bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATH434, a promising iron-targeting compound for treating iron regulation disorders
Authors: Pall Ashley E , Bond Silas , Bailey Danielle K , Stoj Christopher S , Deschamps Isabel , Huggins Penny , Parsons Jack , Bradbury Margaret J , Kosman Daniel J , Stemmler Timothy L 
Published: September 2024

Abstract
Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. ≤10−31) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd’s of 1–4 µM), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low/moderate affinities for Fe3+(0.46–9.59 µM) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.
RPFdb v3.0: an enhanced repository for ribosome profiling data and related content
Authors: Wang Yan , Tang Yuewen , Xie Zhi , Wang Hongwei 
Published: September 2024

Abstract
RPFdb (http://www.rpfdb.org or http://sysbio.gzzoc.com/rpfdb/) is a comprehensive repository dedicated to hosting ribosome profiling (Ribo-seq) data and related content. Herein, we present RPFdb v3.0, a significant update featuring expanded data content and improved functionality. Key enhancements include (i) increased data coverage, now encompassing 5018 Ribo-seq datasets and 2343 matched RNA-seq datasets from 496 studies across 34 species; (ii) implementation of translation efficiency, combining Ribo-seq and RNA-seq data to provide gene-specific translation efficiency; (iii) addition of pausing score, facilitating the identification of condition-specific triplet amino acid motifs with enhanced ribosome enrichment; (iv) refinement of open reading frame (ORF) annotation, leveraging RibORF v2.0 for more sensitive detection of actively translated ORFs; (v) introduction of a resource hub, curating advances in translatome sequencing techniques and data analytics tools to support a panoramic overview of the field; and (vi) redesigned web interface, providing intuitive navigation with dedicated pages for streamlined data retrieval, comparison and visualization. These enhancements make RPFdb a more powerful and user-friendly resource for researchers in the field of translatomics. The database is freely accessible and regularly updated to ensure its continued relevance to the scientific community.
Optimized periphery-core interface increases fitness of the Bacillus subtilis glmS ribozyme
Authors: Yu Li-Eng D , White Elise N , Woodson Sarah A 
Published: September 2024

Abstract
Like other functional RNAs, ribozymes encode a conserved catalytic center supported by peripheral domains that vary among ribozyme sub-families. To understand how core-periphery interactions contribute to ribozyme fitness, we compared the cleavage kinetics of all single base substitutions at 152 sites across the Bacillus subtilis glmS ribozyme by high-throughput sequencing (k-seq). The in vitro activity map mirrored phylogenetic sequence conservation in glmS ribozymes, indicating that biological fitness reports all biochemically important positions. The k-seq results and folding assays showed that most deleterious mutations lower activity by impairing ribozyme self-assembly. All-atom molecular dynamics simulations of the complete ribozyme revealed how individual mutations in the core or the IL4 peripheral loop introduce a non-native tertiary interface that rewires the catalytic center, eliminating activity. We conclude that the need to avoid non-native helix packing powerfully constrains the evolution of tertiary structure motifs in RNA.
A multiscale analysis of factors influencing Setophaga striata (Blackpoll Warbler) occupancy and abundance during the nonbreeding season in eastern Colombia
Authors: Morales-Rozo Andrea , Bayly Nicholas J , Taylor Philip D , Hobson Keith A , Colorado Z Gabriel J , Gómez Juan Pablo 
Published: September 2024

ABSTRACT
Setophaga striata (Blackpoll Warbler), one of the few boreal-breeding migratory birds that migrates to the Orinoco and Amazon regions, is experiencing steep population declines. However, knowledge of the species’ distribution and habitat use during the nonbreeding season is limited. Here, we explore how stationary nonbreeding season (December to April) occupancy probabilities vary across regional and landscape scales, and with vegetation structure for S. striata in eastern Colombia. By running single-species, single-season hierarchical occupancy models and N-mixture models, we evaluated how regional (annual precipitation, nonbreeding season precipitation, driest month, elevation, and net primary productivity), landscape (habitat type and % forest in the landscape), and vegetation structure variables influenced occupancy by S. striata. In the regional analysis, occupancy was positively influenced by stationary nonbreeding precipitation and net primary productivity, and was predicted to peak at elevations between 500 and 1,000 m. At the landscape scale, occupancy and abundance were higher in agroforestry systems (in order of magnitude: shade-grown cacao, citrus plantations and silvopastures) than in forested habitats. In relation to vegetation structure, occupancy was negatively correlated with a principal component containing shrub density, canopy height, and canopy cover. Within the Orinoco region, a spatial prediction based on our results supported high occupancy rates in moister areas along and close to the Andean foothills and where the Orinoco grasslands transition into Amazonian forests. Our results highlight the importance of landscapes containing agroforestry systems as stationary nonbreeding habitats for S. striata in Colombia’s Orinoco region and the importance of promoting agroforestry systems, like shade-grown cacao, in areas with higher nonbreeding season precipitation and net primary productivity values in order to increase habitat availability for the species.
Survey of non-thermal electrons around supermassive black holes through polarization flips
Authors: Tsunetoe Yuh , Kawashima Tomohisa , Ohsuga Ken , Mineshige Shin 
Published: September 2024

