bluuebunny/crossref_metadata_2025_split huggingface dataset:
An anchored chromosome‐scale genome assembly of spinach improves annotation and reveals extensive gene rearrangements in euasterids
Authors: Hulse‐Kemp Amanda M , Bostan Hamed , Chen Shiyu , Ashrafi Hamid , Stoffel Kevin , Sanseverino Walter , Li Linzhou , Cheng Shifeng , Schatz Michael C. , Garvin Tyler , du Toit Lindsey J. , Tseng Elizabeth , Chin Jason , Iorizzo Massimo , Van Deynze Allen 
Published: June 2021

AbstractSpinach (Spinacia oleracea L.) is a member of the Caryophyllales family, a basal eudicot asterid that consists of sugar beet (Beta vulgaris L. subsp. vulgaris), quinoa (Chenopodium quinoa Willd.), and amaranth (Amaranthus hypochondriacus L.). With the introduction of baby leaf types, spinach has become a staple food in many homes. Production issues focus on yield, nitrogen‐use efficiency and resistance to downy mildew (Peronospora effusa). Although genomes are available for the above species, a chromosome‐level assembly exists only for quinoa, allowing for proper annotation and structural analyses to enhance crop improvement. We independently assembled and annotated genomes of the cultivar Viroflay using short‐read strategy (Illumina) and long‐read strategies (Pacific Biosciences) to develop a chromosome‐level, genetically anchored assembly for spinach. Scaffold N50 for the Illumina assembly was 389 kb, whereas that for Pacific BioSciences was 4.43 Mb, representing 911 Mb (93% of the genome) in 221 scaffolds, 80% of which are anchored and oriented on a sequence‐based genetic map, also described within this work. The two assemblies were 99.5% collinear. Independent annotation of the two assemblies with the same comprehensive transcriptome dataset show that the quality of the assembly directly affects the annotation with significantly more genes predicted (26,862 vs. 34,877) in the long‐read assembly. Analysis of resistance genes confirms a bias in resistant gene motifs more typical of monocots. Evolutionary analysis indicates that Spinacia is a paleohexaploid with a whole‐genome triplication followed by extensive gene rearrangements identified in this work. Diversity analysis of 75 lines indicate that variation in genes is ample for hypothesis‐driven, genomic‐assisted breeding enabled by this work.
Surgical correction of a persistent right aortic arch in a kitten with concurrent mitral and tricuspid valve insufficiency and long‐term post‐operative management of residual megaoesophagus
Authors: Viljoen Hermien , Boucher Charles , Boustead Keagan , Schoeman Johan P 
Published: June 2021

AbstractA Maine Coon kitten was diagnosed with persistent right aortic arch and concurrent mitral and tricuspid valve insufficiency. Diuretic and positive inotropic treatment were administered before surgical treatment was attempted. Surgical ligation of the ligamentum arteriosum was performed successfully. Regurgitation did not resolve despite efforts to slowly introduce solid food to the diet over a period of two months. The kitten suffered from several incidences of aspiration pneumonia that responded to antibiotic treatment. Follow‐up computed tomography ruled‐out extraluminal constriction of the oesophagus, and oesophagoscopy confirmed a residual megaoesophagus six months post‐operatively. The kitten was euthanised seven months after surgery. The importance of a complete cardiac work‐up and oesophagoscopy in suspected vascular ring anomaly examinations are highlighted in this case study.
Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity
Authors: Natua Subhashis , Dhamdhere Shruti Ganesh , Mutnuru Srinivas Abhishek , Shukla Sanjeev 
Published: June 2021

AbstractThe heterogeneous population of cancer cells within a tumor mass interacts intricately with the multifaceted aspects of the surrounding microenvironment. The reciprocal crosstalk between cancer cells and the tumor microenvironment (TME) shapes the cancer pathophysiome in a way that renders it uniquely suited for immune tolerance, angiogenesis, metastasis, and therapy resistance. This dynamic interaction involves a dramatic reconstruction of the transcriptomic landscape of tumors by altering the synthesis, modifications, stability, and processing of gene readouts. In this review, we categorically evaluate the influence of TME components, encompassing a myriad of resident and infiltrating cells, signaling molecules, extracellular vesicles, extracellular matrix, and blood vessels, in orchestrating the cancer‐specific metabolism and diversity of both mRNA and noncoding RNA, including micro RNA, long noncoding RNA, circular RNA among others. We also highlight the transcriptomic adaptations in response to the physicochemical idiosyncrasies of TME, which include tumor hypoxia, extracellular acidosis, and osmotic stress. Finally, we provide a nuanced analysis of existing and prospective therapeutics targeting TME to ameliorate cancer‐associated RNA metabolism, consequently thwarting the cancer progression.This article is categorized under:
RNA Processing > Splicing Regulation/Alternative Splicing
RNA Turnover and Surveillance > Regulation of RNA Stability
RNA in Disease and Development > RNA in Disease
Tools for computational analysis of moving boundary problems in cellular mechanobiology
Authors: DiNapoli Kathleen T. , Robinson Douglas N. , Iglesias Pablo A. 
Published: June 2021

