bluuebunny/crossref_metadata_2025 huggingface dataset:
Materials screening and characterization for functional printed automotive interiors parts
Authors: Hammes Nathalia , Ribeiro Catarina , Machado Catarina , Ferreira João , Campos Ricardo , Faye Djibril , Cortez Ana , Melo Sandra , Duarte Fernando , Pontes António , Viana Júlio C , Pedrosa Paulo , Homem Natália
Published: June 2023

Flexible printed electronics (PE) has attracted strong interest during the last two decades and is one of the successful trends in material science, representing the future of PEs. This research work evaluates the use of screen-printing technology and materials for producing functional circuits for automotive interior parts, which can be subsequently processed through in-mold electronics (IME). Since the selection of the materials to build the printed system is of utmost importance, this study evaluates combinations of commercial polycarbonate substrates (LEXAN 8A13E, DE 1-4 060007 and LM 905 2-4 160009) and silver-based inks (ME603, ME604 and CP 6680), all suitable for IME. Different electrically conductive tracks varying in width and spacing (0.5, 0.3 and 0.2 mm) and two capacitive sensors were printed. Tensile tests and surface energy characterizations of the different polycarbonate substrates were carried out, then morphological, electrical, and thermoforming studies were performed on the printed substrates. Morphological characterization showed successful printing for wider lines (0.5 and 0.3 mm), but problems with screen clogging occurred for smaller line widths (0.2 mm). The electrical conductivity of printed tracks was in accordance to the printed layer thickness and ink solids percentage. The proof-of-concept of the electrical functionality was successful, when integrating the sensors into the PCB with SMD LEDs. Thermoforming showed limited functionality, with the best overall performance observed for specific combinations of substrate and ink. In essence, the results indicate that although all the selected substrates and silver-based inks have great compatibility among themselves and can be considered as materials for the production of functional automotive interior parts, there is no ideal pairing of inks and substrates. Therefore, this study emphasizes the importance of defining product specifications for a more suitable material selection.
Optical spectra of EGFR inhibitor AG-1478 for benchmarking DFT functionals
Authors: Alagawani Sallam , Vasilyev Vladislav , Wang Feng
Published: June 2023

Optical spectroscopy (UV–vis and fluorescence spectroscopy) is sensitive to the chemical environment and conformation of fluorophores and therefore, serves as an ideal probe for the conformation and solvent responses. Tyrosine kinase inhibitors (TKI) such as AG-1478 of epidermal growth factor receptor when containing a quinazolinamine scaffold are fluorophores. It is, however, very important to benchmark density functional theory (DFT) method against optical spectral measurements, when time-dependent DFT is applied. In this study, the performance of up to 22 DFT functionals is benchmarked with respect to the measured optical spectra of AG-1478 in dimethyl sulfoxide (DMSO) solvent. It is discovered when combined with the 6–311++G(d, p) basis set, there are top seven functionals; B3PW91, B3LYP, B3P86, PBE1PBE, APFD, HSEH1PBE, and N12SX DFT-VXC functionals are identified as the top performers. Becke’s three-parameter exchange functional (B3) tends to generate accurate optical spectra to form the best three functionals, B3LYP, B3PW91 and B3P86. Specifically, B3PW91 was recommended for studying the optical properties of 4-quinazolinamine TKIs, B3LYP was found to be excellent for absorption spectrum, while B3P86 was identified as the best for emission spectrum. Any further corrections to B3LYP, such as CAM-B3LYP, LC-B3LYP, and B3LYP-D3 result in larger errors in the optical spectra of AG-1478 in DMSO solvent. These best three (B3Vc) functionals are reliable tools for optical properties of the TKIs and therefore the design of new agents with larger Stokes shift for medical image applications. To obtain reliable optical spectra for this class of 4-quinazolinamine based TKIs, it is important to include the electron correlation energy.
Infinite neural network quantum states: entanglement and training dynamics
Authors: Luo Di , Halverson James
Published: June 2023

We study infinite limits of neural network quantum states (

∞

-NNQS), which exhibit representation power through ensemble statistics, and also tractable gradient descent dynamics. Ensemble averages of entanglement entropies are expressed in terms of neural network correlators, and architectures that exhibit volume-law entanglement are presented. The analytic calculations of entanglement entropy bound are tractable because the ensemble statistics are simplified in the Gaussian process limit. A general framework is developed for studying the gradient descent dynamics of neural network quantum states (NNQS), using a quantum state neural tangent kernel (QS-NTK). For

∞

-NNQS the training dynamics is simplified, since the QS-NTK becomes deterministic and constant. An analytic solution is derived for quantum state supervised learning, which allows an

∞

-NNQS to recover any target wavefunction. Numerical experiments on finite and infinite NNQS in the transverse field Ising model and Fermi Hubbard model demonstrate excellent agreement with theory.

