bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic determination of optimal systems of Lie subalgebras: The package SymboLie
Authors: Amata Luca , Oliveri Francesco
Published: August 2023

Lie groups of point symmetries of partial differential equations constitute a fundamental tool for constructing group–invariant solutions. The number of subgroups is potentially infinite and so the number of group–invariant solutions. An important goal is a classification in order to have an optimal system of inequivalent group–invariant solutions from which all other solutions can be derived by action of the group itself. In turn, a classification of inequivalent subgroups induces a classification of inequivalent Lie subalgebras, and vice versa. A general method for classifying the Lie subalgebras of a finite–dimensional Lie algebra relies on the use of inner automorphisms. We present a novel effective algorithm that can automatically determine optimal systems of Lie subalgebras of a generic finite–dimensional Lie algebra; here, we limit the analysis to one–dimensional Lie subalgebras, though the same approach still works well for higher dimensional Lie subalgebras. The algorithm is implemented in the computer algebra system Wolfram Mathematica™ and illustrated by means of some examples.
Mathematical etudes on quantum computation
Authors: Bocharov Alexei
Published: August 2023

Recent expansion in the field of quantum computing has been so dramatic that even a cursory review of the field easily spans over dozens of pages. Rather than attempting an overview of quantum computing the purpose of this paper is to attract interest of professional mathematicians through a handful of succinct etudes each focusing on a particular mathematically rich aspect of quantum. By focusing on such aspects, we strive to highlight research challenges that are likely to require full power of modern mathematics for their resolution.
Gender- and Age-Related Characterization of Lip Morphology: A Three-Dimensional Analysis in a Chinese Population
Authors: Yang Yuyan , Zhang Mengyuan , Jin Lin , Long Xiao , Zeng Ang , Yu Nanze , Wang Xiaojun
Published: August 2023

Background

Establishing facial anthropometric reference values is essential for diagnosis of deformity, assessment of aging, and planning for aesthetic and reconstructive treatment.

Objectives

This study aimed to provide detailed perioral anthropometric data in relation to sex and age in Chinese persons with a standardized 3-dimensional protocol.

Methods

Three-dimensional facial photographs were obtained of 60 male and 64 female healthy Chinese participants ages 20 to 35 and 50 to 65 years old, as well as 2 acromegaly patients, with the VECTRA 3D camera. A standardized evaluation was performed to locate 37 perioral landmarks and generate corresponding measurements, including 26 linear distances, 5 ratios, 2 curvatures, 4 areas, and 9 angles. Measurements of different age groups and of different genders were compared, as were measurements of healthy individuals with those of acromegaly patients.

Results

Sex discrepancy was noted in philtrum length, width, and area, lip width, and vermilion and cutaneous upper lip area; these were larger in Chinese males than females. However, vermilion heights were similar in both genders. With age, philtrum and cutaneous upper lip height and area, lip width, and angles related to cupid's bow significantly increased, whereas vermilion height and mouth corner angles decreased, and philtrum width, vermilion areas, and lip protrusion remained unchanged. Compared to healthy Chinese patients, acromegaly patients had a larger value for most measurements. Perioral rejuvenation based on detailed 3-dimensional anthropometry showed good results.

Conclusions

Chinese males have wider but not thicker lips than females, and aging features thin, flattened, and wide vermilions with a lengthened philtrum in both genders. These data can serve as a reference standard for disease diagnosis, aesthetic procedures, and reconstructive lip surgeries.

Level of Evidence: 4
AntiRef: reference clusters of human antibody sequences
Authors: Briney Bryan
Published: August 2023

Motivation

Genetic biases in the human antibody repertoire result in publicly available antibody sequence datasets that contain many duplicate or highly similar sequences. Available datasets are further skewed by the predominance of studies focused on specific disease states, primarily cancer, autoimmunity, and a small number of infectious diseases that includes HIV, influenza, and SARS-CoV-2. These biases and redundancies are a barrier to rapid similarity searches and reduce the efficiency with which these datasets can be used to train statistical or machine-learning models. Identity-based clustering provides a solution; however, the extremely large size of available antibody sequence datasets makes such clustering operations computationally intensive and potentially out of reach for many scientists and researchers who would benefit from such data.

Results

Antibody Reference Clusters (AntiRef), which is modeled after UniRef, provides clustered datasets of filtered human antibody sequences. Due to the modular nature of recombined antibody genes, the clustering thresholds used by UniRef for general protein sequences are suboptimal for antibody clustering. Starting with an input dataset of ∼451M full-length, productive human antibody sequences, AntiRef provides reference datasets clustered at a range of antibody-optimized identity thresholds. AntiRef90 is one-third the size of the input dataset and less than half the size of the non-redundant AntiRef100.

