bluuebunny/crossref_metadata_2025_split huggingface dataset:
T‐cell Immunoglobulin and ITIM Domain Contributes to CD8+ T‐cell Immunosenescence
Authors: Song Yangzi , Wang Beibei , Song Rui , Hao Yu , Wang Di , Li Yuxin , Jiang Yu , Xu Ling , Ma Yaluan , Zheng Hong , Kong Yaxian , Zeng Hui 
Published: January 2018

SummaryAging is associated with immune dysfunction, especially T‐cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T‐cell exhaustion and T‐cell senescence. In this study, we showed that T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif (ITIM) domain (TIGIT), a novel co‐inhibitory receptor, was upregulated in CD8+ T cells of elderly adults. Aged TIGIT+ CD8+ T cells expressed high levels of other inhibitory receptors including PD‐1 and exhibited features of exhaustion such as downregulation of the key costimulatory receptor CD28, representative intrinsic transcriptional regulation, low production of cytokines, and high susceptibility to apoptosis. Importantly, their functional defects associated with aging were reversed by TIGIT knockdown. CD226 downregulation on aged TIGIT+ CD8+ T cells is likely involved in TIGIT‐mediated negative immune suppression. Collectively, our findings indicated that TIGIT acts as a critical immune regulator during aging, providing a strong rationale for targeting TIGIT to improve dysfunction related to immune system aging.
Hybrid Continuous‐Flow Total Artificial Heart
Authors: Fox Carson , Chopski Steven , Murad Nohra , Allaire Paul , Mentzer Robert , Rossano Joseph , Arabia Francisco , Throckmorton Amy 
Published: January 2018

AbstractClinical studies using total artificial hearts (TAHs) have demonstrated that pediatric and adult patients derive quality‐of‐life benefits from this form of therapy. Two clinically‐approved TAHs and other pumps under development, however, have design challenges and limitations, including thromboembolic events, neurologic impairment, infection risk due to large size and percutaneous drivelines, and lack of ambulation, to name a few. To address these limitations, we are developing a hybrid‐design, continuous‐flow, implantable or extracorporeal, magnetically‐levitated TAH for pediatric and adult patients with heart failure. This TAH has only two moving parts: an axial impeller for the pulmonary circulation and a centrifugal impeller for the systemic circulation. This device will utilize the latest generation of magnetic bearing technology. Initial geometries were established using pump design equations, and computational modeling provided insight into pump performance. The designs were the basis for prototype manufacturing and hydraulic testing. The study results demonstrate that the TAH is capable of delivering target blood flow rates of 1–6.5 L/min with pressure rises of 1–92 mm Hg for the pulmonary circulation and 24–150 mm Hg for the systemic circulation at 1500–10 000 rpm. This initial design of the TAH was successful and serves as the foundation to continue its development as a novel, more compact, nonthrombogenic, and effective therapeutic alternative for infants, children, adolescents, and adults with heart failure.
The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real‐world experience
Authors: El‐Khayat H. R. , Kamal E. M. , El‐Sayed M. H. , El‐Shabrawi M. , Ayoub H. , RizK A. , Maher M. , El Sheemy R. Y. , Fouad Y. M. , Attia D. 
Published: January 2018

SummaryBackgroundThe combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12‐17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients.AimTo investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world.MethodsThis prospective multicentre (six centres) open‐label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males). All patients received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir once daily for 12 weeks. Laboratory and virological markers were evaluated at baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment (SVR12).ResultsSVR12 was observed in 142/144 patients (99%). The relapsers occurred in previous naïve patients (n = 2/128, 2%), while the experienced patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100% in F2 patients (P = 0.552). No serious side effects were observed, nor was treatment discontinuation or death. Headache was the most common side effect in all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea (44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naïve patients.ConclusionsA ledipasvir plus sofosbuvir regimen is well tolerated and effective, and can be used safely in treating adolescent patients with chronic hepatitis C genotype 4.
Experiential learning, community engagement, and student experience: Undergraduate field school course in rural British Columbia
Authors: McPhee Siobhán , Przedpelska Sarah 
Published: January 2018

