bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salicylates Ameliorate Intestinal Inflammation by Activating Macrophage AMPK
Authors: Banskota Suhrid , Wang Huaqing , Kwon Yun Han , Gautam Jaya , Gurung Pallavi , Haq Sabah , Hassan F M Nazmul , Bowdish Dawn M , Kim Jung-Ae , Carling David , Fullerton Morgan D , Steinberg Gregory R , Khan Waliul I 
Published: November 2020

AbstractBackgroundInflammatory bowel diseases are the most common chronic intestinal inflammatory conditions, and their incidence has shown a dramatic increase in recent decades. Limited efficacy and questionable safety profiles with existing therapies suggest the need for better targeting of therapeutic strategies. Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of cellular metabolism and has been implicated in intestinal inflammation. Macrophages execute an important role in the generation of intestinal inflammation. Impaired AMPK in macrophages has been shown to be associated with higher production of proinflammatory cytokines; however, the role of macrophage AMPK in intestinal inflammation and the mechanism by which it regulates inflammation remain to be determined. In this study, we investigated the role of AMPK with a specific focus on macrophages in the pathogenesis of intestinal inflammation.MethodsA dextran sodium sulfate-induced colitis model was used to assess the disease activity index, histological scores, macroscopic scores, and myeloperoxidase level. Proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β were measured by enzyme-linked immunosorbent assay. Transient transfection of AMPKβ1 and LC3-II siRNA in RAW 264.7 cells was performed to elucidate the regulation of autophagy by AMPK. The expression of p-AMPK, AMPK, and autophagy markers (eg, LC3-II, p62, Beclin-1, and Atg-12) was analyzed by Western blot.ResultsGenetic deletion of AMPKβ1 in macrophages upregulated the production of proinflammatory cytokines, aggravated the severity of dextran sodium sulfate-induced colitis in mice, which was associated with an increased nuclear translocation of nuclear factor-κB, and impaired autophagy both in vitro and in vivo. Notably, the commonly used anti-inflammatory 5-aminosalicylic acid (ie, mesalazine) and sodium salicylate ameliorated dextran sodium sulfate-induced colitis through the activation of macrophage AMPK targeting the β1 subunit.ConclusionsTogether, these data suggest that the development of therapeutic agents targeting AMPKβ1 may be effective in the treatment of intestinal inflammatory conditions including inflammatory bowel disease.
Reflection on modern methods: demystifying robust standard errors for epidemiologists
Authors: Mansournia Mohammad Ali , Nazemipour Maryam , Naimi Ashley I , Collins Gary S , Campbell Michael J 
Published: November 2020

AbstractAll statistical estimates from data have uncertainty due to sampling variability. A standard error is one measure of uncertainty of a sample estimate (such as the mean of a set of observations or a regression coefficient). Standard errors are usually calculated based on assumptions underpinning the statistical model used in the estimation. However, there are situations in which some assumptions of the statistical model including the variance or covariance of the outcome across observations are violated, which leads to biased standard errors. One simple remedy is to use robust standard errors, which are robust to violations of certain assumptions of the statistical model. Robust standard errors are frequently used in clinical papers (e.g. to account for clustering of observations), although the underlying concepts behind robust standard errors and when to use them are often not well understood. In this paper, we demystify robust standard errors using several worked examples in simple situations in which model assumptions involving the variance or covariance of the outcome are misspecified. These are: (i) when the observed variances are different, (ii) when the variance specified in the model is wrong and (iii) when the assumption of independence is wrong.
Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression
Authors: Rivas-Grajales Ana Maria , Salas Ramiro , Robinson Meghan E , Qi Karen , Murrough James W , Mathew Sanjay J 
Published: November 2020

AbstractBackgroundKetamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor–dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.MethodsResting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.ResultsA reduction in Montgomery–Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P &lt; .0001, FDR-corrected), right temporal pole (t = 4.97, P &lt; .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.ConclusionsThese preliminary results suggest that the Hb might be involved in ketamine’s antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.
Translational Assessments of Reward Responsiveness in the Marmoset
Authors: Wooldridge Lisa M , Bergman Jack , Pizzagalli Diego A , Kangas Brian D 
Published: November 2020

Abstract

Background
Anhedonia, the loss of pleasure in previously rewarding activities, is a prominent feature of major depressive disorder and often resistant to first-line antidepressant treatment. A paucity of translatable cross-species tasks to assess subdomains of anhedonia, including reward learning, presents a major obstacle to the development of effective therapeutics. One assay of reward learning characterized by orderly behavioral and pharmacological findings in both humans and rats is the probabilistic reward task. In this computerized task, subjects make discriminations across numerous trials in which correct responses to one alternative are rewarded more often (rich) than correct responses to the other (lean). Healthy control subjects reliably develop a response bias to the rich alternative. However, participants with major depressive disorder as well as rats exposed to chronic stress typically exhibit a blunted response bias.

