bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic Risk Scores
Authors: Osterman Michael D. , Kinzy Tyler G. , Bailey Jessica N. Cooke 
Published: May 2021

AbstractAs genome‐wide association studies have continued to identify loci associated with complex traits, the implications of and necessity for proper use of these findings, including prediction of disease risk, have become apparent. Many complex diseases have numerous associated loci with detectable effects implicating risk for or protection from disease. A common contemporary approach to using this information for disease prediction is through the application of genetic risk scores. These scores estimate an individual's liability for a specific outcome by aggregating the effects of associated loci into a single measure as described in the previous version of this article. Although genetic risk scores have traditionally included variants that meet criteria for genome‐wide significance, an extension known as the polygenic risk score has been developed to include the effects of more variants across the entire genome. Here, we describe common methods and software packages for calculating and interpreting polygenic risk scores. In this revised version of the article, we detail information that is needed to perform a polygenic risk score analysis, considerations for planning the analysis and interpreting results, as well as discussion of the limitations based on the choices made. We also provide simulated sample data and a walkthrough for four different polygenic risk score software. © 2021 Wiley Periodicals LLC.This article was corrected on 28 July 2022. See the end of the full text for details.
Effects of nitrogen regulation and strip intercropping on faba bean biomass, nitrogen accumulation and distribution, and interspecific interactions
Authors: Luo Chaosheng , Zhu Jinhui , Ma Liankun , Guo Zengpeng , Dong Kun , Dong Yan 
Published: May 2021

AbstractEffects of nitrogen fertilization on the accumulation and distribution of biomass and plant nitrogen content in intercropped faba beans, together with its impact on the interspecific interactions between faba bean and wheat has not been well studied. Here, we have used a logistic model to analyze the cropping systems (i.e., monocropped faba bean, monocropped wheat, and faba bean intercropped with wheat) by evaluating the effects of different levels of nitrogen application on the dynamic changes in biomass and nitrogen accumulation, along with the interspecific interaction. Using monocropped and intercropped faba beans in field experiments spanning two years, we found that nitrogen application increased both monocropped and intercropped faba bean yields. The yield of intercropped faba beans was greatest at the lower nitrogen input for two consecutive years. Nitrogen application increased the biomass and nitrogen accumulation in both monocropped and intercropped faba beans. The simulation parameters that increased were maximum nitrogen accumulation (A') and maximum accumulation rate (R'max) while the initial cumulative rate (r') decreased. Compared with monocropping, intercropped faba bean–wheat showed increased yield and biomass accumulation, along with a significantly increased initial growth rate (r) and a maximum instantaneous growth rate (Rmax). Intercropping reduced stem and leaf biomass and the nitrogen distribution ratio while increasing the pod content. In the early intercropped faba bean growth stage, there was no competition for nutrients or any kind of yield advantage, while in the later stages, the nutrient competitiveness of intercropping was stronger than the intraspecific competition, showing the advantages of intercropping on biomass and yield (i.e., relative crowding coefficient [K] >1, relative interspecific competitiveness [RC] >0, and relative competition intensity [RCI] <0). In summary, nitrogen application of 45 kg ha–1 could be the desired amount that maximizes the nutrient competition and interspecific advantages in the middle and late stages of faba bean growth when intercropped, thus contributing to the yield.
Impairment of episodic memory in genetic frontotemporal dementia: A GENFI study
Authors: Poos Jackie M. , Russell Lucy L. , Peakman Georgia , Bocchetta Martina , Greaves Caroline V. , Jiskoot Lize C. , van der Ende Emma L. , Seelaar Harro , Papma Janne M. , van den Berg Esther , Pijnenburg Yolande A.L. , Borroni Barbara , Sanchez‐Valle Raquel , Moreno Fermin , Laforce Robert , Graff Caroline , Synofzik Matthias , Galimberti Daniela , Rowe James B. , Masellis Mario , Tartaglia Carmela , Finger Elizabeth , Vandenberghe Rik , de Medonça Alexandre , Tagliavini Fabrizio , Butler Chris R. , Santana Isabel , Ber Isabelle Le , Gerhard Alex , Ducharme Simon , Levin Johannes , Danek Adrian , Otto Markus , Sorbi Sandro , Pasquier Florence , van Swieten John C. , Rohrer Jonathan D. ,   the Genetic FTD Initiative, GENFI
Published: May 2021

AbstractIntroductionWe aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT).MethodsThe FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule‐associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel‐based morphometry to investigate the underlying neural substrates of the FCSRT.ResultsAll symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers.DiscussionThe FCSRT detects presymptomatic deficits in C9orf72‐ and MAPT‐associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.
Outdoor life in dementia: How predictable are people with dementia in their mobility?
Authors: Bayat Sayeh , Mihailidis Alex 
Published: May 2021