AbstractA cell's ability to change shape is one of the most fundamental biological processes and is essential for maintaining healthy organisms. When the ability to control shape goes awry, it often results in a diseased system. As such, it is important to understand the mechanisms that allow a cell to sense and respond to its environment so as to maintain cellular shape homeostasis. Because of the inherent complexity of the system, computational models that are based on sound theoretical understanding of the biochemistry and biomechanics and that use experimentally measured parameters are an essential tool. These models involve an inherent feedback, whereby shape is determined by the action of regulatory signals whose spatial distribution depends on the shape. To carry out computational simulations of these moving boundary problems requires special computational techniques. A variety of alternative approaches, depending on the type and scale of question being asked, have been used to simulate various biological processes, including cell motility, division, mechanosensation, and cell engulfment. In general, these models consider the forces that act on the system (both internally generated, or externally imposed) and the mechanical properties of the cell that resist these forces. Moving forward, making these techniques more accessible to the non‐expert will help improve interdisciplinary research thereby providing new insight into important biological processes that affect human health.This article is categorized under:
Cancer > Computational Models
Cancer > Molecular and Cellular Physiology
Fourier Interpolation and Time-Frequency Localization
Authors: Kulikov Aleksei 
Published: June 2021

AbstractWe prove that under very mild conditions for any interpolation formula $$f(x) = \sum _{\lambda \in \Lambda } f(\lambda )a_\lambda (x) + \sum _{\mu \in M} {\hat{f}}(\mu )b_{\mu }(x)$$

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b
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we have a lower bound for the counting functions $$n_\Lambda (R_1) + n_{M}(R_2) \ge 4R_1R_2 - C\log ^{2}(4R_1R_2)$$

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which very closely matches recent interpolation formulas of Radchenko and Viazovska and of Bondarenko, Radchenko and Seip.
Algorithmic abstractions of ‘fashion identity’ and the role of privacy with regard to algorithmic personalisation systems in the fashion domain
Authors: Onitiu Daria 
Published: June 2021

AbstractThis paper delves into the nuances of ‘fashion’ in recommender systems and social media analytics, which shape and define an individual’s perception and self-relationality. Its aim is twofold: first, it supports a different perspective on privacy that focuses on the individual’s process of identity construction considering the social and personal aspects of ‘fashion’. Second, it underlines the limitations of computational models in capturing the diverse meaning of ‘fashion’, whereby the algorithmic prediction of user preferences is based on individual conscious and unconscious associations with fashion identity. I test both of these claims in the context of current concerns over the impact of algorithmic personalisation systems on individual autonomy and privacy: creating ‘filter bubbles’, nudging the user beyond their conscious awareness, as well as the inherent bias in algorithmic decision-making. We need an understanding of privacy that sustains the inherent reduction of fashion identity to literal attributes and protects individual autonomy in shaping algorithmic approximations of the self.
Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K
Authors: Mian Afsar Ali , Haberbosch Isabella , Khamaisie Hazem , Agbarya Abed , Pietsch Larissa , Eshel Elizabeh , Najib Dally , Chiriches Claudia , Ottmann Oliver Gerhard , Hantschel Oliver , Biondi Ricardo M. , Ruthardt Martin , Mahajna Jamal 
Published: June 2021

AbstractResistance remains the major clinical challenge for the therapy of Philadelphia chromosome–positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common “gatekeeper” mutation T315I. Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia. By inhibiting the BCR-ABL1 kinase, crizotinib efficiently suppressed growth of Ph+ cells without affecting growth of Ph− cells. It was also active in Ph+ patient-derived long-term cultures (PD-LTCs) independently of the responsiveness/resistance to other TKIs. The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1T315I-driven chronic myeloid leukemia–like disease and in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). Although crizotinib binds to the ATP-binding site, it also allosterically affected the myristol binding pocket, the binding site of GNF2 and asciminib (former ABL001). Therefore, crizotinib has a seemingly unique double mechanism of action, on the ATP-binding site and on the myristoylation binding pocket. These findings strongly suggest the clinical evaluation of crizotinib for the treatment of advanced and therapy-resistant Ph+ leukemia.
Magnitude effect in intertemporal allocation tasks
Authors: Sun Chen , Potters Jan 
Published: June 2021

