bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadian practice: 2-year results from the observational FαsT-CAN study
Authors: Bessette Louis , Haraoui Boulos , Chow Andrew , Fortin Isabelle , Dixit Sanjay , Khraishi Majed , Haaland Derek , Elmoufti Sami , Staelens Fabienne , Bogatyreva Irina , Syrotuik Jerry , Shaikh Saeed 
Published: March 2019

Background: The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients’ productivity, pain, and fatigue, in Canadian practice. Methods: FαsT-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients’ Assessment of Arthritis Pain (PtAAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set). Results: The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile. Conclusions: CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting.
A prospective study on aetiology and outcome of haemospermia from a urology unit in Sri Lanka
Authors: Sivanandan Sopan , Wijayarathna Suranga N , Balagobi Balasingam , Kumara M G Sagara R , Ambegoda A L A Madura C , Abeygunasekera Anuruddha M 
Published: March 2019

Introduction: Haemospermia is an alarming symptom for ordinary members of the public. The worry become greater as it has been described as a warning sign of a prostate cancer in the media. Objectives: The aim of the study was to identify the aetiological factors and outcome of haemospermia in a cohort of patients. Methods: All patients with newly diagnosed haemospermia treated at the urology unit of Colombo South Teaching Hospital over a period of 5 years (2013–2018) constituted the study sample. Data related to demographics, symptomatology, clinical findings, investigations, treatment given and outcome during follow-up were recorded prospectively. Results: There were 94 men with haemospermia who sought treatment during the study period. Mean age was 43.7 years (range: 23–67, median = 41). Twenty-seven (29%) patients had clinical evidence of prostatitis and/or a positive seminal fluid culture. One patient each had prostate carcinoma, prostatic cyst, severe hypertension, sclerotherapy for haemorrhoids, post-chemotherapy and post-epididymectomy. The patient who had high blood pressure (220/150 mmHg) was found to have mesangio-proliferative glomerulonephritis. In 61 (65%) patients, there was no identifiable cause. Conclusion: The majority of patients with haemospermia are aged < 45 years and have a benign aetiology. As haemospermia is self-limiting in the majority of cases, extensive investigations are unnecessary. Advanced and invasive tests should be confined to those with abnormal clinical findings, and to those with persistent or recurrent haemospermia. Level of evidence: Level IV.
Cardiopulmonary Exercise Testing—A Valuable Tool, Not Gatekeeper When Referring Patients With Adult Congenital Heart Disease for Transplant Evaluation
Authors: Menachem Jonathan N. , Reza Nosheen , Mazurek Jeremy A. , Burstein Danielle , Birati Edo Y. , Fox Arieh , Kim Yuli Y. , Molina Maria , Partington Sara L. , Tanna Monique , Tobin Lynda , Wald Joyce , Goldberg Lee R. 
Published: March 2019

Introduction: Treatment of patients with adult congenital heart disease (ACHD) with advanced therapies including heart transplant (HT) is often delayed due to paucity of objective prognostic markers for the severity of heart failure (HF). While the utility of Cardiopulmonary Exercise Testing (CPET) in non-ACHD patients has been well-defined as it relates to prognosis, CPET for this purpose in ACHD is still under investigation. Methods: We performed a retrospective cohort study of 20 consecutive patients with ACHD who underwent HT between March 2010 and February 2016. Only 12 of 20 patients underwent CPET prior to transplantation. Demographics, standard measures of CPET interpretation, and 30-day and 1-year post transplantation outcomes were collected. Results: Patient Characteristics. Twenty patients with ACHD were transplanted at a median of 40 years of age (range: 23-57 years). Of the 12 patients who underwent CPET, 4 had undergone Fontan procedures, 4 had tetralogy of Fallot, 3 had d-transposition of the great arteries, and 1 had Ebstein anomaly. Thirty-day and one-year survival was 100%. All tests included in the analysis had a peak respiratory quotient _1.0. The median peak oxygen consumption per unit time (_VO2) for all diagnoses was 18.2 mL/kg/min (46% predicted), ranging from 12.2 to 22.6. Conclusion: There is a paucity of data to support best practices for patients with ACHD requiring transplantation. While it cannot be proven based on available data, it could be inferred that outcomes would have been worse or perhaps life sustaining options unavailable if providers delayed referral because of the lack of attainment of CPET-specific thresholds.
Comparing 3 Different Techniques of Patella Fracture Fixation and Their Complications
Authors: Shea Graham Ka-Hon , Hoi-Ting So Karen , Tam Kin-Wai , Yee Dennis King-Hang , Fang Christian , Leung Frankie 
Published: March 2019