∞

-NNQS opens up new opportunities for studying entanglement and training dynamics in other physics applications, such as in finding ground states.
Multivariate spatiotemporal functional principal component analysis for modeling hospitalization and mortality rates in the dialysis population
Authors: Qian Qi , Nguyen Danh V , Telesca Donatello , Kurum Esra , Rhee Connie M , Banerjee Sudipto , Li Yihao , Senturk Damla
Published: June 2023

Dialysis patients experience frequent hospitalizations and a higher mortality rate compared to other Medicare populations, in whom hospitalizations are a major contributor to morbidity, mortality, and healthcare costs. Patients also typically remain on dialysis for the duration of their lives or until kidney transplantation. Hence, there is growing interest in studying the spatiotemporal trends in the correlated outcomes of hospitalization and mortality among dialysis patients as a function of time starting from transition to dialysis across the United States Utilizing national data from the United States Renal Data System (USRDS), we propose a novel multivariate spatiotemporal functional principal component analysis model to study the joint spatiotemporal patterns of hospitalization and mortality rates among dialysis patients. The proposal is based on a multivariate Karhunen–Loéve expansion that describes leading directions of variation across time and induces spatial correlations among region-specific scores. An efficient estimation procedure is proposed using only univariate principal components decompositions and a Markov Chain Monte Carlo framework for targeting the spatial correlations. The finite sample performance of the proposed method is studied through simulations. Novel applications to the USRDS data highlight hot spots across the United States with higher hospitalization and/or mortality rates and time periods of elevated risk.
430 Comparison of effectiveness of topical treatments for atopic dermatitis
Authors: Uddin Sabiha , Upchurch Britton , Chandy Rithi J , Feldman Steven R
Published: June 2023

Atopic dermatitis (AD) is a chronic inflammatory condition that affects 15% of children and 7.3% of adults in the USA. While topical corticosteroids (TCs) and topical calcineurin inhibitors (TCIs) are considered the mainstay of topical treatments for AD management, long-term use is cautioned due to possible adverse effects (AEs). We present and review the efficacy and safety of new FDA-approved topical agents, topical agents currently in clinical trials, and TCs and TCIs that are currently available for AD management. We also present and compare the safety and efficacy of new and old FDA-approved topical agents, along with other topical treatments that are currently in clinical trials for AD management. An extensive review of the literature was performed using the PubMed, Cochrane, Scopus and ClinicalKey databases with year parameters set between 2014 and 2022. Search keywords included ‘atopic dermatitis’, ‘topical treatments’, ‘comparison’, ‘effectiveness’, ‘new topical treatments for AD’, ‘JAK inhibitors’, ‘PDE-4 inhibitors’, ‘delgocitinib’, ‘crisaborole’ and ‘tapinarof’. We identified four topical drug classes that are efficacious in treating AD: corticosteroids, calcineurin inhibitors, phosphodiesterase-4 (PDE-4) inhibitors and aryl hydrocarbon receptor agonists. Criteria for treatment success were an IGA score of 0 or 1 and improvement ≥2 grades from baseline. Treatment varied among studies from 2 to 24 weeks. Topical corticosteroids were the most effective after adjusting for vehicle (0.05% clobetasol propionate emulsion foam, 38%; 0.1% clocortolone pivalate, 31.6% IGA reduction), followed by tapinarof 1% cream with 29% of patients achieving treatment success, TCIs (0.03% tacrolimus ointment, 24.8%; 1% pimecrolimus cream, 32.1% vehicle-adjusted achieving IGA of ≤2) and PDE-4 inhibitors (2% crisaborole ointment, 10.4%). Tapinarof was the most efficacious in treating AD. There is a lack of head-to-head trials for topical treatments for AD. Due to the tremendous burden of AD on patients’ physical and mental health, there is a need for additional therapies.
435 Burden of disease and unmet needs in the diagnosis and management of atopic dermatitis in the Middle East
Authors: Mahmoud Omar , Attia Enas , Yosipovitch Gil
Published: June 2023

Atopic dermatitis (AD) affects diverse ethnic groups with significant disparities in prevalence, disease progression, clinical outcomes and access to care. There are limited data on AD in the Middle East, yet there is a substantial economic and psychosocial burden of AD in this region with a large unmet need with regards to disease management that is critical to address. There is a trend of increasing prevalence of AD in the Middle East; however, due to the large environmental, socioeconomic, and sociocultural heterogeneity of this region, prevalence varies greatly across and within countries. Similarly, clinical differences in disease presentations exist across the Middle East, although regional data ared limited. We will present clinical phenotypes of AD common in different regions of the Middle East, data on prevalence, genetic variations and challenges of treatment. Further studies exploring molecular biomarkers, genetic polymorphisms, immune factors and the microbiome of patients in the Middle East will help to elucidate the mechanism behind ethnic differences in AD in this population as well as to help understand treatment response and susceptibilities.
Physicochemical homeostasis in bacteria
Authors: Poolman Bert
Published: June 2023

In living cells, the biochemical processes such as energy provision, molecule synthesis, gene expression, and cell division take place in a confined space where the internal chemical and physical conditions are different from those in dilute solutions. The concentrations of specific molecules and the specific reactions and interactions vary for different types of cells, but a number of factors are universal and kept within limits, which we refer to as physicochemical homeostasis. For instance, the internal pH of many cell types is kept within the range of 7.0 to 7.5, the fraction of macromolecules occupies 15%–20% of the cell volume (also known as macromolecular crowding) and the ionic strength is kept within limits to prevent salting-in or salting-out effects. In this article we summarize the generic physicochemical properties of the cytoplasm of bacteria, how they are connected to the energy status of the cell, and how they affect biological processes (Fig. 1). We describe how the internal pH and proton motive force are regulated, how the internal ionic strength is kept within limits, what the impact of macromolecular crowding is on the function of enzymes and the interaction between molecules, how cells regulate their volume (and turgor), and how the cytoplasm is structured. Physicochemical homeostasis is best understood in Escherichia coli, but pioneering studies have also been performed in lactic acid bacteria.
The effect of climate on the occurrence and abundance of tree recruitment in the province of Quebec, Canada
Authors: Fortin Mathieu , Power Hugues , Van Couwenberghe Rosalinde , Eskelson Bianca N I
Published: June 2023

