bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of preoxygenation using a tight facemask, humidified high-flow nasal oxygen and a standard nasal cannula – a volunteer, randomised, crossover study
Authors: Sjöblom Albin , Hedberg Magnus , Forsberg Ida-Maria , Hoffman Frida , Jonsson Fagerlund Malin
Published: April 2024

BACKGROUND

Preoxygenation before anaesthesia induction is routinely performed via a tight-fitting facemask or humidified high-flow nasal oxygen. We hypothesised that effective preoxygenation, assessed by end-tidal oxygen (EtO2) levels, can also be performed via a standard nasal cannula.

OBJECTIVE

This study compared the efficacy of preoxygenation between a traditional facemask, humidified high-flow nasal oxygen and a standard nasal cannula.

DESIGN

A volunteer, randomised, crossover study.

SETTING

Karolinska University Hospital, Stockholm. The study was conducted between 2 May and 31 May 2023.

PARTICIPANTS

Twenty cardiopulmonary healthy volunteers aged 25–65 years with a BMI <30.

INTERVENTIONS

Preoxygenation using a traditional facemask, humidified high-flow nasal oxygen and standard nasal cannula. Volunteers were preoxygenated with all three methods, at various flow rates (10–50 l min−1), with open and closed mouths and during vital capacity manoeuvres.

MAIN OUTCOME MEASURES

The study's primary outcome compared the efficacy after 3 min of preoxygenation, assessed by EtO2 levels, between the three methods and various flow rates of preoxygenation.

RESULTS

Three methods generated higher EtO2 levels than others: (i) facemask preoxygenation using normal breathing, (ii) humidified high-flow nasal oxygen, closed-mouth breathing, at 50 l min−1 and (iii) standard nasal cannula, closed-mouth breathing, at 50 l min−1, and expressed as means (SD): 90% (3), 90% (6) and 88% (5), respectively. Preoxygenation efficacy was greater via the bi-nasal cannulae using closed vs. open mouth breathing as well as with 3 min of normal breathing vs. eight vital capacity breaths. Preoxygenation with a facemask and humidified high-flow nasal oxygen was more comfortable than a standard nasal cannula.

CONCLUSION

The efficacy of preoxygenation using a standard nasal cannula at high flow rates is no different to clinically used methods today. The standard nasal cannula provides less comfort but is highly effective and could be an option when alternative methods are unavailable.

TRIAL REGISTRATION

Clinicaltrials.gov, NCT05839665.
The contribution of lower-limb joint quasi-stiffness to theoretical leg stiffness during level, uphill and downhill running at different speeds
Authors: Hirschman Caelyn E. , Montgomery Jana R. , Grabowski Alena M.
Published: April 2024

Humans change joint quasi-stiffness (
k

joint

) and leg stiffness (k
leg
) when running at different speeds on level ground and during uphill and downhill running. These mechanical properties can inform device designs for running such as footwear, exoskeletons and prostheses. We measured kinetics and kinematics from 17 runners (10 M; 7 F) at three speeds on 0°, ±2°, ±4° and ±6° slopes. We calculated ankle and knee
k

joint

, the quotient of change in joint moment and angular displacement, and theoretical leg stiffness (k
legT
) based on the joint external moment arms and
k

joint

. Runners increased
k

ankle

at faster speeds (
p
< 0.01). Runners increased and decreased the ankle and knee contributions to k
legT
, respectively, by 2.89% per 1° steeper uphill slope (
p
< 0.01) during the first half of stance. Runners decreased and increased ankle and knee joint contributions to k
legT
, respectively, by 3.68% during the first half and 0.86% during the second half of stance per 1° steeper downhill slope (
p
< 0.01). Thus, biomimetic devices require stiffer
k

ankle

for faster speeds, and greater ankle contributions and greater knee contributions to k
legT
during the first half of stance for steeper uphill and downhill slopes, respectively.
Psychometric evaluation of the Trust in Science and Scientists Scale
Authors: Wolff Sarah M. , Breakwell Glynis M. , Wright Daniel B.
Published: April 2024

Reliable and valid measurement of trust in science and scientists is important. Assessing levels of such trust is important in determining attitudes and predicting behaviours in response to medical and scientific interventions targeted at managing public crises. However, trust is a complex phenomenon that has to be understood in relation to both distrust and mistrust. The Trust in Science and Scientists Scale has been adopted with increasing frequency in large-scale public health research. Detailed psychometric evaluation of the scale is overdue and makes meaningful comparisons between studies that use the scale difficult. Here, we examine the scale’s dimensionality across five separate samples. We find that two factors emerge that are divided by their item polarity. Implications for scale use and trust in science measurement are discussed.
Why care for humanity?
Authors: Reinhardt Lukas , Whitehouse Harvey
Published: April 2024

