bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIG DATA AND DIGITAL MARKETS CONTESTABILITY: THEORY OF HARM AND DATA ACCESS REMEDIES
Authors: Krämer Jan , Schnurr Daniel 
Published: July 2021

Abstract
This article analyses the crucial role of user data for digital markets contestability and presents policy proposals devised to address growing concerns about the dominance of data-rich incumbents in digital markets. To this end, we discuss a data-driven theory of harm that would warrant ex-ante data access regulation and highlight that niche entry and growth should be the primary economic policy objective in digital markets characterized by strong data-driven network effects. We then evaluate regulatory data access remedies with respect to the involved economic trade-offs and their effectiveness for promoting niche entry and growth. Firstly, we analyse remedies that would limit the collection of user data by data-rich incumbents such as data silos and line of business restrictions. Secondly, we consider remedies that facilitate sharing of (user) data by opening up access to raw behavioural user data collected by data-rich incumbents. In particular, we propose a dual approach with two complementary types of data access remedies: bulk sharing of broad anonymized raw user data and continuous, real-time data portability of deep raw data that contain personally identifiable information. Finally, we comment on the recent proposal for a Digital Markets Act by the European Commission with respect to our findings.
Clostridioides difficile and the Microbiota Early in Life
Authors: Semon Alexa K , Keenan Orlaith , Zackular Joseph P 
Published: July 2021

Abstract
Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease, including pseudomembranous colitis and toxic megacolon, healthy infants are asymptomatically colonized at high rates. The mechanisms leading to high colonization rates and infant protection from C. difficile are currently unknown; however, the ecology and metabolic state of the intestinal microbiome are factors known to influence C. difficile pathogenesis. In this review, we will examine the aspects of the early-life microbiome that may contribute to the incidence of C. difficile and protection from disease manifestation in infants. We will also discuss whether features of the adult microbiota that enable and restrict C. difficile are prevalent during early-life colonization.
International dental tourism in a post-COVID era: pre-travel advice
Authors: Felkai Peter P , Flaherty Gerard , Felkai Thomas 
Published: July 2021

The most significant risk of dental tourism is the timing of air travel after dental interventions in order to avoid the pain or injury caused by barotrauma. Usually the minimum waiting time should be 24 h, but in some cases, it can be up to 2 weeks.
Mass Spectrometry–Based Detection of Beta Lactam Hydrolysis Enables Rapid Detection of Beta Lactamase Mediated Antibiotic Resistance
Authors: Suhandynata Raymond T , Lund Kyle , Caraballo-Rodríguez Andrés M , Reed Sharon L , Dorrestein Pieter C , Fitzgerald Robert L , Bevins Nicholas J 
Published: July 2021

Abstract

Objective
Antibiotic resistance by beta lactamase expression is a serious and growing threat. We aimed to determine whether beta-lactamase activity is detectable in urine specimens to enable faster identification of resistance.

Methods
Urine specimens from patients with extended spectrum beta lactamase (ESBL)-expressing urinary infections were incubated with beta lactam antibiotics. Beta lactam hydrolysis was determined by mass spectrometry methods.

Results
Ceftriaxone hydrolysis was observed in 45 of 45 ESBL-containing specimens from patients not treated with a beta lactamase inhibitor before specimen collection. Ceftriaxone hydrolysis was not observed in 108 of 108 non-ESBL-containing specimens. Spiking studies show that beta lactam hydrolysis can be observed within 30 minutes. Beta lactam hydrolysis is evidenced by mass spectrometry preceded by either liquid chromatography or matrix-assisted laser desorption ionization specimen processing methods.

