bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Language in Economics
Authors: Jelveh Zubin , Kogut Bruce , Naidu Suresh
Published: April 2024

Does academic writing in economics reflect the political orientation of economists? We use machine learning to measure partisanship in academic economics articles. We predict the observed political behaviour of a subset of economists using phrases from their academic articles, show good out-of-sample predictive accuracy and then predict partisanship for all economists. We then use these predictions to examine patterns of political language in economics. We estimate journal-specific effects on predicted ideology, controlling for author and year fixed effects, that accord with existing survey-based measures. We show considerable sorting of economists into fields of research by predicted partisanship. We also show that partisanship is detectable even within fields, even across those estimating the same theoretical parameter. Using policy-relevant parameters collected from previous meta-analyses, we then show that imputed partisanship is correlated with estimated parameters, such that the implied policy prescription is consistent with partisan leaning. For example, we find that going from the most left-wing authored estimate of the taxable top income elasticity to the most right-wing authored estimate decreases the optimal tax rate from 77% to 60%.
Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC
Authors: Ntaios George , Baumgartner Helmut , Doehner Wolfram , Donal Erwan , Edvardsen Thor , Healey Jeff S , Iung Bernard , Kamel Hooman , Kasner Scott E , Korompoki Eleni , Navi Babak B , Pristipino Christian , Saba Luca , Schnabel Renate B , Svennberg Emma , Lip Gregory Y H
Published: April 2024

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.
Diving into drug-screening: zebrafish embryos as an in vivo platform for antimicrobial drug discovery and assessment
Authors: Habjan Eva , Schouten Gina K , Speer Alexander , van Ulsen Peter , Bitter Wilbert
Published: April 2024

The rise of multidrug-resistant bacteria underlines the need for innovative treatments, yet the introduction of new drugs has stagnated despite numerous antimicrobial discoveries. A major hurdle is a poor correlation between promising in vitro data and in vivo efficacy in animal models, which is essential for clinical development. Early in vivo testing is hindered by the expense and complexity of existing animal models. Therefore, there is a pressing need for cost-effective, rapid preclinical models with high translational value. To overcome these challenges, zebrafish embryos have emerged as an attractive model for infectious disease studies, offering advantages such as ethical alignment, rapid development, ease of maintenance, and genetic manipulability. The zebrafish embryo infection model, involving microinjection or immersion of pathogens and potential antibiotic hit compounds, provides a promising solution for early-stage drug screening. It offers a cost-effective and rapid means of assessing the efficacy, toxicity and mechanism of action of compounds in a whole-organism context. This review discusses the experimental design of this model, but also its benefits and challenges. Additionally, it highlights recently identified compounds in the zebrafish embryo infection model and discusses the relevance of the model in predicting the compound’s clinical potential.
The Effects of Computerized Cognitive Training in Older Adults’ Cognitive Performance and Biomarkers of Structural Brain Aging
Authors: Lee Hyun Kyu , Basak Chandramallika , Grant Sarah-Jane , Ray Nicholas R , Skolasinska Paulina A , Oehler Chris , Qin Shuo , Sun Andrew , Smith Evan T , Sherard G Hulon , Rivera-Dompenciel Adriana , Merzenich Mike , Voss Michelle W
Published: April 2024

Objectives

Cognitive training (CT) has been investigated as a means of delaying age-related cognitive decline in older adults. However, its impact on biomarkers of age-related structural brain atrophy has rarely been investigated, leading to a gap in our understanding of the linkage between improvements in cognition and brain plasticity. This study aimed to explore the impact of CT on cognitive performance and brain structure in older adults.

Methods

One hundred twenty-four cognitively normal older adults recruited from 2 study sites were randomly assigned to either an adaptive CT (n = 60) or a casual game training (active control, AC, n = 64).

Results

After 10 weeks of training, CT participants showed greater improvements in the overall cognitive composite score (Cohen’s d = 0.66, p < .01) with nonsignificant benefits after 6 months from the completion of training (Cohen’s d = 0.36, p = .094). The CT group showed significant maintenance of the caudate volume as well as significant maintained fractional anisotropy in the left internal capsule and in left superior longitudinal fasciculus compared to the AC group. The AC group displayed an age-related decrease in these metrics of brain structure.

Discussion

Results from this multisite clinical trial demonstrate that the CT intervention improves cognitive performance and helps maintain caudate volume and integrity of white matter regions that are associated with cognitive control, adding to our understanding of the changes in brain structure contributing to changes in cognitive performance from adaptive CT.

