bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant melanoma showing a rapid response to nivolumab
Authors: Tsutsumi Miho , Asai Jun , Wada Makoto , Takenaka Hideya , Katoh Norito 
Published: April 2015

AbstractMalignant melanoma is a highly aggressive skin tumour, with a recent rise in incidence. Nivolumab is a recently developed anti‐programmed cell death‐1 immune checkpoint inhibitor and its usage has resulted in a significant improvement in the overall survival of patients with metastatic melanomas. We report a case of advanced melanoma that showed a significant and rapid response to nivolumab treatment. The patient displayed multiple melanoma‐associated vitiligo prior to treatment; this symptom was theorised to indicate potentially immunoreactive melanoma and the need for nivolumab. In addition, interferon‐β was injected prior to nivolumab treatment. The significant rapid response to nivolumab suggested the induction of a marked immune response against melanoma by interferon‐β. Therefore, interferon‐β could be a useful and effective adjuvant for nivolumab therapy.
Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells
Authors: Contoli M. , Ito K. , Padovani A. , Poletti D. , Marku B. , Edwards M. R. , Stanciu L. A. , Gnesini G. , Pastore A. , Spanevello A. , Morelli P. , Johnston S. L. , Caramori G. , Papi A. 
Published: April 2015

AbstractBackgroundAsthma and other Th2 inflammatory conditions have been associated with increased susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune responses to infections are largely unknown.MethodsWe measured the effects of Th2 cytokines (IL‐4 and IL‐13) on bronchial epithelial cell innate immune antiviral responses by assessing interferon (IFN‐β and IFN‐λ1) induction following rhinovirus (RV)‐16 infection. We also investigated the modulatory effects of Th2 cytokines on Toll‐like receptor 3 (TLR3), interferon‐responsive factor 3 (IRF3) and nuclear factor (NF)‐kB, that is key molecules and transcription factors involved in the rhinovirus‐induced interferon production and inflammatory cascade. Pharmacological and redox modulation of these pathways was also assessed.ResultsTh2 cytokines impaired RV‐16‐induced interferon production, increased rhinovirus replication and impaired TLR3 expression in bronchial epithelial cells. These results were replicated in vivo: we found increased IL‐4 mRNA levels in nasal epithelial cells from nasal brushing of atopic rhinitis patients and a parallel reduction in TLR3 expression and increased RV‐16 replication compared to nonatopic subjects. Mechanistically, Th2 cytokines impaired RV‐16‐induced activation of IRF3, but had no effects on RV‐16‐induced NF‐kB activation in bronchial epithelial cell cultures. N‐acetylcysteine and phosphoinositide 3‐kinase (PI3K) inhibitor restored the inhibitory effects of Th2 cytokines over RV‐16‐induced activation of IRF3.ConclusionsIL‐4 and IL‐13, through inhibition of TLR3 expression and signalling (IRF3), impair immune response to RV‐16 infection. These data suggest that Th2 conditions increase susceptibility to infections and identify pharmacological approaches with potential to restore impaired immune response in these conditions.
NSAID‐exacerbated respiratory disease: a meta‐analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity
Authors: Morales D. R. , Guthrie B. , Lipworth B. J. , Jackson C. , Donnan P. T. , Santiago V. H. 
Published: April 2015

AbstractBackgroundThe prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID‐exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified.MethodsA systematic review was performed by identifying studies diagnosing NERD using blinded, placebo‐controlled oral provocation challenge tests (OPCTs) or by self‐reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random‐effects meta‐analysis.ResultsThe prevalence of NERD in adults with asthma was 9.0% (95% CI 6–12%) using OPCTs and 9.9% (95% CI 9.4–10.5%) using self‐reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9–97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25–3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15–2.16) and RR 1.59 (95% CI 1.21–2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29–2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12–1.67)) compared to people with NSAID‐tolerant asthma.ConclusionsRespiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self‐reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow‐up.
Loneliness and the social monitoring system: Emotion recognition and eye gaze in a real‐life conversation
Authors: Lodder Gerine M. A. , Scholte Ron H. J. , Goossens Luc , Engels Rutger C. M. E. , Verhagen Maaike 
Published: April 2015

