bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond 2D: A scalable and highly sensitive method for a comprehensive 3D analysis of kidney biopsy tissue
Authors: Yamada Hiroyuki , Makino Shin-ichi , Okunaga Issei , Miyake Takafumi , Yamamoto-Nonaka Kanae , Oliva Trejo Juan Alejandro , Tominaga Takahiro , Empitu Maulana A , Kadariswantiningsih Ika N , Kerever Aurelien , Komiya Akira , Ichikawa Tomohiko , Arikawa-Hirasawa Eri , Yanagita Motoko , Asanuma Katsuhiko
Published: January 2024

The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-μm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology.
Multiple sclerosis and hypogonadism: is there a relationship?
Authors: Hammad Muhammed A M , Rush Adriana , Loeb Charles A , Banton Jasmin , Abou Chawareb Elia , Khanmammadova Narmina , Gevorkyan Rafael R , Barham David W , Yafi Faysal A , Jenkins Lawrence C
Published: January 2024

Introduction

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is widely recognized as a disease primarily affecting women. The relationship between MS and hypogonadism is complex and not fully understood, with recent evidence showing that hypogonadism may have a significant impact on the quality of life and disease progression of patients with MS.

Objectives

This review aims to provide an overview of the current knowledge regarding the relationship between MS and hypogonadism, including the mechanisms underlying this relationship; the effects of hypogonadism on patients with MS; and the potential benefits and drawbacks of testosterone replacement therapy for patients with MS and hypogonadism.

Methods

This scientific review analyzed 19 articles that investigated the potential relationship among MS, testosterone levels, and hypogonadism. The articles were published between November 2008 and March 2022 and were identified through a comprehensive search of the PubMed database. The search terms used included “multiple sclerosis,” “testosterone,” “hypogonadism,” and “MS and testosterone levels.”

Results

Of the 19 articles reviewed, 11 described a positive correlation between low testosterone levels and dysfunction within the hypothalamic-pituitary-gonadal axis in individuals with MS. These findings suggest that low testosterone levels may contribute to dysfunction within the hypothalamus-pituitary-gonadal axis, which plays a crucial role in regulating testosterone production. The results also showed a relationship between sexual dysfunction and low testosterone levels, as well as a positive correlative relationship between these factors.

Conclusion

The reviewed articles indicate a complex relationship among MS, testosterone levels, and the hypothalamic-pituitary-gonadal axis, with low testosterone levels potentially contributing to dysfunction in this axis and to sexual dysfunction. Further research is needed to better understand the effects of testosterone therapy on MS and sexual dysfunction in patients with MS.
Deep Learning and Likelihood Approaches for Viral Phylogeography Converge on the Same Answers Whether the Inference Model Is Right or Wrong
Authors: Thompson Ammon , Liebeskind Benjamin J , Scully Erik J , Landis Michael J
Published: January 2024

Analysis of phylogenetic trees has become an essential tool in epidemiology. Likelihood-based methods fit models to phylogenies to draw inferences about the phylodynamics and history of viral transmission. However, these methods are often computationally expensive, which limits the complexity and realism of phylodynamic models and makes them ill-suited for informing policy decisions in real-time during rapidly developing outbreaks. Likelihood-free methods using deep learning are pushing the boundaries of inference beyond these constraints. In this paper, we extend, compare, and contrast a recently developed deep learning method for likelihood-free inference from trees. We trained multiple deep neural networks using phylogenies from simulated outbreaks that spread among 5 locations and found they achieve close to the same levels of accuracy as Bayesian inference under the true simulation model. We compared robustness to model misspecification of a trained neural network to that of a Bayesian method. We found that both models had comparable performance, converging on similar biases. We also implemented a method of uncertainty quantification called conformalized quantile regression that we demonstrate has similar patterns of sensitivity to model misspecification as Bayesian highest posterior density (HPD) and greatly overlap with HPDs, but have lower precision (more conservative). Finally, we trained and tested a neural network against phylogeographic data from a recent study of the SARS-Cov-2 pandemic in Europe and obtained similar estimates of region-specific epidemiological parameters and the location of the common ancestor in Europe. Along with being as accurate and robust as likelihood-based methods, our trained neural networks are on average over 3 orders of magnitude faster after training. Our results support the notion that neural networks can be trained with simulated data to accurately mimic the good and bad statistical properties of the likelihood functions of generative phylogenetic models.
Crime and Gender Segregation: Evidence from the Bogota “Pico y Genero” Lockdown
Authors: Knight Brian , Ponce de Leon Maria Mercedes , Tribin Ana
Published: January 2024