Clinical Trial Registration

NCT03197454
Enhancing physical activity participation among female employees: evaluating the effectiveness of an educational intervention
Authors: Ghaffari Mohtasham , Sadeghi Bita , Dadipoor Sara , Safari-Moradabadi Ali
Published: April 2024

This paper evaluates the effectiveness of an educational intervention based on the transtheoretical model aimed at increasing physical activity (PA) participation among female employees in Bandar Abbas city (Iran) healthcare centers in December 2017 and August 2018. Using a semi-experimental interventional study design with a randomized and multi-stage method, 100 participants were included in both the intervention (n = 50) and control groups (n = 50). Data collection involved questionnaires assessing demographic information (age, gender, marital status and education), stages of change in PA behavior, Perceived Benefits, Barriers and Self-efficacy. The data were analyzed using SPSS-16, employing both descriptive (mean, SD, frequency, percentage) and inferential statistics (t-tests, chi-squared tests, etc.). Prior to the educational intervention, 19 participants (0.38%) in the intervention group engaged consistently in PA (stages 4–5). After 3 and 6 months of intervention, these numbers increased to 29 (0.58%) and 25 (0.50%), respectively. This improvement was statistically significant compared to the pre-intervention stage (P < 0.001). The findings highlight the importance of theory-based behavior change models and health education programs in promoting PA and combating sedentary lifestyles. Although focused on a specific population in Bandar Abbas, the intervention can serve as a model for similar programs targeting diverse social classes and populations.
Elements of a doctrine of transnational constitutional norms
Authors: Perju Vlad
Published: April 2024

This article uses the traditions of constitutionalism to develop the building blocks of a doctrine of transitional constitutional norms. After arguing that existing doctrines of implicit constitutional unamendability, such as the basic structure and constitutional replacement doctrines, are derivative, the article provides an account of the underlying primary doctrine: transnational constitutional norms. From the perspective of the form of government, constitutional norms are divided into peremptory and voluntary norms. Unearthing an old, but now largely forgotten, tradition of political thought, it defines peremptory norms as norms that derive from or constitute the form of government. These constitutional norms have a complex nature: domestic and transnational. The transnational dimension immunizes the people’s choice in favor of the democratic form of government by protecting peremptory norms from deselection, defined as the impermissible alteration or replacement of that form of government through piecemeal derogation from peremptory norms. Only the people as pouvoirconstituant, but not their representatives, may chose the form of government and only through a full-scale process of constitution-making. The article uses judicial independence to illustrate the idea of peremptory constitutional norms. The doctrine of transnational constitutional norms helps to resist attempts at undermining judicial independence and to protect the integrity of the democratic form of government against impermissible deselection.
Effect of Leptin Receptor Q223R Polymorphism on Clostridioides difficile Infection–Induced Macrophage Migration Inhibitory Factor Production
Authors: Mathew Ann M , Huber Alexander , Sous Rowis D , Weghorn Kristin N , Powers-Fletcher Margaret V , Jose Shinsmon , Madan Rajat
Published: April 2024

Proinflammatory cytokine levels and host genetic makeup are key determinants of Clostridioides difficile infection (CDI) outcomes. We previously reported that blocking the inflammatory cytokine macrophage migration inhibitory factor (MIF) ameliorates CDI. Here, we determined kinetics of MIF production and its association with a common genetic variant in leptin receptor (LEPR) using blood from patients with CDI. We found highest plasma MIF early after C difficile exposure and in individuals who express mutant/derived LEPR. Our data suggest that early-phase CDI provides a possible window of opportunity in which MIF targeting, potentially in combination with LEPR genotype, could have therapeutic utility.
Reduced Effectiveness of Repeat Influenza Vaccination: Distinguishing Among Within-Season Waning, Recent Clinical Infection, and Subclinical Infection
Authors: Bi Qifang , Dickerman Barbra A , Nguyen Huong Q , Martin Emily T , Gaglani Manjusha , Wernli Karen J , Balasubramani G K , Flannery Brendan , Lipsitch Marc , Cobey Sarah ,   the US Flu Vaccine Effectiveness Network Investigators, Murthy Kempapura , Raiyani Chandni , Dunnigan Kayan , Mamawala Muffadal , Chung Jessie R , Patel Manish , Lamerato Lois , Jackson Michael L , Phillips C Hallie , Kiniry Erika , Belongia Edward A , King Jennifer P , Monto Arnold S , Zimmerman Richard K , Nowalk Mary Patricia , Geffel Krissy Moehling
Published: April 2024

Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness Network (2011–2012 to 2018–2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by 1 week. After accounting for waning VE, we determined that repeat vaccinees were still more likely to test positive for A(H3N2) (odds ratio, 1.11; 95% CI, 1.02–1.21) but not influenza B or A(H1N1). We documented clinical infection influenced individuals' decision to vaccinate in the following season while protecting against clinical infection of the same type/subtype. However, adjusting for recent documented clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical or undocumented infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on vaccine effectiveness.
Taking Civilians: Terrorist Kidnapping in Civil War
Authors: Welsh Blair
Published: April 2024

Why do insurgents resort to kidnapping in civil war? What explains variation in the selection and intensity of the tactic over time and space? Despite an increase in the use of kidnapping over time, existing research has yet to develop an explanation that explains spatiotemporal variation and extends beyond financial motivations. I argue the decision to kidnap hostages is shaped by insurgents’ behavioral interactions in the conflict environment. It occurs under two conditions: to generate support and reinstate bargaining capacity when organizations suffer military losses on the battlefield and to enforce loyalties and display strength when organizations face violent competition from other non-state actors. The observable implications of the theory are tested at the macro- and micro levels. At the macro-level, I conduct a quantitative cross-group analysis on over 200 organizations involved in an armed intrastate conflict (1989–2018). At the micro level, I consider the kidnapping strategy of the Taliban in Afghanistan over time and space (2010–2018). Taken together, the analyses provide robust support for the theory.
Local large language models for privacy-preserving accelerated review of historic echocardiogram reports
Authors: Vaid Akhil , Duong Son Q , Lampert Joshua , Kovatch Patricia , Freeman Robert , Argulian Edgar , Croft Lori , Lerakis Stamatios , Goldman Martin , Khera Rohan , Nadkarni Girish N
Published: April 2024

Objectives

The study developed framework that leverages an open-source Large Language Model (LLM) to enable clinicians to ask plain-language questions about a patient’s entire echocardiogram report history. This approach is intended to streamline the extraction of clinical insights from multiple echocardiogram reports, particularly in patients with complex cardiac diseases, thereby enhancing both patient care and research efficiency.

Materials and Methods

Data from over 10 years were collected, comprising echocardiogram reports from patients with more than 10 echocardiograms on file at the Mount Sinai Health System. These reports were converted into a single document per patient for analysis, broken down into snippets and relevant snippets were retrieved using text similarity measures. The LLaMA-2 70B model was employed for analyzing the text using a specially crafted prompt. The model’s performance was evaluated against ground-truth answers created by faculty cardiologists.

Results

The study analyzed 432 reports from 37 patients for a total of 100 question-answer pairs. The LLM correctly answered 90% questions, with accuracies of 83% for temporality, 93% for severity assessment, 84% for intervention identification, and 100% for diagnosis retrieval. Errors mainly stemmed from the LLM’s inherent limitations, such as misinterpreting numbers or hallucinations.

Conclusion

The study demonstrates the feasibility and effectiveness of using a local, open-source LLM for querying and interpreting echocardiogram report data. This approach offers a significant improvement over traditional keyword-based searches, enabling more contextually relevant and semantically accurate responses; in turn showing promise in enhancing clinical decision-making and research by facilitating more efficient access to complex patient data.
Pre-treatment bone mineral density and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project
Authors: Schini Marian , Vilaca Tatiane , Lui Li-Yung , Ewing Susan K , Thompson Austin , Vittinghoff Eric , Bauer Douglas C , Bouxsein Mary L , Black Dennis M , Eastell Richard
Published: April 2024

Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into FN BMD T-score subgroups (≤−2.5, > −2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ −2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ −2.5 and > −2.5 subgroups. Compared to those with FN BMD T-score > −2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ −2.5, but only the all-fracture outcome reached statistical significance (interaction P = .001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all, and all clinical fractures in the lower BMD quintiles (all interaction P ≤ .03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above −2.5, though effects tended to be larger and more significant in those with baseline T-scores <−2.5.
Update on the composition and distribution of the mosquito fauna (Diptera: Culicidae) in Cabo Verde, a country at risk for mosquito-borne diseases
Authors: Da Veiga Leal Silvânia , Varela Isaias Baptista Fernandes , Monteiro Davidson Daniel Sousa , Ramos de Sousa Celivianne Marisia , da Luz Lima Mendonça Maria , De Pina Adilson José , Gonçalves Adéritow Augusto Lopes Macedo , Costa Osório Hugo
Published: April 2024

