bluuebunny/crossref_metadata_2025 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

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

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

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

Objectives

It 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.

Method

Data 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 < 20), normal weight (20 < BMI < 25), and overweight (25 < BMI) individuals were expected to live without difficulty in activities of daily living (ADLs) or instrumental ADLs.

Results

We 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.

Discussion

Being 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

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

We 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

Background

The 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.

Methods

Plasma 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.

Results

Within-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 <22 mg/dL.

Conclusions

Plasma 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

The 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

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

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

Many 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

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

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

Background

The 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.

Methods

C57BL/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.

Results

Delta24-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 < .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.

Conclusions

This study demonstrates the potential of using low-dose Delta24-RGD therapy to sensitize glioma for combination with anti-PD-1 antibody therapy.
Neuropsychological outcomes on Head Start III: a prospective, multi-institutional clinical trial for young children diagnosed with malignant brain tumors
Authors: O’Neil Sharon H , Whitaker Ashley M , Kayser Kimberly , Nelson Mary Baron , Finlay Jonathan L , Dhall Girish , Sands Stephen
Published: February 2020

Background

Current pediatric brain tumor treatment focuses on titrating toxicity based on risk factors while simultaneously improving survivorship. The Head Start (HS) protocols I to IV (1991-present) use high-dose chemotherapy (HDCTx) with an aim of reducing or eliminating cranial irradiation in very young children, the most vulnerable to its effects.

Methods

We examined estimated Full Scale IQ, overall Adaptive Functioning, Working Memory, Processing Speed, and Verbal and Nonverbal Memory outcome data for 43 HS III patients diagnosed between ages 2 months and 7 years from 15 institutions in the United States and Canada.

Results

At a mean of 5.12 years postdiagnosis, the HS III patients performed within the average to low-average ranges across these variables; however, individual variability was noted with scores ranging from superior to impaired, and the sample as a whole performed lower than age expectations. Performance did not significantly differ by sex or ethnicity, diagnosis, or for those treated with an intravenous methotrexate dose of 400 mg/kg vs 270 mg/kg. Additionally, performance did not significantly differ by age at diagnosis or length of follow-up.

Conclusions

The results, indicating overall average to low-average neurocognitive functioning, are encouraging, though significant individual variability was noted. Those who were younger at diagnosis, received more intensive methotrexate, and were further out from treatment were not at significantly increased risk of cognitive decline within our sample, suggesting a strategy of using HDCTx and autologous hematopoietic progenitor cell rescue to reduce or eliminate irradiation may allow for continued CNS development in young children treated for a brain tumor.
Efficacy and safety of bevacizumab in progressive pediatric low-grade glioma: a systematic review and meta-analysis of outcome rates
Authors: Lu Victor M , Welby John P , Nesvick Cody L , Daniels David J
Published: February 2020

Background

Successful management of pediatric low-grade glioma (pLGG) can be complicated by eloquent anatomical location, as well as specific pathologic and molecular features. Some authors have proposed using the VEGF inhibitor bevacizumab to improve disease control, but its safety and efficacy are poorly defined. Correspondingly, our aim was to pool systematically identified clinical data in the literature to assess the clinical utility of bevacizumab for pLGG at progression.

Methods

A systematic search of 7 electronic databases from inception to June 2019 was conducted following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Articles were screened against prespecified criteria. Outcomes were then pooled by random-effects meta-analyses of proportions.

Results

Seven pertinent studies described the outcomes of 110 progressive pLGG patients managed with bevacizumab in largely multiagent regimens. While on treatment, the rate of clinical response was 58% (95% CI, 43%-72%), and the rate of response on imaging was 80% (95% CI, 58%-96%). The rate of grade 3 or higher toxicity was 8% (95% CI, 2%-17%), with proteinuria the most commonly described. In the off-treatment period up to median 1 year, the rate of progression was estimated to be 51% (95% CI, 28%-74%).