AbstractIntertemporal choices are affected by both discount rate and utility curvature. We investigate how the two aspects of time preference are affected by the size of the total budget using an intertemporal allocation task. At the aggregate level as well as at the individual level, we find magnitude effects both on the discount rate and on intertemporal substitutability (i.e., utility curvature). Individuals are more patient when dealing with larger budgets and also regard larger budgets to be more fungible. The latter effect suggests that the degree of asset integration is increasing in the stake.
Machine learning models for classification tasks related to drug safety
Authors: Rácz Anita , Bajusz Dávid , Miranda-Quintana Ramón Alain , Héberger Károly 
Published: June 2021

AbstractIn this review, we outline the current trends in the field of machine learning-driven classification studies related to ADME (absorption, distribution, metabolism and excretion) and toxicity endpoints from the past six years (2015–2021). The study focuses only on classification models with large datasets (i.e. more than a thousand compounds). A comprehensive literature search and meta-analysis was carried out for nine different targets: hERG-mediated cardiotoxicity, blood–brain barrier penetration, permeability glycoprotein (P-gp) substrate/inhibitor, cytochrome P450 enzyme family, acute oral toxicity, mutagenicity, carcinogenicity, respiratory toxicity and irritation/corrosion. The comparison of the best classification models was targeted to reveal the differences between machine learning algorithms and modeling types, endpoint-specific performances, dataset sizes and the different validation protocols. Based on the evaluation of the data, we can say that tree-based algorithms are (still) dominating the field, with consensus modeling being an increasing trend in drug safety predictions. Although one can already find classification models with great performances to hERG-mediated cardiotoxicity and the isoenzymes of the cytochrome P450 enzyme family, these targets are still central to ADMET-related research efforts.
Graphical abstract
Survey on general practitioners’ and pharmacists’ opinions regarding patient-initiated treatment of recurring urinary tract infections
Authors: van der Zande Rian Lelie- , Koster Ellen S. , Teichert Martina , Bouvy Marcel L. 
Published: June 2021

AbstractBackground The Dutch general practitioners (GP) guideline for urinary tract infections (UTI) recommends patient-initiated treatment for women with recurring UTI. In countries other than the Netherlands, community pharmacists play a role in dispensing antibiotics for recurring UTI without preceding GP consultation. Objective To study GP and pharmacist opinions regarding the desirability of patient-initiated treatment, including potential pharmacist support for, and consequences of, facilitated access to antibiotics. Setting Dutch community pharmacies that cooperate with at least two GPs in their regional primary care network. Method Pharmacists in a postgraduate education program invited their residency pharmacist and 2–3 GPs to anonymously complete an online questionnaire. Questions related to diagnosis, treatment and potential role of the pharmacist. Answers were formulated as multiple-choice or ratings on a 5-point Likert scale. Data were analysed per professional group using descriptive statistics. Answers of pharmacists and GP to corresponding questions were analysed using a Chi-square test (p < 0.05). Main outcome measure Desirability of patient-initiated treatment and supporting role of the pharmacist. Results A total of 170 GPs and 76 pharmacists completed the questionnaires. Of the GPs, 35.1% supported patient-initiated treatment. Of the pharmacists, 69.7% were willing to dispense an antibiotic to a patient without preceding GP consultation after performing a probability check. In total, 65.7% of GPs and 44.7% of pharmacists thought that facilitated access to antibiotics would increase use of antibiotics (p < 0.05). Conclusion Support of GPs for facilitated access to antibiotic treatment by patient-initiated UTI treatment was limited, even with pharmacist support. The majority of pharmacists were willing to dispense an antibiotic after a probability check of an episode of recurring UTI, but both pharmacists and GPs were concerned about overuse of antibiotics.
Beyond Microsatellite Instability: Evolving Strategies Integrating Immunotherapy for Microsatellite Stable Colorectal Cancer
Authors: Pecci Federica , Cantini Luca , Bittoni Alessandro , Lenci Edoardo , Lupi Alessio , Crocetti Sonia , Giglio Enrica , Giampieri Riccardo , Berardi Rossana 
Published: June 2021

Opinion statementAdvanced colorectal cancer (CRC) is a heterogeneous disease, characterized by several subtypes with distinctive genetic and epigenetic patterns. During the last years, immune checkpoint inhibitors (ICIs) have revamped the standard of care of several tumors such as non-small cell lung cancer and melanoma, highlighting the role of immune cells in tumor microenvironment (TME) and their impact on cancer progression and treatment efficacy. An “immunoscore,” based on the percentage of two lymphocyte populations both at tumor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite stable (MSS) CRC. This group includes roughly 95% of all advanced CRC, and standard chemotherapy, in addition to anti-EGFR or anti-angiogenesis drugs, still represents first treatment choice. Hopefully, deeper understanding of CRC immune landscape and of the impact of specific genetic and epigenetic alterations on tumor immunogenicity might lead to the development of new drug combination strategies to overcome ICIs resistance in pMMR CRC, thus paving the way for immunotherapy even in this subgroup.
Oculomotor control in children with Special Educational Needs (SEN): the development and piloting of a novel app-based therapeutic intervention
Authors: Clark Rosie , Williams Cathy , Gilchrist Iain D. 
Published: June 2021

