bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amisulpride augmentation of clozapine for treatment-refractory schizophrenia: a double-blind, placebo-controlled trial
Authors: Barnes Thomas R.E. , Leeson Verity , Paton Carol , Marston Louise , Osborn David P. , Kumar Raj , Keown Patrick , Zafar Rameez , Iqbal Khalid , Singh Vineet , Fridrich Pavel , Fitzgerald Zachary , Bagalkote Hemant , Haddad Peter M. , Husni Mariwan , Amos Tim 
Published: March 2018

Background: A second antipsychotic is commonly added to clozapine to treat refractory schizophrenia, notwithstanding the limited evidence to support such practice. Methods: The efficacy and adverse effects of this pharmacological strategy were examined in a double-blind, placebo-controlled, 12-week randomized trial of clozapine augmentation with amisulpride, involving 68 adults with treatment-resistant schizophrenia and persistent symptoms despite a predefined trial of clozapine. Results: There were no statistically significant differences between the amisulpride and placebo groups on the primary outcome measure (clinical response defined as a 20% reduction in total Positive and Negative Syndrome Scale score) or other mental state measures. However, the trial under recruited and was therefore underpowered to detect differences in the primary outcome, meaning that acceptance of the null hypothesis carries an increased risk of type II error. The findings suggested that amisulpride-treated participants were more likely to fulfil the clinical response criterion, odds ratio 1.17 (95% confidence interval 0.40–3.42) and have a greater reduction in negative symptoms, but these numerical differences were not statistically significant and only evident at 12 weeks. A significantly higher proportion of participants in the amisulpride group had at least one adverse event compared with the control group ( p = 0.014), and these were more likely to be cardiac symptoms. Conclusions: Treatment for more than 6 weeks may be required for an adequate trial of clozapine augmentation with amisulpride. The greater side-effect burden associated with this treatment strategy highlights the need for safety and tolerability monitoring, including vigilance for indicators of cardiac abnormalities, when it is used in either a clinical or research setting.
Validation of the 2016 USPSTF recommendations for primary cardiovascular prevention in a large contemporary cohort
Authors: Schonmann Yochai , Bleich Oz , Matalon Andre , Yeshua Hanny 
Published: March 2018

Aims The aim of this study was to evaluate the performance of the US Preventive Services Task Force (USPSTF) cholesterol recommendations in a contemporary non-US cohort. Methods and results This is a historical cohort analysis of electronic records from Israel's largest health provider. All patients in the Tel Aviv district eligible for primary cardiovascular prevention were followed between January 2005 and December 2015. Risk was estimated by the pooled cohort equations. Statin eligibility was determined by USPSTF and American College of Cardiology and American Heart Association (ACC/AHA) recommendations. Atherosclerotic cardiovascular disease events were retrieved from electronic registration. The mean ± standard deviation age of the 10,889 (98,258 person-years) participants was 60.3 ± 9.4 years, and 69.1% were women. Outcome events were recorded for 1351 patients (12.4%). Treatment recommendations were discordant in 901 patients (8.3%) whose treatment was indicated only by the ACC/AHA guidelines, implying a 26% reduction in newly eligible patients for statin treatment had the USPSTF recommendations been implemented. Among the statin-naive patients, the pooled cohort equations underestimated the risk, with a predicted-to-observed event ratio of 0.88. The recommended treatment thresholds provided excellent calibration, with ratios of 1.0 for USPSTF and 0.98 for ACC/AHA-eligible patients. Both models showed similar discrimination (Harrel's C = 0.63 (0.62–0.65) for USPSTF vs. 0.64 (0.63–0.66) for ACC/AHA, P = 0.26). The USPSTF recommendations were less sensitive and more specific for the detection of outcome events than the ACC/AHA recommendations (61% vs. 75% and 68% vs. 55%, respectively). The net reclassification index was −0.01. Conclusions Calibration, discrimination and net reclassifications were very similar for USPSTF and ACC/AHA recommendations. Applying the USPSTF recommendations could reduce over-treatment.
What We Do and Do Not Know About Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day
Authors: Piccoli Giorgina B. , Alrukhaimi Mona , Liu Zhi-Hong , Zakharova Elena , Levin Adeera 
Published: March 2018