Abstract
Optically thick non-thermal synchrotron sources notably produce linear polarization vectors that are parallel to projected magnetic field lines on the observer’s screen, although they are perpendicular in well-known optically thin cases. To elucidate the complex relationship between the vectors and fields, and to investigate the energy and spatial distribution of non-thermal electrons through the images, we perform polarization radiative transfer calculations at submillimeter wavelengths. Here the calculations are based on semi-analytic force-free jet models with non-thermal electrons with a power-law energy distribution. In the calculated images, we find a $90{^\circ }$-flip of linear polarization vectors at the base of counter-side (receding) jet near a black hole, which occurs because of large optical depths for the synchrotron self-absorption effect. The $90{^\circ }$-flip of LP vectors is also seen on the photon ring at a high frequency, since the optical depth along the rays is large there due to the light bending effect. In addition, we see the flip of the sign of circular polarization components on the counter-jet and photon ring. Furthermore, we show that these polarization flips are synthesized with large values in the spectral index map, and also give rise to outstanding features in the Faraday Rotation Measure map. Since the conditions of flipping depend on the magnetic field strength and configuration and the energy distribution of electrons, we can expect that the polarization flips will provide us with observational evidence for the presence of non-thermal electrons around the black hole, and a clue to the magnetic driving mechanism of plasma jets.
The nuclear exosome subunit HEN2 acts independently of the core exosome to assist transcription in Arabidopsis
Authors: Bhat Susheel Sagar , Asgari Mishaneh , Mermet Sarah , Mishra Priyanka , Kindgren Peter 
Published: September 2024

Abstract
Regulation of gene expression is at the frontier of plant responses to various external stimuli including stress. RNA polymerase-based transcription and post-transcriptional degradation of RNA play vital roles in this regulation. Here, we show that HUA ENHANCER 2 (HEN2), a co-factor of the nuclear exosome complex, influences RNAPII transcription elongation in Arabidopsis (Arabidopsis thaliana) under cold conditions. Our results demonstrate that a hen2 mutant is cold sensitive and undergoes substantial transcriptional changes compared to wild type when exposed to cold conditions. We found an accumulation of 5′ fragments from a subset of genes (including C-repeat binding factors 1–3 [CBF1–3]) that do not carry over to their 3′ ends. In fact, hen2 mutants have lower levels of full-length mRNA for a subset of genes. This distinct 5′-end accumulation and 3′-end depletion was not observed in other NEXT complex members or core exosome mutants, highlighting HEN2's distinctive role. We further used RNAPII-associated nascent RNA to confirm that the transcriptional phenotype is a result of lower active transcription specifically at the 3′ end of these genes in a hen2 mutant. Taken together, our data point to the unique role of HEN2 in maintaining RNAPII transcription dynamics especially highlighted under cold stress.
Structure-based validation of recombinant light-harvesting complex II
Authors: Seki Soichiro , Miyata Tomoko , Norioka Naoko , Tanaka Hideaki , Kurisu Genji , Namba Keiichi , Fujii Ritsuko 
Published: September 2024

Abstract
Light-harvesting complex II (LHCII) captures sunlight and dissipates excess energy to drive photosynthesis. To elucidate this mechanism, the individual optical properties of pigments in the LHCII protein must be identified. In vitro reconstitution with apoproteins synthesized by Escherichia coli and pigment–lipid mixtures from natural sources is an effective approach; however, the local environment surrounding each pigment within reconstituted LHCII (rLHCII) has only been indirectly estimated using spectroscopic and biochemical methods. Here, we used cryo-electron microscopy to determine the 3D structure of the rLHCII trimer and found that rLHCII exhibited a structure that was virtually identical to that of native LHCII, with a few exceptions: some C-terminal amino acids were not visible, likely due to aggregation of the His-tags; a carotenoid at the V1 site was not visible; and at site 614 showed mixed occupancy by both chlorophyll a and b molecules. Our observations confirmed the applicability of the in vitro reconstitution technique.
Predictors of driving risk in patients with obstructive sleep apnea syndrome treated by continuous positive airway pressure: a French multicenter prospective cohort
Authors: Coelho Julien , Bailly Sébastien , Baillieul Sébastien , Sagaspe Patricia , McNicholas Walter T , Taillard Jacques , Micoulaud-Franchi Jean-Arthur , Sapène Marc , Grillet Yves , Tamisier Renaud , Pépin Jean-Louis , Philip Pierre 
Published: September 2024

Abstract

Study Objectives
To investigate the predictors of persistent driving risk related to sleepiness in patients with obstructive sleep apnea syndrome (OSAS) treated by continuous positive airway pressure (CPAP).

