bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Methodology for Estimating External Doses to Individuals and Populations Exposed to Radioactive Fallout from Nuclear Detonations
Authors: Bouville André , Beck Harold L. , Anspaugh Lynn R. , Gordeev Konstantin , Shinkarev Sergey , Thiessen Kathleen M. , Hoffman F. Owen , Simon Steven L. 
Published: December 2021

Abstract
A methodology of assessment of the doses from external irradiation resulting from the ground deposition of radioactive debris (fallout) from a nuclear detonation is proposed in this paper. The input data used to apply this methodology for a particular location are the outdoor exposure rate at any time after deposition of fallout and the time-of-arrival of fallout, as indicated and discussed in a companion paper titled “A Method for Estimating the Deposition Density of Fallout on the Ground and on Vegetation from a Low-yield Low-altitude Nuclear Detonation.” Example doses are estimated for several age categories and for all radiosensitive organs and tissues identified in the most recent ICRP publications. Doses are calculated for the first year after the detonation, when more than 90% of the external dose is delivered for populations close to the detonation site over a time period of 70 y, which is intended to represent the lifetime dose. Modeled doses in their simplest form assume no environmental remediation, though modifications can be introduced. Two types of dose assessment are considered: (1) initial, for a rapid but only approximate dose estimation soon after the nuclear detonation; and (2) improved, for a later, more accurate, dose assessment following the analysis of post-detonation measurements of radiation exposure and fallout deposition and the access of information on the lifestyle of the exposed population.
Stereotactic Body Radiotherapy in Oligomestatic/Oligoprogressive Sarcoma
Authors: Greto Daniela , Loi Mauro , Stocchi Giulia , Salvestrini Viola , Muratori Francesco , Scoccianti Guido , Roselli Giuliana , Palomba Annarita , Lorenzetti Victoria , Cerbai Cecilia , Desideri Isacco , Francolini Giulio , Bonomo Pierluigi , Campanacci Domenico Andrea , Livi Lorenzo 
Published: December 2021

Background
Metastatic soft tissue sarcoma (STS) patients may benefit from local ablative treatments due to modest efficacy of systemic chemotherapy. However, use of stereotactic body radiotherapy (SBRT) is controversial because of presumed radioresistance of STS.

Methods
Patients treated with SBRT for oligometastatic and oligoprogressive metastatic STS were retrospectively reviewed to assess results in terms of local control (LC), disease-free survival (DFS), and overall survival (OS). Incidence and grade of adverse events were reported. Statistical analysis was performed to identify variables correlated with outcome and toxicity.

Results
Forty patients were treated with SBRT to a median biologic effective dose (BED) of 105 (66–305) Gy5 to 77 metastases. Two-year LC, DFS, and OS were 67%, 23%, and 40%. Improved LC was shown in patients receiving a BED >150 Gy5 (hazard ratio [HR], 3.9; 95% confidence interval [CI], 1.6–9.7; P = 0.028). A delay >24 months between primary tumor diagnosis and onset of metastases was associated with improved DFS (HR, 0.46; 95% CI, 0.22–0.96; P = 0.01) and OS (HR, 0.48; 95% CI, 0.23–0.99; P = 0.03). No toxicity grade ≥3 was observed.

Conclusions
Stereotactic body radiotherapy is effective in metastatic STS with a benign toxicity profile. A BED >150 Gy5 is required to maximize tumor control rates. Metastatic relapse >24 months after diagnosis is correlated to improved survival.
Integrated, Integral, and Exploratory Biomarkers in the Development of Poly(ADP-Ribose) Polymerase Inhibitors
Authors: Konecny Gottfried E. , Chander Cinthiya , Zhang Liying 
Published: December 2021

Abstract
In this article, we highlight biomarkers for poly(ADP-ribose) polymerase inhibitor (PARPi) sensitivity and resistance and discuss their implications for the clinic. We review the predictive role of a range of DNA repair genes, genomic scars, mutational signatures, and functional assays available or in development. The biomarkers used for patient selection in the specific Food and Drug Administration–approved indications for breast, ovarian, prostate, and pancreatic cancer vary across tumor type and likely depend on disease-specific DNA repair deficiencies but also the specifics of the individual clinical trials that were conducted. Mutations in genes involved in homologous recombination and/or replication fork protection are synthetic lethal with PARPi. Cancers with homologous recombination deficiency exhibit high genomic instability, characterized by genome-wide loss of heterozygosity, among other genomic aberrations. Next-generation sequencing can identify multiple patterns of genomic changes including copy number variations, single-nucleotide variations, insertions/deletions, and structural variations rearrangements characteristic of homologous recombination deficiency. Clinical trial evidence supports the use of BRCA mutation testing for patient selection, and for ovarian cancer, there are 3 commercial assays available that additionally incorporate genomic instability for identifying subgroups of patients that derive different magnitudes of benefit from PARPi therapy. Finally, we summarize new strategies for extending the benefit of PARPi therapy toward broader populations of patients through the use of novel biomarkers. Ultimately, design of a composite biomarker test combining multiple mutational signatures or development of a dynamic assay for functional assessments of homologous recombination may help improve the test accuracy for future patient stratification.
Human cumulative culture and the exploitation of natural phenomena
Authors: Derex Maxime 
Published: December 2021