Some of the most pressing challenges facing our planet—such as climate change, biodiversity loss, warfare and extreme poverty—require social cohesion and prosocial action on a global scale. How can this be achieved? Previous research suggests that identity fusion—a strong form of group cohesion motivating prosocial action—results from perceptions of shared personally transformative experiences or of common biological essence. Here, we present results from two studies with United States samples exploring each pathway to identity fusion on a global scale. Study 1 focused on globally shared motherhood experiences and found that US mothers were more fused with women around the world if they shared motherhood experiences with them, which was also reflected in money allocation behaviour. Study 2 showed that exposure to a talk about globally shared biology increased fusion with humanity at large, Americans and the extended family suggesting that fusion with humanity does not need to weaken fusion with nation or extended family. We discuss implications of our results for future research on bonding with humanity at large and for addressing collective action problems on a global scale.
Comparative genomics of a novel Erwinia species associated with the Highland midge (Culicoides impunctatus)
Authors: Pilgrim Jack
Published: April 2024

Erwinia (Enterobacterales: Erwiniaceae) are a group of cosmopolitan bacteria best known as the causative agents of various plant diseases. However, other species in this genus have been found to play important roles as insect endosymbionts supplementing the diet of their hosts. Here, I describe Candidatus Erwinia impunctatus (Erwimp) associated with the Highland midge Culicoides impunctatus (Diptera: Ceratopogonidae), an abundant biting pest in the Scottish Highlands. The genome of this new Erwinia species was assembled using hybrid long and short read techniques, and a comparative analysis was undertaken with other members of the genus to understand its potential ecological niche and impact. Genome composition analysis revealed that Erwimp is similar to other endophytic and ectophytic species in the genus and is unlikely to be restricted to its insect host. Evidence for an additional plant host includes the presence of a carotenoid synthesis operon implicated as a virulence factor in plant-associated members in the sister genus Pantoea. Unique features of Erwimp include several copies of intimin-like proteins which, along with signs of genome pseudogenization and a loss of certain metabolic pathways, suggests an element of host restriction seen elsewhere in the genus. Furthermore, a screening of individuals over two field seasons revealed the absence of the bacteria in Culicoides impunctatus during the second year indicating this microbe-insect interaction is likely to be transient. These data suggest that Culicoides impunctatus may have an important role to play beyond a biting nuisance, as an insect vector transmitting Erwimp alongside any conferred impacts to surrounding biota.
Gamified interventions to improve the knowledge, awareness and practice on rational use of antibiotics among school children in Mysuru, South India to curb the growing antimicrobial resistance (AMR)
Authors: Neelambike Sumana M , Shettar Supreeta R , Maheshwarappa Yogeesh , Kulkarni Praveen
Published: April 2024

Introduction

Antimicrobial resistance (AMR) is a global problem. It’s important to create awareness of the rational use of antibiotics to curb AMR.

Objective

To improve the awareness of the rational use of antibiotics through innovative games for High School Students.

Design

Prospective interventional study

Setting

Twelve High Schools in the city of Mysuru, South India.

Participants

2195 Students between 13 and 16 years.

Intervention

Innovative gamified interventions to educate on the rational use of antibiotics. Use of antibiotics only in bacterial infections of the respiratory tract, gut, urinary tract and skin was introduced through black blackboard. An animated video was shown on the effects of irrational antibiotic use. Situations in which antibiotics can be avoided in respiratory infections and gastroenteritis were taught through Bucketing the Ball and Monkeying with Donkey games. Pre-test and Post-test questionnaires were administered and evaluated.

Main outcome measures

To assess the improvement in awareness of the rational use of antibiotics.

Results

After the intervention, knowledge of the use of antibiotics only for bacterial infections improved from 11.5% to 82.5% and ill-effects of antibiotics improved from 2.5% to 82.5%. Awareness of when not to use and when to use antibiotics for respiratory infections and gastroenteritis improved from 5.1% to 96.77%, awareness of better use of antibiotics for urinary and skin infections improved from 19.6% to 90.38% and not buying antibiotics directly from the pharmacy without prescription, and completing the antibiotic course improved from 20.3% to 91.92%. p-value < 0.05 for all components.

Conclusions

Awareness of the rational use of antibiotics is very poor among the general public. The need of the hour is to create awareness not only among healthcare providers but also among the general public. Innovative gamified interventions create better and long-lasting awareness of this.

Strength and Limitations of the study

The strength was using gamified interventions to create knowledge and awareness about rational use of antibiotics.

The limitation is, awareness about adverse effects of antibiotics could not be converted to gamified intervention, and it was shown as an animated video since adverse effects of antibiotics include long term complications.

Though the students may not be able to remember in the long run the difference between viral and bacterial infections, they will definitely be able to remember that not all respiratory tract infections and gastro enteritis require antibiotics and henceforth they will not pressurize the physicians to prescribe antibiotics.

Limitation
Integrating bulk and single-cell RNA sequencing revealsSH3D21promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway
Authors: Tong Wangxia , Lu Tao , Liu Li , Liu Rong , Chen Jibing , Luo Ning
Published: April 2024

