bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large‐scale genome‐wide association study, using historical data, identifies conserved genetic architecture of cyanogenic glucoside content in cassava (Manihot esculenta Crantz) root
Authors: Ogbonna Alex C. , Braatz de Andrade Luciano Rogerio , Rabbi Ismail Y. , Mueller Lukas A. , Jorge de Oliveira Eder , Bauchet Guillaume J. 
Published: November 2020

SummaryManihot esculenta (cassava) is a root crop originating from South America that is a major staple in the tropics, including in marginal environments. This study focused on South American and African germplasm and investigated the genetic architecture of hydrogen cyanide (HCN), a major component of root quality. HCN, representing total cyanogenic glucosides, is a plant defense component against herbivory but is also toxic for human consumption. We genotyped 3354 landraces and modern breeding lines originating from 26 Brazilian states and 1389 individuals were phenotypically characterized across multi‐year trials for HCN. All plant material was subjected to high‐density genotyping using genotyping by sequencing. We performed genome‐wide association mapping to characterize the genetic architecture and gene mapping of HCN. Field experiments revealed strong broad‐ and narrow‐sense trait heritability (0.82 and 0.41, respectively). Two major loci were identified, encoding for an ATPase and a MATE protein, and contributing up to 7 and 30% of the HCN concentration in roots, respectively. We developed diagnostic markers for breeding applications, validated trait architecture consistency in African germplasm and investigated further evidence for the domestication of sweet and bitter cassava. Fine genomic characterization revealed: (i) the major role played by vacuolar transporters in regulating HCN content; (ii) the co‐domestication of sweet and bitter cassava major alleles are dependent upon geographical zone; and (iii) the major loci allele for high HCN in M. esculenta Crantz seems to originate from its ancestor, M. esculenta subsp. flabellifolia. Taken together, these findings expand our insights into cyanogenic glucosides in cassava roots and its glycosylated derivatives in plants.
Are herbicide mixtures unaffected by resistance? A case study with Lolium rigidum
Authors: Busi Roberto , Beckie Hugh J. 
Published: November 2020

AbstractLolium rigidum Gaud., a grass weed species infesting winter field crops, has evolved resistance to the largest number of herbicide modes of action. In this study, 140 field populations of L. rigidum were screened with 14 herbicide treatments. Herbicide resistance at the recommended label dosage of pre‐emergence (PRE), post‐emergence (POST) and binary herbicide mixtures was considered present when plant survival was ≥6%. Plant survival to four acetyl‐CoA carboxylase (ACCase) POST herbicides averaged across all populations was approximately 15%, indicating substantial herbicide resistance. In contrast, the mean survival to the PRE treatments was only 2%, reflecting effective control of L. rigidum. Herbicide mixtures were the most effective treatments, with a significantly lower resistance frequency than stand‐alone herbicides. For example, only 12% of the tested samples were resistant to the mixture of clethodim + butroxydim in comparison with 40% and 61% to either butroxydim or clethodim, respectively. Similarly, 8% of the samples were resistant to the mixture of trifluralin + prosulfocarb versus a much greater frequency of 36% and 51% resistance to prosulfocarb and trifluralin, respectively. Surprisingly, the binary mixtures of trifluralin + triallate or pyroxasulfone + triallate are not affected by resistance (presently) due to the greater efficacy than that of either stand‐alone herbicide. Thus, herbicide mixtures can delay the onset of resistance and mitigate the existing levels of herbicide resistance and cross‐resistance in L. rigidum. Systematic screenings of a large number of field populations could identify the most (cost‐) effective herbicide mixtures and foster their informed adoption on farm to mitigate the rapid evolution of weed resistance in lieu of expert assumptions or modelling simulations.
Attached and Attaching Three-Dimensional Jets From Circular Nozzles: Analytical Model
Authors: Pease Leonard F. , Bamberger Judith Ann , Minette Michael J. 
Published: November 2020

