bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short‐term interleukin‐37 treatment improves vascular endothelial function, endurance exercise capacity, and whole‐body glucose metabolism in old mice
Authors: Ballak Dov B. , Brunt Vienna E. , Sapinsley Zachary J. , Ziemba Brian P. , Richey James J. , Zigler Melanie C. , Johnson Lawrence C. , Gioscia‐Ryan Rachel A. , Culp‐Hill Rachel , Eisenmesser Elan Z. , D'Alessandro Angelo , Dinarello Charles A. , Seals Douglas R. 
Published: November 2019

AbstractAging is associated with vascular endothelial dysfunction, reduced exercise tolerance, and impaired whole‐body glucose metabolism. Interleukin‐37 (IL‐37), an anti‐inflammatory cytokine of the interleukin‐1 family, exerts salutary physiological effects in young mice independent of its inflammation‐suppressing properties. Here, we assess the efficacy of IL‐37 treatment for improving physiological function in older age. Old mice (26–28 months) received daily intraperitoneal injections of recombinant human IL‐37 (recIL‐37; 1 µg/200 ml PBS) or vehicle (200 ml PBS) for 10–14 days. Vascular endothelial function (ex vivo carotid artery dilation to increasing doses of acetylcholine, ACh) was enhanced in recIL‐37 vs. vehicle‐treated mice via increased nitric oxide (NO) bioavailability (all p < .05); this effect was accompanied by enhanced ACh‐stimulated NO production and reduced levels of reactive oxygen species in endothelial cells cultured with plasma from IL‐37‐treated animals (p < .05 vs. vehicle plasma). RecIL‐37 treatment increased endurance exercise capacity by 2.4‐fold, which was accompanied by a 2.9‐fold increase in the phosphorylated AMP‐activated kinase (AMPK) to AMPK ratio (i.e., AMPK activation) in quadriceps muscle. RecIL‐37 treatment also improved whole‐body insulin sensitivity and glucose tolerance (p < .05 vs. vehicle). Improvements in physiological function occurred without significant changes in plasma, aortic, and skeletal muscle pro‐inflammatory proteins (under resting conditions), whereas pro‐/anti‐inflammatory IL‐6 was greater in recIL‐37‐treated animals. Plasma metabolomics analysis revealed that recIL‐37 treatment altered metabolites related to pathways involved in NO synthesis (e.g., increased L‐arginine and citrulline/arginine ratio) and fatty acid metabolism (e.g., increased pantothenol and free fatty acids). Our findings provide experimental support for IL‐37 therapy as a novel strategy to improve diverse physiological functions in old age.
Molecular and geographical heterogeneity of hemoglobinopathy mutations in Azerbaijanian populations
Authors: Aliyeva Gunay , Asadov Chingiz , Mammadova Tahira , Gafarova Surmaya , Guliyeva Yegana , Abdulalimov Eldar 
Published: November 2019

AbstractWith the carrier rate of 4%–8.6%, β‐thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β‐thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Α‐ and β‐globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of β‐thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [–AA]–34.96%, IVS‐II‐1 [G > A]–16.35%, and IVS‐I‐110 [G > A]–10.12% leading the spectrum. Analysis of associations of β‐thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [–AA] and Shaki‐Zaqatala, and codon 5 [–CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD‐Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with β‐thalassemia than in the homozygous state. We identified nine α‐thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α‐thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.
Toll‐like receptor 4 polymorphisms were associated with low serum pro‐inflammatory cytokines in BCG osteitis survivors
Authors: Korppi Matti , Teräsjärvi Johanna , Lauhkonen Eero , Huhtala Heini , Nuolivirta Kirsi , He Qiushui 
Published: November 2019