Background: Chronic kidney disease affects approximately 10% of the world’s adult population: It is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus giving an occasion to reflect on open questions on the importance of kidney health in women for the present and the future generations. Objectives: In this review, we summarize some aspects that are unique to women’s kidney health, offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Findings: Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is not only a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. Conclusion: Improving knowledge on women, kidney health, and kidney disease, may be a way to improve outcomes of kidney diseases worldwide.
Traumatic L7 articular processes fracture and spondylolisthesis following dorsal lumbosacral laminectomy in a cat
Authors: Suñol Anna , Montoliu Patricia , López Marta , Mascort Joan , Morales Carles 
Published: March 2018

Case summary A 12-year-old neutered male domestic shorthair cat was presented to our referral hospital with a chronic history of tenesmus and lumbosacral pain. A diagnosis of degenerative lumbosacral stenosis (DLSS) was made and a standard dorsal L7–S1 laminectomy was performed uneventfully, with complete recovery within 1 month. The cat was brought back 4 months later for investigation of lumbosacral pain after having suffered a minor traumatic event. Neurological examination identified a low tail carriage, weakness, exercise intolerance, left pelvic limb lameness and diminished withdrawal reflexes in both pelvic limbs with severe sacrocaudal pain. A traumatic facet fracture of the L7 articular processes and subsequent spondylolisthesis was diagnosed. A second surgery was performed to stabilise the region. The cat was normal on neurological examination 1 month later and no further clinical signs were noted. Relevance and novel information This is the first description of a fracture and spondylolisthesis as a possible postoperative complication after L7–S1 dorsal laminectomy in a cat. The case highlights the importance of postoperative changes in the supportive structures of the lumbosacral spine in cats after surgical treatment of DLSS.
Development and internal validation of a prediction rule for post-stroke infection and post-stroke pneumonia in acute stroke patients
Authors: Westendorp Willeke F , Vermeij Jan-Dirk , Hilkens Nina A , Brouwer Matthijs C , Algra Ale , van der Worp H. Bart , Dippel Diederik WJ , van de Beek Diederik , Nederkoorn Pual J 
Published: March 2018

Introduction Patients with acute stroke are at high risk for infection. These infections are associated with unfavourable outcome after stroke. A prediction rule can identify the patients at the highest risk for strategies to prevent infection. We aim to develop a prediction rule for post-stroke pneumonia and other infections in patients with acute stroke. Patients and methods We used data from the Preventive Antibiotics in Stroke Study, a multicentre randomised trial comparing preventive ceftriaxone vs. standard stroke care in patients with acute stroke. Possible predictors for post-stroke pneumonia or infection were selected from the literature. Backward elimination logistic regression analysis was used to construct prediction rules for pneumonia or infection. Internal validation was performed and a risk chart was constructed. We adjusted for preventive antibiotic use. Results Pneumonia was diagnosed in 159 of the 2538 included patients, and infection in 348. Pneumonia was predicted by higher age, male sex, pre-stroke disability, medical history of chronic obstructive pulmonary disease, more severe stroke, dysphagia and intracerebral haemorrhage (rather than ischaemic stroke). Infections were predicted by higher age, male sex, history of diabetes, chronic obstructive pulmonary disease, more severe stroke, dysphagia, use of bladder catheter, preventive antibiotic use and intracerebral haemorrhage. With the prediction rule developed, risks for pneumonia ranged from 0.4% to 56.2% and from 1.8% to 88.0% for infection. Discrimination of the score was good (C-statistic, 0.84; 95% CI: 0.81–0.87 and 0.82; 95% CI: 0.79–0.84 for pneumonia and infection). Conclusions The Preventive Antibiotics in Stroke Study pneumonia and infection rule identify patients at the highest risk for post-stroke pneumonia or infection and may be used for future studies and novel therapies, after confirmation in an external population.
Active enhancer and chromatin accessibility landscapes chart the regulatory network of primary multiple myeloma
Authors: Jin Yi , Chen Kenian , De Paepe Ayla , Hellqvist Eva , Krstic Aleksandra D. , Metang Lauren , Gustafsson Charlotte , Davis Richard E. , Levy Yair M. , Surapaneni Rakesh , Wallblom Ann , Nahi Hareth , Mansson Robert , Lin Yin C. 
Published: March 2018

