bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk
Authors: Kranke Peter , Bergese Sergio D. , Minkowitz Harold S. , Melson Timothy I. , Leiman David G. , Candiotti Keith A. , Liu Ngai , Eberhart Leopold , Habib Ashraf S. , Wallenborn Jan , Kovac Anthony L. , Diemunsch Pierre , Fox Gabriel , Gan Tong J. 
Published: March 2018

Abstract

Background
Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated.

Methods
This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period.

Results
Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo.

Conclusions
Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia.
Risk for Cervical Intraepithelial Neoplasia Grade 3 or Higher in Follow-Up of Women With a Negative Cervical Biopsy
Authors: Tverelv Liv Reidun , Sørbye Sveinung Wergeland , Skjeldestad Finn Egil 
Published: March 2018

Objective
The Norwegian Cervical Cancer Screening Programme recommends follow-up of histologically confirmed normal/cervical intraepithelial neoplasia (CIN) 1 with combined cytology and human papillomavirus testing within 6 to 12 months. This study examines adherence to guidelines and subsequent risk for CIN 3+ within this subset of women.

Materials and Methods
Women aged 25 to 69 years attending the Norwegian Cervical Cancer Screening Programme in Norway's 2 northernmost counties were included. An exposed cohort with histologically confirmed normal/CIN 1 after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion or atypical squamous cells – cannot exclude high-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion enrolment cytology (n = 374) was compared with a nonexposed cohort with a normal enrolment cytology attending primary screening (N = 25,948). Risk calculations were stratified by outcomes of the first follow-up cytology. The study end point was CIN 3+ or censored at 78 months of follow-up.

Results
In the exposed cohort, the 42-month cumulative incidence of CIN 3+ was 9.4% (95% CI = 4.1–14.7) for women with an abnormal first follow-up cytology and 1.6% (95% CI = 0.0–3.4) for women with a normal first follow-up cytology versus 0.21% (95% CI = 0.15–0.27) in the nonexposed cohort (p < .01). The CIN 3+ risk was higher in the exposed cohort when the first follow-up cytology was abnormal (hazard ratio = 20.4, 95% CI = 11.2–37.1) compared with normal (hazard ratio = 4.7, 95% CI = 1.9–11.6) with the nonexposed cohort as reference.

Conclusions
After a negative cervical biopsy, a normal first follow-up cytology provided a CIN 3+ risk considered acceptable to recommend return to routine screening in 3 years. Cytology and human papillomavirus co-testing in post-colposcopy follow-up of negative biopsies may improve risk stratification.
NOTCH regulation of the endothelial cell phenotype
Authors: Mack Julia J. , Iruela-Arispe M. Luisa 
Published: March 2018

Purpose of reviewThe formation of a hierarchical vascular network is a complex process that requires precise temporal and spatial integration of several signaling pathways. Amongst those, Notch has emerged as a key regulator of multiple steps that expand from endothelial sprouting to arterial specification and remains relevant in the adult. This review aims to summarize major concepts and rising hypotheses on the role of Notch signaling in the endothelium.Recent findingsA wealth of new information has helped to clarify how Notch signaling cooperates with other pathways to orchestrate vascular morphogenesis, branching, and function. Endothelial vascular endothelial growth factor, C-X-C chemokine receptor type 4, and nicotinamide adenine dinucleotide phosphate oxidase 2 have been highlighted as key regulators of the pathway. Furthermore, blood flow forces during vascular development induce Notch1 signaling to suppress endothelial cell proliferation, enhance barrier function, and promote arterial specification. Importantly, Notch1 has been recently recognized as an endothelial mechanosensor that is highly responsive to the level of shear stress to enable differential Notch activation in distinct regions of the vessel wall and suppress inflammation.SummaryAlthough it is well accepted that the Notch signaling pathway is essential for vascular morphogenesis, its contributions to the homeostasis of adult endothelium were uncovered only recently. Furthermore, its exquisite regulation by flow and impressive interface with multiple signaling pathways indicates that Notch is at the center of a highly interactive web that integrates both physical and chemical signals to ensure vascular stability.
Global Variation in Use of Enteral Nutrition for Pediatric Crohn Disease
Authors: Lawley Morgan , Wu Jessica W. , Navas‐López Victor M. , Huynh Hien Q. , Carroll Matthew W. , Chen Min , Medvedev Pavel , Day Andrew S. , Hussey Séamus , Sigall‐Boneh Rotem , Levine Arie , Wine Eytan 
Published: March 2018