AbstractIntroductionPeople with dementia (PWD) often become disoriented, which increases their risk of getting lost. This article explores the extent to which we can predict future whereabouts of PWD by learning from their past mobility patterns using Global Positioning System (GPS) tracking devices.MethodsSeven older adults with dementia and eight healthy older adults completed 8 weeks of GPS data collection. We computed the probability that an appropriate algorithm can correctly predict the participant's future destinations using spatial and temporal patterns in each participant's GPS trajectories.ResultsRelying on both spatial and temporal patterns, our results suggest that a 4‐week record of mobility patterns displays 95% potential predictability across the dementia group, which is significantly higher than 92% potential predictability among the controls, t(13) = –3.39, P < .01, d = –1.75. That is, we can hope to be able to predict destinations of PWD about 95% of the time and destinations of controls about 92% of the time.DiscussionsOur findings on predictability of mobility patterns among PWD offer new perspectives on predictive mobility models that can be used to locate missing persons with dementia.
Seven‐year follow‐up of persistent postsurgical pain in cardiac surgery patients: A prospective observational study of prevalence and risk factors
Authors: Harrogate Suzanne R. , Cooper Jackie A. , Zawadka Mateusz , Anwar Sibtain 
Published: May 2021

AbstractBackgroundOur aim was to describe the long‐term prevalence, risk factors and impact on quality of life of persistent postsurgical pain (PPP) following cardiac surgery.MethodsAll patients undergoing sternotomy in a single centre over 6 months were prospectively interviewed by telephone at six months and seven years following surgery.ResultsWe analysed data from 174 patients at six months and 146 patients at seven years following surgery, revealing a PPP prevalence of 39.7% (n = 69) and 9.6% (n = 14) respectively.At six post‐operative months, younger age, higher acute pain score, intraoperative remifentanil infusion and more prolonged surgery were associated with sternotomy‐site PPP. These variables, in combination, predict PPP in this study group with area under the receiver operating curve of 0.91 (95% CI 0.86–0.94) at 6 months and 0.74 (95% CI 0.57–0.86) at 7 years. Quality of life scores were significantly lower with PPP (median change in EQ‐5D score = −0.23 [−0.57, −0.09] compared to 0.00 [0–0.24] without PPP at 7 years, p < 0.001). At7 years, younger age, prolonged surgery and intraoperative remifentanil infusion were associated with sternotomy‐site PPP.ConclusionsTo the best of our knowledge, this is the longest follow‐up of PPP across all surgical specialities and certainly within cardiac surgery. Prevalence of PPP and impact on QOL after cardiac surgery are high and associated with young age, high acute pain score, use of remifentanil and long operative time. We present a predictive score to highlight patients at risk of developing PPP.SignificanceSeven years after cardiac surgery, almost 10% of patients in this cohort described persistent pain in and around the incision. While higher than previous reports in the literature (limited to up to five post‐operative years), this assessment was made following three maximal coughs and therefore is movement or function evoked. High incident of persistent postsurgical pain may adversely affect long‐term quality of life which is measured using a validated tool.
Amantadine prevented hypersensitivity and decreased oxidative stress by NMDA receptor antagonism after spinal cord injury in rats
Authors: Mata‐Bermudez Alfonso , Ríos Camilo , Burelo Masha , Pérez‐González Cuauhtémoc , García‐Martínez Betzabé Anahí , Jardon‐Guadarrama Gustavo , Calderón‐Estrella Francisco , Manning‐Balpuesta Norman , Diaz‐Ruiz Araceli 
Published: May 2021

AbstractBackgroundNeuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N‐methyl‐D‐aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, an NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI.MethodsTo produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25 mm and 12.5 mm. Nociceptive behaviour, was evaluated with the use of von Frey filaments for 31 days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15 days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25–50 mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue.ResultsAcute treatment with amantadine reduced nociceptive behaviour. Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine.ConclusionsData from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated with N‐methyl‐D‐aspartate receptors activation.SignificanceThis study suggests that acute treatment with amantadine decreases hypersensitivity threshold and frequency of hypersensitivity response in a dose‐dependent manner, in rats with SCI, by decreasing oxidative stress. Since amantadine is an easily accessible drug and has fewer adverse effects than current treatments for hypersensitivity threshold and frequency of hypersensitivity response, amantadine could represent a safe and effective therapy for the treatment of neuropathic pain. However, further research is required to provide evidence of the effectiveness and feasibility.
Long‐term opioid treatment and endocrine measures in chronic non‐cancer pain patients: A systematic review and meta‐analysis
Authors: Diasso Pernille D. K. , Frederiksen Benedikte S. , Nielsen Susanne D. , Main Katharina M. , Sjøgren Per , Kurita Geana P. 
Published: May 2021

