bluuebunny/crossref_metadata_2025 huggingface dataset:
The proposed Code of Conduct for Research in South Africa: despite good progress, unresolved issues remain
Authors: Gooden Amy , Thaldar Donrich
Published: February 2024

After a 3-year development process and several drafts, the Academy of Science of South Africa (ASSAf) has submitted its proposed Code of Conduct for Research (proposed CCR) to the South African Information Regulator for its consideration and approval. When approved, the proposed CCR will be an important legal instrument that will complement the Protection of Personal Information Act 4 of 2013 (POPIA) in governing research activity in the country—including data sharing by South African researchers with their collaborators in other countries. The proposed CCR resolves important issues that were present in previous drafts. However, three important issues require attention: (1) how the identifiability of data subjects is to be determined in research data; (2) how research data can be repurposed for commercial use; and (3) how open access genomic databases should be established in the South African legal framework. In addition, the proposed CCR introduces a new issue: a legally unsustainable exception from POPIA application for genetic data. All these issues considered, the proposed CCR needs revision ahead of its approval by the Information Regulator. Recommendations are made on how to resolve the remaining issues.
Exploring low-carbon and sustainable urban transformation design using ChatGPT and artificial bee colony algorithm
Authors: Yu Shuhui , Yang Ya , Li Jiamin , Guo Keyu , Wang Zeyu , Liu Yuwei
Published: February 2024

The aim of this study is to provide effective solutions to promote the transition of resource-based cities to low carbon and sustainable development. Firstly, this study investigates the background of low-carbon transformation of resource-based cities. Secondly, it introduces the application method of Chat Generative Pre-trained Transformer (ChatGPT) in detail. Finally, this study proposes a comprehensive application of ChatGPT and artificial bee colony (ABC) algorithm. The results show that the average energy utilization efficiency improvement index of the group using ChatGPT is 0.11. The average energy efficiency improvement index of the group using ABC algorithm is 0.02 higher than that of the control group. The integrated application of ChatGPT and ABC algorithm can further improve the low-carbon transformation effect of resource-based cities and achieve the goal of green development.
Primary and secondary care service use and costs associated with frailty in an ageing population: longitudinal analysis of an English primary care cohort of adults aged 50 and over, 2006–2017
Authors: Fogg Carole , England Tracey , Zhu Shihua , Jones Jeremy , de Lusignan Simon , Fraser Simon D S , Roderick Paul , Clegg Andy , Harris Scott , Brailsford Sally , Barkham Abigail , Patel Harnish P , Walsh Bronagh
Published: February 2024

Background

Frailty becomes more prevalent and healthcare needs increase with age. Information on the impact of frailty on population level use of health services and associated costs is needed to plan for ageing populations.

Aim

To describe primary and secondary care service use and associated costs by electronic Frailty Index (eFI) category.

Design and Setting

Retrospective cohort using electronic health records. Participants aged ≥50 registered in primary care practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre, 2006–2017.

Methods

Primary and secondary care use (totals and means) were stratified by eFI category and age group. Standardised 2017 costs were used to calculate primary, secondary and overall costs. Generalised linear models explored associations between frailty, sociodemographic characteristics. Adjusted mean costs and cost ratios were produced.

Results

Individual mean annual use of primary and secondary care services increased with increasing frailty severity. Overall cohort care costs for were highest in mild frailty in all 12 years, followed by moderate and severe, although the proportion of the population with severe frailty can be expected to increase over time. After adjusting for sociodemographic factors, compared to the fit category, individual annual costs doubled in mild frailty, tripled in moderate and quadrupled in severe.

Conclusions

Increasing levels of frailty are associated with an additional burden of individual service use. However, individuals with mild and moderate frailty contribute to higher overall costs. Earlier intervention may have the most potential to reduce service use and costs at population level.
Gradualism, bifurcation and fading qualia
Authors: Sebastián Miguel Ángel , Martínez Manolo
Published: February 2024

When reasoning about dependence relations, philosophers often rely on gradualist assumptions, according to which abrupt changes in a phenomenon of interest can result only from abrupt changes in the low-level phenomena on which it depends. These assumptions, while strictly correct if the dependence relation in question can be expressed by continuous dynamical equations, should be handled with care: very often the descriptively relevant property of a dynamical system connecting high- and low-level phenomena is not its instantaneous behaviour but its stable fixed points (those in the vicinity of which it spends most of the time, after comparatively short transitory periods), and stable fixed points can change abruptly as a result of infinitesimal changes of the low-level phenomenon. We illustrate this potential gradualist trap by showing that Chalmers’ fading qualia argument falls into it.
Network propagation for GWAS analysis: a practical guide to leveraging molecular networks for disease gene discovery
Authors: Visonà Giovanni , Bouzigon Emmanuelle , Demenais Florence , Schweikert Gabriele
Published: February 2024

Motivation

Genome-wide association studies (GWAS) have enabled large-scale analysis of the role of genetic variants in human disease. Despite impressive methodological advances, subsequent clinical interpretation and application remains challenging when GWAS suffer from a lack of statistical power. In recent years, however, the use of information diffusion algorithms with molecular networks has led to fruitful insights on disease genes.

