bluuebunny/crossref_metadata_2025 huggingface dataset:
The Analytical Failures of Law and Economics
Authors: Bayern Shawn
Published: September 2023

The law-and-economics movement remains a dominant force in American private law, even though courts and commentators recognize that many of its assumptions are implausible and that efficiency is not the law's only goal. This book adds to the debate by showing that many leading law-and-economics arguments fail on their own terms, even for those who accept their most important assumptions and goals. Adopting an analytical approach and using some law-and-economics methods against the leading arguments in that field, Shawn Bayern shows that economic thinking fails to explain or justify most rules in the common law. Bayern masterfully surveys leading law-and-economics arguments in tort, contract, and property law and shows them to be fragile, self-contradictory, or otherwise problematic. Those who accept that efficiency is important should not be persuaded by the kind of law-and-economics arguments that have remained in vogue among legal scholars for decades.
Cognitive and Emotional Study Strategies for Students with Dyslexia in Higher Education
Authors: Abbott-Jones Amanda T.
Published: September 2023

Amanda T. Abbott-Jones provides practical and motivational guidance for dyslexic learners in higher education. It presents effective strategies appropriate for dealing with an array of study tasks including note taking, essay writing, reading, exams etc., while also delivering targeted emotional support. Pragmatic methods are delivered from the voices of students with dyslexia who have first-hand experience of fine-tuning study techniques, making learning suitable for how the dyslexic brain processes and memorises information to become successful in the academic world. As such, this book does not simply present strategies from an educational perspective, but instead draws on the wealth of empirical knowledge from the source of dyslexia – the dyslexic people themselves. This gives readers a collective shared identity, which has been previously lacking, teamed with valuable advice on ways to overcome cognitive and emotional difficulties by using appropriate strategies to enable people with dyslexia to flourish in the university environment.
Online Child Sexual Grooming Discourse
Authors: Lorenzo-Dus Nuria , Evans Craig , Mullineux-Morgan Ruth
Published: September 2023

This Element examines technology-assisted grooming of children for sex – henceforth, online grooming – as an illegal practice of communicative manipulation and, as such, something that research within the academic field of forensic linguistics is ideally placed to help counter. The analysis draws upon online grooming datasets of different sizes and provenance, including from law enforcement, and deploys different analytic techniques from primarily discourse analysis. Three features of online grooming discourse are focussed on: groomers' use of manipulation tactics; groomers' abuse of power asymmetries; and children's communication during online grooming. The Element also discusses ways in which findings derived from richly contextualised analysis of online grooming discourse can – when combined with co-creation projects involving child-safeguarding groups, children and lived-experience experts – add considerable value to societal efforts to counter online grooming and other forms of online child sexual exploitation and abuse.
What Was Shakespeare Really Like?
Authors: Wells Stanley , Fry Stephen
Published: September 2023

Sir Stanley Wells is one of the world's greatest authorities on William Shakespeare. Here he brings a lifetime of learning and reflection to bear on some of the most tantalising questions about the poet and dramatist that there are. How did he think, feel, and work? What were his relationships like? What did he believe about death? What made him laugh? This freshly thought and immensely engaging study wrestles with fundamental debates concerning Shakespeare's personality and life. The mysteries of how Shakespeare lived, whom and how he loved, how he worked, how he produced some of the greatest and most abidingly popular works in the history of world literature and drama, have fascinated readers for centuries. This concise, crystalline book conjures illuminating insights to reveal Shakespeare as he was. Wells brings the writer and dramatist alive, in all his fascinating humanity, for readers of today.
An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges
Authors: Fecho Karamarie , Bizon Chris , Issabekova Tursynay , Moxon Sierra , Thessen Anne E. , Abdollahi Shervin , Baranzini Sergio E. , Belhu Basazin , Byrd William E. , Chung Lawrence , Crouse Andrew , Duby Marc P. , Ferguson Stephen , Foksinska Aleksandra , Forero Laura , Friedman Jennifer , Gardner Vicki , Glusman Gwênlyn , Hadlock Jennifer , Hanspers Kristina , Hinderer Eugene , Hobbs Charlotte , Hyde Gregory , Huang Sui , Koslicki David , Mease Philip , Muller Sandrine , Mungall Christopher J. , Ramsey Stephen A. , Roach Jared , Rubin Irit , Schurman Shepherd H. , Shalev Anath , Smith Brett , Soman Karthik , Stemann Sarah , Su Andrew I. , Ta Casey , Watkins Paul B. , Williams Mark D. , Wu Chunlei , Xu Colleen H. ,   The Biomedical Data Translator Consortium
Published: September 2023

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
Do NBA teams avoid trading within their own division?
Authors: adams jimi , Bojanowski Michał
Published: September 2023

