bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia
Authors: Cui Liang , Zheng Dahai , Lee Yie Hou , Chan Tze Khee , Kumar Yadunanda , Ho Wanxing Eugene , Chen Jian Zhu , Tannenbaum Steven R. , Ong Choon Nam 
Published: May 2016

AbstractInfluenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI-induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process.
TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation
Authors: Yoshida Ayaka , Furube Eriko , Mannari Tetsuya , Takayama Yasunori , Kittaka Hiroki , Tominaga Makoto , Miyata Seiji 
Published: May 2016

AbstractTransient receptor potential vanilloid receptor 1 (TRPV1) is a non-selective cation channel that is stimulated by heat (>43 °C), mechanical/osmotic stimuli, and low pH. The importance of TRPV1 in inflammatory responses has been demonstrated, whereas its participation in brains remains unclear. In the present study, the intracerebroventricular (icv) administration of the TRPV1 agonist resiniferatoxin (RTX) induced the activation of signal transducer and activator of transcription 3 (STAT3) in circumventricular organs (CVOs) and thermoregulation-associated brain regions with a similar patttern to the peripheral and icv administration of lipopolysaccharide (LPS). With the peripheral and icv LPS stimuli, STAT3 activation was significantly lower in Trpv1−/− mice than in Trpv1+/+ mice. The icv administration of RTX induced transient hypothermia, whereas that of the TRPV1 antagonist capsazepine enhanced the magnitude and period of LPS-induced hyperthermia. These results indicate that TRPV1 is important for activating proinflammatory STAT3 signaling and thermoregulation-associated brain pathways in the brain.
Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma
Authors: Mahon Megan , Xu Jie , Yi Xianghua , Liu Xiuli , Gao Nan , Zhang Lanjing 
Published: May 2016

AbstractRecent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells’ associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell-containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021) and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC and seems to warrant further studies.
Long-term expression of miRNA for RNA interference using a novel vector system based on a negative-strand RNA virus
Authors: Honda Tomoyuki , Yamamoto Yusuke , Daito Takuji , Matsumoto Yusuke , Makino Akiko , Tomonaga Keizo 
Published: May 2016

AbstractRNA interference (RNAi) has emerged as a promising technique for gene therapy. However, the safe and long-term expression of small RNA molecules is a major concern for the application of RNAi therapies in vivo. Borna disease virus (BDV), a non-segmented, negative-strand RNA virus, establishes a persistent infection without obvious cytopathic effects. Unique among animal non-retroviral RNA viruses, BDV persistently establishes a long-lasting persistent infection in the nucleus. These features make BDV ideal for RNA virus vector persistently expressing small RNAs. Here, we demonstrated that the recombinant BDV (rBDV) containing the miR-155 precursor, rBDV-miR-155, persistently expressed miR-155 and efficiently silenced its target gene. The stem region of the miR-155 precursor in rBDV-miR-155 was replaceable by any miRNA sequences of interest and that such rBDVs efficiently silence the expression of target genes. Collectively, BDV vector would be a novel RNA virus vector enabling the long-term expression of miRNAs for RNAi therapies.
Reduced tonic inhibition after stroke promotes motor performance and epileptic seizures
Authors: Jaenisch Nadine , Liebmann Lutz , Guenther Madlen , Hübner Christian A. , Frahm Christiane , Witte Otto W. 
Published: May 2016

AbstractStroke survivors often recover from motor deficits, either spontaneously or with the support of rehabilitative training. Since tonic GABAergic inhibition controls network excitability, it may be involved in recovery. Middle cerebral artery occlusion in rodents reduces tonic GABAergic inhibition in the structurally intact motor cortex (M1). Transcript and protein abundance of the extrasynaptic GABAA-receptor complex α4β3δ are concurrently reduced (δ-GABAARs). In vivo and in vitro analyses show that stroke-induced glutamate release activates NMDA receptors, thereby reducing KCC2 transporters and down-regulates δ-GABAARs. Functionally, this is associated with improved motor performance on the RotaRod, a test in which mice are forced to move in a similar manner to rehabilitative training sessions. As an adverse side effect, decreased tonic inhibition facilitates post-stroke epileptic seizures. Our data imply that early and sometimes surprisingly fast recovery following stroke is supported by homeostatic, endogenous plasticity of extrasynaptic GABAA receptors.
Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14α-demethylase
Authors: Sagatova Alia A. , Keniya Mikhail V. , Wilson Rajni K. , Sabherwal Manya , Tyndall Joel D. A. , Monk Brian C. 
Published: May 2016