Cumulative cultural evolution (CCE)—defined as the process by which beneficial modifications are culturally transmitted and progressively accumulated over time—has long been argued to underlie the unparalleled diversity and complexity of human culture. In this paper, I argue that not just any kind of cultural accumulation will give rise to human-like culture. Rather, I suggest that human CCE depends on the gradual exploitation of natural phenomena, which are features of our environment that, through the laws of physics, chemistry or biology, generate reliable effects which can be exploited for a purpose. I argue that CCE comprises two distinct processes: optimizing cultural traits that exploit a given set of natural phenomena (Type I CCE) and expanding the set of natural phenomena we exploit (Type II CCE). I argue that the most critical features of human CCE, including its open-ended dynamic, stems from Type II CCE. Throughout the paper, I contrast the two processes and discuss their respective socio-cognitive requirements.This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Paradox of diversity in the collective brain
Authors: Schimmelpfennig Robin , Razek Layla , Schnell Eric , Muthukrishna Michael 
Published: December 2021

Human societies are collective brains. People within every society have cultural brains—brains that have evolved to selectively seek out adaptive knowledge and socially transmit solutions. Innovations emerge at a population level through the transmission of serendipitous mistakes, incremental improvements and novel recombinations. The rate of innovation through these mechanisms is a function of (1) a society's size and interconnectedness (sociality), which affects the number of models available for learning; (2) fidelity of information transmission, which affects how much information is lost during social learning; and (3) cultural trait diversity, which affects the range of possible solutions available for recombination. In general, and perhaps surprisingly, all three levers can increase and harm innovation by creating challenges around coordination, conformity and communication. Here, we focus on the ‘paradox of diversity’—that cultural trait diversity offers the largest potential for empowering innovation, but also poses difficult challenges at both an organizational and societal level. We introduce ‘cultural evolvability’ as a framework for tackling these challenges, with implications for entrepreneurship, polarization and a nuanced understanding of the effects of diversity. This framework can guide researchers and practitioners in how to reap the benefits of diversity by reducing costs.This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
The origins of human cumulative culture: from the foraging niche to collective intelligence
Authors: Migliano Andrea Bamberg , Vinicius Lucio 
Published: December 2021

Various studies have investigated cognitive mechanisms underlying culture in humans and other great apes. However, the adaptive reasons for the evolution of uniquely sophisticated cumulative culture in our species remain unclear. We propose that the cultural capabilities of humans are the evolutionary result of a stepwise transition from the ape-like lifestyle of earlier hominins to the foraging niche still observed in extant hunter–gatherers. Recent ethnographic, archaeological and genetic studies have provided compelling evidence that the components of the foraging niche (social egalitarianism, sexual and social division of labour, extensive co-residence and cooperation with unrelated individuals, multilocality, fluid sociality and high between-camp mobility) engendered a unique multilevel social structure where the cognitive mechanisms underlying cultural evolution (high-fidelity transmission, innovation, teaching, recombination, ratcheting) evolved as adaptations. Therefore, multilevel sociality underlies a ‘social ratchet’ or irreversible task specialization splitting the burden of cultural knowledge across individuals, which may explain why human collective intelligence is uniquely able to produce sophisticated cumulative culture. The foraging niche perspective may explain why a complex gene-culture dual inheritance system evolved uniquely in humans and interprets the cultural, morphological and genetic origins ofHomo sapiensas a process of recombination of innovations appearing in differentiated but interconnected populations.This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Shared intentionality, reason-giving and the evolution of human culture
Authors: O'Madagain Cathal , Tomasello Michael 
Published: December 2021

The biological approach to culture focuses almost exclusively on processes of social learning, to the neglect of processes of cultural coordination including joint action and shared intentionality. In this paper, we argue that the distinctive features of human culture derive from humans' unique skills and motivations for coordinating with one another around different types of action and information. As different levels of these skills of ‘shared intentionality’ emerged over the last several hundred thousand years, human culture became characterized first by such things as collaborative activities and pedagogy based on cooperative communication, and then by such things as collaborative innovations and normatively structured pedagogy. As a kind of capstone of this trajectory, humans began to coordinate not just on joint actions and shared beliefs, but on the reasons for what we believe or how we act. Coordinating on reasons powered the kinds of extremely rapid innovation and stable cumulative cultural evolution especially characteristic of the human species in the last several tens of thousands of years.
This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Experiments in artificial culture: from noisy imitation to storytelling robots
Authors: Winfield Alan F. T. , Blackmore Susan 
Published: December 2021

