bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling neural representations of value and salience in the human brain
Authors: Kahnt Thorsten , Park Soyoung Q , Haynes John-Dylan , Tobler Philippe N. 
Published: March 2014

Significance
The value and salience of predictive cues are important signals for regulating approach–avoidance behavior and attentional processing, respectively. However, the two signals often are confounded in studies of decision-making. Indeed, recent results suggest that neural signals in the primate posterior parietal cortex (PPC) which previously were thought to encode value actually reflect salience. This finding has created considerable uncertainty about previously identified value signals. Here we experimentally dissociate value and salience and use pattern-based functional MRI to demonstrate distinct encoding of both signals in the PPC, thereby reinforcing the earlier reports of value in the PPC. Moreover, we show that the orbitofrontal cortex encodes the predicted value of appetitive and aversive outcomes on a common neural scale.
On the mechanism of photoinduced dimer dissociation in the plant UVR8 photoreceptor
Authors: Voityuk Alexander A. , Marcus Rudolph A. , Michel-Beyerle Maria-Elisabeth 
Published: March 2014

Significance
In contrast to other chromophore/protein systems in photobiology, the UV-B photoreceptor UV resistance locus 8 (UVR8) utilizes tryptophan residues as light absorbers. The initial step of a signaling pathway that ultimately leads to UV-B protection and damage repair in plants is the breaking of salt bridges that stabilize the UVR8 protein consisting of two identical subunits. On the basis of the known X-ray structure and high-level quantum-chemical computations, we propose a mechanism that implies excitation energy transfer to the “special tryptophan” W233 near the monomer interface, followed by the formation of a charge-transfer state involving W233 and W285. In the calculations, the large dipole moment of W233(−)-W285(+) facilitates the breaking of arginine–aspartate salt bridges between the two subunits.
Quantitative theory of entropic forces acting on constrained nucleotide sequences applied to viruses
Authors: Greenbaum Benjamin D. , Cocco Simona , Levine Arnold J. , Monasson Rémi 
Published: March 2014

Significance
This paper proposes a simple theory, inspired by statistical mechanics, of the interplay of entropic forces and selective forces on dinucleotide frequencies in viral genomes that occur when a virus migrates to a new host. The theory is quantitatively developed, and leads to many predictions about statistical features of viral evolution. The approach is general, and could be easily extended to other genomic data and have wider applications. For example, an analysis of avian influenza entering the human genome has identified selection against CpG dinucleotides, which have been shown to trigger a response of the innate immune system and interferon production.
Piglet Model of Chronic Pulmonary Hypertension
Authors: Mercier Olaf , Tivane Adriano , Dorfmüller Peter , de Perrot Marc , Raoux François , Decante Benoît , Eddahibi Saadia , Dartevelle Philippe , Fadel Elie 
Published: March 2014

None of the animal models have been able to reproduce all aspects of CTEPH because of the rapid resolution of the thrombi in the pulmonary vasculature. The aim of this study was to develop an easily reproducible large‐animal model of chronic pulmonary hypertension (PH) related to the development of a postobstructive and overflow vasculopathy. Chronic PH was induced in 5 piglets by ligation of the left pulmonary artery (PA) through a midline sternotomy followed by weekly transcatheter embolization of the right lower‐lobe arteries. Sham‐operated piglets (n = 5) served as controls. Hemodynamics, RV function, lung morphometry, and endothelin‐1 (ET‐1) pathway gene expression (ET‐1 and its receptors ETA and ETB) were assessed after 5 weeks in the obstructed (left lung and right lower lobe) and unobstructed (right upper lobe) territories. All animals developed chronic PH within 5 weeks. Compared to controls, chronic‐PH animals had higher mean PA pressure (28.5 ± 1.7 vs. 11.6 ± 1.8 mmHg, P = 0.0001) and total pulmonary resistance (784 ± 160 vs. 378 ± 51 dyn s−1 cm−5, P = 0.05). Echocardiography showed RV enlargement, RV wall thickening (56 ± 5 vs. 30 ± 4 mm, P = 0.0003), decreased tricuspid annular plane systolic excursion (11.3 ± 0.9 vs. 14.4 ± 0.4 mm, P = 0.01), and paradoxical septal motion. In obstructed territories, morphometry demonstrated increases in the number of bronchial arteries per bronchus (8.7 ± 0.9 vs. 2 ± 0.17, P < 0.0001) and in distal PA media thickness (60% ± 2.8% vs. 29% ± 0.9%, P < 0.0001), consistent with postobstructive vasculopathy. Distal PA media thickness was increased in unobstructed territories (70% ± 2.4% vs. 29% ± 0.9%, P < 0.0001). ET‐1 was overexpressed in unobstructed territories, compared to controls and obstructed territories. In conclusion, the large‐animal model described here is reproducible and led to the development of PH in a relatively short time frame.
Study Design and Rationale for Investigating Phosphodiesterase type 5 Inhibition for the Treatment of Pulmonary Hypertension Due to Chronic Obstructive Lung Disease: The TADA‐PHiLD (TADAlafil for Pulmonary Hypertension Associated with Chronic Obstructive Lung Disease) Trial
Authors: Maron Bradley A. , Goldstein Ronald H. , Rounds Sharon I. , Shapiro Shelley , Jankowich Matthew , Garshick Eric , Moy Marilyn L. , Gagnon David , Choudhary Gaurav 
Published: March 2014