Introduction: Patella fractures managed by fixation with metal implants often cause local soft tissue irritation and necessitate implant removal. An alternative is to utilize suture-based fixation methods. We have adopted suture and hybrid fixation in the routine management of patella fractures. Here, we compare the results of 3 fixation techniques. Materials and Methods: Eighty-seven eligible patients underwent patella fracture fixation over a 3-year period. As determined by fracture configuration, patients received (1) suture fixation (transosseous sutures and figure-of-eight tension banding with FiberWire), (2) hybrid fixation (transosseous FiberWire sutures and metal tension banding), or (3) metal fixation. Primary outcome measures included reoperation rate and soft tissue irritation. Secondary outcomes included surgical complications, radiological, and functional parameters. Results: Reoperation rate was highest for metal fixation (25/57, 43.9%) and lowest for suture fixation (2/13, 15.4%). Soft tissue irritation necessitating implant removal was the predominant reason for reoperation and was significantly less prevalent following suture fixation (1/13, 7.7%, P < .01). Hybrid fixation resulted in similar rates of soft tissue irritation (6/17, 35.3%) and implant removal (7/17, 41.2%) as compared to metal fixation. There was a significant increase in patella baja (13/17, 76.5%) and reduction in Insall-Salvati ratio (0.742; 95% confidence interval: 0.682-0.802) following hybrid fixation as compared to the other 2 fixation methods ( P < .05). Discussion: Suture fixation results in the least amount of soft tissue irritation and lowest reoperation rate, but these advantages are negated with the addition of a metal tension band wire. Hybrid fixation also unbalances the extensor mechanism. Conclusion: Patients should be counseled as to the expected sequelae of their fixation method. Suture fixation is the favored means to fix distal pole fractures of the patella. An additional metal tension band loop may confer additional stability but should be applied with caution.
High risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant
Authors: Gebhart Johanna , Posch Florian , Koder Silvia , Quehenberger Peter , Perkmann Thomas , Kuessel Lorenz , Ay Cihan , Pabinger Ingrid 
Published: March 2019

Abstract
Lupus anticoagulant (LA) has been associated with pregnancy complications and pregnancy loss. Identification of predictive factors could aid in deciding on therapeutic management. To identify risk factors for adverse pregnancy outcomes in high-risk women with persistently positive LA, we prospectively followed 82 women of childbearing age, of whom 23 had 40 pregnancies within the Vienna Lupus Anticoagulant and Thrombosis Study. Pregnancy complications occurred in 28/40 (70%) pregnancies, including 22 (55%) spontaneous abortions (&lt;10th week of gestation [WOG]: n = 12, 10th to 24th WOG: n = 10) and 6 deliveries &lt;34th WOG (15%, 3 due to severe preeclampsia/HELLP [hemolysis, elevated liver enzymes, and a low platelet count] syndrome, 3 due to placental insufficiency). One abortion was followed by catastrophic antiphospholipid syndrome. Neither a history of pregnancy complications nor of thrombosis, or prepregnancy antiphospholipid antibody levels were associated with adverse pregnancy outcomes. In logistic regression analysis, higher age was associated with a lower risk of adverse pregnancy outcome (per 5 years’ increase: odds ratio [OR] = 0.41, 95% confidence interval [CI]: 0.19-0.87), a high Rosner index (index of circulating anticoagulant) predicted an increased risk (OR = 4.51, 95% CI: 1.08-18.93). Live birth rate was 15/28 (54%) in women on the combination of low-molecular-weight heparin and low-dose aspirin and 3/12 (25%) in those with no treatment or a single agent. We conclude that the risk of severe, even life-threatening pregnancy complications and adverse pregnancy outcomes is very high in women with persistent LA. A high Rosner index indicates an increased risk. Improved treatment options for women with persistently positive LA are urgently needed.
Glass confers rhabdomeric photoreceptor identity in Drosophila, but not across all metazoans
Authors: Bernardo-Garcia F. Javier , Syed Maryam , Jékely Gáspár , Sprecher Simon G. 
Published: March 2019

