bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute alcohol consumption and arrhythmias in young adults: the MunichBREW II study
Authors: Brunner Stefan , Krewitz Christina , Winter Raphaela , von Falkenhausen Aenne S , Kern Anna , Brunner Dorothee , Sinner Moritz F
Published: October 2024

Background and Aims

Acute excessive alcohol intake may cause the holiday heart syndrome, characterized by cardiac arrhythmias including atrial fibrillation. Since underlying data are scarce, the study aimed to prospectively investigate the temporal course of occurring cardiac arrhythmias following binge drinking in young adults.

Methods

A total of 202 volunteers planning acute alcohol consumption with expected peak breath alcohol concentrations (BACs) of ≥1.2 g/kg were enrolled. The study comprised 48 h electrocardiogram monitoring covering baseline (Hour 0), ‘drinking period’ (Hours 1–5), ‘recovery period’ (Hours 6–19), and two control periods corresponding to 24 h after the ‘drinking’ and ‘recovery periods’, respectively. Acute alcohol intake was monitored by BAC measurements during the ‘drinking period’. Electrocardiograms were analysed for mean heart rate, atrial tachycardia, premature atrial complexes, premature ventricular complexes (PVCs), and heart rate variability measures.

Results

Data revealed an increase in heart rate and an excess of atrial tachycardias with increasing alcohol intake. Heart rate variability analysis indicated an autonomic modulation with sympathetic activation during alcohol consumption and the subsequent ‘recovery period’, followed by parasympathetic predominance thereafter. Premature atrial complexes occurred significantly more frequently in the ‘control periods’, whereas PVCs were more frequent in the ‘drinking period’. Ten participants experienced notable arrhythmic episodes, including atrial fibrillation and ventricular tachycardias, primarily during the ‘recovery period’.

Conclusions

The study demonstrates the impact of binge drinking on heart rate alterations and increased atrial tachycardias during ‘drinking period’, and the occurrence of clinically relevant arrhythmias during the ‘recovery period’, emphasizing the holiday heart syndrome as a health concern.
Essential oils from Cuminum cyminum and Laurus nobilis and their principal constituents: evaluation of antifungal and antimycotoxigenic potential in Aspergillus species
Authors: Campolina Gabriela Aguiar , Cardoso Maria das Graças , Freire Carolina Salles , Caetano Alex Rodrigues Silva , Campos Anna Beatriz de Souza , Ferreira Vanuzia Rodrigues Fernandes , Alves Eduardo , Nelson David Lee , Batista Luis Roberto
Published: October 2024

The antifungal and antimycotoxigenic activities of the essential oils (EO) from Cuminum cyminum and Laurus nobilis, and their respective principal compounds, cuminaldehyde and 1,8-cineole, were evaluated against fungi of the genus Aspergillus: A. carbonarius, A. niger, A. ochraceus, and A. westerdijkiae. The antifungal activity was determined by the contact method and the mycelial growth of the fungi was evaluated. Scanning electron microscopic (SEM) images were obtained to suggest modes of action of the compounds analysed. The antimycotoxigenic activity was determined by high-performance liquid chromatograph. Aspergillus carbonarius was completely inhibited by cumin EO (500 µl l−1), by laurel EO and by cuminaldehyde (5000 µl l−1). The cumin EO (500 µl l−1) completely inhibited the growth of A. niger. All the samples inhibited the mycelial growth of A. ochraceus, especially cumin EO and cuminaldehyde (250 µl l−1). Aspergillus westerdijkiae was completely inhibited by cumin EO and cuminaldehyde (1000 µl l−1), by laurel EO and 1,8-cineole (10 000 µl l−1). A decrease in the production of ochratoxin A (OTA) was observed post-treatment, except in A. ochraceus, only inhibited by laurel EO. SEM images showed morphological changes in fungal structures and spore inhibition post-treatment. The results confirmed the antifungal and antimycotoxigenic effect of EO and their principal constituents on fungi evaluated.
Healthy worker hire and survivor effects in a cohort of medical radiation workers
Authors: Lee Won Jin , Jeong Jaeho , Bang Ye Jin , Kim Young Min
Published: October 2024

Background

The healthy worker effect may distort the association between exposure and health effects in workers. However, few studies have investigated both the healthy worker hire and survival effects simultaneously, and they are limited to mortality studies in male workers.

Methods

We utilized a data set comprising South Korean diagnostic medical radiation workers registered in the National Dose Registry between 1996 and 2011, and merged it with mortality and cancer incidence data. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were computed for comparison with the general population. To account for time-varying confounders influenced by prior occupational radiation exposure, we applied g-estimation using structural nested accelerated failure time models and compared the outcomes with those from Weibull regression.

Results

A total of 1831 deaths and 3759 first primary cancer cases were identified among 93 918 workers. Both male (SMR = 0.44; 95% CI: 0.42, 0.46) and female workers (SMR = 0.53; 95% CI: 0.46, 0.60) showed lower mortality rates compared with national rates. In the SIR analysis, male workers exhibited reduced risks of solid cancer whereas female workers had increased risks. The g-estimation-derived hazard ratios (HRs) from radiation exposure exceeded those from Weibull regression estimates for all-cause death (HR = 2.55; 95% CI: 1.97, 3.23) and all-cancer incidence (HR = 1.96; 95% CI: 1.52, 2.55) in male workers whereas female workers showed the opposite results.