Based on the belongingness regulation theory (Gardner et al., 2005, Pers. Soc. Psychol. Bull., 31, 1549), this study focuses on the relationship between loneliness and social monitoring. Specifically, we examined whether loneliness relates to performance on three emotion recognition tasks and whether lonely individuals show increased gazing towards their conversation partner's faces in a real‐life conversation. Study 1 examined 170 college students (Mage = 19.26; SD = 1.21) who completed an emotion recognition task with dynamic stimuli (morph task) and a micro(‐emotion) expression recognition task. Study 2 examined 130 college students (Mage = 19.33; SD = 2.00) who completed the Reading the Mind in the Eyes Test and who had a conversation with an unfamiliar peer while their gaze direction was videotaped. In both studies, loneliness was measured using the UCLA Loneliness Scale version 3 (Russell, 1996, J. Pers. Assess., 66, 20). The results showed that loneliness was unrelated to emotion recognition on all emotion recognition tasks, but that it was related to increased gaze towards their conversation partner's faces. Implications for the belongingness regulation system of lonely individuals are discussed.
Effects of Climate History and Environmental Grain on Species’ Distributions in Africa and South America
Authors: Nakazawa Yoshinori , Peterson Andrew Townsend 
Published: April 2015

AbstractClimate changes during the Pleistocene produced shifts, reductions, and expansions of biomes that, in turn, have been hypothesized to have driven speciation and extinction and shaped patterns of biodiversity. Here, we explore effects of Late Pleistocene climatic changes on environmentally and geographically cohesive areas mimicking species’ distributions. We analyzed persistence of these ‘species’ over the transition from the warm Last Interglacial period to the cool Last Glacial Maximum period to warm present‐day conditions, for four levels of environmental restriction (5, 10, 15 and 20% of overall variation; akin to niche breadths). African environments were overall much less conserved over these periods than those of South America, matching diversity contrasts between the two continents. Results thus indicate that biodiversity patterns relate closely to historical patterns of environmental grain and their stability through time; this view is a step toward an integral understanding of the role of environmental and geographic factors in the process of biological diversification.
Clinical features and prognosis of eyeball rupture: eye injury vitrectomy study
Authors: Feng Kang , Wang Chang‐guan , Hu Yun‐tao , Yao Yi , Jiang Yan‐rong , Shen Li‐jun , Pang Xiu‐qin , Nie Hong‐ping , Ma Zhi‐zhong 
Published: April 2015

AbstractBackgroundThe objective of the study was to delineate clinical characteristics, surgical interventions, anatomic and visual outcomes of ruptured eye balls after trauma, and establish the prognostic indicators, which can assist clinicians in making correct surgical decisions during globe exploration for ruptured eyes.DesignThe study design used was a multicentre prospective cohort study, including six university‐affiliated tertiary hospitals.ParticipantsWe selected 242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until 31 December 2012.MethodsAll selected cases underwent vitreoretinal surgery, enucleation or evisceration, and were followed up for at least 6 months. Age, visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal laceration, scleral wound, extrusion of iris or lens, ciliary body damage, intraocular haemorrhage, retinal detachment or defect, proliferative vitreoretinopathy (PVR) and choroidal damage were the predisposing factors evaluated by logistic regression models.Main Outcome MeasuresWe compared the pre‐surgical indicators between cases of anatomically restored eyes with VA of 4/200 or better, or eyes with initial no light perception restored light perception or better, and cases of VA worse than 4/200, silicone oil‐sustained eyes, phthisis or enucleation.ResultsNearly 40% of cases with ruptured globe were anatomically restored through vitreoretinal surgery. The closed‐funnel retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026), PVR‐C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were correlated with poor outcomes.ConclusionThe closed‐funnel retinal detachment or extensive retinal loss, PVR‐C, and choroidal damage are the risk factors for unfavourable outcomes in globe ruptures.
A prospective, multicenter study assessing the DENTSPLY Implants, OsseoSpeed™TX, length 6 mm in the posterior maxilla and mandible: a 1‐year follow‐up study
Authors: Han Jie , Zhang Xiao , Tang Zhihui , Zhang Li , Shi Dong , Meng Huanxin 
Published: April 2015