Within US professional sports, trades within one’s own division are often perceived to be disadvantageous. We ask how common this practice is. To examine this question, we construct a date-stamped network of all trades in the National Basketball Association between June 1976 and May 2019. We then use season-specific weighted exponential random graph models to estimate the likelihood of teams avoiding within-division trade partners, and how consistent that pattern is across the observed period. In addition to the empirical question, this analysis serves to demonstrate the necessity and difficulty of constructing the proper baseline for statistical comparison. We find limited-to-no support for the popular perception.
HOW THE INCORPORATION OF 14C IN LEAD WHITE MAKES ITS ABSOLUTE DATING POSSIBLE
Authors: Beck Lucile , Messager Cyrielle , Germain Tom , Hain Stéphane
Published: September 2023

Known as lead white, lead carbonates were used as white pigment or cosmetics from the 4th century BC to the 20th century AD. Lead white was produced by the corrosion of metallic lead by vinegar and horse manure up to the 19th c. In order to document the incorporation of carbon in the corrosion mechanism, lead carbonates were produced in the laboratory under monitored experimental conditions using materials with different isotope signatures in 14C and 13C. Six experimental setups were defined combining vinegar, acetic acid, horse manure and fossil CO2 gas. The corrosion products were characterized by X-ray diffraction. 14C content and δ13C values of the initial reactants and the final products were measured by accelerator and isotopic ratio mass spectrometry (AMS and IRSM). The reaction between lead and vinegar or acetic acid resulted in lead acetates with a carbon isotopic signature close to that of the corrosive reagent. In the presence of CO2, the carbonatation reaction occurred and the cerussite produced had a predominant 14C signature of the carbon dioxide source. These experiments demonstrate that the CO2 produced by horse manure fermentation is incorporated into the corrosion products, allowing the absolute dating of lead white by the radiocarbon method.
Quantitative assessment of spicule length in Heligmosomoides spp. (Nematoda, Heligmosomidae): distinction between H. bakeri, H. polygyrus and H. glareoli
Authors: Musah-Eroje Mayowa , Burton Laura , Kerr Nicola , Behnke Jerzy M.
Published: September 2023

Nematode spicules play a vital role in the reproductive activity of species that possess them. Our primary objective was to compare the lengths of spicules of the laboratory mouse (Mus musculus) – maintained isolate H. bakeri – with those of H. polygyrus from naturally infected wood mice (Apodemus sylvaticus). On a more limited scale, we also included H. glareoli from bank voles (Myodes glareolus), a species reputed to possess longer spicules than either of the 2 former species. In total, we measured 1264 spicules (H. bakeri, n = 614; H. polygyrus n = 582; and H. glareoli, n = 68). There was a highly significant difference between the spicule lengths of the Nottingham-maintained H. bakeri (mean = 0.518 mm) and H. polygyrus (0.598 mm) from 11 different localities across the British Isles. A comparison of the spicules of H. bakeri maintained in 4 different laboratories in 3 continents revealed a range in the mean values from 0.518 to 0.540 mm, while those of worms from Australian wild house mice were shorter (0.480 mm). Mean values for H. polygyrus from wood mice from the British Isles ranged from 0.564 to 0.635 mm, although isolates of this species from Norway had longer spicules (0.670 mm). In agreement with the literature, the spicules of H. glareoli were considerably longer (1.098 mm). Since spicules play a vital role in the reproduction of nematode species that possess them, the difference in spicule lengths between H. bakeri and H. polygyrus adds to the growing evidence that these 2 are quite distinct species and likely reproductively isolated.
Cognitive individual differences in the process and product of L2 writing
Authors: Granena Gisela
Published: September 2023

This paper examines how research in second language acquisition has approached the study of cognitive individual differences in the process and product of L2 writing from a theoretical and empirical perspective, paying special attention to the three empirical studies included in this special issue. The paper is divided into three sections. The first section examines the cognitive abilities that have been investigated in L2 writing research, among which working memory stands out as the most widely studied. The second section synthesizes the findings reported by the empirical studies in this issue in relation to the role of working memory in L2 writing behaviors and outcomes. The last section suggests future lines of research that can broaden the current scope of research on writing and cognitive individual differences, mostly centered on the components of the working memory system. This research has important theoretical implications, as little is known about how different cognitive individual differences are implicated in writing, as well as pedagogical implications, as the findings can inform about optimal performance and learning conditions for learners with diverse cognitive ability profiles.
Processing of noun plural marking in German-speaking children: an eye-tracking study
Authors: GRANDON Bénédicte , SCHLECHTWEG Marcel , RUIGENDIJK Esther
Published: September 2023

The ability to process plural marking of nouns is acquired early: at a very young age, children are able to understand if a noun represents one item or more than one. However, little is known about how the segmental characteristics of plural marking are used in this process. Using eye-tracking, we aim at understanding how five to twelve-year old children use the phonetic, phonological, and morphological information available to process noun plural marking in German (i.e., a very complex system) compared to adults. We expected differences with stem vowels, stem-final consonants or different suffixes, alone or in combination, reflecting different processing of their segmental information. Our results show that for plural processing: 1) a suffix is the most helpful cue, an umlaut the least helpful, and voicing does not play a role; 2) one cue can be sufficient and 3) school-age children have not reached adult-like processing of plural marking.
A Good Investment: Expanding Capacity to Care for Older Adults in the Home and Community Care Sector Through Increased Personal Support Worker Wages
Authors: Zagrodney Katherine A. P. , King Emily C. , Simon Deborah , Nichol Kathryn A. , McKay Sandra M.
Published: September 2023