Availability and implementation

AntiRef datasets are available on Zenodo (zenodo.org/record/7474336). All code used to generate AntiRef is available on GitHub (github.com/briney/antiref). The AntiRef versioning scheme (current version: v2022.12.14) refers to the date on which sequences were retrieved from OAS.
Pretrained transformer models for predicting the withdrawal of drugs from the market
Authors: Mazuz Eyal , Shtar Guy , Kutsky Nir , Rokach Lior , Shapira Bracha
Published: August 2023

Motivation

The process of drug discovery is notoriously complex, costing an average of 2.6 billion dollars and taking ∼13 years to bring a new drug to the market. The success rate for new drugs is alarmingly low (around 0.0001%), and severe adverse drug reactions (ADRs) frequently occur, some of which may even result in death. Early identification of potential ADRs is critical to improve the efficiency and safety of the drug development process.

Results

In this study, we employed pretrained large language models (LLMs) to predict the likelihood of a drug being withdrawn from the market due to safety concerns. Our method achieved an area under the curve (AUC) of over 0.75 through cross-database validation, outperforming classical machine learning models and graph-based models. Notably, our pretrained LLMs successfully identified over 50% drugs that were subsequently withdrawn, when predictions were made on a subset of drugs with inconsistent labeling between the training and test sets.

Availability and implementation

The code and datasets are available at https://github.com/eyalmazuz/DrugWithdrawn.
Coherent pathway enrichment estimation by modeling inter-pathway dependencies using regularized regression
Authors: Jablonski Kim Philipp , Beerenwinkel Niko
Published: August 2023

Motivation

Gene set enrichment methods are a common tool to improve the interpretability of gene lists as obtained, for example, from differential gene expression analyses. They are based on computing whether dysregulated genes are located in certain biological pathways more often than expected by chance. Gene set enrichment tools rely on pre-existing pathway databases such as KEGG, Reactome, or the Gene Ontology. These databases are increasing in size and in the number of redundancies between pathways, which complicates the statistical enrichment computation.

Results

We address this problem and develop a novel gene set enrichment method, called pareg, which is based on a regularized generalized linear model and directly incorporates dependencies between gene sets related to certain biological functions, for example, due to shared genes, in the enrichment computation. We show that pareg is more robust to noise than competing methods. Additionally, we demonstrate the ability of our method to recover known pathways as well as to suggest novel treatment targets in an exploratory analysis using breast cancer samples from TCGA.

Availability and implementation

pareg is freely available as an R package on Bioconductor (https://bioconductor.org/packages/release/bioc/html/pareg.html) as well as on https://github.com/cbg-ethz/pareg. The GitHub repository also contains the Snakemake workflows needed to reproduce all results presented here.
metGWAS 1.0: an R workflow for network-driven over-representation analysis between independent metabolomic and meta-genome-wide association studies
Authors: Khan Saifur R , Obersterescu Andreea , Gunderson Erica P , Razani Babak , Wheeler Michael B , Cox Brian J
Published: August 2023

Motivation

The method of genome-wide association studies (GWAS) and metabolomics combined provide an quantitative approach to pinpoint metabolic pathways and genes linked to specific diseases; however, such analyses require both genomics and metabolomics datasets from the same individuals/samples. In most cases, this approach is not feasible due to high costs, lack of technical infrastructure, unavailability of samples, and other factors. Therefore, an unmet need exists for a bioinformatics tool that can identify gene loci-associated polymorphic variants for metabolite alterations seen in disease states using standalone metabolomics.

Results

Here, we developed a bioinformatics tool, metGWAS 1.0, that integrates independent GWAS data from the GWAS database and standalone metabolomics data using a network-based systems biology approach to identify novel disease/trait-specific metabolite-gene associations. The tool was evaluated using standalone metabolomics datasets extracted from two metabolomics-GWAS case studies. It discovered both the observed and novel gene loci with known single nucleotide polymorphisms when compared to the original studies.

Availability and implementation

The developed metGWAS 1.0 framework is implemented in an R pipeline and available at: https://github.com/saifurbd28/metGWAS-1.0.
MULGA, a unified multi-view graph autoencoder-based approach for identifying drug–protein interaction and drug repositioning
Authors: Ma Jiani , Li Chen , Zhang Yiwen , Wang Zhikang , Li Shanshan , Guo Yuming , Zhang Lin , Liu Hui , Gao Xin , Song Jiangning
Published: August 2023

Motivation

Identifying drug–protein interactions (DPIs) is a critical step in drug repositioning, which allows reuse of approved drugs that may be effective for treating a different disease and thereby alleviates the challenges of new drug development. Despite the fact that a great variety of computational approaches for DPI prediction have been proposed, key challenges, such as extendable and unbiased similarity calculation, heterogeneous information utilization, and reliable negative sample selection, remain to be addressed.

Results

To address these issues, we propose a novel, unified multi-view graph autoencoder framework, termed MULGA, for both DPI and drug repositioning predictions. MULGA is featured by: (i) a multi-view learning technique to effectively learn authentic drug affinity and target affinity matrices; (ii) a graph autoencoder to infer missing DPI interactions; and (iii) a new “guilty-by-association”-based negative sampling approach for selecting highly reliable non-DPIs. Benchmark experiments demonstrate that MULGA outperforms state-of-the-art methods in DPI prediction and the ablation studies verify the effectiveness of each proposed component. Importantly, we highlight the top drugs shortlisted by MULGA that target the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), offering additional insights into and potentially useful treatment option for COVID-19. Together with the availability of datasets and source codes, we envision that MULGA can be explored as a useful tool for DPI prediction and drug repositioning.

