bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sarcoma and the 100,000 Genomes Project: our experience and changes to practice
Authors: Prendergast Sophie C , Strobl Anna‐Christina , Cross William , Pillay Nischalan , Strauss Sandra J , Ye Hongtao , Lindsay Daniel , Tirabosco Roberto , Chalker Jane , Mahamdallie Shazia S , Sosinsky Alona ,   RNOH Pathology Laboratory and Biobank Team,   Genomics England Research Consortium, Flanagan Adrienne M , Amary Fernanda 
Published: June 2020

AbstractThe largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5 years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. Herein, we recount the lessons learned by a specialist sarcoma centre that recruited close to 1000 patients to the project, so that we and others may learn from our experience. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. We showed that this loss of genomic data could be mitigated by sequencing whole genomes from needle core biopsies. Storage of resection specimens at 4 °C for up to 96 h overcame the challenge of freezing tissue out of hours including weekends. Removing access to formalin increased compliance to these storage arrangements. With over 70 different sarcoma subtypes described, WGS was a useful tool for refining diagnoses and identifying novel alterations. Genomes from 350 of the cohort of 597 patients were analysed in this study. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant‐calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design.
Alterations in driver genes are predictive of survival in patients with resected pancreatic ductal adenocarcinoma
Authors: McIntyre Caitlin A. , Lawrence Sharon A. , Richards Allison L. , Chou Joanne F. , Wong Winston , Capanu Marinela , Berger Michael F. , Donoghue Mark T. A. , Yu Kenneth H. , Varghese Anna M. , Kelsen David P. , Park Wungki , Balachandran Vinod P. , Kingham T. Peter , D’Angelica Michael I. , Drebin Jeffrey A. , Jarnagin William R. , Iacobuzio‐Donahue Christine A. , Allen Peter J. , O’Reilly Eileen M. 
Published: June 2020

BackgroundKRAS, TP53, CDKN2A, and SMAD4 are established driver genes in pancreatic ductal adenocarcinoma (PDAC). This study was aimed at determining whether the mutational status of driver genes and those involved in DNA repair pathways are associated with clinical outcomes for individuals who undergo resection.MethodsEligible individuals were those who underwent resection of PDAC and consented to targeted sequencing of their primary tumor via Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK‐IMPACT). Genomic alterations were determined on the basis of MSK‐IMPACT results from formalin‐fixed, paraffin‐embedded samples. Associations between genomic alterations and clinical outcomes were assessed.ResultsTargeted sequencing was performed on 283 primary tumors resected between 2004 and 2017. The median follow‐up was 23 months among survivors. Alterations in KRAS and TP53 were associated with worse overall survival (OS) in comparison to wild type (median for KRAS, 38.8 months [95% CI, 33.0‐45.5 months] vs 91.0 months [95% CI, 34.8 months to not available (NA)]; P = .043; median for TP53, 37.4 months [95% CI, 32.1‐42.8 months] vs 65.0 months [95% CI, 33.0 months to NA]; P = .035). KRAS G12D mutations were associated with worse OS (median, 31.6 months [95% CI, 25.3‐45.5 months] vs 39.2 months [95% CI, 37.4‐75.2 months]; P = .012). TP53 truncating mutations (median, 39.6 months [95% CI, 32.4‐75.2 months] vs 33.9 months [95% CI, 24.0‐39.0 months]; P = .020) and those associated with loss of heterozygosity (median, 26.6 months [95% CI, 21.6‐44.2 months] vs 39.2 months [95% CI, 34.5‐49.1 months]; P = .048) had decreased OS. TP53 alterations were independently associated with OS in a multivariate analysis (hazard ratio, 1.54; 95% CI, 1.01‐2.33; P = .042). Individuals with germline alterations in homologous recombination deficiency (HRD) genes had improved OS in comparison with those without them (median, not reached vs 37.0 months; 95% CI, 33.0‐49.8 months; P = .035).ConclusionsIn patients with resected PDAC, genomic alterations in KRAS and TP53 are associated with worse outcomes, whereas alterations in HRD genes are associated with a favorable prognosis. Further studies are needed to better define these alterations as biomarkers in resected PDAC.
QuoVadoPro, an Autonomous Tool for Measuring Intracellular Dynamics Using Temporal Variance
Authors: Basu Himanish , Schwarz Thomas L. 
Published: June 2020