As a novel genetic biomarker, the potential role ofSH3D21in hepatocellular carcinoma remains unclear. Here, we decipher the expression and function ofSH3D21in human hepatocellular carcinoma. The expression level and clinical significance ofSH3D21in hepatocellular carcinoma patients, the relationship betweenSH3D21and the features of tumor microenvironment (TME) and role ofSH3D21in promoting hepatocellular carcinoma progression were analyzed based on the bulk samples obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Single-cell sequencing samples from Gene Expression Omnibus (GEO) database were employed to verify the prediction mechanism. Additionally, different biological effects ofSH3D21on hepatocellular carcinoma cells were investigated by qRT-PCR, CCK-8 assay, colony forming assay and Western blot analysis. Bioinformatics analysis andin vitroexperiments revealed that the expression level ofSH3D21was up-regulated in hepatocellular carcinoma and correlated with the poor prognosis in hepatocellular carcinoma patients.SH3D21effectively promoted the proliferation, invasion, and migration as well as the formation of immunosuppressive microenvironment of hepatocellular carcinoma. In addition,SH3D21can activate the PI3K/AKT/mTOR signaling pathway.SH3D21stimulates the progression of hepatocellular carcinoma by activating the PI3K/AKT/mTOR signaling pathway, andSH3D21can serve as a prognostic biomarker and therapeutic target for hepatocellular carcinoma.
Trends and hotspots in research on osteoporosis and nutrition from 2004 to 2024: a bibliometric analysis
Authors: Li Min , Yu Binyang , Yang Haiyan , He Haiyan , Li Ning , Lv Aili , Zhou Xiaoling , Gao Rui
Published: April 2024

Objectives

This study aimed to perform a bibliometric analysis utilizing the Web of Science database on osteoporosis and nutrition-related research published from 2004 to 2024.

Background

In recent years, the intricate association between nutrition and osteoporosis has garnered increasing attention. However, there is currently no published bibliometric research on this topic.

Methods

The data were extracted from the Web of Science Core Collection (WOSCC) from inception to 2024-01-31 and analyzed using bibliometric methods and CiteSpace, incorporating variables such as annual publication volume, author patterns, institutional affiliations, country/region contributions, journal publications, highly cited literature, and keyword clustering.

Results

A total of 2138 articles were assessed, revealing a consistent upward trend in published works in this domain, with the majority originating from the United States. Seoul National University was identified as the most prolific institution. Among the authors, Geng, Bin were the most prolific, while Kanis J.A. garnered the highest citation count. Research hotspots included bone density, postmenopausal women, vitamin D, hip fractures, etc. Research subjects included physical activity, sarcopenia, calcium intake, machine learning, etc.

Conclusions

Our comprehensive analysis offers overviews of research trends and hotspots in the field of osteoporosis and nutrition over the past two decades, highlighting some shortcomings and hopefully providing valuable insights and guidance for future researchers and decision-makers.
Contribution ofde novoretroelements to birth defects and childhood cancers
Authors: Chu Chong , Ljungström Viktor , Tran Antuan , Jin Hu , Park Peter J.
Published: April 2024

Insertion of active retroelements—L1s,Alus, and SVAs—can disrupt proper genome function and lead to various disorders including cancer. However, the role ofde novoretroelements (DNRTs) in birth defects and childhood cancers has not been well characterized due to the lack of adequate data and efficient computational tools. Here, we examine whole-genome sequencing data of 3,244 trios from 12 birth defect and childhood cancer cohorts in the Gabriella Miller Kids First Pediatric Research Program. Using an improved version of our tool xTea (x-Transposable element analyzer) that incorporates a deep-learning module, we identified 162 DNRTs, as well as 2 pseudogene insertions. Several variants are likely to be causal, such as ade novo Aluinsertion that led to the ablation of a whole exon in theNF1gene in a proband with brain tumor. We observe a highde novoSVA insertion burden in both high-intolerance loss-of-function genes and exons as well as more frequentde novo Aluinsertions of paternal origin. We also identify potential mosaic DNRTs from embryonic stages. Our study reveals the important roles of DNRTs in causing birth defects and predisposition to childhood cancers.
COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children
Authors: Tang Ying , Boribong Brittany P. , Swank Zoe N. , Demokritou Melina , Luban Maria A.F. , Fasano Alessio , Du Michelle , Wolf Rebecca L. , Griffiths Joseph , Shultz John , Borberg Ella , Chalise Sujata , Gonzalez Wanda I. , Walt David R. , Yonker Lael M. , Horwitz Bruce H.
Published: April 2024

Key points

Current COVID-19 mRNA vaccine induces salivary and nasal SARS-CoV-2 specific IgG but not IgA production in children under 5 years of age

Mucosal anti-spike IgA is important for immune complex-mediated neutrophil extracellular trap formation against SARS-CoV-2 in the airway

Background

Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children.

Methods

We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples, N=116) or on convenience samples of children under 5 years of age presenting to a pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation.

Results

Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process.

Conclusions

Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.
Improved multi-ancestry fine-mapping identifiescis-regulatory variants underlying molecular traits and disease risk
Authors: Lu Zeyun , Wang Xinran , Carr Matthew , Kim Artem , Gazal Steven , Mohammadi Pejman , Wu Lang , Gusev Alexander , Pirruccello James , Kachuri Linda , Mancuso Nicholas
Published: April 2024

