bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelets and infections in the resource‐limited countries with a focus on malaria and viral haemorrhagic fevers
Authors: Thachil Jecko 
Published: March 2017

SummaryInfections continue to cause a high incidence of mortality and morbidity in resource‐poor nations. Although antimicrobial therapy has aided mostly in dealing with the pathogenic micro‐organisms themselves, the collateral damage caused by the infections continue to cause many deaths. Intensive care support and manipulation of the hosts’ abnormal response to the infection have helped to improve mortality in well‐resourced countries. But, in those areas with limited resources, this is not yet the case and simpler methods of diagnosis and interventions are required. Thrombocytopenia is one of the most common manifestations in all these infections and may be used as an easily available prognostic indicator and marker for the severity of the infections. In this review, the relevance of platelets in infections in general, and specifically to tropical infections, malaria, and viral haemorrhagic fevers in the emerging countries is discussed. Better understanding of the pathophysiology and the role of platelets in particular in such conditions is likely to translate into better patient care and thus reduce morbidity and mortality.
Modified retroperitoneal lymph node dissection for post‐chemotherapy residual tumour: a long‐term update
Authors: Cho Jane S. , Kaimakliotis Hristos Z. , Cary Clint , Masterson Timothy A. , Beck Stephen , Foster Richard 
Published: March 2017

ObjectiveTo update previously reported outcomes of modified‐template post‐chemotherapy retroperitoneal lymph node dissection (PC‐RPLND) in appropriately selected patients with metastatic non‐seminomatous germ cell tumour (NSGCT), as our previous report was criticised for short follow‐up and so we now provide a long‐term update on this cohort.Patients and MethodsIn all, 100 patients with normal serum markers after cisplatin‐based chemotherapy and residual retroperitoneal tumour underwent modified PC‐RPLND between 1991 and 2004. Using a prospectively managed institutional testicular cancer database, long‐term follow‐up was obtained.ResultsAs previously reported, 43 patients underwent a right‐modified template, 18 patients underwent a full‐left‐modified template, and 39 patients underwent a left‐modified template. The updated long‐term median follow‐up for the entire cohort is 125 months. Seven patients developed recurrent disease with a median (range) time to recurrence of 11 (6–102) months, and one patient died from recurrent disease in the chest 4 years after surgery. All recurrences were outside the boundaries of a full‐bilateral template RPLND, with the most common location of recurrence being the chest. The 5‐ and 10‐year recurrence‐free survival rates were 93% and 92%, respectively. The overall survival at 10 years was 99%.ConclusionsIn appropriately selected patients with low‐volume disease before and after chemotherapy, a modified template has durable long‐term efficacy without risk of in‐field recurrences at a median follow‐up of 125 months.
Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: an update
Authors: Crespi Arianna , Colombo Sara Francesca , Gotti Cecilia 
Published: March 2017

Neuronal nicotinic ACh receptors (nAChRs) are a family of ACh‐gated cation channels, and their homeostasis or proteostasis is essential for the correct physiology of the central and peripheral nervous systems. The proteostasis network regulates the folding, assembly, degradation and trafficking of nAChRs in order to ensure their efficient and functional expression at the cell surface. However, as nAChRs are multi‐subunit, multi‐span, integral membrane proteins, the folding and assembly is a very inefficient process, and only a small proportion of subunits can form functional pentamers. Moreover, the efficiency of assembly and trafficking varies widely depending on the nAChR subtypes and the cell type in which they are expressed. A detailed understanding of the mechanisms that regulate the functional expression of nAChRs in neurons and non‐neuronal cells is therefore important. The purpose of this short review is to describe more recent findings concerning the chaperone proteins and target‐specific and target‐nonspecific pharmacological chaperones that modulate the expression of nAChR subtypes, and the possible mechanisms that underlie the dynamic changes of cell surface nAChRs.Linked ArticlesThis article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors
Authors: Bryant A H , Menzies G E , Scott L M , Spencer-Harty S , Davies L B , Smith R A , Jones R H , Thornton C A 
Published: March 2017

SummaryThe role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal–fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, −7, −8 and −9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes.
Constitutional LZTR1 mutation presenting with a unilateral vestibular schwannoma in a teenager
Authors: Gripp K.W. , Baker L. , Kandula V. , Piatt J. , Walter A. , Chen Z. , Messiaen L. 
Published: March 2017