Mosquitoes play a critical role as vectors of pathogens affecting both humans and animals. Therefore, understanding their biodiversity and distribution is crucial to developing evidence-based vector control strategies. The current study updated the composition and distribution of mosquito species through a comprehensive survey of all municipalities of Cabo Verde. From October 2017 to September 2018, mosquito larvae and pupae were collected from 814 aquatic habitats. Anopheles gambiae (Giles, 1902) and Culex pipiens (Linnaeus, 1758) complexes were subjected to PCR-based techniques for sibling species identification. Ten mosquito species from 5 genera were identified: Aedes aegypti (Linnaeus, 1762), Aedes caspius (Pallas, 1771), Anopheles arabiensis (Patton, 1905), Anopheles pretoriensis (Theobald, 1903), Culex bitaeniorhynchus (Giles, 1901), Cx. pipiens, Culex quinquefasciatus (Say, 1823), Culex tritaeniorhynchus (Giles, 1901), Culiseta longiareolata (Macquart, 1838), and Lutzia tigripes (de Grandpre & de Charmoy, 1901). Santiago Island reported the highest number of species (n = 8). Ae. aegypti and Cx. quinquefasciatus were the most widely distributed species across the country. An. arabiensis was the sole species identified within the An. gambiae complex. The findings from our study will help guide health policy decisions to effectively control mosquito-borne diseases.
The Domains of Monotonicity Processing
Authors: Tan I-An , Segal Nir , Grodzinsky Yosef
Published: April 2024

This paper reports an investigation into the nature of Negative Polarity Item (NPI) licensing conditions from a processing perspective. We found that the processing cost of Downward Entailingness (a k a the Monotonicity Effect) is determined by the number of monotonicity reversals of NPI domains, rather than by the number of Downward-Entailing (DE) operators. This conclusion is not based on the standard judgment paradigm, but rather, on the measurement of continuous variables (error rates, Reaction Times (RTs)) in a verification task, in which the truth value of a sentence is determined against a scenario. We conducted two experiments with sentences that contained one or two DE operators, which featured in different syntactic configurations. We explored how RT is affected by the manipulation of both the number of DE operators, and the syntactic environments in which they reside. We ran these experiments in Hebrew and in English, with different participant populations and different testing methods. Despite the linguistic subtlety of the theoretical issues, our results were remarkably sharp, leading to two firm conclusions: (i) that processing time is determined not by the number of DE operators, but rather, by the monotonicity of the minimal constituent in which they reside; (ii) that DE-ness is not a property of operators, but of environments. We show how our results bear directly on the current debate about the nature of monotonicity, which we describe below. Finally, we provide quantitative tests of alternative, non-semantic explanations, and show how our results do not support them.
Impact of an anemia diagnostic management team on follow-up test ordering by primary care providers
Authors: Soder Julie , Zahner Christopher , Salazar Jose H
Published: April 2024

Background

Anemia is a complex condition with diverse causes and poses diagnostic challenges amid the expanding landscape of laboratory testing. Implementation of an anemia diagnostic management team (DMT) can aid health care providers in navigating this complexity.

Methods

This quasi-experimental study assessed the impact of an anemia DMT on laboratory test ordering by primary care providers for anemic patients. This study included adult patients (≥18 years) with anemia (hemoglobin <12.0 g/dL for nonpregnant women, hemoglobin <13.0 g/dL for men) presenting to a family medicine clinic. Cases reviewed by the DMT (n = 100) were compared with a control group (n = 95).

Results

The DMT recommended additional testing for 76 patients. Significantly more patients in the DMT group underwent follow-up tests compared with controls (59% vs 34%; P < .001). Moreover, the DMT group underwent a higher mean number of tests per patient (1.70 ± 2.2 vs 0.95 ± 1.9; P = .01).

Conclusion

Implementation of an anemia DMT influenced follow-up testing patterns in anemic patients, potentially enhancing diagnostic thoroughness and patient care.
Mycobiome of the external ear canal of healthy cows
Authors: Díaz Leyna , Castellá Gemma , Bragulat M Rosa , Paytuví-Gallart Andreu , Sanseverino Walter , Cabañes F Javier
Published: April 2024

Malassezia yeasts belong to the normal skin microbiota of a wide range of warm-blooded animals. However, their significance in cattle is still poorly understood. In the present study, the mycobiota of the external ear canal of 20 healthy dairy Holstein cows was assessed by cytology, culture, PCR, and next-generation sequencing. The presence of Malassezia was detected in 15 cows by cytology and PCR. The metagenomic analysis revealed that Ascomycota was the predominant phylum but M. pachydermatis the main species. The Malassezia phylotype 131 was detected in low abundance. Nor M. nana nor M. equina were detected in the samples.
Copper-binding proteins and exonic splicing enhancers and silencers
Authors: Bakhtiar Dara , Vorechovsky Igor
Published: April 2024