AbstractAcross metazoans, visual systems employ different types of photoreceptor neurons (PRs) to detect light. These include rhabdomeric PRs, which exist in distantly related phyla and possess an evolutionarily conserved phototransduction cascade. While the development of rhabdomeric PRs has been thoroughly studied in the fruit fly Drosophila melanogaster, we still know very little about how they form in other species. To investigate this question, we tested whether the transcription factor Glass, which is crucial for instructing rhabdomeric PR formation in Drosophila, may play a similar role in other metazoans. Glass homologues exist throughout the animal kingdom, indicating that this protein evolved prior to the metazoan radiation. Interestingly, our work indicates that glass is not expressed in rhabdomeric photoreceptors in the planarian Schmidtea mediterranea nor in the annelid Platynereis dumerilii. Combined with a comparative analysis of the Glass DNA-binding domain, our data suggest that the fate of rhabdomeric PRs is controlled by Glass-dependent and Glass-independent mechanisms in different animal clades.
Documentation of paintings restoration through photogrammetry and change detection algorithms
Authors: Abate Dante 
Published: March 2019

Abstract
The philosophical and theoretical foundations of the Theory of Restoration, envisioned by Cesare Brandi in 1975, are established around clear and straightforward guidelines on what is ethically acceptable, and unacceptable, in conservation. Specifically, the Italian scholar advocates for the complete reversibility of restoration work and respect for the history of an artwork. Indeed, according to these concepts, all interventions should be fully reversible so to return the object to its initial conditions without any damage. Bearing in mind these assumptions, a detailed documentation of all the steps of the conservation process, and the possibility to retrieve them a posteriori, must be considered essential. This concept especially applies when dealing with paintings restoration characterized by fine and small details. In recent years, the tendency is to favour minimal invasive interventions ranging from consolidation actions, cleaning samples, and colours retouching. Materials change more or less conspicuously over time according to their consistency and the intensity of the changing factors. Icons do not make an exception to this rule. This process affects the icon’s whole structure: the support, the painting itself and the varnish coating. This paper investigates the performance of change detection algorithms, developed in the remote sensing domain, and, in the framework of this research applied at a microscale (paintings). Each phase of the restoration process is documented exploiting a multi-epoch image acquisition. A monitoring methodology coupled with photogrammetry and 3D shape analysis is tested and described. It is anticipated that the proposed innovative use of change detection techniques can be applied to different kinds of painted surfaces. An icon, today preserved at the Byzantine Museum Makarios III Foundation in Nicosia and restored by the Department of Antiquities of Cyprus labs, has been used as a case study.
Suicide attempts and non-suicidal self-harm among university students: prevalence study
Authors: Sivertsen Børge , Hysing Mari , Knapstad Marit , Harvey Allison G. , Reneflot Anne , Lønning Kari Jussie , O'Connor Rory C. 
Published: March 2019