AbstractAimThe aim of the study was to evaluate the association of Toll‐like receptor 4 (TLR4) gene variations with osteitis risk after Bacillus Calmette‐Guérin (BCG) vaccination given at birth and with serum cytokine levels measured in adulthood.MethodsWe determined the TLR4 rs4986790 single‐nucleotide polymorphism (SNP) in 132 study subjects with BCG osteitis in infancy and compared the genotype distributions and allele frequencies between them and population controls. Serum concentrations of 11 cytokines measured in adulthood were compared between study subjects with the wild vs variant TLR4 rs4986790 genotype.ResultsThe genotypes and allele frequencies of the TLR4 rs4986790 SNP did not differ between BCG osteitis cases and population controls. Instead, subjects with the variant genotype presented with lower serum interleukin (IL) concentrations of the pro‐inflammatory IL‐6, IL‐17A and IL‐12 cytokines and with marginally lower interferon‐γ concentrations, but with higher serum anti‐inflammatory IL‐4 concentration. The results concern also the TLR4 rs4986791, since these two SNPs are co‐segregating in the Finnish population.ConclusionThe findings suggest that TLR4 has no significant role in the emergence of osteitis after newborn BCG vaccination, but the variant genotypes of the TLR4 rs4986790 and rs4986791 may impair the production of pro‐inflammatory cytokines.
Discovery of N‐(2‐(Benzylamino)‐2‐oxoethyl)benzamide analogs as a novel scaffold of pancreatic β‐cell protective agents against endoplasmic reticulum stress
Authors: Eeda Venkateswararao , Herlea‐Pana Oana , Lim Hui‐Ying , Wang Weidong 
Published: November 2019

AbstractEndoplasmic reticulum (ER) stress‐induced pancreatic β‐cell dysfunction and death play important roles in the development of diabetes. The 1,2,3‐triazole derivative 1 is one of only a few structures that have thus far been identified that protect β cells against ER stress. However, this compound has narrow activity range and limited aqueous solubility. To overcome these, we designed and synthesized a new scaffold in which the triazole pharmacophore was substituted with a glycine‐like amino acid. Structure–activity relationship studies on this scaffold identified a N‐(2‐(Benzylamino)‐2‐oxoethyl)benzamide analog WO5m that possesses β‐cell protective activity against ER stress with much improved potency (maximal activity at 100% with EC50 at 0.1 ± 0.01 µm) and water solubility. Identification of this novel β‐cell protective scaffold thus provides a new promising modality for the treatment of diabetes.
Treatment with a platelet‐activating factor receptor antagonist improves hemodynamics and reduces epinephrine requirements, in a lethal rodent model of anaphylactic shock
Authors: Tacquard Charles , Oulehri Walid , Collange Olivier , Garvey Lene H. , Nicoll Susan , Tuzin Nicolas , Geny Bernard , Mertes Paul M. 
Published: November 2019

AbstractBackgroundIn some cases, anaphylactic shock (AS) is still lethal, despite rapid use of epinephrine. High doses of epinephrine are associated with severe complications. Platelet‐activating factor (PAF) is secreted in massive amounts during AS, and a high plasma level is correlated with increased AS severity.ObjectiveTo assess the effect of ABT‐491, a PAF‐receptor antagonist and possible adjunct treatment, alone or in combination with epinephrine during AS.MethodsAS was induced by intravenous injection of 1 mg ovalbumin into ovalbumin‐sensitized rats. Rats were then randomly assigned to 5 groups (n = 10 per group): SHAM (vehicle only), SHOCK (no treatment), ABT (ABT‐491 1 mg/kg), EPI (epinephrine 5 µg as a bolus then 10 µg kg−1 min−1 by continuous infusion, followed by a reducing protocol) and EPI‐ABT (both treatments).ResultsOvalbumin injection resulted in a severe decrease in mean arterial pressure, left ventricular inotropy (max dP/dt) and left ventricular shortening fraction (LVSF). All rats from the ABT group survived until the end of the experiment. ABT‐491 prevented the LVSF decrease observed in the SHOCK group (at T15: ABT 50% ± 11% vs SHOCK 36% ± 9%, P = .01), significantly reduced the dose of epinephrine needed to treat anaphylactic shock (EPI‐ABT 314 ± 67 µg/kg vs EPI 475 ± 69 µg/kg, P < .001) and reduced the time to restore basal MAP (ABT 23 ± 7 minutes vs EPI‐ABT 13 ± 5 minutes, P < .01).Conclusions and Clinical RelevanceAS was characterized by early cardiac dysfunction in our model. Treatment with ABT‐491 allowed survival until the end of the experiment and reduced cardiac dysfunction. Use of the PAF‐R antagonist had a synergistic effect with epinephrine and allowed a significant reduction in epinephrine consumption. Use of PAF‐R antagonists during AS could reduce epinephrine‐related complications and improve the treatment of epinephrine refractory cases.
Flapless immediate implant placement and provisionalization in periodontal patients: A retrospective consecutive case‐series study of single‐tooth sites with dehiscence‐type osseous defects
Authors: Sicilia‐Felechosa Alberto , Pereira‐Fernández Adolfo , García‐Lareu Javier , Bernardo‐González Julio , Sicilia‐Blanco Pelayo , Cuesta‐Fernández Isabel 
Published: November 2019