Schwannomatosis is a rare neurofibromatosis clinically diagnosed by age‐dependent criteria, with bilateral vestibular schwannoma and/or a constitutional NF2 mutation representing exclusion criteria. Following SMARCB1 germline mutations, constitutional mutations in LZTR1 were discovered. We report on the molecular investigation in a patient presenting at 14 years with a unilateral vestibular schwannoma, ultimately causing blindness and unilateral hearing loss, in the absence of other schwannomas or a positive family history.In DNA derived from frozen tumor tissue, a comprehensive NF2, SMARCB1 and LZTR1 analysis showed an NF2 truncating mutation c.1006_1021delins16; an LZTR1 mutation c.791+1G>A; and a partial 22q deletion including NF2, SMARCB1 and LZTR1. Sequence analysis on peripheral blood derived DNA showed the LZTR1 mutation to be constitutional, but the NF2 mutation and partial 22q deletion were not found, indicating them to be somatic events. RNA‐based targeted analysis confirmed missplicing of LZTR1 intron 8, predicted to result in a premature stop codon. This LZTR1 mutation was paternally inherited.While isolated vestibular schwannoma or NF2 may be considered in a young individual with a unilateral vestibular schwannoma, this report suggests that
LZTR1
‐related schwannomatosis be added to this differential diagnosis.
Gaze‐based rehearsal in children under 7: a developmental investigation of eye movements during a serial spatial memory task
Authors: Morey Candice C. , Mareva Silvana , Lelonkiewicz Jaroslaw R. , Chevalier Nicolas 
Published: March 2017

AbstractThe emergence of strategic verbal rehearsal at around 7 years of age is widely considered a major milestone in descriptions of the development of short‐term memory across childhood. Likewise, rehearsal is believed by many to be a crucial factor in explaining why memory improves with age. This apparent qualitative shift in mnemonic processes has also been characterized as a shift from passive visual to more active verbal mnemonic strategy use, but no investigation of the development of overt spatial rehearsal has informed this explanation. We measured serial spatial order reconstruction in adults and groups of children 5–7 years old and 8–11 years old, while recording their eye movements. Children, particularly the youngest children, overtly fixated late‐list spatial positions longer than adults, suggesting that younger children are less likely to engage in covert rehearsal during stimulus presentation than older children and adults. However, during retention the youngest children overtly fixated more of the to‐be‐remembered sequences than any other group, which is inconsistent with the idea that children do nothing to try to remember. Altogether, these data are inconsistent with the notion that children under 7 do not engage in any attempts to remember. They are most consistent with proposals that children's style of remembering shifts around age 7 from reactive cue‐driven methods to proactive, covert methods, which may include cumulative rehearsal.
Salsalate improves glycaemia in overweight persons with diabetes risk factors of stable statin‐treated cardiovascular disease: A 30‐month randomized placebo‐controlled trial
Authors: Salastekar Ninad , Desai Tanvi , Hauser Thomas , Schaefer Ernst J. , Fowler Kristen , Joseph Stacey , Shoelson Steven E. , Goldfine Allison B. ,   on behalf of the TINSAL‐CVD study team
Published: March 2017

ObjectiveTo assess long‐term efficacy and safety of salsalate to improve glycemia in persons with diabetes risk, who are overweight with statin‐treated, stable coronary heart disease.MethodsGlycemic status was assessed in 192 persons without diabetes at baseline in a pre‐specified secondary analysis from Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL‐CVD), a multi‐center, double‐masked, randomized (1:1), placebo‐controlled, parallel clinical trial.ResultsParticipants were mostly Caucasian males, age 60±7 years, BMI 31.4±3.0 kg/m2, fasting glucose 92.8±11.0 mg/dL, and HbA1c 5.8±0.3%. Reductions in mean fasting glucose ‐5.70 mg/dL (95%CI: ‐7.44 to ‐3.97 mg/dL, P<0.001), HbA1c ‐0.11% (95%CI: ‐0.210 to ‐0.002%, P=0.046) and glycated serum protein ‐81.8 μg/mL (95%CI: ‐93.7 to ‐69.9 μg/mL, P<0.001) were demonstrated in salsalate compared to placebo‐assigned groups over 30 months. Reductions in fasting glucose and glycated serum protein were greater with salsalate compared to placebo in participants with prediabetes compared to a normoglycemic sub‐group (Pinteraction=0.018). Salsalate lowered total white blood cell counts (mean difference ‐0.7x103/μL, 95%CI: ‐1.0 to ‐0.4 x103/μL, P<0.001) and increased adiponectin (mean difference 1.8 μg/mL, 95%CI: 0.9 to 2.6 μg/mL, P<0.001) and albuminurea (16.7 μg/mg, 95%CI: 6.4 to 27.1 μg/mg, P<0.001) compared to placebo, consistent with previous results for patients with type 2 diabetes taking salsalate for shorter times.ConclusionsSalsalate improves glycemia in obese persons at increased risk for diabetes, and hence may decrease risk of incident type 2 diabetes. Salsalate may inform new therapeutic approaches for diabetes prevention, but renal safety may limit clinical utility.
Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: Results of a Phase IV open‐label randomized controlled study (the SMART study)
Authors: Du Jin , Liang Li , Fang Hui , Xu Fengmei , Li Wei , Shen Liya , Wang Xueying , Xu Chun , Bian Fang , Mu Yiming 
Published: March 2017