The city of Bogota implemented a lockdown during the pandemic under which only men were allowed out on odd days and only women were allowed out on even days. Crime rates in Bogota increased, relative to a synthetic Bogota and relative to the pre-period, during this gender-based lockdown. Moreover, this increase is driven by more crime on men-only days and, more specifically, more robberies with male victims on men-only days. There is no evidence that higher crime rates on men-only days are offset by lower crime rates on women-only days. In fact, there is evidence of some increases in crimes with female victims on women-only days. In particular, there was an increase in robberies involving female victims on women-only days during the second half of the lockdown, when some restrictions were eased and more men, and thus more potential perpetrators, were on the streets. Overall, the gender-based lockdown, if anything, increased crime.
Patterns of work and retirement in a pension system with a flexible old-age retirement age: a register study of Finnish employees and self-employed persons born in 1949
Authors: Polvinen Anu , Riekhoff Aart-Jan , Nivalainen Satu , Kuivalainen Susan
Published: January 2024

The aims of this study were to explore patterns of work and retirement of Finnish employees and self-employed persons in a pension system with a flexible old-age retirement age and how income develops in these patterns. We used individual-level register data from Statistics Finland of the total Finnish birth cohort born in 1949. The cohort was 62–70 years old over the study period 2011–2019. Sequence and cluster analyses were used to identify typical trajectories of individuals’ transitions in and out of salaried work and self-employment and work in old-age retirement. Our analysis yielded a ten-cluster solution: four clusters were found for employees who did not continue working in retirement (62%), four clusters for those employees who continued working in retirement (26%), and two clusters for the self-employed (12%). The clusters differed by the timing of retirement. The results showed that employees who retired earlier on an old-age pension and who were not working afterwards had lower incomes. Their incomes also decreased after old-age retirement. Employees who worked for several years in retirement had higher incomes which remained stable between the ages of 62 and 70. We found two types of self-employed persons: those who continued working in retirement with high incomes and those who stopped working earlier and had lower incomes. The results indicate that inequalities between lower and higher income groups might become exacerbated in a flexible retirement system.
The first fossil record of an aquatic caecilian (Gymnophiona: Typhlonectidae)
Authors: Santos Rodolfo Otávio , Wilkinson Mark , do Couto Ribeiro Graziella , Carvalho Alberto B , Zaher Hussam
Published: January 2024

The lissamphibian clade Gymnophiona includes approximately 220 recognized modern species known by the English vernacular as caecilians and characterized by their elongated and annulated bodies, without girdles or limbs. Fossils of caecilians are particularly rare and mostly limited to isolated vertebrae. Until now, only four bona fide Gymnophionomorpha species have been named based on fossils. Only one of these (Apodops pricei) is a crown-group caecilian, but its affinities with modern caecilians are uncertain because the material is limited to one damaged vertebra and is currently lost. Here we describe a new genus and species of caecilian from the Oligocene Tremembé Formation, Brazil, based on a partially preserved fossil skeleton (including elements of the skull and postcranium) that is damaged but still partly articulated. We investigated the fossil caecilian’s anatomy using high-resolution microcomputed tomography, and then compared it to the osteology of modern species. We interpret the fossil as a member of Typhlonectidae, a family of caecilians well known for their aquatic and semi-aquatic lifestyles. This new record represents the first record for caecilians from the Oligocene and also the first fossil species confidently assigned to an extant caecilian family.
Identification of HLB Susceptibility Genes in a Citrus Population Generated Using Multiplexed CRISPR/Cas9 Gene Editing
Authors: Sagawa Cintia
Published: January 2024

Citrus greening or Huanglongbing (HLB) disease is caused by the bacteria Candidatus Liberibacter spp. which is a major threat to the citrus industry worldwide. This has led to the generation of a large number of genomic databases characterizing HLB at the molecular level. Based on the genomic information of 71 published transcriptomic and proteomic datasets we selected 1,200 potential susceptibility genes associated with HLB in citrus. By using CRISPR/Cas9 technology combined with a multiplex approach, we generated 300 constructs targeting a combination of four of those genes in each construct. We currently have a population of over 3,000 transformed lines of Carrizo, a commercial rootstock hybrid (Citrus sinensis 'Washington' sweet orange X Poncirus trifoliata) and population of Valencia sweet orange lines with a diversified combination of mutations. To aid in genotyping, our group is performing a whole genome sequencing of the hybrid Carrizo. Biallelic/homozygous mutants were confirmed by Sanger sequencing of target sites and alignment with respective genomes. Confirmed mutants are currently being tested for bacterial resistance. Identification and stacking of susceptibility gene mutations will be valuable in developing tolerance to HLB and these mutations can subsequently be introduced into other economically significant citrus cultivars and evaluated in the field.
State-of-art review: intravascular imaging in percutaneous coronary interventions
Authors: Nafee Tarek , Shah Areeb , Forsberg Michael , Zheng Jingsheng , Ou Jiafu
Published: January 2024