Results

We present an overview of the design choices and pitfalls that prove crucial in the application of network propagation methods to GWAS summary statistics. We highlight general trends from the literature, and present benchmark experiments to expand on these insights selecting as case study three diseases and five molecular networks. We verify that the use of gene-level scores based on GWAS P-values offers advantages over the selection of a set of ‘seed’ disease genes not weighted by the associated P-values if the GWAS summary statistics are of sufficient quality. Beyond that, the size and the density of the networks prove to be important factors for consideration. Finally, we explore several ensemble methods and show that combining multiple networks may improve the network propagation approach.
SynergyX: a multi-modality mutual attention network for interpretable drug synergy prediction
Authors: Guo Yue , Hu Haitao , Chen Wenbo , Yin Hao , Wu Jian , Hsieh Chang-Yu , He Qiaojun , Cao Ji
Published: February 2024

Discovering effective anti-tumor drug combinations is crucial for advancing cancer therapy. Taking full account of intricate biological interactions is highly important in accurately predicting drug synergy. However, the extremely limited prior knowledge poses great challenges in developing current computational methods. To address this, we introduce SynergyX, a multi-modality mutual attention network to improve anti-tumor drug synergy prediction. It dynamically captures cross-modal interactions, allowing for the modeling of complex biological networks and drug interactions. A convolution-augmented attention structure is adopted to integrate multi-omic data in this framework effectively. Compared with other state-of-the-art models, SynergyX demonstrates superior predictive accuracy in both the General Test and Blind Test and cross-dataset validation. By exhaustively screening combinations of approved drugs, SynergyX reveals its ability to identify promising drug combination candidates for potential lung cancer treatment. Another notable advantage lies in its multidimensional interpretability. Taking Sorafenib and Vorinostat as an example, SynergyX serves as a powerful tool for uncovering drug-gene interactions and deciphering cell selectivity mechanisms. In summary, SynergyX provides an illuminating and interpretable framework, poised to catalyze the expedition of drug synergy discovery and deepen our comprehension of rational combination therapy.
On the core segmentation algorithms of copy number variation detection tools
Authors: Zhang Yibo , Liu Wenyu , Duan Junbo
Published: February 2024

Shotgun sequencing is a high-throughput method used to detect copy number variants (CNVs). Although there are numerous CNV detection tools based on shotgun sequencing, their quality varies significantly, leading to performance discrepancies. Therefore, we conducted a comprehensive analysis of next-generation sequencing-based CNV detection tools over the past decade. Our findings revealed that the majority of mainstream tools employ similar detection rationale: calculates the so-called read depth signal from aligned sequencing reads and then segments the signal by utilizing either circular binary segmentation (CBS) or hidden Markov model (HMM). Hence, we compared the performance of those two core segmentation algorithms in CNV detection, considering varying sequencing depths, segment lengths and complex types of CNVs. To ensure a fair comparison, we designed a parametrical model using mainstream statistical distributions, which allows for pre-excluding bias correction such as guanine-cytosine (GC) content during the preprocessing step. The results indicate the following key points: (1) Under ideal conditions, CBS demonstrates high precision, while HMM exhibits a high recall rate. (2) For practical conditions, HMM is advantageous at lower sequencing depths, while CBS is more competitive in detecting small variant segments compared to HMM. (3) In case involving complex CNVs resembling real sequencing, HMM demonstrates more robustness compared with CBS. (4) When facing large-scale sequencing data, HMM costs less time compared with the CBS, while their memory usage is approximately equal. This can provide an important guidance and reference for researchers to develop new tools for CNV detection.
Are brake response times altered post CT-guided cervical spine nerve root injections?
Authors: Hanley Marion , Eustace Sarah K , Ryan David T , McLoughlin Stephen , Hynes John P , Kavanagh Eoin C , Eustace Stephen J
Published: February 2024

Objectives

To assess if brake response times are altered pre and post CT-guided cervical spine nerve root injections.

Methods

Brake response times were assessed before and after CT-guided cervical spine nerve root injections in a cohort of patients. The average of 3 brake response times was recorded before and 30 min after injection. Statistical analysis was performed using GraphPad. A paired Student t-test was used to compare the times before and after the injections.

Results

Forty patients were included in this study. The mean age was 55 years. There were 17 male and 23 female patients. There was no significant difference in the mean pre and post CT-guided cervical spine nerve root injection brake response times; 0.94 s (range 0.4-1.2 s) and 0.93 s (range 0.5-1.25 s), respectively (P = .77).