AbstractTrafficking of intracellular cargo is essential to cellular function and can be defective in pathological states including cancer and neurodegeneration. Tools to quantify intracellular traffic are thus necessary for understanding this fundamental cellular process, studying disease mechanisms, and testing the effects of therapeutic pharmaceuticals. In this article we introduce an algorithm called QuoVadoPro that autonomously quantifies the movement of fluorescently tagged intracellular cargo. QuoVadoPro infers the extent of intracellular motility based on the variance of pixel illumination in a series of time‐lapse images. The algorithm is an unconventional approach to the automatic measurement of intracellular traffic and is suitable for quantifying movements of intracellular cargo under diverse experimental paradigms. QuoVadoPro is particularly useful to measure intracellular cargo movement in non‐neuronal cells, where cargo trafficking occurs as short movements in mixed directions. The algorithm can be applied to images with low temporal or spatial resolutions and to intracellular cargo with varying shapes or sizes, like mitochondria or endoplasmic reticulum: situations in which conventional methods such as kymography and particle tracking cannot be applied. In this article we present a stepwise protocol for using the QuoVadoPro software, illustrate its methodology with common examples, discuss critical parameters for reliable data analysis, and demonstrate its use with a previously published example. © 2020 Wiley Periodicals LLC.Basic Protocol: QuoVadoPro, an autonomous tool for measuring intracellular dynamics using temporal variance
In Silico Design of Cylindrophanes: The Role of Functional Groups in a Fluoride Selective Host
Authors: Østrøm Ina , Ortolan Alexandre O. , Caramori Giovanni F. , Mascal Mark , Muñoz‐Castro Alvaro , Parreira Renato L. T. 
Published: June 2020

AbstractMolecular recognition is the key driver in the formation of supramolecular complexes, enabling the selective encapsulation of specific guests. Here, we explore the delicate balance between different energetic terms in the formation of an efficient host for fluoride anions based on a cylindrophane structure, which can be achieved by the incorporation of ligand sites into a cyanuric acid based cyclophane framework, resulting a close proximity between the ammonium hydrogens and the anion. This study describes the character and contribution of different energetic and repulsive terms that favor the efficient inclusion of fluoride. Our findings are useful for further rational design and synthesis of efficient and highly selective fluoride hosts, which have been generally less well described than complexing agents for other halides.
Negative Ion Formation by Thermal Surface Ionization of Sulfur Dioxide
Authors: Marciszuk Karolina , Pieńkos Tomasz , Gontarz Patryk , Pelc Andrzej 
Published: June 2020

AbstractThe generation of negative ions from SO2 in the gas phase was studied using the thermal surface ionization method. Six anion types were measured: O−, S−, SO−, and SO2− and anions with m/z=96 and m/z=128. The most abundant anion formed was S− and the formation routes are discussed for each of the six anions. O−, S−, and SO− are formed via dissociative electron attachment to the molecule, whereas the generation of SO2− and anions with m/z=96 and m/z=128 are probably associated with the formation of H2SO4 in the gas inlet system and the ion source. Using statistical thermodynamics the dissociation temperatures of SO2 and SO in the gas phase are calculated and values of above 1800 °C are obtained for both molecules. We also estimated the optimal filament temperatures for the formation of all anions measured, indicating that for SO2 the optimal temperature is related to the electron affinity of the molecules: the optimal temperature increases with decreasing value of the electron affinity for the molecule corresponding to the respective anion.
Politically connected firms and corporate social responsibility implementation expenditure in sub‐Saharan Africa: Evidence from Ghana
Authors: Adomako Samuel , Nguyen Nguyen P. 
Published: June 2020