Availability and implementation

MULGA is publicly available for academic purposes at https://github.com/jianiM/MULGA/.
Clinical features and imaging characteristics in achiasmia
Authors: Pilat Anastasia , McLean Rebecca J , Vanina Anna , Dineen Robert A , Gottlob Irene
Published: August 2023

Achiasmia is a rare visual pathway maldevelopment with reduced decussation of the axons in the optic chiasm. Our aim was to investigate clinical characteristics, macular, optic nerve and brain morphology in achiasmia. A prospective, cross-sectional, observational study of 12 participants with achiasmia [8 males and 4 females; 29.6 ± 18.4 years (mean ± standard deviation)] and 24 gender-, age-, ethnicity- and refraction-matched healthy controls was done. Full ophthalmology assessment, eye movement recording, a high-resolution spectral-domain optical coherence tomography of the macular and optic disc, five-channel visual-evoked responses, eye movement recordings and MRI scans of the brain and orbits were acquired. Achiasmia was confirmed in all 12 clinical participants by visual-evoked responses. Visual acuity in this group was 0.63 ± 0.19 and 0.53 ± 0.19 for the right and left eyes, respectively; most participants had mild refractive errors. All participants with achiasmia had see-saw nystagmus and no measurable stereo vision. Strabismus and abnormal head position were noted in 58% of participants. Optical coherence tomography showed optic nerve hypoplasia with associated foveal hypoplasia in four participants. In the remaining achiasmia participants, macular changes with significantly thinner paracentral inner segment (P = 0.002), wider pit (P = 0.04) and visual flattening of the ellipsoid line were found. MRI demonstrated chiasmatic aplasia in 3/12 (25%), chiasmatic hypoplasia in 7/12 (58%) and a subjectively normal chiasm in 2/12 (17%). Septo-optic dysplasia and severe bilateral optic nerve hypoplasia were found in three patients with chiasmic aplasia/hypoplasia on MRI. In this largest series of achiasmia patients to date, we found for the first time that neuronal abnormalities occur already at the retinal level. Foveal changes, optic nerve hypoplasia and the midline brain anomaly suggest that these abnormalities could be part of the same spectrum, with different manifestations of events during foetal development occurring with varying severity.
Short-term percutaneous mechanical circulatory support: no promise without positioning!
Authors: Balthazar Tim , Van Mieghem Nicolas M , Raes Matthias , Van Loo Ines , Verbrugge Frederik H
Published: August 2023

Short-term percutaneous mechanical circulatory support by a micro-axial flow pump is increasingly used to support the left ventricle in cardiogenic shock. After a correct indication and placement, appropriate device management in the cardiac intensive care unit is vital to ensure optimal pump function and adequate haemodynamic support. A key element hereby is a correct percutaneous ventricular assist device (pVAD) position. This review explains how an optimal left-sided pVAD position can be achieved and maintained, focusing on the correct insertion depth and rotational angle. Useful imaging techniques, placement and replacement manoeuvres, and monitoring options through the console are discussed. The frequently encountered problem of mal-rotation towards the mitral valve, which may cause suction alarms, haemolysis, aortic regurgitation, and inadequate haemodynamic support, is explained. Finally, a practical bedside approach to assess pVAD position and discern suction alarms due to mal-positioning from haemodynamic problems is proposed.
Comparative genome analysis of the freshwater fungus Filosporella fistucella indicates potential for plant-litter degradation at cold temperatures
Authors: Vasconcelos Rissi Daniel , Ijaz Maham , Baschien Christiane
Published: August 2023

Freshwater fungi play an important role in the decomposition of organic matter of leaf litter in rivers and streams. They also possess the necessary mechanisms to endure lower temperatures caused by habitat and weather variations. This includes the production of cold-active enzymes and antifreeze proteins. To better understand the physiological activities of freshwater fungi in their natural environment, different methods are being applied, and genome sequencing is one in the spotlight. In our study, we sequenced the first genome of the freshwater fungus Filosporella fistucella (45.7 Mb) and compared the genome with the evolutionary close-related species Tricladium varicosporioides (48.2 Mb). The genomes were annotated using the carbohydrate-active enzyme database where we then filtered for leaf-litter degradation-related enzymes (cellulase, hemicellulase, laccase, pectinase, cutinase, amylase, xylanase, and xyloglucanase). Those enzymes were analyzed for antifreeze properties using a machine-learning approach. We discovered that F. fistucella has more enzymes to participate in the breakdown of sugar, leaf, and wood than T. varicosporioides (855 and 719, respectively). Filosporella fistucella shows a larger set of enzymes capable of resisting cold temperatures than T. varicosporioides (75 and 66, respectively). Our findings indicate that in comparison with T. varicosporioides, F. fistucella has a greater capacity for aquatic growth, adaptability to freshwater environments, and resistance to low temperatures.
Associations Between Change in Kidney Functioning, Age, Race/Ethnicity, and Health Indicators in the Health and Retirement Study
Authors: Zhao Erfei , Ailshire Jennifer , Kim Jung Ki , Wu Qiao , Crimmins Eileen M
Published: August 2023

Background

The aging process is accompanied by decline in kidney functioning. It remains unknown to what extent age-related decline in kidney functioning can be attributed to health indicators, and whether rate of decline differs across sociodemographic groups.