Conclusions

Comprehensive consideration of the healthy worker effect by sex is essential for estimating the unbiased impact of occupational exposure on health outcomes, notably in studies focusing on male mortality.
Dirac Eigenvalue Optimisation and Harmonic Maps to Complex Projective Spaces
Authors: Karpukhin Mikhail , Métras Antoine , Polterovich Iosif
Published: October 2024

Consider a Dirac operator on an oriented compact surface endowed with a Riemannian metric and spin structure. Provided the area and the conformal class are fixed, how small can the $k$-th positive Dirac eigenvalue be? This problem mirrors the maximization problem for the eigenvalues of the Laplacian, which is related to the study of harmonic maps into spheres. We uncover the connection between the critical metrics for Dirac eigenvalues and harmonic maps into complex projective spaces. Using this approach we show that for many conformal classes on a torus the first nonzero Dirac eigenvalue is minimised by the flat metric. We also present a new geometric proof of Bär’s theorem stating that the first nonzero Dirac eigenvalue on the sphere is minimised by the standard round metric.
Academic Freedom and Protected Philosophical Belief: Strengthening the Legal Analysis
Authors: Waltham-Smith Naomi , Murray James
Published: October 2024

This article evaluates the state of protection for academic freedom and academic freedom of expression in English law, specifically the effectiveness of protected philosophical belief (PPB) as a vector for protecting them. We argue that the category of PPB (circumscribed by the test in Grainger v Nicholson) is inherently inappropriate as a means of protecting values that are of signal importance in the academic employment context. Furthermore, this framing poses a risk that the concepts of academic freedom and academic freedom of expression may be overlooked or misconstrued in the analysis when applying legal tests (eg of harassment) or in carrying out balancing exercises with the rights of others. We offer critiques of the analytical approach in two recent employment tribunal decisions—Phoenix v The Open University and Miller v University of Bristol—identifying how these problems arise in the reasoning of both tribunals in relation to academic freedom and academic freedom fo expression. Examining how the Higher Education (Freedom of Speech) Act 2023 fails to remedy these issues, we set out the approach that tribunals and courts should in fact take in cases concerning AF and AFoE with reference to the jurisprudence of the European Court of Human Rights and international instruments.
The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of multidrug-resistant Salmonella enteritidis causing multisite invasive infections
Authors: Yu Lifei , Han Xinhong , Zhang Wang , Fu Ying , Yang Shaoxue , Wu Shenghai , Jin Jie , Li Siying , Chen Yan , Jiang Yan , Yu Yunsong
Published: October 2024

Objectives

To assess the impact of mutations in the two-component sensor envZ on antibiotic resistance and virulence in the evolutionary dynamics of MDR Salmonella enteritidis (S. enteritidis).

Methods

Five S. enteritidis isolates obtained from a patient with multisite invasive infections were analysed. Analysis of antibiotic resistance genes, virulence genes and SNP was performed through WGS. RNA sequencing, quantitative RT–PCR, virulence testing in a Galleria mellonella (G. mellonella) infection model and in vitro cell experiments were used to examine the effects of envZ mutations.

Results

WGS revealed identical resistance and virulence genes on an IncFIB(S)/IncFII(S)/IncX1 fusion plasmid in all strains. The faecal strains harboured envZ mutations, reducing outer membrane protein ompD and ompF transcriptional level. Virulence testing demonstrated elevated virulence in envZ mutant strains. In vitro experiments revealed increased adhesion, invasion and phagocytosis resistance in envZ mutants, along with reduced biofilm formation and growth rates.

Conclusions

These findings highlight novel genetic locations on envZ influencing antibiotic resistance and virulence in clinical S. enteritidis strains. envZ mutations impact antibiotic resistance by down-regulating ompD and ompF expression and enhance virulence, contributing to multisite infections with increased fitness costs.
Consumption zones
Authors: Batch Andrea , Bridgman Benjamin , Dunn Abe , Gholizadeh Mahsa
Published: October 2024

Economic geography data are typically reported using political units, such as counties, which often do not match economic units. Commuting zones (CZs) group counties into labor markets. However, CZs are not the most appropriate grouping for other economic activities. We introduce consumption zones (ConZs), groupings of counties appropriate for the analysis of consumption. We apply CZ methodology to payment card data, which report spending flows across US counties for fifteen industries. We find that different industries have different market sizes. Grocery stores have more than five times the number of ConZs as entertainment. We apply ConZs to measuring industry concentration.
The genome of the Australian water dragon (Intellagama lesueurii), an agamid model for urban adaptation
Authors: Powell Daniel , Jackson Nicola , Kaur Parwinder , Dudchenko Olga , Aiden Erez Lieberman , Georges Arthur , Frère Céline Henria
Published: October 2024

Squamate reptiles are a highly diverse and intriguing group of tetrapods, offering valuable insights into the evolution of amniotes. The Australian water dragon (Intellagama lesueurii) is a member of the Agamidae and sister to the core mesic Australian endemic radiation (Amphibolurinae). The species is renowned for its urban adaptability and complex social systems. We report a 1.8 Gb chromosome-length genome assembly together with the annotation of 23,675 protein-coding genes. Comparative analysis with other squamate genomes highlights gene family expansions associated with immune function, energetic homeostasis, and wound healing. This reference genome will serve as a valuable resource for studies of evolution and environmental resilience in lizards.
Characterization of undifferentiated carcinomas of the pancreas with and without osteoclast-like giant cells
Authors: Mills Jamie N , Gunchick Valerie , McGue Jake , Qin Zhaoping , Kumar-Sinha Chandan , Bednar Filip , Brown Noah , Shi Jiaqi , Udager Aaron M , Frankel Timothy , Zalupski Mark M , Sahai Vaibhav
Published: October 2024

