bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-occurrence of the cephalosporinase cepA and carbapenemase cfiA genes in a Bacteroides fragilis division II strain, an unexpected finding
Authors: Valdezate S , Medina-Pascual M J , Villalón P , Garrido N , Monzón S , Cuesta I , Cobo F
Published: May 2024

Background

Bacteroides fragilis, an anaerobic gut bacterium and opportunistic pathogen, comprises two genetically divergent groups (or divisions) at the species level. Differences exist both in the core and accessory genomes and the beta-lactamase genes, with the cephalosporinase gene cepA represented only in division I and the carbapenemase gene cfiA only in division II.

Methods

Multidrug resistance in a clinical B. fragilis strain was examined by whole-genome sequencing.

Results

Strain CNM20200260 carried the antimicrobial resistance genes cepA, cfiA2, ant(6’), erm(F), mef(En2), est(T), tet(Q) and cat(A), along with 82-Phe mutation in gyrA (together with 47 amino acid changes in gyrA/B and parC/parE). bexA/B and other efflux pump genes were also observed. None of the detected insertion sequences was located upstream of cfiA2. The genome-based taxonomy coefficients (average nucleotide identity, DNA–DNA hybridization similarity and difference in genomic G + C%) with respect to genomes of the strains of B. fragilis division II and the novel species Bacteroides hominis (both cfiA-positive) met the criteria for CNM20200260 to belong to either species (>95%, >70% and <1%, respectively). No such similarity was seen with type strain NCTC 9343 or the representative genome FDAARGOS 1225 of B. fragilis (division I, cfiA-negative). Strain CNM20200260 harboured four out of nine Kyoto Encyclopedia of Genes and Genomes orthologues defined for division I and one of two defined for division II.

Conclusions

This is the first description of the co-occurrence of cepA and cfiA in a Bacteroides strain, confirming the complexity of the taxonomy of this species.
Population pharmacokinetics of daptomycin in critically ill patients receiving extracorporeal membrane oxygenation
Authors: Zhang Li-Chen , Li Qiu-Yue , Zhang Yu-Qiu , Shan Ti-Chao , Li Yuan , Li Yi-Hui , Han Hui , Qin Wei-Dong , Guo Hai-Peng , Zhao Wei , Tang Bo-Hao , Chen Xiao-Mei
Published: May 2024

Background

Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations.

Methods

A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations.

Results

Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are  ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min.

Conclusions

This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.
Clinical outcomes in OPAT patients treated with ceftriaxone 4 g and ceftazidime 6 g extended interval dosing regimens
Authors: Wareham David , Melzer Mark
Published: May 2024

Background

New dosing regimens for ceftriaxone 4 g/24 hours and ceftazidime 3 g/12 hours are convenient for patients receiving OPAT. To date, these have not been clinically validated.

Aim

To assess the tolerability, toxicity and effectiveness of once daily ceftriaxone (4 g) and 12 hourly ceftazidime regimens (3 g twice a day) in the OPAT setting.

Patients and methods

From April 2018 until March 2023; demographic, clinical, microbiological and outcome data were collected on all adult patients discharged to a community-based OPAT team in East London.

Results

There were 487 OPAT episodes. Fifty-three (10.9%) patients received ceftriaxone 4 g once a day and 20 (4.1%) ceftazidime 3 g twice a day. In the ceftriaxone group, the commonest conditions treated were orthopaedic, neurosurgical or diabetic foot infections. OPAT was used to expedite the discharge of 45 (84.9%) patients, the remainder were admission avoidance episodes. The commonest isolate causing infection was MSSA 23 (43.4%). There were no tolerability or toxicity episodes recorded. All patients were cured and bed days saved were 1266.

In the smaller twice-daily ceftazidime cohort, seven (35%) patients were treated for necrotizing otitis externa, six (30%) for bronchiectasis and six (30%) for urinary tract infections. The commonest cause of infection was P. aeruginosa, 18 (90%). One case of nephrotoxicity was recorded. All patients were cured and bed days saved were 896.

Conclusions

Regimens of ceftriaxone 4 g once a day and ceftazidime 3 g twice a day were well tolerated and highly effective. If widely adopted, these regimens will save OPAT and nursing time and enable more patients to be treated.
The Socio-Economic Impact of Coal Mining in Mozambique
Authors: Egger Eva-Maria , Keller Michael , Mouco Jorge Benjamim
Published: May 2024

This study assesses the impact of four coal mines in Mozambique on socio-economic outcomes of the local population. We combine four waves of household surveys with coal mine locations and employ a difference-in-differences model. The timing of the surveys allows us to control for pre-trends and differentiate between the effects during the investment and production periods. The mines led to a causal increase in consumption and a correlational decline in poverty. The mine introduced higher-paying jobs, often obtained by women, which shifted them from agriculture and unpaid work to the mining, service sectors and wage work. This shift impacted family labour dynamics, in particular young males and to a lesser extent young females worked less. The decrease in child labour reduced overall employment. Access to basic services, such as drinking water, electricity and health services, improved. Primary education completion rates increased, while children's schooling was unaffected. Negative consequences were found related to the incidence of sickness and a decline in market access.
Constructing knowledge: the role of AI in medical learning
Authors: Lawson McLean Aaron
Published: May 2024