Abstract
Here we consider velocity profiles of three dimensional attaching and attached jets emerging from circular nozzles. Like their well-studied two-dimensional counterparts, these wall jets lose momentum due to interactions with nearby surfaces. Unlike their two-dimensional counterparts, simple and quantitative expressions for the velocity profiles of three-dimensional wall jets remain elusive. Here we present a quantitative analytical model of the three-dimensional velocity profiles of attached jets inclusive of a local skin coefficient of friction. We compare these expressions to experimental velocity profiles at moderate and high nozzle Reynolds numbers to find reasonable quantitative agreement. This work has implications for a variety of industries including nuclear waste processing, where jet flows in mixing vessels suspend solids and gases trapped in radioactive waste tanks.
Kinematic Analysis and Design of a Six-Degrees of Freedom 3-RRPS Mechanism for Bone Reduction Surgery
Authors: Essomba Terence , Nguyen Phu Sinh 
Published: November 2020

Abstract
Robot-assisted bone reduction surgery consists in using robots to reposition the bone fragments into their original place prior to fracture healing. This study presents the application of a 3-RRPS augmented tripod mechanism with six degrees-of-freedom for longitudinal bone reduction surgery. First, the inverse and forward kinematic models of the mechanism are investigated. Particularly, the forward kinematic is solved by applying Sylvester's dialytic method. Second, the velocity model is studied and its singular configurations are identified. The workspace of the 3-RRPS mechanism is then outlined and compared with the Stewart platform, which is a classical mechanism for the targeted application. The results show that this mechanism provides a larger workspace, especially its rotation angle about the vertical axis, which is an important aspect in the bone reduction. A series of simulations on the numerical and graphic software is performed to verify the entire analysis of the parallel mechanism. A physiguide and mscadams software are used to carry out a simulation of a real case of femur fracture reduction using the proposed mechanism to validate its suitability. Finally, a robotic prototype based on the mechanism is manufactured and experimented using an artificial bone model to evaluate the feasibility of the mechanism.
Self-reported sports injuries and later-life health status in 3357 retired Olympians from 131 countries: a cross-sectional survey among those competing in the games between London 1948 and PyeongChang 2018
Authors: Palmer Debbie , Cooper Dale J , Emery Carolyn , Batt Mark E , Engebretsen Lars , Scammell Brigitte E , Schamasch Patrick , Shroff Malav , Soligard Torbjørn , Steffen Kathrin , Whittaker Jackie L , Budgett Richard 
Published: November 2020

ObjectiveDescribe the self-reported prevalence and nature of Olympic-career injury and general health and current residual symptoms in a self-selected sample of retired Olympians.Methods3357 retired Olympians from 131 countries completed a cross-sectional online survey, distributed by direct email through World Olympians Association and National Olympian Associations databases. The survey captured Olympic sport exposure, significant training and competition injury history (lasting>1 month), general health (eg, depression) during the athlete’s career, and current musculoskeletal pain and functional limitations.Results55% were men (44% women, 1% unknown), representing 57 sports (42 Summer, 15 Winter), aged 44.7 years (range 16–97). A total of 3746 injuries were self-reported by 2116 Olympians. This equated, 63.0% (women 68.1%, men 59.2%) reporting at least one significant injury during their Olympic career. Injury prevalence was highest in handball (82.2%) and lowest in shooting (40.0%) for Summer Olympians; and highest in alpine skiing (82.4%) and lowest in biathlon (40.0%) for Winter Olympians. The knee was the most frequently injured anatomical region (20.6%, 120 median days severity), followed by the lumbar spine (13.1%, 100 days) and shoulder/clavicle (12.9%, 92 days). 6.6% of Olympians said they had experienced depression during their career. One-third of retired Olympians reported current pain (32.4%) and functional limitations (35.9%).ConclusionsAlmost two-thirds of Olympians who completed the survey reported at least one Olympic-career significant injury. The knee, lumbar spine and shoulder/clavicle were the most commonly injured anatomical locations. One-third of this sample of Olympians attributed current pain and functional limitations to Olympic-career injury.
Comparison of detection rate of 16 sampling methods for respiratory viruses: a Bayesian network meta-analysis of clinical data and systematic review
Authors: Hou Nianzong , Wang Kai , Zhang Haiyang , Bai Mingjian , Chen Hao , Song Weidong , Jia Fusen , Zhang Yi , Han Shiliang , Xie Bing 
Published: November 2020