Most older adults prefer to age in place, which for many will require home and community care (HCC) support. Unfortunately, HCC capacity is insufficient to meet demand due in part to low wages, particularly for personal support workers (PSWs) who provide the majority of paid care. Using Ontario as a case study, this paper estimates the cost and capacity impacts of implementing wage parity between PSWs employed in HCC and institutional long-term care (ILTC). Specifically, we consider the cost of increased HCC PSW wages versus expected savings from avoiding unnecessary ILTC placement for those accommodated by HCC capacity growth. The expected increase in HCC PSW retention would create HCC capacity for approximately 160,000 people, reduce annual health system costs by approximately $7 billion, and provide an 88 per cent return on investment. Updating wage structures to reduce turnover and enable HCC capacity growth is a cost-efficient option for expanding health system capacity.
Explaining the “parenting – callous-unemotional traits – antisocial behavior” axis in early adolescence: The role of affiliative reward
Authors: Roman Gabriela D. , Dobrean Anca , Florean Ionuţ Stelian
Published: September 2023

In explaining the “parenting – callous-unemotional traits – antisocial behavior” axis, recent theoretical advances postulate a critical role for affiliative reward. Existing empirical studies focus on early childhood and the appetitive phase of the reward process (i.e. affiliation-seeking behavior) rather than the consummatory phase (i.e. affective rewards). This study focuses on experienced affiliative reward (i.e. companionship, intimacy, affection, and worth) in relation to parents and best friends in early adolescence. The Alabama Parenting Questionnaire, Network of Relationships Inventory, Inventory of Callous and Unemotional Traits, and Youth Self Report were completed by 1132 12-year-olds and analyzed via structural equation models. In this cross-sectional sample, parent-related affiliative reward mediated the path from perceived parenting practices to callousness and further to aggression and rule-breaking. Parent-related affiliative reward was also related to uncaring traits and further to aggression and rule-breaking. In contrast, friend-related affiliative reward was not a mediator in this theoretical causal chain and largely not related to perceived parenting practices or CU traits. Low parent-related experienced affiliative reward is a mechanism through which corporal punishment, poor monitoring, and low involvement translate into callousness, and therefore to aggression and rule-breaking. Friend-related affiliative reward does not yet play a role in early adolescence.
The mirrors from Chiapa de Corzo: an early example for the Classic pyrite mirrors?
Authors: Gallaga Emiliano , Melgar Emiliano , Lowe Lynneth
Published: September 2023

Smith and Kidder (1951:44) were among the first to highlight pyrite pre-Hispanic mirrors as “marvels of painstaking craftsmanship.” These mirrors present reflective surfaces consisting of 20–50 pyrite tesserae with beveled edges, perfectly cut, and average 2 mm in thickness. The first known examples of mirrors in Mesoamerica were the “Olmec” type—a concave mirror created from a single hematite piece developed during the Middle Preclassic period. Later, in the Classic period, pyrite mosaic mirrors replaced them. Unfortunately, we do not understand the changes from one type to the other. In this work, we present two pyrite mirrors found at the site of Chiapa de Corzo, Chiapas, Mexico, dating around 700–500b.c., as possible forerunners of Classic pyrite mirrors. Also, we present traceological analysis of their manufacturing process using experimental archaeology and scanning electron microscopy. Based on these examinations, we identify likely materials and techniques employed in crafting them. We posit that production of these mirrors could have been the result of the development of specialized artisans at distinct workshops, increasing the complexity and labor investment in the lapidary objects as prestige goods.
New Woman
Authors: Das Riya
Published: September 2023

The ideal of the British New Woman, variously representing feminist, activist, fashion reformer, and writer, has been the subject of renewed critical interest since the late twentieth century. Although symptomatic of its situation in the fin de siècle, which “names those things that were never quite assimilated into the high-Victorian moment,” since the 1980s the New Woman has transcended its polemical Victorian conceptualization to represent “prequels to modernism as well as sequels to Victorianism.” As Sally Ledger has argued, the New Woman, despite being largely a “discursive phenomenon,” was nonetheless historically significant and central to late Victorian literary culture.
Self-reported mid- to late-life physical and recreational activities: Associations with late-life cognition
Authors: Gavett Brandon E. , Widaman Keith F. , McKenzie Cathryn , De Leon Fransia S. , Fletcher Evan , Tomaszewski Farias Sarah , Mungas Dan
Published: September 2023

Objective:

Physical and recreational activities are behaviors that may modify risk of late-life cognitive decline. We sought to examine the role of retrospectively self-reported midlife (age 40) physical and recreational activity engagement – and self-reported change in these activities from age 40 to initial study visit – in predicting late-life cognition.

