bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine
Authors: Armitage Emily G. , Alqaisi Amjed Q. I. , Godzien Joanna , Peña Imanol , Mbekeani Alison J. , Alonso-Herranz Vanesa , López-Gonzálvez Ángeles , Martín Julio , Gabarro Raquel , Denny Paul W. , Barrett Michael P. , Barbas Coral 
Published: February 2018

ABSTRACTWith the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabolome and lipidome ofLeishmania donovaniaxenic amastigotes treated with miltefosine. Miltefosine caused a dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid pools, while sphingolipids (SLs) and sterols increased.Leishmania majorpromastigotes devoid of SL biosynthesis through loss of the serine palmitoyl transferase gene (ΔLCB2) were 3-fold less sensitive to miltefosine than wild-type (WT) parasites. Changes in the metabolome and lipidome of miltefosine-treatedL. majormirrored those ofL. donovani. A lack of SLs in the ΔLCB2 mutant was matched by substantial alterations in sterol content. Together, these data indicate that SLs and ergosterol are important for miltefosine sensitivity and, perhaps, MoA.
Alginate Oligosaccharide-Induced Modification of the
lasI-lasR
and
rhlI-rhlR
Quorum-Sensing Systems in Pseudomonas aeruginosa
Authors: Jack Alison A. , Khan Saira , Powell Lydia C. , Pritchard Manon F. , Beck Konrad , Sadh Hina , Sutton Lucy , Cavaliere Alessandra , Florance Hannah , Rye Philip D. , Thomas David W. , Hill Katja E. 
Published: February 2018

ABSTRACT

Pseudomonas aeruginosa
plays a major role in many chronic infections. Its ability to readily form biofilms contributes to its success as an opportunistic pathogen and its resistance/tolerance to antimicrobial/antibiotic therapy. A low-molecular-weight alginate oligomer (OligoG CF-5/20) derived from marine algae has previously been shown to impair motility in
P. aeruginosa
biofilms and disrupt pseudomonal biofilm assembly. As these bacterial phenotypes are regulated by quorum sensing (QS), we hypothesized that OligoG CF-5/20 may induce alterations in QS signaling in
P. aeruginosa
. QS regulation was studied by using
Chromobacterium violaceum
CV026 biosensor assays that showed a significant reduction in acyl homoserine lactone (AHL) production following OligoG CF-5/20 treatment (≥2%;
P
< 0.05). This effect was confirmed by liquid chromatography-mass spectrometry analysis of C
4
-AHL and 3-oxo-C
12
-AHL production (≥2%;
P
< 0.05). Moreover, quantitative PCR showed that reduced expression of both the
las
and
rhl
systems was induced following 24 h of treatment with OligoG CF-5/20 (≥0.2%;
P
< 0.05). Circular dichroism spectroscopy indicated that these alterations were not due to steric interaction between the AHL and OligoG CF-5/20. Confocal laser scanning microscopy (CLSM) and COMSTAT image analysis demonstrated that OligoG CF-5/20-treated biofilms had a dose-dependent decrease in biomass that was associated with inhibition of extracellular DNA synthesis (≥0.5%;
P
< 0.05). These changes correlated with alterations in the extracellular production of the pseudomonal virulence factors pyocyanin, rhamnolipids, elastase, and total protease (
P
< 0.05). The ability of OligoG CF-5/20 to modify QS signaling in
P. aeruginosa
PAO1 may influence critical downstream functions such as virulence factor production and biofilm formation.
Common Hydraulic Fracturing Fluid Additives Alter the Structure and Function of Anaerobic Microbial Communities
Authors: Mumford Adam C. , Akob Denise M. , Klinges J. Grace , Cozzarelli Isabelle M. 
Published: February 2018