The history of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) reflects the relentless pursuit of innovation in interventional cardiology. These intravascular imaging technologies have played a pivotal role in our understanding of coronary atherosclerosis, vascular pathology, and the interaction of coronary stents with the vessel wall. Two decades of clinical investigations demonstrating the clinical efficacy and safety of intravascular imaging modalities have established these technologies as staples in the contemporary cardiac catheterization lab’s toolbox and earning their place in revascularization clinical practice guidelines. In this comprehensive review, we will delve into the historical evolution, mechanisms, and technical aspects of IVUS and OCT. We will discuss the expanding evidence supporting their use in complex percutaneous coronary interventions, emphasizing their crucial roles in optimizing patient outcomes and ensuring procedural success. Furthermore, we will explore the substantial advances that have propelled these imaging modalities to the forefront of contemporary interventional cardiology. Finally, we will survey the latest developments in the field and explore the promising future directions that have the potential to further revolutionize coronary interventions.
Brugada syndrome: from genetics, diagnosis to clinical therapy
Authors: Huang Kexin , Ren Jun
Published: January 2024

Brugada syndrome is an inherited disease closely associated with genetic mutations, resulting in ventricular fibrillation and sudden cardiac death. To date, more than 40 genes have been identified to participate in the etiology of this devastating myocardial pathology, among which SCN5A is the predominant cause. Although considerable advances have been made in the molecular genetics of Brugada syndrome over the past decades, a comprehensive view of gene variants associated with Brugada syndrome pathogenicity and their pathophysiological mechanisms is still lacking. Recent studies have reanalyzed and reevaluated relevant genes and further elaborated genetic mechanisms underneath Brugada syndrome. Currently, gene-specific therapies based on culprit pathogenic genes are rapidly evolving, thus offering prospects for future research.
SGLT2 Inhibition in Heart Failure: Clues to Cardiac Effects?
Authors: Savage Patrick , Dixon Lana , Grieve David , Watson Chris
Published: January 2024

Following the publication of several landmark clinical trials such as dapagliflozin in patients with heart failure and reduced ejection fraction, dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure, and empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction, sodium-glucose cotransport 2 inhibitors have been rapidly incorporated as a guideline-directed therapy in the treatment of heart failure. Moreover, their benefits appear to extend across the spectrum of left ventricular dysfunction which in some respects, can be seen as the holy grail of heart failure pharmacotherapy. Despite its plethora of proven cardioprotective benefits, the mechanisms by which it exerts these effects remain poorly understood, however, it is clear that these extend beyond that of promotion of glycosuria and natriuresis. Several hypotheses have emerged over the years including modification of cardiovascular risk profile via weight reduction, improved glucose homeostasis, blood pressure control, and natriuretic effect; however, these mechanisms do not fully explain the potent effects of the drug demonstrated in large-scale randomized trials. Other mechanisms may be at play, specifically the down-regulation of inflammatory pathways, improved myocardial sodium homeostasis, modulation of profibrotic pathways, and activation of nutrient deprivation signaling pathways promoting autophagic flux. This review seeks to summarize the cardioprotective benefits demonstrated in major clinical trials and provide a succinct review of the current theories of mechanisms of action, based on the most recent evidence derived from both clinical and laboratory data.
Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study
Authors: Kadambari Seilesh , Feng Shuo , Liu Xinxue , Andersson Monique , Waterfield Rebecca , Fodder Harriet , Jacquemot Aimee , Galal Ushma , Rafferty Aisling , Drew Richard J. , Rodrigues Charlene , Sadarangani Manish , Riordan Andrew , Martin Natalie G. , Defres Sylviane , Solomon Tom , Pollard Andrew J. , Paulus Stephane
Published: January 2024

Background:

Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children’s Health Ireland at Temple Street in Dublin.

Methods:

Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012–2016), presenting before implementation of the FilmArray.

Results:

The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli, which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days).

Conclusions:

The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.
The effect of a music-based caregiving intervention on pain intensity in nursing home patients with dementia. A cluster-randomized controlled study
Authors: Myrenget Martin Elstad , Rustøen Tone , Myskja Audun , Småstuen Milada , Rangul Vegar , Håpnes Odd , Borchgrevink Petter C. , Butler Stephen , Selbæk Geir , Husebø Bettina , Sandvik Reidun
Published: January 2024

Treatment of chronic pain in patients with dementia is challenging because they have reduced ability to report pain and are particularly vulnerable to side effects of analgesics. Different types of music-based therapy have been recommended and are used as an alternative to analgesics, but the evidence is lacking. Therefore, we performed a cluster-randomized controlled study (RCT) to reduce pain intensity using music-based caregiving (MBC) over 8 weeks in nursing home patients with dementia and chronic pain. We also investigated if the amount of MBC and different chronic pain syndromes would impact on the effect. Of the 645 patients, 498 patients from 36 wards in 12 nursing homes were screened for dementia and pain. Using the Clinical Dementia Rating Scale and the Mobilization–Observation–Behavior–Intensity–Dementia Pain Scale (range 0-10), 279 (71% females, 42% severe dementia) nursing home patients were randomized to intervention group (n = 134, 18 wards) or control group (n = 145, 18 wards). The main outcome was change in pain intensity before and after the intervention. The study did not reveal any effect of MBC on pain intensity when compared with the control group (B = −0.15, 95% CI [−0.72 to 0.43]). No significant difference was found within the intervention group analyzing the impact of intervention time (B = 0.73, 95% CI [−0.55 to 2.02]) or chronic primary vs secondary pain syndromes (B = 0.45, 95% CI [−0.05 to 0.96]). Our data from this first RCT on music and pain intensity in patients with dementia and chronic pain did not find an effect of MBC on pain.
Emergency Care for Pediatric and Adult Patients Affected by Complex Vascular Malformations
Authors: Sisk Bryan A. , Bereitschaft Christine , Goldberg Jessica , Kerr Anna M.
Published: January 2024