The integration of large language models (LLMs) like ChatGPT into medical education presents potential benefits and challenges. These technologies, aligned with constructivist learning theories, could potentially enhance critical thinking and problem-solving through inquiry-based learning environments. However, the actual impact on educational outcomes and the effectiveness of these tools in fostering learning require further empirical study. This technological shift necessitates a reevaluation of curriculum design and the development of new assessment methodologies to measure its effects accurately. Additionally, the use of LLMs introduces significant ethical concerns, particularly in addressing inherent AI biases to ensure equitable educational access. LLMs may also help reduce global disparities in medical education by providing broader access to contemporary medical knowledge and practices, though their deployment must be managed carefully to truly support the training of competent, ethical medical professionals.
MENDS-on-FHIR: leveraging the OMOP common data model and FHIR standards for national chronic disease surveillance
Authors: Essaid Shahim , Andre Jeff , Brooks Ian M , Hohman Katherine H , Hull Madelyne , Jackson Sandra L , Kahn Michael G , Kraus Emily M , Mandadi Neha , Martinez Amanda K , Mui Joyce Y , Zambarano Bob , Soares Andrey
Published: May 2024

Objectives

The Multi-State EHR-Based Network for Disease Surveillance (MENDS) is a population-based chronic disease surveillance distributed data network that uses institution-specific extraction-transformation-load (ETL) routines. MENDS-on-FHIR examined using Health Language Seven’s Fast Healthcare Interoperability Resources (HL7® FHIR®) and US Core Implementation Guide (US Core IG) compliant resources derived from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to create a standards-based ETL pipeline.

Materials and Methods

The input data source was a research data warehouse containing clinical and administrative data in OMOP CDM Version 5.3 format. OMOP-to-FHIR transformations, using a unique JavaScript Object Notation (JSON)-to-JSON transformation language called Whistle, created FHIR R4 V4.0.1/US Core IG V4.0.0 conformant resources that were stored in a local FHIR server. A REST-based Bulk FHIR $export request extracted FHIR resources to populate a local MENDS database.

Results

Eleven OMOP tables were used to create 10 FHIR/US Core compliant resource types. A total of 1.13 trillion resources were extracted and inserted into the MENDS repository. A very low rate of non-compliant resources was observed.

Discussion

OMOP-to-FHIR transformation results passed validation with less than a 1% non-compliance rate. These standards-compliant FHIR resources provided standardized data elements required by the MENDS surveillance use case. The Bulk FHIR application programming interface (API) enabled population-level data exchange using interoperable FHIR resources. The OMOP-to-FHIR transformation pipeline creates a FHIR interface for accessing OMOP data.

Conclusion

MENDS-on-FHIR successfully replaced custom ETL with standards-based interoperable FHIR resources using Bulk FHIR. The OMOP-to-FHIR transformations provide an alternative mechanism for sharing OMOP data.
Genomic insights into the critically endangered King Island scrubtit
Authors: Crates Ross , von Takach Brenton , Young Catherine M , Stojanovic Dejan , Neaves Linda E , Murphy Liam , Gautschi Daniel , Hogg Carolyn J , Heinsohn Robert , Bell Phil , Farquharson Katherine A
Published: May 2024

Small, fragmented, or isolated populations are at risk of population decline due to fitness costs associated with inbreeding and genetic drift. The King Island scrubtit Acanthornis magna greeniana is a critically endangered subspecies of the nominate Tasmanian scrubtit A. m. magna, with an estimated population of <100 individuals persisting in three patches of swamp forest. The Tasmanian scrubtit is widespread in wet forests on mainland Tasmania. We sequenced the scrubtit genome using PacBio HiFi and undertook a population genomic study of the King Island and Tasmanian scrubtits using a double-digest restriction site-associated DNA (ddRAD) dataset of 5,239 SNP loci. The genome was 1.48 Gb long, comprising 1,518 contigs with an N50 of 7.715 Mb. King Island scrubtits formed one of four overall genetic clusters, but separated into three distinct subpopulations when analyzed independently of the Tasmanian scrubtit. Pairwise FST values were greater among the King Island scrubtit subpopulations than among most Tasmanian scrubtit subpopulations. Genetic diversity was lower and inbreeding coefficients were higher in the King Island scrubtit than all except one of the Tasmanian scrubtit subpopulations. We observed crown baldness in 8/15 King Island scrubtits, but 0/55 Tasmanian scrubtits. Six loci were significantly associated with baldness, including one within the DOCK11 gene which is linked to early feather development. Contemporary gene flow between King Island scrubtit subpopulations is unlikely, with further field monitoring required to quantify the fitness consequences of its small population size, low genetic diversity, and high inbreeding. Evidence-based conservation actions can then be implemented before the taxon goes extinct.
Effects of vitamin D supplementation on a deep learning–based mammographic evaluation in SWOG S0812
Authors: McGuinness Julia E , Anderson Garnet L , Mutasa Simukayi , Hershman Dawn L , Terry Mary Beth , Tehranifar Parisa , Lew Danika L , Yee Monica , Brown Eric A , Kairouz Sebastien S , Kuwajerwala Nafisa , Bevers Therese B , Doster John E , Zarwan Corrine , Kruper Laura , Minasian Lori M , Ford Leslie , Arun Banu , Neuhouser Marian L , Goodman Gary E , Brown Powel H , Ha Richard , Crew Katherine D
Published: May 2024