AbstractWhile previous research has emphasized the role of stakeholder pressures, firm‐specific factors, as well as CEO characteristics as important drivers of corporate social responsibility (CSR) implementation, our understanding of how political connections impact small and medium‐sized enterprises' (SMEs') CSR implementation expenditure is quite limited. In this study, we contribute to filling this gap by investigating the effects of political connections and CSR expenditure and explain the conditions that impact this relationship. Using data from 473 SMEs in Ghana, we find that political connections negatively influence CSR implementation expenditure. However, the negative effect is weakened when a firms' reputation and competitive CSR implementation pressures are high. Implications for theory and practice are discussed.
The National Institutes of Health Chemical Countermeasures Research Program (NIH CCRP): A collaborative opportunity to develop effective and accessible chemical medical countermeasures for the American people
Authors: Yeung David T. , Harper Jill R. , Platoff Gennady E. 
Published: June 2020

AbstractThe United States Department of Health and Human Services (HHS) leads the nation in preventing, preparing for, and responding to the adverse health effects of public health emergencies and disasters. In addition to biological, radiological and nuclear agents, the risk of a high consequence public health emergency due to the intentional and/or accidental release of chemical agents is a major growing concern of the US government. As such, the federal government is fully committed to address public health security threats posed by chemicals. To enhance chemical emergency preparedness and response, HHS oversees the interdepartmental research, advanced development, regulatory review and approval, procurement, and stockpiling of medical countermeasures (MCMs). Within the National Institute of Health (NIH/HHS), the National Institute of Allergy and Infectious Diseases (NIAID) is responsible for the fundamental research and early development of MCMs to prevent deaths and/or treat injuries during and after emergencies due to large scale chemical exposure. This commentary provides an overview of the NIAID/NIH Chemical Countermeasures Research Program (CCRP) and resources to facilitate the research, discovery, and early development of chemical MCMs. Available product development resources include research funding opportunities, expert advice from the NIH, and preclinical and efficacy service support cores to reduce opportunity costs and entry barriers for prospective developers interested in entering or accelerating the development of chemical MCMs.
Scalable Synthesis of LiF‐rich 3D Architected Li Metal Anode via Direct Lithium‐Fluoropolymer Pyrolysis to Enable Fast Li Cycling
Authors: Shang Yuanyuan , Chu Tiankuo , Shi Baohui , Fu Kun (Kelvin) 
Published: June 2020

Lithium metal anode holds an important position in fast‐charging batteries. But lithium dendrite issues tend to exacerbate at high currents. LiF can be considered as an effective way to improve the Li metal surface electrochemical stability to achieve high power and high energy. However, most of reported work are relying on in situ formation of a 2D LiF on Li metal in liquid electrolyte, which limits the scalability and plated Li quantity. Here, we address this challenge and report a scalable synthesis of LiF‐rich 3D architected Li metal anode via a direct pyrolysis of molten lithium and fluoropolymer to enable fast Li charging with high current density (20 mA cm−2) and high areal capacity (20 mAh cm−2). The 3D structure is synthesized by the pyrolysis of fluoropolymer with Li metal and results show high similarity to the pristine electrolyte‐derived solid‐electrolyte‐interphase (SEI). This concept using pyrolysis of fluoropolymer with Li‐containing active materials could be also extended to modify Li metal oxide cathode (e.g., LiNi0.5Mn1.5O4) for mixed conductive interphase and engineer Li solid ion conductors (e.g., Li garnet‐type oxides) for interface stabilization and framework design.
Cushing syndrome cardiomyopathy: an unusual manifestation of small‐cell lung cancer
Authors: Pingle Srinath‐Reddi , Shah Tanvi , Mosleh Wassim , Kim Agnes S. 
Published: June 2020