BackgroundSuicide attempts and non-suicidal self-harm (NSSH) are major public health concerns that affect millions of young people worldwide. Consequently, there is a strong need for up-to-date epidemiological data in this population.AimsTo provide prevalence and trend estimates of suicidal thoughts and behaviours and NSSH thoughts and behaviour in university students.MethodData are from a 2018 national health survey for higher education in Norway. A total of 50 054 full-time students (69.1% women) aged 18–35 years participated (response rate 31%). Suicidal ideation, suicide attempts and NSSH were assessed with three items drawn from the Adult Psychiatric Morbidity Survey, and thoughts of NSSH were assessed with one item from the Child and Adolescent Self-Harm in Europe study.ResultsLifetime suicidal thoughts were reported by 21.0%, and 7.2% reported having such thoughts within the past year. In total, 4.2% reported a suicide attempt, of whom 0.4% reported attempting suicide within the past year. The prevalence of lifetime NSSH behaviour and thoughts was 19.6% and 22.6%, respectively. All four suicidal behaviour and NSSH variables were more common among students who were single, living alone and with a low annual income, as well as among immigrants. There was an increase in suicidal thoughts from 2010 (7.7%) to 2018 (11.4%), which was evident in both men and women.ConclusionsThe observed high and increasing prevalence of suicidal thoughts and NSSH among college and university students is alarming, underscoring the need for further research, preferably registry-linked studies, to confirm whether the reported prevalence is representative of the student population as a whole.Declaration of interestNone.
Integrated care in mental health: next steps after the NHS Long Term Plan
Authors: Tracy Derek K. , Hanson Kara , Brown Tom , James Adrian J. B. , Paulsen Holly , Mulliez Zoé , Shergill Sukhwinder S. 
Published: March 2019

SummaryHealth and social care face growing and conflicting pressures: mounting complex needs of an ageing population, restricted funding and a workforce recruitment and retention crisis. In response, in the UK the NHS Long Term Plan promises increased investment and an emphasis on better ‘integrated’ care. We describe key aspects of integration that need addressing.Declaration of interestD.K.T. and S.S.S. are on the editorial board of the British Journal of Psychiatry and executives of the Academic Faculty at the Royal College of Psychiatrists. A.J.B.J., H.P. and Z.M. have roles at the Royal College of Psychiatrists that include evaluation of integrated care systems. A.J.B.J. is married to Dr Sarah Wollaston, Member of Parliament for Totnes and Chair of the Health Select Committee.
Liver Cancer in Guatemala: An Analysis of Mortality and Incidence Trends From 2012 to 2016
Authors: Kihn-Alarcón Alba J. , Toledo-Ponce María F. , Velarde Angel , Xu Ximing 
Published: March 2019

PURPOSE Guatemala has the highest mortality and incidence of liver cancer in Central and South America. The aim of this study is to describe the extent of liver cancer in the country from 2012 to 2016 and the associated risk factors. METHODS A secondary analysis was performed using liver cancer mortality and morbidity data and data on risk factors, such as hepatitis B virus infection, cirrhosis, and alcoholism. RESULTS Analysis revealed that liver cancer causes approximately 20% of cancer deaths in the country, is more frequent in the population older than age 65 years old, and is increasing in those age 30 to 44 years. More than 25% of deaths occurred in the North and West regions. The incidence of major risk factors for development of liver cancer has decreased. CONCLUSION The high mortality of liver cancer compared with its incidence indicates that most patients are diagnosed at late stages. To reduce the burden of liver cancer, creation of strategies for earlier detection is needed.
The 1ALCTL and 1BLCTL isoforms of Arg/Abl2 induce fibroblast activation and extra cellular matrix remodelling differently
Authors: Torsello Barbara , De Marco Sofia , Bombelli Silvia , Chisci Elisa , Cassina Valeria , Corti Roberta , Bernasconi Davide , Giovannoni Roberto , Bianchi Cristina , Perego Roberto A. 
Published: March 2019

