bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should fractional flow reserve follow angiographic visual inspection to guide preventive percutaneous coronary intervention in ST-elevation myocardial infarction?
Authors: Wald David S , Hadyanto Steven , Bestwick Jonathan P 
Published: February 2020

Abstract

Aims
We aimed to quantify the effect of preventive percutaneous coronary intervention (PCI to non-infarct arteries) on cardiac death and non-fatal myocardial infarction (MI) in patients with ST-elevation myocardial infarction (STEMI) according to whether the decision to carry out preventive PCI was based on angiographic visual inspection (AVI alone) or AVI plus fractional flow reserve (FFR) if AVI showed significant stenosis (AVI plus FFR).

Methods and results
Randomized trials comparing preventive PCI with no preventive PCI in STEMI without shock were identified by a systematic literature search and categorized according to whether they used AVI alone or AVI plus FFR to select patients for preventive PCI. Random effects meta-analyses and tests of heterogeneity were used to compare the two categories in respect of cardiac death and MI as a combined outcome and individually. Eleven eligible trials were identified. For cardiac death and MI, the relative risk estimates for AVI alone vs. AVI plus FFR were 0.39 (0.25–0.61) and 0.85 (0.57–1.28), respectively (P = 0.01 for difference), for cardiac death, alone the estimates were 0.36 (0.19–0.71) and 0.79 (0.36–1.77), respectively (P = 0.15 for difference), and for MI alone, 0.41 (0.23–0.73) and 0.98 (0.62–1.56), respectively (P = 0.04 for difference).

Conclusion
In preventive PCI among STEMI patients, AVI alone achieves a ∼60% reduction in cardiac death and MI but selecting patients using FFR in AVI positive patients loses much of the benefit. Angiographic visual inspection is best used without FFR in this group of patients.
Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells
Authors: Aveleira Célia A , Ferreira-Marques Marisa , Cortes Luísa , Valero Jorge , Pereira Dina , Pereira de Almeida Luís , Cavadas Cláudia 
Published: February 2020

Abstract
Hutchinson-Gilford progeria syndrome (HGPS, or classical progeria) is a rare genetic disorder, characterized by premature aging, and caused by a de novo point mutation (C608G) within the lamin A/C gene (LMNA), producing an abnormal lamin A protein, termed progerin. Accumulation of progerin causes nuclear abnormalities and cell cycle arrest ultimately leading to cellular senescence. Autophagy impairment is a hallmark of cellular aging, and the rescue of this proteostasis mechanism delays aging progression in HGPS cells. We have previously shown that the endogenous Neuropeptide Y (NPY) increases autophagy in hypothalamus, a brain area already identified as a central regulator of whole-body aging. We also showed that NPY mediates caloric restriction-induced autophagy. These results are in accordance with other studies suggesting that NPY may act as a caloric restriction mimetic and plays a role as a lifespan and aging regulator. The aim of the present study was, therefore, to investigate if NPY could delay HGPS premature aging phenotype. Herein, we report that NPY increases autophagic flux and progerin clearance in primary cultures of human dermal fibroblasts from HGPS patients. NPY also rescues nuclear morphology and decreases the number of dysmorphic nuclei, a hallmark of HGPS cells. In addition, NPY decreases other hallmarks of aging as DNA damage and cellular senescence. Altogether, these results show that NPY rescues several hallmarks of cellular aging in HGPS cells, suggesting that NPY can be considered a promising strategy to delay or block the premature aging of HGPS.
Trajectories of Frailty and Cognitive Decline Among Older Mexican Americans
Authors: Howrey Bret T , Al Snih Soham , Middleton Joyce A , Ottenbacher Kenneth J 
Published: February 2020

Abstract

Background
Progressive physical frailty and cognitive decline in older adults is associated with increased risk of falls, disability, institutionalization, and mortality; however, there is considerable heterogeneity in progression over time. We identified heterogeneous frailty and cognitive decline trajectory groups and examined the specific contribution of health conditions to these trajectories among older Mexican origin adults.

