bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality
Authors: Lehmann Jennifer M. , Claus Karina , Jansen Christian , Pohlmann Alessandra , Schierwagen Robert , Meyer Carsten , Thomas Daniel , Manekeller Steffen , Claria Joan , Strassburg Christian P. , Trautwein Christian , Wasmuth Hermann E. , Berres Marie‐Luise , Trebicka Jonel 
Published: November 2017

AbstractBackground & AimsCXCR% ligands play an important role in hepatic injury, inflammation and fibrosis. While CXCL9 and CXCL11 are associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL10 in severe portal hypertension remains unknown.MethodsA total of 89 cirrhotic patients were analysed. CXCL10 protein levels were measured in portal and hepatic blood at TIPS insertion and 2 weeks later in 24 patients. CXCL10 and IL8 levels were assessed in portal, hepatic, cubital vein and right atrium blood in a further 25 patients at TIPS insertion. Furthermore, real‐time PCR determined hepatic CXCL10‐mRNA in 40 cirrhotic patients.ResultsHepatic CXCL10 showed no association with decompensation. By contrast, circulating CXCL10‐levels were higher in portal than in hepatic vein blood, suggesting an extrahepatic source of CXCL10 in cirrhosis. However, CXCL10 protein in blood samples from portal, hepatic, cubital veins and right atrium correlated excellently with each other and with IL‐8 levels. Higher CXCL10 circulating levels were associated with presence of ascites and higher Child scores. Higher CXCL10 circulating protein levels were associated with acute decompensation, acute‐on‐chronic liver failure (ACLF) and independently with mortality. Moreover, a decrease in CXCL10 protein levels after TIPS insertion was associated with better survival in each cohort and analysed together.DiscussionCirculating CXCL10 possibly reflects systemic inflammation and it is correlated with acute decompensation, ACLF and complications in patients with severe portal hypertension receiving TIPS. CXCL10 predicts survival in these patients and a decrease in CXCL10 after TIPS may be considered a good prognostic factor.
Possible role of hyposensitivity of C‐fiber afferents at the proximal urethra in the development of urge urinary incontinence in patients with detrusor overactivity
Authors: Ichiyanagi Osamu , Nagaoka Akira , Naito Sei , Tsukigi Masaaki , Yagi Mayu , Kato Tomoyuki , Ishigooka Manabu , Tsuchiya Norihiko 
Published: November 2017

ObjectiveThe aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO).MethodsThe medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO‐negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO‐negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square‐wave stimulation at 3 Hz to activate C‐fiber afferents.ResultsMedian CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non‐UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO‐positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11).ConclusionHyposensitive C‐fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.
Trend and business cycles with external markets: Non‐capacity generating semi‐autonomous expenditures and effective demand
Authors: Fiebiger Brett , Lavoie Marc 
Published: November 2017

AbstractThe Global Financial Crisis has underlined the importance of developments in the household sector to explaining macro patterns. Some recent papers have discussed the role of non‐capacity generating semi‐autonomous expenditures in growth theory. This literature ties together several aspects of heterodox thought: growth and distribution; the Sraffian supermultiplier; Duesenberry's relative income hypothesis; the endogenous money approach and Kalecki–Luxemburg external markets. The basic message is that non‐wage sources of effective demand, based on mortgage and consumer credit, can play a key role in inducing capacity investment and driving long‐run output growth. This article gives a broad overview of the role of financed‐induced semi‐autonomous expenditures in growth, cycles and crises, and thus criticizes some of the previous approaches that claim to mimic actual cycles while abstracting from these crucial determinants of economic activity.
Singular case of the driving instructor: Temporal and topographical disorientation
Authors: Futamura Akinori , Honma Motoyasu , Shiromaru Azusa , Kuroda Takeshi , Masaoka Yuri , Midorikawa Akira , Miller Michael W , Kawamura Mitsuru , Ono Kenjiro 
Published: November 2017