Key Points
Gene regulatory features in MM patients reveal a key regulatory network and epigenetic changes that underpin the disease.
Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms
Authors: Peeken Jan C. , Jutzi Jonas S. , Wehrle Julius , Koellerer Christoph , Staehle Hans F. , Becker Heiko , Schoenwandt Elias , Seeger Thalia S. , Schanne Daniel H. , Gothwal Monika , Ott Christopher J. , Gründer Albert , Pahl Heike L. 
Published: March 2018

Key Points
Overexpression of NFE2 in MPNs is associated with H3Y41 phosphorylation by JAK2V617F. JMJD1C is an NFE2 target gene and acts in a positive feedback loop contributing to NFE2 overexpression in MPNs.
Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human β-globin locus
Authors: Antoniani Chiara , Meneghini Vasco , Lattanzi Annalisa , Felix Tristan , Romano Oriana , Magrin Elisa , Weber Leslie , Pavani Giulia , El Hoss Sara , Kurita Ryo , Nakamura Yukio , Cradick Thomas J. , Lundberg Ante S. , Porteus Matthew , Amendola Mario , El Nemer Wassim , Cavazzana Marina , Mavilio Fulvio , Miccio Annarita 
Published: March 2018

Key Points
CRISPR/Cas9-mediated disruption of the β-globin locus architecture reactivates fetal γ-globin expression in adult erythroblasts. Fetal γ-globin reactivation and sickle β-globin downregulation leads to the amelioration of the SCD cell phenotype.
Sporadic and recurrent non-suicidal self-injury before age 14 and incident onset of psychiatric disorders by 17 years: prospective cohort study
Authors: Wilkinson Paul O. , Qiu Tianyou , Neufeld Sharon , Jones Peter B. , Goodyer Ian M. 
Published: March 2018

BackgroundNon-suicidal self-injury (NSSI) is highly prevalent in adolescents and may be a behavioural marker for emergent mental illnesses.AimsTo determine whether sporadic or recurrent NSSI up to the age of 14 years predicted increased risk of new onset of psychiatric disorder in the subsequent 3 years, independent of psychiatric symptoms and social risk factors.MethodIn total, 945 individuals aged 14 years with no past/present history of mental illness completed a clinical interview and completed a questionnaire about NSSI at the ages of 14 and 17 years.ResultsRecurrent NSSI at baseline predicted total disorders, depression and eating disorders. Sporadic baseline NSSI predicted new onset of anxiety disorders only.ConclusionsNSSI (especially recurrent NSSI) in the early-adolescent years is a behavioural marker of newly emerging mental illnesses. Professionals should treat both recurrent and sporadic NSSI as important risk factors, and prevention strategies could be targeted at this vulnerable group.Declaration of interestNone.
Vitamin D deficiency in the ApcPirc/+ rat does not exacerbate colonic tumorigenesis, while low dietary calcium might be protective
Authors: Irving Amy A. , Duchow Elizabeth G. , Plum Lori A. , DeLuca Hector F. 
Published: March 2018

