bluuebunny/crossref_metadata_2025 huggingface dataset:
CytogeneticsComparability of Beckman Coulter Access Cardiac Troponin I Assays
Authors: Stanek Caroline , Martin Deirdra , Lima Jose , Cao Liyun
Published: November 2023

Cardiac troponins (cTn) are the most sensitive and specific biomarkers of myocardial injury. The rise and/or fall of cardiac troponins above the 99th percentile of the upper reference limit (URL) is required in the assessment of acute myocardial infarction. In our institution, high sensitivity troponin I (hsTnI) is performed on four Access 2 Immunoassay Systems and three DXI 800 Access Immunoassay Systems. As a regional medical center, we accept patients from outside hospitals where contemporary cardiac troponin I (cTnI) were performed. The results from different assays and platforms may disagree and lead to incorrect explanation of the results as false rise and/or fall of cTn. To harmonize results among these assays, we analyzed the variation between the two assays of cTnI and hsTnI, and the concordance of same assay hsTnI on different instruments using patient specimens. To investigate the between-method variance, 424 patient specimens with troponin levels ranging from 0-23370 ng/L were used to measure both cTnI and hsTnI on DXI 800 instruments. To investigate the within-method agreement, 43 patient specimens with troponin levels ranging from 2-114394 ng/L were used to measure hsTnI on Access 2 and DXI instruments. The between-method comparison of cTnI and hsTnI on DXI showed a slope of 1.003 with intercept of -43.31 and correlation coefficient (CC) of 0.9590. The mean bias was -5.1%, which was within the analytical imprecision range determined in our laboratory (2.2%-10.7%). However, comparison of cTnI and hsTnI in patients with troponin <20ng/L (n=103), the 99th percentile of the URL for males, showed the slope was 1.325 with intercept of -0.97 and CC of 0.7462. The mean bias was 1.91 (21.53%), which was much larger than the analytical imprecision. This is consistent with the fact that cTnI results are not reliable at the lower level due to the imprecision problem. Comparison of cTnI and hsTnI in patients with troponin >20ng/L (n=321) showed the slope was 1.006 with intercept of –60.09 and CC of 0.9576. The mean bias was -54.30 (-5.23%), which was within the analytical imprecision range. The within-method comparison of hsTnI on Access 2 and DXI 800 showed the slope was 1.138 with intercept of -633.0 and CC of 0.9888. The mean bias was 2126.4 (10.6%), within the analytical imprecision range. These data indicate that cTnI results above the 99th percentile URL are comparable with hsTnI results if both are tested on DXI 800, and hsTnI results tested on Access 2 and DXI 800 are comparable. Thus, to use the cardiac troponins assay properly, we suggest the laboratory report cardiac troponins with the assay and instrument names to reduce confusion during results comparison.
Exploration and utilization of novel aldoxime, nitrile, and nitro compounds metabolizing enzymes from plants and arthropods
Authors: Yamaguchi Takuya
Published: November 2023

Aldoxime (R1R2C=NOH) and nitrile (R−C≡N) are nitrogen-containing compounds that are found in species representing all kingdoms of life. The enzymes discovered from the microbial “aldoxime-nitrile” pathway (aldoxime dehydratase, nitrile hydratase, amidase, and nitrilase) have been thoroughly studied because of their industrial importance. Although plants utilize cytochrome P450 monooxygenases to produce aldoxime and nitrile, many biosynthetic pathways are yet to be studied. Cyanogenic millipedes accumulate various nitrile compounds, such as mandelonitrile. However, no such aldoxime- and nitrile-metabolizing enzymes have been identified in millipedes. Here, I review the exploration of novel enzymes from plants and millipedes with characteristics distinct from those of microbial enzymes, the catalysis of industrially useful reactions, and applications of these enzymes for nitrile compound production.
ExRec: a python pipeline for generating recombination-filtered multi-locus datasets
Authors: McCarthy Potter Sam , Jennings W Bryan
Published: November 2023

ExRec (Exclusion of Recombined DNA) is a dependency-free Python pipeline that implements the four-gamete test to automatically filter out recombined DNA blocks from thousands of DNA sequence loci. This procedure helps all loci better meet the “no intralocus recombination” assumption common to many coalescent-based analyses in population genomic, phylogeographic, and shallow-scale phylogenomic studies. The user-friendly pipeline contains five standalone applications—four file conversion scripts and one main script that performs the recombination filtering procedures. The pipeline outputs recombination-filtered data in a variety of common formats and a tab-delimited table that displays descriptive statistics for all loci and the analysis results. A novel feature of this software is that the user can select whether to output the longest nonrecombined sequence blocks from recombined loci (current best practice) or randomly select nonrecombined blocks from loci (a newer approach). We tested ExRec with six published phylogenomic datasets that ranged in size from 27 to 2237 loci and came in a variety of input file formats. In all trials the data could be easily analyzed in only seconds for the smaller datasets and <30 min for the largest using a simple laptop computer.