Tree recruitment is affected by numerous biotic and abiotic factors, including climate. However, the relative importance of climate variables in empirical models of tree recruitment remains to be evaluated. We fitted models of tree recruitment to 26 species in the province of Quebec, Canada. For a better understanding of the recruitment process, we used a two-part model to distinguish recruitment occurrence from abundance. The relative importance of the different variables was assessed using Akaike weights. Our main hypothesis was that climate is one of the major drivers of tree recruitment. Our results showed that growing degree-days counted among the major drivers of recruitment occurrence but not of recruitment abundance. Stand variables, such as the presence and abundance of adult trees of the species, and broadleaved and coniferous basal areas were found to be relatively more important than all the climate variables for both recruitment occurrence and abundance. Species occupancy within a 10-km radius also had a significant effect on recruitment occurrence for two-thirds of the species, but it was less important than growing degree-days and other stand variables. Climate change is expected to improve the suitability of habitats located at the northern edge of species distributions. However, our model predictions point to a low probability of colonization in newly suitable habitats in the short term.
Partial Harvest Effects on the Forest Floor at Four Northern Hardwood Sites in the Green Mountains of Vermont, USA
Authors: Ross Donald S , Knowles Meghan E
Published: June 2023

Harvesting activities are known to decrease forest floor carbon pools, but the response varies with harvest intensity. We examined partial harvesting (33–55% of basal area removed) effects on the forest floor at four northern hardwood sites in Vermont, USA. Six baseline quantitative samples were taken at each site and 9–36 new locations were sampled 1.5–2.6 years after harvesting. Forest soil disturbance was estimated, and basal area was tallied pre- and post-harvest. The forest floor consisted primarily of Oi and Oe horizons. The pre-harvest site means in carbon stock ranged from 6.8 to 12.3 Mg ha-1 and were not significantly different after harvesting. The pre-harvest site means in depth ranged from 2.8 to 4.5 cm and, post-harvest, there was significantly decreased thickness at one site and significantly greater density at two sites postharvest. This compaction was also visually observed in the field. Partial harvesting, which included single-tree and group selection, created highly variable conditions that challenged our experimental design. However, the two sites with the higher number of resampling locations (35–36) had relatively low variability in forest floor metrics and showed significant responses in thickness and density. Continued monitoring is needed to determine long-term trends.
Sex estimation from virtual models: exploring the potential of stereolithic 3D crania models for morphoscopic trait scoring
Authors: Robles Madeline , Carew Rachael M , Rando Carolyn , Nakhaeizadeh Sherry , Morgan Ruth M
Published: June 2023

Modern computed tomography (CT) databases are becoming an accepted resource for the practice and development of identification methods in forensic anthropology. However, the utility of 3D models created using free and open-source visualization software such as 3D Slicer has not yet been thoroughly assessed for morphoscopic biological profiling methods where virtual methods of analysis are becoming more common. This paper presents a study that builds on the initial findings from Robles et al. (2020) to determine the feasibility of estimating sex on stereolithic (STL) 3D cranial models produced from CT scans from a modern, living UK population (n = 80) using equation 2 from the Walker’s (2008) morphoscopic method. Kendall’s coefficients of concordance (KCC) indicated substantial agreement using cranial features scores in an inter-observer test and a video-inter-observer test. Fleiss’ Kappa scores showed moderate agreement (0.50) overall between inter-observer sex estimations, and for observer sex estimations in comparison to recorded sexes (0.56). It was found that novice users could virtually employ morphoscopic sex estimation methods effectively on STL 3D cranial models from modern individuals. This study also highlights the potential that digital databases of modern living populations can offer forensic anthropology.

Key points
Chromosome-scale genome assembly of the rusty patched bumble bee, Bombus affinis (Cresson) (Hymenoptera: Apidae), an endangered North American pollinator
Authors: Koch Jonathan Berenguer Uhuad , Sim Sheina B , Scheffler Brian , Geib Scott M , Smith Tamara A
Published: June 2023

The rusty patched bumble bee, Bombus affinis, is an important pollinator in North America and a federally listed endangered species. Due to habitat loss and large declines in population size, B. affinis is facing imminent extinction unless human intervention and recovery efforts are implemented. To better understand B. affinis biology and population genetic and genomic landscapes, we sequenced and assembled the B. affinis genome from a single haploid male. Whole genome HiFi sequencing on PacBio coupled with HiC sequencing resulted in a complete and highly contiguous contig assembly that was scaffolded into a chromosomal context, resolving 18 chromosomes distributed across the 365.1 Mb assembly. All material for both HiFi and HiC sequencing was derived from a single abdominal tissue segment from the single male. These assembly results, coupled with the minimal amount of tissue destructively sampled, demonstrate methods for generating contiguous and complete genomic resources for a rare and endangered species with limited material available and highlight the importance of sample preservation. Precise methods and applications of these methods are presented for potential applications in other species with similar limitations in specimen availability and curation considerations.
Transcriptomic approach to uncover dynamic events in the development of mid-season sunburn in apple fruit
Authors: Waite Jessica M , Kelly Elizabeth A , Zhang Huiting , Hargarten Heidi L , Waliullah Sumyya , Altman Naomi S , dePamphilis Claude W , Honaas Loren A , Kalcsits Lee
Published: June 2023

