bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of cats treated with robenacoxib after gastrointestinal surgery
Authors: Rogers Joseph B , Mazepa Allison S , Kaufman Kathryn L , Eskander Bishoy S , Jackson Andrew H
Published: November 2024

Objectives

The aim of the study was to determine if cats administered robenacoxib immediately after gastrointestinal surgery have a similar complication rate to cats that were not administered robenacoxib.

Methods

Medical records were reviewed for 154 cats that underwent gastrointestinal surgery between December 2015 and September 2021 in this retrospective study. Data collected included patient signalment, presenting complaint, surgical procedure(s) performed, robenacoxib administration and major postoperative complications. Cats were excluded if they did not have a 2-week postoperative follow-up examination. Two groups were analyzed: group R (postoperative robenacoxib administration) consisted of 43 cats; and group C (no postoperative robenacoxib administration) consisted of 111 cats.

Results

Complications occurred in 10/43 (23.2%) cats in group R and 34/111 (30.6%) cats in group C. Major complications occurred in 1/43 (2.3%) in group R and 14/111 (12.6%) in group C. Minor complications occurred in 9/43 (20.9%) cats in group R and 20/111 (18.0%) cats in group C. One of 43 cats (2.3%) in group R and 10/111 (9.0%) cats in group C were euthanized or died within 0–16 days after gastrointestinal surgery.

Conclusions and relevance

Cats that were administered robenacoxib postoperatively did not have an increase in major postoperative complications after gastrointestinal surgery compared with cats that were administered an alternative analgesic medication. The use of robenacoxib in cats after gastrointestinal surgery may be a safe analgesic option for postoperative pain control.
A Novel Scale of Lifestyle Physical Activity: Measure Description and Intervention Responsiveness
Authors: Browne Julia , Halverson Tate F. , Battle Cynthia L. , Stein Michael D. , Bergeron Alicia , Abrantes Ana M.
Published: November 2024

Lifestyle physical activity (LPA) interventions emphasize small bouts of movement that can be flexibly integrated into one’s everyday routine. Despite research illustrating benefits for LPA on health outcomes, few LPA interventions and measurement tools have been developed and tested. The purpose of this study was to present a novel LPA self-report scale, including its content, scoring, and internal consistency reliability, and summarize its intervention responsiveness. The LPA scale was administered in a pilot randomized controlled trial that tested a 12-week LPA + Fitbit intervention against a health education (HE) control (matched to LPA + Fitbit on contact time) in a sample of 50 women with depression in alcohol treatment. The LPA scale includes 22 items covering five domains relevant to LPA. Results demonstrated good internal consistency reliability for the total score (ω = 0.84) but poor-to-acceptable internal consistency reliability for the domain scores (ω range: 0.43-0.80). Participants randomized to the LPA + Fitbit intervention had significantly greater improvements in the LPA total score and two domain scores compared to HE participants. Overall, results demonstrate good internal consistency reliability and intervention responsiveness of the LPA scale total score. A larger, more comprehensive psychometric evaluation is needed for validation of this scale.
A Low-Cost Workflow to Generate Virtual and Physical Three-Dimensional Models of Cardiac Structures
Authors: Grieshaber Philippe , Schneller Alexander , Fonseca-Escalante Elizabeth , Farag Mina , Krey Rebecca , Czundel Angéla , Jaschinski Christoph , Karck Matthias , Gorenflo Matthias , Loukanov Tsvetomir
Published: November 2024

Purpose

Three-dimensional modeling and printing (3DMP) of anatomical structures from cross-sectional imaging data can enhance the understanding of spatial relationships in complex congenital heart defects. Partially due to the substantial financial, material and personnel resources required, 3DMP is not yet universally used. Here, we describe a workflow that addresses and eliminates these drawbacks.

Description

The workflow utilizes the open-source software “3D Slicer” (The Slicer Community) and “Blender” (Blender Foundation) for segmentation and post-editing of datasets. This approach enables the generation of virtual or physical 3D models. The physical models are printed using a standard fused deposition modeling printer.