BackgroundRespiratory viruses (RVs) is a common cause of illness in people of all ages, at present, different types of sampling methods are available for respiratory viral diagnosis. However, the diversity of available sampling methods and the limited direct comparisons in randomised controlled trials (RCTs) make decision-making difficult. We did a network meta-analysis, which accounted for both direct and indirect comparisons, to determine the detection rate of different sampling methods for RVs.MethodsRelevant articles were retrieved comprehensively by searching the online databases of PubMed, Embase and Cochrane published before 25 March 2020. With the help of R V.3.6.3 software and ‘GeMTC V.0.8.2’ package, network meta-analysis was performed within a Bayesian framework. Node-splitting method andI2test combined leverage graphs and Gelman-Rubin-Brooks plots were conducted to evaluate the model’s accuracy. The rank probabilities in direct and cumulative rank plots were also incorporated to rank the corresponding sampling methods for overall and specific virus.Results16 sampling methods with 54 438 samples from 57 literatures were ultimately involved in this study. The model indicated good consistency and convergence but high heterogeneity, hence, random-effect analysis was applied. The top three sampling methods for RVs were nasopharyngeal wash (NPW), mid-turbinate swab (MTS) and nasopharyngeal swab (NPS). Despite certain differences, the results of virus-specific subanalysis were basically consistent with RVs: MTS, NPW and NPS for influenza; MTS, NPS and NPW for influenza-a and b; saliva, NPW and NPS for rhinovirus and parainfluenza; NPW, MTS and nasopharyngeal aspirate for respiratory syncytial virus; saliva, NPW and MTS for adenovirus and sputum; MTS and NPS for coronavirus.ConclusionThis network meta-analysis provides supporting evidences that NPW, MTS and NPS have higher diagnostic value regarding RVs infection, moreover, particular preferred methods should be considered in terms of specific virus pandemic. Of course, subsequent RCTs with larger samples are required to validate our findings.
Improved cancer-related fatigue in a randomised clinical trial: methylphenidate no better than placebo
Authors: Centeno Carlos , Rojí Rocío , Portela Maria Angustias , De Santiago Ana , Cuervo Miguel Angel , Ramos Daniel , Gandara Alvaro , Salgado Esteban , Gagnon Bruno , Sanz Alvaro 
Published: November 2020

IntroductionMethylphenidate is a psychostimulant drug used to treat fatigue in patients with advanced cancer, for which there is no gold standard of treatment.ObjectiveTo explore the efficacy of methylphenidate in the relief of fatigue in patients with advanced cancer.Materials and methodsA randomised double-blind placebo-controlled multicentre clinical trial, stratified according to the intensity of fatigue. The treatment was considered effective if the improvement in mean fatigue intensity between baseline values and day 6 was significantly higher in the methylphenidate group than in the placebo group. The responses were measured using the Edmonton Symptoms Assessment System (ESAS) and the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scales.Results35 patients received placebo and 42 patients received methylphenidate. The populations of both groups were homogeneous. Patients receiving methylphenidate did not exhibit statistically significant improvement of fatigue in comparison to patients receiving placebo (p=0.52). The mean improvement of fatigue (ESAS) on day 6 was −1.9 (±2.5) in the placebo group, and −2.3 (±2.6) in the methylphenidate group (p=0.52). The results obtained with the FACT-F were congruent with those obtained by the ESAS. The responses in patients with severe fatigue were −2.4 (±2.9) in the placebo group and −3.4 (±2.5) in the methylphenidate group; the difference was not statistically significant (p=0.3).ConclusionMethylphenidate was not more efficient than placebo to treat cancer-related fatigue. Fatigue improved significantly after 3 days of treatment and was stabilised on day 6, both with placebo and methylphenidate. The side effects of methylphenidate were mild and infrequent.Trial registration numberEudraCT Registry (2008-002171-27).
Educational needs of nursing home staff: does a needs-based palliative care course make a difference?
Authors: Phua Gillian Li Gek , Toh Hui Jin , Tan Laurence , Low James Alvin Yiew Hock 
Published: November 2020