Conclusion
Clinically significant beta lactamase activity is detectable directly from urine specimens. The described methods would enable the detection of beta lactam resistance 24 to 48 hours sooner than culture based methods.
Ultracompact X-ray binaries with He star companions
Authors: Wang Bo , Chen Wen-Cong , Liu Dong-Dong , Chen Hai-Liang , Wu Cheng-Yuan , Tang Wen-Shi , Guo Yun-Lang , Han Zhan-Wen 
Published: July 2021

ABSTRACT
Ultracompact X-ray binaries (UCXBs) are low-mass X-ray binaries with hydrogen-deficient mass donors and ultrashort orbital periods. They have been suggested to be the potential Laser Interferometer Space Antenna (LISA) sources in the low-frequency region. Several channels for the formation of UCXBs have been proposed so far. In this paper, we carried out a systematic study on the He star donor channel, in which a neutron star (NS) accretes matter from a He main-sequence (MS) star through Roche lobe overflow, where the mass transfer is driven by the gravitational wave radiation. First, we followed the long-term evolution of the NS+He MS binaries by employing the stellar evolution code Modules for Experiments in Stellar Astrophysics (mesa ), and thereby obtained the initial parameter spaces for the production of UCXBs. We then used these results to perform a detailed binary population synthesis approach to obtain the Galactic rates of UCXBs through this channel. We estimate the Galactic rates of UCXBs appearing as LISA sources to be ${\sim} 3.1\!-\!11.9\, \rm Myr^{-1}$ through this channel, and the number of such UCXB-LISA sources in the Galaxy can reach about 1–26 calibrated by observations. This work indicates that the He star donor channel may contribute significantly to the Galactic UCXB formation rate. We found that the evolutionary tracks of UCXBs through this channel can account for the location of the five transient sources with relatively long orbital periods quite well. We also found that such UCXBs can be identified by their locations in the mass-transfer rate versus the orbital period diagram.
The COP9 signalosome subunit 3 is necessary for early embryo survival by way of a stable protein deposit in mouse oocytes
Authors: Israel Steffen , Drexler Hannes C A , Fuellen Georg , Boiani Michele 
Published: July 2021

ABSTRACTInvestigations of genes required in early mammalian development are complicated by protein deposits of maternal products, which continue to operate after the gene locus has been disrupted. This leads to delayed phenotypic manifestations and underestimation of the number of genes known to be needed during the embryonic phase of cellular totipotency. Here we expose a critical role of the gene Cops3 by showing that it protects genome integrity during the 2-cell stage of mouse development, in contrast to the previous functional assignment at postimplantation. This new role is mediated by a substantial deposit of protein (94th percentile of the proteome), divided between an exceptionally stable cortical rim, which is prevalent in oocytes, and an ancillary deposit in the embryonic nuclei. Since protein abundance and stability defeat prospects of DNA- or RNA-based gene inactivation in oocytes, we harnessed a classical method next to an emerging method for protein inactivation: antigen masking (for functional inhibition) versus TRIM21-mediated proteasomal degradation, also known as ‘Trim away’ (for physical removal). Both resulted in 2-cell embryo lethality, unlike the embryos receiving anti-green fluorescent protein. Comparisons between COPS3 protein-targeted and non-targeted embryos revealed large-scale transcriptome differences, which were most evident for genes associated with biological functions critical for RNA metabolism and for the preservation of genome integrity. The gene expression abnormalities associated with COPS3 inactivation were confirmed in situ by the occurrence of DNA endoreduplication and DNA strand breaks in 2-cell embryos. These results recruit Cops3 to the small family of genes that are necessary for early embryo survival. Overall, assigning genes with roles in embryogenesis may be less safe than assumed, if the protein products of these genes accumulate in oocytes: the inactivation of a gene at the protein level can expose an earlier phenotype than that identified by genetic techniques such as conventional gene silencing.
SNO 2020 diversity survey: defining demographics, racial biases, career success metrics and a path forward for the field of neuro-oncology
Authors: Chukwueke Ugonma N , Vera Elizabeth , Acquaye Alvina , Hervey-Jumper Shawn L , Odia Yazmin , Klesse Laura J , Dunbar Erin , Sharma Akanksha , Fonkem Ekokobe , Thomas Alissa A , Werbowetski-Ogilvie Tamra E , Camelo-Piragua Sandra , Gatson Na Tosha N , de la Fuente Macarena I , Armstrong Terri S , Porter Alyx B , Jackson Sadhana 
Published: July 2021

Abstract

Background
Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals.

Methods
In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population.