Methods
Longitudinal analysis of a prospective national database including 5308 patients with OSAS and an indication of CPAP. Near misses related to sleepiness, accidents related to sleepiness, and sleepiness at the wheel (SAW) were assessed before initiation and after ≥90 days of treatment. Multivariable associations with the cumulative incidence of near-misses and accidents under treatment were calculated using Cox models adjusted for age, sex, obesity, sleep duration, SAW, accidents/near-misses history, depressive symptoms, residual apnea–hypopnea index, and adherence to treatment.

Results
Residual SAW under treatment was associated with an eight-fold higher incidence of near-misses related to sleepiness (hazard ratios [HR] = 8.63 [6.08–12.2]) and five-fold higher incidence of accidents related to sleepiness (HR = 5.24 [2.81–9.78]). Adherence ≤4 h/night was also a significant predictor of persistent driving risk (HR = 1.74 [1.12–2.71] for near-misses and HR = 3.20 [1.37–7.49] for accidents).

Conclusions
Residual SAW and treatment adherence ≤4 h/night are easy-to-assess markers to detect persistent driving risk during the follow-up evaluations of patients under treatment. Health professionals, but also policymakers, should be aware of the crucial importance of systematically evaluating these elements during the follow-up evaluations of the patients with OSAS treated by CPAP to better evaluate their driving risk.
Emerging antibiotic resistance in Plesiomonasshigelloides: insights from surface waters in Southwest Nigeria
Authors: Adepoju Oluwarinu A , Adefisoye Jumoke M , Adesiyan Ibukun M 
Published: September 2024

Abstract
This study aimed to investigate the antibiotic resistance pattern, extended-spectrum β-lactamase (ESBL) production, and biofilm formation potential of Plesiomonas shigelloides in selected surface waters in southwestern Nigeria. Isolates were identified using the spread plate technique on inositol brilliant green bile agar and confirmed molecularly by polymerase chain reaction. Antibiotic susceptibility was determined using the Kirby–Bauer disc diffusion method, ESBL production by the double disc synergistic test, and biofilm formation by the test tube method. A total of 111 P. shigelloides isolates were identified and confirmed. Significant resistance rates were observed against cefuroxime (71%), cefotaxime (92%), and ceftazidime (92%), while high susceptibility was noted for ciprofloxacin (94%), gentamicin (96%), and chloramphenicol (100%). A higher prevalence of multiple drug resistant phenotypes was observed during the dry season, reaching 79% and 60% along sampled rivers. Biofilm-producing phenotypes exhibited robust homogeneous biofilm formation. In this study, P. shigelloides exhibited high resistance to critical antibiotics such as third-generation cephalosporins. However, isolates displayed susceptibility to ciprofloxacin, gentamicin, and chloramphenicol. The presence of ESBL phenotypes and strong biofilm formation emphasizes the potential threat of P. shigelloides as an emerging environmental pathogen, highlighting the importance of monitoring and understanding antibiotic resistance patterns for effective public health management strategies.
Molecular phylogenetic analyses reveal a radiation of freshwater Gammarus (Amphipoda: Gammaridae) in the northern Chihuahuan Desert
Authors: Cannizzaro Andrew G , Berg David J 
Published: September 2024

Abstract
Isolation of desert springs often leads to the evolution of unique biodiversity. We investigated the taxonomy and evolutionary relationships of members of the Gammarus pecos complex, an assemblage of narrowly endemic amphipod species in the Chihuahuan Desert of the USA. Morphological and molecular phylogenetic analyses, including newly obtained COI sequences from the now-extinct type population of Gammarus desperatus, reveal the presence of two undescribed species and lead to redescription of G. desperatus. Gammarus acerbatus sp. nov. is split from G. desperatus and Gammarus balmorhea sp. nov. is split from G. hyalelloides. Each of these species is endemic to a single spring system. Speciation in the Gammarus pecos complex was likely promoted by the lineage’s ties to marine/riverine systems and geological events during the Oligocene/Miocene. The additional diversity discovered within the complex highlights the effects of both habitat and evolutionary history on the processes of speciation at local and regional spatial scales. The entire complex of at least six species is imperilled due to the narrow ranges occupied by each species and human water-use that threatens the existence of their spring habitats.
UA influences the progression of breast cancer via the AhR/p27Kip1/cyclin E pathway
Authors: Wang Zhiying , Zhang Yuanqi , Huang Shengchao , Liao Zhihong , Huang Mingzhang , Lei Wei , Shui Xiaorong 
Published: September 2024