AbstractObjectiveTo assess the clinical outcomes of flapless, immediate implant placement with simultaneous augmentation of dehiscence defects and immediate provisional restoration.Materials and MethodsRetrospective evaluation of 40 periodontal patients who received a flapless immediate implant for single‐tooth replacement with simultaneous augmentation of dehiscence defects and immediate provisional restoration, at follow‐up periods ranging from 1 year minimum to 7 years maximum. Dehiscence defects were augmented using autogenous bone grafts and/or deproteinized bovine bone mineral, and autogenous or allogeneic connective tissue grafts. The following aspects were evaluated: clinical success (Clinical Oral Implants Research, 8, 1997, 161), crestal bone loss (calibrated digital periapical X‐rays) and aesthetics (Pink Esthetic Score, PES). Additionally, a questionnaire was devised to obtain patient's subjective evaluation.ResultsA 98.3% (95% CI: 91%–99%) success rate was observed. At 8 weeks, mean bone loss was 0.47 mm (n = 39); between 8 weeks and 1 year, this va	lue attained 0.24 mm and between years 1 and 5 years 0.06 mm (n = 9). The evaluated PES in 37 single‐tooth implants was 12.4, with PES = 7 (aesthetic failures) in two cases, and aesthetic outcomes were excellent (PES ≥ 12) in 29 cases (78.4%). When compared with the contralateral tooth, a recession under 1 mm was observed in 78% of cases. The patient's subjective satisfaction value ranged from 98% to 100%.ConclusionThis type of minimally invasive treatment of alveoli with buccal plate deficiencies delivers, in the hands of an experienced clinician, a high clinical and aesthetic success percentage being rated by patients as satisfactory. Clinicians should be aware that 1–2 mm comparative recession could be observed.
Lactate reduces epileptiform activity through HCA1 and GIRK channel activation in rat subicular neurons in an in vitro model
Authors: Jorwal Pooja , Sikdar Sujit Kumar 
Published: November 2019

AbstractObjectiveMuch evidence suggests that the subiculum plays a significant role in the regulation of epileptic activity. Lactate acts as a neuroprotective agent against many conditions that cause brain damage. During epileptic seizures, lactate formation reaches up to ~6 mmol/L in the brain. We investigated the effect of lactate on subicular pyramidal neurons after induction of epileptiform activity using 4‐aminopyridine (4‐AP‐0Mg2+) in an in vitro epilepsy model in rats. The signaling mechanism associated with the suppression of epileptiform discharges by lactate was also investigated.MethodsWe used patch clamp electrophysiology recordings on rat subicular neurons of acute hippocampal slices. Immunohistochemistry was used for demonstrating the expression of hydroxycarboxylic acid receptor 1 (HCA1) in the subiculum.ResultsOur study showed that application of 6 mmol/L lactate after induction of epileptiform activity reduced spike frequency (control 2.5 ± 1.23 Hz vs lactate 1.01 ± 0.91 Hz,P = .049) and hyperpolarized the subicular neurons (control −51.8 ± 1.9 mV vs lactate −57.2 ± 3.56 mV,P = .002) in whole cell patch‐clamp experiments. After confirming the expression of HCA1 in subicular neurons, we demonstrated that lactate‐mediated effect occurs via HCA1 by using its specific agonist. All values are mean ±SD. Electrophysiological recordings revealed the involvement of Gβγ and intracellular cAMP in the lactate‐induced effect. Furthermore, current‐clamp and voltage‐clamp experiments showed that the G protein–coupled inwardly rectifying potassium (GIRK) channel blocker tertiapin‐Q, negated the lactate‐induced inhibitory effect, which confirmed that lactate application results in outward GIRK current.SignificanceOur finding points toward the potential role of lactate as an anticonvulsant by showing lactate‐induced suppression of epileptiform activity in subicular neurons. The study gives a different insight by suggesting importance of endogenous metabolite and associated signaling factors, which can aid in improving the present therapeutic approach for treating epilepsy.
Segregation of seizures and spreading depolarization across cortical layers
Authors: Zakharov Andrey , Chernova Kseniya , Burkhanova Gulshat , Holmes Gregory L. , Khazipov Roustem 
Published: November 2019