Method:

Data were obtained from 898 participants in a longitudinal study of cognitive aging in demographically and cognitively diverse older adults (Age: range = 49–93 years, M = 75, SD = 7.19). Self-reported physical and recreational activity participation at age 40 and at the initial study visit were quantified using the Life Experiences Assessment Form. Change in activities was modeled using latent change scores. Cognitive outcomes were obtained annually (range = 2–17 years) using the Spanish and English Neuropsychological Assessment Scales, which measure verbal episodic memory, semantic memory, visuospatial processing, and executive functioning.

Results:

Physical activity engagement at age 40 was strongly associated with cognitive performance in all four domains at the initial visit and with global cognitive slope. However, change in physical activities after age 40 was not associated with cognitive outcomes. In contrast, recreational activity engagement – both at age 40 and change after 40 – was predictive of cognitive intercepts and slope.

Conclusions:

Retrospectively self-reported midlife physical and recreational activity engagement were strongly associated with late-life cognition – both level of performance and rate of future decline. However, the data suggest that maintenance of recreational activity engagement (e.g., writing, taking classes, reading) after age 40 is more strongly associated with late-life cognition than continued maintenance of physical activity levels.
Analysing the potential impacts of three interventions on fruit and vegetable consumption in urban Kenya using participatory systems modelling
Authors: Nicholson Charles F , Monterrosa Eva
Published: September 2023

Objective:

This study uses participatory modelling with stakeholders to assess the potential impacts of three interventions intended to increase fruit and vegetable (F&V) consumption in urban Kenya.

Design:

A participatory process using Group Model Building (GMB) developed a conceptual model of the determinants of vegetable consumption. A subsequent quantitative System Dynamics model using data from primary and secondary sources simulated vegetable consumption from 2020 to 2024 under three proposed interventions suggested by stakeholders: increasing consumer awareness, reducing post-harvest losses and increasing farm yields. Model analyses assumed mean parameter values and assessed uncertainty using 200 simulations with randomised parameter values.

Setting:

The research was implemented in Nairobi, Kenya with simulation analyses of mean per capita consumption in this location.

Participants:

Workshops convened diverse F&V value chain stakeholders (farmers, government officials, NGO staff and technical experts) to develop the conceptual model, data inputs and intervention scenarios.

Results:

Increasing consumer awareness was simulated to increase vegetable consumption by relatively modest amounts by 2024 (5 g/person/d from a base of 131 g/person/d) under mean assumed value of value chain response parameters. Reducing perishability was simulated to reduce consumption due to the higher costs required to reduce losses. Increasing farm yields was simulated to have the largest impact on consumption at assumed parameter values (about 40 g/person/d) but would have a negative impact on farm profits, which could undermine efforts to implement this intervention.

Conclusions:

The combination of GMB and simulation modelling informed intervention priorities for an important public health nutrition issue.
3rd Palaeontological Virtual Congress: palaeontology in the virtual era
Authors: CRESPO Vicente D. , RÍOS María , MARTÍN ARNAL Fernando A. , GAMONAL Arturo , CRUZADO-CABALLERO Penélope , GONZÁLEZ-DIONIS Javier , VLACHOS Evangelos , GUERRERO-ARENAS Rosalía , SÁNCHEZ-GARCÍA Alba
Published: September 2023

After the success of the first two editions of the Palaeontological Virtual Congress in 2019 (first PVC) and 2021 (second PVC; Crespo & Manzanares 2019; Crespo & Citton 2021), we have decided to try to replicate the success with a third meeting of the PVC (Fig. 1). The appearance of new applications and technological advances has played a crucial role in paving the way for enhanced avenues of effective scientific communication. This became even more pronounced from more than two years of challenges stemming from the COVID-19 pandemic. Due to this crisis, online platforms gained more relevance and proved key to keeping up the drive for science communication and the dissemination of scientific results (Barral 2020).
Prediction of Proton Pressure in the Outer Part of the Inner Magnetosphere Using Machine Learning
Authors: Li S. Y. , Kronberg E. A. , Mouikis C. G. , Luo H. , Ge Y. S. , Du A. M.
Published: September 2023

The information on plasma pressure in the outer part of the inner magnetosphere is important for simulations of the inner magnetosphere and a better understanding of its dynamics. Based on 17‐year observations from both Cluster Ion Spectrometry and Research with Adaptive Particle Imaging Detector instruments onboard the Cluster mission, we used machine‐learning‐based models to predict proton plasma pressure at energies from ∼40 eV to 4 MeV in the outer part of the inner magnetosphere ( = 5–9). Proton pressure distributions are assumed to be isotropic. The location in the magnetosphere, the property of stably trapped particles, and parameters of solar, solar wind, and geomagnetic activity from the OMNI database are used as predictors. We trained several different machine‐learning‐based models and compared their performances with observations. The results demonstrate that the Extra‐Trees Regressor has the best predicting performance. The Spearman correlation between the observations and predictions by the model is about 70%. The most important parameter for predicting proton pressure in our model is the value, which relates to the property of stably trapped particles. The most important predictor of solar and geomagnetic activity is F10.7 index. Based on the observations and predictions by our model, we find that no matter under quiet or disturbed geomagnetic conditions, both the dusk‐dawn asymmetry at the dayside with higher pressure at the duskside and the day‐night asymmetry with higher pressure at the nightside occur. Our results have direct practical applications, for instance, inputs for simulations of the inner magnetosphere or the reconstruction of the 3‐D magnetospheric electric current system based on the magnetostatic equilibrium.
High Intra‐Seasonal Variability in Greenhouse Gas Emissions From Temperate Constructed Ponds
Authors: Ray Nicholas E. , Holgerson Meredith A.
Published: September 2023

