bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bed‐scale spatial patterns in dolomite abundance: Part II. Effect of varied fluid chemistry, flow rate, precursor mineralogy, temperature, textural heterogeneity, nucleation density and bed geometry
Authors: Budd David A. , Park Anthony J. 
Published: April 2019

AbstractReaction‐transport modelling shows that a lateral, metre‐scale pattern in dolomite abundance can form during replacive dolomitization of calcite and aragonite precursors by Mississippian, Triassic and modern seawaters advecting at >20 cm year−1 in low temperature (≤60°C) hydrogeological systems. The modelled pattern develops best in beds >1 m thick with a relatively uniform nucleate density and a low variance in reactive surface area (for example, grainstones). These conditions suggest that a lateral pattern in dolomite abundance should be expected in dolomites formed by any shallow hydrodynamic system that advects dolomitizing fluid horizontally, including the down‐gradient portion of a reflux system, the oceanward reaches of geothermal (Kohout) convection systems, and the seaward reaches of a seawater entrainment zone below a freshwater aquifer. However, even in those systems, a pattern will not form in all dolomites. Pattern will be muted in thinner (≤ ca 50 cm thick) beds and non‐emergent where the precursor had a high variance in reactive surface area (for example, a skeletal wackestone) and/or large variation in nucleate density. Pattern also did not form at temperatures above ca 60°C, which implies that pattern should not be expected in dolomites formed at intermediate to deep burial depths. As the patterns are horizontal, they also should not be expected where dolomitizing fluids moved vertically (for example, reflux immediately below a brine source). Pattern metrics (short‐range correlation length, and wavelength and amplitude of the longer cyclic component) vary with flow rate, fluid chemistry, bed thickness, porosity, grain size, temperature and the flow complexity (one‐dimensional, two‐dimensional or three‐dimensional) within the bed. However, no modelled pattern produced metrics larger than those documented on dolomite outcrops. The results thus constrain the length scales of porosity and permeability variance to include in petrophysical models of dolomite reservoirs, as well as the geological scenarios in which to consider metre‐scale lateral petrophysical variability.
International Association of Athletics Federations Consensus Statement 2019: Nutrition for Athletics
Authors: Burke Louise M. , Castell Linda M. , Casa Douglas J. , Close Graeme L. , Costa Ricardo J. S. , Desbrow Ben , Halson Shona L. , Lis Dana M. , Melin Anna K. , Peeling Peter , Saunders Philo U. , Slater Gary J. , Sygo Jennifer , Witard Oliver C. , Bermon Stéphane , Stellingwerff Trent 
Published: April 2019

The International Association of Athletics Federations recognizes the importance of nutritional practices in optimizing an Athlete’s well-being and performance. Although Athletics encompasses a diverse range of track-and-field events with different performance determinants, there are common goals around nutritional support for adaptation to training, optimal performance for key events, and reducing the risk of injury and illness. Periodized guidelines can be provided for the appropriate type, amount, and timing of intake of food and fluids to promote optimal health and performance across different scenarios of training and competition. Some Athletes are at risk of relative energy deficiency in sport arising from a mismatch between energy intake and exercise energy expenditure. Competition nutrition strategies may involve pre-event, within-event, and between-event eating to address requirements for carbohydrate and fluid replacement. Although a “food first” policy should underpin an Athlete’s nutrition plan, there may be occasions for the judicious use of medical supplements to address nutrient deficiencies or sports foods that help the athlete to meet nutritional goals when it is impractical to eat food. Evidence-based supplements include caffeine, bicarbonate, beta-alanine, nitrate, and creatine; however, their value is specific to the characteristics of the event. Special considerations are needed for travel, challenging environments (e.g., heat and altitude); special populations (e.g., females, young and masters athletes); and restricted dietary choice (e.g., vegetarian). Ideally, each Athlete should develop a personalized, periodized, and practical nutrition plan via collaboration with their coach and accredited sports nutrition experts, to optimize their performance.
Modeling Infectious Diseases in Mice with a “Humanized” Immune System
Authors: Li Yan , Di Santo James P. 
Published: April 2019