Methods

Using data from the Health and Retirement Study from 2006/2008 through 2014/2016, we estimated kidney functioning trajectories, determined by cystatin C, among adults aged over 51 over 8 years. We evaluated the role of age, health conditions/behaviors, and genetics in the decline and also examined sociodemographic differentials.

Results

Kidney function declined with age and accelerated at older ages, even after adjusting for health conditions/behaviors and genetic differences (eg, 0.019 mg/L annual increase in cystatin C among 70–79 compared to 0.007 mg/L among 52–59 at baseline). Decline occurred faster among those with uncontrolled diabetes (0.008, p = .009), heart conditions (0.007, p < .000), and obesity (0.005, p = .033).Hispanic participants (0.007, p = .039) declined faster than non-Hispanic White persons due to diabetes, heart conditions, and obesity; non-Hispanic Black participants had worse baseline kidney functioning (0.099, p < .000), but only one fourth of this Black–White difference was explained by investigated risk factors. People with higher education experienced slower decline (−0.009, p = .004).

Conclusions

Age was a significant predictor of decline in kidney functioning, and its association was not fully explained by health conditions/behaviors, or genetics. Better management of diabetes, heart conditions, and obesity is effective in slowing this decline. Baseline differences in kidney functioning (eg, between non-Hispanic White and Black persons; those with and without hypertension) suggest disparities occur early in the life course and require early interventions.
Pain, Physical Demands at Work, and Future Work Expectations Among Older Adults in the United States
Authors: Andrasfay Theresa , Fennell Gillian , Crimmins Eileen
Published: August 2023

Background and Objectives

In the United States, pain is becoming increasingly prevalent among older adults at the same time as policies are incentivizing work longer. Given that pain and physically demanding jobs are both linked to early retirement and they often go hand-in-hand, it is important to assess how the unique effects of pain and physical work demands may interact in predicting future work expectations.

Research Design and Methods

Using Health and Retirement Study data (1998, 2004, 2010, and 2016 waves), we assess how pain and physical job demands influence future work expectations of 10,358 adults at midlife (ages 51–56), after accounting for sociodemographic, job, health, and financial characteristics.

Results

Compared to men with no pain, activity-interfering pain was associated with low expectations of full-time work past 62 regardless of job demands, while noninterfering pain was associated with 62% higher odds (odds ratio [OR] = 1.62, 95% confidence interval [CI]: 1.35–1.93) of expecting not to work full-time past age 62 only among those with physically demanding jobs. Having both interfering pain and a physically demanding job was associated with increased odds of expecting not to work full-time past age 65 for men (OR = 1.25, 95% CI: 1.06–1.47) and past age 62 for women (OR = 1.18, 95% CI: 1.00–1.39).

Discussion and Implications

The co-occurrence of physically demanding work with pain—particularly activity-interfering pain—is associated with low expectations of full-time work past ages 62 and 65 for adults at midlife. Working longer may be feasible for older adults whose pain does not interfere with work, but unrealistic for individuals facing both pain and physically demanding work.
Participatory Research Approaches in Alzheimer’s Disease and Related Dementias Literature: A Scoping Review
Authors: Reyes Laurent , Scher Clara J , Greenfield Emily A
Published: August 2023

Background and Objectives

Given the increase in methodological pluralism in research on brain health, cognitive aging, and neurodegenerative diseases, this scoping review aims to provide a descriptive overview and qualitative content analysis of studies stating the use of participatory research approaches within Alzheimer’s disease and related dementias (ADRD) literature globally.

Research Design and Methods

We conducted a systematic search across four multidisciplinary databases (CINAHL, SCOPUS, PsycInfo, PubMed) for peer-reviewed, English-language studies addressing ADRD that explicitly described their use of a participatory research approach. We employed a systematic process for selecting articles that yielded a final sample of 163 studies. Data from articles were analyzed to chart trends from 1990 to 2022 in terminology, descriptions, application of participatory approaches, and the extent and nature of partnerships with nonacademics.

Results

Results demonstrated geographic differences in the use of stated approaches between North America—where community-based participatory research predominates—and Europe, where Action Research is most common. We further found that only 73% of papers in this systematic review had identifiable definitions or descriptions of the participatory approach used. Findings also showed that 14% of articles demonstrated no evidence of engaged partnership beyond activities typical of research participants, while 23% of articles identified partnering with people with dementia, and an additional 16% reported partnerships with members from Indigenous, Black, Asian, or Latinx communities.