Availability and implementation

ExRec was written in Python 3 under the MIT license. The program applications, user manual (including step-by-step tutorials), and sample data are freely available at https://github.com/Sammccarthypotter/ExRec.
ProteinMAE: masked autoencoder for protein surface self-supervised learning
Authors: Yuan Mingzhi , Shen Ao , Fu Kexue , Guan Jiaming , Ma Yingfan , Qiao Qin , Wang Manning
Published: November 2023

The biological functions of proteins are determined by the chemical and geometric properties of their surfaces. Recently, with the booming progress of deep learning, a series of learning-based surface descriptors have been proposed and achieved inspirational performance in many tasks such as protein design, protein–protein interaction prediction, etc. However, they are still limited by the problem of label scarcity, since the labels are typically obtained through wet experiments. Inspired by the great success of self-supervised learning in natural language processing and computer vision, we introduce ProteinMAE, a self-supervised framework specifically designed for protein surface representation to mitigate label scarcity. Specifically, we propose an efficient network and utilize a large number of accessible unlabeled protein data to pretrain it by self-supervised learning. Then we use the pretrained weights as initialization and fine-tune the network on downstream tasks. To demonstrate the effectiveness of our method, we conduct experiments on three different downstream tasks including binding site identification in protein surface, ligand-binding protein pocket classification, and protein–protein interaction prediction. The extensive experiments show that our method not only successfully improves the network’s performance on all downstream tasks, but also achieves competitive performance with state-of-the-art methods. Moreover, our proposed network also exhibits significant advantages in terms of computational cost, which only requires less than a tenth of memory cost of previous methods.

Availability and implementation

https://github.com/phdymz/ProteinMAE.
Limited clinical validity of univariate resting-state EEG markers for classifying seizure disorders
Authors: Faiman Irene , Sparks Rachel , Winston Joel S , Brunnhuber Franz , Ciulini Naima , Young Allan H , Shotbolt Paul
Published: November 2023

Differentiating between epilepsy and psychogenic non-epileptic seizures presents a considerable challenge in clinical practice, resulting in frequent misdiagnosis, unnecessary treatment and long diagnostic delays. Quantitative markers extracted from resting-state EEG may reveal subtle neurophysiological differences that are diagnostically relevant. Two observational, retrospective diagnostic accuracy studies were performed to test the clinical validity of univariate resting-state EEG markers for the differential diagnosis of epilepsy and psychogenic non-epileptic seizures. Clinical EEG data were collected for 179 quasi-consecutive patients (age > 18) with a suspected diagnosis of epilepsy or psychogenic non-epileptic seizures who were medication-naïve at the time of EEG; 148 age- and gender-matched patients subsequently received a diagnosis from specialist clinicians and were included in the analyses. Study 1 is a hypothesis-driven study testing the ability of theta power and peak alpha frequency to classify people with epilepsy and people with psychogenic non-epileptic seizures, with an advanced machine learning pipeline. The next study (Study 2) is data-driven; a high number of quantitative EEG features are extracted and a similar machine learning approach as Study 1 assesses whether previously unexplored univariate EEG measures show promise as diagnostic markers. The results of Study 1 suggest that EEG markers that were previously identified as promising diagnostic indicators (i.e. theta power and peak alpha frequency) have limited clinical validity for the classification of epilepsy and psychogenic non-epileptic seizures (mean accuracy: 48%). The results of Study 2 indicate that identifying univariate markers that show good correlation with a categorical diagnostic label is challenging (mean accuracy: 45–60%). This is due to a considerable overlap in neurophysiological features between the diagnostic classes considered in this study, and to the presence of more dominant EEG dynamics such as alterations due to temporal proximity to epileptiform discharges. Markers that were identified in the context of previous epilepsy research using visually normal resting-state EEG were found to have limited clinical validity for the classification task of distinguishing between people with epilepsy and people with psychogenic non-epileptic seizures. A search for alternative diagnostic markers uncovered the challenges involved and generated recommendations for further research.
Risk factors for COVID-19 hospitalization and mortality in patients with chronic kidney disease: a nationwide cohort study
Authors: Artborg Angelica , Caldinelli Aurora , Wijkström Julia , Nowak Alexandra , Fored Michael , Stendahl Maria , Evans Marie , Rydell Helena
Published: November 2023

Background

Several studies have demonstrated an increased risk of severe coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. However, few have investigated the impact of CKD stage and dialysis modality. The primary aim of this study was to investigate the association between CKD stage, dialysis modality and risk of severe COVID-19. Secondly, we aimed to study the impact of comorbidities and drugs on the risk of severe COVID-19 in the CKD population.

Methods

This nationwide observational study was based on data from the Swedish Renal Registry and three other national registries. Patients with non-dialysis CKD stage 3b–5 or dialysis on 1 January 2020 were included and followed until 31 December 2021. The primary outcome was COVID-19 hospitalization; the secondary outcome was COVID-19 mortality. Associations were investigated using logistic regression models, adjusting for confounders.