Conclusions

Brake response time did not significantly differ pre and 30 min post CT-guided cervical spine nerve root injections.

Advances in knowledge

To the authors’ best knowledge, there are no current studies assessing brake response times post CT-guided cervical spine nerve root injections. While driving safety cannot be proven by a single metric, it is a useful study in demonstrating that this is not inhibited in a cohort of patients.
Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis
Authors: White Yasmine N , Solans Belen P , Denti Paolo , van der Laan Louvina E , Schaaf H Simon , Vonasek Bryan , Malik Amyn A , Draper Heather R , Hussain Hamidah , Hesseling Anneke C , Garcia-Prats Anthony J , Savic Radojka M
Published: February 2024

Background

Each year 25 000–32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children.

Methods

Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)–recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses.

Results

Data from 242 children (2.8 years [0.2–16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16–33 mg/kg for dispersible tablets or 16–50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax.

Conclusions

Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.
A metagenomic alpha-diversity index for microbial functional biodiversity
Authors: Finn Damien R
Published: February 2024

Alpha-diversity indices are an essential tool for describing and comparing biodiversity. Microbial ecologists apply indices originally intended for, or adopted by, macroecology to address questions relating to taxonomy (conserved marker) and function (metagenome-based data). In this Perspective piece, I begin by discussing the nature and mathematical quirks important for interpreting routinely employed alpha-diversity indices. Secondly, I propose a metagenomic alpha-diversity index (MD) that measures the (dis)similarity of protein-encoding genes within a community. MD has defined limits, whereby a community comprised mostly of similar, poorly diverse protein-encoding genes pulls the index to the lower limit, while a community rich in divergent homologs and unique genes drives it toward the upper limit. With data acquired from an in silico and three in situ metagenome studies, I derive MD and typical alpha-diversity indices applied to taxonomic (ribosomal rRNA) and functional (all protein-encoding) genes, and discuss their relationships with each other. Not all alpha-diversity indices detect biological trends, and taxonomic does not necessarily follow functional biodiversity. Throughout, I explain that protein Richness and MD provide complementary and easily interpreted information, while probability-based indices do not. Finally, considerations regarding the unique nature of microbial metagenomic data and its relevance for describing functional biodiversity are discussed.
Benchmarking Algorithms for Gene Set Scoring of Single-cell ATAC-seq Data
Authors: Wang Xi , Lian Qiwei , Dong Haoyu , Xu Shuo , Su Yaru , Wu Xiaohui
Published: February 2024

Gene set scoring (GSS) has been routinely conducted for gene expression analysis of bulk or single-cell RNA sequencing (RNA-seq) data, which helps to decipher single-cell heterogeneity and cell type-specific variability by incorporating prior knowledge from functional gene sets. Single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) is a powerful technique for interrogating single-cell chromatin-based gene regulation, and genes or gene sets with dynamic regulatory potentials can be regarded as cell type-specific markers as if in single-cell RNA-seq (scRNA-seq). However, there are few GSS tools specifically designed for scATAC-seq, and the applicability and performance of RNA-seq GSS tools on scATAC-seq data remain to be investigated. Here, we systematically benchmarked ten GSS tools, including four bulk RNA-seq tools, five scRNA-seq tools, and one scATAC-seq method. First, using matched scATAC-seq and scRNA-seq datasets, we found that the performance of GSS tools on scATAC-seq data was comparable to that on scRNA-seq, suggesting their applicability to scATAC-seq. Then, the performance of different GSS tools was extensively evaluated using up to ten scATAC-seq datasets. Moreover, we evaluated the impact of gene activity conversion, dropout imputation, and gene set collections on the results of GSS. Results show that dropout imputation can significantly promote the performance of almost all GSS tools, while the impact of gene activity conversion methods or gene set collections on GSS performance is more dependent on GSS tools or datasets. Finally, we provided practical guidelines for choosing appropriate preprocessing methods and GSS tools in different application scenarios.
The Artistic Use Defence in Trademark Dilution Cases – Hermès’ Legal Setback in Its Attempt to Prevent Others from Using Its Iconic Birkin Handbag
Authors: Duhanic Ines
Published: February 2024

This opinion explores what constitutes a trademark parody in an artistic context and when it crosses the line of trademark infringement in dilution cases which occur beyond the traditional trademark protection from the likelihood of confusion. This is shown by analysing the latest two decisions regarding trademark parody handed down by the German Frankfurt am Main Regional Court in a case in which Hermès has suffered a setback in its attempt to prevent a fashion label from using its iconic Birkin handbag at the Berlin fashion show in 2023.