Eukaryotic DNA codes not only for proteins but contains a wealth of information required for accurate splicing of messenger RNA precursors and inclusion of constitutively or alternatively spliced exons in mature transcripts. This “auxiliary” splicing code has been characterized as exonic splicing enhancers and silencers (ESE and ESS). The exact interplay between protein and splicing codes is, however, poorly understood. Here, we show that exons encoding copper-coordinating amino acids in human cuproproteins lack ESEs and/or have an excess of ESSs, yet RNA sequencing and expressed sequence tags data show that they are more efficiently included in mature transcripts by the splicing machinery than average exons. Their largely constitutive inclusion in messenger RNA is facilitated by stronger splice sites, including polypyrimidine tracts, consistent with an important role of the surrounding intron architecture in ensuring high expression of metal-binding residues during evolution. ESE/ESS profiles of codons and entire exons that code for copper-coordinating residues were very similar to those encoding residues that coordinate zinc but markedly different from those that coordinate calcium. Together, these results reveal how the traditional and auxiliary splicing motifs responded to constraints of metal coordination in proteins.
The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication
Authors: Dupont Maud , Krischuns Tim , Gianetto Quentin Giai , Paisant Sylvain , Bonazza Stefano , Brault Jean-Baptiste , Douché Thibaut , Arragain Benoît , Florez-Prada Alberto , Perez-Perri Joel I , Hentze Matthias W , Cusack Stephen , Matondo Mariette , Isel Catherine , Courtney David G , Naffakh Nadia
Published: April 2024

Genome-wide approaches have significantly advanced our knowledge of the repertoire of RNA-binding proteins (RBPs) that associate with cellular polyadenylated mRNAs within eukaryotic cells. Recent studies focusing on the RBP interactomes of viral mRNAs, notably SARS-Cov-2, have revealed both similarities and differences between the RBP profiles of viral and cellular mRNAs. However, the RBPome of influenza virus mRNAs remains unexplored. Herein, we identify RBPs that associate with the viral mRNA encoding the nucleoprotein (NP) of an influenza A virus. Focusing on TDP-43, we show that it binds several influenza mRNAs beyond the NP-mRNA, and that its depletion results in lower levels of viral mRNAs and proteins within infected cells, and a decreased yield of infectious viral particles. We provide evidence that the viral polymerase recruits TDP-43 onto viral mRNAs through a direct interaction with the disordered C-terminal domain of TDP-43. Notably, other RBPs found to be associated with influenza virus mRNAs also interact with the viral polymerase, which points to a role of the polymerase in orchestrating the assembly of viral messenger ribonucleoproteins.
BGCFlow: systematic pangenome workflow for the analysis of biosynthetic gene clusters across large genomic datasets
Authors: Nuhamunada Matin , Mohite Omkar S , Phaneuf Patrick V , Palsson Bernhard O , Weber Tilmann
Published: April 2024

Genome mining is revolutionizing natural products discovery efforts. The rapid increase in available genomes demands comprehensive computational platforms to effectively extract biosynthetic knowledge encoded across bacterial pangenomes. Here, we present BGCFlow, a novel systematic workflow integrating analytics for large-scale genome mining of bacterial pangenomes. BGCFlow incorporates several genome analytics and mining tools grouped into five common stages of analysis such as: (i) data selection, (ii) functional annotation, (iii) phylogenetic analysis, (iv) genome mining, and (v) comparative analysis. Furthermore, BGCFlow provides easy configuration of different projects, parallel distribution, scheduled job monitoring, an interactive database to visualize tables, exploratory Jupyter Notebooks, and customized reports. Here, we demonstrate the application of BGCFlow by investigating the phylogenetic distribution of various biosynthetic gene clusters detected across 42 genomes of the Saccharopolyspora genus, known to produce industrially important secondary/specialized metabolites. The BGCFlow-guided analysis predicted more accurate dereplication of BGCs and guided the targeted comparative analysis of selected RiPPs. The scalable, interoperable, adaptable, re-entrant, and reproducible nature of the BGCFlow will provide an effective novel way to extract the biosynthetic knowledge from the ever-growing genomic datasets of biotechnologically relevant bacterial species.
ChemoDOTS: a web server to design chemistry-driven focused libraries
Authors: Hoffer Laurent , Charifi-Hoareau Guillaume , Barelier Sarah , Betzi Stéphane , Miller Thomas , Morelli Xavier , Roche Philippe
Published: April 2024

