8 T cells. Our studies thus provide novel insight into how CD137 costimulation of effector T cells, independent of plaque-antigen recognition, instigates their retention and promotes innate-like responses from immune infiltrates within atherogenic foci. NEW & NOTEWORTHY Our studies identify CD137 costimulation as a stimulus for effector CD8 T-cell infiltration and persistence within atherogenic foci, regardless of atherosclerotic-antigen recognition. These costimulated effector cells, which are generated in pathological states such as viral infection and autoimmunity, have innate-like proinflammatory programs in circulation and within the atherosclerotic microenvironment, providing mechanistic context for clinical correlations of cardiovascular morbidity with increased CD8 T-cell infiltration and markers of activation in the absence of established antigen specificity. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/effector-cd8-t-cells-seed-atherogenic-foci/ .
Noncanonical TGFβ Pathway Relieves the Blockade of IL1β/TGFβ-Mediated Crosstalk between Tumor and Stroma: TGFBR1 and TAK1 Inhibition in Colorectal Cancer
Authors: Guillén Díaz-Maroto Natalia , Sanz-Pamplona Rebeca , Berdiel-Acer Mireia , Cimas Francisco J. , García Elena , Gonçalves-Ribeiro Samuel , Albert Nerea , Garcia-Vicién Gemma , Capella Gabriel , Moreno Victor , Salazar Ramon , Villanueva Alberto , Molleví David G. 
Published: April 2019

AbstractPurpose:The aim of the study is blocking the recruitment of a protective stroma by altering the crosstalk between normal stromal cells and tumor cells for stripping tumors of the protection conferred by the microenvironment.Experimental Design:A transcriptomic analysis of cocultured normal colonic fibroblasts and colorectal tumor cells was performed. We focused on the study of molecules that mediate the communication between both compartments and that entail fibroblasts’ activation and the alteration of the sensitivity to chemotherapy. We identified targets for the blocking of the tumor–stroma interaction. Finally, we tested, in vivo, the blockade of the tumor–stroma interaction in orthotopic models derived from patients and in models of acquired resistance to oxaliplatin.Results:IL1β/TGFβ1 are the triggers for fibroblasts’ recruitment and conversion into carcinoma-associated fibroblasts (CAF) in colorectal cancer. CAFs then secrete proinflammatory factors that alter sensitivity in tumor cells, activating JAK/STAT and PI3KCA/AKT pathways. Blocking such crosstalk with a neutralizing IL1β antibody and a TGFBR1 inhibitor is relieved by the TAK1-mediated activation of the noncanonical TGFβ pathway, which induces a change in the cytokine/chemokine repertoire that maintains a sustained activation of AKT in tumor cells. TAK1 plus TGFBR1 inhibition blocks IL1β/TGFβ1-mediated fibroblast activation, decreasing the secretion of proinflammatory cytokines. In turn, tumor cells became more sensitive to chemotherapy. In vivo, the combination of a TAK1 inhibitor plus TGFBR1 inhibitor reduced the metastatic capacity of tumor cells and the recruitment of fibroblasts.Conclusions:Our findings provide a translational rationale for the inhibition of TAK1 and TGFBR1 to remove the chemoprotection conferred by CAFs.
oXiris® Use in Septic Shock: Experience of Two French Centres
Authors: Schwindenhammer Victor , Girardot Thibaut , Chaulier Kevin , Grégoire Arnaud , Monard Céline , Huriaux Laetitia , Illinger Julien , Leray Véronique , Uberti Thomas , Crozon-Clauzel Jullien , Rimmelé Thomas 
Published: April 2019