While parody is considered a protected form of speech or artistic expression, no clear-cut legal rule separates a legitimate parody from an infringing use, in particular in cases of so-called mixed expressions where the reference to the protected trademark is not closely tied to commercial use but still happens outside of a purely artistic context. Compared to the statutory copyright’s flexible fair use defence, there is simply too little case law available to draw on in trademark dilution law. The few rigid defences German courts have cobbled together in trademark cases illustrate that trademark could benefit from a clearer identification of use categories. The following analysis of these decisions aims at highlighting that urgent trademark reforms are necessary in the area of art-related fair use defences. Furthermore, the following analysis will illustrate how big corporations like Hermès can fail when attempting to use trademark rights to control the meaning not only of wealth and exclusivity but also of conspicuous consumption and the equally conspicuous display of wealth, status and power in male-dominated domains.
Using a Computational Cognitive Model to Understand Phishing Classification Decisions of Email Users
Authors: Shonman Matthew , Shi Xiaoyu , Kang Mingqing , Wang Zuo , Li Xiangyang , Dahbura Anton
Published: February 2024

Numerous studies of human user behaviours in cybersecurity tasks have used traditional research methods, such as self-reported surveys or empirical experiments, to identify relationships between various factors of interest and user security performance. This work takes a different approach, applying computational cognitive modelling to research the decision-making of cybersecurity users. The model described here relies on cognitive memory chunk activation to analytically simulate the decision-making process of a user classifying legitimate and phishing emails. Suspicious-seeming cues in each email are processed by examining similar, past classifications in long-term memory. We manipulate five parameters (Suspicion Threshold, Maximum Cues Processed, Weight of Similarity, Flawed Perception Level, Legitimate-to-Phishing Email Ratio in long-term memory) to examine their effects on accuracy, email processing time and decision confidence. Furthermore, we have conducted an empirical, unattended study of US participants performing the same task. Analyses on the empirical study data and simulation output, especially clustering analysis, show that these two research approaches complement each other for more insightful understanding of this phishing detection task. The analyses also demonstrate several limitations of this computational model that cannot easily capture certain user types and phishing detection strategies, calling for a more dynamic and sophisticated model construction.
Current Practice and Variation in Same-Day Services in Breast Imaging: A Multi-Institutional National Survey of the Society of Breast Imaging Membership
Authors: Dontchos Brian N , Dodelzon Katerina , Sonnenblick Emily , Reig Beatriu , Coffey Kristen , Kacharia Vidhi S , Grimm Lars J
Published: February 2024

Objective

The availability of same-day services in breast imaging is an important topic given potential advantages for timely diagnoses and patient experiences, but there are potential barriers that lead facilities to not offer these services. We sought to understand current practice patterns and radiologist perspectives on offering same-day services.

Methods

The Society of Breast Imaging (SBI) Patient Care & Delivery Committee developed a 19-question survey that was emailed to all 3449 active members of the SBI in May 2023. An exemption from the institutional review board was obtained at the lead author’s institution. The survey consisted of 19 questions that were designed to understand the scope, perceptions, barriers, and logistics of same-day services. Comparisons were made between responses for offering same-day services (screening interpretation, diagnostic examinations, biopsies) and respondent demographics.

Results

A total of 437 American and Canadian members participated, yielding a response rate of 12.7%. Respondents were most commonly in private practice (43.0%, 188/437), working in an outpatient medical center–based clinic (41.9%, 183/437), and without trainees (64.5%, 282/437). Respondents estimated 12.1% of screening examinations were interpreted while patients waited, which was significantly more common in free-standing breast imaging clinics (P = .028) and practices without trainees (P = .036). Respondents estimated 15.0% of diagnostic examinations were performed same day, which was more common in academic and private practices (P = .03) and practices without trainees (P = .01). Respondents estimated 11.5% of biopsies were performed the same day as the recommendation, which had no association with practice type/context, presence of trainees, number of mammography units, number of radiologists, or number of technologists. Long patient travel distance and limited patient mobility were the most cited reasons for offering patients same-day services.

Conclusion

Offering same-day breast imaging services varies among institutions and may be influenced by factors such as practice context and type and the presence of trainees.
Brochosome size variation and its influence on leafhopper (Hemiptera: Cicadellidae) wing wettability
Authors: Bello Elizabeth , Alleyne Marianne
Published: February 2024