Methods
The present studies validated a touchscreen-based probabilistic reward task for the marmoset, a small nonhuman primate with considerable translational value. First, probabilistic reinforcement contingencies were parametrically examined. Next, the effects of ketamine (1.0–10.0 mg/kg), a US Food and Drug Administration-approved rapid-acting antidepressant, and phencyclidine (0.01–0.1 mg/kg), a pharmacologically similar N-methyl-D-aspartate receptor antagonist with no known antidepressant efficacy, were evaluated.

Results
Increases in the asymmetry of rich:lean probabilistic contingencies produced orderly increases in response bias. Consistent with their respective clinical profiles, ketamine but not phencyclidine produced dose-related increases in response bias at doses that did not reduce task discriminability.

Conclusions
Collectively, these findings confirm task and pharmacological sensitivity in the marmoset, which may be useful in developing medications to counter anhedonia across neuropsychiatric disorders.
251 Evaluation of Condensed Algal Residue Solubles as an Ingredient in Cattle Finishing Diets
Authors: Gibbons Calvin , Watson Andrea K , Erickson Galen E , Boyd Bradley M , McPhillips Levi J , Wilson Hannah C , Wilson Jonathan W 
Published: November 2020

Abstract
Algae oil production for Omega-3 fatty acid supplementation yields a byproduct called Condensed Algal Residue Solubles (CARS; 25.4% DM, 19.3% CP, 8.3% Fat, 9.96% Na on DM basis), de-oiled algae cells with residual fermentation substrates. This study evaluated the use of CARS in feedlot finishing diets. Crossbreed steers, (n=480) were blocked and stratified by initial body weight (BW) into 4 blocks, and assigned randomly to treatments. Treatments were designed as a 2 x 3 factorial with 3 inclusions of CARS (0, 2.5, 5% of diet DM) and 2 different base diets representing Northern and Southern Great Plains diets. The Southern diets contained steam flaked corn and dry distillers grains while the Northern diets had dry rolled and high moisture corn with wet distillers grains. CARS replaced corn in both diets. All blocks were harvested after 148 days on feed. Performance data were analyzed as a randomized block design with CARS inclusion, base diet, and interactions as fixed effects, BW block as a random effect and pen (n=48) as the experimental unit. Orthogonal contrasts were used to test linear and quadratic effects of CARS inclusion. There were no significant interactions between CARS inclusion and diet type (P ≥ 0.49). Main effects of CARS indicated positive quadratic responses for carcass adjusted ADG, G:F, 12th rib back fat, yield grade (P &lt; 0.01; increasing to 2.5% inclusion, decreasing at 5%) and hot carcass weight was both linear and quadratic (P ≤ 0.01 and P ≥ 0.06 respectively; 969, 977, 935 as CARS increased). Linear decrease in DMI, final adjusted BW and ribeye area (P ≤ 0.01) as CARS increased. Cattle fed the Southern diets had greater ADG and G:F compared to Northern diets (P &lt; 0.01). Including 2.5% CARS in the diet improved feed efficiency in both Northern and Southern based feedlot diets.
369 Amino acid nutrition in monogastrics: going beyond the ideal protein
Authors: Htoo John K 
Published: November 2020

Abstract
In addition to serving as building blocks for protein synthesis, AA are also involved in various important metabolic pathways in the body. Amino acids that regulates key metabolic pathways to improve health, growth, development and reproduction are considered as functional AA. The roles of AA for immune function have received more attention in recent years. Methionine serves as a methyl donor for important processes such as DNA methylation, polyamine synthesis and is a precursor to form Cys, which is needed for the synthesis of a major antioxidant glutathione. Tryptophan is involved in various metabolic pathways, including immune response and the formation of serotonin which involves in feed intake regulation. Threonine plays a key role in immune function through its incorporation into immunoglobulins and is preferentially utilized by the gut in pigs partly for synthesis of mucosal proteins including mucins which are high in Thr. The branched-chain amino acids (Leu, Val, Ile) are involved in maintaining intestinal barrier function, enterocyte proliferation and immune defenses in pigs. The other functional AA include Gln, Arg and Gly which are involved in immune system functioning and gut health. During sub-clinical level of diseases or inflammation, nutrients are prioritized to form tissues involved in immune response compromising growth, implying that the requirement of some key AA is increased to maintain immune function. Adjusting the ideal ratio of these functional AA to Lys in diets may maintain gut health and promote growth, because it can enhance immune status and gut integrity for weaned pigs, especially when sanitary and climatic conditions are challenging, and antibiotics are not or less used in the diets. Future research is warranted to quantitatively estimate the increased need of these functional AA in pigs raised under sub-optimal conditions as well as evaluate the interaction or synergistic effect of these AA on animals’ immunity.
425 Effects of pre-mortem stress on protein expression, steak color, and myofibrillar fragmentation index in the longissimus lumborum following harvest
Authors: Briggs Reganne K , Legako Jerrad F , Broadway Paul R , Carroll Jeff A , Burdick-Sanchez Nicole C , Smith Zachary K , Thornton Kara J , Ramanathan Ranjith 
Published: November 2020