ABSTRACTThe development of unconventional oil and gas (UOG) resources results in the production of large volumes of wastewater containing a complex mixture of hydraulic fracturing chemical additives and components from the formation. The release of these wastewaters into the environment poses potential risks that are poorly understood. Microbial communities in stream sediments form the base of the food chain and may serve as sentinels for changes in stream health. Iron-reducing organisms have been shown to play a role in the biodegradation of a wide range of organic compounds, and so to evaluate their response to UOG wastewater, we enriched anaerobic microbial communities from sediments collected upstream (background) and downstream (impacted) of an UOG wastewater injection disposal facility in the presence of hydraulic fracturing fluid (HFF) additives: guar gum, ethylene glycol, and two biocides, 2,2-dibromo-3-nitrilopropionamide (DBNPA) and bronopol (C3H6BrNO4). Iron reduction was significantly inhibited early in the incubations with the addition of biocides, whereas amendment with guar gum and ethylene glycol stimulated iron reduction relative to levels in the unamended controls. Changes in the microbial community structure were observed across all treatments, indicating the potential for even small amounts of UOG wastewater components to influence natural microbial processes. The microbial community structure differed between enrichments with background and impacted sediments, suggesting that impacted sediments may have been preconditioned by exposure to wastewater. These experiments demonstrated the potential for biocides to significantly decrease iron reduction rates immediately following a spill and demonstrated how microbial communities previously exposed to UOG wastewater may be more resilient to additional spills.IMPORTANCEOrganic components of UOG wastewater can alter microbial communities and biogeochemical processes, which could alter the rates of essential natural attenuation processes. These findings provide new insights into microbial responses following a release of UOG wastewaters and are critical for identifying strategies for the remediation and natural attenuation of impacted environments.
Whole-Genome Sequence Analysis of Streptococcus pneumoniae Strains That Cause Hospital-Acquired Pneumonia Infections
Authors: Chang Bin , Morita Masatomo , Lee Ken-ichi , Ohnishi Makoto 
Published: February 2018

ABSTRACT

Streptococcus pneumoniae
colonizes the nasopharyngeal mucus in healthy individuals and can cause otitis media, pneumonia, and invasive pneumococcal diseases. In this study, we analyzed
S. pneumoniae
strains that caused 19 pneumonia episodes in long-term inpatients with severe underlying disease in a hospital during a period of 14 months (from January 2014 to February 2015). Serotyping and whole-genome sequencing analyses revealed that 18 of the 19 pneumonia cases were caused by
S. pneumoniae
strains belonging to 3 genetically distinct groups: clonal complex 9999 (CC9999), sequence type 282 (ST282), and ST166. The CC9999 and ST282 strains appeared to have emerged separately by a capsule switch from the pandemic PMEN 1 strain (Spain
23F
-ST81). After all the long-term inpatients were inoculated with the 23-valent pneumococcal polysaccharide vaccine, no other nosocomial pneumonia infections occurred until March 2016.
Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus
Authors: Carossino Mariano , Dini Pouya , Kalbfleisch Theodore S. , Loynachan Alan T. , Canisso Igor F. , Shuck Kathleen M. , Timoney Peter J. , Cook R. Frank , Balasuriya Udeni B. R. 
Published: February 2018

ABSTRACT

Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the
CXCL16
gene (
CXCL16S
) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion.

IMPORTANCE
Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the
CXCL16
gene (
CXCL16S
) and is maintained despite induction of local inflammatory, humoral, and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first time, this study suggests complex interactions between eca-mir-128 and cellular elements at the site of EAV persistence and implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the reproductive tract during long-term persistence.
Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey
Authors: Chen Liang , Zhou Fei , Li Hui , Xing Xiqian , Han Xiudi , Wang Yiming , Zhang Chunxiao , Suo Lijun , Wang Jingxiang , Yu Guohua , Wang Guangqiang , Yao Xuexin , Yu Hongxia , Wang Lei , Liu Meng , Xue Chunxue , Liu Bo , Zhu Xiaoli , Li Yanli , Xiao Ying , Cui Xiaojing , Li Lijuan , Uyeki Timothy M , Wang Chen , Cao Bin 
Published: February 2018

ObjectivesTo describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China.DesignThis was a multicentre, retrospective, observational study.Setting13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014ParticipantsInformation on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms.Primary and secondary outcome measuresResource use for CAP management.ResultsOf 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0–1 and Pneumonia Severity Index risk class I–II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%.ConclusionsThese data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China.Trial registration numberNCT02489578; Results.
Coronary artery bypass grafting in patients treated with thoracic radiation: a case–control study
Authors: Fender Erin Amanda , Chandrashekar Pranav , Liang Jackson J , Dhar Priyank R , Sio Terence T , Stulak John M , Lennon Ryan J , Slusser Joshua P , Ashman Jonathan B , Miller Robert C , Herrmann Joerg , Prasad Abhiram , Sandhu Gurpreet S 
Published: February 2018