Discussion and Implications

This scoping review identifies three areas in need of greater attention in ADRD literature using participatory research approaches. First, findings indicate the importance of strengthening the use, transparency, and rigor of participatory methods. Second, results suggest the need for greater inclusion of historically marginalized groups who are most affected by ADRD as research partners. Finally, the findings highlight the need for integrating social justice values of participatory approaches into research project designs.
The Disappearing ‘Minimum Rights’ of Article 6 ECHR: the Unfortunate Legacy of Ibrahim and Beuze
Authors: Goss Ryan
Published: August 2023

This article critiques the European Court of Human Rights’ recent extensive case law on the right to a fair trial under Article 6 of the European Convention on Human Rights (ECHR), and particularly the right to legal assistance in criminal trials. The article examines the significant and ongoing impact of the judgments in Ibrahim (2016) and Beuze (2018) and argues that the recent case law reflects buyer’s remorse on the part of the Court for its landmark judgment in Salduz (2008). Article 6 is among the most heavily litigated provisions of the ECHR, and this article is the first extended scholarly analysis of the post-Beuze case law. The article identifies two interrelated trends in the most recent case law: first, the Court taking a number of analytical steps that allow it to overlook the text of Article 6(3) in favour of an impressionistic assessment of the overall fairness of the proceedings; and, second, the Court providing Governments with multiple opportunities to advance public interest justification arguments despite continued pronouncements that Article 6 is an unqualified right. The article suggests that the jurisprudence is weakening the Article 6 guarantees.
The role of local colleagues in establishing international scientific collaboration: Social capital in emerging science systems
Authors: Müller Moritz , Cowan Robin , Barnard Helena
Published: August 2023

International collaborations are important for developing science systems. Using a dataset of South African university scientists, we ask whether social capital relevant to international collaboration held by one scientist spills over to local colleagues. Distinguishing between different ways of acquiring foreign ties, we find that 20% of our cases resemble the most-studied form of international collaborations, via the unique ties of an individual with specific characteristics, e.g., foreign research training. In all other cases, both personal and local peers’ international social capital is relevant for foreign tie formation. Underlining the systemic functioning of science, international social capital is activated through scientific collaboration among local scientists. The mediating effect of local scientific collaboration is present across all scientific fields and holds for scientists trained locally or abroad. Our findings thus imply that local collaboration is a relevant mechanism to strengthen international collaboration and the formation of international social capital.
The Dimension of Thurston’s Spine
Authors: Fortier Bourque Maxime
Published: August 2023

We show that for every ${\varepsilon }>0$, there exists some $g\geq 2$ such that the set of closed hyperbolic surfaces of genus $g$ whose systoles fill has dimension at least $(5-{\varepsilon }) g$. In particular, the dimension of this set—proposed as a spine for moduli space by Thurston—is larger than the virtual cohomological dimension of the mapping class group.
Computational phenotyping with the All of Us Research Program: identifying underrepresented people with HIV or at risk of HIV
Authors: Yang Xueying , Zhang Jiajia , Cai Ruilie , Liang Chen , Olatosi Bankole , Weissman Sharon , Li Xiaoming
Published: August 2023

Objective

This study aims to identify the people living with HIV (PWH) and pre-exposure prophylaxis (PrEP) users in the All of Us (AoU) database by integrating information from both electronic health record (EHR)- and self-reported survey data.

Methods

We identified PWH and PrEP users if they met the inclusion criterion by conditions, lab measurements, or medications related to HIV in EHR data or confirmed questions in the Survey data.

Results

We evaluated the latest data release through July 1, 2022 in AoU. Through computational phenotyping, we identified 4575 confirmed and 3092 probable adult PWH and 564 PrEP users. PWH was most identified by a combination of medications and conditions (3324, 43.4%) and drug exposure alone (2191, 28.6%), then less commonly by survey data alone (608, 7.9%) and lab alone (81, 1.1%).

Discussion and conclusion

Our methods serve as an overall framework for other researchers using AoU data for conducting HIV-related research.
A Simple UV Spectrophotometric Method Based on Continuous Wavelet Transform and Multivariate Calibration Model for the Concurrent Analysis of Three Water-Soluble Vitamins in Fertility Supplements
Authors: Lohrdy Mahla , Sohrabi Mahmoud Reza , Davallo Mehran
Published: August 2023

Background

Owing to the presence of overlapping spectra in pharmaceutical components, classical spectrophotometry is hard for concurrent determination. The advance of chemometrics along with UV-Vis spectrophotometry has contributed to solving this problem.

Objective

In this study, a fast, easy, precise, accurate, low-cost, and eco-friendly spectrophotometric technique was introduced and validated for the simultaneous analysis of vitamin B6, vitamin B12, and vitamin C in fertility supplements for men and women using continuous wavelet transform (CWT) and partial least squares (PLS) techniques without using time-consuming extraction process and organic solvents.

Method

In the CWT method, the zero-crossing technique was applied to obtain the optimum points for plotting calibration curves for each component. The validation of both methods was evaluated by analyzing several mixtures with different concentrations. The efficiency of the proposed methods was also surveyed on commercial capsules.

Results

Wavelet families, including Symlet (sym2) at 230, Biorthogonal (bior1.3) at 378 nm, and Daubechies (db2) at 261, were considered for vitamins B6, B12, and C, respectively. The linear range was found to be 8–20, 8–20, and 10–25 μg/mL with the coefficient of determination (R2) equal to 0.9982, 0.9978, and 0.9701 for B6, B12, and C, respectively. Low limit of detection (LOD) (<0.09 μg/mL) and limit of quantification (LOQ) <0.9 μg/mL were achieved. The mean recovery values in synthetic mixtures were from 98.38 to 98.89% and from 99.83 to 99.99%, where root-mean-square error (RMSE) of not more than 0.4 and 0.05 using the CWT and PLS methods, respectively.