ABSTRACTObjectives:Exclusive enteral nutrition (EEN) is an effective induction treatment for pediatric Crohn disease. Given the center‐based variation in use and diversity in practice, we constructed a survey aimed at sharing experience and strategies in administering EEN, stimulating further research, and optimizing therapy.Methods:This survey was constructed after consultation with experts and designed to address key knowledge gaps. The survey was disseminated through the Pediatric IBD Porto Group of ESPGHAN, Canadian Children IBD Network, selective experts, and was sent twice through the Pediatric Gastrointestinal‐Bulletin Board (PEDGI‐BB). Data were collected into REDCap and analyzed using descriptive statistics.Results:In total, 146 participants from 26 countries completed the survey. Sixty‐five percentage of participants were general, non‐inflammatory bowel diseases (IBD)‐focused pediatric gastroenterologists, 21% were IBD‐focused, and 10% were dietitians. The most common indications (~90% use) were for ileocecal and ileocolonic disease (Paris L1 and L3). The most common duration was 8 weeks and 66% preferred oral to nasogastric administration. Most (63%) did not allow any additional intake and 69% instructed patients to continue partial enteral nutrition (EN) after completing treatment. Dietitians were identified as essential to EEN success while the primary challenges of EEN programs were adherence and lack of support. Regional and professional practice differences were observed in EEN indication, age, exclusivity, program structure/support, and cost coverage.Conclusions:We found significant variation in practice and use of EEN with several regional and professional differences. Global variation offers opportunities for research and improving care. This survey establishes a framework and provides resources for collaboration and information sharing.
Use of National Syphilis Surveillance Data to Develop a Congenital Syphilis Prevention Cascade and Estimate the Number of Potential Congenital Syphilis Cases Averted
Authors: Kidd Sarah , Bowen Virginia B. , Torrone Elizabeth A. , Bolan Gail 
Published: March 2018

Background
Recent increases in reported congenital syphilis have led to an urgent need to identify interventions that will have the greatest impact on congenital syphilis prevention. We sought to create a congenital syphilis prevention cascade using national syphilis surveillance data to (1) estimate the proportion of potential congenital syphilis cases averted with current prevention efforts and (2) develop a classification framework to better describe why reported cases were not averted.

Methods
We reviewed national syphilis and congenital syphilis case report data from 2016, including pregnancy status of all reported female syphilis cases and data on prenatal care, testing, and treatment status of mothers of reported congenital syphilis cases to derive estimates of the proportion of pregnant women with syphilis who received prenatal care, syphilis testing, and adequate syphilis treatment at least 30 days before delivery, as well as the proportion of potential congenital syphilis cases averted.

Results
Among the 2508 pregnant women who were reported to have syphilis, an estimated 88.0% received prenatal care at least 30 days before delivery, 89.4% were tested for syphilis at least 30 days before delivery, and 76.9% received an adequate treatment regimen that began at least 30 days before delivery. Overall, an estimated 1928 (75.0%) potential congenital syphilis cases in the United States were successfully averted. Among states that reported at least 10 syphilis cases among pregnant women, the estimated proportion of potential congenital syphilis cases averted ranged from 55.0% to 92.3%.

Conclusions
Although the majority of potential congenital syphilis cases in the United States were averted in 2016, there was substantial geographic variation, and significant gaps in delivering timely prenatal care, syphilis testing, and adequate treatment to pregnant women with syphilis were identified. The congenital syphilis prevention cascade is a useful tool to quantify programmatic successes and identify where improvements are needed.
Low-Level Viremia Is Associated With Clinical Progression in HIV-Infected Patients Receiving Antiretroviral Treatment
Authors: Bernal Enrique , Gómez Jose M. , Jarrín Inma , Cano Alfredo , Muñoz Angeles , Alcaraz Antonia , Imaz Arkaitz , Iribarren Jose A. , Rivero María , Arazo Piedad , Gutiérrez Félix ,   CoRIS Study Group
Published: March 2018

Background:
The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART).