Abstract
Undesirable variation in beef tenderness and stability of flavor and color may be associated with the abundance of heat shock proteins (HSP). This study aimed to determine whether pre-mortem stress impacts HSP expression in the skeletal muscle following harvest. Forty Holstein steers were administered an i.v. bolus dose of adrenocorticotropic hormone (ACTH; 0.1 IU/Kg BW) to mimic an acute pre-mortem stress. Longissimus lumborum (LD) biopsy samples were taken prior to the ACTH challenge. Serum cortisol was measured every 0.5 h from -2 to 6 h relative to the ACTH challenge. Skeletal muscle and blood samples from 10 steers were collected at each harvest timepoint at (2, 12, 24 and 48 h post-challenge). Samples were collected from the LD immediately after harvest and after 14 d of aging. Protein expression of HSPβ1, P-HSPβ1, HSPβ5, and DJ-1 was analyzed in muscle samples taken prior to the ACTH challenge, at harvest, and after 14 d of post-mortem wet aging. In addition, steak color and myofibrillar fragmentation index (MFI) was analyzed in 14 d aged samples. Harvest time point following the ACTH challenge affected (P &lt; 0.05) protein expression of HSPβ1 and P-HSPβ1. Protein expression of DJ-1 prior to the ACTH challenge was different (P &lt; 0.05) among steers harvested at different timepoints. In addition, time of harvest had no effect on HSPβ5 expression (P &gt; 0.05). Regarding steak color, time of harvest had an effect (P &lt; 0.01) on a*, b*, hue, chroma, and ratio, but no effect (P &gt; 0.05) on L*. Lastly, time of harvest had an effect (P &lt; 0.05) on MFI. These data indicate that HSP expression, steak color, and MFI in the LD after harvest may be related to time of harvest following a stressful event pre-mortem.
Port site hernia repair using the VersaOne™ Fascial Closure System: a case report
Authors: Hagui Emi , Kimura Masahiro , Katada Takeyasu , Nagasaki Takaya , Nakaya Seiichi , Eguchi Yuki , Sugita Saburo , Sawai Misato , Kuwabara Yoshiyuki , Mitsui Akira 
Published: November 2020

Abstract
The use of laparoscopic surgery has become widespread in recent years. One of its complications is port site hernia (PHS). It can be difficult to close the fascia at the time of laparoscopy, especially in obese patients, and there is a risk of herniation through a fascial defect with incomplete closure. It is important to ascertain closure of the defect when repairing PHS to prevent recurrence. We report a 47-year-old woman who developed a PHS at the superior aspect of the umbilicus. We repaired the defect using the VersaOneTM Fascial Closure System with laparoscopic guidance. This system allows the port site to be reliably closed while observing the suture from the abdominal cavity. The incision is the same size as a port site. If the abdominal wall is thick and the PHS has a diameter of ~10 mm, this method is considered to be indicated, regardless of the site.
The Central Benzodiazepine Receptor
Authors: Ossipov Michael H. 
Published: November 2020

Abstract
Benzodiazepines have been used clinically now for more than a half century for the management of anxiety and other conditions. Despite their widespread use, only now are their mechanisms of action and their pharmacologic implications, especially with long-term use, beginning to be appreciated. In the central nervous system, benzodiazepines act on an allosteric site of the GABAA receptor to enhance the activity of this inhibitory neurotransmitter. The GABA receptor consists of 5 subunits, which can vary among 19 different subtypes, resulting in a large number of possible configurations for the GABA receptor. Subunit structure can affect the binding of benzodiazepines to the receptor and can alter the nature of the interaction between the benzodiazepine binding site and the GABA binding site, resulting in different levels of receptor activation and allosteric enhancement. Moreover, the distribution of these different subtypes within the central nervous system, with their varying levels of benzodiazepine efficacy, can mean that benzodiazepines can have differential effects among the different sites of the brain. Consequently, in may be possible to design novel drugs that favor particular subunit configurations and thus produce different pharmacologic profiles. Drugs acting at the benzodiazepine site can be agonists, enhancing the activity of GABA; antagonists, blocking the effect of benzodiazepines at the binding site; or inverse agonists, producing an effect antipodal to that of benzodiazepine agonists.
Benzodiazepines Today and Tomorrow
Authors: Coleman John J. 
Published: November 2020

