bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gingival crevicular fluid levels of human beta‐defensin 1 in individuals with and without chronic periodontitis
Authors: Costa L. C. M. , Soldati K. R. , Fonseca D. C. , Costa J. E. , Abreu M. H. N. G. , Costa F. O. , Zandim‐Barcelos D. L. , Cota L. O. M. 
Published: April 2018

Background and ObjectiveHuman beta‐defensins (hBDs) contribute to innate immunity antimicrobial activity. They are also effective in the adaptive immune response and may play a crucial role in the susceptibility to diseases of the oral cavity. This study aimed to evaluate the levels of hBD‐1 in the gingival crevicular fluid of individuals with and without chronic periodontitis.Material and MethodsTwenty periodontally healthy individuals (H) and 20 individuals with chronic periodontitis were recruited. Gingival crevicular fluid samples were collected from: healthy sites (Hh) from periodontally healthy individuals; and healthy sites (Ph), sites with gingivitis (Pg), and sites with periodontitis (Pp) from individuals with periodontitis. The levels of hBD‐1 (pg/mL) were measured using enzyme‐linked immunosorbent assay. Comparisons of hBD‐1 between individuals (H and chronic periodontitis) and among sites (Hh, Ph, Pg, Pp) were performed through hierarchical linear modeling.ResultsGingival crevicular fluid levels of hBD‐1 were: Hh = 229.52 ± 138.96 (median 199.26), Ph = 53.88 ± 58.17 (median 35.75), Pg = 57.11 ± 40.18 (median 39.90) and Pp = 55.31 ± 37.28 (median 54.19). No influence of site diagnosis (level 1; health/gingivitis/periodontitis) was observed; however, individual diagnosis (level 2; health/periodontitis) influenced the levels of hBD‐1 (P < .001).ConclusionPeriodontally healthy individuals showed higher gingival crevicular fluid levels of hBD‐1 when compared to individuals with chronic periodontitis. This suggests a potential protective role of hBD‐1 in the susceptibility to chronic periodontitis.
Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co‐incubated dexamethasone and prednisolone
Authors: Morassi A. , Rivera-Vélez S. M. , Slovak J. E. , Court M. H. , Villarino N. F. 
Published: April 2018

Mycophenolic acid (MPA) has been shown to be promising for the treatment of autoimmune diseases in dogs and cats. In humans, MPA is highly bound to plasma proteins (~97%). It has been recommended to monitor free drug plasma concentrations because the free MPA correlates with its immunosuppressive effect. However, it is unknown if MPA is highly bound to plasma proteins in dogs and cats. The objectives of this study were to determine the extent of plasma protein binding of MPA and evaluate the effect of prednisolone and dexamethasone on the extent of protein binding of MPA in dogs and cats. The extent of plasma protein binding of MPA was determined in plasma collected from clinically healthy adult cats (n = 13) and dogs (n = 14) by combining high‐throughput dialysis and ultra‐high‐liquid chromatography. This study reveals that MPA is highly bound to plasma proteins (>90%) in dogs and cats, mean extent of binding of MPA at 15 μg/ml to plasma proteins being 96% (range, 95%–97%) and 92% (range, 90%–93%) for dogs and cats, respectively. In dog plasma, MPA is primarily bound to albumin. In vitro, prednisolone increased the unbound MPA in dogs (p < .01) but not in cats (p = .07) while dexamethasone had no effect on MPA plasma binding in either species (p > .05). Results of this study provide valuable information for designing future pharmacokinetic and pharmacodynamic studies and also therapeutic monitoring programs for dogs and cats.
Altered structural and functional connectivity of the insula in functional dyspepsia
Authors: Liu P. , Fan Y. , Wei Y. , Zeng F. , Li R. , Fei N. , Qin W. 
Published: April 2018