Conclusions

The obtained results from the commercial capsules, applying the suggested techniques, were compared to those yielded by the high-performance liquid chromatography (HPLC) method using the analysis of variance (ANOVA) test. According to the results, there are no significant differences, and they were in good agreement. According to all the mentioned cases, the proposed approaches can replace the time-consuming and costly HPLC method in quality control laboratories.

Highlights

Green spectrophotometry coupling chemometrics methods were proposed. Simultaneous determination of three water-soluble vitamins in fertility supplements was done using these approaches. Rapidity, simplicity, low cost, and accuracy are the benefits of the proposed methods. A HPLC technique was used as a reference method to compare with the chemometrics methods.
Stability and Biosimilarity Assessment of Bevacizumab Monoclonal Antibody; Orthogonal Testing Protocol Coupled With Peptide Mapping–Principal Component Analysis
Authors: Abdelghaffar Sara H , Hegazy Maha A , Eltanany Basma M
Published: August 2023

Background

Biologics are essential in cancer treatment because they stimulate the body’s natural response to fight cancer, but they are expensive. Biosimilars are more affordable compared to patent biologicals, but it must be verified that they are as effective as their innovators. Characterization of biosimilars and assessment of interchangeability requires many data points for verification.

Objective

The proposed study provides a quality assessment of two new bevacizumab (BVZ) biosimilars, produced by Amgen and Biocad, Inc., through the development and greenness assessment of an orthogonal testing protocol and purity indicating assay, including size-exclusion (SE-HPLC), reversed-phase (RP-HPLC), and cation exchange chromatography (CEX-HPLC) in addition to dynamic light scattering (DLS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

Methods

SE-HPLC method was performed and validated to screen the BVZ monomer and its aggregates and/or fragments. Peak purity and system suitability parameters were calculated. Results indicate that the orthogonal protocol is a useful tool for assessing monoclonal antibody stability. It is a key criterion for biosimilarity assessment. DLS and SDS-PAGE results were compared to each other to reveal close retention times and banding patterns between BVZ innovator and its biosimilars. These results showed that Avastin® and the investigated biosimilars have the same profile in terms of peak area of related compounds within the acceptance limit and apparent molecular weight, and the SDS-PAGE technique was found to be the most eco-friendly technique among others.

Conclusions

The results obtained highlighted the importance of assessing similarities and differences in ensuring the biosimilarity and interchangeability of the studied products.

Highlights

BVZ is one of the essential monoclonal antibodies in the treatment of colorectal cancer (CRC). BVZ biosimilars were evaluated by developing an orthogonal testing protocol and a purity-indicating assay. The size-exclusion (SE)-HPLC method was applied and validated to monitor the BVZ monomer and its aggregates. The results demonstrated the importance of assessing the stability and biosimilarity of BVZ.
Spontaneous epiglottic abscess: pathophysiology and airway management options
Authors: Alotaibi Fahad Z
Published: August 2023

Laryngeal abscesses are rare in the modern antibiotic era. This report presents a novel case of an epiglottic abscess in a patient with diabetes who developed respiratory distress and was managed by awake intubation in the emergency room followed by transoral incision and drainage of the abscess and tracheostomy. Full recovery after 1 week of intravenous antibiotic treatment was observed. Surgical intervention is necessary for treatment and culture-directed antimicrobial therapy. Poorly controlled diabetes is a newly described risk factor for spontaneous epiglottic abscess development.
Analysis of Military–Civilian Patient Handoff at Vista Forge Multi-Agency Nuclear Disaster Exercise 2022
Authors: Davis Terri , Taubman Cara , Cheng Lenard , Pigeon Marc-Antoine , Storr Latoya , Nouaime Georgina , Shin Heejun , Vear Kathryn , Obernier Robert , Ciottone Gregory
Published: August 2023

Introduction

The leadership of Vista Forge 2022 requested evaluation of the handoff process between military assets and civilian emergency medical services (EMS) providers by the Beth Israel Deaconess Fellowship in Disaster Medicine (BIDMF). Vista Forge was a multi-agency military–civilian full-scale disaster exercise coordinated by the U.S. Military. The exercise, held in Atlanta, Georgia, simulated response to a nuclear bomb in an urban setting by military and civilian disaster teams.

Materials and Methods

BIDMF had several two-person teams who monitored handoff procedures between military assets after decontamination and civilian emergency medical services providers during the exercise evaluation.

Results

A verbal handoff between military and civilian entities was usually not done. Triage tags placed on mannequins before decontamination remained attached to the bodies and were sent with them to civilian hospitals. Triage tags were generic military forms without specific radiation or chemical exposure information. Not all decontamination groups had the same medical capabilities, and in a disaster it is unclear how these teams would manage medical emergencies.