Inland waters play a major role in global greenhouse gas (GHG) budgets. The smallest of these systems (i.e., ponds) have a particularly large—but poorly constrained—emissions footprint at the global scale. Much of this uncertainty is due to a poor understanding of temporal variability in emissions. Here, we conducted high‐resolution temporal sampling to quantify GHG exchange between four temperate constructed ponds and the atmosphere on an annual basis. We show these ponds are a net source of GHGs to the atmosphere (564.4 g CO2‐eq m−2 yr−1), driven by highly temporally variable diffusive methane (CH4) emissions. Diffusive CH4 release to the atmosphere was twice as high during periods when the ponds had a stratified water column than when it was mixed. Ebullitive CH4 release was also higher during stratification. Building ponds to favor mixed conditions thus presents an opportunity to minimize the global GHG footprint of future pond construction.
The Bay of Bengal: An Enigmatic Diazotrophic Niche
Authors: Saxena Himanshu , Sahoo Deepika , Nazirahmed Sipai , Chaudhari Diptaraj , Rahi Praveen , Kumar Sanjeev , Benavides Mar , Krishna Aswathy Vijaya , Sudheer A. K. , Singh Arvind
Published: September 2023

Biological dinitrogen (N2) fixation is meagerly explored in the Bay of Bengal (Bay). Stratified, warm, oligotrophic (but relatively high iron and phosphate) and oxygen minimum zone (OMZ) waters of the Bay might be a niche for diazotrophs. Therefore, we conducted N2 fixation rate measurements during the spring inter‐monsoon in the euphotic zone, the OMZ and below the OMZ down to 1,500 m depth near the coastal and in the central Bay. We further assessed primary production and cyanobacterial community composition along with their potential environmental controlling parameters. N2 fixation rates in the euphotic zone were low (0.02–0.38 nmol N L−1 d−1) and their contribution to primary production was small (<2%). Despite conducive conditions for diazotrophy in the Bay, the reason for the relatively low euphotic zone and OMZ N2 fixation rates remained unclear and enigmatic. Interestingly, significantly higher N2 fixation rates occurred below the OMZ (>600 m depth), ranging from 0.06 to 0.11 nmol N L−1 d−1 where oxygen concentrations ranged between 0.5 and 1.6 mL L−1, rather than within the OMZ where rates ranged from 0.02 to 0.08 nmol N L−1 d−1 and oxygen concentrations were ≤0.5 mL L−1. Euphotic zone N2 fixation showed seasonality in the Bay with increasing rates from spring to summer season, perhaps owing to increasing Fe flux as the summer monsoon approaches its peak.
Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies
Authors: Falconnier Camille , Caparros-Roissard Alba , Decraene Charles , Lutz Pierre-Eric
Published: September 2023

In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a dramatic toll on western countries. OUD is a chronic relapsing disease associated with a lifetime struggle to control drug consumption, suggesting that opioids trigger long-lasting brain adaptations, notably through functional genomic and epigenomic mechanisms. Current understanding of these processes, however, remain scarce, and have not been previously reviewed systematically. To do so, the goal of the present work was to synthesize current knowledge on genome-wide transcriptomic and epigenetic mechanisms of opioid action, in primate and rodent species. Using a prospectively registered methodology, comprehensive literature searches were completed in PubMed, Embase, and Web of Science. Of the 2709 articles identified, 73 met our inclusion criteria and were considered for qualitative analysis. Focusing on the 5 most studied nervous system structures (nucleus accumbens, frontal cortex, whole striatum, dorsal striatum, spinal cord; 44 articles), we also conducted a quantitative analysis of differentially expressed genes, in an effort to identify a putative core transcriptional signature of opioids. Only one gene, Cdkn1a, was consistently identified in eleven studies, and globally, our results unveil surprisingly low consistency across published work, even when considering most recent single-cell approaches. Analysis of sources of variability detected significant contributions from species, brain structure, duration of opioid exposure, strain, time-point of analysis, and batch effects, but not type of opioid. To go beyond those limitations, we leveraged threshold-free methods to illustrate how genome-wide comparisons may generate new findings and hypotheses. Finally, we discuss current methodological development in the field, and their implication for future research and, ultimately, better care.
Behavioral and neurocognitive factors distinguishing post-traumatic stress comorbidity in substance use disorders
Authors: Houghton David C. , Spratt Heidi M. , Keyser-Marcus Lori , Bjork James M. , Neigh Gretchen N. , Cunningham Kathryn A. , Ramey Tatiana , Moeller F. Gerard
Published: September 2023

