bluuebunny/crossref_metadata_2025 huggingface dataset:
Compound hot–dry events greatly prolong the recovery time of dryland ecosystems
Authors: Yao Ying , Fu Bojie , Liu Yanxu , Zhang Yao , Ding Jingyi , Li Yan , Zhou Sha , Song Jiaxi , Wang Shuai , Li Changjia , Zhao Wenwu
Published: August 2024

Compound hot–dry events cause more severe impacts on terrestrial ecosystems than dry events, while the differences in recovery time (ΔRT) between hot–dry and dry events and their contributing factors remain unclear. Both remote sensing observations and eddy covariance measurements reveal that hot–dry events prolong the recovery time compared with dry events, with greater prolongation of recovery time in drylands than in humid regions. Random forest regression modeling demonstrates that the difference in vapor pressure deficit between hot–dry and dry events, with an importance score of 35%, is the major factor contributing to ΔRT. The severity of stomatal restriction exceeds that of non-stomatal limitation, which restricts the vegetation productivity that is necessary for the recovery process. These results emphasize the negative effect of vapor pressure deficit on vegetation recovery during hot–dry events and project an extension of drought recovery time considering elevated vapor pressure deficit in a warming world.
Nanorepair medicine for treatment of organ injury
Authors: Wang Han , Hsu Jessica C , Song Wenyu , Lan Xiaoli , Cai Weibo , Ni Dalong
Published: August 2024

Organ injuries, such as acute kidney injury, ischemic stroke, and spinal cord injury, often result in complications that can be life-threatening or even fatal. Recently, many nanomaterials have emerged as promising agents for repairing various organ injuries. In this review, we present the important developments in the field of nanomaterial-based repair medicine, herein referred to as ‘nanorepair medicine’. We first introduce the disease characteristics associated with different types of organ injuries and highlight key examples of relevant nanorepair medicine. We then provide a summary of existing strategies in nanorepair medicine, including organ-targeting methodologies and potential countermeasures against exogenous and endogenous pathologic risk factors. Finally, we offer our perspectives on current challenges and future expectations for the advancement of nanomedicine designed for organ injury repair.
The Impoverished Publicness of Algorithmic Decision Making
Authors: Frost Neli
Published: August 2024

The increasing use of machine learning (ML) in public administration requires that we think carefully about the political and legal constraints imposed on public decision making. These developments confront us with the following interrelated questions: can algorithmic public decisions be truly ‘public’? And, to what extent does the use of ML models compromise the ‘publicness’ of such decisions? This article is part of a broader inquiry into the myriad ways in which digital and AI technologies transform the fabric of our democratic existence by mutating the ‘public’. Focusing on the site of public administration, the article develops a conception of publicness that is grounded in a view of public administrations as communities of practice. These communities operate through dialogical, critical and synergetic interactions that allow them to track—as faithfully as possible—the public’s heterogeneous view of its interests, and reify these interests in decision making. Building on this theorisation, the article suggests that the use of ML models in public decision making inevitably generates an impoverished publicness, and thus undermines the potential of public administrations to operate as a locus of democratic construction. The article thus advocates for a reconsideration of the ways in which administrative law problematises and addresses the harms of algorithmic decision making.
Cellular network measurements can unravel spatiotemporal properties of bird movement to enhance basic and applied knowledge globally
Authors: Ben Moshe Daniel , Messer Hagit , Werber Yuval , Sapir Nir
Published: August 2024

A major problem in studying bird movement in many countries is data scarcity, precluding information about the spatial and temporal properties of avian distribution and dynamics as well as their consequences for human lives. We address this problem by proposing an innovative approach based on the relation between counts of signal attenuation of wireless communication to the presence of birds across or near wireless links of cellular backhaul networks. Wireless point-to-point communication links, on either ground level or earth-satellite links, cover the globe. We statistically relate between signal attenuation in terrestrial Commercial Microwave Links (CMLs) and bird migration. Because modern communication systems measure and often log signal levels routinely, we propose using existing signal level measurements of cellular and other wireless communication systems around the world as sensors for monitoring bird movement. Using actual measurements from operational CMLs, we show that the daily cycle of signal attenuation during bird migration periods matched that of the water-bird migration traffic rate recorded by nearby bird radar. This demonstrates the potential of the proposed method for opportunistic bird movement monitoring by CMLs across the globe, with no additional hardware installation, maintenance, or communication costs.
Can digital technology be affordable on industrial level? An exploration by integrating the sports and health industries
Authors: Li Jiannan
Published: August 2024

While the significance of digital technologies like big data marketing is recognized in sport and health industries, the deployment is not in a fast pace as expected. Previous investigations argue that the financial issue can be the reason explaining such hesitation for sport and health firms to widely adopt advanced digital technologies. Through integrating firms in global sport and health industries, it is shown that the digital technology adoption can be negatively associated with firms’ financial status. Therefore, the digital technologies are expensive, and the provision of sufficient financial incentives can be important to facilitate the promotion of digital technologies in sport and health industries.
Short- and long-term outcomes of patients with pure membranous lupus nephritis compared with patients with proliferative disease
Authors: Kharouf Fadi , Li Qixuan , Whittall Garcia Laura P , Jauhal Arenn , Gladman Dafna D , Touma Zahi
Published: August 2024

Objectives

Membranous LN (MLN) is thought to have a more benign course than proliferative LN (PLN). We aimed to determine the differences in short- and long-term outcomes between patients with MLN and PLN.