Key Messages

Field courses are important for geographical education and for developing transferable skills.
Community partners add richness and depth to student experiences in field course design.
Students are regarded as possessors of their own learning experience, with the role of the instructor as a facilitator.
Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma
Authors: Looi K. , Buckley A. G. , Rigby P. J. , Garratt L. W. , Iosifidis T. , Zosky G. R. , Larcombe A. N. , Lannigan F. J. , Ling K.‐M. , Martinovich K. M. , Kicic‐Starcevich E. , Shaw N. C. , Sutanto E. N. , Knight D. A. , Kicic A. , Stick S. M. 
Published: January 2018

SummaryBackgroundBronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma.ObjectivesTo investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AECs) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children.MethodsPrimary AECs were obtained from children with and without asthma, differentiated into air‐liquid interface (ALI) cultures and infected with rhinovirus. Expression of claudin‐1, occludin and zonula occluden‐1 (ZO‐1) was assessed via qPCR, immunocytochemistry (ICC), in‐cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER; RT) and permeability to fluorescent dextran.ResultsBasal TJ gene expression of claudin‐1 and occludin was significantly upregulated in asthmatic children compared to non‐asthmatics; however, no difference was seen with ZO‐1. Interestingly, claudin‐1, occludin and ZO‐1 protein expression was significantly reduced in AEC of asthmatic children compared to non‐asthmatic controls suggesting possible post‐transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non‐asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction in TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed.ConclusionThis study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma.
Measurement properties of gingival biotype evaluation methods
Authors: Alves Patrick Henry Machado , Alves Thereza Cristina Lira Pacheco , Pegoraro Thiago Amadei , Costa Yuri Martins , Bonfante Estevam Augusto , de Almeida Ana Lúcia Pompéia Fraga 
Published: January 2018

AbstractBackgroundThere are numerous methods to measure the dimensions of the gingival tissue, but few have compared the effectiveness of one method over another.ObjectiveThis study aimed to describe a new method and to estimate the validity of gingival biotype assessment with the aid of computed tomography scanning (CTS).Materials and MethodsIn each patient different methods of evaluation of the gingival thickness were used: transparency of periodontal probe, transgingival, photography, and a new method of CTS). Intrarater and interrater reliability considering the categorical classification of the gingival biotype were estimated with Cohen's kappa coefficient, intraclass correlation coefficient (ICC), and ANOVA (P < .05). The criterion validity of the CTS was determined using the transgingival method as the reference standard. Sensitivity and specificity values were computed along with theirs 95% CI.ResultsTwelve patients were subjected to assessment of their gingival thickness. The highest agreement was found between transgingival and CTS (86.1%). The comparison between the categorical classifications of CTS and the transgingival method (reference standard) showed high specificity (94.92%) and low sensitivity (53.85%) for definition of a thin biotype.ConclusionThe new method of CTS assessment to classify gingival tissue thickness can be considered reliable and clinically useful to diagnose thick biotype.
The Preference for Pointing With the Hand Is Not Universal
Authors: Cooperrider Kensy , Slotta James , Núñez Rafael 
Published: January 2018

AbstractPointing is a cornerstone of human communication, but does it take the same form in all cultures? Manual pointing with the index finger appears to be used universally, and it is often assumed to be universally preferred over other forms. Non‐manual pointing with the head and face has also been widely attested, but it is usually considered of marginal significance, both empirically and theoretically. Here, we challenge this assumed marginality. Using a novel communication task, we investigated pointing preferences in the Yupno of Papua New Guinea and in U.S. undergraduates. Speakers in both groups pointed at similar rates, but form preferences differed starkly: The Yupno participants used non‐manual pointing (nose‐ and head‐pointing) numerically more often than manual pointing, whereas the U.S. participants stuck unwaveringly to index‐finger pointing. The findings raise questions about why groups differ in their pointing preferences and, more broadly, about why humans communicate in the ways they do.
Patent foramen ovale repair at the time of double lung transplantation: Necessary or not?
Authors: Hess Nicholas R. , Esper Stephen A. , Awori Hayanga J. W. , Tuft Marie , Morrell Matthew , D'Cunha Jonathan 
Published: January 2018

