bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radial shock waves prevent growth retardation caused by the clinically used drug vismodegib in ex vivo cultured bones
Authors: Ramesh Sowmya , Sävendahl Lars , Madhuri Vrisha , Zaman Farasat 
Published: August 2020

AbstractIn childhood medulloblastoma patients, the hedgehog antagonist vismodegib is an effective anti-cancer treatment but unfortunately induces irreversible growth arrests and growth impairment limiting its use in skeletally immature patients. We hypothesized that radial shock wave treatment (rSWT) may protect drug-induced growth impairment owing to its osteogenic effects. Fetal rat metatarsal bones were exposed to vismodegib (day 0–5; 100 nM) and/or rSWT (single session); other bones from day 1 were continuously exposed to a Gli1 antagonist (GANT61; 10 µM) and/or rSWT (single session). Control bones were untreated. The bone length was measured at intervals; histomorphometric analysis and immunostaining for PCNA, Gli1, and Ihh were performed on the sectioned bones. Bones treated with vismodegib showed impaired bone growth, reduced height of the resting-proliferative zone and reduced hypertrophic cell size compared to control. In vismodegib treated bones, a single session of rSWT partially rescued bone growth, increased the growth velocity, hypertrophic cell size, and restored growth plate morphology. Bones exposed to GANT61 showed impaired bone growth and disorganized growth plate while when combined with rSWT these effects were partially prevented. Locally applied rSWT had a chondroprotective effect in rat metatarsal bones and suggest a novel strategy to prevent growth impairment caused by vismodegib.
Development and validation of a 1-year survival prognosis estimation model for Amyotrophic Lateral Sclerosis using manifold learning algorithm UMAP
Authors: Grollemund Vincent , Chat Gaétan Le , Secchi-Buhour Marie-Sonia , Delbot François , Pradat-Peyre Jean-François , Bede Peter , Pradat Pierre-François 
Published: August 2020

AbstractAmyotrophic Lateral Sclerosis (ALS) is an inexorably progressive neurodegenerative condition with no effective disease modifying therapies. The development and validation of reliable prognostic models is a recognised research priority. We present a prognostic model for survival in ALS where result uncertainty is taken into account. Patient data were reduced and projected onto a 2D space using Uniform Manifold Approximation and Projection (UMAP), a novel non-linear dimension reduction technique. Information from 5,220 patients was included as development data originating from past clinical trials, and real-world population data as validation data. Predictors included age, gender, region of onset, symptom duration, weight at baseline, functional impairment, and estimated rate of functional loss. UMAP projection of patients shows an informative 2D data distribution. As limited data availability precluded complex model designs, the projection was divided into three zones with relevant survival rates. These rates were defined using confidence bounds: high, intermediate, and low 1-year survival rates at respectively $$90\%$$

90
%

($$\pm 4\%$$

±
4
%

), $$80\%$$

80
%

($$\pm 4\%$$

±
4
%

) and $$58\%$$

58
%

($$\pm 4\%$$

±
4
%

). Predicted 1-year survival was estimated using zone membership. This approach requires a limited set of features, is easily updated, improves with additional patient data, and accounts for results uncertainty.
Fully biological production of adipic acid analogs from branched catechols
Authors: Kruyer Nicholas S. , Wauldron Natalia , Bommarius Andreas S. , Peralta-Yahya Pamela 
Published: August 2020

AbstractMicrobial production of adipic acid from lignin-derived monomers, such as catechol, is a greener alternative to the petrochemical-based process. Here, we produced adipic acid from catechol using catechol 1,2-dioxygenase (CatA) and a muconic acid reductase (MAR) in Escherichia coli. As the reaction progressed, the pH of the media dropped from 7 to 4-5 and the muconic acid isomerized from the cis,cis (ccMA) to the cis,trans (ctMA) isomer. Feeding experiments suggested that cells preferentially uptook ctMA and that MAR efficiently reduced all muconic isomers to adipic acid. Intrigued by the substrate promiscuity of MAR, we probed its utility to produce branched chiral diacids. Using branched catechols likely found in pretreated lignin, we found that while MAR fully reduced 2-methyl-muconic acid to 2-methyl-adipic acid, MAR reduced only one double bond in 3-substituted muconic acids. In the future, MAR’s substrate promiscuity could be leveraged to produce chiral-branched adipic acid analogs to generate branched, nylon-like polymers with reduced crystallinity.
Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow
Authors: Kono Yosuke , Yokota Shigefumi , Fukushi Isato , Arima Yosuke , Onimaru Hiroshi , Okazaki Shuntaro , Takeda Kotaro , Yazawa Itaru , Yoshizawa Masashi , Hasebe Yohei , Koizumi Keiichi , Pokorski Mieczyslaw , Toda Takako , Sugita Kanji , Okada Yasumasa 
Published: August 2020

AbstractPsychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifier of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.
Association of change in alcohol consumption with cardiovascular disease and mortality among initial nondrinkers
Authors: Chang Jun Young , Choi Seulggie , Park Sang Min 
Published: August 2020

AbstractThere is a paucity of studies on the influence of alcohol intake among non-drinkers. We evaluated the association between an increase in alcohol consumption and primary prevention of major adverse cardiovascular events (MACE) among non-drinkers. Data collected by the National Health Insurance Service in the Korea between 2007 and 2013 were analysed. A total of 112,403 subjects were included and followed up from 1 January 2011 to 31 December 2013. Increases in alcohol consumption, measured as glasses per day, at the second medical check-up, were categorized into maintenance of nondrinking (0), > 0– ≤ 1, > 1– ≤ 2, > 2– ≤ 4, and > 4. Hazard ratios (HRs) for MACE and all-cause mortality on increase in alcohol consumption were calculated. Compared to that in non-drinkers at the second check-up, the risk of MACE significantly decreased among the subjects with an increase in alcohol consumption to ≤ 1 glass per day (HR 0.79, 95% CI 0.68–0.92). However, a light increase in alcohol consumption did not reduce the risk of stroke or all-cause mortality (stroke, HR 0.83, 95% CI 0.68–1.02; all-cause mortality, HR 0.89, 95% CI 0.73–1.09). Compared to continual non-drinkers, those who drank > 2 glass per day had higher risk for death due to external causes (aHR 2.06, 95% CI 1.09–3.90). The beneficial effect of light increments in alcohol consumption on the occurrence of MACE may have resulted from the inappropriate inclusion of sick quitters, who maintained a nondrinking status, in the reference group.
NF-κB inhibitor with Temozolomide results in significant apoptosis in glioblastoma via the NF-κB(p65) and actin cytoskeleton regulatory pathways
Authors: Avci Naze G. , Ebrahimzadeh-Pustchi Sadaf , Akay Yasemin M. , Esquenazi Yoshua , Tandon Nitin , Zhu Jay-Jiguang , Akay Metin 
Published: August 2020

AbstractGlioblastoma (GBM) is the most malignant brain tumor characterized by intrinsic or acquired resistance to chemotherapy. GBM tumors show nuclear factor-κB (NF-κB) activity that has been associated with tumor formation, growth, and increased resistance to therapy. We investigated the effect of NF-κB inhibitor BAY 11-7082 with Temozolomide (TMZ) on the signaling pathways in GBM pathogenesis. GBM cells and patient-derived GBM cells cultured in 3D microwells were co-treated with BAY 11-7082 and TMZ or BAY 11-7082 and TMZ alone, and combined experiments of cell proliferation, apoptosis, wound healing assay, as well as reverse-phase protein arrays, western blot and immunofluorescence staining were used to evaluate the effects of drugs on GBM cells. The results revealed that the co-treatment significantly altered cell proliferation by decreasing GBM viability, suppressed NF-κB pathway and enhanced apoptosis. Moreover, it was found that the co-treatment of BAY 11-7082 and TMZ significantly contributed to a decrease in the migration pattern of patient-derived GBM cells by modulating actin cytoskeleton pathway. These findings suggest that in addition to TMZ treatment, NF-κB can be used as a potential target to increase the treatment’s outcomes. The drug combination strategy, which is significantly improved by NF-κB inhibitor could be used to better understand the underlying mechanism of GBM pathways in vivo and as a potential therapeutic tool for GBM treatment.
Strong positively diversity–productivity relationships in the natural sub-alpine meadow communities across time are up to superior performers
Authors: Jiang Kai , Tan Zhaoyuan , He Qifang , Wang Lu , Zhao Yang , Sun Xinhang , Hou Weichen , Long Wenxing , Zhang Hui 
Published: August 2020