Methods
We use a sample from the Hispanic Established Population for the Epidemiological Study of the Elderly (HEPESE) with at least two measures of frailty criteria during 18 years follow-up: slow gait, weak handgrip strength, exhaustion, and unexplained weight loss (n = 1362, mean age 72). Cognition was measured using the Mini-Mental State Examination (MMSE).

Results
Using group-based trajectory models we identified three frailty groups—non-frail (n = 331), moderate progressive (n = 855), and progressive high (n = 149)—and three cognitive decline groups—non-cognitively impaired (476), moderate decline (677) and rapid decline (n = 209). The probability of membership in a high-frailty group given membership in a progressive cognitive decline group was 63%, while the probability of being in a non-frail group given membership in a non-cognitively impaired group was 68%. Predictors of membership into both the progressive high frailty and rapid cognitive decline groups combined were low education and diabetes. Weekly church attendance was associated with a 66% reduction in the odds of being in the combined groups.

Conclusions
Interventions to reduce frailty rates and cognitive decline might focus on the management of underlying chronic disease and on increasing participation in activities outside the home.
The Role of Underweight in Active Life Expectancy Among Older Adults in Japan
Authors: Minagawa Yuka , Saito Yasuhiko 
Published: February 2020

AbstractObjectivesIt is underweight, rather than overweight or obesity, that has been a pressing public health concern in Japan. This study examines the impact of being underweight on the health of older Japanese men and women, measured by active life expectancy at age 65. Following the Japanese government’s guideline, underweight in this study is defined using the body mass index (BMI) value of 20.MethodData came from five waves (1999–2009) of the Nihon University Japanese Longitudinal Study of Aging (NUJLSOA). We used the Interpolation of Markov Chain approach to estimate the number of years underweight (BMI &lt; 20), normal weight (20 &lt; BMI &lt; 25), and overweight (25 &lt; BMI) individuals were expected to live without difficulty in activities of daily living (ADLs) or instrumental ADLs.ResultsWe found differences in life and health expectancies across the three weight categories. Underweight people were expected to live the shortest lives and spend the fewest years in an active state compared with normal and overweight individuals. Results remained unchanged even when accounting for educational attainment, smoking history, and a count of existing chronic conditions.DiscussionBeing underweight is associated with poor quality of life lived among Japanese older adults. This finding suggests the importance of maintaining proper weight and avoids nutritional risks at advanced ages.
Engineering mammalian cells to produce plant-specific N-glycosylation on proteins
Authors: Larsen Joachim Steen , Karlsson Richard Torbjörn Gustav , Tian Weihua , Schulz Morten Alder , Matthes Annemarie , Clausen Henrik , Petersen Bent Larsen , Yang Zhang 
Published: February 2020

Abstract
Protein N-glycosylation is an essential and highly conserved posttranslational modification found in all eukaryotic cells. Yeast, plants and mammalian cells, however, produce N-glycans with distinct structural features. These species-specific features not only pose challenges in selecting host cells for production of recombinant therapeutics for human medical use but also provide opportunities to explore and utilize species-specific glycosylation in design of vaccines. Here, we used reverse cross-species engineering to stably introduce plant core α3fucose (α3Fuc) and β2xylose (β2Xyl) N-glycosylation epitopes in the mammalian Chinese hamster ovary (CHO) cell line. We used directed knockin of plant core fucosylation and xylosylation genes (AtFucTA/AtFucTB and AtXylT) and targeted knockout of endogenous genes for core fucosylation (fut8) and elongation (B4galt1), for establishing CHO cells with plant N-glycosylation capacities. The engineering was evaluated through coexpression of two human therapeutic N-glycoproteins, erythropoietin (EPO) and an immunoglobulin G (IgG) antibody. Full conversion to the plant-type α3Fuc/β2Xyl bi-antennary agalactosylated N-glycosylation (G0FX) was demonstrated for the IgG1 produced in CHO cells. These results demonstrate that N-glycosylation in mammalian cells is amenable for extensive cross-kingdom engineering and that engineered CHO cells may be used to produce glycoproteins with plant glycosylation.
Adaptive cubic regularization methods with dynamic inexact Hessian information and applications to finite-sum minimization
Authors: Bellavia Stefania , Gurioli Gianmarco , Morini Benedetta 
Published: February 2020