Background and aimThoracic radiation therapy (XRT) for cancer is associated with the development of significant coronary artery disease that may require coronary artery bypass grafting surgery (CABG). Contemporary acute surgical outcomes and long-term postoperative survival of patients with prior XRT have not been well characterised.MethodsThis was a retrospective, single-centre study of patients with a history of thoracic XRT who required CABG and who were propensity matched against 141 controls who underwent CABG over the same time period. The objectives were to assess early CABG outcomes and long-term survival in patients with prior XRT.ResultsThirty-eight patients with a history of previous thoracic XRT underwent CABG from 1994 to 2013. The median time from XRT exposure to surgery was 7.9 years (IQR: 2.5–18.4 years). Perioperative adverse events were similar in the XRT group and controls; however, there was a trends lower utilisation of internal mammary artery (IMA) grafts in the XRT group (89%vs98%, P=0.13). After a median postoperative follow-up of 5.4 years (IQR 0.9–9.4 years), no difference in long-term all-cause mortality was observed.ConclusionPatients with prior thoracic XRT who undergo CABG have similar long-term all-cause mortality compared with controls. Isolated CABG after thoracic XRT is not associated with higher perioperative complications, but IMA graft use may be limited by prior XRT.
Wilson disease: more than meets the eye
Authors: Kelly Claire , Pericleous Marinos 
Published: February 2018

AbstractWilson disease is a rare but important disorder of copper metabolism, with a failure to excrete copper appropriately into bile. It is a multisystem condition with presentations across all branches of medicine. Diagnosis can be difficult and requires a high index of suspicion. It should be considered in unexplained liver disease particularly where neuropsychiatric features are also present. Treatments are available for all stages of disease. A particularly important presentation not to overlook is acute liver failure which carries a high mortality risk and may require urgent liver transplantation. Here, we provide an overview of this complex condition.
P–V criticality of conformal gravity holography in four dimensions
Authors: Pradhan Parthapratim 
Published: February 2018

We examine the critical behavior, i.e. P–V criticality of conformal gravity (CG) in an extended phase space in which the cosmological constant should be interpreted as a thermodynamic pressure and the corresponding conjugate quantity as a thermodynamic volume. The main potential point of interest in CG is that there exists a nontrivial Rindler parameter [Formula: see text] in the spacetime geometry. This geometric parameter has an important role to construct a model for gravity at large distances where the parameter “[Formula: see text]” actually originates. We also investigate the effect of the said parameter on the black hole (BH) thermodynamic equation of state, critical constants, Reverse Isoperimetric Inequality, first law of thermodynamics, Hawking–Page phase transition and Gibbs free energy for this BH. We speculate that due to the presence of the said parameter, there has been a deformation in the shape of the isotherms in the P–V diagram in comparison with the charged-anti de Sitter (AdS) BH and the chargeless-AdS BH. Interestingly, we find that the critical ratio for this BH is [Formula: see text], which is greater than the charged AdS BH and Schwarzschild–AdS BH, i.e. [Formula: see text]. The symbols are defined in the main work. Moreover, we observe that the critical ratio has a constant value and it is independent of the nontrivial Rindler parameter [Formula: see text]. Finally, we derive the reduced equation of state in terms of the reduced temperature, the reduced volume and the reduced pressure, respectively.
Abstract ES1-2: Guidelines for postmastectomy radiotherapy
Authors: Recht A 
Published: February 2018

Abstract
A joint panel of the American Society of Clinical Oncology (ASCO), American Society for Radiation Oncology (ASTRO), and Society of Surgical Oncology (SSO) convened in 2015 to develop an update of the prior ASCO guideline (J Clin Oncol 2001;19:1539-1569) concerning the use of postmastectomy radiation therapy (PMRT). This effort focused on common scenarios where there have been substantial controversy. Their conclusions and supporting evidence have been published (J Clin Oncol 2016;34:4431-4442).
The Panel unanimously agreed that PMRT reduces the risks of local-regional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with 1-3 positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. The Panel however could not find sufficient evidence to recommend a specific formula or method of how to combine clinical, pathologic, and biologic data to calculate the risk of LRF. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT or not requires a great deal of clinical judgement. The Panel agreed clinicians making such recommendations for an individual patient should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase the risks of complications from PMRT.
When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the Panel recommended that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.
Patients with axillary nodal involvement following neoadjuvant systemic therapy should receive PMRT. The role of PMRT in other patients with clinical Stage I or II breast cancer is uncertain.
Finally, the Panel recommended that radiation therapy generally be given to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast when PMRT is used. However, there may be subgroups that will have limited, if any, benefits from treating both these nodal areas compared to treating only one of them or, perhaps, treating only the chest wall or reconstructed breast. There is insufficient evidence at this time to define such subgroups in detail.
This lecture will address selected elements of the data leading to the Panel's decisions.
Citation Format: Recht A. Guidelines for postmastectomy radiotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES1-2.
Abstract ES2-3: Managing increased breast cancer risk based on high and moderate penetrance gene mutations
Authors: Garber JE 
Published: February 2018