Multi-ancestry statistical fine-mapping ofcis-molecular quantitative trait loci (cis-molQTL) aims to improve the precision of distinguishing causalcis-molQTLs from tagging variants. However, existing approaches fail to reflect shared genetic architectures. To solve this limitation, we present the Sum of Shared Single Effects (SuShiE) model, which leverages LD heterogeneity to improve fine-mapping precision, infer cross-ancestry effect size correlations, and estimate ancestry-specific expression prediction weights. We apply SuShiE to mRNA expression measured in PBMCs (n=956) and LCLs (n=814) together with plasma protein levels (n=854) from individuals of diverse ancestries in the TOPMed MESA and GENOA studies. We find SuShiE fine-mapscis-molQTLs for 16%more genes compared with baselines while prioritizing fewer variants with greater functional enrichment. SuShiE infers highly consistentcis-molQTL architectures across ancestries on average; however, we also find evidence of heterogeneity at genes with predicted loss-of-function intolerance, suggesting that environmental interactions may partially explain differences incis-molQTL effect sizes across ancestries. Lastly, we leverage estimatedcis-molQTL effect-sizes to perform individual-level TWAS and PWAS on six white blood cell-related traits in AOU Biobank individuals (n=86k), and identify 44 more genes compared with baselines, further highlighting its benefits in identifying genes relevant for complex disease risk. Overall, SuShiE provides new insights into thecis-genetic architecture of molecular traits.
Task-Oriented Predictive (Top)-BERT: Novel Approach for Predicting Diabetic Complications Using a Single-Center EHR Data
Authors: Islam Humayera , Bartlett Gillian , Pierce Robert , Rao Praveen , Waitman Lemuel R. , Song Xing
Published: April 2024

In this study, we assess the capacity of the BERT (Bidirectional Encoder Representations from Transformers) framework to predict a 12-month risk for major diabetic complications—retinopathy, nephropathy, neuropathy, and major adverse cardiovascular events (MACE) using a single-center EHR dataset. We introduce a task-oriented predictive (Top)-BERT architecture, which is a unique end-to-end training and evaluation framework utilizing sequential input structure, embedding layer, and encoder stacks inherent to BERT. This enhanced architecture trains and evaluates the model across multiple learning tasks simultaneously, enhancing the model’s ability to learn from a limited amount of data. Our findings demonstrate that this approach can outperform both traditional pretraining-finetuning BERT models and conventional machine learning methods, offering a promising tool for early identification of patients at risk of diabetes-related complications. We also investigate how different temporal embedding strategies affect the model’s predictive capabilities, with simpler designs yielding better performance. The use of Integrated Gradients (IG) augments the explainability of our predictive models, yielding feature attributions that substantiate the clinical significance of this study. Finally, this study also highlights the essential role of proactive symptom assessment and the management of comorbid conditions in preventing the advancement of complications in patients with diabetes.
Latent Class Analysis of COVID-19 Deaths by Comorbidities— United States, February-May 2020
Authors: Siegel David A. , Bentley William A. , Li Rongxia , Gould Carolyn V. , McCormick David W. , McLaughlin Joseph , Vyas Anjali , Clark Charles R. , Richardson Gillian , Krueger Anna , Holzbauer Stacy , Kollmann Leslie , Thomas Deepam , Ojo Mojisola , Paladini Marc , Reilly Kathleen H. , McLafferty Meagan , Sidelinger Dean E. , Chambers Laura C. , Read Jennifer S. , Saraiya Mona , Young Paul R , Wortham Jonathan M. , Koumans Emilia H.
Published: April 2024

Purpose

Risk factors for coronavirus disease 2019 (COVID-19) mortality include older age, cardiovascular disease, diabetes, and other comorbidities. Latent class analysis (LCA) can identify unrecognized morbidity patterns for decedents with COVID-19.

Methods

Data were collected from 23 U.S. jurisdictions about decedents with COVID-19 early in the COVID-19 pandemic (February 12–May 12, 2020). LCA identified groups of individuals based upon pre-existing comorbidities: cardiovascular, renal, lung, neurologic, and liver disease; obesity; diabetes; and immunocompromised state. Results were stratified by sex, age, race/ethnicity, and location of death.

Results

Of 12,340 decedents, LCA identified three classes, which included classes with prominent cardiovascular disease and diabetes (32%), prominent cardiovascular disease without diabetes (19%), and a “minimal prevalence” class (49%) with a low frequency of comorbidities. Individuals in the “minimal prevalence” class had risk factors in <2 comorbidity groups, where cardiovascular disease was the most common for individuals with a single comorbidity.

Conclusions

LCA analysis reaffirms the importance of diabetes and cardiovascular disease as risk factors for COVID-19 mortality and indicates that about half of decedents were in the “minimal prevalence” group. Results could guide vaccination and treatment messaging to groups with no or few underlying conditions.

Disclaimer

The conclusions, findings, and opinions expressed by the authors do not necessarily reflect the offical position of the Centers for Disease Control and Prevention or the authors’ affililated institutions.
Prevalence of physical and mental health problems among internally displaced persons in white nile state, sudan 2023
Authors: Ali Ahmed Mohamed Ahmed , Adam Omran aldoma Mohammed , Salem Sarah Altayeb Mustafa , Hamad Sara Hamad Ibrahim , Ahmed Nosiba Elnair Musa , Ali Hassan Mohamed Ahmed , Abass Aseel Abass Mohamed , Abass Hiba-Allah Abass Mohamed , Albasher Abubaker Izz-Eldein , Yousif Mawada Eltagi Elsayid , Abdalla Fadwa Elfadil Ahmed , Abd-alaziz Osman AlShazly Osman , Ahmed Samar Bushra Mohammed , Al-Obaid Shaima Abdelbagi Ahmed , Osman Abdelgadir H.
Published: April 2024

INTRODUCTION

Despite efforts globally, internally displaced persons (IDPs) face poor living conditions and limited healthcare access compared to refugees. They commonly suffer from malaria, malnutrition, diarrhoea, and respiratory infections, along with mental health issues like depression and PTSD. Severe malnutrition poses significant health risks in the short and long term, especially in developing countries.