Insect wing surfaces have nano- and microscale features that enable multi-functionality. Leafhoppers (Hemiptera: Cicadellidae) are unique in that they produce and excrete nanoscale particles, called brochocosomes, that are spread onto the integument by the insect. Brochosomes are extra-cuticular, removable, and make the integument both superhydrophobic and anti-reflective, 2 greatly desired properties in engineering and material science fields. Adaptations like this have captured the interest of researchers looking to draw inspiration from the natural world to create novel solutions and optimize current technologies. Here, we compare brochosome size and wettability across 8 species of leafhoppers using scanning electron microscopy and microgoniometry. We demonstrate that brochosome size is variable within species and that size and wettability are both significantly impacted by species. We report the extent of variability in each case and examine the relationship between brochosome size, body length, and hydrophobicity. In discussing potential applications for brochosomes, we comment on an emerging and rapid analysis technique for evaluating small biological particles. Additionally, we discuss a few recent brochosome-inspired designs and comment on important considerations. Our work provides valuable insight on a unique system that can guide the design of functionalized materials with enhanced hydrophobic and self-cleaning properties.
Unraveling biotypes of the northern house mosquito, Culex pipiens s.l. (Diptera: Culicidae): molecular differentiation and morphometric analysis
Authors: Alvial Ingrid E , Hernández-P Raquel , Suazo Manuel J , González Christian R , Véliz David , Benítez Hugo A
Published: February 2024

Geometric morphometrics was used to determine whether geographic isolation could explain differences in wing size and shape between and within continental (27°S to 41°S) and insular (Rapa Nui) populations of Culex pipiens s.s. Linnaeus and their biotypes (f. pipiens and f. molestus). Molecular protocols based on polymorphisms in the second intron of nuclear locus ace-2 (acetylcholinesterase-2) were used to differentiate Cx. pipiens s.s. from Cx. quinquefasciatus Say, and an assay based on polymorphisms in the flanking region of a microsatellite locus (CQ11) was used to identify biotypes. Culex pipiens f. molestus and hybrids shared larval habitats in all continental sites, while Cx. pipiens f. pipiens was found in 5 of the 10 sites. Only biotype molestus was found in Rapa Nui (Easter Island) Pipiens and molestus biotypes occur sympatrically in aboveground locations, and only molestus was found in the underground site (ME). Biotype molestus was dominant in rural locations and preferably anthropophilic. These results agree with the ecological descriptions previously reported for the biotypes of Cx. pipiens s.s. Procrustes ANOVA only showed differences in centroid size between biotypes in females and males and did not show significant differences in wing shape. However, we found significant differences among the geographic areas in the centroid size and wing shape of both females and males. Particularly, the population of Rapa Nui Island had shorter wings than the continental populations. The results highlight the effects of geographic and environmental processes on morphotypes in vector mosquitoes.
Effects of hormone receptor status on patient clinic and survival in HER2 positive breast cancer
Authors: Yılmaz Mukaddes , Erdiş Eda , Uçar Mahmut , Demir Necla , Alandağ Celal , Yücel Birsen
Published: February 2024

Background

In the current study, the effect of hormone receptor (HR) status on clinical and survival in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer was investigated.

Methods

Two hundred ninety-one patients with HER2- positive were examined in two categories as HR-positive and HR-negative.

Results

Of these, 197 (68%) were HR-positive and 94 (32%) were HR-negative with a mean follow-up period of 68 ± 2.7 months. The groups were found to be similar in terms of age, menopausal status, comorbidity, pathologic type, stage, T stage, N stage, lymphovascular invasion, presence and percentage of intraductal component, multicentricity/focality and extracapsular invasion. Family history (P = 0.038), stage 2 tumor rate (P < 0.001), and perineural invasion (P = 0.005) were significantly higher in the HR-positive group. In the HR-negative group, mean Ki-67 value (P = 0.014), stage 3 tumor rate (P < 0.001), tumor necrosis (P = 0.004) and strong (3+) HER2 staining on immunohistochemical staining (P = 0.003) were higher. The incidence of relapse and metastasis, and the localization of metastasis were similar in both patient groups. The rate of locoregional relapse during the first 2 years was higher in the HR-negative patients than in the HR-positive patients (P = 0.023). Overall survival (OS) and disease-free survival (DFS) did not differ between the groups in univariate analysis. However, HR status was determined as an independent prognostic factor (HR: 2.11, 95% CI: 1.17–3.79; P = 0.012) for OS was not found to be significant for DFS in multivariate analysis.

Conclusion

Both clinicopathologic features and OS outcomes of HR-negative patients were worse than those of HR-positive patients.
Life history data of a Triatoma protracta nahuatlae, T. sinaloensis, and their laboratory hybrids (Hemiptera: Reduviidae)
Authors: Martínez-Ibarra José Alejandro , Grant-Guillén Yunuen , Nogueda-Torres Benjamín , Meraz-Medina Tzintli , Martínez-Grant Diana Monserrat
Published: February 2024