AbstractBackgroundFunctional dyspepsia (FD) is a common functional gastrointestinal disease. Neuroimaging studies have identified that insula is involved in the pathogenesis of FD. However, less is known about structural and functional connectivity of insula in FD.MethodsIn this study, 67 FD patients and 46 healthy controls (HCs) underwent structural MRI, resting‐state functional MRI, diffusion tensor imaging (DTI) scans, and clinical assessment. We used the 3 neuroimaging modalities to investigate structural and functional connectivity of insula between FD patients and HCs, and we examined relationships between the neuroimaging findings and clinical symptoms.Key ResultsCompared with HCs, (i) FD patients had decreased gray matter density in right insula according to voxel‐based morphometry method, which region was targeted as region of interest for further analysis of structural and functional connectivity; (ii) FD patients had lower connection probability in right anterior insula with right thalamus, right internal capsule (IC), and right external capsule (EC); (iii) FD patients had decreased functional connectivity of the right anterior insula with right thalamus and right pregenual anterior cingulate cortex (pACC); and (iv) FD patients had negative correlation between disease duration and the functional connectivity of right anterior insula with thalamus.Conclusions and InferencesThe present findings reveal that alterations of structural and/or functional connectivity of right anterior insula with regions, including thalamus, IC, EC, and pACC, may be mainly implicated in abnormalities of visceral sensory processing and related affective responses in FD patients. Finally, this study could enhance understanding of the pathophysiology of FD.
Higher prevalence of joint hypermobility in constipation predominant irritable bowel syndrome
Authors: Zweig A. , Schindler V. , Becker A. S. , van Maren A. , Pohl D. 
Published: April 2018

AbstractBackgroundJoint hypermobility syndrome (JHS) is characterized by excessive connective tissue laxity manifest as joint hypermobility (JH) together with musculoskeletal symptoms. Previous studies have shown an association between JH/JHS and gastrointestinal symptoms, including irritable bowel syndrome (IBS), although its association with specific IBS subtypes is incompletely understood. We aimed to determine the prevalence of JH according to the subtypes of IBS, in particular IBS‐C and IBS‐D.MethodsData of 228 consecutive IBS patients were analyzed. IBS was subtyped into constipation and diarrhea predominant IBS (IBS‐C and IBS‐D), IBS with mixed bowel habits (IBS‐M) and unsubtyped IBS (IBS‐U). JH was defined as a Beighton Score ≥4/9 points and JHS diagnosed according to revised Brighton Criteria. Data of IBS patients were analyzed for psychological comorbidities assessed by Hospital Anxiety and Depression Scale (HADS) and Visceral Sensitivity Index (VSI).Key ResultsOf 228 IBS patients, 64 (28.1%) suffered from IBS‐C, 89 (39.0%) from IBS‐D, 48 (21.1%) from IBS‐M, and 27 (11.8%) from IBS‐U. JH was diagnosed in 95 patients (41.7%). The prevalence of JH was significantly higher in IBS‐C than IBS‐D (57.8% vs 34.8%, P = .031). There was no significant difference in VSI and HADS according to JH or IBS subtype.Conclusions and InterferencesThe prevalence of JH was significantly higher in IBS‐C compared to IBS‐D. Abnormalities in the connective tissue biomechanics in those with JH may contribute to a degree of colonic inertia which could result in constipation in JH‐positive IBS patients. Further work is needed to determine the colonic biomechanics in patients with JH.
Inferring pathogen dynamics from temporal count data: the emergence of Xylella fastidiosa in France is probably not recent
Authors: Soubeyrand Samuel , de Jerphanion Pauline , Martin Olivier , Saussac Mathilde , Manceau Charles , Hendrikx Pascal , Lannou Christian 
Published: April 2018

Summary

Unravelling the ecological structure of emerging plant pathogens persisting in multi‐host systems is challenging. In such systems, observations are often heterogeneous with respect to time, space and host species, and may lead to biases of perception. The biased perception of pathogen ecology may be exacerbated by hidden fractions of the whole host population, which may act as infection reservoirs.

We designed a mechanistic‐statistical approach to help understand the ecology of emerging pathogens by filtering out some biases of perception. This approach, based on SIR (Susceptible–Infected–Removed) models and a Bayesian framework, disentangles epidemiological and observational processes underlying temporal counting data.

We applied our approach to French surveillance data on Xylella fastidiosa, a multi‐host pathogenic bacterium recently discovered in Corsica, France. A model selection led to two diverging scenarios: one scenario without a hidden compartment and an introduction around 2001, and the other with a hidden compartment and an introduction around 1985.