AbstractIn experiments that test plant diversity–productivity relationships, the common practice of weeding unsown species and disallowing species colonization may have the unintended consequence of favoring priority effects that maintain niche complementarity in determining productivity. However, in naturally assembled communities where colonization occurs, resource competition may favor dominant traits, which eventually have the greatest influence on productivity. Here, in naturally developed long-term subalpine meadows (from 4-year to at least 40 years meadows) in the Qinghai-Tibetan Plateau, we investigated the relationships between species richness and productivity to testify whether positive diversity–productivity relationships can still exist in naturally developed long-term communities. We also measured five functional traits (specific leaf area, photosynthesis rate, leaf proline content, seed mass and seed germination rate) to calculate two functional diversity indices: community-weighted mean trait values (CWM) and Rao’s quadratic entropy (RaoQ) which are highly correlated to functional traits of dominating species and variety of functional trait among all species. Finally, we quantified the relative contribution of species diversity, functional traits of dominating species and functional diversity among all species to productivity along the succession. We demonstrated strong positively diversity–productivity relationships in the natural sub-alpine meadow communities across time. The five traits of dominating species explained a large proportion (54–80%) of the variation in productivity during succession, whereas species diversity and functional diversity (FD) for each of the five traits explained much less (24–48% for species richness and 0–40% for FD for each of the five traits respectively). We found unequivocal evidence that significantly positive diversity–productivity relationships in the natural sub-alpine meadow communities across time are up to superior performers (dominant traits) in naturally developed communities where colonization occurs. As a result, understanding diversity–productivity relationships under the full range of community assembly processes therefore merits further investigation.
Discovery and predictive modeling of urine microbiome, metabolite and cytokine biomarkers in hospitalized patients with community acquired pneumonia
Authors: Pierre Joseph F. , Akbilgic Oguz , Smallwood Heather , Cao Xueyuan , Fitzpatrick Elizabeth A. , Pena Senen , Furmanek Stephen P. , Ramirez Julio A. , Jonsson Colleen B. 
Published: August 2020

AbstractPneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5–10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (Streptococcus pneumoniaeandStaphylococcus aureus) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a + 90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes.
The origin of pulsating ultra-luminous X-ray sources: Low- and intermediate-mass X-ray binaries containing neutron star accretors
Authors: Misra D. , Fragos T. , Tauris T. M. , Zapartas E. , Aguilera-Dena D. R. 
Published: August 2020

Context.Ultra-luminous X-ray sources (ULXs) are those X-ray sources located away from the centre of their host galaxy with luminosities exceeding the Eddington limit of a stellar-mass black hole (LX >  1039 erg s−1). Observed X-ray variability suggests that ULXs are X-ray binary systems. The discovery of X-ray pulsations in some of these objects (e.g. M82 X-2) suggests that a certain fraction of the ULX population may have a neutron star as the accretor.Aims.We present systematic modelling of low- and intermediate-mass X-ray binaries (LMXBs and IMXBs; donor-star mass range 0.92–8.0 M⊙and neutron-star accretors) to explain the formation of this sub-population of ULXs.Methods.Using MESA, we explored the allowed initial parameter space of binary systems consisting of a neutron star and a low- or intermediate-mass donor star that could explain the observed properties of ULXs. These donors are transferring mass at super-Eddington rates while the accretion is limited locally in the accretion disc by the Eddington limit. Thus, our simulations take into account beaming effects and also include stellar rotation, tides, general angular momentum losses, and a detailed and self-consistent calculation of the mass-transfer rate.Results.Exploring the initial parameters that lead to the formation of neutron-star ULXs, we study the conditions that lead to dynamical stability of these systems, which depends strongly on the response of the donor star to mass loss. Using two values for the initial neutron star mass (1.3 M⊙and 2.0 M⊙), we present two sets of mass-transfer calculation grids for comparison with observations of NS ULXs. We find that LMXBs/IMXBs can produce NS-ULXs with typical time-averaged isotropic-equivalent X-ray luminosities of between 1039and 1041 erg s−1on a timescale of up to ∼1.0 Myr for the lower luminosities. Finally, we estimate their likelihood of detection, the types of white-dwarf remnants left behind by the donors, and the total amount of mass accreted by the neutron stars.Conclusions.We show that observed super-Eddington luminosities can be achieved in LMXBs/IMXBs undergoing non-conservative mass transfer while assuming geometrical beaming. We also compare our results to the observed pulsating ULXs and infer their initial parameters. Our results suggest that a large subset of the observed pulsating ULX population can be explained by LMXBs/IMXBs in a super-Eddington mass-transfer phase.
Lower gastrointestinal polypectomy competencies in the United Kingdom: a retrospective analysis of Directly Observed Polypectomy Skills (DOPyS)
Authors: Rajendran Arun , Thomas-Gibson Siwan , Bassett Paul , Dunckley Paul , Rameshshanker Rajaratnam , Sevdalis Nick , Haycock Adam 
Published: August 2020