Chagas disease is one of the most significant vector-borne diseases in Mexico. The presence of “sylvatic” triatomine vectors of Trypanosoma cruzi (Chagas) inside human dwellings necessitates estimating their vectorial capacity. To estimate this capacity in Triatoma protracta nahuatlae (Ryckman), Triatoma sinaloensis (Ryckman), and their laboratory hybrids, 6 biological parameters were examined. Triatoma sinaloensis exhibited the shortest development time (155 days), with a median of 12 blood meals. Mortality rates varied from 35% to 45% in the 3 studied cohorts. All 3 cohorts were aggressive, initiating feeding within 0.5–1 min, and had similar feeding periods ranging from 10 to 18 min. A majority (75.3–97.9%) of the hybrids defecated when feeding, immediately after feeding, or in less than 1 min post-feeding. In contrast, only 7–42% of nymphs of T. sinaloensis defecated during the same period. Our results regarding the 6 parameters studied confirm the potential role of T. p. nahuatlae as an efficient vector of T. cruzi. Triatoma sinaloensis, on the other hand, exhibited limited vectorial capacity primarily due to its poor defecation behavior. Continued surveillance of these “sylvatic” triatomine populations is necessary to prevent an epidemiological problem.
Current and future potential distribution of Culex (Melanoconion) (Diptera: Culicidae) of public health interest in the Neotropics
Authors: Laurito Magdalena , Arias-Alzate Andrés
Published: February 2024

Anthropogenic activities are altering ecosystem stability and climate worldwide, which is disturbing and shifting arbovirus vector distributions. Although the overall geographic range of some epidemiologically important species is recognized, the spatiotemporal variation for other species in the context of climate change remains poorly understood. Here we predict the current potential distribution of 9 species of Culex (Melanoconion) based on an ecological niche modeling (ENM) approach and assess spatiotemporal variation in future climate change in the Neotropics. The most important environmental predictors were the mean temperature of the warmest season (27 °C), precipitation during the driest month (50 mm), and precipitation during the warmest season (>200 mm). The best current model for each species was transferred to the future general circulation model IPSL-CM6A-LR, using 2 shared socioeconomic pathway scenarios (ssp1-2.6, ssp5-8.5). Under both scenarios of climatic change, an expansion of suitable areas can be observed followed by a strong reduction for the medium–long future under the worst scenario. The multivariate environmental similarity surface analysis indicated future novel climates outside the current range. However, none of the species would occur in those areas. Even if many challenges remain in improving methods for forecasting species responses to global climate change and arbovirus transmission, ENM has strong potential to be applied to the geographic characterization of these systems. Our study can be used for the monitoring of Culex (Melanoconion) species populations and their associated arboviruses, contributing to develop region-specific public health surveillance programs.
YHWH as a Woman in Labour: The Controlled Pregnant Female Body in Labour
Authors: Langton Karen
Published: February 2024

In the Hebrew Bible, there are 14 similes of a woman in labour. Thirteen of these similes describe a crisis in which the uncontrollable pregnant female body is used to depict death, crisis, destruction, and even annihilation. However, when YHWH is like a woman in labour (Isa. 42:14), the pregnant body in labour is described as controlled, restrained, and, one could say, desirous. Rather than interpret this image in light of the simile of YHWH as a warrior in the preceding verse (Isa. 42:13), I argue that the image is purposefully in opposition. Rather than a display of warrior-like strength, YHWH as a woman in labour is calm and controlled. To support my argument, I look at the simile through the lens of the experience of the female body. Using examples of women in labour in ancient texts and current women’s narratives, I show how ancient writers draw upon the pregnant female bodily experience of being in labour to communicate YHWH’s complete control over humanity’s relationship with him.
Exploring the origin of the distance bimodality of stars in the periphery of the Small Magellanic Cloud with APOGEE and Gaia
Authors: Almeida Andres , Majewski Steven R , Nidever David L , Olsen Knut A G , Monachesi Antonela , Kallivayalil Nitya , Hasselquist Sten , Choi Yumi , Povick Joshua T , Wilson John C , Geisler Doug , Lane Richard R , Nitschelm Christian , Sobeck Jennifer S , Stringfellow Guy S
Published: February 2024

The Magellanic Cloud system represents a unique laboratory for study of both interacting dwarf galaxies and the ongoing process of the formation of the Milky Way and its halo. We focus on one aspect of this complex, three-body interaction – the dynamical perturbation of the Small Magellanic Cloud (SMC) by the Large Magellanic Cloud (LMC), and specifically potential tidal effects on the SMC’s eastern side. Using Gaia astrometry and the precise radial velocities (RVs) and multielement chemical abundances from Apache Point Observatory Galactic Evolution Experiment (APOGEE-2) Data Release 17, we explore the well-known distance bimodality on the eastern side of the SMC. Through estimated stellar distances, proper motions, and RVs, we characterize the kinematics of the two populations in the bimodality and compare their properties with those of SMC populations elsewhere. Moreover, while all regions explored by APOGEE seem to show a single chemical enrichment history, the metallicity distribution function (MDF), of the ‘far’ stars on the eastern periphery of the SMC is found to resemble that for the more metal-poor fields of the western periphery, whereas the MDF for the ‘near’ stars on the eastern periphery resembles that for stars in the SMC Centre. The closer eastern periphery stars also show RVs (corrected for SMC rotation and bulk motion) that are, on average, approaching us relative to all other SMC populations sampled. We interpret these trends as evidence that the near stars on the eastern side of the SMC represent material pulled out of the central SMC as part of its tidal interaction with the LMC.
Probing the magnetic field and dust grain properties of two dark clouds L1495 and L1498 through photopolarimetry
Authors: Choudhury G B , Goswami B , Das H S , Medhi B J , Pandey J C
Published: February 2024