Methods:
We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter. Multivariable Cox models were used to estimate the association of LLV with AIDS events/death, non-AIDS events, and virological failure.

Results:
Of 5986 patients included, 237 (4.0%) experienced LLV50-199 and 168 (2.8%) developed LLV200–499. One hundred seventy-one patients died or developed an AIDS event, 245 had any serious NAE and 280 had virological failure. LLV200-499 was strongly associated with a higher risk of both AIDS events/death [adjusted hazard ratio (aHR), 2.89; 95% confidence interval (CI), 1.41 to 5.92] and virological failure (aHR, 3.25; 95% CI: 1.77 to 5.99), whereas no differences were observed between LLV50-199 and no LLV neither for AIDS events/death (aHR, 1.84; 95% CI: 0.89 to 3.82) nor virological failure (aHR, 1.42; 95% CI: 0.78 to 2.58). LLV was not associated with the occurrence of any serious NAE.

Conclusions:
In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.
The mysteries of remote memory
Authors: Albo Zimbul , Gräff Johannes 
Published: March 2018

Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process—the standard theory of memory consolidation—would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might alreadyab ovobe encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Dissociable temporal effects of bupropion on behavioural measures of emotional and reward processing in depression
Authors: Walsh Annabel E. L. , Browning Michael , Drevets Wayne C. , Furey Maura , Harmer Catherine J. 
Published: March 2018

Antidepressants remediate negative biases in emotional processing early in treatment, prior to mood improvement. However, the effects on reward processing potentially relevant to the treatment of anhedonia are less clear. Here we investigate the early and sustained effects of the dopamine and noradrenaline reuptake inhibitor bupropion on behavioural measures of emotional and reward processing in currently depressed individuals. Forty-six currently depressed patients and 42 healthy controls participated in a repeated measures study, during which open-label bupropion was administered to only the patient group over a six week period without a placebo group. All participants completed the Emotional Test Battery and a probabilistic instrumental learning task at week 0, week 2 and week 6. Currently depressed patients displayed negative biases in emotional processing and blunted response bias for high-probability wins compared to the healthy controls at baseline. Bupropion was found to reduce the negative biases in emotional processing early in treatment, including a significant decrease in the percentage misclassification of other face emotions as sad and the number of negative self-referent words falsely recalled between baseline and week 2. Conversely, bupropion was found to initially further reduce the response bias for high-probability wins between baseline and week 2. This effect reversed with six weeks' bupropion treatment and reward processing was normalized compared to the healthy controls. Early in treatment, bupropion acts to reduce negative biases in emotional processing but exacerbates impaired reward processing. The beneficial actions of bupropion on reward processing then occur later in treatment. Such dissociation in the temporal effects of bupropion on emotional and reward processing has implications for the treatment of the different symptom domains of negative affect and anhedonia in depression.
This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Can we use mice to study schizophrenia?
Authors: Canetta Sarah , Kellendonk Christoph 
Published: March 2018

The validity of rodent models for the study of psychiatric disorders is controversial. Despite great efforts from academic institutions and pharmaceutical companies, as of today, no major therapeutic intervention has been developed for the treatment of psychiatric disorders based on mechanistic insights from rodent models. Here, we argue that despite these historical shortcomings, rodent studies are nevertheless instrumental for identifying neuronal circuit mechanisms underlying behaviours that are affected in psychiatric disorders. Focusing on schizophrenia, we will give four examples of rodent models that were generated based on genetic and environmental risk factors or pathophysiological evidence as entry points. We will then discuss how circuit analysis in these specific examples can be used for testing hypotheses about neuronal mechanisms underlying symptoms of schizophrenia, which will then guide the development of new therapies.
This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats
Authors: Shumake Jason , Jones Carolyn , Auchter Allison , Monfils Marie-Hélène 
Published: March 2018