AbstractWe consider the adaptive regularization with cubics approach for solving nonconvex optimization problems and propose a new variant based on inexact Hessian information chosen dynamically. The theoretical analysis of the proposed procedure is given. The key property of ARC framework, constituted by optimal worst-case function/derivative evaluation bounds for first- and second-order critical point, is guaranteed. Application to large-scale finite-sum minimization based on subsampled Hessian is discussed and analyzed in both a deterministic and probabilistic manner, and equipped with numerical experiments on synthetic and real datasets.
Automated Measurement of Plasma Cell-Free Hemoglobin Using the Hemolysis Index Check Function
Authors: Barbhuiya Mustafa A , Pederson Edward C , Straub Monica L , Neibauer Terri L , Salter Wayne F , Saylor Eric L , Scott Sofia C , Zhu Yusheng 
Published: February 2020

AbstractBackgroundThe Roche Cobas chemistry analyzer’s hemolysis index (HI) check function can directly report hemoglobin (Hb) concentrations. We aimed to validate the HI check function for the measurement of plasma cell-free Hb.MethodsPlasma samples (6 μl) were taken by the analyzer and diluted in normal saline to measure the absorbance for Hb at 570 and 600 nm. Hb concentrations were calculated based on the molar extinction coefficient. Imprecision, lower limit of quantification (LLOQ), and analytical measurement range (AMR) of the assay were evaluated. The accuracy was determined by comparing the results between the new method and an existing spectrophotometric method. We further studied interference of icterus and lipemia and carryover. The performance of the assay in proficiency testing was also evaluated. The reference range was transferred from the existing method.ResultsWithin-run and total CVs were 1.7%–4.2% and 2.1%–7.0%, respectively (n = 20). The LLOQ was 11 mg/dL (CV = 8.1%) with the upper limit of AMR of 506 mg/dL. The results of the new method correlated well with the existing reference assay: Y (new method) = 0.974 x (reference method) + 4.9, r = 0.9990, n = 52. Bilirubin with a concentration up to 60 mg/dL and lipemic index up to 389 did not show significant interference. No significant carryover was detected. The average standard deviation index in proficiency testing was 0.03 ± 0.29. The reference range was &lt;22 mg/dL.ConclusionsPlasma cell-free Hb measurement using the HI check function meets the analytical requirements of the plasma cell-free Hb assays. It is simple and cost-effective.
Moving Toward ‘Home’: Love and Relationships through War and Displacement
Authors: Porter Holly 
Published: February 2020

AbstractThe processual nature of affinal relationships is well established in Africanist anthropology. This article calls for greater attention to spatial considerations and proposes the concept of movement as an integral dimension of understanding affinal relationships. This observation springs from reflections on how the experiences of displacement and return in northern Uganda have reshaped constructions of ‘home’ in relation to love and intimate relationships. Reflecting on ethnographic research over ten years in northern Uganda where a two-decade-long war (1986–2006) occurred, the article examines movements in relationships between public and private spaces against the backdrop of wider societal movements from the spatial moral geography of camp to home. It reflects on how the spatial dynamics of camps entailed profound disruptions to ‘normal’ gendered orderings of life and how ‘home’ is being reconfigured in the aftermath of war.
Acculturation of Syrian Refugees in the Netherlands: Religion as Social Identity and Boundary Marker
Authors: Şafak-AyvazoĞlu AyŞe , KünüroĞlu Filiz , Van de Vijver Fons , YaĞmur Kutlay 
Published: February 2020

Abstract
We studied the acculturation processes of Syrian refugees in the Netherlands, based on semi-structured in-depth interviews. The study aims to investigate how Syrian refugees perceive the cultural distance caused by the differences and boundaries between Syrian and Dutch culture; how they cope with the boundaries and prejudice that they perceive; and which acculturation orientations they prefer. The research builds mainly on the framework of Berry’s acculturation model. Religion emerges as a prominent issue in the acculturation process and is found to impact acculturation as it is perceived to be a cause of cultural distance, a salient social identity, a bright boundary and a source of prejudice in the host country. Our findings suggest that refugees’ religious identity strongly influences their coping strategies and preferred acculturation orientations. Refugees with low/no religious affiliation were more in favour of an assimilation orientation whereas refugees with strong religious identity preferred an integration orientation.
Dynamic myelopathy as a result of C1 posterior arch aplasia and os odontoideum. A case report
Authors: Choy Wen Jie , Shivapathasundram Ganeshwaran , Cassar Lachlan , Mobbs Ralph J 
Published: February 2020