Results
The 386 respondents were predominantly female (58%) with a median age range of 40–49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field.

Conclusions
The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.
Inhibition of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress
Authors: Sharma Pratibha , Xu Jihong , Williams Katie , Easley Michelle , Elder J Brad , Lonser Russell , Lang Frederick F , Lapalombella Rosa , Sampath Deepa , Puduvalli Vinay K 
Published: July 2021

Abstract

Background
Tumor-specific metabolic processes essential for cell survival are promising targets to potentially circumvent intratumoral heterogeneity, a major resistance factor in gliomas. Tumor cells preferentially using nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway for synthesis of NAD, a critical cofactor for diverse biological processes including cellular redox reactions, energy metabolism, and biosynthesis. NAMPT is overexpressed in most malignancies, including gliomas, and can serve as a tumor-specific target.

Methods
Effects of pharmacological inhibition of NAMPT on cellular oxygen consumption rate, extracellular acidification, mitochondrial respiration, cell proliferation, invasion, and survival were assessed through in vitro and ex vivo studies on genetically heterogeneous glioma cell lines, glioma stem-like cells (GSCs), and mouse and human ex vivo organotypic glioma slice culture models.

Results
Pharmacological inhibition of the NAD salvage biosynthesis pathway using a highly specific inhibitor, KPT-9274, resulted in the reduction of NAD levels and related downstream metabolites, inhibited proliferation, and induced apoptosis in vitro in cell lines and ex vivo in human glioma tissue. These effects were mediated by mitochondrial dysfunction, DNA damage, and increased oxidative stress leading to apoptosis in GSCs independent of genotype, IDH status, or MGMT promoter methylation status. Conversely, NAMPT inhibition had minimal in vitro effects on normal human astrocytes (NHA) and no apparent in vivo toxicity in non-tumor-bearing mice.

Conclusions
Pharmacological NAMPT inhibition by KPT9274 potently targeted genetically heterogeneous gliomas by activating mitochondrial dysfunction. Our preclinical results provide a rationale for targeting the NAMPT-dependent alternative NAD biosynthesis pathway as a novel clinical strategy against gliomas.
Self-evaluating participatory research projects: A content validation of the InSPIRES online impact evaluation tool
Authors: Gignac Florence , Gresle Anne-Sophie , Santoro Lamelas Valeria , Yepes-Baldó Montserrat , de la Torre Leonardo , Pinazo Maria-Jesus 
Published: July 2021

Abstract
Research projects involving science shops and citizen science in their promotion of participatory approaches are flourishing globally. However, an instrument evaluating the impacts of such approaches at different stages of a participatory research processes has yet to be validated. The InSPIRES H2020 project developed an impact evaluation tool for just this purpose, consisting of 64 items that reflect upon the dimensions of knowledge democracy, citizen-led research, participatory dynamics, transformative change, and integrity. In this article, we seek to test the content validity of this tool and to provide recommendations that can ensure its validity. A panel of nine experts was created to evaluate each item as regards the following three criteria: representativeness, relevance, and clarity. The Aiken’s V and Wilson Score methods were used to assess the tool’s content validity based on the experts’ ratings. Experts’ written comments were also reviewed. At the panel level, 75% of the items were considered satisfactory in relation to each of the three validity criteria. However, at the population level, 72% of the items suggested that parts of the tool were not valid and required revision. The main suggestions from the experts pointed to the need to reformulate items in which the separation between science and society appeared reinforced and to develop more items about the gender perspective of a research project. The revised version of the tool should serve as a well-founded, comprehensive evaluation instrument for on-going and future projects whose goal is to self-reflect and compare participatory research processes.
Social thinking is for doing: the posterior cerebellum supports predictions of social actions based on personality traits
Authors: Haihambo Naem , Ma Qianying , Baeken Chris , Deroost Natacha , Baetens Kris , Heleven Elien , Overwalle Frank Van 
Published: July 2021