In patients with chronic obstructive pulmonary disease (COPD), moderate or severe pulmonary hypertension (COPD‐PH) is associated with increased rates of morbidity and mortality. Despite this, approaches to treatment and the efficacy of phosphodiesterase type 5 inhibition (PDE‐5i) in COPD‐PH are unresolved. We present the clinical rationale and study design to assess the effect of oral tadalafil on exercise capacity, cardiopulmonary hemodynamics, and clinical outcome measures in COPD‐PH patients. Male and female patients 40–85 years old with GOLD stage 2 COPD or higher and pulmonary hypertension diagnosed on the basis of invasive cardiac hemodynamic assessment (mean pulmonary artery pressure [mPAP] >30 mmHg, pulmonary vascular resistance [PVR] >2.5 Wood units, and pulmonary capillary wedge pressure ≤18 mmHg at rest) will be randomized at a 1:1 ratio to receive placebo or oral PDE‐5i with tadalafil (40 mg daily for 12 months). The primary end point is change from baseline in 6‐minute walk distance at 12 months. The secondary end points are change from baseline in PVR and mPAP at 6 months and change from baseline in peak volume of oxygen consumption (o2) during exercise at 12 months. Changes in systemic blood pressure and/or oxyhemoglobin saturation (SaO2) at rest and during exercise will function as safety outcome measures. TADA‐PHiLD (TADAlafil for Pulmonary Hypertension assocIated with chronic obstructive Lung Disease) is the first sufficiently powered randomized clinical trial testing the effect of PDE‐5i on key clinical and drug safety outcome measures in patients with at least moderate PH due to COPD.
Safety of Epoprostenol and Treprostinil in Children Less than 12 Months of Age
Authors: McIntyre Chelsey M. , Hanna Brian D. , Rintoul Natalie , Ramsey E. Zachary 
Published: March 2014

There is a paucity of data on infant intravenous prostacyclin use, the gold standard for therapy for severe pulmonary hypertension (PH). This review aimed to evaluate the safety, tolerability, and outcomes of infant prostacyclin use. A retrospective observational study was performed in a large pediatric hospital with a dedicated pediatric PH program. Subject medical records, bedside flow sheets, and progress notes were reviewed to identify use of intravenous epoprostenol or treprostinil within the first year of life. The indication for prostacyclin use was recalcitrant hemodynamic compromise associated with PH, identified as either idiopathic PH, persistent PH of the newborn, PH associated with congenital diaphragmatic hernia, congenital heart disease, bronchiolitis, or chronic lung disease. Prostacyclin‐related adverse events included 7 episodes of hypotension, 6 episodes of perceived pain, 2 episodes of cyanosis, and 1 episode of feeding intolerance. Prostacyclin was stopped only for cyanotic episodes associated with use in severe chronic lung disease. Two hemorrhagic events occurred during extracorporeal membrane oxygenation, which were unlikely to be prostacyclin related. Outcomes included 21 deaths unrelated to prostacyclin, 1 lung transplant, 6 PH resolutions, 8 transitions to oral PH medications, and 1 continuation of treprostinil. In conclusion, efficacy could not be evaluated in this study because of the loss of equipoise for neonatal prostacyclin use. Prostacyclin use was well tolerated in neonatal diseases associated with PH, but dose titration was limited by hypotension and hypoxemia.
Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health
Authors: Vogel JP , Souza JP , Mori R , Morisaki N , Lumbiganon P , Laopaiboon M , Ortiz‐Panozo E , Hernandez B , Pérez‐Cuevas R , Roy M , Mittal S , Cecatti JG , Tunçalp Ö , Gülmezoglu AM ,   on behalf of the WHO Multicountry Survey on Maternal and Newborn Health Research Network
Published: March 2014