ABSTRACTHuman immune system (HIS) mice are created by transplanting human immune cells or their progenitor cells into highly immunodeficient recipient mouse hosts, thereby “humanizing” their immune systems. Over past decades, the field of HIS mice has evolved rapidly, as modifications of existing immunodeficient mouse strains have been developed, resulting in increasing levels of human tissue engraftment as humanization is optimized. Current HIS mouse models not only permit elevated levels of human cell engraftment but also demonstrate graft stability. As such, HIS mice are being extensively used to study the human innate and adaptive immune response against microbial infectionsin vivo. Compared to nonhumanized animal models, which are frequently infected with surrogate or adapted microbes, the HIS mouse models allow the analysis of interactions between human immune cells andbona fidepathogenic microbes, making them a more clinically relevant model. This article reviews the development of HIS mice and covers the different strategies used to humanize mice, as well as discussing the use of HIS mice for studying bacterial infections that cause human disease.
Regulation of
Staphylococcus aureus
Virulence
Authors: Jenul Christian , Horswill Alexander R. 
Published: April 2019

ABSTRACT

Staphylococcus aureus
is a Gram-positive opportunistic pathogen that has evolved a complex regulatory network to control virulence. One of the main functions of this interconnected network is to sense various environmental cues and respond by altering the production of virulence factors necessary for survival in the host, including cell surface adhesins and extracellular enzymes and toxins. Of these
S. aureus
regulatory systems, one of the best studied is the accessory gene regulator (
agr
), which is a quorum-sensing system that senses the local concentration of a cyclic peptide signaling molecule. This system allows
S. aureus
to sense its own population density and translate this information into a specific gene expression pattern. Besides
agr
, this pathogen uses other two-component systems to sense specific cues and coordinates responses with cytoplasmic regulators of the SarA protein family and alternative sigma factors. These divergent regulatory systems integrate the various environmental and host-derived signals into a network that ensures optimal pathogen response to the changing conditions. This article gives an overview of the most important and best-studied
S. aureus
regulatory systems and summarizes the functions of these regulators during host interactions. The regulatory systems discussed include the
agr
quorum-sensing system; the SaeRS, SrrAB, and ArlRS two-component systems, the cytoplasmic SarA-family regulators (SarA, Rot, and MgrA); and the alternative sigma factors (SigB and SigH).
Biological and Structural Diversity of Type IV Secretion Systems
Authors: Li Yang Grace , Hu Bo , Christie Peter J. 
Published: April 2019

ABSTRACT

The bacterial type IV secretion systems (T4SSs) are a functionally diverse superfamily of secretion systems found in many species of bacteria. Collectively, the T4SSs translocate DNA and monomeric and multimeric protein substrates to bacterial and eukaryotic cell types. T4SSs are composed of two large subfamilies, the conjugation machines and the effector translocators that transmit their cargoes through establishment of direct donor-target cell contacts, and a third small subfamily capable of importing or exporting substrates from or to the milieu. This review summarizes recent mechanistic and structural findings that are shedding new light on how T4SSs have evolved such functional diversity. Translocation signals are now known to be located C terminally or embedded internally in structural folds; these signals in combination with substrate-associated adaptor proteins mediate the docking of specific substrate repertoires to cognate VirD4-like receptors. For the
Legionella pneumophila
Dot/Icm system, recent work has elucidated the structural basis for adaptor-dependent substrate loading onto the VirD4-like DotL receptor. Advances in definition of T4SS machine structures now allow for detailed comparisons of nanomachines closely related to the
Agrobacterium tumefaciens
VirB/VirD4 T4SS with those more distantly related, e.g., the Dot/Icm and
Helicobacter pylori
Cag T4SSs. Finally, it is increasingly evident that T4SSs have evolved a variety of mechanisms dependent on elaboration of conjugative pili, membrane tubes, or surface adhesins to establish productive contacts with target cells. T4SSs thus have evolved extreme functional diversity through a plethora of adaptations impacting substrate selection, machine architecture, and target cell binding.
A guided and unguided internet- and mobile-based intervention for chronic pain: health economic evaluation alongside a randomised controlled trial
Authors: Paganini Sarah , Lin Jiaxi , Kählke Fanny , Buntrock Claudia , Leiding Delia , Ebert David D , Baumeister Harald 
Published: April 2019