ABSTRACT
Human studies have shown that individuals with colon cancer tend to have lower serum 25-hydroxy-vitamin D3 [25(OH)D3] levels compared with healthy controls, but whether this link is causative, a result of the disease or an indicator of another factor altogether has yet to be demonstrated. In humans, vitamin D, calcium and UV exposure are inextricably linked; therefore, understanding the individual and combined roles of each of these will require animal models specifically designed to address these questions. To begin to untangle this network, our group has employed the ApcPirc/+ rat, which contains a truncating mutation in the Apc gene, leading to the development of colonic tumors. Our group previously utilized this model to demonstrate that vitamin D supplementation above normal does not reduce colonic tumor burden and, in fact, increased tumor multiplicity in a dose-dependent manner. In the current study, we tested whether vitamin D deficiency plays a causative role in tumor development using two strains which differ in their susceptibility to intestinal tumorigenesis. In the colon, vitamin D deficiency did not increase the development of tumors in either strain, and was actually protective in one strain. Unexpectedly, low dietary calcium combined with vitamin D deficiency significantly suppressed tumor development in the small intestine and colon of both strains. The vast majority of tumors in the human intestine occur in the colon, and we find no evidence to support a direct role of vitamin D deficiency in increasing colonic tumorigenesis, and low calcium might protect against tumor development.
This article has an associated First Person interview with the first author of the paper.
Mitotic spindle assembly and γ-tubulin localisation depend on the integral nuclear membrane protein Samp1
Authors: Larsson Veronica J. , Jafferali Mohammed Hakim , Vijayaraghavan Balaje , Figueroa Ricardo A. , Hallberg Einar 
Published: March 2018

ABSTRACT
We have investigated a possible role for the inner nuclear membrane protein Samp1 (also known as TMEM201) in the mitotic machinery. Live-cell imaging showed that Samp1a–YFP (Samp1a is the short isoform of Samp1) distributed as filamentous structures in the mitotic spindle, partially colocalising with β-tubulin. Samp1 depletion resulted in an increased frequency of cells with signs of chromosomal mis-segregation and prolonged metaphase, indicating problems with spindle assembly and/or chromosomal alignment. Consistent with this, mitotic spindles in Samp1-depleted cells contained significantly lower levels of β-tubulin and γ-tubulin, phenotypes that were rescued by overexpression of Samp1a–YFP. We found that Samp1 can bind directly to γ-tubulin and that Samp1 co-precipitated with γ-tubulin and the HAUS6 subunit of the Augmin complex in live cells. The levels of HAUS6, in the mitotic spindle also decreased after Samp1 depletion. We show that Samp1 is involved in the recruitment of HAUS6 and γ-tubulin to the mitotic spindle. Samp1 is the first inner nuclear membrane protein shown to have a function in mitotic spindle assembly.
Are we what we eat? Changes to the feed fatty acid composition of farmed salmon and its effects through the food chain
Authors: Sissener Nini H. 
Published: March 2018

ABSTRACT
‘Are we what we eat?’ Yes and no. Although dietary fat affects body fat, there are many modifying mechanisms. In Atlantic salmon, there is a high level of retention of the n-3 fatty acid (FA) docosahexaenoic acid (DHA, 22:6n-3) relative to the dietary content, whereas saturated FAs never seem to increase above a specified level, which is probably an adaptation to low and fluctuating body temperature. Net production of eicosapentaenoic acid (EPA, 20:5n-3) and especially DHA occurs in salmon when dietary levels are low; however, this synthesis is not sufficient to maintain EPA and DHA at similar tissue levels to those of a traditional fish oil-fed farmed salmon. The commercial diets of farmed salmon have changed over the past 15 years towards a more plant-based diet owing to the limited availability of the marine ingredients fish meal and fish oil, resulting in decreased EPA and DHA and increased n-6 FAs. Salmon is part of the human diet, leading to the question ‘Are we what the salmon eats?’ Dietary intervention studies using salmon have shown positive effects on FA profiles and health biomarkers in humans; however, most of these studies used salmon that were fed high levels of marine ingredients. Only a few human intervention studies and mouse trials have explored the effects of the changing feed composition of farmed salmon. In conclusion, when evaluating feed ingredients for farmed fish, effects throughout the food chain on fish health, fillet composition and human health need to be considered.
Exercise-induced adaptations to white and brown adipose tissue
Authors: Lehnig Adam C. , Stanford Kristin I. 
Published: March 2018