ABSTRACT
The fibrotic tissue and the stroma adjacent to cancer cells are characterised by the presence of activated fibroblasts (myofibroblasts) which play a role in creating a supportive tissue characterised by abundant extracellular matrix (ECM) secretion. The myofibroblasts remodel this tissue through secreted molecules and modulation of their cytoskeleton and specialized contractile structures. The non-receptor protein tyrosine kinase Arg (also called Abl2) has the unique ability to bind directly to the actin cytoskeleton, transducing diverse extracellular signals into cytoskeletal rearrangements. In this study we analysed the 1ALCTL and 1BLCTL Arg isoforms in Arg−/− murine embryonal fibroblasts (MEF) cell line, focusing on their capacity to activate fibroblasts and to remodel ECM. The results obtained showed that Arg isoform 1BLCTL has a major role in proliferation, migration/invasion of MEF and in inducing a milieu able to modulate tumour cell morphology, while 1ALCTL isoform has a role in MEF adhesion maintaining active focal adhesions. On the whole, the presence of Arg in MEF supports the proliferation, activation, adhesion, ECM contraction and stiffness, while the absence of Arg affected these myofibroblast features.
This article has an associated First Person interview with the first author of the paper.
Escort cell encapsulation ofDrosophilagermline cells is maintained by irre cell recognition module proteins
Authors: Ben-Zvi Doreen S. , Volk Talila 
Published: March 2019

ABSTRACTDifferentiation of germline stem cells (GSCs) in the Drosophila ovary is induced by somatic escort cells (ECs), which extend membrane protrusions encapsulating the germline cells (GCs). Germline encapsulation requires activated epidermal growth factor receptor (Egfr) signaling within the ECs, following secretion of its ligands from the GCs. We show that the conserved family of irre cell recognition module (IRM) proteins is essential for GC encapsulation by ECs, with a requirement for roughest (rst) and kin of irre (kirre) in the germline and for sticks and stones (sns) and hibris (hbs) in ECs. In the absence of IRM components in their respective cell types, EC extensions are reduced concomitantly with a decrease in Egfr signaling in these cells. Reintroducing either activated Egfr in the ECs, or overexpressing its ligand Spitz (Spi) from the germline, rescued the requirement for IRM proteins in both cell types. These experiments introduce novel essential components, the IRM proteins, into the process of inductive interactions between GCs and ECs, and imply that IRM-mediated activity is required upstream of the Egfr signaling.
bif1, a new BMP signaling inhibitor, regulates embryonic hematopoiesis in the zebrafish
Authors: Ghersi Joey J. , Mahony Christopher B. , Bertrand Julien Y. 
Published: March 2019

ABSTRACT
Hematopoiesis maintains the entire blood system, and dysregulation of this process can lead to malignancies (leukemia), immunodeficiencies or red blood cell diseases (anemia, polycythemia vera). We took advantage of the zebrafish model that shares most of the genetic program involved in hematopoiesis with mammals to characterize a new gene of unknown function, si:ch73-299h12.2, which is expressed in the erythroid lineage during primitive, definitive and adult hematopoiesis. This gene, required during primitive and definitive erythropoiesis, encodes a C2H2 zinc-finger protein that inhibits BMP signaling. We therefore named this gene blood-inducing factor 1 and BMP inhibitory factor 1 (bif1). We identified a bif1 ortholog in Sinocyclocheilus rhinocerous, another fish, and in the mouse genome. Both genes also inhibit BMP signaling when overexpressed in zebrafish. In conclusion, we have deorphanized a new zebrafish gene of unknown function: bif1 codes for a zinc-finger protein that inhibits BMP signaling and also regulates primitive erythropoiesis and definitive hematopoiesis.
A branching gene regulatory network dictating different aspects of a neuronal cell identity
Authors: Stratmann Johannes , Ekman Helen , Thor Stefan 
Published: March 2019

ABSTRACT
The nervous system displays a daunting cellular diversity. Neuronal subtypes differ from each other in several aspects, including their neurotransmitter expression and axon projection. These aspects can converge, but can also diverge, such that neurons expressing the same neurotransmitter may project axons to different targets. It is not well understood how regulatory programs converge/diverge to associate/dissociate different cell fate features. Studies of the Drosophila Tv1 neurons have identified a regulatory cascade, ladybird early→collier→apterous/eyes absent→dimmed, that specifies Tv1 neurotransmitter expression. Here, we conduct genetic and transcriptome analysis to address how other aspects of Tv1 cell fate are governed. We find that an initiator terminal selector gene triggers a feedforward loop that branches into different subroutines, each of which establishes different features of this one unique neuronal cell fate.