AimTo investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy.Methods
SMART was a 24‐week, multicentre, randomized, parallel‐group, open‐label Phase IV study conducted at 35 sites in China (September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events (GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication.ResultsFour‐hundred and eighty‐eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre‐ and ≥1 post‐baseline efficacy values recorded. Saxagliptin was non‐inferior to acarbose for glycaemic control [Week 24 HbA1c change: −0.82% and −0.78%, respectively; difference (95% confidence interval): −0.04 (−0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose.ConclusionBoth therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice.Clinical trial registration number: NCT02243176, clinicaltrials.gov.
Larger right atrium than left atrium is associated with all‐cause mortality in elderly patients with heart failure
Authors: Almodares Qays , Wallentin Guron Cecilia , Thurin Anders , Fu Michael , Kontogeorgos Silvana , Thunstrom Erik , Johansson Magnus C. 
Published: March 2017

BackgroundWhile left atrial (LA) enlargement is known as an early sign of left heart disease with prognostic implications in heart failure (HF), the importance of right atrial (RA) enlargement is less well studied, and the prognostic implications of interatrial size comparison are insufficiently understood. The aim of this study was to test the hypothesis that RA area larger than LA area in apical four‐chamber view is associated with all‐cause mortality in elderly patients with HF independent of left ventricular ejection fraction (LVEF).MethodsRetrospectively, 289 patients above 65 years hospitalized for HF between April 2007 and April 2008, and who underwent an echocardiogram, were enrolled. All‐cause mortality was registered during a follow‐up of at least 56 months. Baseline parameters measured were RA area, LA area, LA volume, LVEF, left ventricular mass (LVM), tissue Doppler systolic velocity of right ventricular free wall (SmRV), presence of severe tricuspid regurgitation (TR), tricuspid gradient, central venous pressure, systolic pulmonary artery pressure, as well as some parameters of diastolic function.ResultsIn univariate analysis RA larger than LA was associated with all‐cause mortality (hazard ratio [HR] of 1.88, P<.001). The relation of RA larger than LA to all‐cause mortality remained even after adjusting for age, heart rate, LVEF, atrial fibrillation, percutaneous coronary intervention, LVM index, LA volume index, SmRV, and the presence of severe TR (HR: 1.79, P=.04).ConclusionRA larger than LA, independently of LVEF, is associated with all‐cause mortality in elderly patients hospitalized due to HF.
Rule‐Following and Rule‐Breaking: Kierkegaard and Wittgenstein
Authors: Watts Daniel 
Published: March 2017

AbstractMy aim in this paper is twofold: to establish that Kierkegaard's so‐called theory of the leap strongly anticipates a line of argument that is central to Wittgenstein's so‐called rule‐following considerations; and to begin to show how Kierkegaard's work has fruitful contributions of its own to make to on‐going discussions about rules and rule‐following. The paper focuses throughout on the question of how, if at all, human rule‐following can be distinguished from behaviour that is merely mechanical or instinctual. I identify a central line of argument in Wittgenstein that problematizes this question by establishing the basis our ability to follow rules in our spontaneous responses. I argue that Kierkegaard not only strongly anticipates this line of argument but also offers a distinctive story about what, at bottom, makes the difference between human rule‐following and behaviour that is merely mechanical or instinctual. In a word, on Kierkegaard's story, what makes the difference is: anxiety.
Climatic changes can drive the loss of genetic diversity in a Neotropical savanna tree species
Authors: Lima Jacqueline S. , Ballesteros‐Mejia Liliana , Lima‐Ribeiro Matheus S. , Collevatti Rosane G. 
Published: March 2017