Evaluation

The financial challenges that likely constrain the wider use of 3DMP are largely addressed by this approach. However, the workflow still requires a considerable amount of time to manually segment the imaging data.

Conclusions

Three-dimensional modeling and printing might improve planning and safety of congenital cardiac surgical treatment. Furthermore, it is a useful tool for education of parents and medical professionals. This workflow increases its suitability for routine use also in regions with low economic resources.
Effects of Planning Conditions on L2 Writing in Relation to Task Complexity
Authors: Fan Ning , Ma Yingying
Published: November 2024

Researchers have been investigating the effects of different planning conditions on learners’ second language (L2) writing performance. However, whether such effects differ regarding specific planning conditions and task complexity has remained underexplored. This study examined the effects of pre-task planning (PTP) versus unpressured online planning (OLP) on L2 writing, particularly in relation to task complexity manipulated in terms of the reasoning demands. Participants were 60 low-intermediate Chinese English as a Foreign Language (EFL) learners who were divided into a PTP group and an unpressured OLP group. Each group completed two writing tasks differing in complexity manipulated as more or less reasoning demands. The participants’ texts were examined in terms of lexical and syntactic complexity, accuracy, and fluency. The results revealed that there were no significant differences between PTP and unpressured OLP in lexical and syntactic complexity. However, unpressured OLP benefited accuracy and fluency, and the benefits reached a significant level. In addition, its effects on accuracy were affected by task complexity in that it was much more beneficial to a simple task than to a complex one. For lexical and syntactic complexity and fluency, no such effects were found. The pedagogical implications and limitations of the study were discussed.
Clinical Profiles of Retinal Vasoproliferative Tumors
Authors: Subramanian Brughanya , Nangia Purna , Rishi Pukhraj , Walinjkar Jaydeep Avinash , Ratra Dhanashree , Vadivelu Jaya Prakash , Majumder Parthopratim Dutta , Biswas Jyotirmay , Raman Rajiv
Published: November 2024

Purpose: To describe the clinical features and treatment outcomes of patients with retinal vasoproliferative tumors. Methods: This retrospective case series comprised patients diagnosed with a retinal vasoproliferative tumor. Electronic medical records were reviewed, and patients’ demographic details, clinical presentation, and treatment outcomes were analyzed. Results: Nineteen eyes of 19 patients with vasoproliferative tumors were included. The mean age (±SD) at presentation was 37.0 ± 16.95 years. No eye had bilateral tumors, and 1 eye had multiple tumors. Three eyes (15%) had primary tumors, while 16 (84%) had secondary tumors. Primary tumors mainly affected the inferotemporal quadrant (n = 3). Secondary tumors involved the inferior quadrant (n = 4), inferotemporal quadrant (n = 5), and inferonasal quadrant (n = 5). Secondary tumors were associated with Coats disease (n = 6), intermediate uveitis (n = 3), traumatic chorioretinopathy (n = 2), familial exudative vitreoretinopathy (n = 2), retinal vasculitis (n = 2), and retinal vascular occlusion (n = 1). Retinochoroidal features included intraretinal and subretinal exudates, subretinal fluid, intraretinal hemorrhaging, vitreous hemorrhaging, cystoid macular edema, vitritis, preretinal fibrosis, dilated feeding vessel, epiretinal membranes, and tractional retinal detachment. Treatment modalities included cryotherapy, laser photocoagulation, and local steroids. The mean follow-up was 25.3 months, during which 18 eyes had tumor regression and 1 had a worsening condition. Conclusions: Secondary vasoproliferative tumors were more frequently observed than primary tumors, often presenting as unilateral, unifocal tumors situated posterior to the equator in the inferior fundus. Conventional treatment approaches, such as cryotherapy and laser photocoagulation, were effective at tumor regression and often required multiple sessions.
Pediatric Facial Trauma in Rural Versus Urban Areas: Challenges and Opportunities for Intervention With Safety Device Usage in Motorized Vehicles
Authors: Hinson Madison , Wright Avery , Davidson Amelia , Kogan Samuel , Runyan Christopher
Published: November 2024

Study design:

Retrospective chart review.