This paper presents a series of experiments in collective social robotics, spanning more than 10 years, with the long-term aim of building embodied models of (aspects of) cultural evolution. Initial experiments demonstrated the emergence of behavioural traditions in a group of social robots programmed to imitate each other’s behaviours (we call these Copybots). These experiments show that the noisy (i.e. less than perfect fidelity) imitation that comes for free with real physical robots gives rise naturally to variation in social learning. More recent experimental work extends the robots’ cognitive capabilities with simulation-based internal models, equipping them with a simple artificial theory of mind. With this extended capability we explore, in our current work, social learning not via imitation but robot–robot storytelling, in an effort to model this very human mode of cultural transmission. In this paper, we give an account of the methods and inspiration for these experiments, the experiments and their results, and an outline of possible directions for this programme of research. It is our hope that this paper stimulates not only discussion but suggestions for hypotheses to test with the Storybots.This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Differences between plasma and CSF p-tau181 and p-tau231 in early Alzheimer’s disease
Authors: Pilotto Andrea , Parigi Marta , Bonzi Giulio , Battaglio Beatrice , Ferrari Elisabetta , Mensi Lorenza , Benussi Alberto , Caratozzolo Salvatore , Cosseddu Maura , Turrone Rosanna , Archetti Silvana , Ashton Nicholas J , Zetterberg Henrik , Giliani Silvia , Padovani Alessandro 
Published: December 2021

ABSTRACTPlasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer’s disease pathology. In this cross-sectional study incuding ninety-one subjects, plasma p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD, with similar levels than those of CSF. Plasma p-tau231 and p-tau181 were strongly related to CSF tau and amyloid and exhibited a high accuracy – close to CSF p-tau231 and p-tau181 – to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings.
Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant
Authors: Schubert Maren , Bertoglio Federico , Steinke Stephan , Heine Philip Alexander , Ynga-Durand Mario Alberto , Zuo Fanglei , Du Likun , Korn Janin , Milošević Marko , Wenzel Esther Veronika , Maass Henrike , Krstanović Fran , Polten Saskia , Pribanić-Matešić Marina , Brizić Ilija , Piralla Antonio , Baldanti Fausto , Hammarström Lennart , Dübel Stefan , Šustić Alan , Marcotte Harold , Strengert Monika , Protić Alen , Pan-Hammarström Qiang , Čičin-Šain Luka , Hust Michael 
Published: December 2021

AbstractThe COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and classified as a variant of concern (VOC). Omicron shows substantially more mutations in the spike protein than any previous variant, mostly in the receptor binding domain (RBD). We analyzed the binding of the Omicron RBD to the human ACE2 receptor (hACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta or Delta RBDs variants.All RBDs were produced in insect cells. RBD binding to hACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 58 fully vaccinated individuals and 16 booster recipients were titrated by ELISA on the fixed RBDs from the original Wuhan strain, Beta, Delta and Omicron VOC.Surprisingly, the Omicron RBD showed a weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. However, a difference of 2.5 times was observed in RBD binding while in other studies the neutralization of Omicron SARS-CoV-2 was reduced by a magnitude of 10x and more. These results indicate an immune escape focused on neutralizing antibodies.The reduced binding of sera to Omicron RBD adds evidence that current vaccination protocols may be less efficient against the Omicron variant.
Resources Required for Implementation of SARS-CoV-2 Screening in Massachusetts K-12 Public Schools in Winter/Spring 2021
Authors: Lee Stephanie S. , Weitz Michelle , Ardlie Kristin , Bantham Amy , Schuckel Michele Fronk , Goehringer Katey , Hogue Caitlin , Hosking Rosy , Mortimer Kathleen , Saadat Alham , Seaman-Chandler Jill , Linas Benjamin P. , Ciaranello Andrea 
Published: December 2021