AbstractLesions of the medio‐parietal lobes are linked with topographical and temporal disorientation, and are of interest to understanding mental time. We examined a 39‐year‐old man who worked as a driving instructor before cerebral hemorrhage, and followed his case for 8 years including neuropsychological testing and brain imaging. The patient had mild anterograde episodic amnesia, but no semantic amnesia. He felt that time passed too quickly, and developed a compulsive routine to compensate, although he was able to count time at a normal speed. Furthermore, he was unable to accurately sketch the layout of his house and to make a cross‐reference type timetable for the future. Brain magnetic resonance imaging showed lesions of the left anterior–posterior cingulate gyrus, and N‐isopropyl‐[123I] p‐iodoamphetamine single‐photon emission computed tomography showed decreased blood flow mainly of the left medio‐parietal lobe.
Modeling the energy future
Authors: Case James 
Published: November 2017

AbstractA bare‐bones dynamic model of an island economy is constructed for the purpose of discovering “socially optimal” fossil fuel depletion schedules. An entire family of candidates is identified, all members being significantly more gradual than the one currently in force. The active ingredient in the model is a real‐valued function of two real variables―the current extraction rate and the quantity extracted to date―which quantifies the need to expend energy in the course of delivering it to end users. The main conclusions are that fossil fuels are currently being extracted far too fast for the common good, while a wide variety of socially preferable schedules are overlooked.Summary for ManagersConsider conservation! Several methods have proven successful in the past.
Before World War I, Standard Oil did it by monopolizing the industry.
During the 1930s, the Texas Railroad Commission invoked martial law.
OPEC has achieved intermittent success by forming a cartel.
The proposed carbon tax may be the fairest alternative.
Any method of slowing the extraction of fossil fuels will encounter resistance, as the public has long been addicted to cheap energy. Yet conservation will slow global warming, even as it economizes an increasingly scarce resource. Expect no painless alternative―there is none!
Gene effects of Cicer reticulatum on qualitative and quantitative traits in the cultivated chickpea
Authors: Adak Alper , Sari Duygu , Sari Hatice , Toker Cengiz 
Published: November 2017

AbstractThe gene effects of Cicer reticulatum on both double‐podding as qualitative traits and yield criteria as quantitative traits in interspecific hybridization with cultivated chickpea (Cicer arietinum) have not yet been elucidated, despite the easy acquisition of hybrid progeny between two species. This study sought to answer three questions concerning qualitative and quantitative traits in reciprocal crosses between C. arietinum and C. reticulatum. (i) Is there a similarity in the gene effects of flower colour, pigmentation and double‐podded traits in reciprocal interspecific crosses? (ii) What are the expressivity and penetrance of the double‐podded trait in interspecific crosses? (iii) Which heterosis predicts the occurrence and the extent of transgressive variation? The materials for this study were F1, F2 and F3 progeny derived from a reciprocal cross between C. arietinum and C. reticulatum. As qualitative traits, purple flower colour, pigmentation and single‐podded traits in C. reticulatum were governed by a dominant single gene. Purple flower colour and pigmentation were detected to be linked traits as all progeny had the same phenotypes. As quantitative traits, yield criteria in progeny which were double‐podded had higher values than the single‐podded counterparts. Expressivity and penetrance of the double‐podding trait were superior in progeny derived from C. reticulatum × C. arietinum. The results showed that fruitful heterosis was more useful than residual heterosis in F3 as residual heterosis was mostly negative and fruitful heterosis was suggested in self‐pollinated species such as chickpea that lacks inbreeding depression. Interspecific transgression was significant with respect to chickpea improvement because it represented a potential source of novel genetic variation.
A systematic review and meta‐analysis of tertiary interventions in clinical burnout
Authors: Perski Olga , Grossi Giorgio , Perski Aleksander , Niemi Maria 
Published: November 2017