Results

The study population comprised 7856 non-dialysis CKD patients and 4018 dialysis patients. The adjusted odds ratios (aOR) for COVID-19 hospitalization and mortality were highest in the dialysis group [aOR 2.24, 95% confidence interval (CI) 1.79–2.81; aOR 3.10, Cl 95% 2.03–4.74], followed by CKD 4 (aOR 1.33, 95% CI 1.05–1.68; aOR 1.66, Cl 95% 1.07–2.57), as compared with CKD 3b. No difference in COVID-19 outcomes was observed between patients on hemodialysis and peritoneal dialysis. Overall comorbidity burden was one of the strongest risk factors for severe COVID-19 and the risk was also increased in patients prescribed insulin, proton pump inhibitors, diuretics, antiplatelets or immunosuppressants.

Conclusions

Worsening CKD stage and comorbidity are independent risk factors for severe COVID-19 in the Swedish CKD population.
All-cause and immune checkpoint inhibitor–associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality
Authors: Chen Jia-Jin , Lee Tao-Han , Kuo George , Yen Chieh-Li , Lee Cheng-Chia , Chang Chih-Hsiang , Tu Kun-Hua , Chen Yung-Chang , Fang Ji-Tseng , Hung Cheng-Chieh , Yang Chih-Wei , Chou Wen-Chi , Chi Ching-Chi , Tu Yu-Kang , Yu Yang Huang-
Published: November 2023

Background

Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI.

Methods

This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results

A total of 120 studies comprising 46 417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43–2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96–2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10–2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68–3.93) for ICI-related AKI.

Conclusions

Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis.
Nur77 influences immunometabolism to regulate the release of proinflammatory cytokines and the formation of lipid bodies during Mycobacterium tuberculosis infection of macrophages
Authors: Birari Pankaj , Mal Soumya , Majumder Debayan , Sharma Arun K , Kumar Manish , Das Troyee , Ghosh Zhumur , Jana Kuladip , Gupta Umesh D , Kundu Manikuntala , Basu Joyoti
Published: November 2023

Infection of macrophages with Mycobacterium tuberculosis induces innate immune responses designed to clear the invading bacterium. However, bacteria often survive within the intracellular environment by exploiting these responses triggered by macrophages. Here, the role of the orphan nuclear receptor Nur77 (Nr4a1) in regulating the response of macrophages infected with M. tuberculosis (Mtb) has been delineated. Nur77 is induced early during infection, regulates metabolism by binding directly at the promoter of the TCA cycle enzyme, isocitrate dehydrogenase 2 (IDH2), to act as its repressor, and shifts the balance from a proinflammatory to an anti-inflammatory phenotype. Depletion of Nur77 increased transcription of IDH2 and, consequently, the levels of intracellular succinate, leading to enhanced levels of the proinflammatory cytokine IL-1β. Further, Nur77 inhibited the production of antibacterial nitric oxide and IL-1β in a succinate dehydrogenase (SDH)-dependent manner, suggesting that its induction favors bacterial survival by suppressing bactericidal responses. Indeed, depletion of Nur77 inhibited the intracellular survival of Mtb. On the other hand, depletion of Nur77 enhanced lipid body formation, suggesting that the fall in Nur77 levels as infection progresses likely favors foamy macrophage formation and long-term survival of Mtb in the host milieu.
King Henry VII and the case of the missing treaty: Anglo-Hungarian crusading diplomacy reconsidered
Authors: Gauthier Charlotte
Published: November 2023

Henry VII of England has never been considered a ‘crusader king’; his monetary contributions towards anti-Ottoman crusading have been characterized by his biographers as little more than bribes designed to constrain the ambitions of would-be pretenders to the English throne. However, an unpublished Anglo-Hungarian treaty of alliance calls such simplistic explanations into question, showing that after the death of his son Arthur, prince of Wales, in spring 1502, Henry VII attempted to insert England into a pan-European platform of anti-Ottoman alliances using the provision of crusade financing as a diplomatic lever. This article shows just how Henry VII’s ‘crusade diplomacy’ worked in practice, arguing for a reassessment of what has long appeared to be the settled question of Henry VII’s foreign policy aims and demonstrating the centrality of the ‘Turkish question’ to early sixteenth-century European diplomacy.
Asymptotically Autonomous Robustness of Non-autonomous Random Attractors for Stochastic Convective Brinkman-Forchheimer Equations on ℝ3
Authors: Kinra Kush , Mohan Manil T , Wang Renhai
Published: November 2023