ABSTRACT
The beneficial effects of exercise on skeletal muscle and the cardiovascular system have long been known. Recent studies have focused on investigating the effects of exercise on adipose tissue and the effects that these exercise-induced adaptations have on overall metabolic health. Examination of exercise-induced adaptations in both white adipose tissue (WAT) and brown adipose tissue (BAT) has revealed marked differences in each tissue with exercise. In WAT, there are changes to both subcutaneous WAT (scWAT) and visceral WAT (vWAT), including decreased adipocyte size and lipid content, increased expression of metabolic genes, altered secretion of adipokines and increased mitochondrial activity. Adaptations specific to scWAT include lipidomic remodeling of phospholipids and, in rodents, the beiging of scWAT. The changes to BAT are less clear: studies evaluating the effect of exercise on the BAT of humans and rodents have revealed contradictory data, making this an important area of current investigation. In this Review, we discuss the exercise-induced changes to WAT and BAT that have been reported by different studies and highlight the current questions in this field.
Adipogenesis in fish
Authors: Salmerón Cristina 
Published: March 2018

ABSTRACT
White adipose tissue (AT) is the main lipid storage depot in vertebrates. Initially considered to be a simple lipid store, AT has recently been recognized as playing a role as an endocrine organ that is implicated in processes such as energy homeostasis and as a rich source of stem cells. Interest in adipogenesis has increased not only because of the prevalence of obesity, metabolic syndrome and type 2 diabetes in humans, but also in aquaculture because of the excessive fat deposition experienced in some cultured fish species, which may compromise both their welfare and their final product quality. Adipocyte development is well conserved among vertebrates, and this conservation has facilitated the rapid characterization of several adipogenesis models in fish. This Review presents the main findings of adipogenesis research based in primary cultures of the preadipocytes of farmed fish species. Zebrafish has emerged as an excellent model for studying the early stages of adipocyte fish development in vivo. Nevertheless, larger fish species are more suitable for the isolation of preadipocytes from visceral AT and for studies in which preadipocytes are differentiated in vitro to form mature adipocytes. Differentiated adipocytes contain lipid droplets and express adipocyte marker genes such as those encoding the peroxisome proliferator activated receptor γ (pparγ), CCAAT-enhancer-binding protein α (c/ebpα), lipoprotein lipase (lpl), fatty acid synthase (fas), fatty acid binding protein 11 (fabp11), fatty acid transporter protein1 (fatp1), adiponectin and leptin. Differentiated adipocytes also have elevated glycerol 3-phosphate (G3P) dehydrogenase (GPDH) activity. To better understand fish adipocyte development and regulation, different adipokines, fatty acids, growth factors and PPAR agonists have been studied, providing relevant insights into which factors affect these processes and counterbalance AT dysregulation.
A draft genome sequence for the Ixodes scapularis cell line, ISE6
Authors: Miller Jason R. , Koren Sergey , Dilley Kari A. , Harkins Derek M. , Stockwell Timothy B. , Shabman Reed S. , Sutton Granger G. 
Published: March 2018

Background:The tick cell line ISE6, derived fromIxodes scapularis, is commonly used for amplification and detection of arboviruses in environmental or clinical samples.Methods:To assist with sequence-based assays, we sequenced the ISE6 genome with single-molecule, long-read technology.Results:The draft assembly appears near complete based on gene content analysis, though it appears to lack some instances of repeats in this highly repetitive genome. The assembly appears to have separated the haplotypes at many loci. DNA short read pairs, used for validation only, mapped to the cell line assembly at a higher rate than they mapped to theIxodes scapularisreference genome sequence.Conclusions:The assembly could be useful for filtering host genome sequence from sequence data obtained from cells infected with pathogens.