Methods

We included patients with first biopsy-proven MLN and PLN. Short-term outcomes included complete proteinuria recovery (CPR), complete renal response (CRR) and primary efficacy renal response (PERR). Long-term outcomes included a sustained ≥40% reduction in baseline estimated glomerular filtration rate, end-stage kidney disease (ESKD), cardiovascular (CV) events, ≥2 increase in SLICC/ACR Damage Index and death. Univariable and multivariable Cox proportional hazard models were used to examine the effect of baseline characteristics on long-term outcomes.

Results

Of 215 patients, 51 had pure MLN and 164 had PLN. We found no significant differences between the two groups in achieving CPR, CRR and PERR at 1 and 2 years. Median time to outcomes was slightly, but insignificantly, longer in the MLN group. For long-term outcomes, PLN was associated with worse renal and non-renal outcomes, but this was not statistically significant. In the multivariable Cox proportional hazard models, ESKD was associated with the following baseline variables: younger age [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.87–0.97], higher creatinine (HR 1.01, 95% CI 1.01–1.02), low complement (HR 4.0, 95% CI 1.04–11.10) and higher chronicity index (HR 1.28, 95% CI 1.08–1.51).

Conclusion

The resolution of proteinuria in LN is slow. MLN is not a benign disease and may be associated with deterioration of renal function, ESKD, damage, CV events and death.
The first-night effect of sleep occurs over nonconsecutive nights in unfamiliar and familiar environments
Authors: Wick Anna Zoé , Combertaldi Selina Ladina , Rasch Björn
Published: August 2024

The first night in an unfamiliar environment is marked by reduced sleep quality and changes in sleep architecture. This so-called first-night effect (FNE) is well established for two consecutive nights and lays the foundation for including an adaptation night in sleep research to counteract FNEs. However, adaptation nights rarely happen immediately before experimental nights, which raises the question of how sleep adapts over nonconsecutive nights. Furthermore, it is yet unclear, how environmental familiarity and hemispheric asymmetry of slow-wave sleep (SWS) contribute to the explanation of FNEs. To address this gap, 45 healthy participants spent two weekly separated nights in the sleep laboratory. In a separate study, we investigated the influence of environmental familiarity on 30 participants who spent two nonconsecutive nights in the sleep laboratory and two nights at home. Sleep was recorded by polysomnography. Results of both studies show that FNEs also occur in nonconsecutive nights, particularly affecting wake after sleep onset, sleep onset latency, and total sleep time. Sleep disturbances in the first night happen in both familiar and unfamiliar environments. The degree of asymmetric SWS was not correlated with the FNE but rather tended to vary over the course of several nights. Our findings suggest that nonconsecutive adaptation nights are effective in controlling for FNEs, justifying the current practice in basic sleep research. Further research should focus on trait- and fluctuating state-like components explaining interhemispheric asymmetries.
Model Guardians: The Gendered Racialization of Asian American Police Officers
Authors: Nishimura Michael
Published: August 2024

21st century police departments in the United States actively promote a community policing model based on mutual trust and cooperation, with a focus on increasing the racial diversity of their workforce. This article focuses on the racialization processes and self-perceptions of Asian American men police officers in Southern California. Drawing on 26 semi-structured interviews, I find that Asian American men police officers, citing their cultural values of hard work, respect, and cooperativeness, position themselves as modern ideal officers, what I call model guardians. Bringing together literatures on police masculinity, Asian American masculinity and model minority politics, I illustrate how Asian American men use model minority capital to symbolically distance themselves from Black, Latinx, and women officers, thereby accumulating status. Even as Asian American men officers experience marginalization, they incorporate their struggles into a model minority perseverance narrative while also claiming relatability to the racialized people they police. Model guardian ideology demonstrates how even within an ostensibly diversifying field, police officers sustain and repackage carceral logics in racialized and gendered ways.
Neonatal autopsy—is it relevant in today’s era?
Authors: Mishra Purbasha , Mohanty Pankaj Kumar , Som Tapas Kumar , Sahoo Tanushree , Devi Usha , Purkait Suvendu , Sable Mukund Namdev , Mishra Pritinanda , Ayyanar Pavithra
Published: August 2024