ABSTRACTImportanceCDC guidance emphasizes the importance of in-person education for students in grades kindergarten to 12 (K-12) during the COVID-19 pandemic. CDC encourage weekly SARS-CoV-2 testing of asymptomatic, unvaccinated students and staff (“screening”) to reduce infection risk and provide data about in-school SARS-CoV-2 prevalence where community incidence is high. The financial costs of screening assays have been described, but the human resource requirements at the school and district level to implement a SARS-CoV-2 screening program are not well known.ObjectiveTo quantify the resources required to implement a screening program in K-12 schools.Design, Setting, and ParticipantsA consortium of Massachusetts public K-12 schools was formed to implement and evaluate a range of SARS-CoV-2 screening approaches. Participating districts were surveyed weekly about their programs, including: type of assay used, individual vs. pooled screening, approaches to return of results and deconvolution (identification of positive individual specimens) of positive pools, number and type of personnel implementing the screening program, and hours spent on program implementation.Main Outcomes and MeasuresCosts, resource utilizationResultsIn 21 participating districts, over 21 weeks from January to June 2021, the positivity rate was 0.0%-0.21% among students and 0.0%-0.13% among educators/staff, and 4 out of 21 (19%) districts had at least one classroom transition to remote learning at any point due to a positive case. The average weekly cost to implement a screening program, including assay and personnel costs, was $17.00 per person tested; this was $46.68 for individual screenings and $15.61 for pooled screenings. The total weekly costs by district ranged from $1,644-$93,486, and districts screened between 58 and 3,675 people per week. The reported number of personnel working per week ranged from 1-5 to >50, and the total number of hours worked by all personnel ranged from 5-10 to >50.Conclusion and RelevanceThe human resources required to implement SARS-CoV-2 screening in Massachusetts public K-12 schools were substantial. Where screening is recommended for the 2021-22 school year due to high COVID-19 incidence (e.g., where vaccination uptake is low and/or more infectious variants predominate), understanding the human resources required to implement screening will assist districts policymakers in planning.
Antibiotic use for typhoid in India: Estimation from private sector prescription data during 2013-15
Authors: Koya Shaffi Fazaludeen , Farooqui Habib Hasan , Mehta Aashna , Selvaraj Sakthivel , Galea Sandro 
Published: December 2021

AbstractBackgroundIndia’s typhoid burden estimates are based on a limited number of population-based studies and data from a grossly incomplete disease surveillance system. In this study, we estimated the total and sex- and age-specific antibiotic prescription rates for typhoid.MethodsWe used systematic antibiotic prescription by private sector primary care physicians in India. We categorized antibiotics using the WHO classification system and calculated the prescription for various classes of antibiotics.ResultsWe analyzed 671 million prescriptions for the three-year period (2013-2015), of which an average of 8.98 million antibiotic prescriptions per year was for typhoid, accounting for 714 prescriptions per 100,000 population. Combination antibiotics are the preferred choice of prescribers in the adult age group, while cephalosporins are the preferred choice in children and young age. The prescription rate decreased from 792/100,000 in 2013 to 635 in 2015.ConclusionWe report a higher rate of antibiotic prescription for typhoid using prescription data, indicating a higher disease burden than previously estimated. Quinolones are still widely used in monotherapy, and children less than 10 years account for more than a million cases annually, which calls for a routine vaccination program.What we already knowTyphoid is a major cause of morbidity in India especially among young adults and children.The reported incidences are based on data from limited number of population-based studies and the disease surveillance program which is largely limited to public healthcare system in India.The emergence of antibiotic resistance among typhoid is a growing concern.What this article addsAge-specific typhoid antibiotic prescription estimate for India, using a large volume of geographically representative medical audit data.We report a high rate of antibiotic prescription (714/100,000 population) for typhoid indicating a higher disease burden than previously estimated.Fluroquinolones are still widely used as monotherapy for the treatment of typhoid in India.
OptDesign: Identifying Optimum Design Strategies in Strain Engineering for Biochemical Production
Authors: Jiang Shouyong , Otero-Muras Irene , Banga Julio R. , Wang Yong , Kaiser Marcus , Krasnogor Natalio 
Published: December 2021

AbstractComputational tools have been widely adopted for strain optimisation in metabolic engineering, contributing to numerous success stories of producing industrially relevant biochemicals. However, most of these tools focus on single metabolic intervention strategies (either gene/reaction knockout or amplification alone) and rely on hypothetical optimality principles (e.g., maximisation of growth) and precise gene expression (e.g., fold changes) for phenotype prediction. This paper introduces OptDesign, a new two-step strain design strategy. In the first step, OptDesign selects regulation candidates that have a noticeable flux difference between the wild type and production strains. In the second step, it computes optimal design strategies with limited manipulations (combining regulation and knockout) leading to high biochemical production. The usefulness and capabilities of OptDesign are demonstrated for the production of three biochemicals in E. coli using the latest genome-scale metabolic model iML1515, showing highly consistent results with previous studies while suggesting new manipulations to boost strain performance. Source code is available at https://github.com/chang88ye/OptDesign.