Conclusions

Bevacizumab has the potential to control clinical and radiographic disease with relatively low grade 3 or higher toxicity risk in progressive pLGG patients. However, the long-term off-treatment benefits of this therapy are not yet well defined. Heterogeneity in the literature precludes any formal recommendations regarding its use until larger, more standardized investigations can be performed.
Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report
Authors: Whiles Emily , Joshi Hareesh , Prachi Prachi , Kavuri Venkaiah , Sagi Satyanarayana V
Published: February 2020

Autoantibodies to leucine-rich glioma-inactivated protein 1 (LGI-1) are associated with inflammation of the limbic system. Faciobrachial dystonic seizures are pathognomonic for LGI1-antibiodies and their treatment with immunotherapy is effective in seizure control with a potential to prevent cognitive decline. We report a 57-year-old man who presented to the emergency department with recurrent seizures, visual hallucinations and severe memory impairment over a seven-week period; he reported a background of alcohol excess. Initial investigations revealed hyponatremia, indicating syndrome of inappropriate anti-diuretic hormone secretion. Magnetic resonance imaging of the brain revealed bilateral asymmetrical high-T2 and low-T1 signal in the medial temporal lobes. Serum immunofluorescence assay tested positive for LGI-1 antibody. Patient responded to treatment with levetiracetam, intravenous methylprednisolone and five plasma exchange sessions. Patient remains on a maintenance dose of prednisolone and azathioprine. It is imperative that clinicians recognize signs of autoimmune encephalitis in order to curb long-term sequelae and improve clinical outcomes.
The Full-Length Transcriptome of Spartina alterniflora Reveals the Complexity of High Salt Tolerance in Monocotyledonous Halophyte
Authors: Ye Wenbin , Wang Taotao , Wei Wei , Lou Shuaitong , Lan Faxiu , Zhu Sheng , Li Qinzhen , Ji Guoli , Lin Chentao , Wu Xiaohui , Ma Liuyin
Published: February 2020

Spartina alterniflora (Spartina) is the only halophyte in the salt marsh. However, the molecular basis of its high salt tolerance remains elusive. In this study, we used Pacific Biosciences (PacBio) full-length single-molecule long-read sequencing and RNA-seq to elucidate the transcriptome dynamics of high salt tolerance in Spartina by salt gradient experiments. High-quality unigenes, transcription factors, non-coding RNA and Spartina-specific transcripts were identified. Co-expression network analysis found that protein kinase-encoding genes (SaOST1, SaCIPK10 and SaLRRs) are hub genes in the salt tolerance regulatory network. High salt stress induced the expression of transcription factors but repressed the expression of long non-coding RNAs. The Spartina transcriptome is closer to rice than Arabidopsis, and a higher proportion of transporter and transcription factor-encoding transcripts have been found in Spartina. Transcriptome analysis showed that high salt stress induced the expression of carbohydrate metabolism, especially cell-wall biosynthesis-related genes in Spartina, and repressed its expression in rice. Compared with rice, high salt stress highly induced the expression of stress response, protein modification and redox-related gene expression and greatly inhibited translation in Spartina. High salt stress also induced alternative splicing in Spartina, while differentially expressed alternative splicing events associated with photosynthesis were overrepresented in Spartina but not in rice. Finally, we built the SAPacBio website for visualizing full-length transcriptome sequences, transcription factors, ncRNAs, salt-tolerant genes and alternative splicing events in Spartina. Overall, this study suggests that the salt tolerance mechanism in Spartina is different from rice in many aspects and is far more complex than expected.
A review of compensatory growth following lysine restriction in grow-finish pigs1
Authors: Menegat Mariana B , Dritz Steve S , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Goodband Robert D
Published: February 2020

Compensatory growth induced by lysine (Lys) restriction in grow-finish pigs is a complex physiological process affected by many factors and interactions, principally genotype, stage of growth at restriction, nature of nutritional restriction, and patterns of restriction and recovery. The scarcity of standard comparisons across the literature has hindered the characterization of important determinants of compensatory growth. Therefore, the present publication aims to review the current state of knowledge on compensatory growth induced by Lys restriction in grow-finish pigs, develop a database from peer-reviewed literature to standardize comparisons to characterize the occurrence of compensatory growth, and provide practical considerations for compensatory growth under field conditions. The literature search focused on publications directly or indirectly evaluating compensatory growth by having a period of Lys restriction followed by a recovery period of Lys sufficiency for grow-finish pigs. The database included 14 publications and 57 comparisons expressed as relative differences of restricted pigs compared to nonrestricted pigs. The database analysis described compensatory growth into complete, incomplete, and no compensatory growth categories and characterized the patterns of restriction and recovery in each category. The review of literature and database analysis supports the occurrence of compensatory growth induced by Lys restriction in grow-finish pigs. The degree of Lys restriction and duration of restriction and recovery periods seem to be critical in explaining differences between complete and incomplete compensatory growth, whereas Lys level in the recovery period seems to be critical between incomplete or no compensatory growth. Compensatory growth seems to be more likely if: 1) the degree of Lys restriction is between 10% and 30%; 2) Lys restriction is induced before pigs reach their maximum protein deposition; 3) duration of Lys restriction is short (maximum 40–45% overall duration) and duration of recovery period is long (minimum 55–60% overall duration); and 4) Lys level in recovery is close to or above the estimated requirements. In addition, compensatory growth can occur under commercial conditions and there seems to be an opportunity to exploit compensatory growth in grow-finish pigs to reduce feed cost and improve feed efficiency under certain market conditions.
Mutations in the coat protein of a begomovirus result in altered transmission by different species of whitefly vectors
Authors: Pan Li-Long , Chi Yao , Liu Chao , Fan Yun-Yun , Liu Shu-Sheng
Published: February 2020