Deep learning–based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network–based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.
Harnessing controlled-environment systems for enhanced production of medicinal plants
Authors: Dsouza Ajwal , Dixon Mike , Shukla Mukund , Graham Thomas
Published: May 2024

Medicinal plants are valued for their contributions to human health. However, the growing demand for medicinal plants and the concerns regarding their quality and sustainability have prompted the reassessment of conventional production practices. Controlled-environment cropping systems, such as vertical farms, offer a transformative approach to production of medicinal plants. By enabling precise control over environmental factors, such as light, carbon dioxide, temperature, humidity, nutrients, and airflow, controlled environments can improve the consistency, concentration, and yield of bioactive phytochemicals in medicinal plants. This review explores the potential of controlled-environment systems for enhancing production of medicinal plants. First, we describe how controlled environments can overcome the limitations of conventional production in improving the quality of medicinal plants. Next, we propose strategies based on plant physiology to manipulate environmental conditions for enhancing the levels of bioactive compounds in plants. These strategies include improving photosynthetic carbon assimilation, light spectrum signalling, purposeful stress elicitation, and chronoculture. We describe the underlying mechanisms and practical applications of these strategies. Finally, we highlight the major knowledge gaps and challenges that limit the application of controlled environments, and discuss future research directions.
The wall-associated receptor-like kinase CsWAKL01, positively regulated by the transcription factor CsWRKY53, confers resistance to citrus bacterial canker via regulation of phytohormone signaling
Authors: Yu Qiyuan , He Houzheng , Xian Baohang , Zhang Chenxi , Zhong Xin , Liu Yiqi , Zhang Miao , Li Man , He Yongrui , Chen Shanchun , Li Qiang
Published: May 2024

Citrus bacterial canker (CBC) is a disease that poses a major threat to global citrus production and is caused by infection with Xanthomonas citri subsp. citri (Xcc). Wall-associated receptor-like kinase (WAKL) proteins play an important role in shaping plant resistance to various bacterial and fungal pathogens. In a previous report, CsWAKL01 was identified as a candidate Xcc-inducible gene found to be up-regulated in CBC-resistant citrus plants. However, the functional role of CsWAKL01 and the mechanisms whereby it may influence resistance to CBC have yet to be clarified. Here, CsWAKL01 was found to localize to the plasma membrane, and the overexpression of the corresponding gene in transgenic sweet oranges resulted in pronounced enhancement of CBC resistance, whereas its knockdown had the opposite effect. Mechanistically, the effect of CsWAKL01 was linked to its ability to reprogram jasmonic acid, salicylic acid, and abscisic acid signaling activity. CsWRKY53 was further identified as a transcription factor capable of directly binding to the CsWAKL01 promoter and inducing its transcriptional up-regulation. CsWRKY53 silencing conferred greater CBC susceptibility to infected plants. Overall, these data support a model wherein CsWRKY53 functions as a positive regulator of CsWAKL01 to enhance resistance to CBC via the reprogramming of phytohormone signaling. Together these results offer new insights into the mechanisms whereby WAKLs shape phytopathogen resistance while underscoring the potential value of targeting the CsWRKY53–CsWAKL01 axis when seeking to breed CBC-resistant citrus plant varieties.
Spatial multi-omics characterizes GPR35-relevant lipid metabolism signatures across liver zonation in MASLD
Authors: Otkur Wuxiyar , Zhang Yiran , Li Yirong , Bao Wenjun , Feng Tingze , Wu Bo , Ma Yaolu , Shi Jing , Wang Li , Pei Shaojun , Wang Wen , Wang Jixia , Zhao Yaopeng , Liu Yanfang , Li Xiuling , Xia Tian , Wang Fangjun , Chen Di , Liang Xinmiao , Piao Hai-long
Published: May 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and cancer. The zonal distribution of biomolecules in the liver is implicated in mediating the disease progression. Recently, G-protein-coupled receptor 35 (GPR35) has been highlighted to play a role in MASLD, but the precise mechanism is not fully understood, particularly, in a liver-zonal manner. Here, we aimed to identify spatially distributed specific genes and metabolites in different liver zonation that are regulated by GPR35 in MASLD, by combining lipid metabolomics, spatial transcriptomics (ST), and spatial metabolomics (SM). We found that GPR35 influenced lipid accumulation, inflammatory and metabolism-related factors in specific regions, notably affecting the anti-inflammation factor ELF4 (E74 like E-twenty six (ETS) transcription factor 4), lipid homeostasis key factor CIDEA (cell death-inducing DNA fragmentation factor alpha (DFFA)-like effector A), and the injury response-related genes SAA1/2/3 (serum amyloid A1/2/3), thereby impacting MASLD progression. Furthermore, SM elucidated specific metabolite distributions across different liver regions, such as C10H11N4O7P (3ʹ,5ʹ-cyclic inosine monophosphate (3ʹ,5ʹ-IMP)) for the central vein, and this metabolite significantly decreased in the liver zones of GPR35-deficient mice during MASLD progression. Taken together, GPR35 regulates hepatocyte damage repair, controls inflammation, and prevents MASLD progression by influencing phospholipid homeostasis and gene expression in a zonal manner.
Introduction to Clinical Neurology
Authors: Gelb Douglas J.
Published: May 2024