This article is concerned with the asymptotically autonomous robustness (almost surely and in probability) of random attractors for stochastic version of 3D convective Brinkman-Forchheimer (CBF) equations defined on $\mathbb {R}^{3}$: $$ \begin{align*} &\frac{\partial\boldsymbol{v}}{\partial\mathrm{t}}-\mu\Delta\boldsymbol{v}+(\boldsymbol{v}\cdot\nabla)\boldsymbol{v}+\alpha\boldsymbol{v}+\beta|\boldsymbol{v}|^{r-1}\boldsymbol{v}+\nabla{p}=\boldsymbol{f}+``\mbox{stochastic terms}",\quad\nabla\cdot\boldsymbol{v}=0,\end{align*}$$where $\mu ,\alpha ,\beta > 0$, $r\geq 1$ and $\boldsymbol {f}(\cdot )$ is a given time-dependent external force field. Our goal is to study the asymptotically autonomous robustness for 3D stochastic CBF equations perturbed by a linear multiplicative or additive noise when time-dependent forcing converges towards a time-independent function. The main procedure to achieve our goal is how to justify that the usual pullback asymptotic compactness of the solution operators is uniform on some uniformly tempered universes over an infinite time-interval $(-\infty ,\tau ]$. This can be done by showing the backward uniform “tail-smallness” and “flattening-property” of the solutions over $(-\infty ,\tau ]$.
Simultaneous Determination of Amphenicols in Animal-Derived Foods by Solvent and Solid Phase Extraction With Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry
Authors: Liu Feng , Yan Yaya , Yao Yi , Qin Yingxu , Xu Fei
Published: November 2023

Background

The consumption of foods containing amphenicols, a type of antibiotic, is a major concern for human health. A stable and accurate detection method can provide technical support for food-safety monitoring.

Objective

An effective and efficient method was established for determining amphenicols in animal-derived foods through the simultaneous use of solid-phase extraction (SPE) cleanup and ultrahigh-performance liquid chromatography/mass spectrometry (UPLC-MS/MS).

Method

Samples were extracted using 1.0% ammoniated ethyl acetate solution, degreased with n-hexane, and then concentrated and cleaned using a C18 SPE column. Next, gradient elution was performed using methanol and 0.05% aqueous ammonia as the mobile phase, followed by separation using a C18 column. The target compound was detected using electrospray ionization, both in positive and negative modes, through multiple reaction monitoring, and quantified using an internal-standard method.

Results

The content of chloramphenicol (CAP), florfenicol (FF), and florfenicol amine (FFA) (content range: 0.2–8.0 µg/kg) as well as that of thiamphenicol (TAP; content range: 1.0–40.0 µg/kg) show a good linear relationship, with a correlation coefficient of r > 0.999. Furthermore, recoveries of 86.7–111.9% and relative standard deviations of <9.0% were achieved. The limits of detection and quantification are obtained as 0.03–0.33 and 0.1–1.0 μg/kg, respectively.

Conclusions

The proposed method has excellent stability and accuracy, and can be successfully used for the qualitative and quantitative determination of amphenicols, i.e., CAP, TAP, FF, and FFA residues in 210 animal-derived food samples, of which FF and FFA were detected in four samples.

Highlights

A stable and accurate method was successfully established for the simultaneous determination of CAP, TAP, FF, and FFA in animal-derived foods using UPLC-MS/MS. Effective sample pretreatment was established, lipids were removed using n-hexane, concentration and cleanup were achieved with the C18 SPE column, and matrix effects were effectively reduced, thus improving the method’s accuracy and stability. The method was validated for eight common animal-source foods, including beef, lamb, pork, chicken, egg, milk, fish, and honey. This method has good applicability for CAP, TAP, FF, and FFA in animal-derived foods.
The Impact of Virtual Reality on Anxiety and Pain During US-Guided Breast Biopsies: A Randomized Controlled Clinical Trial
Authors: Prabhu Vishnunarayan G , Sprouse Harper A , Brignull Calleigh G , Snider Rebecca , Tanner Stephanie , Adams Kyle J , B. Nisonson Andrea , Hand William R , Epling James A
Published: November 2023

Objective

To investigate the efficacy of immersive virtual reality (VR) in combination with standard local anesthetic for mitigating anxiety and pain during US-guided breast biopsies compared to local anesthetic alone.

Methods

Patients scheduled for US-guided biopsy were invited to participate. Eligible patients were females 18 years of age or older. Patients were randomized to VR or control group at a 1:1 ratio. Patients in the VR group underwent biopsy with the addition of a VR experience and patients in the control group underwent usual biopsy. Patient-perceived levels of anxiety and pain were collected before and after biopsy via the State-Trait Anxiety Inventory (STAI) and Visual Analog Scale (VAS). Physiological data were captured during biopsy using a clinically validated wristband. Differences in anxiety, pain, and physiologic data were compared between the VR and control group.

Results

Sixty patients were enrolled. After excluding 2 patients with VR device malfunction, there were 29 patients in the VR and 29 patients in the control group for analysis. The VR group had reduced anxiety compared to the control group based on postintervention STAI (P <.001) and VAS (P = .036). The VR group did not have lower pain based on postintervention VAS (P = .555). Physiological measures showed higher RR intervals and decreased skin conductance levels, which are associated with lower anxiety levels in the VR group.