Abstract
Can we predict the future by reading others’ minds? This study explores whether attributing others’ personality traits facilitates predictions about their future actions and the temporal order of these future actions. Prior evidence demonstrated that the posterior cerebellar crus is involved in identifying the temporal sequence of social actions and the person’s traits they imply. Based on this, we hypothesized that this area might also be recruited in the reverse process; that is, knowledge of another person’s personality traits supports predictions of temporal sequences of others’ actions. In this study, participants were informed about the trait of a person and then had to select actions that were consistent with this information and arrange them in the most likely temporal order. As hypothesized, the posterior cerebellar crus 1 and crus 2 were strongly activated when compared to a control task which involved only the selection of actions (without temporal ordering) or which depicted non-social objects and their characteristics. Our findings highlight the important function of the posterior cerebellar crus in the prediction of social action sequences in social understanding.
Predictors of Lack of Relapse After Random Discontinuation of Oral and Long-acting Injectable Antipsychotics in Clinically Stabilized Patients with Schizophrenia: A Re-analysis of Individual Participant Data
Authors: Schoretsanitis Georgios , Kane John M , Correll Christoph U , Rubio Jose M 
Published: July 2021

Abstract

Objective
To quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment.

Methods
We re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of “relapse-free” individuals by the end of follow-up (median = 118 days, IQR = 52.0–208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for &gt;5 half-lives of the stabilizing antipsychotic, and studied predictors of “rebound psychosis” in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal.

Results
29.9% (95%CI = 23.2–38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65–21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4–46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19–2.00), female sex (aHR = 1.37, 95%CI = 1.08–1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68–4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5–7.1). “Rebound psychosis” did not show predictors.

Conclusions and relevance
Our results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk.
The all-E. coliTXTL toolbox 3.0: new capabilities of a cell-free synthetic biology platform
Authors: Garenne David , Thompson Seth , Brisson Amaury , Khakimzhan Aset , Noireaux Vincent 
Published: July 2021

AbstractThe new generation of cell-free gene expression systems enables the prototyping and engineering of biological systems in vitro over a remarkable scope of applications and physical scales. As the utilization of DNA-directed in vitro protein synthesis expands in scope, developing more powerful cell-free transcription–translation (TXTL) platforms remains a major goal to either execute larger DNA programs or improve cell-free biomanufacturing capabilities. In this work, we report the capabilities of the all-E. coli TXTL toolbox 3.0, a multipurpose cell-free expression system specifically developed for synthetic biology. In non-fed batch-mode reactions, the synthesis of the fluorescent reporter protein eGFP (enhanced green fluorescent protein) reaches 4 mg/ml. In synthetic cells, consisting of liposomes loaded with a TXTL reaction, eGFP is produced at concentrations of &gt;8 mg/ml when the chemical building blocks feeding the reaction diffuse through membrane channels to facilitate exchanges with the outer solution. The bacteriophage T7, encoded by a genome of 40 kb and ∼60 genes, is produced at a concentration of 1013 PFU/ml (plaque forming unit/ml). This TXTL system extends the current cell-free expression capabilities by offering unique strength and properties, for testing regulatory elements and circuits, biomanufacturing biologics or building synthetic cells.
Pathogenic characteristics and treatment in 43 cases of acute colchicine poisoning
Authors: Lu Xiaoxia , Liu Yanqing , Wang Chunyan , Dong Jianguang , Bai Lili , Zhang Chengcheng , Zhang Renzheng , Sun Chengwen , Qiu Zewu 
Published: July 2021

Abstract
Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5–0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries， include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration.
Consensus in Brazil on the renaming of leprosy to Hansen's disease
Authors: Delboni Lucas , Deps Patrícia 
Published: July 2021

Abstract
Brazil has been at the forefront in replacing the stigmatising term ‘leprosy’ with the non-pejorative alternative ‘Hansen's disease’ (‘hanseníase’), with use of the former word prohibited by law since 1995. This change followed decades of advocacy, including by civil society organisations representing people affected by the disease. A survey of people affected by Hansen's disease in Brazil found that 111/112 respondents preferred the alternative term, supporting the view that consideration of non-stigmatising terminology that respects the wishes of people affected by the disease should be part of the WHO Global Leprosy (Hansen's disease) Strategy to achieve ‘zero stigma’ by 2030.