AbstractObjectiveCortical spreading depolarization (SD) and seizures are often co‐occurring electrophysiological phenomena. However, the cross‐layer dynamics of SD during seizures and the effect of SD on epileptic activity across cortical layers remain largely unknown.MethodsWe explored the spatial‐temporal dynamics of SD and epileptic activity across layers of the rat barrel cortex using direct current silicone probe recordings during flurothyl‐induced seizures.ResultsSD occurred in half of the flurothyl‐evoked seizures. SD always started from the superficial layers and spread downward either through all cortical layers or stopping at the L4/L5 border. In cases without SD, seizures were characterized by synchronized population firing across all cortical layers throughout the entire seizure. However, when SD occurred, epileptic activity was transiently silenced in layers involved with SD but persisted in deeper layers. During partial SD, epileptiform activity persisted in deep layers throughout the entire seizure, with positive signals at the cortical surface reflecting passive sources of population spikes generated in deeper cortical layers. During full SD, the initial phase of SD propagation through the superficial layers was similar to partial SD, with suppression of activity at the superficial layers and segregation of seizures to deep layers. Further propagation of SD to deep layers resulted in a wave of transient suppression of epileptic activity through the entire cortical column. Thus, vertical propagation of SD through the cortical column creates dynamic network states during which epileptiform activity is restricted to layers without SD.SignificanceOur results point to the importance of vertical SD spread in the SD‐related depression of epileptiform activity across cortical layers.
Exploration of the effect of farm, breed, sex and animal on detailed mineral profile of beef and their latent explanatory factors
Authors: Patel Nageshvar , Bergamaschi Matteo , Cagnin Massimo , Bittante Giovanni 
Published: November 2019

SummaryMinerals in meat vary with different extrinsic and intrinsic sources; therefore, we aimed to quantify different sources of variation in mineral profile of beef. Longissimus thoracis muscle (N.182) from young bulls and heifers was analysed using ICP‐OES for 6 macrominerals, 5 essential microminerals and 9 environmental microminerals. Results of mixed models show that breed and sex have little effect on mineral profile. Major sources of variation, such as farm, individual animal within farm and side/sample within animal, differed markedly from mineral to mineral, affecting reproducibility coefficients. Multivariate factor analysis revealed that five latent factors explained 69% of the co‐variance of 20 minerals. The first was a quantitative factor, followed by others based on Na‐Fe‐Cu, on K‐B‐Pb, on Fe‐Mn and on Zn content, respectively. In conclusion, minerals’ major source of variation depends on complex relationships between the animal’s genetics, physiology, farm environment, management and feeding, whose understanding is favoured by latent factor analyses.
Depletion of Foxp3+ regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome
Authors: Kehrmann Jan , Effenberg Laura , Wilk Camilla , Schoemer Davina , Ngo Thi Phuong Nhi , Adamczyk Alexandra , Pastille Eva , Scholtysik René , Klein‐Hitpass Ludger , Klopfleisch Robert , Westendorf Astrid M. , Buer Jan 
Published: November 2019

SummaryA reciprocal interaction exists between the gut microbiota and the immune system. Regulatory T (Treg) cells are important for controlling immune responses and for maintaining the intestinal homeostasis but their precise influence on the gut microbiota is unclear. We studied the effects of Treg cell depletion on inflammation of the intestinal mucosa and analysed the gut microbiota before and after depletion of Treg cells using the DEpletion of REGulatory T cells (DEREG) mouse model. DNA was extracted from stool samples of DEREG mice and wild‐type littermates at different time‐points before and after diphtheria toxin application to deplete Treg cells in DEREG mice. The V3/V4 region of the 16S rRNA gene was used for studying the gut microbiota with Illumina MiSeq paired ends sequencing. Multidimensional scaling separated the majority of gut microbiota samples from late time‐points after Treg cell depletion in DEREG mice from samples of early time‐points before Treg cell depletion in these mice and from gut microbiota samples of wild‐type mice. Treg cell depletion in DEREG mice was accompanied by an increase in the relative abundance of the phylum Firmicutes and by intestinal inflammation in DEREG mice 20 days after Treg cell depletion, indicating that Treg cells influence the gut microbiota composition. In addition, the variables cage, breeding and experiment number were associated with differences in the gut microbiota composition and these variables should be respected in murine studies.
The Great Crash of 1929: A Look Back After 90 Years
Authors: Bruner Robert F. , Miller Scott C. 
Published: November 2019