ObjectiveIn Singapore, more elderly are living in nursing homes (NHs), with a resultant increase in deaths occurring in NHs. However, palliative care training is limited in Singapore’s core nursing curriculum, and many NHs rely on foreign-trained staff who may not have previous palliative care training. Our study aimed to evaluate whether a needs-based course can improve the palliative care knowledge and attitudes of NH nurses in Singapore.MethodsTwenty-five nurses participated in the study. The intervention was an 8-week palliative care course developed based on needs assessment and led by a multidisciplinary faculty. A 50-item knowledge test was administered at baseline and 0 day and 3 and 6 months postcourse. Semistructured interviews were conducted at 3 months to assess for changes in attitudes and nursing practices.ResultsThe mean knowledge score increased significantly from 31.4 (±4.4) precourse to 35.1 (±5.1) at 3 months. Knowledge scores in end-of-life care increased up to 6 months, and scores for pain and symptom management increased significantly at 3 months. Participants reported a positive change with improved communication skills and increased compassion. There was a lack of opportunities to apply some new knowledge and skills due to regulations and perceived residents’ preferences to engage more local senior staff.ConclusionThe multidisciplinary needs-based palliative care course using various teaching modalities with follow-up knowledge tests helped to increase knowledge and improve communication skills and attitudes of NH nurses towards palliative care. The increase in knowledge and positive change in attitudes was noted to be sustained for at least 3 months postcourse.
Spinning black holes with a separable Hamilton–Jacobi equation from a modified Newman–Janis algorithm
Authors: Junior Haroldo C. D. Lima , Crispino Luís C. B. , Cunha Pedro V. P. , Herdeiro Carlos A. R. 
Published: November 2020

AbstractObtaining solutions of the Einstein field equations describing spinning compact bodies is typically challenging. The Newman–Janis algorithm provides a procedure to obtain rotating spacetimes from a static, spherically symmetric, seed metric. It is not guaranteed, however, that the resulting rotating spacetime solves the same field equations as the seed. Moreover, the former may not be circular, and thus expressible in Boyer–Lindquist-like coordinates. Amongst the variations of the original procedure, a modified Newman–Janis algorithm (MNJA) has been proposed that, by construction, originates a circular, spinning spacetime, expressible in Boyer–Lindquist-like coordinates. As a down side, the procedure introduces an ambiguity, that requires extra assumptions on the matter content of the model. In this paper we observe that the rotating spacetimes obtained through the MNJAalwaysadmit separability of the Hamilton–Jacobi equation for the case of null geodesics, in which case, moreover, the aforementioned ambiguity has no impact, since it amounts to an overall metric conformal factor. We also show that the Hamilton–Jacobi equation for light rays propagating in a plasma admits separability if the plasma frequency obeys a certain constraint. As an illustration, we compute the shadow and lensing of some spinning black holes obtained by the MNJA.
Thermodynamic constraints on matter creation models
Authors: Valentim R. , Jesus J. F. 
Published: November 2020

AbstractEntropy is a fundamental concept from Thermodynamics and it can be used to study models on context of Creation Cold Dark Matter (CCDM). From conditions on the first ($$\dot{S}\ge 0$$

S
˙

≥
0

) (throughout the present work we will use dots to indicate time derivatives and dashes to indicate derivatives with respect to scale factor) and second order ($$\ddot{S}<0$$

S
¨

<
0

) time derivatives of total entropy in the initial expansion of Sitter through the radiation and matter eras until the end of Sitter expansion, it is possible to estimate the intervals of parameters. The total entropy ($$S_{t}$$

S
t

) is calculated as sum of the entropy at all eras ($$S_{\gamma }$$

S
γ

and $$S_{m}$$

S
m

) plus the entropy of the event horizon ($$S_h$$

S
h

). This term derives from the Holographic Principle where it suggests that all information is contained on the observable horizon. The main feature of this method for these models are that thermodynamic equilibrium is reached in a final de Sitter era. Total entropy of the universe is calculated with three terms: apparent horizon ($$S_{h}$$

S
h

), entropy of matter ($$S_{m}$$

S
m

) and entropy of radiation ($$S_{\gamma }$$

S
γ

). This analysis allows to estimate intervals of parameters of CCDM models.
Targeting PAK4 Inhibits Ras-Mediated Signaling and Multiple Oncogenic Pathways in High-Risk Rhabdomyosarcoma
Authors: Dasgupta Atreyi , Sierra Laura , Tsang Susan V. , Kurenbekova Lyazat , Patel Tajhal , Rajapakse Kimal , Shuck Ryan L. , Rainusso Nino , Landesman Yosef , Unger Thaddeus , Coarfa Cristian , Yustein Jason T. 
Published: November 2020