Background

Undifferentiated carcinoma (UC) is a rare subtype of pancreatic cancer distinguished from UC with osteoclast-like giant cells (UC-OGC) in 2019, affecting interpretation of literature that does not distinguish these subtypes. We sought to identify translationally relevant differences between these 2 variants and compared with pancreatic ductal adenocarcinoma.

Methods

We characterized clinical and multiomic differences between UC (n = 32) and UC-OGC (n = 15) using DNA sequencing, RNA sequencing, and multiplex immunofluorescence and compared these findings with pancreatic ductal adenocarcinoma.

Results

Characteristics at diagnosis were similar between UC and UC-OGC, though the latter was more resectable (P = .009). Across all stages, median overall survival was shorter for UC than for UC-OGC (0.4 years vs 10.8 years, respectively; P = .003). This shorter survival was retained after stratification by resection, albeit without statistical significance (1.8 years vs 11.9 years, respectively; P = .08). In a subset of patients with available tissue, the genomic landscape was similar among UC (n = 9), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 159). Bulk RNA sequencing was deconvoluted and, along with multiplex immunofluorescence in UC (n = 13), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 16), demonstrated statistically significantly increased antigen-presenting cells, including M2 macrophages and natural killer cells, and decreased cytotoxic and regulatory T cells in UC and UC-OGC vs pancreatic ductal adenocarcinoma. Findings were similar between UC and UC-OGC , except for decreased regulatory T cells in UC-OGC (P = .04).

Conclusions

In this series, UC was more aggressive than UC-OGC, with these variants having more antigen-presenting cells and fewer regulatory T cells than pancreatic ductal adenocarcinoma, suggesting potential for immune-modulating therapies in the treatment of these pancreatic cancer subtypes.
Serologic and molecular identification of the variation on ABO*B.01 gene in ABO glycosyltransferases associated with Bw phenotype: a case report
Authors: Li Xiaoshuai , Wang Qiushi
Published: October 2024

AB antigen is formed by glycosyltransferase enzyme, which catalyzes the corresponding substrates to be connected to the galactose of the precursor substance H antigen. To study the effect of the α-1,3-D galactosyltransferase (GTB) gene mutation on B antigen expression, we explored its molecular mechanism by combining molecular biological methods with bioinformatics. The ABO blood type of the patients was identified using conventional serologic methods, and the polymerase chain reaction (PCR) products of exons 1-7 of the ABO gene were directly sequenced using gene-specific primers and direct sequencing. Proteins in the secretory supernatant of transfected cells were collected in vitro, and GTB content was quantitatively analyzed using western blotting. Bioinformatics software was used to simulate the 3-dimensional structure of the mutant protein. In this case, the patient’s serologic test results revealed subtype B. Gene sequencing results confirmed a mutation at base 278 of exon 6. The mutation (c.278C>T) changed the 93rd amino acid of the protein polypeptide chain from proline to leucine (p.P93L). The variant p.P93L did not affect the expression and secretion of GTB, but affected enzyme activity and stability, ultimately manifesting as weakened expression of the B antigen and reduced affinity.
UV-light fluorescence as a confirmation method for presumptive Legionella colonies isolated from water samples
Authors: Badoux Paul , Atsma Adrie , van Harmelen-Vrins Esther , Euser Sjoerd
Published: October 2024

Legionnaires’ disease (LD) is a severe and potentially fatal form of bacterial pneumonia caused by Legionella spp. We evaluated the use of UV-light for detecting Legionella non-pneumophila in water samples according to the NEN-EN-ISO 11731:2017 methodology (reference method) in a collaborative effort involving 10 laboratories. First, a test panel was constructed of 298 strains: 157 Legionella strains and 141 non-Legionella strains were cultured on buffered charcoal yeast extract (BCYE)-medium and confirmed according to ISO 11731: 2017 (cultured on BCYE agar plates with and without l-cysteine), and by matrix-assisted laser desorption-ionization time of flight or next generation sequencing. All strains were additionally exposed to an UV-light to assess if they showed a bright blue fluorescence effect (UV-positive) or not (UV-negative). Second, in an interlaboratory study, 10 laboratories analyzed a blinded set of 16 Legionella strains and 8 non-Legionella strains using both methods. The test panel analyses showed 100% accordance between the UV-light and reference method. In addition, the interlaboratory study results showed full agreement between both methods. Our results support the implementation of UV-light detection to confirm Legionella presumptive colonies during analyses of water samples according to the NEN-EN-ISO 11731:2017 methodology. Implementation of UV-light confirmation could reduce workload, time-to-result and costs for the analyses of water samples for the presence of Legionella.
Discovery of persistent quasi-periodic oscillations in accreting white dwarfs: a new link to X-ray binaries
Authors: Veresvarska M , Scaringi S , Knigge C , Paice J , Buckley D A H , Segura N Castro , de Martino D , Groot P J , Ingram A , Irving Z A , Szkody P
Published: October 2024