AbstractEmergence of fungal strains showing resistance to triazole drugs can make treatment of fungal disease problematic. Triazole resistance can arise due to single mutations in the drug target lanosterol 14α-demethylase (Erg11p/CYP51). We have determined how commonly occurring single site mutations in pathogenic fungi affect triazole binding using Saccharomyces cerevisiae Erg11p (ScErg11p) as a target surrogate. The mutations Y140F/H were introduced into full-length hexahistidine-tagged ScErg11p. Phenotypes and high-resolution X-ray crystal structures were determined for the mutant enzymes complexed with short-tailed (fluconazole and voriconazole) or long-tailed (itraconazole and posaconazole) triazoles and wild type enzyme complexed with voriconazole. The mutations disrupted a water-mediated hydrogen bond network involved in binding of short-tailed triazoles, which contain a tertiary hydroxyl not present in long-tailed triazoles. This appears to be the mechanism by which resistance to these short chain azoles occurs. Understanding how these mutations affect drug affinity will aid the design of azoles that overcome resistance.
Ferromagnetism controlled by electric field in tilted phosphorene nanoribbon
Authors: Farooq M. Umar , Hashmi Arqum , Hong Jisang 
Published: May 2016

AbstractStudy on phosphorene nanoribbon was mostly focused on zigzag and armchair structures and no ferromagnetic ground state was observed in these systems. Here, we investigated the magnetic property of tilted black phosphorene nanoribbons (TPNRs) affected by an external electric field. We also studied the edge passivation effect on the magnetism and thermal stability of the nanoribbons. The pure TPNR displayed an edge magnetic state, but it disappeared in the edge reconstructed TPNR due to the self-passivation. In addition, we found that the bare TPNR was mechanically unstable because an imaginary vibration mode was obtained. However, the imaginary vibration mode disappeared in the edge passivated TPNRs. No edge magnetism was observed in hydrogen and fluorine passivated TPRNs. In contrast, the oxygen passivated TPNR was more stable than the pure TPNR and the edge-to-edge antiferromagntic (AFM) ground state was obtained. We found that the magnetic ground state could be tuned by the electric field from antiferromagnetic (AFM) to ferromagnetic (FM) ground state. Interestingly, the oxygen passivated TPNR displayed a half-metallic state at a proper electric field in both FM and AFM states. This finding may provoke an intriguing issue for potential spintronics application using the phosphorene nanoribbons.
Wideband balun bandpass filter explored for a balanced dipole antenna with high selectivity
Authors: Zhang Gang , Wang Jianpeng , Wu Wen 
Published: May 2016

A novel microstrip wideband balun bandpass filter (BPF) is presented for development of a balanced dipole antenna with wide operating band and high frequency selectivity. By utilising the standing‐wave property of current distribution along a half‐wavelength (λ/2) open‐ended microstrip line, out‐of‐phase signals are ideally obtained at two output ports of a balun. Meanwhile, proper coupling topologies between the open‐circuited λ/2 microstrip transmission line and the quadruple‐mode resonators are selected to achieve a balun BPF with both characteristics of balanced performance and wideband filtering properties. A balun BPF operating at 1.65 GHz with 32% fractional bandwidth is at first designed. The derived results not only exhibit good performance with 0.49 dB amplitude imbalance and 7.2° phase imbalance, but also achieve high selectivity relying on two transmission zeros. Next, this balun BPF is integrated with a balanced dipole antenna with a flat shape towards wideband and high‐selective radiation. Both simulated and measured results achieve higher than 10 dB return loss and 2.4 dBi radiation gain over a band of 1.4–1.9 GHz.
Source‐switched charge pump with reverse leakage compensation technique for spur reduction of wideband PLL
Authors: Zhang Zhao , Yang Jincheng , Liu Liyuan , Feng Peng , Liu Jian , Wu Nanjian 
Published: May 2016

A source‐switched charge pump (SSCP) with reverse leakage compensation technique is proposed to reduce spur level of wideband PLL induced by the reverse sub‐threshold leakage of the charge pump. This technique can set the source–drain voltage of current‐source N‐type MOS (NMOS)/P‐type MOS to be close to zero at off‐state of the charge pump and thus reduce the reverse leakage. Compared with the conventional SSCP, only one NMOS capacitor, two CMOS switches and two inverters are added in the proposed charge pump. So, there is negligible extra power and extra area cost. A 0.7–1.6 GHz PLL is designed with the conventional and the proposed charge pumps in 65 nm CMOS process. Simulation results show the proposed SSCP can reduce orders of the magnitude of the reverse leakage without the penalty of current matching, compared with the conventional charge pump. The PLL with the proposed charge pump achieves up to 28 dB spur level reduction.
Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study
Authors: Domen Patrick , Peeters Sanne , Michielse Stijn , Gronenschild Ed , Viechtbauer Wolfgang , Roebroeck Alard , Os Jim van , Marcelis Machteld ,   for Genetic Risk and Outcome of Psychosis (G.R.O.U.P.)
Published: May 2016