AbstractIntroductionPatient foramen ovale (PFO) is a common and often incidental intraoperative finding during lung transplantation (LTx). We sought to characterize the potential outcomes related to the decision making of whether the PFO was repaired or left unrepaired.MethodsWe retrospectively evaluated bilateral LTx recipients between 2005 and 2015 from our prospective database. Incidence of postoperative stoke, 90‐day mortality, and overall survival was compared between the PFO‐positive and PFO‐negative groups, and secondly compared between repaired PFO (rPFO) and non‐repaired PFO (nrPFO) groups.ResultsA total of 831 LTx recipients were analyzed: 185 PFO‐positive (140 nrPFO, 45 rPFO) and 646 PFO‐negative. Study groups were similar with regard to age and comorbidity. The presence of PFO was not associated with a difference in postoperative stroke (P = .89) or 90‐day mortality (P = .64). In patients with PFO, intraoperative repair resulted in a lower, but non‐significant rate of stroke (0% vs 5%; P = .20) and no difference in mortality (P = .26). As expected, PFO and PFO repair were both associated with a higher incidence of cardiopulmonary bypass utilization, but no difference in pump‐related complications.ConclusionsThe protective effect of PFO repair remains unclear. However, it is not associated with an increased incidence of stroke or postoperative mortality following LTx.
Primary cardiac angiosarcoma: A case report
Authors: Ambrus Nóra , Havasi Kálmán , Kalapos Anita , Sághy László , Makai Attila , Bogáts Gábor , Hegedűs Zoltán , Iványi Béla , Besenyi Zsuzsanna , Pápai Zsuzsanna , Nagy László , Forster Tamás , Nemes Attila 
Published: January 2018

Cardiac angiosarcomas are the most common primary malignant cardiac tumors in adults. The diagnosis is often delayed due to nonspecific clinical symptoms at presentation. The cornerstones of diagnosis are echocardiography and the histological evaluation of the cardiac biopsy. The knowledge on the treatment is limited; the outcomes of chemotherapy, radiotherapy, complete surgical removal, and heart transplantation are controversial. We report a 38‐year‐old woman with a primary heart tumor which infiltrated the right atrial wall and the pericardium and caused pericardial effusion. Angiosarcoma was verified histologically. The surgical excision could not be radical, and the patient died 3 months from diagnosis.
Thrombectomy outcomes for acute stroke patients with anterior circulation tandem lesions: a clinical registry and an update of a systematic review with meta‐analysis
Authors: Sadeh‐Gonik U. , Tau N. , Friehmann T. , Bracard S. , Anxionnat R. , Derelle A.‐L. , Tonnelet R. , Liao L. , Richard S. , Armoiry X. , Gory B. 
Published: January 2018