Conclusion

Use of VR in addition to standard local anesthetic for US-guided breast biopsies was associated with reduced patient anxiety. Virtual reality may be a useful tool to improve the patient biopsy experience.
BRepGAT: Graph neural network to segment machining feature faces in a B-rep model
Authors: Lee Jinwon , Yeo Changmo , Cheon Sang-Uk , Park Jun Hwan , Mun Duhwan
Published: November 2023

In recent years, there have been many studies using artificial intelligence to recognize machining features in three-dimensional models in the computer-aided design (CAD)/computer-aided manufacturing field. Most of these studies converted the original CAD data into images, point clouds, or voxels for recognition. This led to information loss during the conversion process, resulting in decreased recognition accuracy. In this paper, we propose a novel deep learning model called the boundary representation graph attention network (BRepGAT) to segment faces in an original boundary representation (B-rep) model containing machining features. We define descriptors that represent information about the faces and edges of the B-rep model from the perspective of feature recognition. These descriptors are extracted from the B-rep model and transformed into homogeneous graph data, which are then passed to graph networks. BRepGAT recognizes machining features from the graph data input. Our experimental results using the MFCAD18++ dataset showed that BRepGAT achieved state-of-the-art recognition accuracy (99.1%). Furthermore, BRepGAT showed relatively robust performance on other datasets besides MFCAD18++.
Treaty Bodies and Special Procedures: Can They Work Better Together?
Authors: Steinerte Elina , Ploton Vincent
Published: November 2023

This article is a conversation between the authors on areas of complementarity between these two mechanisms, gaps, and potential avenues for enhanced mutual cooperation between the two.
Measuring the knowledge and perception of Jordanian health science students towards self-prescribed medications: a descriptive analysis study
Authors: Shudifat Ra’ed M , Mosleh Sultan , Almakhzomi Suhair , Al Shdifat Mohammad , Alnajar Malek , Alkhawaldeh Ja’far M , Al-Halaseh Lidia K
Published: November 2023

Objectives

To assess the level of perception and awareness of health science students towards using over-the-counter (OTC) medicines and reveal any malpractice.

Methods

A descriptive cross-sectional correlational study employing an internet-based self-administered questionnaire collected data from 342 participants. The study model comprised four compartments: introductory, socio-demographic, utilizing OTC medications, and estimating the perception level. Descriptive statistics were used to describe participants’ demographics and main study variables. Non-parametric descriptive analysis and chi-squared tests were used to determine significance across the three medical schools. The response rate among students in their first academic year (33.9%) was the highest.

Findings

Most participants rely on OTC to treat minor conditions like pain and the common cold. Nutraceuticals have been used heavily. The participants showed a positive attitude towards self-treatment; the average perception score was 3.45 (SD = 0.60; 95%CI: 3.38–3.51). Besides, participants on regularly prescribed medications still determined the interaction between their treatments and non-prescribed medications. No significant association between attitude average score and participant age (r = −0.06; P = .273). Likewise, no differences were found in perceived attitude towards OTC based on gender (P = .41), academic level (P = .223), and college (P = .84).

Conclusion

This study provides an overview of the level of medical student’s perception towards self-treatment; despite the promising levels of knowledge and perception, it is necessitated to introduce interprofessional medical education to get an integrated knowledge and qualified graduates to provide the best health services.
Eccentric binaries in retrograde discs
Authors: Tiede Christopher , D’Orazio Daniel J
Published: November 2023

Modern numerical hydrodynamics tools have recently enabled detailed examinations of binaries accreting from prograde circumbinary discs. These have reframed the current understanding of binary-disc interactions and disc driven orbital evolution. We present the first full-domain grid-based hydrodynamics simulations of equal-mass, eccentric binaries accreting from retrograde circumbinary discs. We study binary eccentricities that span e = 0.0 to e = 0.8 continuously, and explore the influence of retrograde accretion on the binary orbital response, disc morphology, and observational properties. We find that, at all eccentricities, retrograde accretion shrinks the binary semimajor axis and pumps its eccentricity leading to the previously identified possibility of highly eccentric mergers. Contrary to past studies and models, we observe gravitational forces to dominate the binary’s orbital evolution as opposed to the physical accretion of mass and momentum. Retrograde accretion variability also differs strongly from prograde solutions. Preeminently, binaries with e > 0.55 reveal a unique two-period, double-peaked accretion signature that has not previously been identified. We additionally find evidence for the emergence of retrograde Lindblad resonances at large eccentricities in accordance with predictions from linear theory. Our results suggest that some astrophysical binaries for which retrograde accretion is possible will experience factors-of-a-few times faster orbital decay than in prograde discs and will have their eccentricities pumped beyond the limits found from prograde solutions. Such effects could lead to rapid inward migration for some young stellar binaries, the detection of highly eccentric LISA mergers, and the tentatively observed turnover at the low-frequency end of the gravitational wave background.
WISDOM project – XVIII. Molecular gas distributions and kinematics of three megamaser galaxies
Authors: Liang Fu-Heng , Smith Mark D , Bureau Martin , Gao Feng , Davis Timothy A , Cappellari Michele , Elford Jacob S , Greene Jenny E , Iguchi Satoru , Lelli Federico , Lu Anan , Ruffa Ilaria , Williams Thomas G , Zhang Hengyue
Published: November 2023