Almost all accreting black hole and neutron star (NS) X-ray binary systems (XRBs) exhibit prominent brightness variations on a few characteristic time-scales and their harmonics. These quasi-periodic oscillations (QPOs) are thought to be associated with the precession of a warped accretion disc, but the physical mechanism that generates the precessing warp remains uncertain. Relativistic frame dragging (Lense–Thirring precession) is one promising candidate, but a misaligned magnetic field is an alternative, especially for NS XRBs. Here, we report the discovery of five accreting white dwarf systems (AWDs) that display strong optical QPOs with characteristic frequencies and harmonic structures that suggest they are the counterpart of the QPOs seen in XRBs. Since AWDs are firmly in the classical (non-relativistic) regime, Lense–Thirring precession cannot account for these QPOs. By contrast, a weak magnetic field associated with the white dwarf can drive disc warping and precession in these systems, similar to what has been proposed for NS XRBs. Our observations confirm that magnetically driven warping is a viable mechanism for generating QPOs in disc-accreting astrophysical systems, certainly in AWDs and possibly also in NS XRBs. Additionally, they establish a new way to estimate magnetic field strengths, even in relatively weak-field systems where other methods are not available.
A Systematic Review of the Beneficial Effects of Berry Extracts on Non-Alcoholic Fatty Liver Disease in Animal Models
Authors: García-Beltrán Alejandro , Lozano Melero Aida , Martínez Martínez Rosario , Porres Foulquie Jesús María , López Jurado Romero de la Cruz María , Kapravelou Garyfallia
Published: October 2024

Context

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is strongly associated with several metabolic disorders. Plant-derived bioactive extracts, such as berry extracts, with high antioxidant capacity have been used for the treatment and prevention of this pathology. Moreover, they promote circular economy and sustainability.

Objective

To study the beneficial effects of extracts from different parts of berry plants in animal models of NAFLD.

Data Sources

A systematic research of the MEDLINE (via PubMed), Cochrane, and Scopus databases was conducted to identify relevant studies published after January 2011. In vivo animal studies of NAFLD were included in which berry extracts of different parts of the plant were administered and significantly improved altered biomarkers related to the pathology, such as lipid metabolism and hepatic steatosis, glucose and glycogen metabolism, and antioxidant and anti-inflammatory biomarkers.

Data Extraction

Of a total of 203 articles identified, 31 studies were included after implementation of the inclusion and exclusion criteria.

Data Analysis

Most of the studies showed a decrease in steatosis and a stimulation of genes related to β-oxidation and downregulation of lipogenic genes, with administration of berry extracts. Berry extracts also attenuated inflammation and oxidative stress.

Conclusions

Administration of berry extracts seems to have promising potential in the design of enriched foodstuffs or nutraceuticals for the treatment of NAFLD.
Geography, altitude, agriculture, and hypoxia
Authors: Holdsworth Michael J , Liu Huanhuan , Castellana Simone , Abbas Mohamad , Liu Jianquan , Perata Pierdomenico
Published: October 2024

Reduced oxygen availability (hypoxia) represents a key plant abiotic stress in natural and agricultural systems, but conversely it is also an important component of normal growth and development. We review recent advances that demonstrate how genetic adaptations associated with hypoxia impact the known plant oxygen-sensing mechanism through the PLANT CYSTEINE OXIDASE N-degron pathway. Only 3 protein substrates of this pathway have been identified, and all adaptations identified to date are associated with the most important of these, the group VII ETHYLENE RESPONSE FACTOR transcription factors. We discuss how geography, altitude, and agriculture have all shaped molecular responses to hypoxia and how these responses have emerged at different taxonomic levels through the evolution of land plants. Understanding how ecological and agricultural genetic variation acts positively to enhance hypoxia tolerance will provide novel tools and concepts to improve the performance of crops in the face of increasing extreme flooding events.
Memory of shear flow in soft jammed materials
Authors: Vinutha H A , Marchand Manon , Caggioni Marco , Vasisht Vishwas V , Del Gado Emanuela , Trappe Veronique
Published: October 2024

Cessation of flow in yield stress fluids results in a stress relaxation process that eventually leads to a finite residual stress. Both the rate of stress relaxation and the magnitude of the residual stresses systematically depend on the preceding flow conditions. To assess the microscopic origin of this memory effect, we combine experiments with large-scale computer simulations, exploring the behavior of jammed suspensions of soft repulsive particles. A spatiotemporal analysis of particle motion reveals that memory formation during flow is primarily governed by the emergence of domains of spatially correlated nonaffine displacements. These domains imprint the configuration of stress imbalances that drive dynamics upon flow cessation, as evidenced by a striking equivalence of the spatial correlation patterns in particle displacements observed during flow and upon flow cessation. Additional contributions to stress relaxation result from the particle packing that reorganizes to minimize the resistance to flow by decreasing the number of locally stiffer configurations. Regaining rigidity upon flow cessation drives further relaxation and effectively sets the magnitude of the residual stress. Our findings highlight that flow in yield stress fluids can be seen as a training process during which the material stores information of the flowing state through the development of domains of correlated particle displacements and the reorganization of particle packings optimized to sustain the flow. This encoded memory can then be retrieved in flow cessation experiments.
Art law issues in international estate planning—from the UK lens
Authors: Harney Patrick , Lines Olivia
Published: October 2024