Conclusions

Future studies should develop a standardized handoff procedure to be used in mass casualty situations, and trial it in future multi-agency disaster exercises. Radiation specific triage tags should be considered.
Return to Duty in Military Service Members Following Minimally Invasive Sacroiliac Joint Fusion
Authors: Cognetti Daniel J , Anderson Kevin D , Handcox Jordan E , Jorgensen Anton Y
Published: August 2023

Introduction

As the utilization of minimally invasive sacroiliac joint fusion (SIJF) continues to expand, a better understanding of postoperative outcomes is needed, particularly in young and active individuals. The purpose of this study is to assess the outcomes of this procedure in an active duty military population by examining return-to-duty (RTD) rates.

Materials and Methods

A retrospective review of the electronic medical record from a tertiary military medical center was performed for active duty service members undergoing SIJF from January 2013 to January 2019. The primary outcome measured was RTD at 6 months, with active duty status at 1 year, last follow-up, and revision surgery as secondary outcomes. Demographic and surgical variables recorded included patient age, gender, military rank, utilization of navigation, and implant type.

Results

Sixteen service members met the inclusion criteria, with a mean age of 40.5 ± 6.7 years. The mean follow-up after surgery was 24 ± 15 months. Patients received either cylindrical (n = 6) or triangular (n = 10) implants placed with (n = 6) or without (n = 10) navigation. Within 6 months of surgery, 56% of patients were able to RTD. Patients undergoing navigation-assisted procedures were significantly more likely to RTD at 6 months (100% vs. 30%, P = .011) compared to those undergoing surgery performed with orthogonal fluoroscopic imaging. Compared to those with cylindrical implants, patients with triangular implants were also more likely to RTD at 6 months (80% vs. 17%, P = .035).

Conclusions

Following SIJF, a small majority of service members were able to return to full active duty status by 6 months. Further studies are needed to assess the potential benefits of navigation and implant selection, as our retrospective review noted differences in outcomes based on these variables.
A novel EGFR variant EGFRx maintains glioblastoma stem cells through STAT5
Authors: Huang Wei , Li Jing , Zhu Hongtao , Qin Xuhui , Chen Chao , Wang Bing , Wei Jinxia , Song Yanyang , Lu Xia , Li Zhongyu , Xia Wenqing , He Aodi , Cheng Lidong , Yu Xingjiang , Shu Kai , Wang Wei
Published: August 2023

Background

Glioblastomas are universally lethal brain tumors containing tumor-propagating glioblastoma stem cells (GSCs). EGFR gene amplification or mutation is frequently detected in GBMs and is associated with poor prognosis. However, EGFR variants in GSCs and their role in the maintenance of GSCs and progression of GBM are unclear.

Methods

EGFR variants were detected through bioinformatic HISAT-StringTie-Ballgown pipeline and verified through 5ʹ RACE, RT-PCR, ribonuclease protection, and northern blotting assays. EGFRx function was investigated through neurosphere, cell viability, intracranial xenograft and RNA-seq assays. EGFRx-STAT5 signaling was investigated through western blotting, coimmunoprecipitation, immunofluorescence, luciferase reporter, RT-PCR and CUT&Tag assays.

Results

We identified a novel EGFR variant (EGFRx), that is specifically expressed in GSCs. Unlike the EGFRvIII variant, which lacks exons 2–7, EGFRx is characterized by the absence of exons 2–14, and encodes an EGFR protein that does not possess the entire extracellular ligand-binding domain. We observed that EGFRx exhibits significant glycosylation, is required for GSC self-renewal, proliferation, and tumorigenesis, and highly active in glioblastomas compared to normal brain tissue. Mechanistically, EGFRx constitutively and specifically activates STAT5 in GSCs through spontaneous asymmetric dimerization of the kinase domain.

Conclusions

EGFRx plays essential roles in the maintenance of the GSC phenotype through constitutive activation of STAT5 and promotes GBM progression, suggesting that EGFRx-STAT5 signaling represents a promising therapeutic target for GBM.
Bio-based materials for antimicrobial films in food applications: beyond the COVID-19 pandemic era
Authors: Perumal Pillai Bharath , Balasubramaniam Bhuvaneshwari , Gupta Raju Kumar , Tyagi Ankit
Published: August 2023

The global pandemic caused by COVID-19 has increased awareness of the need for best practices to prevent the transmission of virus diseases. Antimicrobial films have been employed in packaging food items to minimize the spread of foodborne illnesses. However, the ongoing COVID-19 pandemic accelerated the demand for novel antimicrobial materials to prepare packaging films to minimize the virus spread through food items during processing and transportation. Considering the environmental pollution caused by single-use plastics, the demand for biodegradable polymers for packaging films has also increased in the current pandemic. This review aims to outline emerging bio-based antimicrobial materials and their incorporation into biopolymers as carriers for antimicrobial films, highlighting their potential as effective measures in preparing for future pandemics.
Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
Authors: Yang Eun-Jeong , Rahim Md Al , Griggs Elizabeth , Iban-Arias Ruth , Pasinetti Giulio Maria
Published: August 2023