ObjectiveThis study aims at evaluating the cost-effectiveness and cost-utility of a guided and unguided internet-based intervention for chronic pain patients (ACTonPainguidedand ACTonPainunguided) compared with a waitlist control group (CG) as well as the comparative cost-effectiveness of the guided and the unguided version.DesignThis is a health economic evaluation alongside a three-arm randomised controlled trial from a societal perspective. Assessments were conducted at baseline, 9 weeks and 6 months after randomisation.SettingParticipants were recruited through online and offline strategies and in collaboration with a health insurance company.Participants302 adults (≥18 years, pain for at least 6 months) were randomly allocated to one of the three groups (ACTonPainguided, ACTonPainunguided, CG).InterventionsACTonPain consists of seven modules and is based on Acceptance and Commitment Therapy. ACTonPainguidedand ACTonPainunguidedonly differ in provision of human support.Primary and secondary outcome measuresMain outcomes of the cost-effectiveness and the cost-utility analyses were meaningful change in pain interference (treatment response) and quality-adjusted life years (QALYs), respectively. Economic evaluation estimates were the incremental cost-effectiveness and cost-utility ratio (ICER/ICUR).ResultsAt 6-month follow-up, treatment response and QALYs were highest in ACTonPainguided(44% and 0.280; mean costs = €6,945), followed by ACTonPainunguided(28% and 0.266; mean costs = €6,560) and the CG (16% and 0.244; mean costs = €6,908). ACTonPainguidedvs CG revealed an ICER of €45 and an ICUR of €604.ACTonPainunguideddominated CG. At a willingness-to-pay of €0 the probability of being cost-effective was 50% for ACTonPainguided(vs CG, for both treatment response and QALY gained) and 67% for ACTonPainunguided(vs CG, for both treatment response and QALY gained). These probabilities rose to 95% when society’s willingness-to-pay is €91,000 (ACTonPainguided) and €127,000 (ACTonPainunguided) per QALY gained. ACTonPainguidedvs ACTonPainunguidedrevealed an ICER of €2,374 and an ICUR of €45,993.ConclusionsDepending on society’s willingness-to-pay, ACTonPain is a potentially cost-effective adjunct to established pain treatment. ACTonPainunguided(vs CG) revealed lower costs at better health outcomes. However, uncertainty has to be considered. Direct comparison of the two interventions does not indicate a preference for ACTonPainguided.Trial registration numberDRKS00006183.
Chronic hepatitis B virus infection and total and cause-specific mortality: a prospective cohort study of 0.5 million people
Authors: Si Jiahui , Yu Canqing , Guo Yu , Bian Zheng , Meng Ruogu , Yang Ling , Chen Yiping , Jin Jianrong , Liu Jingchao , Guo Ziyan , Chen Junshi , Chen Zhengming , Lv Jun , Li Liming 
Published: April 2019

ObjectivesChronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality.DesignPopulation-based prospective cohort study.SettingChina Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants475 801 participants 30–79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline.Primary and secondary outcome measuresTotal and cause-specific mortality.ResultsA total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants.ConclusionsAmong Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.
Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans
Authors: Che Li , Chi Wenna , Qiao Yu , Zhang Jie , Song Xinhua , Liu Ye , Li Lei , Jia Jiaoyuan , Pilo Maria G , Wang Jingxiao , Cigliano Antonio , Ma Zhilong , Kuang Wenhua , Tang Zefang , Zhang Zemin , Shui Guanghou , Ribback Silvia , Dombrowski Frank , Evert Matthias , Pascale Rosa Maria , Cossu Carla , Pes Giovanni Mario , Osborne Timothy F , Calvisi Diego F , Chen Xin , Chen Ligong 
Published: April 2019