Thus, Xylella fastidiosa was probably introduced into Corsica much earlier than its discovery, and its control could be arduous under the hidden compartment scenario. From a methodological perspective, our approach provides insights into the dynamics of emerging plant pathogens and, in particular, the potential existence of infection reservoirs.
Exosomal biomarkers in oral diseases
Authors: Hadavand Mohammad , Hasni Sarfaraz 
Published: April 2018

AbstractExosomes have emerged as novel nanovesicles that facilitate intracellular communication. The molecular content of exosomes is specific to their cell type of origin and reflective of the cells physiological status. Combined with their stability and accessibility in a variety of biofluids, exosomes may be used as biomarkers in a variety of diseases. Recent evidence suggests that exosomes have immunomodulatory functions that play a role in the severity and development of autoimmune disorders and cancers. This article focuses on the biomarker and therapeutic potential of exosomes for oral manifestation of autoimmune diseases and head and neck cancers.
The growth effects of stabilisation funds and fiscal rules in oil‐rich African economies: empirical evidence and development policy implications from a Nigerian case study
Authors: Ibironke Adesola 
Published: April 2018

AbstractThis paper empirically examines the growth effects of stabilisation funds and fiscal rules in oil‐rich African countries, using Nigeria as a case study. The analysis captures the ‘international standard’ of the two fiscal instruments by empirically comparing the effects of Nigerian instruments with those of non‐African oil‐exporting countries (i.e. Norway and Mexico). The results show that the fiscal instruments are effective in Nigeria and that the effectiveness is comparable to that of non‐African economies, implying that the Nigerian instruments meet ‘international standard’. The paper also discusses the development policy implications of the results, one of which is that the fiscal instruments can be used to control risky behaviours of economic agents in oil‐rich African economies. For example, since the instruments are effective in increasing growth (i.e. real GDP growth) and limiting its volatility, they can be employed to control increases in demand for and supply of risky sex caused by increases in real per capita income during oil booms.
Big Data: a big opportunity for the petroleum and petrochemical industry
Authors: Hassani Hossein , Silva Emmanuel Sirimal 
Published: April 2018

AbstractThe Petroleum and Petrochemical (P&P) industry is home to the most traded commodity in the world, i.e. oil. Recently, this industry has been struggling to make ends meet with top lines being affected by falling oil prices and bottom lines being squeezed further via increasing operational costs. It is against this backdrop that this paper seeks to identify and summarise the positive influence that the adoption of Big Data can have on the P&P industry. Exhaustive research is carried out on the industry's engagement and adoption of Big Data in upstream, midstream and downstream operations to concisely summarise the varied applications and the potential benefits. Our research indicates that the upstream sector is actively engaging with Big Data to achieve efficiency gains while the midstream and downstream sectors are lagging behind. Overall, it is evident that the P&P industry can find solutions to its aching financial and productivity issues by embracing of Big Data.
Long‐term effect of early nutrition on endocrine parameters and liver and endometrial gene expression of the members of the somatotrophic axis in Hereford heifers
Authors: Guggeri D , Meikle A , Carriquiry M , De Barbieri I , Montossi F , Viñoles C 
Published: April 2018

ContentsThis study compared the effect of different management systems on endocrine parameters, and gene expression of members of the somatotrophic axis in the liver and endometrium of beef heifers. Twenty‐two 709‐days‐old heifers submitted to Early Weaning (EW, n = 8), Traditional Weaning (TW, n = 7) and TW plus creep feeding (TW+CF, n = 7) were used. Animals were synchronized with two prostaglandin (PG) injections at 11‐day interval (Oestrus = Day 0). Blood samples were collected daily for progesterone (P4) determination, and endometrial and liver biopsies on Days 7 and 16 for transcript determination of members of the somatotrophic axis. Progesterone concentrations were greater on Days 15 and 16 (p < .02) of the cycle in TW+CF than TW and EW heifers. On Day 7, TW+CF heifers expressed greater liver total growth hormone receptor transcripts than TW heifers (p = .05) and greater insulin‐like growth factor (IGF)‐binding protein 3 mRNA than both EW and TW groups (p < .05). On Days 7 and 16, TW+CF expressed more endometrial IGF1 mRNA than the other groups (p < .01). We conclude that increasing the plane of nutrition of nursing calves may have a long‐term effect on the functioning of the somatotrophic axis both in the liver and in the endometrium.
Running Repairs: Coordinating Meaning in Dialogue
Authors: Healey Patrick G. T. , Mills Gregory J. , Eshghi Arash , Howes Christine 
Published: April 2018