Background and purposeAlthough mechanical thrombectomy (MT) appears to be superior in stroke patients with extracranial carotid disease (ECD) compared to thrombolysis alone, the impact of emergent carotid stenting during MT remains unclear. The MT outcomes were assessed in anterior stroke patients with ECD, especially when combined with carotid stenting.MethodsA retrospective analysis of our registry was performed and an update of a systematic review and meta‐analysis of MT studies with or without stenting for anterior circulation stroke with ECD published between November 2010 and April 2017 was conducted.ResultsIn our registry, 46 patients with ECD underwent MT. In the meta‐analysis including 13 primary studies plus our prospective registry data (590 patients in total), the successful reperfusion rate (modified thrombolysis in cerebral infarction score ≥2b) reached 75% [95% confidence interval (CI) 69%–81%]. The rate of symptomatic intracranial haemorrhage (sICH) was 8% (95% CI 6%–11%), 90‐day favourable outcome was achieved in 50% (95% CI 42%–59%) and mortality rate was 16% (95% CI 11%–22%). When using carotid stenting, rates of successful reperfusion, sICH, 90‐day favourable outcome and mortality were 80% (95% CI 73%–87%), 7% (95% CI 4%–12%), 53% (95% CI 43%–62%) and 14% (95% CI 9%–19%), respectively.ConclusionsOur data report an association between acute stenting and successful reperfusion rates in stroke patients with tandem lesion treated with MT. Further studies are warranted to determine the intracranial bleeding risk after MT and stenting according to the antiplatelet therapy.
Surgical repair of propagating condylar fractures of the third metacarpal/metatarsal bones with cortical screws placed in lag fashion in 26 racehorses (2007–2015)
Authors: Moulin N. , François I. , Coté N. , Alford C. , Cleary O. , Desjardins M. R. 
Published: January 2018

SummaryBackgroundDespite the recommendation of plate fixation for propagating condylar fractures of the third metacarpal (McIII) or third metatarsal bone (MtIII), lag screw fixation can be a viable surgical option.ObjectivesTo evaluate short‐term outcome and long‐term racing performance of horses that underwent lag screw fixation of long condylar fractures of the McIII/MtIII.Study designRetrospective case series.MethodsMedical records, post‐surgical racing performance and outcome of 26 horses with propagating fractures of the medial and/or lateral condyle of McIII/MtIIIwere reviewed. Medical information included were age, breed, sex, physical examination at admission, circumstances of fracture, radiographic evaluation, anaesthesia and recovery records, surgical and post‐operative management, as well as complications. Outcome included racing data and information from telephone interviews.ResultsTwenty‐six horses (9 Standardbreds and 17 Thoroughbreds) were admitted with a long condylar fracture of the McIII/MtIII. Fore‐ and hindlimbs were equally represented with the left hindlimb being more frequently involved. Most of the fractures had a spiralling component (76%) and four (15%) were comminuted. Fifteen (58%) horses raced post‐surgery including nine Standardbreds (100%) and six Thoroughbreds (35%). Twelve of them were placed in at least one race and 11 won at least once. One horse sustained a severe complication in recovery. No significant difference was observed in the racing performances before and after surgery.Main limitationsFollow‐up method and duration were not standardised and there is a low number of cases with six surgeons.ConclusionsLong condylar fractures can be repaired using lag fashion technique combined with a half‐limb or full‐limb tight cast for recovery as a good surgical alternative. Similar results to plate fixation can be expected, with a return to racing of more than 50%, and the prognosis being even better for pacers.
From grey to green: Efficacy of eco‐engineering solutions for nature‐based coastal defence
Authors: Morris Rebecca L. , Konlechner Teresa M. , Ghisalberti Marco , Swearer Stephen E. 
Published: January 2018

AbstractClimate change is increasing the threat of erosion and flooding along coastlines globally. Engineering solutions (e.g. seawalls and breakwaters) in response to protecting coastal communities and associated infrastructure are increasingly becoming economically and ecologically unsustainable. This has led to recommendations to create or restore natural habitats, such as sand dunes, saltmarsh, mangroves, seagrass and kelp beds, and coral and shellfish reefs, to provide coastal protection in place of (or to complement) artificial structures. Coastal managers are frequently faced with the problem of an eroding coastline, which requires a decision on what mitigation options are most appropriate to implement. A barrier to uptake of nature‐based coastal defence is stringent evaluation of the effectiveness in comparison to artificial protection structures. Here, we assess the current evidence for the efficacy of nature‐based vs. artificial coastal protection and discuss future research needs. Future projects should evaluate habitats created or restored for coastal defence for cost‐effectiveness in comparison to an artificial structure under the same environmental conditions. Cost‐benefit analyses should take into consideration all ecosystem services provided by nature‐based or artificial structures in addition to coastal protection. Interdisciplinary research among scientists, coastal managers and engineers is required to facilitate the experimental trials needed to test the value of these shoreline protection schemes, in order to support their use as alternatives to artificial structures. This research needs to happen now as our rapidly changing climate requires new and innovative solutions to reduce the vulnerability of coastal communities to an increasingly uncertain future.
Were we terrorists? History, terrorism, and the French Resistance
Authors: Millington Chris 
Published: January 2018