Abstract
Genetic testing in the modern era increasingly examines multiple genes using next generation technologies. Most assays include the high penetrance genes, which confer lifetime breast cancer risk greater than 5-fold, include BRCA1/2, TP53, CDH1 and PALB2. Moderate penetrance genes are associated with lifetime breast cancer risk in the range of 2-3 fold, and include ATM, NF1, CHEK2 (mutation-specific) and NBN, with BARD1 and others potentially joining the group. Substantial data has emerged from studies of women with BRCA1/2 mutations, evaluating the performance of screening technologies, such as mammogram, breast MRI and ultrasound, and the efficacy of risk-reducing breast and ovarian/fallopian tube surgical procedures. Guidelines exist in the NCCN (US) and ESMO guidelines in Europe, among others, trying to provide recommendations for the age at which to initiate screening or undergo risk-reducing salpingo-oophorectomies, for example. Data are increasing on the moderate penetrance genes but there is still much reliance on extrapolation from the high-penetrance genes, which should be done thoughtfully. One approach is to estimate the age at which lifetime breast cancer risk equals the risk from a high penetrance gene when screening is to begin and initiate imaging surveillance at that time. For example, initiation of annual breast imaging would be at age 40 for ATM (RR 2.8) instead of age 25 as is done for BRCA1/2 or age 20 as for TP53. However, there are no data that this is the correct age at which to initiate screening, so this practical suggestion must meet criteria for reasonableness as well as effectiveness. Other source of data may include more precise gene-specific risk estimates from focused genetic epidemiology studies, and ongoing data from studies of prospectively identified mutation carriers. Further understanding of the mechanisms of carcinogenicity for mutation carriers may also help to provide insights that can guide therapeutic and preventive approaches. For example, the work on RANK ligand by Lindeman et al has led to the development of a definitive breast cancer prevention trial examining the RANK-Ligand inhibitor Denosumab in BRCA1 mutation carriers, entitled BRCA-P, being led by C. Singer of the ABCSG and Dr. Lindeman, and to be conducted in sites around the world. Other approaches are in development and will be discussed.
Citation Format: Garber JE. Managing increased breast cancer risk based on high and moderate penetrance gene mutations [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES2-3.
Abstract ES3-3: Progress, paradigms, and pathways of long non-coding RNAs in cancer
Authors: Yang L 
Published: February 2018

Abstract
Despite recent advances in cancer research, many cancer types continue to be deficient of FDA-approved targeted therapies and also have poor prognoses. One of the fundamental challenges in developing targeted therapies against cancer lies in the absence of characterized molecular mechanisms that underlie tumor initiation and progression. These setbacks demand improved identification of biomarkers for human cancer, among which long non-coding RNAs (lncRNAs) show promise. It has become increasingly apparent that lncRNAs are aberrantly expressed in a broad spectrum of cancers and that they play key roles in promoting and maintaining cancer characteristics, demonstrating their clinical potential as biomarkers and therapeutic targets. In this review, we focus on the recent discoveries of lncRNAs in cancer signaling pathways as key signal transduction mediators. We review the functional roles of lncRNAs as protein, RNA and lipid binding partners in regulating cellular responses to extracellular signals and discuss their clinical potential as diagnostic indicators, stratification markers, and therapeutic targets of combinatorial treatments. Specifically, the following topics will be discussed: 1) Somatic mutations or disease-associated SNPs of lncRNAs implicate lncRNAs as cancer risk genes; 2) Through RNA-protein, RNA-RNA, RNA-lipid interactions, lncRNAs modulate cancer signaling pathways and consequences; 3) Dysregulation of lncRNAs lead to hyper- or hypo-activation of cellular pathways, leading to resistance to current targeted therapies; 4) Targeting lncRNA alone or a co-targeting strategy may help overcome the targeted therapy resistance.
Citation Format: Yang L. Progress, paradigms, and pathways of long non-coding RNAs in cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES3-3.