AbstractPeople give feedback in conversation: both positive signals of understanding, such as nods, and negative signals of misunderstanding, such as frowns. How do signals of understanding and misunderstanding affect the coordination of language use in conversation? Using a chat tool and a maze‐based reference task, we test two experimental manipulations that selectively interfere with feedback in live conversation: (a) “Attenuation” that replaces positive signals of understanding such as “right” or “okay” with weaker, more provisional signals such as “errr” or “umm” and (2) “Amplification” that replaces relatively specific signals of misunderstanding from clarification requests such as “on the left?” with generic signals of trouble such as “huh?” or “eh?”. The results show that Amplification promotes rapid convergence on more systematic, abstract ways of describing maze locations while Attenuation has no significant effect. We interpret this as evidence that “running repairs”—the processes of dealing with misunderstandings on the fly—are key drivers of semantic coordination in dialogue. This suggests a new direction for experimental work on conversation and a productive way to connect the empirical accounts of Conversation Analysis with the representational and processing concerns of Formal Semantics and Psycholinguistics.
Can Strategic Ignorance Explain the Evolution of Love?
Authors: Bear Adam , Rand David G. 
Published: April 2018

AbstractPeople's devotion to, and love for, their romantic partners poses an evolutionary puzzle: Why is it better to stop your search for other partners once you enter a serious relationship when you could continue to search for somebody better? A recent formal model based on “strategic ignorance” suggests that such behavior can be adaptive and favored by natural selection, so long as you can signal your unwillingness to “look” for other potential mates to your current partner. Here, we re‐examine this conclusion with a more detailed model designed to capture specific features of romantic relationships. We find, surprisingly, that devotion does not typically evolve in our model: Selection favors agents who choose to “look” while in relationships and who allow their partners to do the same. Non‐looking is only expected to evolve if there is an extremely large cost associated with being left by your partner. Our results therefore raise questions about the role of strategic ignorance in explaining the evolution of love.
Ethnic minorities and trade: The Soviet Union as a natural experiment
Authors: Gokmen Gunes , Nikishina Elena , Vézina Pierre‐Louis 
Published: April 2018

AbstractThis paper examines the role of ethnic minorities in bilateral trade between countries of the ex‐Soviet Union. We argue that both forced re‐settlement of entire ethnic groups during the Stalin era and artificially drawn borders in Central Asia led to an exogenous ethnic composition within countries. Using data collected by ethnologists on the share of ethnic groups across countries, we build an index of bilateral ethnic networks and estimate its effect on trade using a gravity model. While ethnic networks do not seem to have played a role in inter‐republic trade during the Soviet Union, we find a positive and significant effect of ethnic networks on trade in the years following the collapse of the Soviet Union. This effect, however, eroded steadily from the early 2000s.
Severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog
Authors: Ueda Yu , Wong Christine , Borchers Angela 
Published: April 2018

AbstractObjectiveTo report a case of severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog.Case SummaryA female neutered Rat Terrier was presented for an acute onset of seizure‐like episodes, weakness, and vomiting approximately 14 hours after ingestion of 198 mg/kg of metformin. The dog was found to be laterally recumbent, paddling, and unresponsive shortly before presentation. On physical exam, the dog was in hypovolemic shock and hypothermic. Blood work revealed severe lactic acidosis and hypoglycemia. The dog was volume resuscitated with intravenous crystalloids and dextrose, followed by a continuous infusion of intravenous fluids and dextrose, as well as administration of isotonic sodium bicarbonate. Repeat blood work showed minimal improvement of the hyperlactatemia for 3 hours despite resolution of hypovolemia and hypoglycemia followed by gradual improvement over the next 9 hours of hospitalization. High performance liquid chromatography/tandem mass spectrometry analysis showed markedly increased plasma metformin concentrations at 3.9 μg/mL. The dog was discharged from the hospital within 24 hours and showed no recurrence of clinical signs one year following discharge.New or Unique Information ProvidedMetformin‐associated lactic acidosis and hypoglycemia is a severe complication in human patients, but has not been reported in veterinary medicine. Aggressive treatment with supportive care including IV fluids and dextrose administration resulted in resolution of the clinical signs in this patient. Metformin toxicosis should be considered in dogs with severe hyperlactatemia and hypoglycemia of unknown etiology.
Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens
Authors: Alqahtani Saeed A. , Alsultan Abdullah S. , Alqattan Hussain M. , Eldemerdash Ahmed , Albacker Turki B. 
Published: April 2018