Abstract
Benzodiazepines (BZDs) and related drugs are widely used for treating a variety of conditions (with varying degrees of evidence-base), but their long-term use (more than 2–4 weeks) can be problematic. They were originally thought (or claimed) to be nonproblematic substitutes for barbiturates, but it is now clear that they have their own set of problems. In addition, they are commonly, albeit ill-advisedly, co-prescribed or used nonmedically in combination with other drug substances. The result of such combinations, particularly with the opioids, can be lethal. Administrative and statutory actions notwithstanding, it appears that reducing problems with BZDs will depend on a comprehensive approach that includes improved education for patients, prescribers, regulators, insurers, and the public. First and foremost, however, there is a pressing need for the government to improve its drug-abuse data collection, specifically how it monitors drug-related morbidity and mortality. This chapter reviews the information that demonstrates how an understanding of all of the dynamics is essential for designing effective public-health strategies to reduce BZD-associated problems.
Testing physical models for cosmic ray transport coefficients on galactic scales: self-confinement and extrinsic turbulence at ∼GeV energies
Authors: Hopkins Philip F , Squire Jonathan , Chan T K , Quataert Eliot , Ji Suoqing , Kereš Dušan , Faucher-Giguère Claude-André 
Published: November 2020

ABSTRACT
The microphysics of ∼ GeV cosmic ray (CR) transport on galactic scales remain deeply uncertain, with almost all studies adopting simple prescriptions (e.g. constant diffusivity). We explore different physically motivated, anisotropic, dynamical CR transport scalings in high-resolution cosmological Feedback In Realistic Environment (FIRE) simulations of dwarf and ∼L* galaxies where scattering rates vary with local plasma properties motivated by extrinsic turbulence (ET) or self-confinement (SC) scenarios, with varying assumptions about e.g. turbulent power spectra on un-resolved scales, Alfvén-wave damping, etc. We self-consistently predict observables including γ-rays (Lγ), grammage, residence times, and CR energy densities to constrain the models. We demonstrate many non-linear dynamical effects (not captured in simpler models) tend to enhance confinement. For example, in multiphase media, even allowing arbitrary fast transport in neutral gas does not substantially reduce CR residence times (or Lγ), as transport is rate-limited by the ionized WIM and ‘inner CGM’ gaseous halo (104–106 K gas within $\lesssim 10\!-\!30\,$ kpc), and Lγ can be dominated by trapping in small ‘patches’. Most physical ET models contribute negligible scattering of ∼1–10 GeV CRs, but it is crucial to account for anisotropy and damping (especially of fast modes) or else scattering rates would violate observations. We show that the most widely assumed scalings for SC models produce excessive confinement by factors ≳100 in the warm ionized medium (WIM) and inner CGM, where turbulent and Landau damping dominate. This suggests either a breakdown of quasi-linear theory used to derive the CR transport parameters in SC, or that other novel damping mechanisms dominate in intermediate-density ionized gas.
Low-luminosity Type II supernovae – III. SN 2018hwm, a faint event with an unusually long plateau
Authors: Reguitti A , Pumo M L , Mazzali P A , Pastorello A , Pignata G , Elias-Rosa N , Prentice S J , Reynolds T , Benetti S , Rodrìguez O , Mattila S , Kuncarayakti H 
Published: November 2020

ABSTRACT
In this work, we present photometric and spectroscopic data of the low-luminosity (LL) Type IIP supernova (SN) 2018hwm. The object shows a faint (Mr = −15 mag) and very long (∼130 d) plateau, followed by a 2.7 mag drop in the r band to the radioactive tail. The first spectrum shows a blue continuum with narrow Balmer lines, while during the plateau the spectra show numerous metal lines, all with strong and narrow P-Cygni profiles. The expansion velocities are low, in the 1000–1400 km s−1 range. The nebular spectrum, dominated by H α in emission, reveals weak emission from [O i] and [Ca ii] doublets. The absolute light curve and spectra at different phases are similar to those of LL SNe IIP. We estimate that 0.002 M⊙ of 56Ni mass were ejected, through hydrodynamical simulations. The best fit of the model to the observed data is found for an extremely low explosion energy of 0.055 foe, a progenitor radius of 215 R⊙, and a final progenitor mass of 9–10 M⊙. Finally, we performed a modelling of the nebular spectrum, to establish the amount of oxygen and calcium ejected. We found a low M(16O)$\approx 0.02\, \mathrm{ M}_{\odot }$, but a high M(40Ca) of 0.3 M⊙. The inferred low explosion energy, the low ejected 56Ni mass, and the progenitor parameters, along with peculiar features observed in the nebular spectrum, are consistent with both an electron-capture SN explosion of a superasymptotic giant branch star and with a low-energy, Ni-poor iron core-collapse SN from a 10–12 M⊙ red supergiant.