The Great Crash of 1929 ranks among the climactic events of the last century, apparently heralding the beginning of the Great Depression. This event raises at least four questions that are relevant today:
Why did the “Roaring 20s” roar? Some prominent contemporaries held that the decade roared because of consumerism, credit growth, and the Jazz Age. However, recent research suggests an alternative explanation: a revolution in manufacturing and technology that amplified economic growth and volatility in markets.
Was the boom in equities a “bubble?” Both the authors’ research and other studies show surprisingly weak evidence of a bubble. The boom probably reflected the technology shock of the ‘20s. If there was a bubble, it was limited in time, breadth, and impact.
What caused the Crash? The onset of an ordinary recession, surprising changes in monetary policy by the Fed, growing regulation, and rising protectionism all help to explain a sharp and sudden change in investor sentiment.
Did the Crash cause the Great Depression, as popular opinion has long maintained? No. The cycle of economic contraction had begun well before the crash. Furthermore, the wealth effect of the Crash was limited. The pivot from recession into Great Depression reflected the abandonment of the Gold Exchange Standard, a wave of bank panics and collapse of credit, protectionism, and a number of maladroit public policies. But if the Crash did not cause the Depression, it probably amplified the effects of forces already at work.
Answers to these questions, illuminated by careful research, remind decision‐makers in business and government that the first explanations for historical events are not always the best, that complex systems have unintended consequences, and that gaps in information make the Great Crash a difficult standard by which to assess future events. The use of historical precedent warrants caution and great humility in the makers of public policy.
Two Modes of Investment Banking: Technocrats, Relationship Managers, and Conflict
Authors: Morrison Alan D. , Wilhelm William J. 
Published: November 2019

Efficient capital allocation in a market economy depends on the exchange of reliable information between providers of capital and companies that seek to put capital to work. One challenge, however, is that information exchange is at most only partly subject to verification and contractual arrangements. Take the case of securities issuance, including IPOs; whereas issuers of the new securities have incentives to overstate their prospects to attract higher bids, prospective investors have incentives to understate their interest. In principle, the counterparties could enter into an agreement that would prevent or discourage misrepresentations by both sides, but failure to perform would be very costly, if not impossible, for a court to verify.Investment banks have traditionally addressed this problem by creating extralegal markets for information whose functioning depends on the reputations of the banks for upholding the interests of both their corporate clients and the providers of capital. But committing to strike the right balance among all of the parties’ interests means that relational investment bankers inevitably face conflicts of interest. The authors of this article argue that such bankers exist to absorb and to manage conflicts of interest in financial markets—and that they do so by exercising judgment in ways that support their reputation for fair dealing.Modern full‐service investment banks, when addressing such conflicts, combine, or braid, such relational functions with technocratic banking activities involving the use of technical skills with advanced information technology. In so doing, however, technocratic bankers substitute formal contracts for the informal judgment exercised by relational bankers; and as a result, they are less dependent on their banks’ reputations for fair dealing. Moreover, technocratic bankers often have powerful incentives to pursue a personal reputation by executing complex transactions that demonstrate their skill, even at the expense of their clients and the bank's reputation for fair dealing.Well‐governed braided banks can benefit from complementarities between relational and technocratic skills. Nevertheless, full‐service banks continue to struggle with governance problems. The authors discuss several market responses to these struggles, such as the growing use of boutique banks offering “unconflicted” sell‐side advice in mergers and acquisitions and securities offerings. But the authors view such responses as at most a first step toward achieving a new understanding of the extent of the challenge facing today's investment banks in carrying out their economic function of bringing together and balancing the interests of companies and their investors.