METHODS

To assess IDPs’ health, we conducted interviews. Out of 574 participants aged 10 and above, many reported physical and mental health problems using questionnaires. Additionally, 226 children under five were surveyed for malnutrition using a questionnaire and measurements of mid-upper arm circumference.

RESULTS

The findings revealed that 45% of IDPs experienced poor physical health, with prevalent ailments among adults including minor colds (67%), respiratory infections (43%), prolonged flu episodes (36%), insomnia (38%), headaches (42%), upset stomachs (44%), nausea (35%), and gastrointestinal issues (40%). Depression, PTSD, and anxiety were prevalent among adults at rates of 18%, 20%, and 14% respectively. Moreover, a staggering 72% of children under five suffered from malnutrition, with males accounting for 44% and females 56%.

CONCLUSION

In conclusion, the well-being of IDPs residing in camps is detrimentally impacted by the inadequate management, treatment, and prevention of both communicable and non-communicable diseases. Government authorities must recognise and address the complexities associated with multiple agencies involved in delivering healthcare services to IDPs. The implementation of efficient systems to monitor, track, and support IDP healthcare could represent a cost-effective strategy to enhance overall health outcomes.
Telehealth Equity and Access Communication Skills Pilot Simulation for Practicing Clinicians
Authors: Nash Christopher J. , Farrell Susan E. , Carreras Tartak Jossie A. , Wagner Alexei , Brandt Lea C. , Hayden Emily M.
Published: April 2024

Objectives

This pilot study evaluated a telehealth training simulation program for practicing clinicians, specifically focused on addressing patient issues of equity and access to healthcare via improving telehealth communication.

Methods

Participants participated in a one-hour simulation experience with two cases. Performance was assessed pre- and post-intervention using a checklist measuring communication domains related to equity and access in telehealth. Participant satisfaction was secondarily measured via survey.

Results

Results showed measurable gains in clinicians’ abilities to effectively incorporate equity and access communication skills. Participants found the session useful and recommended the training experience.

Conclusions

The findings of this pilot study highlight the potential of simulation-based telehealth training for practicing clinicians, emphasizing clinicians’ attention to patients’ equitable access to healthcare. Future studies should aim to explore the durability of learning and investigate the generalizability of this training approach to other telehealth competencies and settings.
Multi-Omics after O-GlcNAc Alteration Identifies Cellular Processes Working Synergistically to Promote Aneuploidy
Authors: Boyd Samuel S. , Robarts Dakota R. , Nguyen Khue , Villar Maite , Alghusen Ibtihal , Kotulkar Manasi , Denson Aspin , Fedosyuk Halyna , Whelan Stephen A. , Lee Norman C.Y. , Hanover John , Dias Wagner B. , Tan Ee Phie , McGreal Steven R. , Artigues Antonio , Swerdlow Russell H. , Thompson Jeffrey A. , Apte Udayan , Slawson Chad
Published: April 2024

Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due to the pleotropic nature of O-GlcNAc and the vast signaling pathways it regulates. To address this issue, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, or pharmacological inhibition of OGA coupled with multi-Omics analysis and bioinformatics. We identified numerous genes, proteins, phospho-proteins, or metabolites that were either inversely or equivalently changed between conditions. Moreover, we identified pathways in OGT knockout samples associated with increased aneuploidy. To test and validate these pathways, we induced liver growth in OGT knockouts by partial hepatectomy. OGT knockout livers showed a robust aneuploidy phenotype with disruptions in mitosis, nutrient sensing, protein metabolism/amino acid metabolism, stress response, and HIPPO signaling demonstrating how OGT is essential in controlling aneuploidy pathways. Moreover, these data show how a multi-Omics platform can discern how OGT can synergistically fine-tune multiple cellular pathways.
Utility of Cellular Measurements of Non-Specific Endocytosis to Assess the Target-Independent Clearance of Monoclonal Antibodies
Authors: Bryniarski Mark A. , Tuhin Md Tariqul Haque , Shomin Carolyn D. , Nasrollahi Fatemeh , Ko Eunkyung Clare , Soto Marcus , Chung Kyu , Poon-Andersen Carrie , Primack Ronya , Wong Diana , Ojeda Esperanza , Chung John , Cook Kevin D. , Conner Kip P.
Published: April 2024