ObjectiveWe aimed to determine the prevalence and risks of late fetal deaths (LFDs) and early neonatal deaths (ENDs) in women with medical and obstetric complications.DesignSecondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS).SettingA total of 359 participating facilities in 29 countries.PopulationA total of 308 392 singleton deliveries.MethodsWe reported on perinatal indicators and determined risks of perinatal death in the presence of severe maternal complications (haemorrhagic, infectious, and hypertensive disorders, and other medical conditions).Main outcome measuresFresh and macerated LFDs (defined as stillbirths ≥ 1000 g and/or ≥28 weeks of gestation) and ENDs.ResultsThe LFD rate was 17.7 per 1000 births; 64.8% were fresh stillbirths. The END rate was 8.4 per 1000 liveborns; 67.1% occurred by day 3 of life. Maternal complications were present in 85.6, 86.5, and 88.6% of macerated LFDs, fresh LFDs, and ENDs, respectively. The risks of all three perinatal mortality outcomes were significantly increased with placental abruption, ruptured uterus, systemic infections/sepsis, pre‐eclampsia, eclampsia, and severe anaemia.ConclusionsPreventing intrapartum‐related perinatal deaths requires a comprehensive approach to quality intrapartum care, beyond the provision of caesarean section. Early identification and management of women with complications could improve maternal and perinatal outcomes.
Development of criteria for identifying neonatal near‐miss cases: analysis of two WHO multicountry cross‐sectional studies
Authors: Pileggi‐Castro C , Camelo Jr JS , Perdoná GC , Mussi‐Pinhata MM , Cecatti JG , Mori R , Morisaki N , Yunis K , Vogel JP , Tunçalp Ö , Souza JP ,   on behalf of the WHO Multicountry Survey on Maternal and Newborn Health Research Network
Published: March 2014

ObjectiveTo develop and test markers of neonatal severe morbidity for the identification of neonatal near‐miss cases.DesignThis is a database analysis of two World Health Organization cross‐sectional studies: the Global Survey on Maternal and Perinatal Health (WHOGS) and the Multicountry Survey on Maternal and Newborn Health (WHOMCS).SettingThe WHOGS was performed in 373 health facilities in 24 countries (2004–2008). The WHOMCS was conducted in 359 health facilities in 29 countries (2010–2011).PopulationData were collected from hospital records of all women admitted for delivery and their respective neonates.MethodsPragmatic markers (birthweight <1750 g, Apgar score at 5 minutes <7, and gestational age <33 weeks) were developed with WHOGS data and validated with WHOMCS data. The diagnostic accuracy of neonatal characteristics and management markers of severity was determined in the WHOMCS.ResultsThis analysis included 290 610 liveborn neonates from WHOGS and 310 436 liveborn neonates from WHOMCS. The diagnostic accuracy of pragmatic and management markers of severity for identifying early neonatal deaths was very high: sensitivity, 92.8% (95% CI 91.8–93.7%); specificity, 92.7% (95% CI 92.6–92.8%); positive likelihood ratio, 12.7 (95% CI 12.5–12.9); negative likelihood ratio, 0.08 (95% CI 0.07–0.09); diagnostic odds ratio, 163.4 (95% CI 141.6–188.4). A positive association was found between the frequency of neonatal near‐miss cases and Human Development Index.ConclusionNewborn infants presenting selected markers of severity and surviving the first neonatal week could be considered as neonatal near‐miss cases. This definition and criteria may be seen as a basis for future applications of the near‐miss concept in neonatal health. These tools can be used to inform policy makers on how best to apply scarce resources for improving the quality of care and reducing neonatal mortality.
Prison Suicides in South Australia: 1996–2010
Authors: Austin Amy E. , van den Heuvel Corinna , Byard Roger W. 
Published: March 2014