For many crop pathogens including viruses, high genetic variation provides them with potential to adapt to and prevail in a changing environment. Understanding genetic variation in viruses and their significance is a key to elaborate virus epidemiology and evolution. While genetic variation of plant viruses has been documented to impact virus–host interactions, how it affects virus–insect vector interactions remains elusive. Here, we report the impact of mutations in the coat protein of squash leaf curl China virus (SLCCNV), a begomovirus, on the interaction between the virus and its whitefly vectors. We characterized mutations in the coat protein of SLCCNV and found that some residues exhibited higher mutation frequency than the others. We assayed the impact of mutation on infectivity using agroinoculation and found these mutations marginally affect virus infectivity. We further analyze their functions using virus acquisition and transmission trials and found some of mutations resulted in altered transmission of SLCCNV by different species of the whitefly Bemisia tabaci complex. We then identified the key amino acid residue(s) involved by constructing several mutant viruses and found that a single-residue mutation in the coat protein of SLCCNV was sufficient to significantly alter the whitefly transmission characteristics of SLCCNV. We examined the competition between different genotypes of SLCCNV in plant infection and whitefly transmission. We found that mutations in the coat protein did not alter the fitness of SLCCNV in plants, but they rendered the virus more competitive in transmission by certain species of whiteflies. Our findings indicate that mutations in the coat protein may play a key role in both the adaptation of begomoviruses to the changing vector populations and the evolution of begomoviruses.
Outcomes of Older Patients with NPM1 Mutated and FLT3‐ITD Negative Acute Myeloid Leukemia Receiving Allogeneic Transplantation
Authors: Jentzsch Madlen , Grimm Juliane , Bill Marius , Goldmann Karoline , Schulz Julia , Niederwieser Dietger , Platzbecker Uwe , Schwind Sebastian
Published: February 2020

Supplemental Digital Content is available in the text
Modifiable Lifestyle and Medical Risk Factors Associated With Myeloproliferative Neoplasms
Authors: Duncombe Andrew S. , Anderson Lesley A. , James Glen , de Vocht Frank , Fritschi Lin , Mesa Ruben , Clarke Mike , McMullin Mary Frances
Published: February 2020

Despite the identification of acquired genetic mutations associated with Myeloproliferative Neoplasms (MPNs) there is a paucity of information relating to modifiable risk factors that may lead to these mutations. The MOSAICC Study was an exploratory case‐control study of polycythemia vera (PV), essential thrombocythemia (ET), and Myelofibrosis (MF). MPN patients and population controls (identified by General Practitioners) and non‐blood relative/friend controls were recruited from 2 large UK centers. Participants completed a telephone‐based questionnaire analyzed by unconditional logistic regression analysis adjusting for potential confounders. Risk factors for MPNs identified included increasing childhood household density [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.16–5.62], low childhood socioeconomic status (OR 2.30, 95%CI 1.02–5.18) and high pack years smoking (OR 2.19, 95%CI 1.03–4.66) and current smoking restricted to JAK2 positive PV cases (OR 3.73, 95%CI 1.06–13.15). Obesity was linked with ET (OR 2.59, 95%CI 1.02–6.58) confirming results in previous cohort studies. Receipt of multiple CT scans was associated with a strongly increased risk of MPN although with wide confidence intervals (OR 5.38, 95%CI 1.67–17.3). Alcohol intake was inversely associated with risk of PV (OR 0.41, 95%CI 0.19–0.92) and ET (OR 0.48, 95%CI 0.24–0.98). The associations with childhood household density, high pack years smoking and alcohol were also seen in multivariate analysis. This is the largest case control study in MPNs to date and confirms the previously reported associations with obesity and cigarette smoking from cohort studies in addition to novel associations. In particular, the role of smoking and JAK2 mutation cases merits further evaluation.
Determining Significant Elevation of Intraocular Pressure Using Self-tonometry
Authors: Huang Jessie , Phu Jack , Kalloniatis Michael , Zangerl Barbara
Published: February 2020