Past studies have demonstrated higher clearance for monoclonal antibodies possessing increased rates of non-specific endocytosis. However, this metric is oftentimes evaluated indirectly using biophysical techniques or cell surface binding studies that may not provide insight into the specific rates of cellular turnover. Furthermore, few examples evaluating non-specific endocytosis have been reported for a therapeutic antibody that reached clinical assessment. In the current report, we evaluated a therapeutic human immunoglobulin G2 monoclonal antibody targeted against the interleukin-4 receptor alpha chain (IL-4Rα) that exhibited elevated target independent clearance in previous Phase 1 and 2 studies. We confirmed high non-specific clearance of the anti-IL-4Rα antibody as compared to a reference antibody during pharmacokinetic assessments in wild type mice where target-mediated disposition was absent. We then developed a cell-based method capable of measuring cellular protein endocytosis and demonstrated the anti-IL-4Rα antibody exhibited marked non-specific uptake relative to the reference compound. Antibody homology modeling identified the anti-IL-4Rα antibody possessed positive charge patches whose removal via targeted mutations substantially reduced its non-specific endocytosis. We then expanded the scope of the study by evaluating a panel of consisting of both preclinical and clinical monoclonal antibodies and demonstrate those with the highest rates of non-specific uptakein vitroexhibit elevated target independent clearance, low subcutaneous bioavailability, or both. Our results support the observation that high non-specific endocytosis is a negative attribute in monoclonal antibody development and demonstrate the utility of a generic cell-based screen as a quantitative tool to measure non-specific endocytosis of protein therapeutics at the single-cell level.

Highlights

- Developed a novel, reproducible cellular assay to directly quantify non-specific endocytosis of therapeutic proteins.

- A previous clinical candidate monoclonal antibody with rapid target-independent clearance in mice and humans possessed extensive non-specific endocytosis that was due to exposed positive charge features.

- Demonstration of distinct rates of endocytosis into mammalian cells for disparate monoclonal antibodies, even those with common specificity for targets or isoelectric points.

- Cell-based assay to quantify the potential impact of non-specific endocytosis on target-independent clearance and/or subcutaneous bioavailability of monoclonal antibodies.
Carrollian Fluids and Spontaneous Breaking of Boost Symmetry
Authors: Armas Jay , Have Emil
Published: April 2024

In the hydrodynamic regime, field theories typically have their boost symmetry spontaneously broken due to the presence of a thermal rest frame although the associated Goldstone field does not acquire independent dynamics. We show that this is not the case for Carrollian field theories where the boost Goldstone field plays a central role. This allows us to give a first-principles derivation of the equilibrium currents and dissipative effects of Carrollian fluids. We also demonstrate that the limit of vanishing speed of light of relativistic fluids is a special case of this class of Carrollian fluids. Our results shine light on the thermodynamic properties and thermal partition functions of Carrollian field theories.

Published by the American Physical Society
2024
Dispersion Relations Alone Cannot Guarantee Causality
Authors: Gavassino L. , Disconzi M. , Noronha J.
Published: April 2024

We show that linear superpositions of plane waves involving a single-valued, covariantly stable dispersion relation ω(k) always propagate outside the light cone unless ω(k)=a+bk. This implies that there is no notion of causality for individual dispersion relations since no mathematical condition on the function ω(k) (such as the front velocity or the asymptotic group velocity conditions) can serve as a sufficient condition for subluminal propagation in dispersive media. Instead, causality can only emerge from a careful cancellation that occurs when one superimposes all the excitation branches of a physical model. This happens automatically in local theories of matter that are covariantly stable. Hence, we find that the need for nonhydrodynamic modes in relativistic fluid mechanics is analogous to the need for antiparticles in relativistic quantum mechanics.

Published by the American Physical Society
2024
Slow Fatigue and Highly Delayed Yielding via Shear Banding in Oscillatory Shear
Authors: Cochran James O. , Callaghan Grace L. , Caven Miles J. G. , Fielding Suzanne M.
Published: April 2024

We study theoretically the dynamical process of yielding in cyclically sheared amorphous materials, within a thermal elastoplastic model and the soft glassy rheology model. Within both models we find an initially slow accumulation, over many cycles after the inception of shear, of low levels of damage in the form strain heterogeneity across the sample. This slow fatigue then suddenly gives way to catastrophic yielding and material failure. Strong strain localization in the form of shear banding is key to the failure mechanism. We characterize in detail the dependence of the number of cycles N* before failure on the amplitude of imposed strain, the working temperature, and the degree to which the sample is annealed prior to shear. We discuss our finding with reference to existing experiments and particle simulations, and suggest new ones to test our predictions.

Published by the American Physical Society
2024
Default prediction modeling (DPM) with machine learning algorithms: case of non-financial listed companies in Pakistan
Authors: Alvi Jahanzaib , Arif Imtiaz
Published: April 2024

Purpose

The crux of this paper is to unveil efficient features and practical tools that can predict credit default.

Design/methodology/approach

Annual data of non-financial listed companies were taken from 2000 to 2020, along with 71 financial ratios. The dataset was bifurcated into three panels with three default assumptions. Logistic regression (LR) and k-nearest neighbor (KNN) binary classification algorithms were used to estimate credit default in this research.

Findings

The study’s findings revealed that features used in Model 3 (Case 3) were the efficient and best features comparatively. Results also showcased that KNN exposed higher accuracy than LR, which proves the supremacy of KNN on LR.

Research limitations/implications

Using only two classifiers limits this research for a comprehensive comparison of results; this research was based on only financial data, which exhibits a sizeable room for including non-financial parameters in default estimation. Both limitations may be a direction for future research in this domain.