Forkhead box P3 (Foxp3) is a transcription factor that influences functioning of regulatory T cells (Tregs) that modulate peripheral immune response. Treg-mediated innate immunity and Treg-mediated adaptive immunity are receiving considerable attention for their implication in mechanisms associated with anxiety and depression. Here, we demonstrated that depletion of Foxp3-expressing cells causally promotes transient anxiety- and depression-like behaviors associated with inflammasome activation in “depletion of regulatory T cell” (DEREG) mice. We found that restoration of Foxp3-expressing cells causally reverses neurobehavioral changes through alteration of innate immune responses as assessed by caspase-1 activity and interleukin-1β (IL-1β) release in the hippocampal formation of DEREG mice. Moreover, we found that depletion of Foxp3-expressing cells induces a significant elevation of granulocytes, monocytes, and macrophages in the blood, which are associated with transient expression of the matrix metalloprotease-9. Similarly, we found that depletion of Foxp3-expressing cells in 5xFAD, a mouse model of Alzheimer's disease (AD), exhibits elevated activated caspase-1 and promotion of IL-1β secretion and increased the level of amyloid-beta (Aβ)1–42 and Aβ plaque burden in the hippocampal formation that coincided with an acceleration of cognitive decline at a presymptomatic age in the 5xFAD mice. Thus, our study provides evidence supporting the idea that Foxp3 may have a causal influence on peripheral immune responses. This, in turn, can promote an innate immune response within the brain, potentially leading to anxiety- and depression-like behaviors or cognitive decline.
High-Hanging Fruit: How Gender Bias Remains Entrenched in Performance Evaluations
Authors: Wynn Alison T , Carian Emily K
Published: August 2023

Organizations are increasingly engaging in concerted efforts to mitigate bias in processes such as performance evaluations. However, little research examines what makes bias easier for organizations to address through formal initiatives and what makes bias more resistant to such change. When organizations shed light on the biases embedded in a particular organizational process, where are interventions successful, and where do they fall short? Using a longitudinal sample of performance evaluations from an elite professional services firm, we find that managers have an easier time reducing gender differences in the way they view employees’ behaviors, as compared to the way managers value those behaviors. Managers successfully decreased gendered descriptions of personality and communication style. However, when we examine the relationship between language patterns and rating, we find that the same behaviors correspond with a different payoff for women and men. Our findings add to the literature on organizational change by identifying the successes and challenges of bias mitigation efforts aimed at training managers, and we contribute to research on status and stereotypes by identifying new pathways through which cultural ideas about gender impact the evaluation of employees.
Circulating Osteoprogenitor Cells Have a Mixed Immune and Mesenchymal Progenitor Function in Humans
Authors: Feehan Jack , Jacques Macsue , Kondrikov Dmitry , Eynon Nir , Wijeratne Tissa , Apostolopoulos Vasso , Gimble Jeffrey M , Hill William D , Duque Gustavo
Published: August 2023

Background

Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization of COP cells is still required to test and fully develop their use in clinical settings.

Methods

This study characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses.

Results

We demonstrate that COP cells have a distinct gene and protein expression pattern with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar expression pattern to BM-MSCs and ASCs.

Conclusion

COP cells are a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.
Developmental exposure to the Parkinson’s disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice
Authors: Boyd Sierra L , Kuhn Nathan C , Patterson Joseph R , Stoll Anna C , Zimmerman Sydney A , Kolanowski Mason R , Neubecker Joseph J , Luk Kelvin C , Ramsson Eric S , Sortwell Caryl E , Bernstein Alison I
Published: August 2023

Parkinson’s disease (PD) is the fastest-growing neurological disease worldwide, with increases outpacing aging and occurring most rapidly in recently industrialized areas, suggesting a role of environmental factors. Epidemiological, post-mortem, and mechanistic studies suggest that persistent organic pollutants, including the organochlorine pesticide dieldrin, increase PD risk. In mice, developmental dieldrin exposure causes male-specific exacerbation of neuronal susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and synucleinopathy. Specifically, in the α-synuclein (α-syn) pre-formed fibril (PFF) model, exposure leads to increased deficits in striatal dopamine (DA) turnover and motor deficits on the challenging beam. Here, we hypothesized that alterations in DA handling contribute to the observed changes and assessed vesicular monoamine transporter 2 (VMAT2) function and DA release in this dieldrin/PFF 2-hit model. Female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin or vehicle every 3 days by feeding, starting at 8 weeks of age and continuing throughout breeding, gestation, and lactation. Male offspring from independent litters underwent unilateral, intrastriatal injections of α-syn PFFs at 12 weeks of age, and vesicular 3H-DA uptake assays and fast-scan cyclic voltammetry were performed 4 months post-PFF injection. Dieldrin-induced an increase in DA release in striatal slices in PFF-injected animals, but no change in VMAT2 activity. These results suggest that developmental dieldrin exposure increases a compensatory response to synucleinopathy-triggered striatal DA loss. These findings are consistent with silent neurotoxicity, where developmental exposure to dieldrin primes the nigrostriatal striatal system to have an exacerbated response to synucleinopathy in the absence of observable changes in typical markers of nigrostriatal dysfunction and degeneration.