This resource covers the material that clinicians need to know in order to assess and manage the patients they encounter in general medical practice, and includes extensive factual material about individual disease processes while emphasising the importance of understanding why patients with neurologic conditions are managed the way they are.
The Neurologic Examination (What We Localize)
Authors: Gelb Douglas J.
Published: May 2024

This chapter offers general comments on the neurologic examination and provides specific and comprehensive instructions for performing the exam. It discusses the presentation of the exam, including fine points of terminology. It explains how to interpret abnormal exam findings. It concludes with a section on how to modify the neuro exam in certain circumstances, specifically a screening exam, examining a patient in a video interaction, examining patients with altered level of consciousness, and examining patients with inconsistent or anomalous findings.
Seizures
Authors: Gelb Douglas J.
Published: May 2024

This chapter defines seizures and epilepsy and presents the clinical features of common seizure types and epilepsy syndromes. It discusses the pathophysiology and diagnostic approach, including electroencephalography (EEG). It explains the approaches to management principles, including antiseizure medications (ASMs) and when to start them, ablative surgery, vagus nerve stimulation, deep brain stimulation, responsive stimulation, and ketogenic diet. It discusses lifestyle restrictions (especially driving), status epilepticus and issues related to pregnancy.
Sleep Disorders
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with an explanation of sleep physiology and the tests used in diagnosing sleep disorders. This is followed by detailed discussion of the clinical manifestations, pathophysiology, and approach to diagnosis and management of major sleep disorders: insufficient sleep syndrome, obstructive sleep apnea, central sleep apnea, narcolepsy, psychophysiologic insomnia, delayed sleep-wake phase disorder, advanced sleep-wake phase disorder, night terrors, sleepwalking, sleep talking, confusional arousals, enuresis, periodic limb movements, seizures, rapid eye movement (REM) sleep behavior disorder, and nightmares.
Multifocal Central Nervous System Disorders
Authors: Gelb Douglas J.
Published: May 2024

This chapter covers multifocal CNS disorders, including focal conditions with multifocal propagation as well as intrinsically multifocal conditions. It offers a detailed discussion of the clinical manifestations, pathophysiology, and approach to diagnosis and management of metastases to the brain or spinal cord, paraneoplastic syndromes, CNS abscesses, infective endocarditis, human immunodeficiency virus (HIV), neurosyphilis, Lyme disease, tuberculosis, Herpes simplex virus, Varicella zoster virus, COVID-19, anthrax, smallpox, botulism, multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD), systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and coagulation disorders. The chapter concludes with a brief discussion of functional disorders and the confusion surrounding what causes them and the terminology that should be used.
Headache
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins by distinguishing primary from secondary headaches. It then discusses the pathophysiology of migraine, which is presumed to be similar to the mechanisms underlying other types of headache. It then offers a detailed discussion of the clinical manifestations and approach to diagnosis and management of bacterial meningitis and subarachnoid hemorrhage, the two most urgent causes of secondary headache. It then provides a detailed discussion of the clinical manifestations and approach to diagnosis and management of other causes of secondary headache: viral meningitis or encephalitis, fungal or tuberculous meningitis, mass lesions, giant cell arteritis, idiopathic intracranial hypertension (IIH), spontaneous intracranial hypotension (SIH), cerebral venous dissection, arterial dissection, reversible cerebral vasoconstriction syndrome (RCVS), sinus disease, temporomandibular disorders, and post-concussion syndrome. It then presents a discussion of the clinical manifestations and treatment of primary headache disorders: migraine/tension, trigeminal neuralgia, glossopharyngeal neuralgia, cluster headache, trigeminal autonomic cephalalgias, primary stabbing headache, and persistent idiopathic facial pain.
Visual Symptoms
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with an overview of the visual system and an approach to visual symptoms. It next considers causes of monocular vision loss, particularly optic neuritis in young individuals and—in older individuals—retinal artery occlusion and ischemic optic neuropathy. It next discusses the three main causes of episodic monocular vision loss: migraine, TIA, and increased intracranial pressure. This is followed by a brief discussion of persistent binocular vision loss. Finally, there is a discussion of diplopia, particularly lesions of cranial nerves III, IV, or VI or of the medial longitudinal fasciculus (MLF).
Back Pain and Neck Pain
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with a discussion of the causes of neck or back pain that require urgent surgical intervention: metastasis, abscess, or other causes of spinal cord compression. It then presents the other, less urgent reasons to consider surgery. It then discusses specific conditions: musculoskeletal pain, intervertebral disc herniation, and spinal stenosis.
Incontinence
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with a brief discussion of the components of the nervous system that are involved in bladder and bowel control. It then considers non-neurologic causes of incontinence. It then discusses neurologic causes of incontinence, distinguishing the clinical features that are typical of incontinence due to PNS lesions from the features that suggest a CNS lesion.
Star-formation activity of low-mass galaxies at the peak epoch of galaxy formation probed by deep narrow-band imaging
Authors: Daikuhara Kazuki , Kodama Tadayuki , Pérez-Martínez Jose M , Shimakawa Rhythm , Suzuki Tomoko L , Tadaki Ken-ichi , Koyama Yusei , Tanaka Ichi
Published: May 2024