Abstract
The atlas (C1) and axis (C2) have distinct morphologies to support the skull and facilitate head rotation and neck flexion. Congenital defects of C1 posterior arch are rare. We present a case of a 59-year-old man with both an absent C1 posterior arch with concomitant os odontoideum. The patient presented with neck crepitus, moderate neck pain and progressive worsening upper limbs paraesthesia and pain. Computed tomography (CT) revealed non-union between the odontoid process and body of axis as well as absence of C1 posterior arch. An occiput C0–C3 fusion was performed. The patient’s symptoms improved significantly, and he is functioning well at 12 months. CT showed solid fusion without implant migration. Concomitant os odontoideum with aplastic C1 posterior arch is rare with limited evidence to guide management. Posterior fixation and fusion may be a potential solution to prevent dynamic compression, thereby preventing further myelopathy and related complications.
Genetic and molecular basis of floral induction in Arabidopsis thaliana
Authors: Kinoshita Atsuko , Richter René 
Published: February 2020

AbstractMany plants synchronize their life cycles in response to changing seasons and initiate flowering under favourable environmental conditions to ensure reproductive success. To confer a robust seasonal response, plants use diverse genetic programmes that integrate environmental and endogenous cues and converge on central floral regulatory hubs. Technological advances have allowed us to understand these complex processes more completely. Here, we review recent progress in our understanding of genetic and molecular mechanisms that control flowering in Arabidopsis thaliana.
Gulf War Illness Symptom Severity and Onset: A Cross-Sectional Survey
Authors: Fappiano Cayla M , Baraniuk James N 
Published: February 2020

Abstract
Introduction: Gulf War illness (GWI) affects 25 to 32% of the 693,826 veterans of the First Persian Gulf War. The etiology and pathophysiology of GWI remain controversial, but the condition is attributed to toxic exposures and stress in the deployed setting. The Kansas criteria used for GWI diagnosis highlight 37 symptoms that were more prevalent in deployed compared to nondeployed veterans. This study employed the Kansas criteria to identify recent symptom severity, assess the perceived burden of disease for veterans with GWI, and characterize disease course over the past three decades. Materials and Methods: The Kansas criteria were operationalized into a questionnaire to provide a summary of symptom severity, approximate year of onset, and an aid for diagnosis. The online version of the questionnaire was completed by 485 veterans with GWI. Symptom data were grouped for analysis based on observed trends. This study received approval from the Georgetown University Institutional Review Board (IRB 2018–0430). RESULTS: Symptom severity for the past 6 months demonstrated a high burden of disease for veteran participants. Frequency analysis of total severity scores (out of 148) showed a unimodal distribution with a median score of 95 (1st quartile = 78, 3rd quartile = 110), minimum score of 19, and maximum of 146. Over 89% of respondents had moderate or severe fatigue, sleep disturbances, pain, and abdominal symptoms over the past 6 months. The veterans who participated in this study reported cumulative frequencies higher than those in a meta-analysis of 21 GWI large epidemiologic cross-sectional studies for symptoms around 1998. The cumulative frequency of symptoms indicated long duration of symptoms, although recall bias must be taken into consideration. Conclusions: This cross-sectional sample of self-selected veterans with GWI demonstrates a high current burden of disease and reveals symptom onset patterns. The information from this study can be used to better understand the long-term trajectory of GWI and be integrated into the treatment and diagnosis of impacted veterans. It can also be used as historical deployed health data and inform the future medical care of combat veterans experiencing health effects from war exposures.
Mismatch repair systems might facilitate the chromosomal recombination induced by N-nitrosodimethylamine, but not by N-nitrosodiethylamine, in Drosophila
Authors: Negishi Tomoe , Yamada Kenji , Miyamoto Keiko , Mori Emiko , Taira Kentaro , Fujii Asei , Goto Yuki , Arimoto-Kobayashi Sakae , Okamoto Keinosuke 
Published: February 2020