AbstractObjectiveThe aim of this multicenter study was to prospectively assess clinical and radiographic outcomes of short implants (length 6 mm) in the posterior region and early‐loading with splinted‐fixed dental prostheses.Materials and methodsA total of 45 subjects (77.8% with chronic periodontitis) were enrolled at three study sites. In total, 95 implants (diameter 4 mm, length 6 mm; OsseoSpeed™ 4.0 S; DENTSPLY Implants; Mölndal, Sweden) were placed, two or three implants per subject, using one‐stage surgery and loaded with a screw‐retained splinted ceramic‐fixed prosthesis 6 weeks later. Clinical and radiographic examinations were performed preoperatively, post‐surgery, at loading, and 6 and 12 months after prosthesis placement.ResultsFour implants failed before loading; all other implants showed favorable clinical and radiographic findings throughout the observation period (1‐year survival and success rate: 95.8%). Postoperative pain and swelling were negligible. Mean changes in marginal bone levels measured from loading were minimal (0.01 ± 0.37 and −0.13 ± 0.46 mm after 6 months and 1 year, respectively). Bone loss less than 1.00 mm was found in 77.5% implants, and bone gain was found in 15.5% implants. Probing depth change less than 2 mm was found in 98.7% of the implants between loading and 1‐year follow‐up. Prosthetic complications included one ceramic veneer chipping.ConclusionOne‐year data indicate that the use of 6‐mm‐long implants is a predictable treatment. This provides a good treatment option in situations with limited bone height in posterior regions.
Normalized activation in the somatosensory cortex 30 years following nerve repair in children: an fMRI study
Authors: Chemnitz Anette , Weibull Andreas , Rosén Birgitta , Andersson Gert , Dahlin Lars B. , Björkman Anders 
Published: April 2015

AbstractThe clinical outcome following a peripheral nerve injury in the upper extremity is generally better in young children than in teenagers and in adults, but the mechanism behind this difference is unknown. In 28 patients with a complete median nerve injury sustained at the ages of 1–13 years (n = 13) and 14–20 years (n = 15), the cortical activation during tactile finger stimulation of the injured and healthy hands was monitored at a median time since injury of 28 years using functional magnetic resonance imaging (fMRI) at 3 Tesla. The results from the fMRI were compared with the clinical outcome and electroneurography. The cortical activation pattern following sensory stimulation of the median nerve‐innervated fingers was dependent on the patient's age at injury. Those injured at a young age (1–13 years) had an activation pattern similar to that of healthy controls. Furthermore, they showed a clinical outcome significantly superior (P = 0.001) to the outcome in subjects injured at a later age; however, electroneurographical parameters did not differ between the groups. In subjects injured at age 14–20 years, a more extended activation of the contralateral hemisphere was seen in general. Interestingly, these patients also displayed changes in the ipsilateral hemisphere where a reduced inhibition of somatosensory areas was seen. This loss of ipsilateral inhibition correlated to increasing age at injury as well as to poor recovery of sensory functions in the hand. In conclusion, cerebral changes in both brain hemispheres may explain differences in clinical outcome following a median nerve injury in childhood or adolescence.
Joint bleeds in von Willebrand disease patients have significant impact on quality of life and joint integrity: a cross‐sectional study
Authors: van Galen K. P. M. , Sanders Y. V. , Vojinovic U. , Eikenboom J. , Cnossen M. H. , Schutgens R. E. G. , van der Bom J. G. , Fijnvandraat K. , Laros‐Van Gorkom B. A. P. , Meijer K. , Leebeek F. W. G. , Mauser‐Bunschoten E. P. ,   the WiN Study Group
Published: April 2015