ABSTRACT

The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analyzed using an Architect i4000SR immunoassay analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 168 blood samples were analyzed from 28 patients. The pharmacokinetics of vancomycin are best described by a two-compartment model with between-subject variability in clearance (CL), the volume of distribution of the central compartment (
V
1
), and volume of distribution of the peripheral compartment (
V
2
). The CL and the
V
1
of vancomycin were related to creatinine CL (CL
CR
), body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC
0–24
/MIC > 400 for an MIC of 1 mg/liter, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, the administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15- and 20-mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 and 30 mg/kg) of vancomycin.
Metabolism of SKLB-TB1001, a Potent Antituberculosis Agent, in Animals
Authors: Xiong Lu , Gao Chao , Shi Yao-Jie , Tao Xin , Peng Cui-Ting , Rong Juan , Liu Kun-Lin , Lei Qian , Zhang Yi-Wen , Wang Ning-Yu , Yu Luo-Ting 
Published: April 2018

ABSTRACT

Tuberculosis is a major global health problem, and the emergence of multidrug-resistant and extensively drug-resistant strains has increased the difficulty of treating this disease. Among the novel antituberculosis drugs in the pipeline, decaprenylphosphoryl-beta-
d
-ribose-2-epimerase (DprE1) inhibitors such as BTZ043 and pBTZ169 exhibited extraordinary antituberculosis potency. Here, the metabolites of the new DprE1 inhibitor SKLB-TB1001
in vivo
and its inhibition of cytochrome P450 isoforms and plasma protein binding (PPB)
in vitro
were studied. The results showed that rapid transformation and high PPB resulted in inadequate exposure
in vivo
and thus led to the moderate potency of SKLB-TB1001
in vivo
. This study provided explanations for the discrepant potency of this scaffold
in vivo
and
in vitro
. Meanwhile, it also provides a rationale for lead optimization of this very promising scaffold of antituberculosis agents to prevent them from being metabolized, thus improving their exposure
in vivo
.
An ATP-Dependent Ligase with Substrate Flexibility Involved in Assembly of the Peptidyl Nucleoside Antibiotic Polyoxin
Authors: Gong Rong , Qi Jianzhao , Wu Pan , Cai You-Sheng , Ma Hongmin , Liu Yang , Duan He , Wang Meng , Deng Zixin , Price Neil P. J. , Chen Wenqing 
Published: April 2018

ABSTRACT

Polyoxin (POL) is an unusual peptidyl nucleoside antibiotic, in which the peptidyl moiety and nucleoside skeleton are linked by an amide bond. However, their biosynthesis remains poorly understood. Here, we report the deciphering of PolG as an ATP-dependent ligase responsible for the assembly of POL. A
polG
mutant is capable of accumulating multiple intermediates, including the peptidyl moiety (carbamoylpolyoxamic acid [CPOAA]) and the nucleoside skeletons (POL-C and the previously overlooked thymine POL-C). We further demonstrate that PolG employs an ATP-dependent mechanism for amide bond formation and that the generation of the hybrid nucleoside antibiotic POL-N is also governed by PolG. Finally, we determined that the deduced ATP-binding sites are functionally essential for PolG and that they are highly conserved in a number of related ATP-dependent ligases. These insights have allowed us to propose a catalytic mechanism for the assembly of peptidyl nucleoside antibiotic via an acyl-phosphate intermediate and have opened the way for the combinatorial biosynthesis/pathway engineering of this group of nucleoside antibiotics.

IMPORTANCE
POL is well known for its remarkable antifungal bioactivities and unusual structural features. Actually, elucidation of the POL assembly logic not only provides the enzymatic basis for further biosynthetic understanding of related peptidyl nucleoside antibiotics but also contributes to the rational generation of more hybrid nucleoside antibiotics via synthetic biology strategy.