The co-evolution of galaxies and supermassive black holes (SMBHs) underpins our understanding of galaxy evolution, but different methods to measure SMBH masses have only infrequently been cross-checked. We attempt to identify targets to cross-check two of the most accurate methods, megamaser, and cold molecular gas dynamics. Three promising galaxies are selected from all those with existing megamaser SMBH mass measurements. We present Atacama Large Millimeter/sub-millimeter Array (ALMA) 12CO (2–1) and 230-GHz continuum observations with angular resolutions of ≈0${_{.}^{\prime\prime}}$5. Every galaxy has an extended rotating molecular gas disc and 230-GHz continuum source(s), but all also have irregularities and/or non-axisymmetric features: NGC 1194 is highly inclined and has disturbed and lopsided central 12CO (2–1) emission; NGC 3393 has a nuclear disc with fairly regular but patchy 12CO (2–1) emission with little gas near the kinematic major axis, faint emission in the very centre, and two brighter structures reminiscent of a nuclear ring and/or spiral; NGC 5765B has a strong bar and very bright 12CO (2–1) emission concentrated along two bisymmetric offset dust lanes and two bisymmetric nuclear spiral arms. 12CO (2–1) and 12CO (3–2) observations with the James Clerk Maxwell Telescope are compared with the ALMA observations. Because of the disturbed gas kinematics and the impractically long integration times required for higher angular resolution observations, none of the three galaxies is suitable for a future SMBH mass measurement. None the less, increasing the number of molecular gas observations of megamaser galaxies is valuable, and the ubiquitous disturbances suggest a link between large-scale gas properties and the existence of megamasers.
Descriptive study of COVID-19 vaccinations and infections within an NHS workforce
Authors: Ke M , Soothill G , Wilson K , Swietlik S , Leckie A , Sutherland R
Published: November 2023

Background

Healthcare workers were a priority group for coronavirus disease 2019 (COVID-19) vaccination during the pandemic. Occupational exposure may account for some of the increased risk faced.

Aims

Describe COVID-19 vaccine uptake and infection rates in staff across a large NHS board in Scotland to better understand occupational risk during the pandemic.

Methods

Descriptive cross-sectional study. Demographic data were extracted on 5 August 2021 from 26 058 members of staff. COVID-19 vaccination status and positive polymerase chain reaction (PCR) results were extracted on two separate dates to describe the timeline of staff infections between March 2020 and January 2022.

Results

There was high uptake of all three vaccine doses across all demographic groups in hospital staff. PCR positivity decreased with increasing age and Scottish Index of Multiple Deprivation score. Staff and nosocomial COVID-19 infections followed peaks in community infection rates.

Conclusions

NHS Lothian is a typical NHS workforce with good vaccine uptake. Beyond very early cases, there seems to be minimal evidence of occupational acquisition of COVID-19. The large number of nosocomial infections at the start of the pandemic may, in fact, reflect lack of community testing at this time. Despite protection from high vaccine coverage, job type and good Infection Prevention and Control practices, it seems that staff remain at high risk of catching the highly transmissible omicron variant from the community rather than work.
A Clinicopathological Categorization System for Clinical Research in Coccidioidomycosis
Authors: Krogstad Paul , Thompson George R , Heidari Arash , Kuran Rasha , Stephens Alexis V , Butte Manish J , Johnson Royce
Published: November 2023

A wide array of clinical manifestations follow infection with Coccidioides immitis or Coccidioides posadasii, ranging from asymptomatic infection to life-threatening pulmonary disease or extrapulmonary dissemination and meningitis. Epidemiological studies require consistent definitions of cases and their comparative clinical features. Understanding host and pathogen determinants of the severity of coccidioidomycosis also requires that specific clinical features (such as coccidioidal meningitis) and their overlap be precisely defined and quantified. Here we propose a system for categorization of outcomes of coccidioidomycosis in individuals who are not overtly immunocompromised that harmonizes clinical assessments during translational research of this increasingly common disease.
Risk Factors for Serogroup B Meningococcal Disease Among College Students
Authors: Weil Lauren M , Crowe Samuel J , Rubis Amy B , Soeters Heidi M , Meyer Sarah A , Hariri Susan , McNamara Lucy A
Published: November 2023

Background

College students are at increased risk for invasive meningococcal disease, but which students are most at risk is unclear.

Methods

US meningococcal disease cases in persons aged 18–24 years during 2014–2017 were included. Patients were classified as undergraduate students or other persons. Incidence in different student and non-student populations was compared.

Results

During 2014–2017, 229 meningococcal disease cases were reported in persons aged 18–24 years; 120 were in undergraduate students. Serogroup B accounted for 74% of cases in students. Serogroup B disease incidence was 4-fold higher in undergraduate students, 11.8-fold higher among first-year undergraduate students, and 8.6-fold higher among residence hall residents versus non-undergraduates. During outbreaks, students affiliated with Greek life had a 9.8-fold higher risk of disease compared to other students. A significantly higher party school ranking was observed for schools with sporadic or outbreak cases when compared to schools with no cases.