Apples grown in high heat, high light, and low humidity environments are at risk for sun injury disorders like sunburn and associated crop losses. Understanding the physiological and molecular mechanisms underlying sunburn will support improvement of mitigation strategies and breeding for more resilient varieties. Numerous studies have highlighted key biochemical processes involved in sun injury, such as the phenylpropanoid and reactive oxygen species (ROS) pathways, demonstrating both enzyme activities and expression of related genes in response to sunburn conditions. Most previous studies have focused on at-harvest activity of a small number of genes in response to heat stress. Thus, it remains unclear how stress events earlier in the season affect physiology and gene expression. Here, we applied heat stress to mid-season apples in the field and collected tissue along a time course—24, 48, and 72 h following a heat stimulus—to investigate dynamic gene expression changes using a transcriptomic lens. We found a relatively small number of differentially expressed genes (DEGs) and enriched functional terms in response to heat treatments. Only a few of these belonged to pathways previously described to be involved in sunburn, such as the AsA–GSH pathway, while most DEGs had not yet been implicated in sunburn or heat stress in pome fruit.
Clonal reproduction of Moniliophthora roreri and the emergence of unique lineages with distinct genomes during range expansion
Authors: Minio Andrea , Figueroa-Balderas Rosa , Cohen Stephen P , Ali Shahin S , Carriel Denny , Britto Dahyana , Stack Conrad , Baruah Indrani K , Marelli Jean-Philippe , Cantu Dario , Bailey Bryan A
Published: June 2023

The basidiomycete Moniliophthora roreri causes frosty pod rot of cacao (Theobroma cacao) in the western hemisphere. Moniliophthora roreri is considered asexual and haploid throughout its hemibiotrophic life cycle. To understand the processes driving genome modification, using long-read sequencing technology, we sequenced and assembled 5 high-quality M. roreri genomes out of a collection of 99 isolates collected throughout the pathogen's range. We obtained chromosome-scale assemblies composed of 11 scaffolds. We used short-read technology to sequence the genomes of 22 similarly chosen isolates. Alignments among the 5 reference assemblies revealed inversions, translocations, and duplications between and within scaffolds. Isolates at the front of the pathogens' expanding range tend to share lineage-specific structural variants, as confirmed by short-read sequencing. We identified, for the first time, 3 new mating type A locus alleles (5 in total) and 1 new potential mating type B locus allele (3 in total). Currently, only 2 mating type combinations, A1B1 and A2B2, are known to exist outside of Colombia. A systematic survey of the M. roreri transcriptome across 2 isolates identified an expanded candidate effector pool and provided evidence that effector candidate genes unique to the Moniliophthoras are preferentially expressed during the biotrophic phase of disease. Notably, M. roreri isolates in Costa Rica carry a chromosome segment duplication that has doubled the associated gene complement and includes secreted proteins and candidate effectors. Clonal reproduction of the haploid M. roreri genome has allowed lineages with unique genome structures and compositions to dominate as it expands its range, displaying a significant founder effect.
Exploring regression dilution bias using repeat measurements of 2858 variables in ≤49 000 UK Biobank participants
Authors: Rutter Charlotte E , Millard Louise A C , Borges Maria Carolina , Lawlor Deborah A
Published: June 2023

Background

Measurement error in exposures and confounders can bias exposure–outcome associations but is rarely considered. We aimed to assess random measurement error of all continuous variables in UK Biobank and explore approaches to mitigate its impact on exposure–outcome associations.

Methods

Random measurement error was assessed using intraclass correlation coefficients (ICCs) for all continuous variables with repeat measures. Regression calibration was used to correct for random error in exposures and confounders, using the associations of red blood cell distribution width (RDW), C-reactive protein (CRP) and 25-hydroxyvitamin D [25(OH)D] with mortality as illustrative examples.

Results

The 2858 continuous variables with repeat measures varied in sample size from 109 to 49 121. They fell into three groups: (i) baseline visit [529 variables; median (interquartile range) ICC = 0.64 (0.57, 0.83)]; (ii) online diet by 24-h recall [22 variables; 0.35 (0.30, 0.40)] and (iii) imaging measures [2307 variables; 0.85 (0.73, 0.94)]. Highest ICCs were for anthropometric and medical history measures, and lowest for dietary and heart magnetic resonance imaging.

The ICCs (95% confidence interval) for RDW, CRP and 25(OH)D were 0.52 (0.51, 0.53), 0.29 (0.27, 0.30) and 0.55 (0.54, 0.56), respectively. Higher RDW and levels of CRP were associated with higher risk of all-cause mortality, and higher concentration of 25(OH)D with lower risk. After correction for random measurement error in the main exposure, the associations all strengthened. Confounder correction did not influence estimates.