AbstractThe high rates of future climatic changes, compared with the rates reported for past changes, may hamper species adaptation to new climates or the tracking of suitable conditions, resulting in significant loss of genetic diversity. Trees are dominant species in many biomes and because they are long‐lived, they may not be able to cope with ongoing climatic changes. Here, we coupled ecological niche modelling (ENM) and genetic simulations to forecast the effects of climatic changes on the genetic diversity and the structure of genetic clusters. Genetic simulations were conditioned to climatic variables and restricted to plant dispersal and establishment. We used a Neotropical savanna tree as species model that shows a preference for hot and drier climates, but with low temperature seasonality. The ENM predicts a decreasing range size along the more severe future climatic scenario. Additionally, genetic diversity and allelic richness also decrease with range retraction and climatic genetic clusters are lost for both future scenarios, which will lead genetic variability to homogenize throughout the landscape. Besides, climatic genetic clusters will spatially reconfigure on the landscape following displacements of climatic conditions. Our findings indicate that climate change effects will challenge population adaptation to new environmental conditions because of the displacement of genetic ancestry clusters from their optimal conditions.
CO2 exchange and evapotranspiration across dryland ecosystems of southwestern North America
Authors: Biederman Joel A. , Scott Russell L. , Bell Tom W. , Bowling David R. , Dore Sabina , Garatuza‐Payan Jaime , Kolb Thomas E. , Krishnan Praveena , Krofcheck Dan J. , Litvak Marcy E. , Maurer Gregory E. , Meyers Tilden P. , Oechel Walter C. , Papuga Shirley A. , Ponce‐Campos Guillermo E. , Rodriguez Julio C. , Smith William K. , Vargas Rodrigo , Watts Christopher J. , Yepez Enrico A. , Goulden Michael L. 
Published: March 2017

AbstractGlobal‐scale studies suggest that dryland ecosystems dominate an increasing trend in the magnitude and interannual variability of the land CO2 sink. However, such analyses are poorly constrained by measured CO2 exchange in drylands. Here we address this observation gap with eddy covariance data from 25 sites in the water‐limited Southwest region of North America with observed ranges in annual precipitation of 100–1000 mm, annual temperatures of 2–25°C, and records of 3–10 years (150 site‐years in total). Annual fluxes were integrated using site‐specific ecohydrologic years to group precipitation with resulting ecosystem exchanges. We found a wide range of carbon sink/source function, with mean annual net ecosystem production (NEP) varying from ‐350 to +330 gCm−2 across sites with diverse vegetation types, contrasting with the more constant sink typically measured in mesic ecosystems. In this region, only forest‐dominated sites were consistent carbon sinks. Interannual variability of NEP, gross ecosystem production (GEP), and ecosystem respiration (Reco) was larger than for mesic regions, and half the sites switched between functioning as C sinks/C sources in wet/dry years. The sites demonstrated coherent responses of GEP and NEP to anomalies in annual evapotranspiration (ET), used here as a proxy for annually available water after hydrologic losses. Notably, GEP and Reco were negatively related to temperature, both interannually within site and spatially across sites, in contrast to positive temperature effects commonly reported for mesic ecosystems. Models based on MODIS satellite observations matched the cross‐site spatial pattern in mean annual GEP but consistently underestimated mean annual ET by ~50%. Importantly, the MODIS‐based models captured only 20–30% of interannual variation magnitude. These results suggest the contribution of this dryland region to variability of regional to global CO2 exchange may be up to 3–5 times larger than current estimates.
An Update on Non‐Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine
Authors: Puledda Francesca , Goadsby Peter J. 
Published: March 2017

ObjectiveTo review current neuromodulation treatments available for migraine therapy, both in the acute and preventive setting.MethodsThe published literature was reviewed for studies reporting the effects of different neuromodulation strategies in migraine with and without aura. The use of non‐invasive: single pulse transcranial magnetic stimulation, non‐invasive vagal nerve stimulation, supraorbital nerve stimulation, and transcranial direct current stimulation, as well as invasive methods such as occipital nerve stimulation and sphenopalatine ganglion stimulation, are assessed.ResultsThe available evidence shows that non‐invasive techniques represent promising treatment strategies, whereas an invasive approach should only be used where patients are refractory to other preventives, including non‐invasive methods.ConclusionsNeuromodulation is emerging as an exciting approach to migraine therapy, especially in the context of failure of commonly used medicines or for patients who do not tolerate common side effects. More studies with appropriate blinding strategies are needed to confirm the results of these new treatment opportunities.