<b><i>Background:</i></b> Sepsis is a dysregulated host response to an infection and can result in organ dysfunctions and death. Extracorporeal blood purification techniques aim to improve the prognosis of these patients by modulating the unbalanced immune response. This study reports our experience with the use of the oXiris® membrane for septic shock patients requiring continuous renal replacement therapy (CRRT). <b><i>Summary:</i></b> Thirty-one patients were diagnosed with septic shock and underwent CRRT with the oXiris® membrane between 2014 and 2019. We compared the observed hospital mortality with that predicted by the Simplified Acute Physiology Score II (SAPS II). Change in the Sequential Organ Failure Assessment (SOFA) score and of the main clinical and biological parameters over time were analyzed. Hospital mortality was lower than predicted for the most severe patients (60 vs. 91% for the [74–87] SAPS II quartile and 70 vs. 98% for the [87–163] SAPS II quartile, <i>p</i> &#x3c; 0.02). There was no significant improvement in the SOFA score from 0h to 48 h. An 88% relative decrease in norepinephrine infusion was observed (median at 0 h was 1.69 [0.52–2.45] µg/kg/min; at 48 h it was 0.20 [0.09–1.14] µg/kg/min, <i>p</i> = 0.002). Lactataemia and pH were significantly improved over time. Patients with intra-abdominal sepsis as well as those with Gram-negative bacilli (GNB) infections seemed to benefit the most from the therapy. <b><i>Key Messages:</i></b> CRRT with the oXiris® haemofilter resulted in higher observed survival than predicted by a severity score (SAPS II) for the most severe patients. Haemodynamic status and lactataemia appeared to improve, especially in intra-abdominal sepsis and GNB infections.
Оптимізація фіксації сітчастого імплантату при трансабдомінальній преперитонеальній алопластиці у хворих на пахвинну грижу
Authors: Feleshtinsky Ya. P. , Kokhanevich A. V. 
Published: April 2019

Мета роботи: підвищити ефективність трансабдомінальної преперитонеальної алопластики (ТАРР) у хворих на пахвинну грижу шляхом оптимізації фіксації сітчастого імплантату.
Матеріали і методи. За період від 2010 по 2017 р. прооперовано 178 хворих на пахвинну грижу з використанням класичної та удосконаленої ТАРР. Залежно від методики ТАРР хворих розділили на дві групи. У І групі (89 хворих) виконували класичну методику ТАРР. В ІІ групі (89 хворих) за розробленим нами способом ТАРР із комбінованою фіксацією сітчастого імлантату (патент на корисну модель №113997 від 27.02.2017р.).
Результати досліджень та їх обговорення. Безпосередні результати показали: у 6 хворих (6,7 %) І групи спостерігався виражений післяопераційний біль, в ІІ групі в 1 хворого (1,1 %). У хворих І групи серома передочеревинного простору пахвинної ділянки виникла – у 5 пацієнтів (5,6 %), у ІІ групі – у 4 пацієнтів (4,5 %). Гематома калитки у І групі спостерігалася у 2 хворих (2,2 %), а у ІІ групі – у 3 пацієнтів (3,4 %). Віддаленні результати лікування: І група (81 хворий) – хронічний післяопераційний пахвинний біль спостерігався у 5 (6,1%), ІІ група (82 хворих) – у 2 (2,73 %). У 7 (8,6 %) хворих І групи (81 хворий) виявлено рецидив пахвинної грижі. ІІ група (82 хворих) – рецидив пахвинної грижі виявлено в одного хворого (1,2 %).
Порівняльна оцінка ефективності розробленого одномоментного лапароскопічного лікування жовчнокам’яної хвороби та супутньої хірургічної патології
Authors: Nechytailo M. Yu. , Halei M. M. , Dziubanovskyi O. I. 
Published: April 2019