Conclusions

The findings of increased disease risk among first-year students and those living on campus or affiliated with Greek life can inform shared clinical decision-making for serogroup B vaccines to prevent this rare but serious disease. These data also can inform school serogroup B vaccination policies and outbreak response measures.
The first reported case of furuncular myiasis in Syria with no international travel history of the patient to an endemic area
Authors: Al-Dabbagh Jacob , Douri Thaer
Published: November 2023

Myiasis is defined as the infestation of any part of the body by fly larvae. It is particularly common in tropical and subtropical regions. Cutaneous myiasis is the most common manifestation of this infestation. Here, we report a 21-year-old Syrian female who presented with a 10-day history of painful 2 ulcer-like lesions on her scalp and was diagnosed with furuncular myiasis, which included more than 20 larvae. The patient had no history of international travel to myiasis-endemic areas before the onset of the lesions. She probably acquired the infestation while visiting a cattle farm located in a rural region east of Hama governorate. Seborrheic dermatitis developed on her scalp after the myiasis treatment was performed.
Recurrent pulmonary infections as the first manifestation of cow milk intolerance: a rare case report from Syria
Authors: Doya Leen Jamel , Ismaeel Mayya , Mohammad Mohammad Fawaz , Ismaeel Yazan , Dib Ghazal , Alshehabi Zuheir , Ibrahim Ali
Published: November 2023

Cow milk protein intolerance is a common gastrointestinal condition in the first year of life. It is mainly manifested as gastrointestinal and dermatology symptoms. It rarely presents as a respiratory manifestation only without other accompanying symptoms. We report a case of a 5-month-old Syrian boy who presented with a history of recurrent acute bronchitis symptoms (cough, wheezing, tachypnea) for 3 months with no significant personal or family history. Hematological and radiographic investigations were normal. The diagnosis of cow milk intolerance was confirmed by clinical, endoscopically, and histological findings. The child was placed on amino acid hydrolysate milk with restricted cow products. The child improved significantly, and chest symptoms improved within a week of the treatment. Despite the rarity of cow milk intolerance in children with only respiratory symptoms, it should be kept in mind when the patient has recurrent pulmonary infections that are not improving on appropriate therapy.
Public mass shootings cause large surges in Americans’ engagement with gun policy
Authors: Reny Tyler T , Newman Benjamin J , Holbein John B , Hassell Hans J G
Published: November 2023

As public mass shootings continue to plague the United States, a growing scholarly literature seeks to understand the political effects of these tragic events. This literature, however, focuses on public opinion or turnout and vote choice, leaving open to question whether or not public mass shootings affect a range of other important actions citizens may take to engage with gun policy. Leveraging the as-good-as random timing of high-publicity public mass shootings over the past decade and an immense array of publicly available and proprietary data, we demonstrate that these events consistently cause surges in public engagement with gun policy—including internet searches, streaming documentaries, discussion on social media, signing petitions, and donating to political action committees. Importantly, we document the behaviors where shootings induce polarizing upswings in engagement and those where upswings skew toward gun control. Finally, we demonstrate that low-publicity shootings largely exert little-to-no effect on our outcomes.
External financing, technological changes, and employees
Authors: Kim E Han , Li Yuan , Lu Yao , Shi Xinzheng
Published: November 2023

Using exogenous shocks on the ability to issue seasoned equity offerings (SEOs), we show SEOs lead to a higher employee skill composition, that is, a lower (higher) proportion of low (high) skilled workers. The decrease in low-skilled workers exceeds the increase in high-skilled workers, resulting in reduced employment at the firm level. These effects are more significant when firms invest more in technology following SEOs and face greater financial constraints before SEOs, suggesting that SEOs relieve budget constraints on technology investments. These findings demonstrate that while external equity financing helps upgrade technology to improve productivity, it has a dark side for low-skilled workers.
Computational structure‐based approach to study chimeric antigens using a new protein scaffold displaying foreign epitopes
Authors: Cappelli Luigia , Cinelli Paolo , Perrotta Andrea , Veggi Daniele , Audagnotto Martina , Tuscano Giovanna , Pansegrau Werner , Bartolini Erika , Rinaudo Daniela , Cozzi Roberta
Published: November 2023