In drug discovery, the successful optimization of an initial hit compound into a lead molecule requires multiple cycles of chemical modification. Consequently, there is a need to efficiently generate synthesizable chemical libraries to navigate the chemical space surrounding the primary hit. To address this need, we introduce ChemoDOTS, an easy-to-use web server for hit-to-lead chemical optimization freely available at https://chemodots.marseille.inserm.fr/. With this tool, users enter an activated form of the initial hit molecule then choose from automatically detected reactive functions. The server proposes compatible chemical transformations via an ensemble of encoded chemical reactions widely used in the pharmaceutical industry during hit-to-lead optimization. After selection of the desired reactions, all compatible chemical building blocks are automatically coupled to the initial hit to generate a raw chemical library. Post-processing filters can be applied to extract a subset of compounds with specific physicochemical properties. Finally, explicit stereoisomers and tautomers are computed, and a 3D conformer is generated for each molecule. The resulting virtual library is compatible with most docking software for virtual screening campaigns. ChemoDOTS rapidly generates synthetically feasible, hit-focused, large, diverse chemical libraries with finely-tuned physicochemical properties via a user-friendly interface providing a powerful resource for researchers engaged in hit-to-lead optimization.
Systematic identification of cargo-mobilizing genetic elements reveals new dimensions of eukaryotic diversity
Authors: Gluck-Thaler Emile , Vogan Aaron A
Published: April 2024

Cargo-mobilizing mobile elements (CMEs) are genetic entities that faithfully transpose diverse protein coding sequences. Although common in bacteria, we know little about eukaryotic CMEs because no appropriate tools exist for their annotation. For example, Starships are giant fungal CMEs whose functions are largely unknown because they require time-intensive manual curation. To address this knowledge gap, we developed starfish, a computational workflow for high-throughput eukaryotic CME annotation. We applied starfish to 2 899 genomes of 1 649 fungal species and found that starfish recovers known Starships with 95% combined precision and recall while expanding the number of annotated elements ten-fold. Extant Starship diversity is partitioned into 11 families that differ in their enrichment patterns across fungal classes. Starship cargo changes rapidly such that elements from the same family differ substantially in their functional repertoires, which are predicted to contribute to diverse biological processes such as metabolism. Many elements have convergently evolved to insert into 5S rDNA and AT-rich sequence while others integrate into random locations, revealing both specialist and generalist strategies for persistence. Our work establishes a framework for advancing mobile element biology and provides the means to investigate an emerging dimension of eukaryotic genetic diversity, that of genomes within genomes.
Effect of nutritional interventions on the psychological symptoms of premenstrual syndrome in women of reproductive age: a systematic review of randomized controlled trials
Authors: Robinson Jazz , Ferreira Amy , Iacovou Marina , Kellow Nicole J
Published: April 2024

Context

Premenstrual syndrome (PMS) affects approximately 48% of women of reproductive age worldwide. It can lead to functional impairment, lower quality of life, and decreased work productivity. Despite the availability of medical treatment options, women are seeking alternative interventions because of concerns of harmful side effects and limited evidence of efficacy associated with pharmacological treatments. To date, high-quality research investigating the effects of dietary and nutrient intervention on PMS is limited.

Objective

This systematic review investigated the effect of nutritional interventions on the psychological symptoms of PMS.

Data Sources

Five electronic databases were searched for randomized controlled trials (RCTs) published in English from inception to October 2022. Trials eligible for inclusion were nutritional intervention studies involving women of reproductive age that measured PMS-associated psychological outcomes.

Data Extraction

Articles were selected using prespecified inclusion criteria. Data screening and extraction and risk-of-bias assessments were conducted by 3 independent reviewers using article screening software and the Cochrane Risk of Bias 2 tool.

Data Analysis

Thirty-two articles reporting on 31 RCTs involving 3254 participants, ranging in age from 15 to 50 years were included and narratively reviewed. Only 1 of the included studies had a low risk of bias. Treatment with vitamin B6, calcium, and zinc consistently had significant positive effects on the psychological symptoms of PMS. There was insufficient evidence to support the effects of vitamin B1, vitamin D, whole-grain carbohydrates, soy isoflavones, dietary fatty acids, magnesium, multivitamin supplementation, or PMS-specific diets.

Conclusions

There is some evidence to support the use of nutritional interventions for improving psychological symptoms of PMS. However, more research using consistent protocols, procedures to minimize risk of bias, intention-to-treat analysis, and clearer reporting is required to provide conclusive nutritional recommendations for improving PMS-related psychological outcomes.