Objectives:

To characterize the experiences of patients with vascular malformations (VMs) when seeking care for acute or emergent health needs.

Methods:

Semistructured qualitative interviews and survey study.

Setting:

National recruitment through patient advocacy groups and multidisciplinary vascular anomaly clinics.

Patients/Participants:

Adult patients and parents of children with self-reported VM.

Results:

We interviewed 25 young adult patients and 34 parents. We received survey responses from 138 adult patients and 73 parents who answered all items of interest (analytic cohort = 211). Interview participants described negative experiences with emergency care related to 4 themes: (1) delayed or inadequate care, (2) lack of competent, knowledgeable clinicians, (3) lack of collegial collaboration, and (4) insufficient trust of clinicians in parent’s or patient’s knowledge. Patients and parents reported an average of 1.7 and 2.6 VM-related health problems requiring emergent management in the prior year, respectively. In multivariable logistic regression, having at least one acute or emergent problem in the prior year was associated with household income ≥$100 000 (odds ratio = 0.34, 95% confidence interval, 0.17–0.70), but not gender, race, and ethnicity, age, having a VM specialist, or primary care doctor’s knowledge of VMs.

Conclusions:

Many patients with VMs require emergent or acute care for complications of their VM. Patients with lower household incomes are more likely to experience these emergent events. Negative experiences often focused on nonsupportive clinician behaviors. Future studies should develop tools to empower patient self-advocacy and provide high-yield information to nonspecialist clinicians.
A cost comparison of liver acquisition fees for donation after circulatory death versus donation after brain death donors
Authors: Wall Anji E. , Da Graca Briget , Asrani Sumeet K. , Ruiz Richard , Fernandez Hoylan , Gupta Amar , Martinez Eric , Bayer Johanna , McKenna Gregory , He Lee Seung , Trotter James F. , Testa Giuliano
Published: January 2024

Donation after circulatory death (DCD) donors now represent over 30% of the deceased donor pool in the United States. Compared to donation after brain death, DCD is less likely to result in transplantation. For each potential donor whose organs cannot be utilized for transplantation (ie, dry run), fees are associated with the attempted donation, which add to the overall costs of organ acquisition. To better characterize the true costs of DCD liver acquisition, we performed a cost comparison of the fees associated with organ acquisition for DCD versus donation after brain death at a single transplant institute that comprises 2 liver transplant centers. Cost, recipient, and transportation data for all cases, including fees associated with liver acquisition from July 1, 2019, to October 31, 2021, were collected. We found that the total cost of DCD liver acquisition per liver transplant was $15,029 more than that for donation after brain death donation, with 18% of the costs of the DCD transplant attributed to dry runs. Overall, the costs associated with DCD transplantation accounted for 34.5% of the total organ acquisition costs; however, DCD transplantation accounted for 30.3% of the transplantation volume. Because the expansion of DCD is essential to increasing the availability of liver grafts for transplantation, strategies need to be implemented to decrease the costs associated with dry runs, including using local recovery, transferring donors to hospitals close to transplant centers, and performing more prerecovery organ analysis. Moreover, these strategies are needed to ensure that financial disincentives to DCD procurement and utilization do not reverse the gains made by expanding the organ donor pool using machine perfusion technologies.
Association between the remnant cholesterol to high-density lipoprotein cholesterol ratio and the risk of coronary artery disease
Authors: Pan Liting , Jiang Weifang , Liao Liping , Li Weizhen , Wang Fang
Published: January 2024

Background

The purpose of this study was to evaluate the relationship between remnant cholesterol (RC) to high-density lipoprotein cholesterol (HDL-C) ratio and the risk of coronary artery disease (CAD). We also investigated the clinical value of RC/HDL-C ratio in evaluating the severity of CAD and in predicting the short-term prognosis of CAD patients.

Methods

In total, 615 patients were enrolled and they were classified into a CAD group (418 cases) and a normal group (197 cases) according to the results of coronary angiography. Serum RC/HDL-C ratio and Gensini score were calculated. Multivariate logistic regression and receiver operating characteristic (ROC) curves were employed to evaluate the association between RC/HDL-C ratio and CAD. The effect of RC/HDL-C ratio on the progression of major adverse cardiovascular events (MACEs) was also explored.