This article examines the complexities of managing art within estate administration. It emphasises art’s unique nature, requiring specialised handling due to its cultural significance and potential legal and reputational implications. The article discusses international estate planning principles including the relevance of tax treaties and private international law, UK inheritance tax considerations, and the appointment of specialist executors. It covers relevant UK tax exemptions and reliefs, such as Acceptance in Lieu. The article explores how thorough due diligence and proactive collection management can mitigate disputes and tax exposure and highlights how meticulous planning can preserve artwork’s value across generations.
Oral exposure to benzalkonium chlorides in male and female mice reveals alteration of the gut microbiome and bile acid profile
Authors: Lopez Vanessa A , Lim Joe J , Seguin Ryan P , Dempsey Joseph L , Kunzman Gabrielle , Cui Julia Y , Xu Libin
Published: October 2024

Benzalkonium chlorides (BACs) are commonly used disinfectants in a variety of consumer and food-processing settings, and the COVID-19 pandemic has led to increased usage of BACs. The prevalence of BACs raises the concern that BAC exposure could disrupt the gastrointestinal microbiota, thus interfering with the beneficial functions of the microbes. We hypothesize that BAC exposure can alter the gut microbiome diversity and composition, which will disrupt bile acid (BA) homeostasis along the gut-liver axis. In this study, male and female mice were exposed orally to d7-C12- and d7-C16-BACs at 120 µg/g/d for 1 wk. UPLC-MS/MS analysis of liver, blood, and fecal samples of BAC-treated mice demonstrated the absorption and metabolism of BACs. Both parent BACs and their metabolites were detected in all exposed samples. Additionally, 16S rRNA sequencing was carried out on the bacterial DNA isolated from the cecum intestinal content. For female mice, and to a lesser extent in males, we found that treatment with either d7-C12- or d7-C16-BAC led to decreased alpha diversity and differential composition of gut bacteria with notably decreased actinobacteria phylum. Lastly, through a targeted BA quantitation analysis, we observed decreases in secondary BAs in BAC-treated mice, which was more pronounced in the female mice. This finding is supported by decreases in bacteria known to metabolize primary BAs into secondary BAs, such as the families of Ruminococcaceae and Lachnospiraceae. Together, these data signify the potential impact of BACs on human health through disturbance of the gut microbiome and gut-liver interactions.
Profiling the endocrine-disrupting properties of triazines, triazoles, and short-chain PFAS
Authors: Carlier Maxim P , Cenijn Peter H , Baygildiev Timur , Irwan Jenny , Escher Sylvia E , van Duursen Majorie B M , Hamers Timo
Published: October 2024

Persistent, mobile, and toxic compounds released to the environment are likely to pollute drinking water sources due to their slow environmental degradation (persistency) and high water solubility (mobility). The aim of the present study was to create in vitro hazard profiles for 16 triazoles, 9 triazines, and 11 poly- and perfluoroalkyl substances (PFAS) based on their agonistic and antagonistic effects in estrogen receptor (ER), androgen receptor (AR), and thyroid hormone receptor (TR) reporter gene assays, their ability to bind human transthyretin (TTR), and their effects on steroidogenesis. The triazole fungicides tetraconazole, bitertanol, fenbuconazole, tebuconazole, cyproconazole, difenoconazole, propiconazole, paclobutrazol, and triadimenol had agonistic or antagonistic effects on the ER and AR. Difenoconazole, propiconazole, and triadimenol were also found to be TR antagonists. The triazine herbicide ametryn was an ER, AR, and TR antagonist. The same 9 triazole fungicides and the triazines atrazine, deethyl-atrazine, and ametryn affected the secretion of steroid hormones. Furthermore, PFAS compounds PFBS, PFHxS, PFHxA, PFOS, PFOA, and GenX and the triazoles bitertanol, difenoconazole, and 4-methyl benzotriazole were found to displace T4 from TTR. These results are in line with earlier in vitro and in vivo studies on the endocrine-disrupting properties of triazines, triazoles, and PFAS. The present study demonstrates that this battery of in vitro bioassays can be used to profile compounds from different classes based on their endocrine-disrupting properties as a first step to prioritize them for further research, emission reduction, environmental remediation, and regulatory purposes.
RNA Sequencing Analysis of Monocytes Exposed to Airway Fluid From Children With Pediatric Acute Respiratory Distress Syndrome
Authors: Grunwell Jocelyn R. , Huang Min , Stephenson Susan T. , Tidwell Mallory , Ripple Michael J. , Fitzpatrick Anne M. , Kamaleswaran Rishikesan
Published: October 2024

OBJECTIVES:

Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor monocytes exposed to the airway fluid of intubated children with and at-risk for PARDS. To determine differences in gene expression at two time points using the donor monocyte assay exposed to airway fluid from intubated children with PARDS obtained 48–96 hours following initial tracheal aspirate sampling.

DESIGN:

In vitro pilot study carried out using airway fluid supernatant.

SETTING:

Academic 40-bed PICU.