Significant trauma histories and post-traumatic stress disorder (PTSD) are common in persons with substance use disorders (SUD) and often associate with increased SUD severity and poorer response to SUD treatment. As such, this sub-population has been associated with unique risk factors and treatment needs. Understanding the distinct etiological profile of persons with co-occurring SUD and PTSD is therefore crucial for advancing our knowledge of underlying mechanisms and the development of precision treatments. To this end, we employed supervised machine learning algorithms to interrogate the responses of 160 participants with SUD on the multidimensional NIDA Phenotyping Assessment Battery. Significant PTSD symptomatology was correctly predicted in 75% of participants (sensitivity: 80%; specificity: 72.22%) using a classification-based model based on anxiety and depressive symptoms, perseverative thinking styles, and interoceptive awareness. A regression-based machine learning model also utilized similar predictors, but failed to accurately predict severity of PTSD symptoms. These data indicate that even in a population already characterized by elevated negative affect (individuals with SUD), especially severe negative affect was predictive of PTSD symptomatology. In a follow-up analysis of a subset of 102 participants who also completed neurocognitive tasks, comorbidity status was correctly predicted in 86.67% of participants (sensitivity: 91.67%; specificity: 66.67%) based on depressive symptoms and fear-related attentional bias. However, a regression-based analysis did not identify fear-related attentional bias as a splitting factor, but instead split and categorized the sample based on indices of aggression, metacognition, distress tolerance, and interoceptive awareness. These data indicate that within a population of individuals with SUD, aberrations in tolerating and regulating aversive internal experiences may also characterize those with significant trauma histories, akin to findings in persons with anxiety without SUD. The results also highlight the need for further research on PTSD-SUD comorbidity that includes additional comparison groups (i.e., persons with only PTSD), captures additional comorbid diagnoses that may influence the PTSD-SUD relationship, examines additional types of SUDs (e.g., alcohol use disorder), and differentiates between subtypes of PTSD.
Evaluation of CTRL: a web application for dynamic consent and engagement with individuals involved in a cardiovascular genetic disorders cohort
Authors: Haas Matilda A. , Madelli Evanthia O. , Brown Rosie , Prictor Megan , Boughtwood Tiffany
Published: September 2023

There has been keen interest in whether dynamic consent should be used in health research but few real-world studies have evaluated its use. Australian Genomics piloted and evaluated CTRL (‘control’), a digital consent tool incorporating granular, dynamic decision-making and communication for genomic research. Individuals from a Cardiovascular Genetic Disorders Flagship were invited in person (prospective cohort) or by email (retrospective cohort) to register for CTRL after initial study recruitment. Demographics, consent choices, experience surveys and website analytics were analysed using descriptive statistics. Ninety-one individuals registered to CTRL (15.5% of the prospective cohort and 11.8% of the retrospective cohort). Significantly more males than females registered when invited retrospectively, but there was no difference in age, gender, or education level between those who did and did not use CTRL. Variation in individual consent choices about secondary data use and return of results supports the desirability of providing granular consent options. Robust conclusions were not drawn from satisfaction, trust, decision regret and knowledge outcome measures: differences between CTRL and non-CTRL cohorts did not emerge. Analytics indicate CTRL is acceptable, although underutilised. This is one of the first studies evaluating uptake and decision making using online consent tools and will inform refinement of future designs.
A maternally programmed intergenerational mechanism enables male offspring to make piRNAs from Y-linked precursor RNAs in Drosophila
Authors: Venkei Zsolt G. , Gainetdinov Ildar , Bagci Ayca , Starostik Margaret R. , Choi Charlotte P. , Fingerhut Jaclyn M. , Chen Peiwei , Balsara Chiraag , Whitfield Troy W. , Bell George W. , Feng Suhua , Jacobsen Steven E. , Aravin Alexei A. , Kim John K. , Zamore Phillip D. , Yamashita Yukiko M.
Published: September 2023

In animals, PIWI-interacting RNAs (piRNAs) direct PIWI proteins to silence complementary targets such as transposons. In Drosophila and other species with a maternally specified germline, piRNAs deposited in the egg initiate piRNA biogenesis in the progeny. However, Y chromosome loci cannot participate in such a chain of intergenerational inheritance. How then can the biogenesis of Y-linked piRNAs be initiated? Here, using Suppressor of Stellate (Su(Ste)), a Y-linked Drosophila melanogaster piRNA locus as a model, we show that Su(Ste) piRNAs are made in the early male germline via 5′-to-3′ phased piRNA biogenesis initiated by maternally deposited 1360/Hoppel transposon piRNAs. Notably, deposition of Su(Ste) piRNAs from XXY mothers obviates the need for phased piRNA biogenesis in sons. Together, our study uncovers a developmentally programmed, intergenerational mechanism that allows fly mothers to protect their sons using a Y-linked piRNA locus.
A simple and efficient process for the synthesis of 2D carbon nitrides and related materials
Authors: Moreira Da Silva Cora , Vallet Maxime , Semion Clément , Blin Thomas , Saint-Martin Romuald , Leroy Jocelyne , Dragoé Diana , Brisset François , Gillet Cynthia , Guillot Régis , Huc Vincent
Published: September 2023