Results

Increased RC/HDL-C ratio was associated with an increased risk of CAD (OR: 11.122; 95% CI: 5.903–20.954; P < 0.001). When stratified by CAD subtypes, increased RC/HDL-C ratio was correlated with a greater risk of acute coronary syndrome (ACS) (OR:1.549; 95% CI: 1.014–2.364; P < 0.05). Compared with the first quartile, the 4th quartile of RC/HDL-C ratio had a 9.774-fold (P = 0.000) increase in the odds ratio for CAD, and a 2.241-fold (P = 0.017) increase in the odds ratio for ACS. RC/HDL-C ratio was an independent determinant of Gensini score ≥32 (OR: 2.138, 95% CI:1.389–3.292, P < 0.01), and multi-branch (MVD) (OR: 2.245; 95% CI: 1.468–3.443; P < 0.001). The prevalence of Gensini score ≥32 and MVD in the 4th quartile of RC/HDL-C ratio group were much higher than that of other quartile groups (P < 0.01). Moreover, the areas under the ROC for the predictive value of RC/HDL-C ratio for CAD, ACS, Gensini score ≥32, and MVD were 0.702, 0.563, 0.602, and 0.669, respectively. Furthermore, the incidence of MACEs was significantly increased in CAD patients with levels of RC/HDL-C ratio (P < 0.05).

Conclusion

RC/HDL-C ratio plays an important role in the progression and severity of CAD.
Small bowel intussusception – aetiology & management
Authors: Sciberras Nicole , Zammit Stefania Chetcuti , Sidhu Reena
Published: January 2024

Purpose of review

Adult small bowel intussusception (SBI) differs in incidence, symptomatology and management from the more commonly encountered paediatric intussusception. This review spans across the multitude of causes of adult SBI, and summarises the diagnostic work-up and management options according to recent literature.

Recent findings

There has been an increase in use of small bowel capsule endoscopy and point-of-care ultrasound for the diagnosis of acute adult SBI.

A high degree of suspicion of a malignant cause of SBI is required in the adult population. Alarm clinical features include weight loss, history of malignancy, and iron deficiency anaemia. CT remains the gold standard imaging technique as it may identify the lead point and thus aid in endoscopic or surgical management. If malignancy is excluded and no lead point is identified, serology and histology may be helpful to look for inflammatory, infective and autoimmune aetiology.
The use and timing of angio-embolization in pediatric blunt liver and spleen injury
Authors: Naiditch Jessica A. , Notrica David M. , Sayrs Lois W. , Linnaus Maria , Stottlemyre Rachael , Garcia Nilda M. , Lawson Karla A. , Cohen Aaron S. , Letton Robert W. , Johnson Jeremy , Maxson R. Todd , Eubanks James W. , Ryan Mark , Alder Adam , Ponsky Todd A , St. Peter Shawn D , Bhatia Amina M. , Leys Charles M.
Published: January 2024

Background

Nonoperative management (NOM) is the standard of care for the management of blunt liver and spleen injuries (BLSI) in the stable pediatric patient. Angiography with embolization (AE) is utilized as an adjunctive therapy in the management of adult BLSI patients, but it is rarely utilized in the pediatric population. In this planned secondary analysis, we describe the current utilization patterns of AE in the management of pediatric BLSI.

Methods

After obtaining IRB approval at each center, cohort data was collected prospectively for children admitted with BLSI confirmed on CT at 10 Level 1 pediatric trauma centers (PTCs) throughout the United States from April 2013 to January 2016. All patients who underwent angiography with or without embolization for a BLSI were included in this analysis. Data collected included patient demographics, injury details, organ injured and grade of injury, CT finding specifics such as contrast blush, complications, failure of NOM, time to angiography and techniques for embolization.

Results

Data were collected for 1004 pediatric patients treated for BLSI over the study period, 30 (3.0%) of which underwent angiography with or without embolization for BLSI. Ten of the patients who underwent angiography for BLSI failed NOM. For patients with embolized splenic injuries, splenic salvage was 100%. Four of 9 patients undergoing embolization of the liver ultimately required an operative intervention, but only one patient required hepatorrhaphy and no patient required hepatectomy after AE. Few angiography studies were obtained early during hospitalization for BLSI, with only 1 patient undergoing angiography within 1 hour of arrival at the PTC, and 7 within 3 hours.

Conclusions

Angioembolization is rarely utilized in the management of BLSI in pediatric trauma patients with blunt abdominal trauma and is generally utilized in a delayed fashion. However, when implemented, angioembolization is associated with 100% splenic salvage for splenic injuries.