Мета роботи: визначити максимально ефективну технологію візуалізації при виконанні лапароскопічного операційного лікування жовчнокам’яної хвороби та супутньої хірургічної патології.
Матеріали і методи. Використано статистичні дані щодо лікування 411 хворих із ЖКХ та супутньою хірургічною патологією. Для обробки статистики використовували методи з нульовою гіпотезою. Для порівняння визначали зону візуалізації. Для порівняння взято власний метод і французький метод виконання лапароскопічної холецистектомії.
Результати досліджень та їх обговорення. За результатами дослідження встановлено, що оцінене маргінальне середнє значення площі зони візуалізації при власному способі симультанних операційних втручань становить (15,24±3,76) см2 і більше на 62,6 % від відповідного показника французького способу – (9,54±2,27) см2 (р=0,715); при застосуванні лапароскопа з кутом спостереження 0 о відстань наближення лапароскопа при власному способі доступу в середньому становить (3,81±0,52) см і більше на 10,5 % порівняно з середнім значенням досліджуваного параметра при французькому способі (3,41±0,478) см (р=0,295); при застосуванні лапароскопа з кутом спостереження 30 о відстань наближення лапароскопа при власному способі доступу в середньому становить (3,64±0,36) см і більше на 9,12 % порівняно з показником французького способу – (3,34±0,728) см (р<0,001).
Селекція отриманої студентами медичного факультету наукової інформації для окреслення смислового поля основних поданих позицій
Authors: Matskevych V. M. , Solomchak D. B. 
Published: April 2019

Мета роботы: визначення вправності пошуку літературних джерел із вибором відомостей, які мають оптимальну доказову базу, та здатності до виокремлення квінтесенції наукового повідомлення з подальшим розвитком аналітичного мислення у студентів факультетів природничих наук.
Матеріали і методи. Протягом 2016–2018 рр. у дослідженні брали участь 80 студентів медичного факультету, яким було дано тему для пошуку та опрацювання з встановленням найінформативніших матеріалів у межах встановленого часу, визначення семантичного поля статті, критичної оцінки тексту та написанні власного рейтингу опрацьованих статей згідно з наявною доказовою базою. Вивчено кількість опрацьованих статей респондентами, витрату продуктивного часу на матеріал, який опосередковано належить до пошукового запиту, правильність вибору квінтесенції текстів, визначення компонентів емпіричного циклу наукових досліджень.
Результати досліджень та їх обговорення. Протягом відведеного часу 42,5 % анкетованих осіб опрацювали 10 і більше статей, 51,25 % – від 5 до 9 статей, 6,25 % – від 1 до 4 статей. Щодо заданих ключових слів у пошукових запитах, то 7,5 % студентів відвели близько третини часу на розгляд інформації, яка не була пов’язана з конкретним запитанням. З правильним вибором квінтесенції текстів справились 57 студентів (71,25 %). Визначили компоненти емпіричного циклу 24 особи (30 %).
Weakened Potential Vorticity Barrier Linked to Recent Winter Arctic Sea Ice Loss and Midlatitude Cold Extremes
Authors: Luo Dehai , Chen Xiaodan , Overland James , Simmonds Ian , Wu Yutian , Zhang Pengfei 
Published: April 2019

AbstractA winter Eurasian cooling trend and a large decline of winter sea ice concentration (SIC) in the Barents–Kara Seas (BKS) are striking features of recent climate changes. The question arises as to what extent these phenomena are related. A mechanism is presented that establishes a link between recent winter SIC decline and midlatitude cold extremes. Such potential weather linkages are mediated by whether there is a weak north–south gradient of background tropospheric potential vorticity (PV). A strong background PV gradient, which usually occurs in North Atlantic and Pacific Ocean midlatitudes, acts as a barrier that inhibits atmospheric blocking and southward cold air intrusion. Conversely, atmospheric blocking is more persistent in weakened PV gradient regions over Eurasia, Greenland, and northwestern North America because of weakened energy dispersion and intensified nonlinearity. The small climatological PV gradients over mid- to high-latitude Eurasia have become weaker in recent decades as BKS air temperatures show positive trends due to SIC loss, and this has led to more persistent high-latitude Ural-region blocking. These factors contribute to increased cold winter trend in East Asia. It is found, however, that in years when the winter PV gradient is small the East Asian cold extremes can even occur in the absence of large negative SIC anomalies. Thus, the magnitude of background PV gradient is an important controller of Arctic–midlatitude weather linkages, but it plays no role if Ural blocking is not present. Thus, the “PV barrier” concept presents a critical insight into the mechanism producing cold Eurasian extremes and is hypothesized to set up such Arctic–midlatitude linkages in other locations.
Role of Stochastic Atmospheric Forcing from the South and North Pacific in Tropical Pacific Decadal Variability
Authors: Sun Tianyi , Okumura Yuko M. 
Published: April 2019