We describe here a new process for the synthesis of very high quality 2D Covalent Organic Frameworks (COFs), such a C2N and CN carbon nitrides. This process relies on the use of a metallic surface as both a reagent and a support for the coupling of small halogenated building blocks. The conditions of the assembly reaction are chosen so as to leave the inorganic salts by-products on the surface, to further confine the assembly reaction on the surface and increase the quality of the 2D layers. We found that under these conditions, the process directly returns few layers material. The structure/quality of these materials is demonstrated by extensive cross-characterizations at different scales, combining optical microscopy, Scanning Electron Microscopy (SEM)/Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDS). The availability of such very large, high-quality layers of these materials opens interesting perspectives, for example in photochemistry and electronics (intrinsic transport properties, high gap substrate for graphene, etc...).
Identification of a novel Sorcin isoform with a different C-terminal but intact dimerization property
Authors: Tanwar Supriya , Qais Faizan Abul , Naaz Farheen , Rashid Naira , Ahmad Faizan , ur Rehman Sayeed
Published: September 2023

Sorcin (Sri), a member of penta EF-hand protein family plays a diverse role in maintaining calcium homeostasis, cell cycle and vesicular trafficking. Sri is highly conserved amongst mammals and consists of N-terminal glycine rich domain and C-terminal calcium binding domain that mediates its dimerization and interacts with different compounds. In the present study, with the help of combination of computational and molecular biology techniques, we have identified a novel isoform (Sri-N) in mouse which differs only in the C-terminal domain with that of Sri reported earlier. The novel isoform contains a new last exon that is different from the one present in the reported transcript (Sri). The presence of the novel isoform was further validated in different tissues by RT-PCR and DNA sequencing. The transcript was conceptually translated and subjected to in-silico analysis using different bioinformatics tools. The novel transcript variant encodes for a longer protein isoform without any change in the sub-cellular localization as predicted by PSORT-II online tool. Molecular modelling was performed to compare the structural changes in Sri-N and Sri isoforms. The structural characterization of the novel isoform using MD simulation depicted its overall stability under the physiological conditions. The molecular docking of proteins with various chemotherapeutic drugs revealed that their binding affinity is more for Sri-N as compared to that for the previously reported transcript Sri.
A principled representation of elongated structures using heatmaps
Authors: Kordon Florian , Stiglmayr Michael , Maier Andreas , Martín Vicario Celia , Pertlwieser Tobias , Kunze Holger
Published: September 2023

The detection of elongated structures like lines or edges is an essential component in semantic image analysis. Classical approaches that rely on significant image gradients quickly reach their limits when the structure is context-dependent, amorphous, or not directly visible. This study introduces a principled mathematical description of elongated structures with various origins and shapes. Among others, it serves as an expressive operational description of target functions that can be well approximated by Convolutional Neural Networks. The nominal position of a curve and its positional uncertainty are encoded as a heatmap by convolving the curve distribution with a filter function. We propose a low-error approximation to the expensive numerical integration by evaluating a distance-dependent function, enabling a lightweight implementation with linear time complexity. We analyze the method’s numerical approximation error and behavior for different curve types and signal-to-noise levels. Application to surgical 2D and 3D data, semantic boundary detection, skeletonization, and other related tasks demonstrate the method’s versatility at low errors.
Accelerating the characterization of dynamic DNA origami devices with deep neural networks
Authors: Wang Yuchen , Jin Xin , Castro Carlos
Published: September 2023

Mechanical characterization of dynamic DNA nanodevices is essential to facilitate their use in applications like molecular diagnostics, force sensing, and nanorobotics that rely on device reconfiguration and interactions with other materials. A common approach to evaluate the mechanical properties of dynamic DNA nanodevices is by quantifying conformational distributions, where the magnitude of fluctuations correlates to the stiffness. This is generally carried out through manual measurement from experimental images, which is a tedious process and a critical bottleneck in the characterization pipeline. While many tools support the analysis of static molecular structures, there is a need for tools to facilitate the rapid characterization of dynamic DNA devices that undergo large conformational fluctuations. Here, we develop a data processing pipeline based on Deep Neural Networks (DNNs) to address this problem. The YOLOv5 and Resnet50 network architecture were used for the two key subtasks: particle detection and pose (i.e. conformation) estimation. We demonstrate effective network performance (F1 score 0.85 in particle detection) and good agreement with experimental distributions with limited user input and small training sets (~ 5 to 10 images). We also demonstrate this pipeline can be applied to multiple nanodevices, providing a robust approach for the rapid characterization of dynamic DNA devices.
A titratable murine model of progressive emphysema using tracheal porcine pancreatic elastase
Authors: Joshi Imani , Devine Andrew J. , Joshi Rashika , Smith Noah J. , Varisco Brian M.
Published: September 2023