Abstract

Rhabdomyosarcoma (RMS) is the most prevalent pediatric soft-tissue sarcoma. Multimodal treatment, including surgery and traditional chemotherapy with radiotherapy, has contributed to improvements in overall survival rates. However, patients with recurrent or metastatic disease have 5-year survival rates of less than 30%. One reason for the lack of therapeutic advancement is identification and targeting of critical signaling nodes. p21-activated kinases (PAK) are a family of serine/threonine kinases downstream of multiple critical tumorigenic receptor tyrosine kinase receptors and oncogenic regulators, including IGFR and RAS signaling, that significantly contribute to aggressive malignant phenotypes. Here, we report that RMS cell lines and tumors exhibit enhanced PAK4 expression levels and activity, which are further activated by growth factors involved in RMS development. Molecular perturbation of PAK4 in multiple RMS models in vitro and in vivo resulted in inhibition of RMS development and progression. Fusion-positive and -negative RMS models were sensitive to two PAK4 small-molecule inhibitors, PF-3758309 and KPT-9274, which elicited significant antitumor and antimetastatic potential in several primary and metastatic in vivo models, including a relapsed RMS patient-derived xenograft model. Transcriptomic analysis of PAK4-targeted tumors revealed inhibition of the RAS-GTPase, Hedgehog, and Notch pathways, along with evidence of activation of antitumor immune response signatures. This PAK4-targeting gene signature showed prognostic significance for patients with sarcoma. Overall, our results show for the first time that PAK4 is a novel and viable therapeutic target for the treatment of high-risk RMS.

Significance:
These data demonstrate a novel oncogenic role for PAK4 in rhabdomyosarcoma and show that targeting PAK4 activity is a promising viable therapeutic option for advanced rhabdomyosarcoma.
Transcriptional Activation of MYC-Induced Genes by GCN5 Promotes B-cell Lymphomagenesis
Authors: Farria Aimee T. , Plummer Joshua B. , Salinger Andrew P. , Shen Jianjun , Lin Kevin , Lu Yue , McBride Kevin M. , Koutelou Evangelia , Dent Sharon Y.R. 
Published: November 2020

Abstract

Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes, including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here, we show that GCN5 is an essential coactivator of cell-cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Eμ-Myc mouse model of B-cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of Myc.

Significance:
Our results provide important proof of principle for Gcn5 functions in formation and progression of Myc-driven cancers, suggesting that GCN5 may be a viable target for development of new cancer therapies.
Cell Softness Prevents Cytolytic T-cell Killing of Tumor-Repopulating Cells
Authors: Liu Yuying , Zhang Tianzhen , Zhang Haizeng , Li Jiping , Zhou Nannan , Fiskesund Roland , Chen Junwei , Lv Jiadi , Ma Jingwei , Zhang Huafeng , Tang Ke , Cheng Feiran , Zhou Yabo , Zhang Xiaohui , Wang Ning , Huang Bo 
Published: November 2020

Abstract

Biomechanics is a fundamental feature of a cell. However, the manner by which actomysin tension affects tumor immune evasion remains unclear. Here we show that although cytotoxic T lymphocytes (CTL) can effectively destroy stiff differentiated tumor cells, they fail to kill soft tumor-repopulating cells (TRC). TRC softness prevented membrane pore formation caused by CTL-released perforin. Perforin interacting with nonmuscle myosin heavy-chain 9 transmitted forces to less F-actins in soft TRC, thus generating an inadequate contractile force for perforin pore formation. Stiffening TRC allowed perforin the ability to drill through the membrane, leading to CTL-mediated killing of TRC. Importantly, overcoming mechanical softness in human TRC also enhanced TRC cell death caused by human CTL, potentiating a mechanics-based immunotherapeutic strategy. These findings reveal a mechanics-mediated tumor immune evasion, thus potentially providing an alternative approach for tumor immunotherapy.

Significance:
Tumor-repopulating cells evade CD8+ cytolytic T-cell killing through a mechanical softness mechanism, underlying the impediment of perforin pore formation at the immune synapse site.