Fear conditioning is widely employed to examine the mechanisms that underlie dysregulations of the fear system. Various manipulations are often used following fear acquisition to attenuate fear memories. In rodent studies, freezing is often the main output measure to quantify ‘fear’. Here, we developed data-driven criteria for defining a standard benchmark that indicates remission from conditioned fear and for identifying subgroups with differential treatment responses. These analyses will enable a better understanding of individual differences in treatment responding.
This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Using mouse transgenic and human stem cell technologies to model genetic mutations associated with schizophrenia and autism
Authors: St. Clair David , Johnstone Mandy 
Published: March 2018

Solid progress has occurred over the last decade in our understanding of the molecular genetic basis of neurodevelopmental disorders, and of schizophrenia and autism in particular. Although the genetic architecture of both disorders is far more complex than previously imagined, many key loci have at last been identified. This has allowedin vivoandin vitrotechnologies to be refined to model specific high-penetrant genetic loci involved in both disorders. Using theDISC1/NDE1andCYFIP1/EIF4Eloci as exemplars, we explore the opportunities and challenges of using animal models and human-induced pluripotent stem cell technologies to further understand/treat and potentially reverse the worst consequences of these debilitating disorders.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Multiple memory systems, multiple time points: how science can inform treatment to control the expression of unwanted emotional memories
Authors: Visser Renée M. , Lau-Zhu Alex , Henson Richard N. , Holmes Emily A. 
Published: March 2018

Memories that have strong emotions associated with them are particularly resilient to forgetting. This is not necessarily problematic, however some aspects of memory can be. In particular, the involuntary expression of those memories, e.g. intrusive memories after trauma, are core to certain psychological disorders. Since the beginning of this century, research using animal models shows that it is possible to change the underlying memory, for example by interfering with its consolidation or reconsolidation. While the idea of targeting maladaptive memories is promising for the treatment of stress and anxiety disorders, a direct application of the procedures used in non-human animals to humans in clinical settings is not straightforward. In translational research, more attention needs to be paid to specifying what aspect of memory (i) can be modified and (ii) should be modified. This requires a clear conceptualization of what aspect of memory is being targeted, and how different memory expressions may map onto clinical symptoms. Furthermore, memory processes are dynamic, so procedural details concerning timing are crucial when implementing a treatment and when assessing its effectiveness. To target emotional memory in its full complexity, including its malleability, science cannot rely on a single method, species or paradigm. Rather, a constructive dialogue is needed between multiple levels of research, all the way ‘from mice to mental health’.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.
Arimoclomol as a potential therapy for neuronopathic Gaucher Disease
Authors: Fog-Tonnesen Cathrine K. , Zago Paola , Malini Erika , Solanko Lukasz M. , Peruzzo Paolo , Bornaes Claus , Magnoni Raffaella , Petersen Nikolaj H. T. , Bembi Bruno , Dardis Andrea , Kirkegaard Thomas 
Published: March 2018

AbstractGaucher Disease (GD) is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase function by perturbing its protein homeostasis rather than its catalytic activity. Heat shock proteins (HSPs) are well known cytoprotective molecules with numerous functions in protein homeostasis and lysosomal function and their manipulation has been suggested as a potential therapeutic strategy for GD. The investigational drug arimoclomol, which is currently in phase II/III clinical trials, is a well-characterized HSP amplifier and has been extensively clinically tested. Importantly, arimoclomol efficiently crosses the blood-brain-barrier hereby presenting an opportunity to target the neurological manifestations of GD, which remains without a disease modifying therapy.In the present study, we found that arimoclomol induced relevant HSPs such as ER-resident HSP70 (BiP) and enhanced the folding, maturation, activity and correct cellular localization of mutated GCase across a number of genotypes including the common L444P and N370S mutations in primary cells from GD patients. These effects where recapitulated in a human neuronal model of GD obtained by differentiation of multipotent adult stem cells. Taken together, these data demonstrate the potential of HSP-targeting therapies in GCase-deficiencies and strongly support the clinical development of arimoclomol as a potential first therapeutic option for the neuronopathic forms of GD.SummaryThese studies provide proof-of-concept for the development of the Heat shock protein amplifier, arimoclomol, as a potential therapy for neuronopathic Gaucher disease as arimoclomol enhances folding, maturation, activity and correct localization of GCase in neuronopathic and non-neuronopathic Gaucher disease models.