Autopsy of infants can provide vital information about the cause of death and contributes to the detection of diagnostic errors, especially in a low- or middle-income country. To observe the clinicopathological agreement in neonatal deaths in neonatal intensive care units (NICU) and comment on the additional information retrieved by autopsy. A retrospective observational study was conducted in the NICU from January 2020 to December 2022. Neonatal deaths were analyzed, and clinical details and autopsy findings were collected. Both clinical and pathological diagnoses were classified according to the Goldman classification. Twenty-two newborn infants were enrolled. The mean gestational age was 33.5 (±4.38) weeks, and the median birth weight was 1510 (1005–2100) g. There was complete concordance between clinical and pathological diagnosis in 11 (50%) cases. Major diagnostic errors occurred in 41% of cases. Respiratory system disorders (lung infections, airway anomalies) accounted for six (54%) cases of missed diagnosis. Our study showed that the diagnosis was revised after autopsy in about one-third of cases, and newer findings were identified in one-fifth of cases.
Regional disparities in BCG vaccination coverage and tuberculosis incidence in infants among Brazilian states
Authors: Procianoy Guilherme S , Procianoy Renato S , Silveira Rita C
Published: August 2024

Bacillus Calmette-Guerin (BCG) vaccination and tuberculosis (TB) incidence in children under 1 year of age are critical public health indicators in Brazil. The coronavirus disease 2019 pandemic disrupted vaccination coverage (VC), potentially impacting TB incidence. Understanding regional disparities in VC and TB incidence can inform targeted interventions. We conducted an observational and ecological study using BCG vaccination data (2019–21) and TB incidence (2020–22) for all births in Brazil. Data were collected from public health databases, stratified by state, and analyzed using descriptive and analytical statistics to explore VC and TB incidence. Between 2019 and 2021, average BCG VC was 79.59%, with significant variation among states (P < .001). Only four states achieved minimum recommended coverage (>90%). TB incidence varied significantly among states (P = .003). There was a notable decline in VC from 2019 (90.72%) to 2021 (78.67%) (P < .001). This study highlights regional disparities in BCG VC and TB incidence among Brazilian states. Lower VC post-pandemic may increase TB incidence, requiring targeted interventions in states with inadequate coverage. The findings underscore the importance of sustaining vaccination programs amidst public health crises and implementing strategies to enhance access and uptake.
Investigation of community knowledge, attitudes and stigma towards leprosy in Nigeria: a mixed-methods study
Authors: Murphy-Okpala Ngozi , Dahiru Tahir , Eze Chinwe , Nwafor Charles , Ekeke Ngozi , Abdullahi Suleiman , Iyama Francis S , Meka Anthony , Njoku Martin , Ezeakile Okechukwu , Ukwaja Kingsley N , Anyaike Chukwuma , Sesere Omayeli , Chukwu Joseph
Published: August 2024

Background

Little is known about community knowledge and stigma towards leprosy in endemic settings. The aim of this study was to evaluate community knowledge, attitudes and stigma towards leprosy in Nigeria.

Methods

This was a mixed-methods study consisting of a quantitative cross-sectional survey of community members and qualitative focus group discussions with community members and people affected by leprosy as well as key informant interviews with healthcare workers and community leaders.

Results

Of the 811 survey participants, 401 (49.4%) had a poor knowledge of leprosy that was driven by cultural beliefs, fear of its contagiousness and poor knowledge of its means of transmission. The participants reported high stigma levels with a mean score of 18.96±7.73 on the Explanatory Model Interview Catalogue Community Stigma Scale and 9.39±7.03 on the Social Distance Scale. Stigma levels were influenced by age, residence, education and knowledge of leprosy. Qualitative data suggested that community members were scared of leprosy infectiousness, and local illness concepts and misconceptions informed attitudes and behaviour towards leprosy in the community.

Conclusion

Community members have a poor knowledge of, and high stigma levels towards leprosy. Culture-specific health education and behavioural change interventions are needed to address the identified gaps.
Africa's Manufacturing Puzzle: Evidence from Tanzanian and Ethiopian Firms
Authors: Diao Xinshen , Ellis Mia , McMillan Margaret , Rodrik Dani
Published: August 2024

Recent growth accelerations in Africa are characterized by declining shares of the labor force employed in agriculture, increasing labor productivity in agriculture, and declining labor productivity in modern sectors such as manufacturing. To shed light on this puzzle, this study disaggregates firms in the manufacturing sector by average size, using two newly created firm-level panels covering Tanzania (2008–2016) and Ethiopia (1996–2017). The analysis identifies a dichotomy between larger firms with superior productivity performance that do not expand employment and small firms that absorb employment but do not experience much productivity growth. Large, more productive firms use highly capital-intensive techniques, in line with global technology trends but significantly greater than what would be expected based on these countries’ income levels or relative factor endowments.
Phylogenomics of Phengodidae (Coleoptera: Elateroidea): towards a natural classification of a bioluminescent and paedomorphic beetle lineage, with recognition of a new subfamily
Authors: Ferreira Vinicius S , Roza André S , Barbosa Felipe F , Vega-Badillo Viridiana , Zaragoza-Caballero Santiago , Mermudes José Ricardo M , Ivie Michael A , Hansen Aslak K , Brunke Adam J , Douglas Hume B , Solodovnikov Alexey , Kundrata Robin
Published: August 2024