Low-mass galaxies at high redshifts are the building blocks of more massive galaxies at later times and are thus key populations for understanding galaxy formation and evolution. We have made deep narrow-band observations for two protoclusters and the general field in COSMOS at z ∼ 2. In a clumpy young protocluster, USS1558−003, at z = 2.53, we find many star-forming galaxies well above the star-forming main sequence of field galaxies at the low-mass end ($M_{\star }/\mathrm{{\rm M}_{\odot }}\lt 10^{8.9}$). This suggests that some environmental effects may be at work in low-mass galaxies in high-density regions to enhance their star-formation activities. In the core of this protocluster, we also find enhanced star-formation activity of middle-mass galaxies ($10^{8.9} \lt M_{\star }/\mathrm{{\rm M}_{\odot }} \lt 10^{10.2}$) while such trends are not observed in a more mature protocluster, PKS1138−262 at z = 2.16. We expect these activities to be mainly due to galaxy mergers/interactions and differences in the amount of cold gas accretion. As one piece of evidence, we show that the star-formation activity within individual galaxies in the protoclusters is more centrally concentrated than those in the field. This is probably due to enhanced interactions between galaxies in the protocluster, which can reduce the angular momentum of the gas, drive the gas towards the galaxy centre, and lead to a central starburst.
Probing intracluster dynamics and evolution of globular clusters through cataclysmic variable populations
Authors: Oh Kwangmin , Hong Jongsuk , Hui C Y , Kim Sangin , Giersz Mirek
Published: May 2024

Dynamical interactions in globular clusters (GCs) significantly impact the formation and evolution of binary sources, including cataclysmic variables (CVs). This study investigates the connection between dynamical states of GCs and X-ray luminosity (Lx) distributions of CV populations through both simulations and actual observations. Utilizing a Monte Carlo simulation tool, mocca, we categorize the simulated GCs into three different evolutionary stages which are referred to as Classes I/II/III. Significant differences are found in the Lx distributions of the CVs among these three Classes. In observational aspects, we have analysed 179 CV candidates in 18 GCs observed by the Chandra X-ray Observatory. By dividing these GCs into three Families of different dynamical ages, namely Families I/II/III, the Lx distributions of the CV candidates also show significant differences among these three Families. Both simulations and observational results suggest that CVs in more dynamically evolved clusters (Class/Family III) exhibit brighter X-ray emission. This highlights the influence of the dynamical status of a GC on the properties of its hosted compact binaries. Similar to blue stragglers, CV populations can serve as tracers of a GC’s dynamical history. Our findings provide insights for understanding the interplay between intracluster dynamics and the evolution of compact binaries in GCs.
The ALPINE-ALMA [C ii] survey: characterization of spatial offsets in main-sequence galaxies at z ∼ 4–6
Authors: Killi Meghana , Ginolfi Michele , Popping Gergö , Watson Darach , Zamorani Giovanni , Lemaux Brian C , Fujimoto Seiji , Faisst Andreas , Bethermin Matthieu , Romano Michael , Fudamoto Yoshinobu , Bardelli Sandro , Boquien Médéric , Carniani Stefano , Dessauges-Zavadsky Miroslava , Gruppioni Carlotta , Hathi Nimish , Ibar Eduardo , Jones Gareth C , Koekemoer Anton M , Langan Ivanna , Méndez-Hernández Hugo , Sugahara Yuma , Vallini Livia , Vergani Daniela
Published: May 2024

The morphology of galaxies is shaped by stellar activity, feedback, gas and dust properties, and interactions with surroundings, and can therefore provide insight into these processes. In this paper, we study the spatial offsets between stellar and interstellar medium emission in a sample of 54 main-sequence star-forming galaxies at z ∼ 4–6 observed with the Atacama Large Millimeter/submillimeter Array (ALMA), and drawn from the ALMA Large Program to INvestigate C+ at Early times (ALPINE). We find no significant spatial offset for the majority (∼70 per cent) of galaxies in the sample among any combination of [C ii], far-infrared continuum, optical, and ultraviolet emission. However, a fraction of the sample (∼30 per cent) shows offsets larger than the median by more than 3σ significance (compared to the uncertainty on the offsets), especially between [C ii] and ultraviolet emission. We find that these significant offsets are of the order of ∼0.5–0.7 arcsec, corresponding to ∼3.5–4.5 kiloparsecs. The offsets could be caused by a complex dust geometry, strong feedback from stars and active galactic nuclei, large-scale gas inflow and outflow, or a combination of these phenomena. However, our current analysis does not definitively constrain the origin. Future, higher resolution ALMA and JWST observations may help resolve the ambiguity. Regardless, since there exist at least some galaxies that display such large offsets, galaxy models and spectral energy distribution fitting codes cannot assume co-spatial emission in all main-sequence galaxies, and must take into account that the observed emission across wavelengths may be spatially segregated.
A role for the S4-domain containing protein YlmH in ribosome-associated quality control in Bacillus subtilis
Authors: Takada Hiraku , Paternoga Helge , Fujiwara Keigo , Nakamoto Jose A , Park Esther N , Dimitrova-Paternoga Lyudmila , Beckert Bertrand , Saarma Merilin , Tenson Tanel , Buskirk Allen R , Atkinson Gemma C , Chiba Shinobu , Wilson Daniel N , Hauryliuk Vasili
Published: May 2024