AbstractBackgroundAlthough widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability.MethodsTwo DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models.ResultsSiblings revealed a significant mean FA decrease over time compared to controls (B = −0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = −0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group × region interaction (χ2 = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata.ConclusionWhole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations.
Coached Peer Review: Developing the Next Generation of Authors
Authors: Sidalak Daniel , Purdy Eve , Luckett-Gatopoulos S. , Murray Heather , Thoma Brent , Chan Teresa M. 
Published: May 2016

Problem
Publishing in academic journals is challenging for learners. Those who pass the initial stages of internal review by an editor often find the anonymous peer review process harsh. Academic blogs offer alternate avenues for publishing medical education material. Many blogs, however, lack a peer review process, which some consumers argue compromises the quality of materials published.

Approach
CanadiEM (formerly BoringEM) is an academic educational emergency medicine blog dedicated to publishing high-quality materials produced by learners (i.e., residents and medical students). The editorial team has designed and implemented a collaborative “coached peer review” process that comprises an open exchange among the learner–author, editors, and reviewers. The goal of this process is to facilitate the publication of high-quality academic materials by learner–authors while providing focused feedback to help them develop academic writing skills.

Outcomes
The authors of this Innovation Report surveyed (February–June 2015) their blog’s learner–authors and external expert “staff” reviewers who had participated in coached peer review for their reactions to the process. The survey results revealed that participants viewed the process positively compared with both traditional journal peer review and academic blog publication processes. Participants found the process friendly, easy, efficient, and transparent. Learner–authors also reported increased confidence in their published material. These outcomes met the goals of coached peer review.

Next Steps
CanadiEM aims to inspire continued participation in, exposure to, and high-quality production of academic writing by promoting the adoption of coached peer review for online educational resources produced by learners.
PERIPHERAL RETINOPATHY ASSOCIATED WITH APLASTIC ANEMIA
Authors: Metelitsina Tatyana I. , Sheth Veeral S. , Patel Shuchi B. , Grassi Michael A. 
Published: May 2016

Purpose:
To report a case of severe, bilateral, rapidly progressing peripheral retinal nonperfusion associated with underlying aplastic anemia.

Methods:
An interventional case report.

Results:
A 4-year-old girl presented with decreased visual acuity. On clinical examination, she was found to have a RAPD, elevated intraocular pressure, 360° rubeosis, vitreous hemorrhage, severe exudative retinal detachment, and telangiectasia with severe peripheral retinal nonperfusion. Laboratory workup was significant for pancytopenia, and a bone marrow biopsy showed extreme hypocellularity with no malignant cells. The patient was diagnosed with primary aplastic anemia. She developed dramatic progression of retinal nonperfusion in the left eye, as well as in the fellow right eye. This bilateral retinopathy was poorly responsive to aggressive management, which included laser photocoagulation and intravitreal injections of anti–vascular endothelial growth factor medications.

Conclusion:
Asymmetric, bilateral quickly progressing peripheral retinal ischemia, in conjunction with pancytopenia and otherwise negative workup may be related to underlying bone marrow failure and aplastic anemia.
Plasma IP-10 Is Increased in Immunological NonResponders and Associated With Activated Regulatory T Cells and Persisting Low CD4 Counts
Authors: Stiksrud Birgitte , Lorvik Kristina Berg , Kvale Dag , Mollnes Tom Eirik , Ueland Per Magne , Trøseid Marius , Taskén Kjetil , Dyrhol-Riise Anne M. 
Published: May 2016

Objective:
To explore immune mechanisms and identify biomarkers associated with an inadequate immune recovery in patients with HIV with efficient antiretroviral therapy.

Design:
A cross-sectional study of 67 HIV-infected patients on antiretroviral therapy for ≥24 months with HIV RNA ≤20 copies per milliliter; 41 were defined as immunological nonresponders (INR) (CD4 < 400 cells per microliter) and 26 as immunological responders (CD4 > 600 cells per microliter). CD4 counts were also registered 2 years after inclusion.

Methods:
Cytokines, soluble markers of microbial translocation, and tryptophan catabolites were measured in plasma by multiplex assay, ELISA, or mass spectrometry. T-cell activation, differentiation, and regulatory T cells (Tregs) were analyzed by flow cytometry in 2 subgroups with comparable nadir CD4 counts.