AbstractCushing syndrome is a rare cause of dilated cardiomyopathy and heart failure with reduced ejection fraction. Cases describing this association are scarce. We describe a patient presenting with acute heart failure, new cardiomyopathy, refractory hypokalaemia, severe hyperglycaemia, and uncontrolled hypertension who was found to have hypercortisolism secondary to an ectopic adrenocorticotropic hormone‐secreting primary lung neoplasm. This case highlights the effects of hypercortisolism on the myocardium. The finding of a non‐dilated cardiomyopathy in this case is unique because the majority of previously reported Cushing syndrome cardiomyopathy cases have described left ventricular dilatation or significant left ventricular hypertrophy. In addition, small‐cell lung cancer with adrenocorticotropic hormone production causing Cushing syndrome cardiomyopathy is rare.
Crying out in pain—A systematic review into the validity of vocalization as an indicator for pain
Authors: Helmer Loreine M.L. , Weijenberg Roxane A.F. , de Vries Ralph , Achterberg Wilco P. , Lautenbacher Stefan , Sampson Elizabeth L. , Lobbezoo Frank 
Published: June 2020

AbstractBackgroundVocalization is often used to assess pain, sometimes combined with other behaviours such as facial expressions. Contrary to facial expressions, however, for vocalization, there is little evidence available on the association with pain. The aim of this systematic review was to critically analyse the association between vocalization and pain, to explore if vocalizations can be used as a “stand‐alone” indicator for pain.MethodsThe search was performed according to the Prisma Guidelines for systematic reviews and meta‐analysis. The following terms were used: “Pain Measurement,” “Vocalization” and “Verbalization.” The study population included verbal and non‐verbal individuals, including older people and children. The search was performed in three different databases: PubMed, Embase and CINAHL. A total of 35 studies were selected for detailed investigation. Quality assessments were made using two grading systems: Grading of Recommendations Assessment Development and Evaluation system and the Newcastle‐Ottawa scale.ResultsAn association between vocalization and pain was found in most studies, particularly when different types of vocalizations were included in the investigation. Different types of vocalization, but also different types of pain, shape this association. The association is observed within all groups of individuals, although age, amongst others, may have an influence on preferred type of vocalization.ConclusionsThere is an association between vocalization and pain. However, vocalization as a “stand‐alone” indicator for pain indicates only a limited aspect of this multifactorial phenomenon. Using vocalization as an indicator for pain may be more reliable if other pain indicators are also taken into account.SignificanceVocalizations are frequently used in pain scales, although not yet thoroughly investigated as a “single indicator” for pain, like, e.g. facial expression. This review confirms the role of vocalizations in pain scales, and stresses that vocalizations might be more reliable if used in combination with other pain indicators.
Flexible Polyester Screen‐printed Electrode Modified with Carbon Nanofibers for the Electrochemical Aptasensing of Cadmium (II)
Authors: Fakude Colani T , Arotiba Omotayo A , Arduini Fabiana , Mabuba Nonhlangabezo 
Published: June 2020

AbstractAn aptasensor was prepared by immobilising a biotinylated aptamer selected for Cd(II) on an activated carbon nanofiber (CNF) and streptavidin modified a screen‐printed electrode. The acid activated CNF was characterised by FTIR, CHNS elemental analysis and electron microscopy. Cyclic voltammetry, square wave voltammetry and electrochemical impedance spectroscopy (EIS) were used to characterise each step in the aptasensor preparation electrochemically. A detection limit of 0.11 ppb and a linear range of 2–100 ppb were obtained for Cd(II) with tolerance for other interfering species. The aptasensor was applied in real water samples and validated with ICPOES.
The extended evolutionary synthesis and human origins: Archaeological perspectives
Authors: Murray John K. , Benitez Robert Acio , O'Brien Michael J. 
Published: June 2020

AbstractRecent developments in evolutionary biology have led to a call for an extension of standard evolutionary theory, with its emphasis on processes such as selection and drift, into a much larger theoretical framework that includes processes such as niche construction, developmental plasticity, inclusive inheritance, and developmental bias. Skeptics argue that these processes are already subsumed within the standard theory and thus an extension is not required. Here, we outline what this evolutionary “rethink” might mean for the study of human origins. Specifically, can paleoanthropologists benefit from an extended theoretical toolkit? The papers in this special issue suggest it can be useful but may not be necessary, depending on the kinds of questions that are being asked.
A causal model for short‐term time series analysis to predict incoming Medicare workload
Authors: Mizan Tasquia , Taghipour Sharareh 
Published: June 2020