Phengodidae (Coleoptera: Elateroidea), commonly known as glowworm beetles, are a small family of bioluminescent and paedomorphic beetles. There are few phylogenetic studies of Phengodidae, and these are mostly discordant, especially when comparing morphology-based and molecular-based phylogenetic hypotheses. Here, we used the anchored hybrid enrichment approach to undertake the first phylogenomic analysis of Phengodidae (≤358 loci and 39 taxa) and evaluate the higher-level classification of the group. In agreement with previous molecular studies, we recovered Phengodidae as sister to Rhagophthalmidae, and the Old World Cydistinae as sister to all New World Phengodidae. In contrast to previous hypotheses, both Phengodinae and Mastinocerinae were each recovered as monophyletic. Cenophengus was found to be sister to Mastinocerinae, in contrast to some previous hypotheses that placed it as sister to all New World Phengodidae. Considering its morphological divergence, we here establish Cenophenginae subfam. nov. Despite the largest and most comprehensive sampling of Phengodidae in any molecular-based study to date, we had only limited success in revealing the relationships among genera within the most species-rich subfamily, Mastinocerinae. Further studies should focus on the phylogeny and classification of this taxonomically neglected subfamily, on the phylogenetic placement of enigmatic Penicillophorinae, and on seeking morphological support for the main clades of Phengodidae.
Cranial anatomy of the Triassic rhynchosaur Mesosuchus browni based on computed tomography, with a discussion of the vomeronasal system and its deep history in Reptilia
Authors: Foster William , Gensbigler Paul , Wilson Jacob D , Smith Roger M H , Lyson Tyler R , Bever Gabriel S
Published: August 2024

The stem lineage of Archosauria is populated by a diverse fossil record that remains notably understudied relative to the crown clade. Prominent among these specimens is a beautifully preserved skull of the early mid-Triassic rhynchosaur Mesosuchus browni [Iziko South African Museum (SAM) 6536], whose phylogenetic position has considerable influence on patterns of pan-archosaurian cranial evolution. We used high-resolution, micro-computed tomography to re-examine the anatomy of this specimen, building on previous studies that were either limited to external observations or restricted to the braincase. A digital segmentation of the cranial elements and primary neurovascular canals of SAM-PK-6536 allows for expanded character scoring and constitutes a foundation for future comparative insights. Our data support the phylogenetically oldest instance of a pneumatized maxilla in a pan-archosaur, bringing the record of antorbital pneumatization into closer alignment with that of the neurocranium. The nasal cavity and primary palate of Mesosuchus includes a complex septomaxilla, a novel element anterior to the vomer, and is likely to have supported a well-developed vomeronasal system. The evolution of this system is discussed in terms of both phylogenetic pattern and how the skeletal architecture of Mesosuchus and other fossils could inform the signalling dynamics that pattern the vomeronasal system during development.
Correlates of Disclosing Sexual Victimization to a Resident Assistant: A Study of College Women
Authors: Rahman Anusha , Collibee Charlene , Orchowski Lindsay M.
Published: August 2024

First-year college women are at a high risk for sexual victimization. Staff within residence halls play an important role in connecting students who experience harm with resources. This study utilized survey assessments to examine correlates of likelihood to disclose sexual victimization to a resident assistant among a sample of first-year college women (N = 374). History of sexual victimization, self-concealment, attitudes toward psychological care, and social support were evaluated as correlates of likelihood to disclose to a resident assistant. A history of sexual victimization, level of self-concealment, and attitudes toward seeking psychological care showed a negative association to perceived likelihood to report sexual victimization to a resident assistant. Self-esteem, tendency to disclose sensitive information, tendency to cope via problem solving, social support grounded in guidance, and social support providing reassurance of worth were positively associated with perceived likelihood to disclose to a resident assistant. Multivariate analyses revealed that having no history of prior sexual victimization, high levels of social support that offered reassurance of worth, and a greater tendency to disclose sensitive information emerged as salient multivariate predictors of college women's perceived likelihood to disclose sexual victimization to a resident assistant. Findings increase our understanding of the individual characteristics that influence whether someone seeks assistance from a resident assistant after sexual assault and which students may benefit from additional outreach to connect with university resources after experiences of sexual violence.
phyddle: software for exploring phylogenetic models with deep learning
Authors: Landis Michael J , Thompson Ammon
Published: August 2024