AbstractForty‐eight deaths occurring in prisons in South Australia were identified between January 1996 and December 2010, including 25 cases of suicide (mean age = 37 years; median age = 34 years; age range = 24–70 years). Most suicides were due to hanging (23/25; 92.0%) with victims using bedding, belts, or shoelaces attached to cell shelves, air vents, doors, or other accessible projections. There were no suicides attributed to drug overdose or sharp force injury. Over a third of all suicides (39.1%) occurred during the first month of confinement, with 26.1% of cases occurring within the first week. There was one suicide reported after 2 years of imprisonment. Given that suicide in state prisons currently occurs at a rate approximately eight times that of the general South Australian community, it appears that the subset of incarcerated individuals represents a group in need of effective preventive strategies to enable more appropriate provisions of existing prisoner resources.
Reliability of solar keratosis clinical diagnosis: A prospective study
Authors: Buinauskaite Evelina , Makstiene Jurgita , Buinauskiene Jurate , Valiukeviciene Skaidra 
Published: March 2014

AbstractUsually solar keratoses (SK) are diagnosed clinically. However other diseases may clinically present as erythematous macules, papules or patches on sun‐exposed areas; therefore the histopathology remains the gold standard diagnostic tool. Our study, which assessed the efficacy of photodynamic therapy (PDT), showed that one in 20 clinically diagnosed SK lesions grade I–II identified by board‐certified dermatologists were rosacea and only one in 40 were malignant lesions. These findings should be considered by clinicians who treat clinically diagnosed grade I–II SK without response to treatment or diagnose the recurrence of SK after PDT.
Nicotinamide and the skin
Authors: Chen Andrew C , Damian Diona L 
Published: March 2014

AbstractNicotinamide, an amide form of vitamin B3, boosts cellular energy and regulates poly‐ADP‐ribose‐polymerase 1, an enzyme with important roles in DNA repair and the expression of inflammatory cytokines. Nicotinamide shows promise for the treatment of a wide range of dermatological conditions, including autoimmune blistering disorders, acne, rosacea, ageing skin and atopic dermatitis. In particular, recent studies have also shown it to be a potential agent for reducing actinic keratoses and preventing skin cancers.
The effects of general anaesthesia on nerve‐motor response characteristics (rheobase and chronaxie) to peripheral nerve stimulation
Authors: Tsui B. C. 
Published: March 2014

SummaryUsing a simple surface nerve stimulation system, I examined the effects of general anaesthesia on rheobase (the minimum current required to stimulate nerve activity) and chronaxie (the minimum time for a stimulus twice the rheobase to elicit nerve activity). Nerve stimulation was used to elicit a motor response from the ulnar nerve at varying pulse widths before and after induction of general anaesthesia. Mean (SD) rheobase before and after general anaesthesia was 0.91 (0.37) mA (95% CI 0.77–1.04 mA) and 1.11 (0.53) mA (95% CI 0.92–1.30 mA), respectively. Mean (SD) chronaxie measured before and after general anaesthesia was 0.32 (0.17) ms (95% CI 0.26–0.38 ms) and 0.29 (0.13) ms (95% CI 0.24–0.33 ms), respectively. Under anaesthesia, rheobase values increased by an average of 20% (p = 0.05), but chronaxie values did not change significantly (p = 0.39). These results suggest that threshold currents used for motor response from nerve stimulation under general anaesthesia might be higher than those used in awake patients.
Comparison of analgesic efficacy of four‐quadrant transversus abdominis plane (TAP) block and continuous posterior TAP analgesia with epidural analgesia in patients undergoing laparoscopic colorectal surgery: an open‐label, randomised, non‐inferiority trial
Authors: Niraj G. , Kelkar A. , Hart E. , Horst C. , Malik D. , Yeow C. , Singh B. , Chaudhri S. 
Published: March 2014

SummaryPosterior transversus abdominis plane blocks have been reported to be an effective method of providing analgesia after lower abdominal surgery. We compared the efficacy of a novel technique of providing continuous transversus abdominis plane analgesia with epidural analgesia in patients on an enhanced recovery programme following laparoscopic colorectal surgery. A non‐inferiority comparison was used. Adult patients undergoing elective laparoscopic colorectal surgery were randomly assigned to receive continuous transversus abdominis plane analgesia (n = 35) vs epidural analgesia (n = 35), in addition to a postoperative analgesic regimen comprising regular paracetamol, regular diclofenac and tramadol as required. Sixty‐one patients completed the study. The transversus group received four‐quadrant transversus abdominis plane blocks and bilateral posterior transversus abdominis plane catheters that were infused with levobupivacaine 0.25% for 48 h. The epidural group received an infusion of bupivacaine and fentanyl. The primary outcome measure was visual analogue scale pain score on coughing at 24 h after surgery. We found no significant difference in median (IQR [range]) visual analogue scores during coughing at 24 h between the transversus group 2.5 (1.0–3.0 [0–5.5]) and the epidural group 2.5 (1.0–5.0 [0–6.0]). The one‐sided 97.5% CI was a 0.0 (∞–1.0) difference in means, establishing non‐inferiority. There were no significant differences between the groups for tramadol consumption. Success rate was 28/30 (93%) in the transversus group vs 27/31 (87%) in the epidural group. Continuous transversus abdominis plane infusion was non‐inferior to epidural infusion in providing analgesia after laparoscopic colorectal surgery.
Ropivacaine plasma levels following local infiltration analgesia for primary total hip arthroplasty
Authors: Gill A. M. , Scott N. B. , Abbas M. , Watson D. G. , Place K. , McDonald D.A. 
Published: March 2014