Ribosomes trapped on mRNAs during protein synthesis need to be rescued for the cell to survive. The most ubiquitous bacterial ribosome rescue pathway is trans-translation mediated by tmRNA and SmpB. Genetic inactivation of trans-translation can be lethal, unless ribosomes are rescued by ArfA or ArfB alternative rescue factors or the ribosome-associated quality control (RQC) system, which in Bacillus subtilis involves MutS2, RqcH, RqcP and Pth. Using transposon sequencing in a trans-translation-incompetent B. subtilis strain we identify a poorly characterized S4-domain-containing protein YlmH as a novel potential RQC factor. Cryo-EM structures reveal that YlmH binds peptidyl-tRNA-50S complexes in a position analogous to that of S4-domain-containing protein RqcP, and that, similarly to RqcP, YlmH can co-habit with RqcH. Consistently, we show that YlmH can assume the role of RqcP in RQC by facilitating the addition of poly-alanine tails to truncated nascent polypeptides. While in B. subtilis the function of YlmH is redundant with RqcP, our taxonomic analysis reveals that in multiple bacterial phyla RqcP is absent, while YlmH and RqcH are present, suggesting that in these species YlmH plays a central role in the RQC.
The developmental and evolutionary characteristics of transcription factor binding site clustered regions based on an explainable machine learning model
Authors: Ouyang Zhangyi , Liu Feng , Li Wanying , Wang Junting , Chen Bijia , Zheng Yang , Li Yaru , Tao Huan , Xu Xiang , Li Cheng , Cong Yuwen , Li Hao , Bo Xiaochen , Chen Hebing
Published: May 2024

Gene expression is temporally and spatially regulated by the interaction of transcription factors (TFs) and cis-regulatory elements (CREs). The uneven distribution of TF binding sites across the genome poses challenges in understanding how this distribution evolves to regulate spatio-temporal gene expression and consequent heritable phenotypic variation. In this study, chromatin accessibility profiles and gene expression profiles were collected from several species including mammals (human, mouse, bovine), fish (zebrafish and medaka), and chicken. Transcription factor binding sites clustered regions (TFCRs) at different embryonic stages were characterized to investigate regulatory evolution. The study revealed dynamic changes in TFCR distribution during embryonic development and species evolution. The synchronization between TFCR complexity and gene expression was assessed across species using RegulatoryScore. Additionally, an explainable machine learning model highlighted the importance of the distance between TFCR and promoter in the coordinated regulation of TFCRs on gene expression. Our results revealed the developmental and evolutionary dynamics of TFCRs during embryonic development from fish, chicken to mammals. These data provide valuable resources for exploring the relationship between transcriptional regulation and phenotypic differences during embryonic development.
Ocular Mpox in a Breastfeeding Healthcare Provider
Authors: Lovett Sara , Griffith Jayne , Lehnertz Nick , Fox Teresa , Siwek Greg , Barnes Aaron M T , Kofman Aaron D , Hufstetler Kaitlin , Greninger Alexander L , Townsend Michael B , Carson William C , Lynfield Ruth , Cash-Goldwasser Shama
Published: May 2024

A healthcare provider unknowingly treated a patient with mpox and subsequently developed ocular mpox without rash. She breastfed during illness; her infant was not infected. This report addresses 3 challenges in mpox management and control: diagnosis in the absence of rash, exposures in healthcare settings, and management of lactating patients.
CVAs in Practice
Authors: Kar Partha , Ziegler Ann-Kathrin , Lacey Sean , Jemmett Thomas , Kassam Karim
Published: May 2024

This chapter expounds on the practical considerations and structure of CVAs and proposes landlord CVAs. Over time, the market developed that CVAs have been utilised for numerous purposes in practices such as restructuring contexts and rationalising lease portfolios. Additionally, CVAs can be used as a tool to implement a commercial compromise arrangement between companies and creditors sans a consensual agreement regardless of the debtor's insolvency. Partial consent can only bind consenting parties instead of shielding dissenting creditors from enforcement actions. Jurisdictions and foreign recognition are considered when invoking a CVA. The chapter also tackles an overview of the CVAs taken by Steinhoff International Holdings NV's affiliates.
Hyperbaric oxygen treatment reveals spatiotemporal OXPHOS plasticity in the porcine heart
Authors: Heidler Juliana , Cabrera-Orefice Alfredo , Wittig Ilka , Heyne Estelle , Tomczak Jan-Niklas , Petersen Bjoern , Henze Dirk , Pohjoismäki Jaakko L O , Szibor Marten
Published: May 2024