Level of Evidence

Level IV, therapeutic/care management
Next-generation tourniquet: Recommendations for future capabilities and design requirements
Authors: Veazey Sena R. , Mike Jared F. , Hull Darke R. , Ryan Kathy L. , Salinas Jose , Kragh John F.
Published: January 2024

BACKGROUND

Advances in tourniquet development must meet new military needs for future large-scale combat operations or civilian mass casualty scenarios. This includes the potential use of engineering and automation technologies to provide advanced tourniquet features. A comprehensive set of design capabilities and requirements for an intelligent or smart tourniquet needed to meet the challenges currently does not exist. The goal of this project was to identify key features and capabilities that should be considered for the development of next-generation tourniquets.

METHODS

We used a modified Delphi consensus technique to survey a panel of 34 tourniquet subject matter experts to rate various statements and potential design characteristics relevant to tourniquets systems and their use scenarios. Three iterative rounds of surveys were held, followed by virtual working group meetings, to determine importance or agreement with any given statement. We used a tiered consensus system to determine final agreement over key features that were viewed as important or unimportant features or capabilities. This information was used to refine and clarify the necessary tourniquet design features and adjust questions for the following surveys.

RESULTS

Key features and capabilities of various were agreed upon by the panelists when consensus was reached. Some tourniquet features that were agreed upon included but are not limited to: Capable of being used longer than 2 hours, applied and monitored by anyone, data displays, semiautomated capabilities with inherent overrides, automated monitoring with notifications and alerts, and provide recommended actions.

CONCLUSION

We were able to identify key tourniquet features that will be important for future device development. These consensus results can guide future inventors, researchers, and manufacturers to develop a portfolio of next-generation tourniquets for enhancing the capabilities of a prehospital medical provider.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level V.
Tissue-specific metabolic enzyme levels covary with whole-animal metabolic rates and life-history loci via epistatic effects
Authors: Prokkola Jenni M. , Chew Kuan Kiat , Anttila Katja , Maamela Katja S. , Yildiz Atakan , Åsheim Eirik R. , Primmer Craig R. , Aykanat Tutku
Published: January 2024

Metabolic rates, including standard (SMR) and maximum (MMR) metabolic rate have often been linked with life-history strategies. Variation in context- and tissue-level metabolism underlying SMR and MMR may thus provide a physiological basis for life-history variation. This raises a hypothesis that tissue-specific metabolism covaries with whole-animal metabolic rates and is genetically linked to life history. In Atlantic salmon (Salmo salar), variation in two loci,vgll3andsix6, affects life history via age-at-maturity as well as MMR. Here, using individuals with known SMR and MMR with differentvgll3andsix6genotype combinations, we measured proxies of mitochondrial density and anaerobic metabolism, i.e. maximal activities of the mitochondrial citrate synthase (CS) and lactate dehydrogenase (LDH) enzymes, in four tissues (heart, intestine, liver, white muscle) across low- and high-food regimes. We found enzymatic activities were related to metabolic rates, mainly SMR, in the intestine and heart. Individual loci were not associated with the enzymatic activities, but we found epistatic effects and genotype-by-environment interactions in CS activity in the heart and epistasis in LDH activity in the intestine. These effects suggest that mitochondrial density and anaerobic capacity in the heart and intestine may partly mediate variation in metabolic rates and life history via age-at-maturity.

This article is part of the theme issue ‘The evolutionary significance of variation in metabolic rates’.
Non-lethal sampling for assessment of mitochondrial function does not affect metabolic rate and swimming performance
Authors: Thoral Elisa , Dargère Lauréliane , Medina-Suárez Ione , Clair Angéline , Averty Laetitia , Sigaud Justine , Morales Anne , Salin Karine , Teulier Loïc
Published: January 2024

A fundamental issue in the metabolic field is whether it is possible to understand underlying mechanisms that characterize individual variation. Whole-animal performance relies on mitochondrial function as it produces energy for cellular processes. However, our lack of longitudinal measures to evaluate how mitochondrial function can change within and among individuals and with environmental context makes it difficult to assess individual variation in mitochondrial traits. The aims of this study were to test the repeatability of muscle mitochondrial metabolism by performing two biopsies of red muscle, and to evaluate the effects of biopsies on whole-animal performance in goldfish
Carassius auratus
. Our results show that basal mitochondrial respiration and net phosphorylation efficiency are repeatable at 14-day intervals. We also show that swimming performance (optimal cost of transport and critical swimming speed) was repeatable in biopsied fish, whereas the repeatability of individual oxygen consumption (standard and maximal metabolic rates) seemed unstable over time. However, we noted that the means of individual and mitochondrial traits did not change over time in biopsied fish. This study shows that muscle biopsies allow the measurement of mitochondrial metabolism without sacrificing animals and that two muscle biopsies 14 days apart affect the intraspecific variation in fish performance without affecting average performance of individuals.