Clinical burnout is one of the leading causes of work absenteeism in high‐ and middle‐income countries. There is hence a great need for the identification of effective intervention strategies to increase return‐to‐work (RTW) in this population. This review aimed to assess the effectiveness of tertiary interventions for individuals with clinically significant burnout on RTW and psychological symptoms of exhaustion, depression and anxiety. Four electronic databases (Ovid MEDLINE, PsychINFO, PubMed and CINAHL Plus) were searched in April 2016 for randomized and non‐randomized controlled trials of tertiary interventions in clinical burnout. Article screening and data extraction were conducted independently by two reviewers. Pooled odds ratios (ORs) and hazard ratios (HRs) were estimated with random‐effects meta‐analyses. Eight articles met the inclusion criteria. There was some evidence of publication bias. Included trials were of variable methodological quality. A significant effect of tertiary interventions compared with treatment as usual or wait‐list controls on time until RTW was found, HR = 4.5, 95% confidence interval (CI) = 2.15–9.45; however, considerable heterogeneity was detected. The effect of tertiary interventions on full RTW was not significant, OR = 1.33, 95% CI = 0.59–2.98. No significant effects on psychological symptoms of exhaustion, depression or anxiety were observed. In conclusion, tertiary interventions for individuals with clinically significant burnout may be effective in facilitating RTW. Successful interventions incorporated advice from labor experts and enabled patients to initiate a workplace dialogue with their employers.
Exhumation history and timing of supergene copper mineralisation in an arid climate: New thermochronological data from the Centinela District, Atacama, Chile
Authors: Sanchez Caroline , Brichau Stéphanie , Riquelme Rodrigo , Carretier Sébastien , Bissig Thomas , Lopez Cristopher , Mpodozis Constantino , Campos Eduardo , Regard Vincent , Hérail Gérard , Marquardt Carlos 
Published: November 2017

AbstractSupergene copper mineralisation (SCM) processes occur during the unroofing of porphyry copper deposits. However, the geomorphological stage during which the main mineralisation occurs is still under debate. Here, we present 24 new thermochronological data from Cenozoic intrusives and compare them with the evolution of supergene mineralisation from the Centinela Mining District in the Atacama Desert. Our results indicate a two‐step cooling path: a rapid Late Eocene exhumation followed by a slow denudation. Previously published supergene mineralisation ages cluster after the main Upper Oligocene exhumation period. Ours is the first study that establishes the relationship between exhumation and supergene processes on the scale of a single mining district. It confirms that SCM took place during pediplanation, likely a required condition for efficient SCM under arid climatic conditions, in contrast to wet tropical environments where SCM occurs during rapid relief growth but has limited preservation potential.
Environmental Triazole Induces Cross-Resistance to Clinical Drugs and Affects Morphophysiology and Virulence of Cryptococcus gattii and C. neoformans
Authors: Bastos Rafael Wesley , Carneiro Hellem Cristina Silva , Oliveira Lorena Vívien Neves , Rocha Karen Maia , Freitas Gustavo José Cota , Costa Marliete Carvalho , Magalhães Thaís Furtado Ferreira , Carvalho Vanessa Silva Dutra , Rocha Cláudia Emanuela , Ferreira Gabriella Freitas , Paixão Tatiane Alves , Moyrand Frédérique , Janbon Guilhem , Santos Daniel Assis 
Published: November 2017

ABSTRACT

Cryptococcus gattii
and
Cryptococcus neoformans
are environmental fungi that cause cryptococcosis, which is usually treated with amphotericin B and fluconazole. However, therapeutic failure is increasing because of the emergence of resistant strains. Because these species are constantly isolated from vegetal materials and the usage of agrochemicals is growing, we postulate that pesticides could be responsible for the altered susceptibility of these fungi to clinical drugs. Therefore, we evaluated the influence of the pesticide tebuconazole on the susceptibility to clinical drugs, morphophysiology, and virulence of
C. gattii
and
C. neoformans
strains. The results showed that tebuconazole exposure caused
in vitro
cross-resistance (CR) between the agrochemical and clinical azoles (fluconazole, itraconazole, and ravuconazole) but not with amphotericin B. In some strains, CR was observed even after the exposure ceased. Further, tebuconazole exposure changed the morphology, including formation of pseudohyphae in
C. neoformans
H99, and the surface charge of the cells. Although the virulence of both species previously exposed to tebuconazole was decreased in mice, the tebuconazole-exposed colonies recovered from the lungs were more resistant to azole drugs than the nonexposed cells. This
in vivo
CR was confirmed when fluconazole was not able to reduce the fungal burden in the lungs of mice. The tolerance to azoles could be due to increased expression of the
ERG11
gene in both species and of efflux pump genes (
AFR1
and
MDR1
) in
C. neoformans
. Our study data support the idea that agrochemical usage can significantly affect human pathogens present in the environment by affecting their resistance to clinical drugs.
Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae
Authors: Sabet Mojgan , Tarazi Ziad , Nolan Thomas , Parkinson Jonathan , Rubio-Aparicio Debora , Lomovskaya Olga , Dudley Michael N. , Griffith David C. 
Published: November 2017