We present the R-band polarimetry of two low-latitude Lynd’s clouds L1495 and L1498 acquired with AIMPOL at Aryabhatta Research Institute of Observational Sciences, Nainital, India. The estimated polarization across the regions of L1495 and L1498 is typically in the range of ∼1–5 per cent and the position angle is typically in the range of ∼100°–137° from which we infer the morphologies of the corresponding magnetic field in the envelope region ($\theta_{\rm B}^{\rm env}$). In both clouds, the magnetic fields are found to be aligned with the galactic field (θGP). Due to their close proximity to the galactic plane, we incorporate the values of offset ($\theta _{\rm off} = |\theta _{\rm B}^{\rm env} - \theta _{\rm GP}|$) from this study into our previously established geometrical correlation between the variation in relative orientation with the galactic longitude. We find that the offsets estimated for two clouds L1495 and L1498 in this investigation are consistent with the offsets predicted by our previous study. We also generate the extinction map for the two clouds using the NICE technique, and the extinction structure is found to be analogous to the dust structure at the denser region of the cloud as obtained from the 500 µm dust continuum emission maps of Herschel1 SPIRE. Three distinct cores with high extinction are detected in L1495, and two such cores are also detected in L1498. We also estimate the mean particle density ($\lt n_{\rm H_2}\gt $) at the peripheral region as well as the high extinction cores of the clouds.
Doppler signature of a possible termination shock in an off-limb solar flare
Authors: French Ryan J , Yu Sijie , Chen Bin , Shen Chengcai , Matthews Sarah A
Published: February 2024

We report striking Doppler velocity gradients observed during the well-observed 2017 September 10 solar flare, and argue that they are consistent with the presence of an above-the-looptop termination shock beneath the flare current sheet. Observations from the Hinode Extreme-ultraviolet Imaging Spectrometer measure plasma sheet Doppler shifts up to 35 km s−1 during the late-phase of the event. By comparing these line-of-sight flows with plane-of-sky (POS) measurements, we calculate total velocity downflows of 200+ km s−1, orientated ≈6–10° out of the POS. The observed velocities drop rapidly at the base of the hot plasma sheet seen in extreme ultraviolet, consistent with simulated velocity profiles predicted by our 2.5D magnetohydrodynamics model that features a termination shock at the same location. Finally, the striking velocity deceleration aligns spatially with the suppression of Fe xxiv non-thermal velocities, and a 35–50 keV hard X-ray looptop source observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager. Together, these observations are consistent with the presence of a possible termination shock within the X8.2-class solar flare.
Calcium complexation by steroids involved in the steroidogenesis
Authors: Siless Gastón E , Cabrera Gabriela M
Published: February 2024

Steroids that take part in the pathways of human steroidogenesis are involved in many biological mechanisms where they interact with calcium. In the present work, the binding selectivities and affinities for calcium of progestagens, mineralocorticoids, androstagens, and estrogens were studied by Electrospray Ionization-Mass Spectrometry (ESI-MS). The adduct profile of each steroid was characterized by high resolution and tandem mass spectrometry. The relative stability of the most important adducts was studied by threshold collision induced dissociation, E1/2. Doubly-charged steroid-calcium complexes [nM + Ca]2+ with n = 1–6 were predominant in the mass spectra. The adduct [5M + Ca]2+ was the base peak for most 3-keto-steroids, while ligands bearing hindered ketones or α-hydroxy-ketones also yielded [nM + Ca + mH2O]2+ with n = 3–4 and m = 0–1. Principal component analysis allowed us to spot the main differences and similarities in the binding behavior of these steroids. The isomers testosterone and dehydroepiandrosterone, androstanolone and epiandrosterone, and 17-α-hydroxyprogesterone and 11-deoxycorticosterone showed remarkable differences in their adduct profiles. Computational modeling of representative adducts was performed by density functional theory methods. The possible binding modes at low and high numbers of steroid ligands were determined by calcium Gas Phase Affinity, and through modeling of the complexes and comparison of their relative stabilities, in agreement with the experimental results.
An evolutionarily conserved phosphoserine-arginine salt bridge in the interface between ribosomal proteins uS4 and uS5 regulates translational accuracy in Saccharomyces cerevisiae
Authors: Joshi Kartikeya , Luisi Brooke , Wunderlin Grant , Saleh Sima , Lilly Anna , Okusolubo Temiloluwa , Farabaugh Philip J
Published: February 2024