This article is part of the theme issue ‘The evolutionary significance of variation in metabolic rates’.
Geographical and taxonomic patterns in aerobic traits of marine ectotherms
Authors: Penn Justin L. , Deutsch Curtis
Published: January 2024

The metabolism and hypoxia tolerance of marine ectotherms play key roles in limiting species geographical ranges, but underlying traits have only been directly measured for a small fraction of biodiversity. Here we diagnose and analyse spatial and phylogenetic patterns in hypoxia tolerance and its temperature sensitivity at ecologically active metabolic rates, by combining a model of organismal oxygen (O
2
) balance with global climate and biogeographic data for approximately 25 000 animal species from 13 phyla. Large-scale spatial trait patterns reveal that active hypoxia tolerance is greater and less temperature sensitive among tropical species compared to polar ones, consistent with sparse experimental data. Species energetic demands for activity vary less with temperature than resting costs, an inference confirmed by available rate measurements. Across the tree of life, closely related species share similar hypoxia traits, indicating that evolutionary history shapes physiological tolerances to O
2
and temperature. Trait frequencies are highly conserved across phyla, suggesting the breadth of global aerobic conditions selects for convergent trait diversity. Our results support aerobic limitation as a constraint on marine habitat distributions and their responses to climate change and highlight the under-sampling of aerobic traits among species living in the ocean's tropical and polar oxythermal extremes.

This article is part of the theme issue ‘The evolutionary significance of variation in metabolic rates’.
Genotypic Characterization of Urinary Tract Infections causing bacteria isolates among Adults at Kiambu Level 5 Hospital, Kenya: Selected Extended Spectrum β-Lactamase genes and Biofilm Formation
Authors: Wanja Fredrick K. , Omwenga Eric O. , Ngugi Caroline W. , Maina John N. , Kiiru John N.
Published: January 2024

The menace of antimicrobial resistance to public health is constantly arising globally. Many pathogenic bacteria use mechanisms such as mutations and biofilm formation, significantly reducing antimicrobial agents' efficacy. In this cross-sectional study, we aimed to determine the prevalence of selected extended spectrum β-lactamase (ESβLs) genes and analyse the biofilm formation abilities of the isolated bacteria causing urinary tract infection among adult patients against selected drug dosages seeking Medicare at Kiambu Level 5 Hospital, Kenya. The double-disk synergy test was used for phenotypic identification of ESβLs producing isolates, while microtiter plate assays with some modifications were used for the biofilm formation test. A total of 10 isolates were bioassayed for ESβL genes presence out of 57 bacteria isolates obtained from urine samples. This study found the blaTEM genes to be the most prevalent ESβLs type 10/10 (100%), followed by blaOXA and blaSHV genes at 4/10 (40%) and 3/10 (30%), respectively. In addition, the co-carriage of blaTEM and blaSHV was 50% lower than that of blaTEM + blaOXA genes at 66.7% among the study Escherichia coli isolates. Biofilm formation was positive in 36/57 (63.2%) of the isolates tested, with most being Gram-negative 25/36 (69.4%). Escherichia coli 15/36 (41.7 %), Klebsiella species 7/36 (19.4%), and Staphylococcus aureus 7/36 (19.4%) were the dominant biofilm formers. However, there was no significant difference in biofilm formation among all tested isolates, with all isolates recording p-values above 0.05. In light of these findings, biofilm formation potential coupled with antimicrobial resistance genes in UTI isolates could likely lead to difficult to treat infections.
Actinoplanes oblitus sp. nov., producing the glycopeptide antibiotic A477
Authors: Yushchuk Oleksandr , Binda Elisa , Rückert-Reed Christian , Berini Francesca , Fedorenko Victor , Kalinowski Jörn , Marinelli Flavia
Published: January 2024

In 1973, Eli Lilly and Company described the filamentous actinomycete producing the glycopeptide antibiotic A477 as an

Actinoplanes

species on the basis of its morphological and physiological features and deposited it as NRRL 3884T. In this paper, we report that the phylogenetic analysis based on the 16S rRNA gene sequence and the whole genome phylogenomic study indicate that NRRL 3884T forms a distinct monophyletic line within the genus

Actinoplanes

, being most closely related to

Actinoplanes octamycinicus

NBRC 14524T [99.6 % 16S rRNA gene similarity, 89.4 % average nucleotide identity (ANI), 46.0 % digital DNA–DNA hybridization (dDDH)] and

Actinoplanes ianthinogenes

NBRC 13996T (98.8 % 16S rRNA gene similarity, 89.0 % ANI, 47.0 % dDDH). NRRL 3884T forms an extensively branched, non-fragmented vegetative mycelium; either sterile aerial hyphae or regular subglobose sporangia are formed depending on cultivation conditions. The cell wall contains meso-2,6-diaminopimelic acid and 2,6-diamino-3-hydroxypimelic acid and the diagnostic sugars are glucose, mannose and ribose with a minor amount of rhamnose. The predominant menaquinone (MK) is MK-9(H4), with minor amounts of MK-9(H2), MK-9(H6) and MK-9(H8). Mycolic acids are absent. The diagnostic phospholipids are diphosphatidylglycerol and phosphatidylethanolamine. The major cellular fatty acids are anteiso-C17 : 0, iso-C16 : 0 and iso-C15 : 0, with moderate amounts of anteiso-C15 : 0 and iso-C17 : 0. The genomic G+C content is 71.5 mol%. Significant differences in the genomic, morphological, chemotaxonomic and biochemical data between NRRL 3884T and the two most closely related