Phylogenies contain a wealth of information about the evolutionary history and process that gave rise to the diversity of life. This information can be extracted by fitting phylogenetic models to trees. However, many realistic phylogenetic models lack tractable likelihood functions, prohibiting their use with standard inference methods. We present phyddle, pipeline-based software for performing phylogenetic modeling tasks on trees using likelihood-free deep learning approaches. phyddle has a flexible command-line interface, making it easy to integrate deep learning approaches for phylogenetics into research workflows. phyddle coordinates modeling tasks through five pipeline analysis steps (Simulate, Format, Train, Estimate, and Plot) that transform raw phylogenetic datasets as input into numerical and visual model-based output. We conduct three experiments to compare the accuracy of likelihood-based inferences against deep learning-based inferences obtained through phyddle. Benchmarks show that phyddle accurately performs the inference tasks for which it was designed, such as estimating macroevolutionary parameters, selecting among continuous trait evolution models, and passing coverage tests for epidemiological models, even for models that lack tractable likelihoods. Learn more about phyddle at https://phyddle.org.
VieMedKG: Knowledge Graph and Benchmark for Traditional Vietnamese Medicine
Authors: Trinh Tam , Dao Anh , Nhung Hy Thi Hong , Truong Son Hy
Published: August 2024

Traditional Vietnamese Medicine (TVM) and Traditional Chinese Medicine (TCM) have shared significant similarities due to their geographical location, cultural exchanges, and hot and humid climatic conditions. However, unlike TCM, which has substantial works published to construct a knowledge graph, there is a notable absence of a comprehensive knowledge graph for TVM. This paper presents the first endeavor to build a knowledge graph for TVM based on extensive existing resources from TCM. We name our knowledge graph as VieMedKG. We propose a translation and filtration process to adapt TCM knowledge graphs to TVM, identifying the overlapping and unique elements of TVM. In addition, the constructed knowledge graph is then exploited further for developing a curated benchmark for the knowledge graph-based question-answering problem with the potential to support doctors and patients in assisting doctors and patients in identifying various diseases. Our work will not only bridge the gap between TCM and TVM but also set the foundation for future research into traditional Vietnamese medicine community. Our source code is publicly available at https://github.com/HySonLab/VieMedKG/ .
Investigating orientation adaptation following naturalistic film viewing
Authors: A-Izzeddin Emily J , Rideaux Reuben , Mattingley Jason B , Harrison William J
Published: August 2024

Humans display marked changes to their perceptual experience of a stimulus following prolonged or repeated exposure to a preceding stimulus. A well-studied example of such perceptual adaptation is the tilt-aftereffect. Here, prolonged exposure to one orientation leads to a shift in the perception of subsequent orientations. Such a capacity to adapt suggests the visual system is dynamically tuned to our current visual environment. However, it remains unclear to what extent adaptation occurs in response to systematic features in naturalistic scenes. We therefore investigated orientation adaptation in response to natural viewing of filtered live-action film stimuli. Within a session, participants freely viewed 45 minutes of a film which had been filtered to include increased contrast energy within a specified orientation band (0°, 45°, 90°, or 135°; i.e., the adaptor). To measure adaptation effects, the film was intermittently interrupted to have participants perform a simple orientation judgement task. Having participants complete behavioural trials throughout the testing session, including 45 minutes of total adaptation time, allowed investigation of the accumulation of response biases and changes in such biases over the course of the session. We found participants exhibited stronger adaptation effects in response to cardinal adaptors compared to obliques. However, overall adaptation effects were weaker than those observed under typical tilt-aftereffect paradigms. Further, within a single session, adaptation effects developed inconsistently. The current findings therefore demonstrate a resistance to adaptation in response to naturalistic viewing conditions, suggesting barriers to understanding perceptual adaptation as experienced in nature.
Scalable information extraction from free text electronic health records using large language models
Authors: Gu Bowen , Shao Vivian , Liao Ziqian , Carducci Valentina , Brufau Santiago Romero , Yang Jie , Desai Rishi J
Published: August 2024

Background

A vast amount of potentially useful information such as description of patient symptoms, family, and social history is recorded as free-text notes in electronic health records (EHRs) but is difficult to reliably extract at scale, limiting their utility in research. This study aims to assess whether an “out of the box” implementation of open-source large language models (LLMs) without any fine-tuning can accurately extract social determinants of health (SDoH) data from free-text clinical notes.

Methods

We conducted a cross-sectional study using EHR data from the Mass General Brigham (MGB) system, analyzing free-text notes for SDoH information. We selected a random sample of 200 patients and manually labeled nine SDoH aspects. Eight advanced open-source LLMs were evaluated against a baseline pattern-matching model. Two human reviewers provided the manual labels, achieving 93% inter-annotator agreement. LLM performance was assessed using accuracy metrics for overall, mentioned, and non-mentioned SDoH, and macro F1 scores.

Results

LLMs outperformed the baseline pattern-matching approach, particularly for explicitly mentioned SDoH, achieving up to 40% higher Accuracymentioned. openchat_3.5 was the best-performing model, surpassing the baseline in overall accuracy across all nine SDoH aspects. The refined pipeline with prompt engineering reduced hallucinations and improved accuracy.