PARTICIPANTS:

Fifty-seven children: 44 children with PARDS and 13 children at-risk for PARDS.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We performed bulk RNA sequencing using a transcriptomic reporter assay of monocytes exposed to airway fluid from intubated children to discover gene networks differentiating PARDS from at-risk for PARDS and those differentiating mild/moderate from severe PARDS. We also report differences in gene expression in children with PARDS 48–96 hours following initial tracheal aspirate sampling. We found that interleukin (IL)-10, IL-4, and IL-13, cytokine/chemokine signaling, and the senescence-associated secretory phenotype are upregulated in monocytes exposed to airway fluid from intubated children with PARDS compared with those at-risk for PARDS. Signaling by NOTCH, histone deacetylation/acetylation, DNA methylation, chromatin modifications (B-WICH complex), and RNA polymerase I transcription and its associated regulatory apparatus were upregulated in children with PARDS 48–96 hours following initial tracheal aspirate sampling.

CONCLUSIONS:

We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a monocyte reporter assay that exposed monocytes to airway fluid from intubated children with and at-risk for PARDS. Mechanistic investigations are needed to validate our findings.
Safety and efficacy of high thoracic epidural analgesia for chest wall surgery in young adolescents
Authors: Coppens Steve , Dewinter Geertrui , Hoogma Danny Feike , Raudsepp Marc , Vogelaerts Randy , Brullot Liesbeth , Neyrinck Arne , Van Veer Hans , Dreelinck Rebekka , Rex Steffen
Published: October 2024

BACKGROUND

Chest wall surgery for the correction of pectus excavatum or pectus carinatum has gained increased interest in recent years. Adequate pain treatment, respiratory physiotherapy and early ambulation are key to improving the outcomes. Although thoracic epidural analgesia is highly effective, its safety is controversial, leading to extensive scrutiny and questioning of its role.

OBJECTIVE(S)

We hypothesise that thoracic epidural analgesia is effective and well tolerated to use in adolescents, with a high success rate and low pain scores.

DESIGN

Observational retrospective cohort study.

SETTING

All adolescent cases in a high-volume academic tertiary chest wall surgery centre between March 1993 and December 2017 were included.

PATIENTS

A total of 1117 patients aged from 12 to 19 years of age and receiving either Ravvitch, Nuss or Abramson chest wall reconstruction for pectus excavatum were identified in our institutional chest wall surgery database. After applying selection and exclusion criteria, 532 patients were included in the current analysis.

MAIN OUTCOME MEASURES

The primary endpoint of this study was the safety of epidural analgesia, assessed by the incidence of acute adverse events. Secondary endpoints were block success rates using a specific novel definition, and analgesic efficacy using recorded postoperative pain scores.

RESULTS

More than 60% of patients experienced one or more adverse events. However, all events were minor and without consequences. No serious or long-term adverse events were detected. The success rate of thoracic epidural placement was 81%. Low postoperative pain scores were observed.

CONCLUSION

Thoracic epidural analgesia is an extremely effective pain control technique, with a surprisingly high number of minor adverse events but safe with regard to serious adverse events.

TRIAL REGISTRATION

The local research ethics committee approved and registered this study on 16 May 2022 (registration number: S66594).
Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda
Authors: Ferguson Toll Jessica , Solà Elsa , Perez Maria Alejandra , Piano Salvatore , Cheng Alice , Subramanian Aruna K. , Kim W. Ray
Published: October 2024

Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.
Effects of the COVID-19 Pandemic on Microbial Keratitis: A 5-Year Comparative Study
Authors: Haro-Morlett Luis , Vera-Duarte Guillermo Raul , Oliveros-Valdes Francisco , Cortes-Moreno Thelma Noemi , Ramirez-Miranda Arturo , Navas Alejandro , Graue-Hernandez Enrique O.
Published: October 2024

Purpose:

To report the clinical and microbiological profiles of microbial keratitis and its antimicrobial resistance before, during, and after COVID-19.

Methods:

This was a retrospective case-note review of all corneal scrape specimens collected from patients with microbial keratitis from January 2018 to December 2023. Case records were analyzed for demographic characteristics, microbiological diagnosis, and antibiograms. All outcome variables were collected, stratified, and compared between 3 periods: the pre–COVID-19 group (January–December 2019), the COVID-19 group (January 2020–December 2022), and the post–COVID-19 group (January–December 2023).

Results:

A total of 947 corneal cultures from 947 patients were reviewed. Gram-positive bacteria predominated in all periods, with no significant differences in their distribution. Staphylococcus epidermidis was the most frequently identified organism. Pseudomonas aeruginosa was the most common Gram-negative bacterium, with its incidence significantly lower in the post-COVID period. Fungal infections showed a significant increase in the post-COVID group, with Fusarium sp. being the most common fungus and showing a significant increase in incidence in the post-COVID group.

Conclusions:

Despite a stable incidence of microbial keratitis, this study highlights a concerning trend in antibiotic resistance. Although some pathogens became less common, those that persisted have become increasingly difficult to treat. Understanding the clinical and microbiological profiles of microbial keratitis and antimicrobial resistance patterns before and after the COVID-19 pandemic is crucial for informed treatment decisions.
The application of mass defect percentage in the evaluation of acute coronary syndrome
Authors: Zhang Man , Sun Yinuo , Zhang Limeng , Xu Yu , Liu Yifan , Li Kun
Published: October 2024

Objectives

White blood cells, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) distribution patterns in patients with anatomic coronary disease have previously been associated with cardiac events such as myocardial infarct size, complications, and prognosis. However, it remains unknown whether myocardial perfusion mass defect percentage (MDP) obtained from gated myocardial perfusion imaging (G-MPI) correlates with these hematological parameters. Therefore, our research aimed to investigate the application of MDP in the evaluation of acute coronary syndrome (ACS).