The identification and recombinant production of functional antigens and/or epitopes of pathogens represent a crucial step for the development of an effective protein‐based vaccine. Many vaccine targets are outer membrane proteins anchored into the lipidic bilayer through an extended hydrophobic portion making their recombinant production challenging. Moreover, only the extracellular loops, and not the hydrophobic regions, are naturally exposed to the immune system. In this work, the Domain 3 (D3) from Group B Streptococcus (GBS) pilus 2a backbone protein has been identified and engineered to be used as a scaffold for the display of extracellular loops of two Neisseria gonorrhoeae membrane proteins (PorB.1b and OpaB). A computational structure‐based approach has been applied to the design of both the scaffold and the model antigens. Once identified the best D3 engineerable site, several different chimeric D3 displaying PorB.1b and OpaB extracellular loops were produced as soluble proteins. Each molecule has been characterized in terms of solubility, stability, and ability to correctly display the foreign epitope. This antigen dissection strategy allowed the identification of most immunogenic extracellular loops of both PorB.1b and OpaB gonococcal antigens. The crystal structure of chimeric D3 displaying PorB.1b immunodominant loop has been obtained confirming that the engineerization did not alter the predicted native structure of this epitope. Taken together, the reported data suggest that D3 is a novel protein scaffold for epitope insertion and display, and a valid alternative to the production of whole membrane protein antigens. Finally, this work describes a generalized computational structure‐based approach for the identification, design, and dissection of epitopes in target antigens through chimeric proteins.
Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface
Authors: Balog Steven , Jeong Soi , Asahina Kinji
Published: November 2023

Upon injury to Glisson's capsule, mesothelial cells covering the liver surface differentiate into myofibroblasts and participate in capsular fibrosis. In the fibrotic area, infiltrating macrophages are present, but their origin and role in capsular fibrosis remain elusive. In the present study, we examined whether macrophages in the peritoneal cavity migrate to the liver and participate in capsular fibrosis. Capsular fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. Chlorhexidine gluconate treatment induced disappearance of CD11bHigh F4/80High large peritoneal macrophages from the peritoneal cavity. Transplantation of TIMD4+ large peritoneal macrophages to the mouse peritoneal cavity resulted in their recruitment to the fibrotic area of the liver. Bone marrow‐derived monocytes were also recruited to the chlorhexidine gluconate‐induced fibrotic area upon their transplantation to the peritoneal cavity. However, bone marrow‐derived macrophages, Kupffer cells, peritoneal B cells, and small peritoneal macrophages prepared from chlorhexidine gluconate‐treated mice did not exhibit such potential. In the hepatic fibrotic area, peritoneal macrophages lost expression of unique markers (Gata6, Timd4) and increased expression of genes involved in inflammation (Il1b, Il6, Tnf) and extracellular matrix remodeling (Mmp13, Timp1). Depletion of peritoneal macrophages by clodronate liposomes reduced capsular fibrosis. Our data indicate that large peritoneal macrophages are recruited to the injured liver surface and promote capsular fibrosis by inducing inflammation and extracellular matrix remodeling. Modulating the function of peritoneal macrophages might be a new approach for suppressing capsular fibrosis.
LPCAT3/LPLAT12 deficiency in the liver ameliorates acetaminophen‐induced acute liver injury
Authors: Inagaki Natsuko F. , Nakanishi Hiroki , Ohto Takayo , Shindou Hideo , Shimizu Takao
Published: November 2023

Acetaminophen (APAP) is a double‐edged sword, mainly depending on the dosage. A moderate dose of APAP is effective for fever and pain relief; however, an overdose induces acute liver injury. The mechanism underlying APAP‐induced acute liver failure is unclear, and its treatment is limited. A recent report has shown that several oxidized phospholipids are associated with APAP‐induced acute liver failure. Lysophosphatidylcholine acyltransferase 3 (Lpcat3, Lplat12), which is highly expressed in the liver, preferentially catalyzes the incorporation of arachidonate into lysophospholipids (PLs). In the present study, we investigated the roles of Lpcat3 on APAP‐induced acute liver injury using liver‐specific Lpcat3‐knockout mice. Hepatic Lpcat3 deficiency reduced the degree of APAP‐induced necrosis of hepatocytes around Zone 3 and ameliorated the elevation of hepatic injury serum marker levels, and prolonged survival. Lipidomic analysis showed that the accumulation of oxidized and hydroperoxidized phospholipids was suppressed in Lpcat3‐knockout mice. The amelioration of APAP‐induced acute liver injury was due not only to the reduction in the lipid synthesis of arachidonic acid PLs because of Lpcat3 deficiency, but also to the promotion of the APAP detoxification pathway by facilitating the conjugation of glutathione and N‐acetyl‐p‐benzoquinone imine. Our findings suggest that Lpcat3 is a potential therapeutic target for treating APAP‐induced acute liver injury.
Xylazine-associated Wounds: Clinical Experience From a Low-barrier Wound Care Clinic in Philadelphia
Authors: McFadden Rachel , Wallace-Keeshen Sara , Petrillo Straub Kristi , Hosey Rebecca A. , Neuschatz Rachel , McNulty Keara , Thakrar Ashish P.
Published: November 2023

The veterinary sedative xylazine is spreading in unregulated opioid supplies across North America. Among people who use drugs with repeated exposure to xylazine, a distinct wound type has emerged. Here, we describe these wounds and share our experience treating them in a nurse-led, low-barrier wound care clinic in Philadelphia, PA. We propose a reimagining of wound treatment across settings to better serve people who use drugs, and we advocate for stronger protections against the harms of an increasingly adulterated drug supply. Our perspective from the epicenter of the xylazine crisis can inform the response of communities across the country who are starting to face harms associated with xylazine.