Conclusions

Open-source LLMs are effective and scalable tools for extracting SDoH from unstructured EHRs, surpassing traditional pattern-matching methods. Further refinement and domain-specific training could enhance their utility in clinical research and predictive analytics, improving healthcare outcomes and addressing health disparities.
Hierarchical Bayesian Augmented Hebbian Reweighting Model of Perceptual Learning
Authors: Lu Zhong-Lin , Yang Shanglin , Dosher Barbara
Published: August 2024

The Augmented Hebbian Reweighting Model (AHRM) has been effectively utilized to model the collective performance of observers in various perceptual learning studies. In this work, we have introduced a novel hierarchical Bayesian Augmented Hebbian Reweighting Model (HB-AHRM) to simultaneously model the learning curves of individual participants and the entire population within a single framework. We have compared its performance to that of a Bayesian Inference Procedure (BIP), which independently estimates the posterior distributions of model parameters for each individual subject without employing a hierarchical structure. To cope with the substantial computational demands, we developed an approach to approximate the likelihood function in the AHRM with feature engineering and linear regression, increasing the speed of the estimation procedure by 20,000 times. The HB-AHRM has enabled us to compute the joint posterior distribution of hyperparameters and parameters at the population, observer, and test levels, facilitating statistical inferences across these levels. While we have developed this methodology within the context of a single experiment, the HB-AHRM and the associated modeling techniques can be readily applied to analyze data from various perceptual learning experiments and provide predictions of human performance at both the population and individual levels. The likelihood approximation concept introduced in this study may have broader utility in fitting other stochastic models lacking analytic forms.
Caution when using network partners for target identification in drug discovery
Authors: Tan Dandan , Chen Yiheng , Ilboudo Yann , Liang Kevin Y. H. , Butler-Laporte Guillaume , Richards J Brent
Published: August 2024

Identifying novel, high-yield drug targets is challenging and often results in a high failure rate. However, recent data indicates that leveraging human genetic evidence to identify and validate these targets significantly increases the likelihood of success in drug development. Two recent papers from Open Targets claimed that around half of FDA-approved drugs had targets with direct human genetic evidence. By expanding target identification to include protein network partners—molecules in physical contact—the proportion of drug targets with genetic evidence support increased to two-thirds. However, the efficacy of using these network partners for target identification was not formally tested. To address this, we tested the approach on a list of robust positive control genes. We used the IntAct database to find molecular interacting proteins of genes identified by exome-wide association studies (ExWAS) and genome-wide association studies (GWAS) combined with a locus-to-gene mapping algorithm called the Effector Index (Ei). We assessed how accurately including interacting genes with the ExWAS and Effector Index selected genes identified positive controls, focusing on precision, sensitivity, and specificity. Our results indicated that although molecular interactions led to higher sensitivity in identifying positive control genes, their practical application is limited by low precision. Hence, expanding genetically identified targets to include network partners did not increase the chance of identifying drug targets, suggesting that such results should be interpreted with caution.
Beyond Differential Expression: Embracing Cell-to-Cell Variability in Single-Cell Gene Expression Data Analysis
Authors: Gatlin Victoria , Gupta Shreyan , Romero Selim , Chapkin Robert S. , Cai James J.
Published: August 2024

Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular variability by capturing gene expression profiles of individual cells. The importance of cell-to-cell variability in determining and shaping cell function has been widely appreciated. Nevertheless, differential expression (DE) analysis remains a cornerstone method in analytic practice, by focusing exclusively on mean expressional differences, current computational analyses overlook the rich information encoded by variability within the single-cell gene expression data. Thus, there is a need for more relevant approaches to assess data variability rather than the mean in order to offer a deeper understanding of cellular systems. Here we present spline-DV, a novel statistical framework for differential variability (DV) analysis using scRNA-seq data. The spline-DV method identifies genes exhibiting significantly increased or decreased expression variability among cells derived from two experimental conditions. Case studies show that DV genes identified using spline-DV are representative, and functionally relevant in the tested cellular conditions including obesity, fibrosis, and cancer.
Hydrocarbon Metabolism and Petroleum Seepage as Ecological and Evolutionary Drivers for Cycloclasticus
Authors: Arrington Eleanor C , Tarn Jonathan , Kivenson Veronika , Nunn Brook L. , Liu Rachel M. , Paul Blair G. , Valentine David L.
Published: August 2024

Aqueous-soluble hydrocarbons dissolve into the ocean interior and structure deep-sea microbial populations influenced by natural oil seeps and spills. n-Pentane is a seawater-soluble, volatile compound abundant in petroleum products and reservoirs and will partially partition to the deep-water column following release from the seafloor. In this study, we explore the ecology and niche partitioning of two free-living Cycloclasticus strains recovered from seawater incubations with n-pentane using and distinguish them as an open ocean variant and a seep-proximal variant, each with distinct capabilities for hydrocarbon catabolism. Comparative metagenomic analysis indicates the open ocean adapted variant encodes more general pathways for hydrocarbon consumption, including short-chain alkanes, aromatics, and long-chain alkanes, and also possesses redox versatility in the form of respiratory nitrate reduction and thiosulfate oxidation; in contrast, the seep variant specializes in short-chain alkanes and relies strictly on oxygen as the terminal electron acceptor. Both variants observed in our work were dominant ecotypes of Cycloclasticus observed during the Deepwater Horizon disaster, a conclusion supported by 16S rRNA analysis and read-recruitment of sequences from the submerged oil plume during active flow. A comparative genomic analysis of Cycloclasticus across various ecosystems suggests distinct strategies for hydrocarbon transformations among each clade. Our findings suggest Cycloclasticus is a versatile and opportunistic consumer of hydrocarbons and may have a greater role in the cycling of sulfur and nitrogen, thus contributing broad ecological impact to various ecosystems globally.
Whole genome sequence improvement with pedigree information and reference genotypic profiles, demonstrated in outcrossing apple
Authors: Vanderzande Stijn , Peace Cameron , van de Weg Eric
Published: August 2024