AbstractThis article argues that scholars of historical terrorism should abandon the practice of defining the phenomenon in favour of prioritising past understandings of terrorist violence. Research into the history of terrorism often uses a definition informed by contemporary concerns to reveal previous incidents and outbreaks of terrorism. This approach speaks more to the concerns of the present than those of the past. We must refocus our attention on how people in history understood terrorism and to whom and to what they applied the term. This approach can open avenues of investigation into neglected or sensitive subjects, with the example of the violence of the French Resistance explored here. Historians have rejected the use of the term “terrorism” to describe resistance action, preferring instead to use military or paramilitary terminology. However, resistance violence was understood in several ways, and the resisters' own rejection of the terrorist label was not total.
Malignant mesothelioma in situ
Authors: Churg Andrew , Hwang Harry , Tan Larry , Qing Gefei , Taher Altaf , Tong Amy , Bilawich Ana M , Dacic Sanja 
Published: January 2018

AimsThe existence of malignant mesothelioma in situ (MIS) is often postulated, but there are no accepted morphological criteria for making such a diagnosis.Methods and resultsHere we report two cases that appear to be true MIS on the basis of in‐situ genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart revealed only visually normal pleura. Biopsies from both thoracoscopies showed only a single layer of mildly reactive mesothelial cells. However, these cells had lost BRCA1‐associated protein 1 (BAP1) and showed loss of cyclin‐dependent kinase inhibitor 2 (CDKN2A) (p16) by fluorescence in‐situ hybridisation (FISH). NF2 was not deleted by FISH but 28% of the mesothelial cells showed hyperploidy. Six months after the second biopsy the patient has persisting effusions but no evidence of pleural malignancy on imaging. The second patient presented with ascites and minimal omental thickening on imaging, but no visual evidence of tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical mesothelial cells with rare tiny foci of superficial invasion of fat. BAP1 immunostain showed loss of nuclear BAP1 in all the surface mesothelial cells and the invasive cells. There was CDKN2A deletion, but no deletion of NF2 by FISH.ConclusionsThese cases show that morphologically bland single‐layered surface mesothelial proliferations with molecular alterations seen previously only in invasive malignant mesotheliomas exist, and presumably represent malignant MIS. More cases are need to understand the frequency of such changes and the time–course over which invasive tumour develops.
Mechanical properties of bioactive glass/polymer composite scaffolds for repairing load bearing bones
Authors: Mohammadkhah Ali , Day Delbert E. 
Published: January 2018

AbstractDeveloping a glass scaffold suitable for repairing defects in load‐bearing bones has been a challenging task due to the brittle and catastrophic failure characteristics of glass, especially when subjected to flexural or tensile stresses. In the present work, the flexural strength of cylindrical scaffolds composed of thermally bonded, unidirectional 13‐93 silicate glass fibers, was compared with the flexural strength of a cylindrical composite scaffold. The composite scaffold consisted of a core of the same thermally bonded, unidirectional glass fibers, but the core was encased within a nominal 500 micron thick layer of a biodegradable polymer, polylactic acid (PLA). The flexural strength of the PLA composite scaffolds (~120 MPa) was more than twice that of the all‐glass “bare” scaffolds (no PLA) and was within the range for the flexural strength of cortical bone. Unlike the brittle, catastrophic failure observed for bare scaffolds, the composite scaffolds behaved as a ductile material under flexural loads and remained load bearing even after significant physical/mechanical damage had occurred during flexural loading. The higher flexural strength of composite scaffolds along with their ductility under flexural loads and their cylindrical geometry are important advantages compared to all‐glass “bare” scaffolds.