Abstract
Stochastic variability of internal atmospheric modes, known as teleconnection patterns, drives large-scale patterns of low-frequency SST variability in the extratropics. To investigate how the decadal component of this stochastically driven variability in the South and North Pacific affects the tropical Pacific and contributes to the observed basinwide pattern of decadal variability, a suite of climate model experiments was conducted. In these experiments, the models are forced with constant surface heat flux anomalies associated with the decadal component of the dominant atmospheric modes, particularly the Pacific–South American (PSA) and North Pacific Oscillation (NPO) patterns. Both the PSA and NPO modes induce basinwide SST anomalies in the tropical Pacific and beyond that resemble the observed interdecadal Pacific oscillation. The subtropical SST anomalies forced by the PSA and NPO modes propagate to the equatorial Pacific mainly through the wind–evaporation–SST feedback. This atmospheric bridge is stronger from the South Pacific than the North Pacific due to the northward displacement of the intertropical convergence zone and the associated northward advection of momentum anomalies. The equatorial ocean dynamics is also more strongly influenced by atmospheric circulation changes induced by the PSA mode than the NPO mode. In the PSA experiment, persistent and zonally coherent wind stress curl anomalies over the South Pacific affect the zonal mean depth of the equatorial thermocline and weaken the equatorial SST anomalies resulting from the atmospheric bridge. This oceanic adjustment serves as a delayed negative feedback and may be important for setting the time scales of tropical Pacific decadal variability.
An Evaluation of Simulated Precipitation Characteristics during OLYMPEX
Authors: Conrick Robert , Mass Clifford F. 
Published: April 2019

Abstract
The OLYMPEX field campaign, which took place around the Olympic Mountains of Washington State during winter 2015/16, provided data for evaluating the simulated microphysics and precipitation over and near that barrier. Using OLYMPEX observations, this paper assesses precipitation and associated microphysics in the WRF-ARW model over the U.S. Pacific Northwest. Model precipitation from the University of Washington real-time WRF forecast system during the OLYMPEX field program (November 2015–February 2016) and an extended period (2008–18) showed persistent underprediction of precipitation, reaching 100 mm yr−1 over the windward side of the coastal terrain. Increasing horizontal resolution does not substantially reduce this underprediction. Evaluating surface disdrometer observations during the 2015/16 OLYMPEX winter, it was found that the operational University of Washington WRF modeling system using Thompson microphysics poorly simulated the rain drop size distribution over a windward coastal valley. Although liquid water content was represented realistically, drop diameters were overpredicted, and, consequently, the rain drop distribution intercept parameter was underpredicted. During two heavy precipitation periods, WRF realistically simulated environmental conditions, including wind speed, thermodynamic structures, integrated moisture transport, and melting levels. Several microphysical parameterization schemes were tested in addition to the Thompson scheme, with each exhibiting similar biases for these two events. We show that the parameterization of aerosols over the coastal Northwest offered only minor improvement.
Some New Aspects of the Joint Effect of Rotation and Topography on Internal Solitary Waves
Authors: Ostrovsky Lev A. , Helfrich Karl R. 
Published: April 2019

AbstractUsing a recently developed asymptotic theory of internal solitary wave propagation over a sloping bottom in a rotating ocean, some new qualitative and quantitative features of this process are analyzed for internal waves in a two-layer ocean. The interplay between different singularities—terminal damping due to radiation and disappearing quadratic nonlinearity, and reaching an “internal beach” (e.g., zero lower-layer depth)—is discussed. Examples of the adiabatic evolution of a single solitary wave over a uniformly sloping bottom under realistic conditions are considered in more detail and compared with numerical solutions of the variable-coefficient, rotation-modified Korteweg–de Vries (rKdV) equation.