Actinoplanes

type strains clearly demonstrate that NRRL 3884T represents a novel species of the genus

Actinoplanes

, for which the name Actinoplanes oblitus sp. nov. is proposed. The type strain is NRRL 3884T (=DSM 116196T).
Spencermartinsiella henanensis fa., sp. nov., a novel yeast species isolated from rotting wood
Authors: Guo Qi-Chao , Liu Shan , Hui Feng-Li
Published: January 2024

Two yeast strains (NYNU 211162 and NYNU 211275) were isolated from rotting wood collected in the Baotianman Nature Reserve, Henan Province, central China. Phylogenetic analysis of the D1/D2 domain of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region revealed that the strains represent a phylogenetically distinct species within the genus Spencermartinsiella. The name Spencermartinsiella henanensis fa., sp. nov. is proposed for this species with holotype CICC 33543T (Mycobank MB 851142). S. henanensis sp. nov. differed by only 3 nt (~0.5 %) substitutions from the closest known species S. europaea NCAIM Y.01817T in the D1/D2 domain, but by 33 nt (~6 %) substitutions, 34 nt (~3.8 %) substitutions, 30 nt (~5.6 %) substitutions and 75 nt (~9.9 %) substitutions in the ITS region and the partial TEF1, COXII and RPB2 genes. Additionally, S. henanensis sp. nov. can be physiologically distinguished from S. europaea by its ability to assimilate inulin, inability to assimilate ethylamine and cadaverine, and incapability of growth at 30 °C.
Multiplex Imaging Reveals Novel Subcellular, Microenvironmental, and Racial Patterns of MRTFA/B Activation in Invasive Breast Cancers and Metastases
Authors: Wilk Stephanie M. , Lee Kihak , Gajda Alexa M. , Haloul Mohamed , Macias Virgilia , Wiley Elizabeth L. , Chen Zhengjia , Liu Xinyi , Wang Xiaowei , Sverdlov Maria , Hoskins Kent F. , Er Ekrem Emrah
Published: January 2024

Breast cancer progression and metastasis involve the action of multiple transcription factors in tumors and in the cells of the tumor microenvironment (TME) and understanding how these transcription factors are coordinated can guide novel therapeutic strategies. Myocardin related transcription factors A and B (MRTFA/B) are two related transcription factors that redundantly control cancer cell invasion and metastasis in mouse models of breast cancer, but their roles in human cancer are incompletely understood. Here, we used a combination of multiplexed immunofluorescence and bioinformatics analyses to show that MRTFA/B are concurrently activated in tumor cells, but they show distinct patterns of expression across different histological subtypes and in the TME. Importantly, MRTFA expression was elevated in metastatic tumors of African American patients, who disproportionately die from breast cancer. Interestingly, in contrast to publicly available mRNA expression data, MRTFA was similarly expressed across estrogen receptor (ER) positive and negative breast tumors, while MRTFB expression was highest in ER+ breast tumors. Furthermore, MRTFA was specifically expressed in the perivascular antigen presenting cells (APCs) and its expression correlated with the expression of the immune checkpoint protein V-set immunoregulatory receptor (VSIR). These results provide unique insights into how MRTFA and MRTFB can promote metastasis in human cancer, into the racial disparities of their expression patterns, and their function within the complex breast cancer TME.

Graphical Abstract
ELViM: Exploring Biomolecular Energy Landscapes through Multidimensional Visualization
Authors: Viegas Rafael G. , Martins Ingrid B. S. , Sanches Murilo N. , Oliveira Antonio B. , de Camargo Juliana B. , Paulovich Fernando V. , Leite Vitor B.P.
Published: January 2024

Abstract

Molecular dynamics (MD) simulations provide a powerful means to explore the dynamic behavior of biomolecular systems at the atomic level. However, analyzing the vast datasets generated by MD simulations poses significant challenges. This manuscript discusses the Energy Landscape Visualization Method (ELViM), a multidimensional reduction technique inspired by energy landscape theory. ELViM transcends one-dimensional representations, offering a comprehensive analysis of the effective conformational phase space without the need for predefined reaction coordinates. We apply ELViM to study the folding landscape of the antimicrobial peptide Polybia-MP1, showcasing its versatility in capturing complex biomolecular dynamics. Using dissimilarity matrices and a force-scheme approach, ELViM provides intuitive visualizations, revealing structural correlations, and local conformational signatures. The method is demonstrated to be adaptable, robust, and applicable to various biomolecular systems.