Originality/value

This study introduces efficient features and tools for credit default prediction using financial data, demonstrating KNN’s superior accuracy over LR and suggesting future research directions.
Determinants of residential land value – a study of Delhi, India
Authors: Sharma Sumant , Bajaj Deepak , Tirumala Raghu Dharmapuri
Published: April 2024

Purpose

Land value in urban areas in India is influenced by regulations, bylaws and the amenities associated with them. Planning interventions play a significant role in enhancing the quality of the neighbourhood, thereby resulting in a change in its value. Land is a distinct commodity due to its fixed location, and planning interventions are also specific to certain locations. Consequently, the factors influencing land value will vary across different areas. While recent literature has explored some determinants of land value individually, conducting a comprehensive study specific to each location would be more beneficial for making informed policy decisions. Therefore, this article aims to examine and identify the critical factors that impact the value of residential land in the National Capital Territory of Delhi, India.

Design/methodology/approach

The study employed a combination of semi-structured and structured interview methods to construct a Relative Importance Index (RII) and ascertain the critical determinants affecting residential land value. A sample of 36 experts, comprising property valuers, urban planners and real estate professionals operating within the National Capital Territory of Delhi, India, were selected using snowball sampling techniques. Subsequently, rank correlation and ANOVA methods were employed to evaluate the obtained results.

Findings

Location and stage of urban development are the most critical determinants in determining residential land values in the National Capital Territory of Delhi, India. The study identifies a total of 13 critical determinants.

Practical implications

A scenario planning approach can be developed to achieve an equitable distribution of values and land use entropy. A land value assessment model can also be developed to assist professional valuers.

Originality/value

There has been a lack of emphasis on assessing the impact of planning interventions and territorial regulation on land values in the context of Delhi. This study will contribute to policy decision-making by developing a rank list of planning-based determinants of land value.
Exploring the utilities of rice straw black liquor (Part X): biomass-derived copper (lignin/silica/fatty acids) complex as a natural antioxidant for EPDM composites (Part V)
Authors: Sabry Othman Hoda Sabry , El-Sabbagh Salwa H. , Nawwar Galal A.
Published: April 2024

Purpose

This study aims to investigate the behavior of the green biomass-derived copper (lignin/silica/fatty acids) complex, copper lignin/silica/fatty acids (Cu-LSF) complex, when incorporated into the nonpolar ethylene propylene diene (EPDFM) rubber matrix, focusing on its reinforcing and antioxidant effect on the resulting EPDM composites.

Design/methodology/approach

The structure of the prepared EPDM composites was confirmed by Fourier-transform infrared spectroscopy, and the dispersion of the additive fillers and antioxidants in the EPDM matrix was investigated using scanning electron microscopy. Also, the rheometric characteristics, mechanical properties, swelling behavior and thermal gravimetric analysis of all the prepared EPDM composites were explored as well.

Findings

Results revealed that the Cu-LSF complex dispersed well in the nonpolar EPDM rubber matrix, in thepresence of coupling system, with enhanced Cu-LSF-rubber interactions and increased cross-linking density, which reflected on the improved rheological and mechanical properties of the resulting EPDM composites. From the various investigations performed in the current study, the authors can suggest 7–11 phr is the optimal effective concentration of Cu-LSF complex loading. Interestingly, EPDM composites containing Cu-LSF complex showed better antiaging performance, thermal stability and fluid resistance, when compared with those containing the commercial antioxidants (2,2,4-trimethyl-1,2-dihydroquinoline and N-isopropyl-N’-phenyl-p-phenylenediamine). These findings are in good agreement with our previous study on polar nitrile butadiene rubber.

Originality/value

The current study suggests the green biomass-derived Cu-LSF complex to be a promising low-cost and environmentally safe alternative filler and antioxidant to the hazardous commercial ones.
Nickelophilic root foraging by the nickel hyperaccumulator, Streptanthus polygaloides subsp. undulatus (Brassicaceae)
Authors: Mincey Katherine A. , Boyd Robert S.
Published: April 2024

Root foraging may allow hyperaccumulator plants to enhance element accumulation. This study compared root proliferation of two annual serpentine endemics: Streptanthus polygaloides (Ni hyperaccumulator) and Streptanthus insignis (nonhyperaccumulator). In a greenhouse experiment, pots were divided by a sealed partition, Ni‐amended soil (800 mg kg −1) in one half, unamended soil in the other. Seeds were germinated over the partition, allowing roots to explore both soils. After 5 months, roots from each side of each pot were harvested, washed, dried, and weighed. Streptanthus polygaloides root biomass was significantly (twofold) greater in Ni‐amended soil whereas S. insignis root biomass was similar in the two soils. In a lab experiment, seedlings were grown in vertical agar‐filled petri dishes to determine if Ni affected seedling root growth. Seedlings were placed on either side of a central filter paper strip soaked in either NiCl2 solution or deionized water. Growth direction of the primary root (toward, away, neutral) and lateral root numbers and lengths were recorded. For seedlings, primary root direction and lateral root numbers/lengths were significantly increased toward Ni‐soaked filter paper only for S. polygaloides. We conclude that S. polygaloides exhibited positive root foraging responses. These may enhance Ni uptake and we suggest the term “nickelophilic root foraging” be applied to this behavior.
Post‐COVID anxiety, depression, and quality of life among Egyptian hemodialysis patients
Authors: Shaban Rehab AlSayed , Abdulgalil Ahmed E. , Bahie Ahmed
Published: April 2024

Introduction

This study examined the impact of Coronavirus disease 2019  on anxiety, depression, and health‐related quality of life (HRQOL) among Egyptian hemodialysis (HD) patients.