Conclusions

Random measurement error varies widely and is often non-negligible. For UK Biobank we provide relevant statistics and adaptable code to help other researchers explore and correct for this.
Punching before the Bell Rings: United Nations Signaling and Pre-Deployment Violence in Civil Wars
Authors: Kathman Jacob D , Benson Michelle , Diehl Paul F
Published: June 2023

In the post-Cold War era, United Nations (UN) peacekeeping has been an effective civil conflict mitigation tool. On the path to peacekeeping, the UN Security Council often signals its growing likelihood to deploy an operation by passing resolutions addressing the conflict. How do these signals affect violence levels in a pre-operation environment? We posit that conflict actors have incentives to improve their relative positions through violence as the UN signals its likelihood to intervene. Using a new dataset that links UNSC resolutions to active civil wars from 1989 to 2014, we find that resolution passage is significantly related to an increase in combatant use of anti-civilian violence. Additionally, as the signal strengthens with the passage of a greater number of resolutions, violence increases. Thus, although deployed peacekeeping operations may effectively protect non-combatants, the process leading to deployment can produce a dangerous environment for civilians.
When are International Organizations Responsive to Policy Problems?
Authors: Lundgren Magnus , Tallberg Jonas , Sommerer Thomas , Squatrito Theresa
Published: June 2023

When are international organizations (IOs) responsive to the policy problems that motivated their establishment? While it is a conventional assumption that IOs exist to address transnational challenges, the question of whether and when IO policy-making is responsive to shifts in underlying problems has not been systematically explored. This study investigates the responsiveness of IOs from a large-n, comparative approach. Theoretically, we develop three alternative models of IO responsiveness, emphasizing severeness, dependence, and power differentials. Empirically, we focus on the domain of security, examining the responsiveness of eight multi-issue IOs to armed conflict between 1980 and 2015, using a novel and expansive dataset on IO policy decisions. Our findings suggest, first, that IOs are responsive to security problems and, second, that responsiveness is not primarily driven by dependence or power differentials but by problem severity. An in-depth study of the responsiveness of the UN Security Council using more granular data confirms these findings. As the first comparative study of whether and when IO policy adapts to problem severity, the article has implications for debates about IO responsiveness, performance, and legitimacy.
Increasing prevalence of designer benzodiazepines in impaired driving: A 5-year analysis from 2017 to 2021
Authors: Papsun Donna M , Chan-Hosokawa Ayako , Lamb Michael E , Logan Barry
Published: June 2023

Designer benzodiazepine (DBZD) use has been increasing over the past decade and poses a threat to human health and safety, particularly when involved in driving under the influence of drug (DUID) cases. Over a 5-year period between 2017 and 2021, there were 1,145 reported DBZDs in 805 blood samples submitted from law enforcement agencies for DUID testing. Eleven different DBZDs were detected, including three metabolite pairs: etizolam/alpha-hydroxyetizolam, clonazolam/8-aminoclonazolam, diclazepam/delorazepam, flualprazolam, flubromazolam, flubromazepam, bromazolam and bromazepam. Etizolam/alpha-hydroxyetizolam (n = 485) and flualprazolam (n = 149) were the most frequently detected DBZDs, at 60% and 18%, respectively. Driving behavior, standardized field sobriety test performance and physical observations of individuals suspected of DUIDs, whose blood sample was toxicologically confirmed for one or more DBZDs, were consistent with the effects caused by central nervous system depressants. Each DBZD has its own unique timeline, and toxicology testing had to be frequently updated to reflect the state of the novel psychoactive substance market. DBZDs play a role in impaired driving and can be the sole intoxicant in DUID cases.
Significant UK Environmental Law Cases 2022–23
Authors: Helme Ned , Boukraa Adam , David Stephanie , Leydon Eleanor
Published: June 2023

This case law overview comments on significant UK environmental law cases for the period 1 April 2022–31 March 2023. It begins with an overarching introduction, which draws some general themes from our selection of cases, focussing on the scope of environmental law, connections between private and public law disputes, and the standard of review in the public law context. It then addresses 12 significant cases concerning statutory trusts over land under section 164 of the Public Health Act 1875 and section 10 of the Open Spaces Act 1906, public rights on Dartmoor Commons, private nuisance, climate change, insurance, environmental impact assessment, delay in judicial review, forestry, contaminated land, and habitats. It ends with some final thoughts on this year’s cases and the year ahead.
Mycotoxin tolerance affects larval competitive ability in Drosophila recens (Diptera: Drosophilidae)
Authors: Kokate Prajakta P , Werner Thomas
Published: June 2023