Cardiomyocytes meet their high ATP demand almost exclusively by oxidative phosphorylation (OXPHOS). Adequate oxygen supply is an essential prerequisite to keep OXPHOS operational. At least two spatially distinct mitochondrial subpopulations facilitate OXPHOS in cardiomyocytes, i.e. subsarcolemmal (SSM) and interfibrillar mitochondria (IFM). Their intracellular localization below the sarcolemma or buried deep between the sarcomeres suggests different oxygen availability. Here, we studied SSM and IFM isolated from piglet hearts and found significantly lower activities of electron transport chain enzymes and F1FO-ATP synthase in IFM, indicative for compromised energy metabolism. To test the contribution of oxygen availability to this outcome, we ventilated piglets under hyperbaric hyperoxic (HBO) conditions for 240 min. HBO treatment raised OXPHOS enzyme activities in IFM to the level of SSM. Complexome profiling analysis revealed that a high proportion of the F1FO-ATP synthase in the IFM was in a disassembled state prior to the HBO treatment. Upon increased oxygen availability, the enzyme was found to be largely assembled, which may account for the observed increase in OXPHOS complex activities. Although HBO also induced transcription of genes involved in mitochondrial biogenesis, a full proteome analysis revealed only minimal alterations, meaning that HBO-mediated tissue remodeling is an unlikely cause for the observed differences in OXPHOS. We conclude that a previously unrecognized oxygen-regulated mechanism endows cardiac OXPHOS with spatiotemporal plasticity that may underlie the enormous metabolic and contractile adaptability of the heart.
A biospecies-derived genomic DNA hybrid gel electrolyte for electrochemical energy storage
Authors: Mitta Sekhar Babu , Kim Jeonghun , Rana Harpalsinh H , Kokkiligadda Samanth , Lim Yong Taik , Bhang Suk Ho , Park Ho Seok , Um Soong Ho
Published: May 2024

Intrinsic impediments, namely weak mechanical strength, low ionic conductivity, low electrochemical performance, and stability have largely inhibited beyond practical applications of hydrogels in electronic devices and remains as a significant challenge in the scientific world. Here, we report a biospecies-derived genomic DNA hybrid gel electrolyte with many synergistic effects, including robust mechanical properties (mechanical strength and elongation of 6.98 MPa and 997.42%, respectively) and ion migration channels, which consequently demonstrated high ionic conductivity (73.27 mS/cm) and superior electrochemical stability (1.64 V). Notably, when applied to a supercapacitor the hybrid gel-based devices exhibit a specific capacitance of 425 F/g. Furthermore, it maintained rapid charging/discharging with a capacitance retention rate of 93.8% after ∼200,000 cycles while exhibiting a maximum energy density of 35.07 Wh/kg and a maximum power density of 193.9 kW/kg. This represents the best value among the current supercapacitors and can be immediately applied to minicars, solar cells, and LED lightning. The widespread use of DNA gel electrolytes will revolutionize human efforts to industrialize high-performance green energy.
American Federalism: A Blessing and a Curse for Transgender Rights
Authors: Taylor Jami , Flores Andrew , Haider-Markel Donald , Lewis Daniel , Miller Patrick
Published: May 2024

The development of transgender rights in the United States has been hobbled by a patchwork of inconsistent state laws. The irregularity is a function of the political opportunity structure in the United States, which is defined by a sharp partisan divide and by the federal system’s division of power. National policymaking on transgender rights has stalled in Congress. Executive branch policymaking is often subject to challenge in the federal courts, and different administrations have varied in their approaches. In addition, the Supreme Court’s decision in Bostock narrowly advanced transgender rights in employment law but also invited challenges in other areas. With inaction and inconsistency at the national level, states are using their reserved powers in the federal system to diverge along the partisan divide. Republican-controlled states are enacting repressive measures, while Democratic-controlled states have done the opposite. For transgender people, their rights are increasingly dependent on which state they are in.
“You Can’t Just Give People Food”: Whiteness in Practice at an Evangelical Food Pantry
Authors: McNeely Andrew
Published: May 2024

Whiteness continues to be a focus of scholarly research particularly as it informs understandings of white evangelical religious structures, organizations, and practices. This study draws on 34 months of ethnographic study to present a case study of an evangelical food pantry in central Texas and analyzes the policies, roles, and norms of the volunteers. The findings document examples of white, conservative, evangelical religious practices that promote the meaning–making and worldviews of evangelical volunteers while erasing and disempowering the recipients. Taken together, these findings add to our understanding of whiteness, which is already evidenced at the structural level by documenting examples of everyday practices in public spaces that promote racialized hierarchies.
The pharynx of the iconic stem-group chondrichthyan Acanthodes Agassiz, 1833 revisited with micro-computed tomography
Authors: Dearden Richard P , Herrel Anthony , Pradel Alan
Published: May 2024