Methods

This multicenter cross‐sectional study was carried out in Egypt in the years 2021–2022, where 300 HD patients from four HD centers were allocated into two groups: post‐COVID and non‐COVID. The Hospital Anxiety and Depression Scale (HADS) and the Kidney Disease QOL‐36 questionnaire were used to assess anxiety, depression, and QOL of the included patients.

Results

In the post‐COVID group, abnormal and borderline cases of anxiety and depression were detected in 38.6% and 62.5% of patients, respectively, with no statistically significant difference between both groups. The post‐COVID group showed higher work status and lower sexual and physical functioning, which correlated negatively with anxiety and depression scores.

Conclusion

Past‐COVID infection did not influence depression and anxiety symptoms in HD patients. Sexual and physical functioning were more affected among COVID‐survivors.
Differences in cancer clinical trial activity and trial characteristics at metropolitan and rural trial sites in Victoria, Australia
Authors: McPhee Narelle J. , Leach Michael , Nightingale Claire E. , Harris Samuel J. , Segelov Eva , Ristevski Eli
Published: April 2024

Objective

Cancer clinical trials (CCTs) provide access to emerging therapies and extra clinical care. We aimed to describe the volume and characteristics of CCTs available across Victoria, Australia, and identify factors associated with rural trial location.

Methods

Quantitative analysis of secondary data from Cancer Council Victoria's Clinical Trials Management Scheme dataset.

Design

A cross‐sectional study design was used.

Setting

CCTs were available Victoria‐wide in 2018.

Participants

There were 1669 CCTs and 5909 CCT participants.

Main Outcome Measures

Rural CCT location was assessed as a binary variable with categories of ‘yes’ (modified Monash [MM] categories 2–7) and ‘no’ (MM category 1). MM categories were determined from postcodes. The highest (‘least rural’) MM category was used for postcodes with multiple MM categories.

Results

Of 1669 CCTs, 168 (10.1%) were conducted in rural areas. Of 5909 CCT participants, 315 (5.3%) participated in rural CCTs. There were 526 CCTs (31.5%) with 1907 (32.3%) newly enrolled participants. Of 1892 newly enrolled participants with postcode data, 488 (25.8%) were rural residents. Of them, 368 (75.4%) participated in metropolitan CCTs. In a multivariable logistic regression analysis for all 1669 CCTs, odds of a rural rather than metropolitan CCT location were significantly (p‐value <0.05) lower for early‐phase than late‐phase trials and non‐solid than solid tumour trials but significantly (p‐value <0.05) higher for non‐industry than industry‐sponsored trials.

Conclusions

In Victoria, 10% of CCTs are at rural sites. Most rural‐residing CCT participants travel to metropolitan sites, where there are more late‐phase, non‐solid‐tumour and industry‐sponsored trials. Approaches to increase the volume and variety of rural CCTs should be considered.
Use of portable single‐lead electrocardiogram device as an alternative for QTc monitoring in critically ill patients
Authors: Rebolledo‐Del Toro Martin , Carvajalino‐Galeano Ana Beatriz , Pinto‐Brito Clarena , Muñoz‐Velandia Oscar Mauricio , García‐Peña Ángel Alberto
Published: April 2024

Purpose

Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user‐friendly single lead, mobile alternative to conventional 12‐lead electrocardiogram (12‐L ECG) that could be more readily available, potentially facilitating more frequent QTc assessments in intensive care units (ICU); however, there is currently no evidence to validate this potential use.

Methods

We conducted a prospective diagnostic test study comparing QT interval measurement using KM1L with conventional 12‐L ECG ordered for any reason in patients admitted to an ICU. We compared the mean difference using a paired t‐test, agreement using Bland–Altman analysis, and Lin's concordance coefficient, numerical precision (proportion of QT measurements with <10 ms difference between KM1L and conventional 12‐L ECG), and clinical precision (concordance for adequate discrimination of prolonged QTc).

Results

We included 114 patients (61.4% men, 60% cardiovascular etiology of hospitalization) with 131 12‐L ECG traces. We found no statistical difference between corrected QT measurements (427 ms vs. 428 ms, p = .308). Lin's concordance coefficient was 0.848 (95% CI 0.801–0.894, p = .001). Clinical precision was excellent in males and substantial in females (Kappa 0.837 and 0.781, respectively). Numerical precision was lower in patients with vasoactive drugs (−13.99 ms), QT‐prolonging drugs (13.84 ms), antiarrhythmic drugs (−12.87 ms), and a heart rate (HR) difference of ≥5 beats per minute (bpm) between devices (−11.26 ms).

Conclusion

Our study validates the clinical viability of KM1L, a single‐lead mobile ECG device, for identifying prolonged QT intervals in ICU patients. Caution is warranted in patients with certain medical conditions that may affect numerical precision.