Abstract
Mismatch repair (MMR) systems play important roles in maintaining the high fidelity of genomic DNA. It is well documented that a lack of MMR increases the mutation rate, including base exchanges and small insertion/deletion loops; however, it is unknown whether MMR deficiency affects the frequency of chromosomal recombination in somatic cells. To investigate the effects of MMR on chromosomal recombination, we used the Drosophila wing-spot test, which efficiently detects chromosomal recombination. We prepared MMR (MutS)-deficient flies (spel1(−/−)) using a fly line generated in this study. The spontaneous mutation rate as measured by the wing-spot test was slightly higher in MutS-deficient flies than in wild-type (spel1(+/−)) flies. Previously, we showed that N-nitrosodimethylamine (NDMA)-induced chromosomal recombination more frequently than N-nitrosodiethylamine (NDEA) in Drosophila. When the wing-spot test was performed using MMR-deficient flies, unexpectedly, the rate of NDMA-induced mutation was significantly lower in spel1(−/−) flies than in spel1(+/−) flies. In contrast, the rate of mutation induced by NDEA was higher in spel1(−/−) flies than in spel1(+/−) flies. These results suggest that in Drosophila, the MutS homologue protein recognises methylated DNA lesions more efficiently than ethylated ones, and that MMR might facilitate mutational chromosomal recombination due to DNA double-strand breaks via the futile cycle induced by MutS recognition of methylated lesions.
Low-dose oncolytic adenovirus therapy overcomes tumor-induced immune suppression and sensitizes intracranial gliomas to anti-PD-1 therapy
Authors: Belcaid Zineb , Berrevoets Cor , Choi John , van Beelen Edward , Stavrakaki Eftychia , Pierson Tessa , Kloezeman Jenneke , Routkevitch Denis , van der Kaaij Mariëlle , van der Ploeg Alicia , Mathios Dimitrios , Sleijfer Stefan , Dirven Clemens , Lim Michael , Debets Reno , Lamfers Martine L M 
Published: February 2020

AbstractBackgroundThe tumor-selective human adenovirus Delta24-RGD is currently under investigation in phase II clinical trials for patients with recurrent glioblastoma (GBM). To improve treatments for patients with GBM, we explored the potential of combining Delta24-RGD with antibodies targeting immune checkpoints.MethodsC57BL/6 mice were intracranially injected with GL261 cells and treated with a low dose of Delta24-RGD virus. The expression dynamics of 10 co-signaling molecules known to affect immune activity was assessed in tumor-infiltrating immune cells by flow cytometry after viral injection. The antitumor activity was measured by tumor cell killing and IFNγ production in co-cultures. Efficacy of the combination viro-immunotherapy was tested in vitro and in the GL261 and CT2A orthotopic mouse GBM models. Patient-derived GBM cell cultures were treated with Delta24-RGD to assess changes in PD-L1 expression induced by virus infection.ResultsDelta24-RGD therapy increased intratumoral CD8+ T cells expressing Inducible T-cell co-stimulator (ICOS) and PD-1. Functionality assays confirmed a significant positive correlation between tumor cell lysis and IFNγ production in ex vivo cultures (Spearman r = 0.9524; P &lt; .01). Co-cultures significantly increased IFNγ production upon treatment with PD-1 blocking antibodies. In vivo, combination therapy with low-dose Delta24-RGD and anti-PD-1 antibodies significantly improved outcome compared to single-agent therapy in both syngeneic mouse glioma models and increased PD-1+ tumor-infiltrating CD8+ T cells. Delta24-RGD infection induced tumor-specific changes in PD-L1 expression in primary GBM cell cultures.ConclusionsThis study demonstrates the potential of using low-dose Delta24-RGD therapy to sensitize glioma for combination with anti-PD-1 antibody therapy.