SummaryWe measured total and free plasma concentrations of ropivacaine following high‐volume, high‐dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri‐capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 μg.ml−1 (mean (SD) 0.953 (0.323) μg.ml−1). Free levels of plasma ropivacaine varied from 0.000 to 0.053 μg.ml−1 (mean (SD) 0.024 (0.011) μg.ml−1). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 μg.ml−1, free 0.15 μg.ml−1) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients.
Therapeutic implications of peptide interactions with G‐protein‐coupled receptors in diabetic vasculopathy
Authors: Carrillo‐Sepulveda M. A. , Matsumoto T. , Nunes K. P. , Webb R. C. 
Published: March 2014

AbstractThe dramatic worldwide increase in the prevalence of diabetes has generated an attempt by the scientific community to identify strategies for its treatment and prevention. Vascular dysfunction is a hallmark of diabetes and frequently leads to the development of atherosclerosis, coronary disease‐derived myocardial infarction, stroke, peripheral arterial disease and diabetic ‘triopathy’ (retinopathy, nephropathy and neuropathy). These vascular complications, developing in an increasingly younger cohort of patients with diabetes, contribute to morbidity and mortality. Despite the development of new anti‐diabetic or anti‐hyperglycaemic drugs, vascular complications remain to be a problem. This warrants a need for new therapeutic strategies to tackle diabetic vasculopathy. There is a growing body of evidence showing that peptide‐binding G‐protein‐coupled receptors (peptide‐binding GPCRs) play an important role in the pathophysiology of vascular dysfunction during diabetes. Thus, in this review, we discuss some of the peptide‐binding GPCRs involved in the regulation of vascular function that have potential to be a therapeutic target in the treatment of diabetic vasculopathy.
The TRPC channel blocker SKF 96365 inhibits glioblastoma cell growth by enhancing reverse mode of the Na+/Ca2+ exchanger and increasing intracellular Ca2+
Authors: Song M , Chen D , Yu S P 
Published: March 2014

Background and PurposeSKF 96365 is well known for its suppressing effect on human glioblastoma growth by inhibiting pre‐activated transient receptor potential canonical (TRPC) channels and Ca2+ influx. The effect of SKF 96363 on glioblastoma cells, however, may be multifaceted and this possibility has been largely ignored.Experimental ApproachThe effects of SKF 96365 on cell cycle and cell viability of cultured human glioblastoma cells were characterized. Western blot, Ca2+ imaging and patch clamp recordings were used to delineate cell death mechanisms. siRNA gene knockdown provided additional evidence.Key ResultsSKF 96365 repressed glioblastoma cell growth via increasing intracellular Ca2+ ([Ca2+]i) irrespective of whether TRPC channels were blocked or not. The effect of SKF 96365 primarily resulted from enhanced reverse operation of the Na+/Ca2+ exchanger (NCX) with an EC50 of 9.79 μM. SKF 96365 arrested the glioblastoma cells in the S and G2 phases and activated p38‐MAPK and JNK, which were all prevented by the Ca2+ chelator BAPTA‐AM or EGTA. The expression of NCX in glioblastoma cells was significantly higher than in normal human astrocytes. Knockdown of the NCX1 isoforms diminished the effect of SKF 96365 on glioblastoma cells.Conclusions and ImplicationsAt the same concentration, SKF 96365 blocks TRPC channels and enhances the reverse mode of the NCX causing [Ca2+]i accumulation and cytotoxicity. This finding suggests an alternative pharmacological mechanism of SKF 96365. It also indicates that modulation of the NCX is an effective method to disrupt Ca2+ homeostasis and suppress human glioblastoma cells.