Abstract
Background Polypectomy is often the most hazardous part of colonoscopy. There is significant variability in polypectomy training and assessment internationally. DOPyS (Directly Observed Polypectomy Skills) is a validated assessment tool and is used to demonstrate polypectomy competency in the UK. This study aimed to describe the learning curve for polypectomy competency in UK trainees.
Methods Retrospective DOPyS data (January 2009 to September 2015) were obtained from the UK Joint Advisory Group (JAG) for intestinal endoscopy training system (JETS) national database. The number of lower gastrointestinal (LGI) procedures, overall cecal intubation rate (CIR), procedure intensity, and time in days to the first DOPyS assessment were recorded, and time to JAG certification was calculated.
Results 4965 DOPyS assessments from 336 trainees were analyzed. Within the study period, 124 and 53 trainees achieved provisional and full colonoscopy certification, respectively. Trainees started formative assessment of polypectomy after > 130 LGI procedures and with a CIR of > 70 %. Within 3 years from the first DOPyS assessment, 94 % of trainees achieved provisional certification, and 50 % full certification. Higher procedure intensity at baseline DOPyS assessment was associated with a higher likelihood of obtaining certification sooner.
Conclusion There is a significant variation in time to competency, and this potentially reflects the time necessary to acquire polypectomy skills. There is a need to start polypectomy training earlier, once sufficient skills, such as tip control, have been achieved to shorten the time to competency. Overall, the CIR could be used as a guide for such technical skills. Increasing exposure to training lists also potentially reduces the time to polypectomy competency.
Integrated weed management in carrot.
Authors: Colquhoun Jed 
Published: August 2020

Abstract

This chapter describes the effects of weed interference in carrot and suggests non-chemical (including crop rotations and systems, planting timing, false sowing, use of competitive varieties, mechanical or physical method, flame weeding, reduced tillage, cover crops and mulch, and hand weeding) and chemical (such as application of linuron, metribuzin, S-metolachlor, pendimethalin, prometryn and trifluralin) methods of weed management. The use of natural herbicides and biological control agents is also mentioned. Future challenges in carrot weed management, as well as current and future areas of carrot weed management research, are briefly discussed.
Arracacha.
Authors: Morillo Eduardo , Madeira Nuno , Jaimez Ramon 
Published: August 2020

Abstract

This chapter provides information on the importance, growing areas, plant development, cropping system, postharvest and product valorization of arracacha (Arracacia xanthorrhiza). Arracacha is an excellent alternative for small and medium producers, especially family farmers, due to its considerable demand for labour, mainly in preparing and planting the seedlings and harvesting the roots. It assumes great socio-economic importance in regions where it is cultivated, generally reaching high market value. In addition, it has the characteristics of low input use and low production cost. Arracacha has a captive and growing market, usually associated with more elaborate cuisine and even high gastronomy. It also enjoys a reputation as a healthy product and a source of highly digestible carbohydrates, besides a good number of vitamins.
Harmonic coordinates of the Kerr metric revisited
Authors: Zang Yunlong , He Xiaokai , Cao Zhoujian 
Published: August 2020

Abstract
Starting from the Kerr–Schild coordinates, a set of horizon penetrating harmonic coordinates for the Kerr metric is worked out and exhibit the explicit form of the whole metric. As a validity check on the calculations, the multipole expansion of the Kerr metric is then derived from the harmonic formulation. The resemblance of the geometry of the harmonic slicing with the ‘1 + log’ slicing and the generalized harmonic gauge in numerical relativity is then further discussed. Together with its horizon penetrating structure, the harmonic formulation is well suited for the numerical simulation of astrophysical electromagnetic phenomena, like for instance the Blanford–Znajek process, in the vicinity of a supermassive black hole.
Review of approximate equations for the pendulum period
Authors: Hinrichsen Peter F 
Published: August 2020

Abstract
Precision measurements of the pendulum period as a function of the amplitude can now be made with a variety of instruments including MEMs gyro/accelerometers, and thus theoretical expressions are required for comparison. Unfortunately exact solution of the pendulum equation involves elliptic integrals, which cannot be expressed in terms of elementary functions, and therefore a wide variety of approximations have been published. These range from simple single-term formulae to more sophisticated equations, which apply to a wider range of amplitudes, to an iterative procedure for calculating the precise period. The published approximations are compared as Taylor series expansions, and graphically to indicate their accuracy and their regions of applicability.