PROSPERO registration no

CRD42022369999.
The Case Against Human Rights Penality
Authors: Mavronicola Natasa
Published: April 2024

This article seeks to make the human rights case against human rights penality—that is, against the reliance upon and foregrounding of penal mechanisms in the protection of (certain) human rights. The rationale for the alliance between human rights and state penality has at least three central dimensions: effectiveness, accountability and equal protection. In particular, the mobilisation of criminal law (enforcement) and punishment is often treated as the most effective means of preventing and/or redressing human rights violations. Moreover, the criminal process and sanction are often understood as the pinnacle of accountability for serious human rights violations. Finally, the egalitarian rationale for human rights penality views it as redistributing protection to under-protected persons. While remaining committed to human rights, I unpack (some of) the ways in which human rights penality ultimately fails to uphold and even undermines the principles that it has been promoted as fulfilling within the human rights frame.
Introduction
Authors: Fazal Tanisha M.
Published: April 2024

This chapter introduces the reader to the topics of military medicine, veterans’ benefits, and the argument of the book: that dramatic improvements in military medicine, alongside the expansion of the veterans’ benefits system, have increased the long-term costs of war in ways that have gone underappreciated This chapter explains the choice of the US, of specific wars, and of military casualties as primary topics of the book. In addition to laying out the plan of the book, this chapter briefly reviews previous research on how the human costs of war are viewed and explains the research involved in writing the book.
From Pestilence to Penicillin
Authors: Fazal Tanisha M.
Published: April 2024

The two world wars saw significant developments in military medicine and veterans’ benefits, especially in comparison to the US Civil War. New knowledge of the germ theory of disease meant that the major cause of death in war became battle wounds rather than illness. Public reaction to the pensions of the Civil War meant that veterans’ benefits were restructured, to include rehabilitation services in World War I and educational and housing assistance as outlined in World War II’s GI Bill. As the medicine improved, more veterans took advantage of these benefits, increasing the long tail of the costs of war.
Blood Is King
Authors: Fazal Tanisha M.
Published: April 2024

The United States’ wars in Afghanistan and Iraq have seen the greatest improvement in military medicine compared to earlier military conflicts. The duration of these wars, as well as the fact that the United States had air superiority in both of them, gave military medical personnel years to develop a significant body of evidence-based research that produced dramatic shifts in evacuation and transfusion procedures. The remarkably low death rate for US military personnel, combined with further expansions of veterans’ benefits in an era of an all-volunteer force, ensured that the long tail of the costs of war continues to grow.
Creating a Civic University
Authors: Morris Peter J.T. , Reed Peter
Published: April 2024

This chapter explores Roscoe’s role in fundraising alongside Thomas Ashton, the tour of German and Swiss institutions conducted by Roscoe and Principal J. G. Greenwood, the move to Oxford Road in 1873 with buildings designed by Alfred Waterhouse (where the University of Manchester remains today), and the creation of chairs in engineering and economics, all of which transformed Owens College. The appointment of Osborne Reynolds to the new Chair of Engineering, and Stanley Jevons to the new Chair of Logic and Mental and Moral Philosophy and Political Economy, reflected Roscoe’s advocacy of a university linking academia with local commercial and manufacturing businesses. In the heated debates over university status among academics, industrialists, and parliamentarians, Roscoe’s forthright stance steered Owens College toward becoming the first college of the federal Victoria University in 1880. Roscoe was also a passionate promoter of women studying in higher education, obtaining degrees, and entering the professions.
Securing Britain’s Economic Future
Authors: Morris Peter J.T. , Reed Peter
Published: April 2024

Following the International Exhibition in Paris in 1867, concern grew in Britain about the country’s position as the world’s most advanced industrial nation, prompting the government to initiate a series of Select Committees and Royal Commissions to which Roscoe contributed. Roscoe gave evidence to the Royal Commission on Scientific Instruction and the Advancement of Science (Devonshire Commission) (1870) and the Select Committee on Scientific Instruction (Samuelson Committee) (1881). These were followed by an increasing focus on technical education, and in 1881 Roscoe was appointed to the Royal Commission on Technical Instruction (Samuelson Commission); for his services to the Samuelson Commission, Roscoe was awarded a knighthood in 1884. Unfortunately, the recommendations from these inquiries were very largely not acted upon by the government of the time.
Introduction
Authors: Gullion Jessica Smartt
Published: April 2024

This introduction begins with the author’s approach to teaching research methods. This is followed by an overview of the book chapters, and a note to instructors about how to use the book.
What Is Qualitative Research?
Authors: Gullion Jessica Smartt
Published: April 2024

Qualitative research methods treat non-numeric empirical materials as data. In other words, Qualitative researchers use words, images, sounds, video, and other data that have not been reduced to numbers to understand some research question of interest. This chapter explores what qualitative research entails and why researchers might want to employ its methods. It begins with a brief history of the emergence of qualitative inquiry. Next, the chapter addresses some of the common misconceptions about qualitative research. It then transitions to an overview of ontology (what is reality) and epistemology (how a person knows a thing) and discusses why understanding one’s own ontological and epistemological preferences is important when approaching how one conducts research. The chapter reviews the use of theory, which is followed by a discussion of decolonizing research.
Interviewing
Authors: Gullion Jessica Smartt
Published: April 2024