Understanding the quality of a whole genome sequence (WGS) is important for its further use. Most WGS quality evaluations are based on bioinformatic quality metrics such as the N50 score, BUSCO score, and number of contigs and scaffolds present, yet genetic information considering principles of inheritance could be used to evaluate and improve assembly and phasing. Furthermore, WGS and genome resequencing data of related individuals could provide useful information when large chromosomal segments are shared with the target individual through common ancestry. Here, we show how high-quality, phased, genome-wide genotypic information is useful to evaluate the quality of a WGS. We provide an R-tool to routinely conduct such quality evaluations. The script also provides a method to accurately determine the WGS positions of reference SNP markers, which is needed for integration of SNP array-based genotypic data sets with WGS data, and the identification and comparison of segments across WGSs that are shared by descent. Finally, we provide suggestions on how such sharing can be used to evaluate and improve new WGSs. The approach is demonstrated in apple, for which improvements in WGS quality are evident from the first collapsed WGS with many inconsistencies in genetic marker order and genotype scores, through well-assembled haploid WGSs, to incorrectly and correctly phased diploid WGSs. This study shows that homozygous regions might need extra attention in phased WGSs and that further improvements to phased WGSs can be achieved by grouping chromosomes of single parental origin into the same haplome.
Footprints of human migration in the population structure of wild wine yeast
Authors: Peña Jacqueline J. , Scopel Eduardo FC , Ward Audrey K. , Bensasson Douda
Published: August 2024

Humans have a long history of fermenting food and beverages that led to domestication of the wine yeast,Saccharomyces cerevisiae.Despite their tight companionship with humans, yeast species that are domesticated or pathogenic can also live on trees. Here we used over 300 genomes ofS. cerevisiaefrom oaks and other trees to determine whether tree-associated populations are genetically distinct from domesticated lineages and estimate the timing of forest lineage divergence. We found populations on trees are highly structured within Europe, Japan, and North America. Approximate estimates of when forest lineages diverged out of Asia and into North America and Europe coincide with the end of the last ice age, the spread of agriculture, and the onset of fermentation by humans. It appears that migration from human-associated environments to trees is ongoing. Indeed, patterns of ancestry in the genomes of three recent migrants from the trees of North America to Europe could be explained by the human response to the Great French Wine Blight. Our results suggest that human-assisted migration affects forest populations, albeit rarely. Such migration events may even have shaped the global distribution ofS. cerevisiae. Given the potential for lasting impacts due to yeast migration between human and natural environments, it seems important to understand the evolution of human commensals and pathogens in wild niches.
Cell-Type-Specific Regulation of TOR-Mediated Microtubule Acetylation Predicts Yki Loss-Induced Squamous Cell Carcinoma inDrosophila
Authors: Bhattacharya Rachita , Agarwal Shruti , Zafar Hamim , Sinha Pradip , Mohan Nitin
Published: August 2024

Flattened squamous epithelial tissues undergo extensive cytoskeletal remodeling and display perpetual nuclear signaling of the Hippo transcription cofactor, YAP/TAZ, in mammals and Yki inDrosophila. Loss of YAP in humans or Yki inDrosophilacauses squamous cell carcinoma (SCC), but only in select cell types. Here, we reveal a mechanism of Yki-loss induced SCC in the lumen-lining squamous epithelium of the male accessory gland (MAG) inDrosophila. Yki loss in the MAG triggers TOR signaling-mediated microtubule hyperacetylation, which causally underpins its SCC. By contrast, Yki loss in the oocyte-enveloping follicular squamous epithelium neither activates TOR nor induce microtubule hyperacetylation. Analysis of available single-cell transcriptomic data further revealed characteristic MAG and follicular squamous cell type-specific signatures of Yki and TOR signaling. Thus, the disparate epigenetic landscapes and distinct mechanosensory cues likely prefigures their susceptibility to Yki-loss, with lumen-lining squamous epithelia being oncogenically more susceptible.
Drosophila ring chromosomes interact with sisters and homologs to produce anaphase bridges in mitosis
Authors: Lin Ho-Chen , Golic Mary M. , Hill Hunter J. , Lemons Katherine F. , Vuong Truc T. , Smith Madison , Golic Forrest , Golic Kent G.
Published: August 2024