SIGNIFICANCE

Icare HOME rebound tonometry is increasingly adopted into clinical practice for IOP phasing of glaucoma patients and suspects. Because of measurement differences with applanation tonometry and diurnal fluctuations, interpretation of the IOP measured with Icare HOME phasing can be challenging.

PURPOSE

The purpose of this study was to use a large patient cohort to develop a practical, analytical tool for interpreting Icare HOME measurements with respect to applanation pressure.

METHODS

IOP measurements using the Icare HOME and an applanation tonometer were taken prospectively in 498 consecutive patients. Bland-Altman, frequency distribution, and linear regression analysis were applied to determine measurement differences. A novel criterion, Threshold Icare HOME IOP, was developed to assist identification of elevation above target applanation pressure, considering the expected diurnal variation and measurement variability.

RESULTS

Icare HOME tended to underestimate applanation tonometry (mean bias, −1.7 mmHg; 95% limits of agreement, −7.0 to +3.6). Overall, differences were within ±3 mmHg in 71.5% and ±5 mmHg in 92% of patients. Based on the novel criterion developed, Icare HOME measurements that exceed target applanation pressure by 6 mmHg or greater are generally outside the 95% limit of expected observations.

CONCLUSIONS

The Threshold Icare HOME IOP is a novel and practical criterion that can assist clinicians in their interpretation of Icare HOME phasing measurements with respect to target applanation pressures. Elevation above the expected thresholds may prompt closer monitoring or even modifications to glaucoma management.
Rebound Self-tonometry Acquisition Time and Ease of Use Evaluated by Newly Trained Optometry Students and Optometrists
Authors: Hyatt Ruth , Furtado Nadine M. , Eberle Darcy , Jensen Katherine , Tsang Timothy , Kwan Justin
Published: February 2020

SIGNIFICANCE

Peak IOP and IOP fluctuations have been implicated as risk factors for glaucoma progression. Peak 24-hour IOP can be significantly higher than in-office measurements. Icare HOME could be a useful adjunct in glaucoma management if positively appraised by individuals familiar with eye care.

PURPOSE

The purpose of this study was to measure the time needed for a nonclinical convenience sample of optometry students and optometrists to self-measure IOP using Icare HOME and to determine their perceptions of rebound self-tonometry.

METHODS

A total of 234 subjects were enrolled, with 226 (97%) having a complete data set. Self-measurement was performed on the study eye using Icare HOME while seated and without contact lenses. Examiners self-measured IOP while subjects observed; examiners then measured subjects' IOP. Subjects then completed self-measurement while timed. Only one attempt was allowed. Time and study eye were recorded, and subjects completed a short survey. Descriptive statistics were conducted.

RESULTS

Mean ± standard deviation age was 34.6 ± 13.3 years (58.3% female, 52.3% contact lens wearers). Test time ranged from 3 to 366 seconds, with 38% able to self-measure in 10 seconds or less, 74% in 60 seconds or less, and 92.8% in 120 seconds or less; 5.8% were unable to self-measure IOP. There was no significant correlation between test time and age (r = −0.03, P = .67). The device was reported to be easy or very easy to use by 69.7% of subjects and comfortable or very comfortable by 90.4% of subjects. After the study, 89.1% of subjects perceived that rebound self-tonometry has a role in the management of patients with glaucoma and suspicion of glaucoma.