AbstractWe have investigated methodologies for predicting radiologists' workload in a short time interval by adopting a machine learning technique. Predicting for shorter intervals requires lower execution time combined with higher accuracy. To deal with this issue, an ensemble model is proposed with the fixed‐batch‐training method. To excel in the execution time, a fixed‐batch‐training method is used. On the other hand, the ensemble of multiple machine learning algorithms provides higher accuracy. The experimental result shows that this predictive model can produce at least 10% higher accuracy in comparison with the other available widely used short‐term time series forecasting models. In the studied medical system, this gain in accuracy for the earlier prediction of workload can reduce the Medicare relative value unit cost by $1.1 million annually, which we have formulated and shown in this paper. The proposed batch‐trained ensemble of experts model has also provided at least a 6% improvement in execution time compared with the other studied models.
Delineating effect of corn microRNAs and matrix, ingested as whole food, on gut microbiota in a rodent model
Authors: Huang Haiqiu , Pham Quynhchi , Davis Cindy D. , Yu Liangli , Wang Thomas T.Y. 
Published: June 2020

AbstractDietary microRNAs (miRNAs) are thought to regulate a wide range of biological processes, including the gut microbiota. However, it is difficult to separate specific effect(s) of miRNA from that of the food matrix. This study aims to elucidate the specific effect(s) of dietary corn miRNAs, ingested as a whole food, on the gut microbiota. We developed an autoclave procedure to remove 98% of miRNA from corn. A mouse feeding study was conducted comparing autoclaved corn to nonautoclaved corn and purified corn miRNA. Compared to nonspecific nucleotides and corn devoid of miRNAs, feeding purified corn miRNAs or corn to C57BL/6 mice via gavage or diet supplementation for two weeks lead to a decrease in total bacteria in the cecum. The effect appeared to be due to changes in Firmicutes. Additionally, corn matrix minus miRNA and processing also affected gut bacteria. In silico analysis identified corn miRNAs that aligned to Firmicutes genome sequences lending further support to the interaction between corn miRNAs and this bacterium. These data support interactions between plant food miRNA, as well as matrix, and the gut microbiota exist but complex. However, it provides additional support for mechanism by which bioactive dietary components interact with the gut microbiota.
The same, but different: Preserved distractor suppression in old age is implemented through an age‐specific reactive ventral fronto‐parietal network
Authors: Ashinoff Brandon K. , Mayhew Stephen D. , Mevorach Carmel 
Published: June 2020

AbstractPrevious studies have shown age‐related impairments in the ability to suppress salient distractors. One possibility is that this is mediated by age‐related impairments in the recruitment of the left intraparietal sulcus (Left IPS), which has been shown to mediate the suppression of salient distractors in healthy, young participants. Alternatively, this effect may be due to a shift in engagement from proactive control to reactive control, possibly to compensate for age‐related impairments in proactive control. Another possibility is that this is due to changes in the functional specificity of brain regions that mediate salience suppression, expressed in changes in spontaneous connectivity of these regions. We assessed these possibilities by having participants engage in a proactive distractor suppression task while in an fMRI scanner. Although we did not find any age‐related differences in behavior, the young (N = 15) and older (N = 15) cohorts engaged qualitatively distinctive brain networks to complete the task. Younger participants engaged the predicted proactive control network, including the Left IPS. On the other hand, older participants simultaneously engaged both a proactive and a reactive network, but this was not a consequence of reduced network specificity as resting state functional connectivity was largely comparable in both age groups. Furthermore, improved behavioral performance for older adults was associated with increased resting state functional connectivity between these two networks. Overall, the results of this study suggest that age‐related differences in the recruitment of a left lateralized ventral fronto‐parietal network likely reflect the specific recruitment of reactive control mechanisms for distractor inhibition.