Acanthodes has long been the primary source of information on the pharyngeal skeleton of ‘acanthodians’. Because of this its anatomy has played a disproportionate role in attempts to understand the evolution of the jawed vertebrate pharynx and the clade as a whole. However, the anatomy of the pharynx of Acanthodes, now understood to be a stem-group chondrichthyan, remains poorly characterized and subject to several competing interpretations. We used computed tomography to image the articulated pharyngeal skeletons of three specimens of Acanthodes confusus from Lebach, Germany. Acanthodes has a mélange of osteichthyan-like and chondrichthyan-like morphologies in its pharyngeal skeleton. Like many other chondrichthyans, Acanthodes lacked hypohyals, and had four pairs of posteriorly oriented pharyngobranchials. Like osteichthyans, Acanthodes possessed an interhyal, but lacked the separate infra- and supra-pharyngobranchial elements present in osteichthyans and the crown-chondrichthyan Ozarcus. Using these new data we built and animated a digital 3D model of the pharyngeal endoskeleton in Acanthodes, showing that the jaws could have swung outwards during the opening cycle, increasing the anteriorly facing area of the gape for suspension feeding. These new data provide a more definitive picture of the anatomy of a taxon that has long been of great significance in early vertebrate palaeontology.
Key Challenges in Plant Pathology in the Next Decade
Authors: Wang Nian , Sundin George W. , Fuente Leonardo De La , Cubero Jaime , Tatineni Satyanarayana , Brewer Marin T. , Zeng Quan , Bock Clive H. , Cunniffe Nik J. , Wang Congli , Candresse Thierry , Chappell Thomas , Coleman Jeffrey J. , Munkvold Gary
Published: May 2024

Plant diseases significantly impact food security and food safety. It was estimated that food production needs to increase by 50% to feed the projected 9.3 billion people by 2050. Yet, plant pathogens and pests are documented to cause up to 40% yield losses in major crops, including maize, rice, and wheat, resulting in annual worldwide economic losses of approximately US$220 billion. Yield losses due to plant diseases and pests are estimated to be 21.5% (10.1 to 28.1%) in wheat, 30.3% (24.6 to 40.9%) in rice, and 22.6% (19.5 to 41.4%) in maize. In March 2023, The American Phytopathological Society (APS) conducted a survey to identify and rank key challenges in plant pathology in the next decade. Phytopathology subsequently invited papers that address those key challenges in plant pathology, and these were published as a special issue. The key challenges identified include climate change effect on the disease triangle and outbreaks, plant disease resistance mechanisms and its applications, and specific diseases including those caused by Candidatus Liberibacter spp. and Xylella fastidiosa. Additionally, disease detection, natural and man-made disasters, and plant disease control strategies were explored in issue articles. Finally, aspects of open access and how to publish articles to maximize the Findability, Accessibility, Interoperability, and Reuse of digital assets in plant pathology were described. Only by identifying the challenges and tracking progress in developing solutions for them will we be able to resolve the issues in plant pathology and ultimately ensure plant health, food security, and food safety.
Sudden Cardiac Death Risk Stratification in Heart Failure With Preserved Ejection Fraction
Authors: Huang Xu , Li Yangjie , Zheng Honglu , Xu Ying
Published: May 2024

Heart failure with preserved ejection fraction (HFpEF) poses a significant clinical challenge, with sudden cardiac death (SCD) emerging as one of the leading causes of mortality. Despite advancements in cardiovascular medicine, predicting and preventing SCD in HFpEF remains complex due to multifactorial pathophysiological mechanisms and patient heterogeneity. Unlike heart failure with reduced ejection fraction, where impaired contractility and ventricular remodeling predominate, HFpEF pathophysiology involves heavy burden of comorbidities such as hypertension, obesity, and diabetes. Diverse mechanisms, including diastolic dysfunction, microvascular abnormalities, and inflammation, also contribute to distinct disease and SCD risk profiles. Various parameters such as clinical factors and electrocardiogram features have been proposed in SCD risk assessment. Advanced imaging modalities and biomarkers offer promise in risk prediction, yet comprehensive risk stratification models specific to HFpEF ar0e lacking. This review offers recent evidence on SCD risk factors and discusses current therapeutic strategies aimed at reducing SCD risk in HFpEF.
Cardiac Manifestations of Lymphoma: A Review of Primary and Secondary Cardiac Lymphoma
Authors: Khurshid Aatif , Okezue Chisom , Frishman William H. , Aronow Wilbert S.
Published: May 2024

Primary cardiac lymphoma (PCL) is a very unique and uncommon disease presentation, with reports in the literature limited to case reports. Most often it is B-cell in origin, predominantly diffuse large B-cell lymphoma. Symptomatic presentation of PCL depends on the location of anatomic involvement, but most often involves the right heart, with presentation consistent with heart failure, pericardial effusions, and atrioventricular nodal blockade. Endomyocardial biopsy is necessary for diagnosis, but cardiac magnetic resonance imaging has been the most useful for staging of the disease. The disease has a poor prognosis but treatment with chemotherapy has been the most successful approach. Particularly, the chemotherapy regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone has been reported to be successful for diffuse large B-cell lymphoma, so it is often utilized first. In newer reports of patients with PCL, there may be a role of autologous stem cell transplant along with consolidative chemotherapy in younger patients diagnosed with PCL. Secondary cardiac lymphoma (SCL) is a more common occurrence that is often asymptomatic and recognized after the patient has passed from either the primary lymphoma or some other reason. Unlike PCL, SCL is more expansive and not often confined to the right heart. However, in patients with SCL who do have cardiac symptoms, the diagnostic approach and treatment are similar to that of PCL.