Progressive emphysema often leads to end-stage lung disease. Most mouse models of emphysema are typically modest (i.e. cigarette smoke exposure), and changes over time are difficult to quantify. The tracheal porcine pancreatic elastase model (PPE) produces severe injury, but the literature is conflicted as to whether emphysema improves, is stable, or progresses over time. We hypothesized a threshold of injury below which repair would occur and above which emphysema would be stable or progress. We treated 8-week-old C57BL6 mixed sex mice with 0, 0.5, 2, or 4 activity units of PPE in 100 µL PBS and performed lung stereology at 21 and 84 days. There were no significant differences in weight gain or mouse health. Despite minimal emphysema at 21-days in the 0.5 units group (2.8 µm increased mean linear intercept, MLI), MLI increased by 4.6 µm between days 21 and 84 (p = 0.0007). In addition to larger MLI at 21 days in 2- and 4-unit groups, MLI increases from day 21 to 84 were 17.2 and 34 µm respectively (p = 0.002 and p = 0.0001). Total lung volume increased, and alveolar surface area decreased with time and injury severity. Contrary to our hypothesis, we found no evidence of alveolar repair over time. Airspace destruction was both progressive and accelerative. Future mechanistic studies in lung immunity, mechano-biology, senescence, and cell-specific changes may lead to novel therapies to slow or halt progressive emphysema in humans.
Folate-conjugated near-infrared fluorescent perfluorocarbon nanoemulsions as theranostics for activated macrophage COX-2 inhibition
Authors: Vichare Riddhi , Crelli Caitlin , Liu Lu , McCallin Rebecca , Cowan Abree , Stratimirovic Stefan , Herneisey Michele , Pollock John A. , Janjic Jelena M.
Published: September 2023

Activated macrophages play a critical role in the orchestration of inflammation and inflammatory pain in several chronic diseases. We present here the first perfluorocarbon nanoemulsion (PFC NE) that is designed to preferentially target activated macrophages and can deliver up to three payloads (two fluorescent dyes and a COX-2 inhibitor). Folate receptors are overexpressed on activated macrophages. Therefore, we introduced a folate-PEG-cholesterol conjugate into the formulation. The incorporation of folate conjugate did not require changes in processing parameters and did not change the droplet size or fluorescent properties of the PFC NE. The uptake of folate-conjugated PFC NE was higher in activated macrophages than in resting macrophages. Flow cytometry showed that the uptake of folate-conjugated PFC NE occurred by both phagocytosis and receptor-mediated endocytosis. Furthermore, folate-conjugated PFC NE inhibited the release of proinflammatory cytokines (TNF-α and IL-6) more effectively than nonmodified PFC NE, while drug loading and COX-2 inhibition were comparable. The PFC NEs reported here were successfully produced on multiple scales, from 25 to 200 mL, and by using two distinct processors (microfluidizers: M110S and LM20). Therefore, folate-conjugated PFC NEs are viable anti-inflammatory theranostic nanosystems for macrophage drug delivery and imaging.
Pipeline validation for the identification of antimicrobial-resistant genes in carbapenem-resistant Klebsiella pneumoniae
Authors: Vieira Andressa de Almeida , Piccoli Bruna Candia , y Castro Thaís Regina , Casarin Bruna Campestrini , Tessele Luiza Funck , Martins Roberta Cristina Ruedas , Schwarzbold Alexandre Vargas , Trindade Priscila de Arruda
Published: September 2023

Antimicrobial-resistant Klebsiella pneumoniae is a global threat to healthcare and an important cause of nosocomial infections. Antimicrobial resistance causes prolonged treatment periods, high mortality rates, and economic impacts. Whole Genome Sequencing (WGS) has been used in laboratory diagnosis, but there is limited evidence about pipeline validation to parse generated data. Thus, the present study aimed to validate a bioinformatics pipeline for the identification of antimicrobial resistance genes from carbapenem-resistant K. pneumoniae WGS. Sequences were obtained from a publicly available database, trimmed, de novo assembled, mapped to the K. pneumoniae reference genome, and annotated. Contigs were submitted to different tools for bacterial (Kraken2 and SpeciesFinder) and antimicrobial resistance gene identification (ResFinder and ABRicate). We analyzed 201 K. pneumoniae genomes. In the bacterial identification by Kraken2, all samples were correctly identified, and in SpeciesFinder, 92.54% were correctly identified as K. pneumoniae, 6.96% erroneously as Pseudomonas aeruginosa, and 0.5% erroneously as Citrobacter freundii. ResFinder found a greater number of antimicrobial resistance genes than ABRicate; however, many were identified more than once in the same sample. All tools presented 100% repeatability and reproducibility and > 75% performance in other metrics. Kraken2 was more assertive in recognizing bacterial species, and SpeciesFinder may need improvements.