Results:
Plasma interferon-inducible protein-10 (IP-10) levels were higher (P < 0.05), the T cells were more activated (CD38+HLA-DR+) (P < 0.05), the naive/effector memory T-cell ratio was lower (P < 0.01) and the proportion of resting Tregs (CD4+CD45RA+FoxP3+) was reduced (P < 0.001) in INR patients compared with immunological responders. INR patients with CD4 counts ≤300 cells per microliter also demonstrated a higher fraction of activated Tregs (aTreg) (CD4+CD147highCD25high) (P < 0.05). In the INR group, the aTreg percentages correlated with plasma IP-10 levels and inversely with CD4 counts (both P < 0.01). IP-10 levels (P < 0.05) and kynurenine/tryptophan ratio (P < 0.01) were negatively associated with the CD4 count 2 years after inclusion.

Conclusion:
Patients with HIV with inadequate CD4 responses had higher levels of IP-10, more activated and differentiated T-cell phenotypes, as well as aTreg, compared with patients with satisfactory CD4 gain. High IP-10 levels were also associated with lower CD4 counts after 2 years.
Reanalysis of the Anthrax Epidemic in Rhodesia, 1978-84
Authors: Wilson James M , Brediger Walter , Albright Tom , Smith-Gagen Julie 
Published: May 2016

ABSTRACTIn the mid-1980s, the largest epidemic of anthrax of the last 200 years was documented in a little known series of studies by Davies inThe Central African Journal of Medicine. This epidemic involved thousands of cattle and 10,738 human cases with 200 fatalities in Rhodesia during the Counterinsurgency. Grossly unusual epidemiological features were noted that, to this day, have not been definitively explained. This study performed a historical reanalysis of the data to reveal an estimated geographic involvement of 245,750 km2, with 171,990 cattle and 17,199 human cases. Geospatial time series analysis is suggestive of multiple, independent geotemporal foci of anthrax introduced via an unknown mechanism rather than re-emergence from native endemic foci.
C. elegansPVD Neurons: A Platform for Functionally Validating and Characterizing Neuropsychiatric Risk Genes
Authors: Aguirre-Chen Cristina , Kim Nuri , Mendivil Ramos Olivia , Kramer Melissa , McCombie W. Richard , Hammell Christopher M. 
Published: May 2016

AbstractOne of the primary challenges in the field of psychiatric genetics is the lack of anin vivomodel system in which to functionally validate candidateneuropsychiatricriskgenes (NRGs) in a rapid and cost-effective manner1−3. To overcome this obstacle, we performed a candidate-based RNAi screen in whichC. elegansorthologs of human NRGs were assayed for dendritic arborization and cell specification defects usingC. elegansPVD neurons. Of 66 NRGs, identified via exome sequencing of autism (ASD)4or schizophrenia (SCZ)5−9probands and whose mutations arede novoand predicted to result in a complete or partial loss of protein function, theC. elegansorthologs of 7 NRGs were found to be required for proper neuronal development and represent a variety of functional classes, including transcriptional regulators and chromatin remodelers, molecular chaperones, and cytoskeleton-related proteins. Notably, the positive hit rate, when selectively assayingC. elegansorthologs of ASD and SCZ NRGs, is enriched >14-fold as compared to unbiased RNAi screening10. Furthermore, we find that RNAi phenotypes associated with the depletion of NRG orthologs is recapitulated in genetic mutant animals, and, via genetic interaction studies, we show that the NRG ortholog of ANK2,unc-44, is required for SAX-7/MNR-1/DMA-1 signaling. Collectively, our studies demonstrate thatC. elegansPVD neurons are a tractable model in which to discover and dissect the fundamental molecular mechanisms underlying neuropsychiatric disease pathogenesis.
Tools and techniques to ensure innovative management education in India
Authors: Rao M.S. 
Published: May 2016

Purpose
– The purpose of this paper is to outline tools and techniques to ensure innovative management education in India.

Design/methodology/approach
– The paper addresses the challenges in the present Indian management education and outlines a blueprint with innovative solutions.

Findings
– It calls for support from all stakeholders including industry, educators, students, educational institutions, government and thought leaders to innovate Indian management education as per the global standards to create world class managers and leaders.

Practical implications
– These tools and techniques can be customized in other countries to ensure quality management education.

Social implications
– The social implications of this research suggests that stakeholders must strive to ensure innovative management education to create effective managers and leaders globally.

Originality/value
– It overhauls Indian management education as per international standards. It explains management education from the perspective of Henry Mintzberg. It reinvents management education as per the dynamic global business environment.