Methods

Thirty-six patients with ACS underwent single-photon emission computed tomography/computed tomography using retrospective electrocardiography gating during the resting state. The primary outcome was the percentage of left ventricular mass with abnormal myocardial perfusion (i.e. MDP) in G-MPI. Furthermore, the correlation between myocardial perfusion MDP and lymphocyte count, neutrophil count, white blood cell count, and NLR was calculated. In addition, we explored the relationship of myocardial perfusion MDP with other cardiac function parameters obtained from G-MPI, such as summed rest score, left ventricular ejection fraction, end-systolic volume, and end-diastolic volume.

Results

Myocardial perfusion MDP significantly correlated with white blood cell count, neutrophil count, and NLR (P < 0.01). Furthermore, these hematological parameters were significantly different between low and high MDP groups. Additionally, myocardial perfusion MDP negatively correlated with end-systolic volume (r = −0.615) and left ventricular ejection fraction (r = −0.657).

Conclusion

Myocardial perfusion MDP has a high correlation with inflammatory cell counts and cardiac function parameters obtained from G-MPI in ACS; this may be of help in the evaluation and treatment of these patients.
Solid versus liquid pulmonary micro-aspiration of reflux disease. Does it make a difference in determining the need for intervention?
Authors: Burton Leticia , Khoma Oleksandr , Gooley Susannah , Falk Gregory L. , Weerasinghe Daminda , Van der Wall Hans
Published: October 2024

Background

Pulmonary micro-aspiration (PMA) is a feared complication of gastroesophageal reflux disease (GORD). A novel scintigraphic test for GORD has been developed and validated. It can demonstrate contamination of the upper and lower airways by refluxate. Current observations have led to the hypothesis that prolongation in solid gastric emptying (SGE) is crical in pulmonary micro-aspiration.

Methods

Standard LGE and SGE studies and the novel reflux test were evaluated in paired studies in patients with severe GORD to measure rates of PMA after each meal. Either water labeled with 99m Technetium Phytate for the LGE or a labeled egg sandwich for the solid meal was utilized. Major symptoms were noted and the cough and reflux severity index (CSI & RSI) was obtained in all patients.

Results

A total of 131 patients were enrolled (59M/72F) with age range of 21–83 years (mean: 52 years). Patients were in the overweight range for BMI (mean: 26.8). Major symptoms were bloating, nausea, belching, and dyspepsia (< 20% had heartburn). SGE was abnormal in 92% (mean 766 min) and LGE abnormal in 53% (mean 82 min). PMA was shown in 35% after the SGE and in 71% after the LGE. PMA+ patients were older. A significant correlation was found between SGE and PMA (P < 0.00) but not LGE. The only significant symptom in the PMA group was bloating. RSI was abnormal in 64% and CSI in 46%.

Conclusion

The majority of patients with PMA do not complain of heartburn. Bloating in patients with severe GORD should raise the possibility of gastroparesis and PMA.
Deep infections after low-velocity ballistic tibia fractures are frequently polymicrobial and recalcitrant
Authors: Chintalapudi Nainisha , Fram Brianna R. , Odum Susan , Seymour Rachel B. , Karunakar Madhav A. ,   EMIT
Published: October 2024

Objectives:

To identify risk factors for developing a fracture-related infection in operatively treated ballistic tibia fractures and to report the microbiologic results of intraoperative cultures.

Design:

Retrospective review.

Setting:

Level 1 trauma center.

Patients/Participants:

One hundred thirty-three adults with operatively treated low-velocity ballistic tibia fractures, from 2011 to 2021.

Intervention:

One dose of prophylactic cefazolin or equivalent as well as perioperative prophylaxis.

Main Outcome Measurements:

Deep infection rate.

Results:

The deep infection rate was 12% (16/134) with no significant difference in injury characteristics, index surgical characteristics, or time to antibiotics between the groups (P > 0.05). Patients who were slightly older (35.5 vs. 27 median years, P = 0.005) and with higher median body mass indexes (BMIs) (30.09 vs. 24.51, P = 0.021) developed a deep infection. 56.3% of patients presented with signs of infection within the first 100 days after injury. Nine patients had polymicrobial infections. There were 29 isolated organisms, 69% were uncovered by first-generation cephalosporin prophylaxis (anaerobes, gram-negative rods, Enterococcus, methicillin resistant Staphylococcus Aureus [MRSA]), and 50% of patients developed recalcitrant infection and required a second reoperation where 6 organisms were isolated, half of which were not covered by first-generation prophylaxis (Enterococcus, Staphylococcus Aureus MRSA).

Conclusions:

We found a deep infection rate of 12% among ballistic tibia fractures receiving standard-of-care antibiotic prophylaxis. Increased age and body mass index were associated with deep infections. Half became recalcitrant requiring a second reoperation. 66.7% of isolated organisms were not covered by first-generation cephalosporin prophylaxis. Consideration should be given to treatment options such as broader prophylaxis or local antibiotic treatment.