AbstractChildren with Special Educational Needs (SEN) often have impaired eye movement control which can impact on a wide range of everyday activities including in the classroom, socialising, participation in sport or crossing a road. Although some health practitioners offer eye movement therapies these tend not to have been systematically developed or evaluated. We have developed a new app to deliver eye movement training, based on detailed scientific understanding of eye movement control and extensive clinical experience with this patient group. We first investigated the acceptability of the app within several schools and made modifications based on detailed feedback from the children. Next, we conducted a pilot study to test the feasibility of using the app with 12 children (5–17 years old) who had SEN. The children successfully undertook app-based training for 10 min per day for 4–5 weeks. There was a high level of attendance and no attrition. We found some variation across participants in their ability to play on the app and the level of engagement. This indicates that pre-assessing children for ability and engagement may be important. This encouraging proof of concept study justifies the development of a full study. Given the time and money spent on existing commercially-offered or internet-based non-validated therapies, this would have substantial patient benefit regardless of the outcome: evidence of no effect could reassure parents that this kind of treatment was not needed, whilst evidence of effect suggests this as a useful treatment for children with poor oculomotor control.
The Distinct Wrong of Deepfakes
Authors: de Ruiter Adrienne 
Published: June 2021

AbstractDeepfake technology presents significant ethical challenges. The ability to produce realistic looking and sounding video or audio files of people doing or saying things they did not do or say brings with it unprecedented opportunities for deception. The literature that addresses the ethical implications of deepfakes raises concerns about their potential use for blackmail, intimidation, and sabotage, ideological influencing, and incitement to violence as well as broader implications for trust and accountability. While this literature importantly identifies and signals the potentially far-reaching consequences, less attention is paid to the moral dimensions of deepfake technology and deepfakes themselves. This article will help fill this gap by analysing whether deepfake technology and deepfakes are intrinsically morally wrong, and if so, why. The main argument is that deepfake technology and deepfakes are morally suspect, but not inherently morally wrong. Three factors are central to determining whether a deepfake is morally problematic: (i) whether the deepfaked person(s) would object to the way in which they are represented; (ii) whether the deepfake deceives viewers; and (iii) the intent with which the deepfake was created. The most distinctive aspect that renders deepfakes morally wrong is when they use digital data representing the image and/or voice of persons to portray them in ways in which they would be unwilling to be portrayed. Since our image and voice are closely linked to our identity, protection against the manipulation of hyper-realistic digital representations of our image and voice should be considered a fundamental moral right in the age of deepfakes.
Reducing unscheduled hospital care for adults with diabetes following a hypoglycaemic event: which community-based interventions are most effective? A systematic review
Authors: Watson Aoife , McConnell Donna , Coates Vivien 
Published: June 2021

AbstractAimTo determine which community-based interventions are most effective at reducing unscheduled hospital care for hypoglycaemic events in adults with diabetes.MethodsMedline Ovid, CINAHL Plus and ProQuest Health and Medical Collection were searched using both key search terms and medical subject heading terms (MeSH) to identify potentially relevant studies. Eligible studies were those that involved a community-based intervention to reduce unscheduled admissions in adults with diabetes. Papers were initially screened by the primary researcher and then a secondary reviewer. Relevant data were then extracted from papers that met the inclusion criteria.ResultsThe search produced 2226 results, with 1360 duplicates. Of the remaining 866 papers, 198 were deemed appropriate based on titles, 90 were excluded following abstract review. A total of 108 full papers were screened with 19 full papers included in the review. The sample size of the 19 papers ranged from n = 25 to n = 104,000. The average ages within the studies ranged from 41 to 74 years with females comprising 57% of the participants. The following community-based interventions were identified that explored reducing unscheduled hospital care in people with diabetes; telemedicine, education, integrated care pathways, enhanced primary care and care management teams.ConclusionsThis systematic review shows that a range of community-based interventions, requiring different levels of infrastructure, are effective in reducing unscheduled hospital care for hypoglycaemia in people with diabetes. Investment in effective community-based interventions such as integrated care and patient education must be a priority to shift the balance of care from secondary to primary care, thereby reducing hospital admissions.