Ring chromosomes are known in many eukaryotic organisms, including humans. They are typically associated with a variety of maladies, including abnormal development and lethality. Underlying these phenotypes are anaphase chromatin bridges that can lead to chromosome loss, nondisjunction and breakage. By cytological examination of ring chromosomes inDrosophila melanogasterwe identified five causes for anaphase bridges produced by ring chromosomes. Catenation of sister chromatids is the most common cause and these bridges frequently resolve during anaphase, presumably by the action of topoisomerase II. Sister chromatid exchange and chromosome breakage followed by sister chromatid union also produce anaphase bridges. Mitotic recombination with the homolog was rare, but was another route to generation of anaphase bridges. Most surprising, was the discovery of homolog capture, where the ring chromosome was connected to its linear homolog in anaphase. We hypothesize that this is a remnant of mitotic pairing and that the linear chromosome is connected to the ring by multiple wraps produced through the action of topoisomerase II during establishment of homolog pairing. In support, we showed that in a ring/ring homozygote the two rings are frequently catenated in mitotic metaphase, a configuration that requires breaking and rejoining of at least one chromosome.
Bayesian estimation yields anti-Weber variability
Authors: Prat-Carrabin Arthur , Gershman Samuel J.
Published: August 2024

A classic result of psychophysics is that human perceptual estimates are more variable for larger magnitudes. This ‘Weber behavior’ has typically not been the focus of the prominent Bayesian paradigm, which models human perception as an optimal statistical inference conducted on the basis of noisy internal signals. Here we examine the variability of the estimates of a Bayesian observer, in comparison with human subjects. In two preregistered experiments, we manipulate the prior distribution and the reward function in a numerosity-estimation task. When the large numerosities are more frequent, and when they are more rewarding, the Bayesian observer exhibits an ‘anti-Weber behavior’, in which larger magnitudes results in less variable responses. Human subjects exhibit a similar pattern, thus breaking a long-standing result of psychophysics by showing the opposite behavior. This allows subjects to minimize the errors they make about the more frequent or the more rewarding magnitudes. Nevertheless, model fitting suggests that subjects’ responses are best captured by a model that features a logarithmic encoding, a proposal of Fechner often regarded as accounting for Weber behavior. We thus obtain an anti-Weber behavior together with a Fechner encoding. Our results suggest that the increasing variability may be primarily due to the skewness of natural priors.
Dynamic Wt1 expression in the gastrulation-stage mouse embryo specifies vascular and visceral smooth muscle cell fate independently from mesothelial fate
Authors: Alsukari Suad H. , Ng Huei Teng , Lang Lilly , Lunn Sharna , Beglinger Shanthi , Carr Lauren , Boyes Michael , Turner David A. , Wilm Bettina
Published: August 2024

The Wilms’ Tumour protein (Wt1) had previously been shown to specify both the mesothelial lineage and vascular smooth muscle cell (vSMC) lineage in the mouse intestine, with evidence suggesting that intestinal vSMCs arise from the mesothelium. Here, we dissect the temporal relationship between these two mesodermal lineages, reporting that unexpectedly, Wt1 expression already in gastrulation stage embryos specifies a population of SMC precursor cells in the lateral plate mesoderm (LPM). Tamoxifen-induced genetic lineage tracing of Wt1-expressing cells revealed that vSMC and visceral smooth muscle cells (visSMCs) of the foetal mid-gut are labelled when Tamoxifen was administered at E7.5 or E8.5. By contrast, intestinal mesothelial cells were labelled after Tamoxifen dosing from E9.5 and later. Analysis of scRNAseq data of gastrulation stage mouse embryos and confocal microscopy demonstrated for the first time Wt1 expression in epiblast and primitive streak, emerging mesoderm and, from E7.5 onwards, in the LPM. In E8.5 mouse embryos, the co-expression of key smooth muscle fate markersTagln,Acta2,MrtfA/BandPdgfrbinWt1-expressing cells revealed that vSMC and visSMC fate is specified independently from visceral mesothelium formation. Together, our study provides insight into the developmental lineage of smooth muscle specified by Wt1 expression at gastrulation stages.
Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity
Authors: Alexander Ryan P. D. , Bender Kevin J.
Published: August 2024

Opioids regulate circuits associated with motivation and reward across the brain. Of the opioid receptor types, delta opioid receptors (DORs) appear to have a unique role in regulating the activity of circuits related to reward without a liability for abuse. In neocortex, DORs are expressed primarily in interneurons, including parvalbumin- and somatostatin-expressing interneurons that inhibit somatic and dendritic compartments of excitatory pyramidal cells, respectively. But how DORs regulate transmission from these key interneuron classes is unclear. We found that DORs regulate inhibition from these interneuron classes using different G-protein signaling pathways that both converge on presynaptic calcium channels, but regulate distinct aspects of calcium channel function. This imposes different temporal filtering effects, via short-term plasticity, that depend on how calcium channels are regulated. Thus, DORs engage differential signaling cascades to regulate inhibition depending on the postsynaptic target compartment, with different effects on synaptic information transfer in somatic and dendritic domains.