Certain mycophagous Drosophila species are the only known eukaryotes that can tolerate some highly potent mycotoxins. This association between mycophagy and mycotoxin tolerance is well established because Drosophila species that switch hosts from mushrooms to other food sources lose their mycotoxin tolerance trait without any evolutionary lag. These findings suggest that mycotoxin tolerance may be a costly trait to maintain. In this study, we attempted to identify whether mycotoxin tolerance has a fitness cost. Larval competitive ability is a vital fitness trait, especially in holometabolous insects, where the larvae cannot move to a new host. Furthermore, larval competitive ability is known to be associated with many critical life-history traits. Here we studied whether mycotoxin tolerance adversely affects larval competitive ability on isofemale lines from 2 distinct locations. We observed that the extent of mycotoxin tolerance affected larval competitive ability, but only in isofemale lines from one location. Additionally, we observed that the high mycotoxin-tolerant isofemale lines from the same location showed poor survival to eclosion. This study shows that mycotoxin tolerance is associated with fitness costs and provides preliminary evidence of an association between local adaptation and mycotoxin tolerance.
Group dynamics and activity patterns of two dolphin species, the Common Dolphin (Delphinus delphis) and Dusky Dolphin (Lagenorhynchus obscurus) in direct sympatry
Authors: Curcio Nadia Soledad , Svendsen Guillermo Martin , Bartes Saia , Romero Maria Alejandra , Arias Magdalena , González Raúl Alberto , Dans Silvana Laura
Published: June 2023

Co-occurrence of species with similar ecological requirements could bring individual advantages, but when resources are scarce, co-occurring species would segregate to reduce competition and thus enable coexistence. We studied co-occurrence, group dynamics, and activity budgets, along with the seasonal and diel variation, of two sympatric species: the Common Dolphin (Delphinus delphis) and Dusky Dolphin (Lagenorhynchus obscurus), in Northern Patagonia, Argentina. Dolphin groups were recorded by nautical surveys between 2006 and 2018, and classified the groups by their constituent species (single- or multispecies groups), group size, age/sex composition, predominant activity, season, and time block. Frequencies were arranged in contingency tables and analyzed by log-linear models. Activity bout duration also was recorded by focal-group follows and compared using nonparametric tests. Single- and multispecies groups’ occurrence varied throughout the year, with a period of high co-occurrence in spring and summer, when both species and most of multispecies groups were present, and a period of low co-occurrence, when mostly common dolphins remained in the area. Common dolphins occur in groups of more than a hundred while dusky dolphins do so in groups of 50 animals at most. Feeding time budget was higher in Dusky Dolphin single- and multispecies groups. Common dolphins showed a seasonal and diurnal pattern in activity budget. During the period of high co-occurrence, dusky dolphins’ group size showed a diurnal pattern, and both species increased their feeding time budgets, a putative indication of more favorable foraging conditions. During this period, dusky dolphins associate occasionally in multispecies groups, increasing feeding time budget and feeding bouts duration, suggesting that the association between the two species is beneficial.
Bioethics: Shaping Medical Practice and Taking Diversity Seriously
Authors: Cherry Mark J
Published: June 2023

Bioethics functions within a world of deep moral pluralism; a universe of discourse debating ethical analysis, public policy, and clinical practice in which a common, generally accepted morality does not exist. While religious thinkers are often approached within a hermeneutic of suspicion for assuming moral standards that cannot be justified in rational terms, secular bioethicists routinely find themselves in exactly the same intellectual predicament. That ethical theory, proposed values, or normative content is secular, that it does not invoke God or any particular religious perspective, does not mean that it is rationally grounded, necessarily true, or universally binding. As the authors in this issue of The Journal of Medicine and Philosophy make clear, this normative reality directly impacts debates regarding concepts of health, illness, and disease, accounts of socially acceptable health-risky behaviors, and the political frameworks that shape public policy. As a result, honest discussion of diverse moral, religious, and political perspectives remains essential in clarifying the intellectual challenges, ethical intuitions, and ideological judgments that shape clinical practice and healthcare policy. Depending on which moral, political, or scientific concepts are guiding bioethical analysis, careful scrutiny will tend to support rather different policies and practices, each of which is likely to be worth careful consideration.
The Ancestral Shape of the Access Proton Path of Mitochondrial ATP Synthases Revealed by a Split Subunit-a
Authors: Wong Jonathan E , Zíková Alena , Gahura Ondřej
Published: June 2023

The passage of protons across membranes through F1Fo-ATP synthases spins their rotors and drives the synthesis of ATP. While the principle of torque generation by proton transfer is known, the mechanisms and routes of proton access and release and their evolution are not fully understood. Here, we show that the entry site and path of protons in the lumenal half channel of mitochondrial ATP synthases are largely defined by a short N-terminal α-helix of subunit-a. In Trypanosoma brucei and other Euglenozoa, the α-helix is part of another polypeptide chain that is a product of subunit-a gene fragmentation. This α-helix and other elements forming the proton pathway are widely conserved across eukaryotes and in Alphaproteobacteria, the closest extant relatives of mitochondria, but not in other bacteria. The α-helix blocks one of two proton routes found in Escherichia coli, resulting in a single proton entry site in mitochondrial and alphaproteobacterial ATP synthases. Thus, the shape of the access half channel predates eukaryotes and originated in the lineage from which mitochondria evolved by endosymbiosis.
Prognostic nutritional index as an indicator for the development of bone fragility fracture in patients with rheumatoid arthritis
Authors: Yoshii Ichiro , Sawada Naoya , Chijiwa Tatsumi
Published: June 2023

Objectives

The validity of prognostic nutritional index (PNI) as an index of incident bone fragility fracture (inc-BFF) in rheumatoid arthritis (RA) patients was investigated.