Interviewing is the cornerstone of most qualitative research. Researchers ask people questions and they answer them, and through that interaction researchers learn about a phenomenon of interest. This conversation is (or at least should be) largely one-sided, with the participant doing the majority of the talking. Good interviewing is a skill that can be developed, and the ability to conduct interviews well is one of the best tools researchers can have in their qualitative toolbox. This chapter discusses how to conduct interviews, different types of interviews (structured, semistructured, and unstructured), how to create a questionnaire, and tips for better interviewing.
Emerging Infections
Authors: Barrett Ron , Zuckerman Molly , Dudgeon Matthew Ryan , Armelagos George J.
Published: April 2024

This book traces the social and environmental determinants of human infectious diseases from the Paleolithic to the present day. Contrary to earlier predictions of disease eradication by the 21st Century, the world new faces outbreaks of new, virulent, and drug resistant diseases such as Ebola, COVID-19, MDRTB, and highly pathogenic influenza viruses. While many of these pathogens are novel to our species, but their primary determinants are quite ancient; they are driven by the human activities of subsistence, settlement, and social organization that have persisted throughout the last ten thousand years. Approaching these activities from a biocultural perspective, this book examines the prehistory and history of human infectious diseases. Much has happened in the decade since the first edition, with significant developments in both disease research and in the evolution of the diseases themselves. As such, this new edition has been expanded to include recent pandemics and the latest research in multiple disciplines. More than collection of disease facts, this book examines the global challenge of emerging infections from a deep-time perspective and provides it with a much-needed explanatory framework. Serving as both an accessible textbook and an original synthesis of interdisciplinary scholarship, Emerging Infections is suitable for advanced undergraduates, graduates, and researchers in the medical social sciences, public health, and the history of medicine. The book will also appeal to a more general readership with an interest in public health and infectious diseases.
Skirmishes in Princeton
Authors: Baggott Jim , Heilbron John L.
Published: April 2024

When Oppenheimer was drawn to Los Alamos, his student David Bohm stepped in to co-present his Berkeley lectures on quantum mechanics. The effort led to a textbook, which Bohm published in 1951. Although inclined towards Copenhagen teachings, he remained enough of a Marxist to explore the possibility that the radical probabilities of the theory might be removed using hidden variables. The book included a detailed analysis of the EPR experiment, cast in a much more accessible form. A subsequent encounter with Einstein at Princeton led him to become interested in whether a deterministic extension of quantum theory could be found. He rediscovered a version of the mathematically equivalent but deterministic pilot wave theory. Its hidden variables were obliged to be non-local, which caused Bohm no discomfort. But Einstein did not like it, calling it ‘too cheap’. Driven from McCarthyite America, Bohm argued his case from exile in Brazil.
Passing the Torch
Authors: Baggott Jim , Heilbron John L.
Published: April 2024

Hugh Everett III’s attention turned to foundational questions in quantum mechanics sometime in 1954 under the indirect influence of Bohr, aided by a ‘slosh or two of sherry’. He took quantum measurement for his thesis, in which he proposed to dispense entirely with von Neumann’s discontinuous, indeterministic, and irreversible ‘collapse’. Instead, the observer ‘splits’ between states, experiencing different outcomes in each. This would later become known as the ‘many worlds’ interpretation. Attempts to bring Everett’s ideas to Copenhagen met with a barrage of criticism (‘hopelessly wrong ideas’). Everett had already left academia for the Pentagon’s Weapons Systems Evaluation Group. But death was now at work among the founders, just as the ‘Sources for History of Quantum Physics’ project sought to immortalize their struggles. Two gatherings either side of 1960 confirmed that the debate was unresolved, and reopened old hostilities with voices both familiar and refreshingly new. The torch passed on.
Epilogue
Authors: Baggott Jim , Heilbron John L.
Published: April 2024

Our drama lies not only in the clash of ideas, but also in the human passions and social contexts in which the ideas were conceived, debated, refined, accepted, or rejected. Like artists and musicians, the creators of quantum mechanics approached their work with the full range of human emotions. In 2022, Clauser, Aspect, and Zeilinger were at last recognized by the Nobel institution, ‘for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science’. Their prize came exactly 100 years after those of Einstein and Bohr. Experiment moved the debate to a new level, but it has by no means removed or resolved the fundamental question. There will be no Nobel prize for an answer. That will not shut off discussion. Our drama will continue beyond our telling of it and is unlikely to reach its final scene before science ceases or the world ends.