ObjectiveIncreased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC).DesignWe investigated the functional contribution of fatty acid synthase (Fasn)-mediated de novo FA synthesis in a murine HCC model induced by loss of Pten and overexpression of c-Met (sgPten/c-Met) using liver-specificFasnknockout mice. Expression arrays and lipidomic analysis were performed to characterise the global gene expression and lipid profiles, respectively, of sgPten/c-Met HCC from wild-type andFasnknockout mice. Human HCC cell lines were used for in vitro studies.ResultsAblation ofFasnsignificantly delayed sgPten/c-Met-driven hepatocarcinogenesis in mice. However, eventually, HCC emerged inFasnknockout mice. Comparative genomic and lipidomic analyses revealed the upregulation of genes involved in cholesterol biosynthesis, as well as decreased triglyceride levels and increased cholesterol esters, in HCC from these mice. Mechanistically, loss ofFasnpromoted nuclear localisation and activation of sterol regulatory element binding protein 2 (Srebp2), which triggered cholesterogenesis. Blocking cholesterol synthesis via the dominant negative form of Srebp2 (dnSrebp2) completely prevented sgPten/c-Met-driven hepatocarcinogenesis inFasnknockout mice. Similarly, silencing ofFASNresulted in increasedSREBP2activation and hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (HMGCR)expression in human HCC cell lines. Concomitant inhibition of FASN-mediated FA synthesis and HMGCR-driven cholesterol production was highly detrimental for HCC cell growth in culture.ConclusionOur study uncovers a novel functional crosstalk between aberrant lipogenesis and cholesterol biosynthesis pathways in hepatocarcinogenesis, whose concomitant inhibition might represent a therapeutic option for HCC.
Direct carotid puncture for endovascular thrombectomy in acute ischemic stroke
Authors: Roche Adam , Griffin Emma , Looby Seamus , Brennan Paul , O’Hare Alan , Thornton John , Boyle Karl , Williams David , Moynihan Barry , Power Sarah 
Published: April 2019

BackgroundMechanical thrombectomy is the standard of care for acute ischemic strokes with proximal intracranial occlusion. Arterial access is commonly achieved with femoral artery puncture, although this is not always possible. In this case series, we describe 11 cases of anterior circulation stroke where direct carotid puncture was used to obtain vascular access.Methods and materialsA review of a prospectively maintained thrombectomy database over a 2-year period (August 2016 – August 2018) was undertaken to identify cases where direct carotid access was performed. CT and angiographic imaging were reviewed. Indications for carotid access, techniques used, technical success of procedure, recanalization rates, procedure-related complications, and patient outcomes were assessed.ResultsEleven patients out of 498 overall thrombectomy procedures (2.2% thrombectomies) underwent direct carotid access. Median National Institutes of Health Stroke Scale was 20. Seventy three percent of patients received intravenous thrombolysis. The direct carotid approach was performed following the failed femoral approach due to unfavorable aortic arch anatomy, vessel tortuosity, and severe atherosclerotic disease. Direct carotid puncture was successful in 10 patients, and unsuccessful in one. Successful recanalization (TICI 2b–3) was achieved in eight patients. One patient had spontaneously recanalized on angiography. There was failed recanalization in one patient with tandem ICA and M1 occlusion. Carotid access complications included one patient with both neck hematoma and asymptomatic ICA dissection, and one of delayed central retinal artery occlusion.ConclusionThis case series highlights direct carotid puncture as a successful alternative when the femoral approach is not possible, allowing thrombectomy in patients who would otherwise be unsuitable.
Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation pain: a multicenter, randomized, placebo-controlled trial
Authors: Gilmore Christopher , Ilfeld Brian , Rosenow Joshua , Li Sean , Desai Mehul , Hunter Corey , Rauck Richard , Kapural Leonardo , Nader Antoun , Mak John , Cohen Steven , Crosby Nathan , Boggs Joseph 
Published: April 2019