Protein-protein and protein–rRNA interactions at the interface between ribosomal proteins uS4 and uS5 are thought to maintain the accuracy of protein synthesis by increasing selection of cognate aminoacyl-tRNAs. Selection involves a major conformational change—domain closure—that stabilizes aminoacyl-tRNA in the ribosomal acceptor (A) site. This has been thought a constitutive function of the ribosome ensuring consistent accuracy. Recently, the Saccharomyces cerevisiae Ctk1 cyclin-dependent kinase was demonstrated to ensure translational accuracy and Ser238 of uS5 proposed as its target. Surprisingly, Ser238 is outside the uS4-uS5 interface and no obvious mechanism has been proposed to explain its role. We show that the true target of Ctk1 regulation is another uS5 residue, Ser176, which lies in the interface opposite to Arg57 of uS4. Based on site specific mutagenesis, we propose that phospho-Ser176 forms a salt bridge with Arg57, which should increase selectivity by strengthening the interface. Genetic data show that Ctk1 regulates accuracy indirectly; the data suggest that the kinase Ypk2 directly phosphorylates Ser176. A second kinase pathway involving TORC1 and Pkc1 can inhibit this effect. The level of accuracy appears to depend on competitive action of these two pathways to regulate the level of Ser176 phosphorylation.
Nucleotide-level distance metrics to quantify alternative splicing implemented in TranD
Authors: Nanni Adalena , Titus-McQuillan James , Bankole Kinfeosioluwa S , Pardo-Palacios Francisco , Signor Sarah , Vlaho Srna , Moskalenko Oleksandr , Morse Alison M , Rogers Rebekah L , Conesa Ana , McIntyre Lauren M
Published: February 2024

Advances in affordable transcriptome sequencing combined with better exon and gene prediction has motivated many to compare transcription across the tree of life. We develop a mathematical framework to calculate complexity and compare transcript models. Structural features, i.e. intron retention (IR), donor/acceptor site variation, alternative exon cassettes, alternative 5′/3′ UTRs, are compared and the distance between transcript models is calculated with nucleotide level precision. All metrics are implemented in a PyPi package, TranD and output can be used to summarize splicing patterns for a transcriptome (1GTF) and between transcriptomes (2GTF). TranD output enables quantitative comparisons between: annotations augmented by empirical RNA-seq data and the original transcript models; transcript model prediction tools for longread RNA-seq (e.g. FLAIR versus Isoseq3); alternate annotations for a species (e.g. RefSeq vs Ensembl); and between closely related species. In C. elegans, Z. mays, D. melanogaster, D. simulans and H. sapiens, alternative exons were observed more frequently in combination with an alternative donor/acceptor than alone. Transcript models in RefSeq and Ensembl are linked and both have unique transcript models with empirical support. D. melanogaster and D. simulans, share many transcript models and long-read RNAseq data suggests that both species are under-annotated. We recommend combined references.
RPA interacts with Rad52 to promote meiotic crossover and noncrossover recombination
Authors: Joo Jeong H , Hong Soogil , Higashide Mika T , Choi Eui-Hwan , Yoon Seobin , Lee Min-Su , Kang Hyun Ah , Shinohara Akira , Kleckner Nancy , Kim Keun P
Published: February 2024

Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3′ single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.
Unraveling the complex relationship between mRNA and protein abundances: a machine learning-based approach for imputing protein levels from RNA-seq data
Authors: Prabahar Archana , Zamora Ruben , Barclay Derek , Yin Jinling , Ramamoorthy Mahesh , Bagheri Atefeh , Johnson Scott A , Badylak Stephen , Vodovotz Yoram , Jiang Peng
Published: February 2024

The correlation between messenger RNA (mRNA) and protein abundances has long been debated. RNA sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq-identified gene signatures directly to protein changes. In this study, we utilized a set of 17 widely assessed immune and wound healing mediators in the context of canine volumetric muscle loss to investigate the correlation of mRNA and protein abundances. Our data reveal an overall agreement between mRNA and protein levels on these 17 mediators when examining samples from the same experimental condition (e.g. the same biopsy). However, we observed a lack of correlation between mRNA and protein levels for individual genes under different conditions, underscoring the challenges in converting transcriptional changes into protein changes. To address this discrepancy, we developed a machine learning model to predict protein abundances from RNA-seq data, achieving high accuracy. Our approach also effectively corrected multiple extreme outliers measured by antibody-based protein assays. Additionally, this model has the potential to detect post-translational modification events, as shown by accurately estimating activated transforming growth factor β1 levels. This study presents a promising approach for converting RNA-seq data into protein abundance and its biological significance.