AbstractBackground and ObjectiveLong‐term opioid treatment (L‐TOT) of chronic non‐cancer pain (CNCP) patients has been suspected to alter the endocrine system. This systematic review and meta‐analysis aimed at investigating the published evidence of L‐TOT effects on the endocrine system in adult CNCP patients.Databases and Data TreatmentA systematic search of the literature in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL was performed. Studies examining measures of endocrine function of the hypothalamic‐pituitary‐gonadal, ‐adrenal, ‐thyroid, ‐somatotropic and ‐prolactin axis in adult CNCP patients in L‐TOT (≥4 weeks of use) were included. Outcomes and the level of evidence were analyzed (The Cochrane Collaboration Tool, modified version of the Newcastle‐Ottawa Scale and Rating of Recommendations Assessment, Development and Evaluation working group).ResultsA total of 2,660 studies were identified; 1981 excluded and finally thirteen studies (one randomized controlled trial (RCT), three longitudinal‐ and nine cross‐sectional studies) were analyzed. L‐TOT was associated with low insulin, suppression of the hypothalamic‐pituitary‐gonadal axis and alterations of the hypothalamic‐pituitary‐adrenal axis in both men and women with CNCP compared to different control groups (CNCP or healthy pain‐free). No other significant differences were reported. The studies had a high risk of bias and the overall quality of evidence was low.ConclusionThere seems to be an impact of L‐TOT in CNCP patients on several components of the endocrine system, but the level of evidence is weak. Given the high prevalence of L‐TOT use systematic studies of larger patient populations are urgently needed.SignificanceThis systematic review and meta‐analysis suggested that long‐term opioid treatment may suppress the hypothalamic‐pituitary‐gonadal axis, and result in lower insulin levels and alter the glucocorticoid adrenal axis in adult chronic non‐cancer pain patients. This adds to the need of more research of both clinical and paraclinical outcomes and their association when initiating and maintaining long‐term opioid treatment.
Tolerance to low phosphorus was enhanced by an alternate wetting and drying regime in rice
Authors: Deng Yaping , Qiao Shengfeng , Wang Weilu , Zhang Weiyang , Gu Junfei , Liu Lijun , Zhang Hao , Wang Zhiqin , Yang Jianchang 
Published: May 2021

AbstractPhosphorus (P) deficiency is a limiting factor for sustainable rice (Oryza sativa L.) production. However, little is known about how rice varieties that differ in tolerance to low P perform under water‐saving irrigation. In this study, we characterized the responses of two rice varieties, ZD88 that has a weak tolerance to low soil P and YJ2 that has a strong tolerance to low soil P to two irrigation regimes under both optimal P (NP, 46.9 mg/kg Olsen‐P) and low P (LP, 6.8 mg/kg Olsen‐P). The first irrigation regime involved continuous flooding (CF), while the second involved alternate wetting and moderate soil drying (AWD). The study was conducted in plants grown in pot over two years. YJ2 exhibited stronger tolerance to LP than ZD88 under both irrigation regimes. Compared to CF, plants grown with AWD produced higher grain yields and had increased phosphorus translocation efficiencies, as well as higher metabolic phosphorus efficiencies and increased phosphorus harvest index values. The water use efficiencies of the two rice varieties were increased under both NP and LP under AWD conditions. The AWD regime also resulted in higher shoot dry weights and increased photosynthesis rates under LP compared with CF. Moreover, the remobilization of non‐structural carbohydrates from stems to the grain was also increased under the AWD regime, together with higher activities of sucrose‐phosphate synthase, sucrose synthase and peroxidases and increased abscisic acid contents in grains. Root dry weights and root to shoot ratios were also increased under AWD conditions, together with increased root acid phosphatase activities. Taken together, these results demonstrate that the AWD regime benefits rice production under LP environment.
Development of a stakeholder identification and analysis method for human factors integration in work system design interventions – Change Agent Infrastructure
Authors: Berlin Cecilia , Bligård Lars‐Ola , Babapour Chafi Maral , Eriksson Siw 
Published: May 2021