Background:
Joint bleeds (JB) are reported in a minority of patients with von Willebrand disease (VWD) but may lead to structural joint damage. Prevalence, severity and impact of JB in VWD are largely unknown.
Objectives:
The aim of this study was to assess JB prevalence, onset, treatment and impact on health‐related quality of life (HR‐QoL) and joint integrity in moderate and severe VWD.
Methods:
In the Willebrand in the Netherlands study 804 moderate and severe VWD patients [von Willebrand factor (VWF) activity ≤30U dL−1] completed a questionnaire on occurrence, sites and consequences of JB. To analyse JB number, onset, treatment and impact on joint integrity we additionally performed a patient–control study on medical file data comparing patients with JB to age, gender, factor VIII (FVIII)‐ and VWF activity matched VWD patients without JB.
Results:
Of all VWD patients 23% (184/804) self‐reported JB. These 184 patients reported joint damage more often (54% vs. 18%, P < 0.001) and had lower HR‐QoL (SF36, P < 0.05) compared to VWD patients not reporting JB. Of 55 patients with available JB data, 65% had the first JB before age 16. These 55 patients used more clotting factor concentrate (CFC; median dose 43 vs. 0 IE FVIII kg−1 year−1, P < 0.001), more often had X‐ray joint damage (44% vs. 11%, P = 0.001] and chronic joint pain (44% vs. 18%, P = 0.008) compared to 55 control VWD patients without JB.
Conclusion:
In conclusion, joint bleeds are reported by 23% of moderate and severe VWD patients, mostly start in childhood, are associated with more CFC use, joint pain, lower HR‐QoL and significantly more radiological and self‐reported joint damage.
Ongoing risk of thrombosis with factor XI concentrate: 5 years experience in two centres
Authors: Batty P. , Honke A. , Bowles L. , Hart D. P. , Pasi K. J. , Uprichard J. , Austin S. K. 
Published: April 2015

IntroductionFactor XI (FXI) deficiency is the commonest of the rare bleeding disorders, affecting 2079 individuals in the United Kingdom. Treatment options for bleeding or surgery include antifibrinolytics, fresh frozen plasma or plasma‐derived (pd) FXI concentrates. There were a number of reports of thrombosis following treatment with FXI concentrates prior to changes in their manufacturing processes made in the mid‐1990's. Aims: The aim of the study was to determine the occurrence of adverse events (haemorrhagic and thrombotic) following usage of pd‐FXI concentrates at two large UK haemophilia centres. Retrospective chart review of all consecutively treated patients with BPL Factor XI® or Hemoleven® over a 5‐year period (11/06–11/11) was performed.ResultsTwenty‐nine patients (median age = 57.1 years) received treatment over 64 treatment episodes (surgery = 56, bleeding = 5, other = 3), using 126 000 U of concentrate. Median baseline FXI:C was 9 U dL−1 (range = <1–51), with 21 having severe and eight partial deficiency. BPL Factor XI® was used in 39 episodes (79 110 U) and Hemoleven® 25 episodes (46 890 U). There were six clinically significant bleeding events, managed either with a single additional dose of FXI concentrate (n = 4) or requiring no further intervention (n = 2). One patient required blood transfusion and one oral iron replacement. Two thrombotic events (transient ischaemic attack and pulmonary emboli), occurred in two patients with severe FXI deficiency, despite cautious FXI concentrate usage in the perioperative period.ConclusionsFXI concentrate use is efficacious and safe in the majority of cases although physicians should remain mindful of the possibility of thrombotic complications.
Prevalence of uremic itching in patients undergoing hemodialysis
Authors: Kavurmacı Mehtap 
Published: April 2015

AbstractUremic itching is a common problem with multifactorial etiology seen in hemodialysis patients. This study was carried out to determine the factors affecting and incidence of itching in patients undergoing hemodialysis treatment. The descriptive study was carried out in 130 patients who underwent hemodialysis treatment because of end‐stage renal disease in Eastern Turkey between October 2014 and December 2014. A questionnaire prepared by the researcher based on the literature and the Visual Analog Scale were used for data collection. The data were collected by the researcher through face‐to‐face interviews in the hemodialysis unit. The evaluation of data obtained in the research has been performed using SPSS 16.0 software using percentages, chi‐square analysis, and t‐test. As a result of the study, 85.4% of the patients were found to have itching, the severity of itching was 4.86 ± 3.01 according to Visual Analog Scale, and itching of the patients was found to be affected by serum phosphorus and parathyroid hormone levels. Uremic itching continues to be seen as a problem in hemodialysis patients.
MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast
Authors: Piscuoglio Salvatore , Murray Melissa , Fusco Nicola , Marchiò Caterina , Loo Florence L , Martelotto Luciano G , Schultheis Anne M , Akram Muzaffar , Weigelt Britta , Brogi Edi , Reis‐Filho Jorge S 
Published: April 2015