AbstractUric acid (UA) is the end product of purine metabolism. In recent years, UA has been found to be associated with the prognosis of clinical cancer patients. However, the intricate mechanisms by which UA affects the development and prognosis of tumor patients has not been well elucidated. In this study, we explored the role of UA in breast cancer, scrutinizing its impact on breast cancer cell function by treating two types of breast cancer cell lines with UA. The role of UA in the cell cycle and proliferation of tumors and the underlying mechanisms were further investigated. We found that the antioxidant effect of UA facilitated the scavenging of reactive oxygen species (ROS) in breast cancer, thereby reducing aryl hydrocarbon receptor (AhR) expression and affecting the breast cancer cell cycle, driving the proliferation of breast cancer cells through the AhR/p27Kip1/cyclin E1 pathway. Moreover, in breast cancer patients, the expression of AhR and its downstream genes may be closely associated with cancer progression in patients. Therefore, an increase in UA could promote the proliferation of breast cancer cells through the AhR/p27Kip1/cyclin E1 pathway axis.
Exploring How Housestaff Unions Impact the Program Director–Resident Educational Alliance
Authors: Krzyzaniak Sara M. , Sebok-Syer Stefanie S. , Akhtar Saadia , Gallahue Fiona 
Published: September 2024

Abstract
In 1999, the National Labor Relations Board determined that residents function as employees, thereby allowing them to freely unionize. From 2020 to 2023, housestaff (i.e., resident physicians and fellows) unions have significantly increased, and 8 physician training centers, representing nearly 4,000 housestaff, have unionized since March 2021. While unions provide residents with an important tool in effecting change in their workplace, their introduction into the educational milieu has the potential to alter the program director (PD)–resident relationship. In this article, the authors use the educational alliance framework to detail 3 factors required to support a quality educational relationship between a resident and their PD. They also elaborate on how the introduction of unions may impact the PD-resident relationship and explore the potential unintended consequences of unionization as it pertains to this relationship. The authors then use 2 social psychology theories, naïve realism and motivated reasoning, to describe common framing dynamics that lead to conflict during collective bargaining processes. They conclude by offering strategies that PDs may use to mitigate tensions that arise in contract negotiations, even without a direct seat at the table. Ultimately, PDs should anticipate continued growth of resident unions and prepare themselves and their programs for the tensions that may arise from this action. The PD role as a neutral third party ought to be preserved, which is possible if all parties set reasonable expectations for the changes in the PD’s role and responsibilities under a union. PDs should understand the 3 core aspects of the educational alliance and the importance of establishing credibility with their residents early on to build a strong foundation.
Determining Root Causes of Poor Academic Performance to Provide Wraparound Support for Preclerkship Medical Students
Authors: Coppola Kristen M. , Rashid Hanin , Terregino Carol A. , Lebeau Robert 
Published: September 2024

Root Cause Analysis
Targeting support for lower performing medical students is a complex process due to the multiple contributing factorsthat derail academic success.1-4 Root cause analysis provides an approach for professionals in student affairs, academicsupport specialists, and teaching faculty to attribute academic difficulty to interrelated contributing causes.
Educational Podcasts: Effect of Content Delivery Timing on Knowledge Acquisition and Retention
Authors: Gottlieb Michael , Fung Cha-Chi , Haas Mary R.C. , Cooney Robert , King Andrew , Riddell Jeffrey 
Published: September 2024

Abstract

Purpose
This study examined whether the order of podcast content influenced knowledge acquisition and retention among emergency medicine (EM) resident physicians.

Method
This preplanned secondary analysis of 2 large, multicenter trials included a randomized, crossover trial conducted from November 2019 to June 2020 of 100 residents that compared driving and seated condition for two 30-minute podcasts and a randomized, crossover trial conducted from September 2022 to January 2023 of 95 EM residents that compared exercise with seated condition for the same two 30-minute podcasts. Each podcast contained 6 journal article reviews, with the segments recorded in forward or backward order. After completing each podcast, participants completed an initial 20-question test and a 40-question delayed recall test with separate questions. Segments were divided into 3 subgroups based on the order in which they were played (primacy group, recency group, and reference group) for assessment of primacy and recency effects. The mean scaled scores from the primacy and recency groups were compared with scores from the reference group.

Results
The study included 195 residents (390 podcasts), with 100 residents listening in the forward order and 95 residents the reverse order. No statistically significant difference was found in immediate recall scores between the primacy and reference groups (d = 0.094; 95% CI, −0.046 to 0.234) or the recency and reference groups (d = −0.041; 95% CI, −0.181 to 0.099) or in 30-day delayed recall score between the primacy and reference groups (d = −0.088; 95% CI, −0.232 to 0.056) or the recency and reference groups (d = −0.083; 95% CI, −0.227 to 0.060).

Conclusions
The order of podcast information did not significantly affect immediate knowledge acquisition or delayed knowledge retention. This finding can inform podcast creators and listeners regarding the order of content when using podcasts for learning.