Methods

RA patients whom continuously followed up for >3 years were picked up. Patients were classified in accordance with inc-BFF positivity (BFF+ and BFF−). Their clinical background including PNI was statistically examined for inc-BFF. The background factors were compared between the two groups. Patients were narrowed into subgroups according to the factor that showed a significant difference between the two groups, and they were statistically examined according to the PNI for the inc-BFF. The two groups were narrowed with propensity score matching and compared to the PNI.

Results

A total of 278 patients with 44 BFF+ and 234 BFF− were recruited. In the background factors, the presence of prevalent BFF and the simplified disease activity index remission rate had a significantly higher risk ratio. In a subgroup who comorbid lifestyle-related diseases, PNI had a significantly higher risk ratio for the inc-BFF. After the propensity score matching, the PNI showed no significant difference between the two groups.

Conclusions

PNI is available when patients with RA comorbid lifestyle-related diseases. PNI is not an independent key for the inc-BFF in RA patients.
Precise characterization of somatic complex structural variations from tumor/control paired long-read sequencing data with nanomonsv
Authors: Shiraishi Yuichi , Koya Junji , Chiba Kenichi , Okada Ai , Arai Yasuhito , Saito Yuki , Shibata Tatsuhiro , Kataoka Keisuke
Published: June 2023

We present our novel software, nanomonsv, for detecting somatic structural variations (SVs) using tumor and matched control long-read sequencing data with a single-base resolution. The current version of nanomonsv includes two detection modules, Canonical SV module, and Single breakend SV module. Using tumor/control paired long-read sequencing data from three cancer and their matched lymphoblastoid lines, we demonstrate that Canonical SV module can identify somatic SVs that can be captured by short-read technologies with higher precision and recall than existing methods. In addition, we have developed a workflow to classify mobile element insertions while elucidating their in-depth properties, such as 5′ truncations, internal inversions, as well as source sites for 3′ transductions. Furthermore, Single breakend SV module enables the detection of complex SVs that can only be identified by long-reads, such as SVs involving highly-repetitive centromeric sequences, and LINE1- and virus-mediated rearrangements. In summary, our approaches applied to cancer long-read sequencing data can reveal various features of somatic SVs and will lead to a better understanding of mutational processes and functional consequences of somatic SVs.
Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Advanced, Refractory Biliary Tract Carcinoma
Authors: Tella Sri Harsha , Foster Nathan , Qian Shi , Nguyen Tran , Borad Mitesh J , McWilliams Robert R , Alberts Steven R , Wee Ma Wen , Chakrabarti Sakti , Fruth Briant , Wessling Jaclynn , Hartgers Mindy , Washburn Leslie , Fernandez-Zapico Martin E , Hogenson Tara L , Pitot Henry , Jin Zhaohui , Mahipal Amit
Published: June 2023

Background

We sought to determine the safety and efficacy of trifluridine/tipiracil in combination with irinotecan in a phase II trial setting for refractory, advanced unresectable biliary tract carcinoma (BTC).

Methods

A total of 28 patients (27 were evaluable) with advanced BTCs who progressed on at least one prior systemic therapy were enrolled and were treated with trifluridine/tipiracil 25 mg/m2 (days 1-5 of 14-day cycle) and irinotecan 180 mg/m2 (day 1 of the 14-day cycle). The primary endpoint for the study was 16-week progression-free survival (PFS16) rate. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were pre-specified secondary endpoints.

Results

Of 27 patients, PFS16 rate was 37% (10/27; 95% CI: 19%-58%), thereby meeting the criteria for success for the primary endpoint. The median PFS and OS of the entire cohort were 3.9 months (95% CI: 2.5-7.4) and 9.1 months (95% CI: 8.0-14.3), respectively. In the patients evaluable for tumor response (n = 20), the ORR and DCR were 10% and 50%, respectively. Twenty patients (74.1%) had at least one grade 3 or worse adverse event (AE), and 4 patients (14.8%) had grade 4 AEs. A total of 37% (n = 10/27) and 51.9% (n = 14/27) experienced dose reductions in trifluridine/tipiracil and irinotecan, respectively. Delay in therapy was noted in 56% of the patients while 1 patient discontinued the therapy, primarily due to hematologic AEs.

Conclusion

The combination of trifluridine/tipiracil plus irinotecan is a potential treatment option for patients with advanced, refractory BTCs with good functional status and no targetable mutations. A larger randomized trial is needed to confirm these results. (ClinicalTrials.gov Identifier: NCT04072445)
Therapeutic Responses to Combination Nivolumab and Temozolomide as Salvage Therapy for Metastatic Melanoma: A Case Series
Authors: Goodman Rachel S , Jung Seungyeon , Quintos Jessica , Johnson Douglas B
Published: June 2023

The management of metastatic melanoma patients that fail multiple lines of systemic therapy remains a significant challenge. There is limited literature regarding combination of anti-PD-1 and temozolomide, or of other chemotherapy agents, in melanoma. Here, we present a series of 3 patients with metastatic melanoma and their responses to nivolumab and temozolomide combination therapy after progression on several local/regional therapies, combination immune checkpoint inhibitors, and/or targeted therapies. The novel combinatory strategy led to remarkable responses in all 3 patients shortly after initiating treatment with tumor remission and symptomatic improvement. The first patient has had ongoing response 15 months after initiating treatment, although he has since discontinued temozolomide due to intolerance. The remaining 2 patients show ongoing response after 4 months, with good tolerability. This case series suggests that nivolumab and temozolomide may be a promising option in the setting of advanced melanoma refractory to standard treatments, and warrants further investigation in larger series.
The Field of Offerings or Field of Reeds
Authors: Álvarez Sosa Milagros
Published: June 2023