AimsSomatic mutations in exon 2 of the mediator complex subunit 12 (MED12) gene have been identified in 60% of breast fibroadenomas (FAs). The aim of this study was to define whether phyllodes tumours (PTs) would harbour MED12 somatic mutations in a way akin to FAs.Methods and resultsA collection of 73 fibroepithelial tumours (including 26 FAs, 25 benign PTs, nine borderline PTs and 13 malignant PTs) from 64 patients was retrieved from the authors' institution. Sections from formalin‐fixed paraffin‐embedded (FFPE) blocks were microdissected to ensure an enrichment in neoplastic stromal elements of >70%. DNA samples extracted from tumour and matched normal tissues were subjected to Sanger sequencing of exon 2 of the MED12 gene. MED12 exon 2 somatic mutations, including 28 somatic single nucleotide variants and 19 insertions and deletions, were found in 65%, 88%, 78% and 8% of FAs, benign PTs, borderline PTs and malignant PTs, respectively. Malignant PTs harboured MED12 exon 2 somatic mutations significantly less frequently than FAs, benign and borderline PTs.ConclusionsAlthough MED12 exon 2 somatic mutations probably constitute the driver genetic event of most FAs, benign and borderline PTs, our results suggest that the majority of malignant PTs may be driven by other genetic/epigenetic alterations.
Trends in nontuberculous mycobacterial disease in hospitalized subjects in Spain (1997–2010) according to HIV infection
Authors: Álvaro‐Meca A , Rodríguez‐Gijón L , Díaz A , Gil Á , Resino S 
Published: April 2015

ObjectivesThe aim of the study was to estimate the incidence of nontuberculous mycobacterial (NTM) disease and the rate of NTM disease‐related mortality and to analyse trends in these variables according to HIV infection.MethodsWe performed a retrospective study for the period 1997–2010 using data from the Minimum Basic Data Set (MBDS) provided by the Spanish Ministry of Health. The exposure variables were: (i) HIV infection (HIV positive versus HIV negative); (ii) calendar period in relation to widespread use of combination antiretroviral therapy (cART) [1997–1999 (early cART period), 2000–2003 (middle cART period) and 2004–2010 (late cART period)]. The outcome variables were (i) new NTM disease diagnosis and (ii) mortality.ResultsA total of 3729 cases of incident NTM disease were collected in MBDS, 1795 in the HIV‐negative group and 1934 in the HIV‐positive group, among whom 602 deaths occurred, 223 in the HIV‐negative group and 379 in the HIV‐positive group. The incidence of NTM disease and the rate of NTM disease‐related mortality were 1000‐fold higher in the HIV‐positive group than in the HIV‐negative group. Regarding the incidence of NTM disease, in the HIV‐negative group the incidence increased from 2.91 to 3.97 events per 1 000 000 patient‐years from 1997–1999 to 2004–2010 (P < 0.001), while in the HIV‐positive group the incidence decreased from 2.29 to 0.71 events per 1000 patient‐years from 1997–1999 to 2004–2010 (P < 0.001). Regarding mortality, in the HIV‐negative group mortality increased from 2.63 to 4.26 events per 10 000 000 patient‐years from 1997–1999 to 2000–2003 (P = 0.059), and then the rate stabilized at around 3.87 events per 10 000 000 patient‐years in 2004–2010 (P = 0.128), while in the HIV‐positive group mortality decreased from 4.28 to 1.39 events per 10 000 patient‐years from 1997–1999 to 2004–2010 (P < 0.001).ConclusionsHIV infection was associated with a higher NTM disease incidence and higher NTM disease‐related mortality than in the general population, but these rates decreased in the HIV‐positive group from 1997–1999 to 2004–2010, whereas the NTM disease incidence increased in the HIV‐negative group.