Background and objectivesChronic neuropathic pain is a common challenging condition following amputation. Recent research demonstrated the feasibility of percutaneously implanting fine-wire coiled peripheral nerve stimulation (PNS) leads in proximity to the sciatic and femoral nerves for postamputation pain. A multicenter, double-blinded, randomized, placebo-controlled study collected data on the safety and effectiveness of percutaneous PNS for chronic neuropathic pain following amputation.MethodsTwenty-eight lower extremity amputees with postamputation pain were enrolled. Subjects underwent ultrasound-guided implantation of percutaneous PNS leads and were randomized to receive PNS or placebo for 4 weeks. The placebo group then crossed over and all subjects received PNS for four additional weeks. The primary efficacy endpoint evaluated the proportion of subjects reporting ≥50% pain reduction during weeks 1–4.ResultsA significantly greater proportion of subjects receiving PNS (n=7/12, 58%, p=0.037) demonstrated ≥50% reductions in average postamputation pain during weeks 1–4 compared with subjects receiving placebo (n=2/14, 14%). Two subjects were excluded from efficacy analysis due to eligibility changes. Significantly greater proportions of PNS subjects also reported ≥50% reductions in pain (n=8/12, 67%, p=0.014) and pain interference (n=8/10, 80%, p=0.003) after 8 weeks of therapy compared with subjects receiving placebo (pain: n=2/14, 14%; pain interference: n=2/13, 15%). Prospective follow-up is ongoing; four of five PNS subjects who have completed 12-month follow-up to date reported ≥50% pain relief.ConclusionsThis work demonstrates that percutaneous PNS therapy may provide enduring clinically significant pain relief and improve disability in patients with chronic neuropathic postamputation pain.Trial registration numberNCT01996254.
FINANCIAL INTERMEDIARIES’ ASSET–LIABILITY DEPENDENCY AND LOW-INTEREST-RATE ENVIRONMENT: EVIDENCE FROM EU LIFE INSURERS
Authors: CURCIO DOMENICO , BORRI NICOLA , CERRONE ROSARIA , COCOZZA ROSA 
Published: April 2019

This research studies the relationships between the two sides of life insurers’ balance sheet and investigates whether and how they changed during recent past years, when European Central Bank monetary policy drove market rates to unprecedented low levels. By using a canonical correlation analysis, we study the internal structure of the links within and between the asset and liability sides of 24 major European Union (EU) life insurers’ balance sheets over the 2007–2015 time horizon. We find strong and substantial evidence that life insurers’ assets and liabilities have become more independent over time. We argue that the declining trend of market interest rates has contributed to the generalized reduction in the linkage between the asset side and the liability side of EU life insurers, and has made insurance companies more exposed to ALM-related risks relative to the period before the financial crisis.
Impact of Smoking Status on Stroke Recurrence
Authors: Chen Jingjing , Li Shun , Zheng Kuo , Wang Huaiming , Xie Yi , Xu Pengfei , Dai Zhengze , Gu Mengmeng , Xia Yaqian , Zhao Min , Liu Xinfeng , Xu Gelin 
Published: April 2019

Background
Smoking is a well‐established risk factor of stroke and smoking cessation has been recommended for stroke prevention; however, the impact of smoking status on stroke recurrence has not been well studied to date.

Methods and Results

Patients with first‐ever stroke were enrolled and followed in the NSRP (Nanjing Stroke Registry Program). Smoking status was assessed at baseline and reassessed at the first follow‐up. The primary end point was defined as fatal or nonfatal recurrent stroke after 3 months of the index stroke. The association between smoking and the risk of stroke recurrence was analyzed with multivariate Cox regression model. At baseline, among 3069 patients included, 1331 (43.4%) were nonsmokers, 263 (8.6%) were former smokers, and 1475 (48.0%) were current smokers. At the first follow‐up, 908 (61.6%) patients quit smoking. After a mean follow‐up of 2.4±1.2 years, 293 (9.5%) patients had stroke recurrence. With nonsmokers as the reference, the adjusted hazard ratios for stroke recurrence were 1.16 (95%
CI
, 0.75–1.79) in former smokers, 1.31 (95%
CI
, 0.99–1.75) in quitters, and 1.93 (95%
CI
, 1.43–2.61) in persistent smokers. Among persistent smokers, hazard ratios for stroke recurrence ranged from 1.68 (95%
CI
, 1.14–2.48) in those who smoked 1 to 20 cigarettes daily to 2.72 (95%
CI
, 1.36–5.43) in those who smoked more than 40 cigarettes daily (
P
for trend <0.001).

Conclusions
After an initial stroke, persistent smoking increases the risk of stroke recurrence. There exists a dose–response relationship between smoking quantity and the risk of stroke recurrence.