The study of the vignettes of the Book of the Dead is a field that has not often been investigated until recently. Its uniqueness lies in the long “lifespan” of its illustrations, which extends over a time frame that allows us to the iconographic variations they underwent. The chapter focuses on the iconographic analysis of vignette 110, which represents the so-called Field of Reeds, Field of Offerings, or Field of Hotep as it appears on papyri, where it is chiefly attested. By comparison, our study will go back to earlier periods: from its first literary texts dating from the Old Kingdom until its first iconographic representation on the coffins of the Middle Kingdom, its standardization with the appearance of the Book of the Dead during the New Kingdom, and the variation of its image until the Ptolemaic Period. The fact that our study covers a very wide span of time allows us to investigate the processes of development that this image and, by extension, the Book of the Dead underwent in the course of its transmission.
The Book of the Dead in Tombs
Authors: Einaudi Silvia
Published: June 2023

The Book of the Dead spells began to be written on tomb walls in the Eighteenth Dynasty, in accordance with the contemporary increasing diffusion of this corpus of funerary texts. The great majority of tombs (private and royal) decorated with BD spells and/or vignettes are in the Theban necropolis and they date mainly to the Ramesside period (Nineteenth Dynasty in particular). At this time, some spells appear to be especially preferred, such as BD 1, 17, 59, 74, 110, 125, and 146. The presence of BD spells on tomb walls decreased first slowly, toward the end of the Twentieth Dynasty and then, drastically, in the Third Intermediate Period, for which only a few cases are known in the necropolises of Tanis and Saqqara. A sort of “revival” in the use of the Book of the Dead for tomb decoration is attested at Thebes in the Late Period, as an aspect of the tendency to display the archaism typical of the Twenty-fifth to Twenty-sixth Dynasties. In fact, the monumental tombs of the high officials in the Assasif necropolis show numerous BD spells on their walls, often arranged in long sequences that reflect, to a great extent, the canonical Saite recension of the Book of the Dead. The use of BD spells in tombs continued sporadically throughout the Ptolemaic and Roman Periods, for which some examples in Atfih, Tuna el-Gebel, Qaw el-Kebir, Akhmim, Hu, and the oases of Siwa and Dakhleh are attested.
Translating the Book of the Dead
Authors: Backes Burkhard
Published: June 2023

When translating texts from the Book of the Dead, one is confronted with multiple challenges, most of which are common to the greater part of, if not all ancient Egyptian texts. The article therefore starts with an overview of the main issues to be considered when rendering texts, especially religious texts, from ancient Egyptian into a modern language. In addition to this, some aspects are of special relevance when dealing with the Book of the Dead. Among these is the problem of variation (e.g., synchronic vs. diachronic, mistakes vs. “true” variants): To what extent should alternative readings be indicated? Can there be a translation of “the” Book of the Dead at all? Different approaches with their respective advantages and weak points are explored, resulting in some programmatic suggestions.
The Book of the Ba
Authors: Kucharek Andrea
Published: June 2023

The modern title Book of the Ba designates a funerary composition known exclusively from Akhmim. Based on prosopographical and iconographical evidence, the papyri can be dated to the Ptolemaic Period, most likely the third century BCE. The text itself most likely originated in the New Kingdom. Only two copies of the Book of the Ba, each attached to a Book of the Dead papyrus, are extant. The eight spells and four vignettes of the composition focus on the ba, the bird-shaped, mobile manifestation of the deceased. While its layout, texts, and vignettes are unique, the Book of the Ba is in several ways closely related to the Book of the Dead.
The Funerary Literature Related to the Book of the Dead
Authors: Scalf Foy
Published: June 2023

The Egyptian Book of the Dead had not been produced and transmitted in a literary vacuum. Many other funerary compositions were being created, copied, and inspired by the Book of the Dead, as well as influencing it. New funerary literature continued to flourish in ancient Egypt even after the rise of the Book of the Dead, beginning with the Netherworld Books of the New Kingdom and ending with the Demotic documents for Breathing in the Roman Period. The material attests to the sustained vitality and creativity alive within the priesthood for a period of over 1500 years. At the end of the tradition, the number of Book of the Dead manuscripts being produced decreases in favor of manuscripts compiled from a multiplicity of sources, some of the most common of which were the Books of Breathing, the Book of Traversing Eternity, and glorification spells, along with lamentations, liturgies, and decrees.
Spell 1 of the Book of the Dead and Its Vignette
Authors: Tawfik Tarek Sayed
Published: June 2023

This chapter provides an overview of a central text and vignette of the Book of the Dead corpus. In fact it is so important that it generally opens the papyri of the New Kingdom as well as of the Late Period and which also occurs on tomb walls until the Late and Greco-Roman Periods. The text will be compared with the vignette of the spell showing the funerary procession and funerary rites performed for the mummy at the tomb. The text, however, is a text recited by the deceased himself and describing the deceased in a self-presentation in her or his mythical existence. Furthermore this chapter analyzes the scene of the funeral depicted in the vignette in detail, and in relation to similar funerary procession scenes depicted in tombs.