AbstractIn any work system design intervention—for example, a physical workplace re‐design, a work process change, or an equipment upgrade—it is often emphasized how important it is to involve stakeholders in the process of analysis and design, to gain their perspectives as input to the development, and ensure their future acceptance of the solution. While theusersof an artifact or workplace are most often regarded as being the most important stakeholders in a design intervention, in a work‐system context there may be additional influential stakeholders who influence and negotiate the design intervention's outcomes, resource allocation, requirements, and implementation. Literature shows that it is uncommon for empirical ergonomics and human factors (EHF) research to apply and report the use of any structured stakeholder identification method at all, leading to ad‐hoc selections of whom to consider important. Conversely, other research fields offer a plethora of stakeholder identification and analysis methods, few of which seem to have been adopted in the EHF context. This article presents the development of a structured method for identification, classification, and qualitative analysis of stakeholders in EHF‐related work system design intervention. It describes the method's EHF‐related theoretical underpinnings, lessons learned from four use cases, and the incremental development of the method that has resulted in the current method procedure and visualization aids. The method, called Change Agent Infrastructure (abbreviated CHAI), has a mainly macroergonomic purpose, set on increasing the understanding of sociotechnical interactions that create the conditions for work system design intervention, and facilitating participative efforts.
Deep convolution neural networks to differentiate between COVID‐19 and other pulmonary abnormalities on chest radiographs: Evaluation using internal and external datasets
Authors: Cho Yongwon , Hwang Sung Ho , Oh Yu‐Whan , Ham Byung‐Joo , Kim Min Ju , Park Beom Jin 
Published: May 2021

AbstractWe aimed to evaluate the performance of convolutional neural networks (CNNs) in the classification of coronavirus disease 2019 (COVID‐19) disease using normal, pneumonia, and COVID‐19 chest radiographs (CXRs). First, we collected 9194 CXRs from open datasets and 58 from the Korea University Anam Hospital (KUAH). The number of normal, pneumonia, and COVID‐19 CXRs were 4580, 3884, and 730, respectively. The CXRs obtained from the open dataset were randomly assigned to the training, tuning, and test sets in a 70:10:20 ratio. For external validation, the KUAH (20 normal, 20 pneumonia, and 18 COVID‐19) dataset, verified by radiologists using computed tomography, was used. Subsequently, transfer learning was conducted using DenseNet169, InceptionResNetV2, and Xception to identify COVID‐19 using open datasets (internal) and the KUAH dataset (external) with histogram matching. Gradient‐weighted class activation mapping was used for the visualization of abnormal patterns in CXRs. The average AUC and accuracy of the multiscale and mixed‐COVID‐19Net using three CNNs over five folds were (0.99 ± 0.01 and 92.94% ± 0.45%), (0.99 ± 0.01 and 93.12% ± 0.23%), and (0.99 ± 0.01 and 93.57% ± 0.29%), respectively, using the open datasets (internal). Furthermore, these values were (0.75 and 74.14%), (0.72 and 68.97%), and (0.77 and 68.97%), respectively, for the best model among the fivefold cross‐validation with the KUAH dataset (external) using domain adaptation. The various state‐of‐the‐art models trained on open datasets show satisfactory performance for clinical interpretation. Furthermore, the domain adaptation for external datasets was found to be important for detecting COVID‐19 as well as other diseases.
Rab3 proteins and cancer: Exit strategies
Authors: Raffaniello Robert D. 
Published: May 2021

AbstractRab proteins are GTPases involved in all stages of vesicular transport and membrane fusion in mammalian cells. Individual Rab proteins localize to specific cellular organelles and regulate a specific membrane trafficking pathway. Recent studies suggest an important role for Rab proteins in cancer. Rab3 isoforms (Rab3A, Rab3B, Rab3C, and Rab3D) are expressed almost exclusively in neurons and secretory cells. In this review, the role of Rab3 isoforms in a variety of tumor types is discussed. Of the four Rab3 isoforms, Rab3D has been studied most extensively in cancer cells and this isoform appears to play an oncogenic role in breast, colon, esophageal, skin, and brain tumors. Overexpression of Rab3A and Rab3C was observed in gliomas and colon cancers, respectively. Increased expression of the Rab3 isoforms is related to increased proliferation, migration, and invasiveness. Moreover, high Rab3 isoform levels are often associated with decreased survival and advanced pathological stage in clinical samples. Rab3 isoform‐dependent activation of the AKT pathway has been observed in several studies. Although the effects of Rab3 isoforms on cancer cell growth and function have been examined in many tumor types, a number of important questions remain. Are the Rab3‐positive vesicles in cancer cells actually secretory in nature? If so, are the contents of these vesicles secreted in a regulated or constitutive manner? How does Rab3‐regulated secretion affect cellular signaling and tumor growth? Finally, can Rab3 isoforms be therapeutically manipulated in cancer cells? The fact that knockout of a single Rab3 isoform does not affect viability, at least in mouse models, suggests that targeting of these proteins may be a safe and effective treatment strategy for tumor cells expressing any of the Rab3 isoforms.