ABSTRACT

Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially
Klebsiella pneumoniae
carbapenemase (KPC)-producing, carbapenem-resistant
Enterobacteriaceae
. The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant
Enterobacteriaceae
, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant
Enterobacteriaceae
.
Evaluation of Oritavancin Dosing Strategies against Vancomycin-Resistant Enterococcus faecium Isolates with or without Reduced Susceptibility to Daptomycin in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model
Authors: Belley Adam , Arhin Francis F. , Moeck Greg 
Published: November 2017

ABSTRACT

The clinical development of nonsusceptibility to the lipopeptide antibiotic daptomycin remains a serious concern during therapy for infections caused by vancomycin-resistant
Enterococcus faecium
(VREfm). The long-acting lipoglycopeptide oritavancin exhibits potent
in vitro
activity against VREfm, although its safety and efficacy for treating clinical VREfm infections have not been established. In this study, novel dosing regimens of daptomycin and oritavancin were assessed against both VREfm and daptomycin-nonsusceptible VREfm isolates in an
in vitro
pharmacokinetic/pharmacodynamic model.
Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration between Diabetic Patients with Wound Infections and Healthy Volunteers via
In Vivo
Microdialysis
Authors: Stainton Sean M. , Monogue Marguerite L. , Baummer-Carr Arlinda , Shepard Ashley K. , Nugent James F. , Kuti Joseph L. , Nicolau David P. 
Published: November 2017

ABSTRACT

Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200 mg every 24 h for 3 doses to achieve steady state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the third dose, 12 blood and 14 dialysate fluid samples were collected over 24 h to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± standard deviation (SD) tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were as follows: maximum concentration (
C
max
), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter (
P
= 0.005); time to
C
max
(
T
max
) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) (
P
= 0.003); half-life (t
1/2
), 9.1 ± 3.6 versus 8.9 ± 2.2 h (
P
= 0.932); and plasma area under the concentration-time curve for the dosing interval (AUC

p

), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter (
P
= 0.004). The tissue area under the concentration-time curve (AUC

t

) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · h/liter (
P
= 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) (
P
= 0.351). Despite lower plasma
C
max
and delayed
T
max
values for patients with DFI relative to healthy volunteers, the penetration into and exposure to tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200 mg once-daily regimen are suitable for further study in treatment of DFI.
Combating Multidrug-Resistant Pathogens with Host-Directed Nonantibiotic Therapeutics
Authors: Andersson Jourdan A. , Sha Jian , Kirtley Michelle L. , Reyes Emily , Fitts Eric C. , Dann Sara M. , Chopra Ashok K. 
Published: November 2017

ABSTRACT

Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), identified from an
in vitro
murine macrophage cytotoxicity screen, provided mice with 40 to 60% protection against pneumonic plague when administered at the time of infection for 1 to 3 days. In the present study, the therapeutic potential of these drugs against pneumonic plague in mice was further evaluated when they were administered at up to 48 h postinfection. While the efficacy of TFP was somewhat diminished as treatment was delayed to 24 h, the protection of mice with AXPN and DXP increased as treatment was progressively delayed to 24 h. At 48 h postinfection, these drugs provided the animals with significant protection (up to 100%) against challenge with the agent of pneumonic or bubonic plague when they were administered in combination with levofloxacin. Likewise, when they were used in combination with vancomycin, all three drugs provided mice with 80 to 100% protection from fatal oral
Clostridium difficile
infection when they were administered at 24 h postinfection. Furthermore, AXPN provided 40 to 60% protection against respiratory infection with
Klebsiella pneumoniae
when it was administered at the time of infection or at 24 h postinfection. Using the same
in vitro
cytotoxicity assay, we identified an additional 76/780 nonantibiotic drugs effective against
K. pneumoniae
. For
Acinetobacter baumannii
, 121 nonantibiotic drugs were identified to inhibit bacterium-induced cytotoxicity in murine macrophages. Of these 121 drugs, 13 inhibited the macrophage cytotoxicity induced by two additional multiple-antibiotic-resistant strains. Six of these drugs decreased the intracellular survival of all three
A. baumannii
strains in macrophages. These results provided further evidence of the broad applicability and utilization of drug repurposing screening to identify new therapeutics to combat multidrug-resistant pathogens of public health concern.