Level of Evidence:

IV.
Tumor Lysis Syndrome Following PSMA Radioligand Therapy
Authors: Sahafi Pegah , Saeed Michael , Samadi Mohammad Hadi , Aryana Kamran , Askari Emran
Published: October 2024

Tumor lysis syndrome (TLS) is a rare complication following treatment in prostate cancer patients. We present a 65-year-old man with history of castration-resistant prostate cancer who developed TLS following 2 sessions of 177Lu-PSMA therapy. The patient presented with bulky axillary and mediastinal lymphadenopathies, an unusual site for prostate cancer metastasis. Although his PSA levels declined following treatment, he reported excessive weakness leading to immobility. Laboratory correlation showed markedly increased lactate dehydrogenase, from 413 to 543,000 U/L, suggesting the occurrence of TLS. Although being considered a relatively safe treatment, 177Lu-PSMA can sometime lead to life-threatening events, which is reviewed here.
Variable Tracer Avidity and Interlesional Heterogeneity on 18F-FDG, 68Ga-DOTATATE, and 68Ga-DOTA-FAPi-04 PET/CT Imaging in a Single Individual Patient With Progressive Metastatic Medullary Thyroid Carcinoma
Authors: Edamadaka Yeshwanth , Parghane Rahul V. , Basu Sandip
Published: October 2024

In medullary thyroid carcinoma (MTC), distant metastases have few therapeutic options with low success rates and substantial toxicity in many patients, warranting exploration of alternate systemic treatments with fewer adverse effects. The fibroblast activation protein inhibitor (FAPI)–based PET/CT opens new avenues for several cancers, including MTC. A case of MTC with varying tracer avidity and interlesional heterogeneity on 18F-FDG, 68Ga-DOTATATE, and 68Ga-DOTA-FAPI-04 PET/CT imaging is presented. 68Ga-DOTA-FAPI-04 PET/CT exhibited superior efficacy in terms of visualization of metastatic soft tissue, lymph nodal, and skeletal lesions, with enhanced target-to-background ratio compared with the other two, facilitating the detection of these lesions, thereby demonstrating the potential for theranostic translation.
A Challenging Case of Hyperfunctioning Submandibular Ectopic Thyroid Successfully Treated With 131I
Authors: Pisano Giusi , Sassano Serena , Rossi Esther Diana , D'Amore Annamaria , Zagaria Luca
Published: October 2024

Ectopic thyroid tissue is a rare condition, caused by aberrancy during thyroid gland embryogenesis. Any pathology involving the thyroid gland can also affect the ectopic tissue, including tumorigenesis. We report a challenging case of relapsed hyperthyroidism in a woman who already underwent subtotal thyroidectomy in 1995 and surgical revision in 2020 for multinodular toxic goiter. 99mTc-pertechnetate scan revealed an area of radiotracer focal uptake at submandibular level, posing a differential diagnosis between salivary gland tumor and ectopic thyroid. Correlation with clinical history and ultimately histopathology led to diagnosis of hyperfunctioning submandibular ectopic tissue, successfully treating the patient with 131I.
16S rRNA Gene Sequencing Reveals Bacterial Diversity in Khewra Salt Mine Walls
Authors: Noor Syeda Wardah , Arshad Sara , Abdullah Syed Muhammad , Kayani Bushra Khudadad , Fazal Sahar
Published: October 2024

The Khewra Salt Mine, also known as the source of Himalayan Pink Salt, is the second-largest salt mine in the world and a significant site for salt export. The mine's salt exhibits both amorphous and crystalline textures, with colors ranging from white to deep red, contributing to its distinctive pink hue. While previous research has extensively explored the mine's soil, plants, and brine samples, little attention has been given to the salt walls, which are a major tourist attraction. This study aimed to investigate the bacterial diversity within the salt walls from four distinct locations, including an under-construction area sampled for the first time.
From these four collection points, seven samples were gathered, yielding 19 isolates cultured on 2% NaCl nutrient agar. Bacterial isolates from the under-construction area (US1-1, US1-2, US2-1, and US2-2) and the museum walls (MS1-1 and MS1-2) underwent further biochemical, antibiotic sensitivity, and salt requirement testing, followed by 16S rRNA sequencing. Biochemical assays identified these isolates as gram positive, catalase and oxidase positive rods. All isolates were sensitive to chloramphenicol (30μg/ml). Salt tolerance tests classified them as slightly halophilic, thriving at 2-4% NaCl concentrations.
Molecular characterization revealed two strains from the under-construction area, US1-1 and US2-2, as uncultured Bacillus species and Bacillus thuringiensis, respectively, both with 94% sequence similarity. These sequences have been submitted to NCBI under accession numbers OQ295687 and OQ692139. The phylogenetic results show monophyletic associations between these two strains which could be due to their shared salt location and common ancestors.
 The sequences of US1-2, US2-1, and MS1-1 were 100% identical to Bacillus licheniformis, while MS1-2 matched Staphylococcus saprophyticus with 100% similarity. These sequences have been submitted to NCBI as OQ978592, OQ978561, OQ978562, and OQ978593, respectively.
The results of this study point towards significant diversity of bacteria, slightly halophilic, cocci or bacillus shaped. These halophilic bacterial strains, possessing salt-tolerant genes, present the need for further identification of bacterial colonies in the mine and their evolutionary patterns, which could also help uncover the role these microbes play in the ecosystem of the salt mine. Additionally, they show promise for industrial enzyme production.