CONCLUSIONS

The majority of neophyte subjects perceived self-measurement of IOP as having a role in the management of glaucoma and suspicion of glaucoma. They rated Icare HOME as comfortable and easy to use and were able to self-measure IOP on the first attempt.
Neonatal Acute Lymphoblastic Leukemia
Authors: Oliver Rachel , Juergens Andrew L. , Hatch Derek , Lucia Dominic , DeLario Melissa
Published: February 2020

Acute lymphoblastic leukemia (ALL) in a neonate can have a similar clinical appearance to other serious pathology and should be considered in the ill-appearing infant. We present the case of a 24-hour-old male infant born to a mother with limited prenatal care who was brought to the pediatric emergency department with a rash and decreased movement. His initial white blood cell count was 822 × 109 cells/L. Cytogenetics showed a complex t (9;19;11) translocation, indicating a diagnosis of neonatal ALL. Given the morbidity and mortality rate among infants with neonatal ALL, his parents elected not to pursue cancer-directed therapy in favor of symptomatic care.
Passive water harvesting by desert plants and animals: lessons from nature
Authors: Gurera Dev , Bhushan Bharat
Published: February 2020

Fresh water sustains human life and is vital for human health. For some of the poorest countries, 1 in 10 people do not have access to safe and easily accessible water sources. Water consumption by man continues to grow with an increasing population. The current supply of fresh water needs to be supplemented to meet future needs. Living nature provides many lessons for water harvesting. It has evolved species which can survive in the most arid regions of the world by passively collecting water from fog and condensation of water vapour in the night. Before the collected water evaporates, species have mechanisms to transport water for storage or consumption. These species possess unique chemistry and structures on or within the body for collection and transport of water. Among the high diversity of species surviving in deserts, only a handful of species have been studied. Based on lessons from nature, bioinspired water harvesters can be designed. In this paper, an overview of various desert plants and animals is given and known water harvesting mechanisms of some are presented.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology (part 3)’.
4D pine scale: biomimetic 4D printed autonomous scale and flap structures capable of multi-phase movement
Authors: Correa David , Poppinga Simon , Mylo Max D. , Westermeier Anna S. , Bruchmann Bernd , Menges Achim , Speck Thomas
Published: February 2020

We developed biomimetic hygro-responsive composite polymer scales inspired by the reversible shape-changes of Bhutan pine (
Pinus wallichiana
) cone seed scales. The synthetic kinematic response is made possible through novel four-dimensional (4D) printing techniques with anisotropic material use, namely copolymers with embedded cellulose fibrils and ABS polymer. Multi-phase motion like the subsequent transversal and longitudinal bending deformation during desiccation of a natural pinecone scale can be structurally programmed into such printed hygromorphs. Both the natural concept generator (Bhutan pinecone scale) and the biomimetic technical structure (4D printed scale) were comparatively investigated as to their displacement and strain over time via three-dimensional digital image correlation methods. Our bioinspired prototypes can be the basis for tailored autonomous and self-sufficient flap and scale structures performing complex consecutive motions for technical applications, e.g. in architecture and soft robotics.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology (part 3)’.
Amyloid-β CSF/PET discordance vs tau load 5 years later: It takes two to tangle
Authors: Reimand Juhan , Collij Lyduine , Scheltens Philip , Bouwman Femke , Ossenkoppele Rik ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2020

OBJECTIVE

To investigate the association between discordant amyloid-β PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.

METHODS

We included 730 ADNI participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]Florbetapir PET and CSF Aβ42 available. Amyloid-β CSF/PET status was determined at baseline using established cut-offs. Longitudinal data was available for [18F]florbetapir (Aβ) PET (baseline to 4.3±1.9 years), CSF (p)tau (baseline to 2.0±0.1 years), cognition (baseline to 4.3±2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2±1.2 years after baseline to 1.6±0.7 years later). We used linear mixed modelling to study the association between amyloid-β CSF/PET status and tau pathology measured in CSF or using PET. Additionally, we calculated the proportion of CSF+/PET-participants who during follow-up (i) progressed to amyloid-β CSF+/PET+, and/or (ii) became tau-positive based on [18F]flortaucipir PET.

RESULTS

Amyloid-β CSF+/PET+ (N=318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET-(N=80) participants were overall similar to the CSF-/PET-(N=306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET-group (1.20±0.13) did not differ from CSF-/PET-(1.18±0.08, p=0.69), but was substantially lower than CSF+/PET+ (1.48±0.44, p<0.001). Of the CSF+/PET-subjects, 21/64 (33%) progressed to amyloid-β CSF+/PET+, whereas only one (3%, difference p<0.05) became tau-positive based on [18F]flortaucipir PET.

CONCLUSIONS

Sufficient amyloid-β load detectable by both CSF and PET is required before substantial tau deposition emerges. Compared to participants with abnormal amyloid-β levels on PET and CSF, the CSF+/PET-group has a distinctly better prognosis.