Objective:

Improper usage of safety devices in motorized vehicles can lead to serious facial injuries in the pediatric population. This study compares pediatric facial trauma patients from rural and urban counties who present to 2 high-volume Level 1 Trauma Centers to investigate factors influencing injury severity and management, and to guide preventative measures to improve patient outcomes.

Methods:

A retrospective chart review of pediatric facial trauma patients (<18 years old) was performed between January 2020 and December 2022 at 2 high-volume Level 1 Trauma Centers. Data on patient demographics, facial injuries, management, and outcomes were collected. Urban and rural county designation was defined according to the Department of Health and Human Services.

Results:

Of 2977 pediatric facial trauma patients evaluated, 206 sustained facial fractures from motorized vehicle accidents (MVA) −176 were from an urban-designated county (UC) and 30 from a rural-designated county (RC) at the time of injury. RC patients were significantly more likely to be transferred from outside institutions ( P = .007) and to sustain injuries from an ATV accident ( P = .006). Lack of safety device use in UC patients were significantly more likely to sustain injuries from low-energy trauma ( P = .01), to have a higher ISS score ( P = .02), and to have a longer hospital stay ( P = .01). RC patients using appropriate safety devices were significantly more likely to receive specialty follow-up for their facial injuries ( P = .04) and to have resolution of their facial trauma injuries within 1 year ( P = .004).

Conclusion:

Proper safety device usage is crucial in the prevention of pediatric facial injuries in motorized vehicles. While the type of facial fractures did not differ, patients not using safety devices had more severe injuries with less specialized follow-up care and longer duration of residual symptoms. Further research should focus on improving follow-up care with a focus on rural patients to enhance long-term recovery.
Ferroptosis regulates hemolysis in stored murine and human red blood cells
Authors: D’Alessandro Angelo , Keele Gregory R. , Hay Ariel , Nemkov Travis , Earley Eric J. , Stephenson Daniel , Vincent Matthew , Deng Xutao , Stone Mars , Dzieciatkowska Monika , Hansen Kirk C. , Kleinman Steven , Spitalnik Steven L. , Roubinian Nareg , Norris Philip J. , Busch Michael P. , Page Grier P. , Stockwell Brent R. , Churchill Gary A. , Zimring James C.
Published: November 2024

Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. On the basis of the breeding of 8 founder strains with extreme genetic diversity, the Jackson Laboratory diversity outbred population can capture the impact of genetic heterogeneity in like manner to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for posttransfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid quantitative trait loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase 6-transmembrane epithelial antigen of the prostate 3 (Steap3), a transcriptional target to p53. Steap3 regulated posttransfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation, and in vitro hemolysis in 13 091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (fatty acid desaturases 1 and 2, epoxide hydrolase 2, lysophosphatidylcholine acetyl-transferase 3, solute carrier family 22 member 16, glucose 6-phosphate dehydrogenase, very long chain fatty acid elongase, and phospholipase A2 group VI) associated with altered levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.
PROTEA study: a protocol for a randomised controlled trial evaluating the efficacy, immune effects and cost-effectiveness of oral bacterial lysate (OM-85) therapy to protect moderate-late preterm infants from respiratory tract infections and wheezing
Authors: van Duuren Inger C. , Smits Hermelijn H. , Duijts Liesbeth , Penders John , Tramper-Stranders Gerdien A.
Published: November 2024

Infants, children and adults born moderate-late preterm (after 30–36 weeks of pregnancy) are at increased risk of respiratory infections, wheezing and lower lung function leading to increased medication use and hospitalisation. Risk-factors frequently present in this population are, at least in part, associated with (lack of) exposure to microbes and subsequent perturbations in microbiome and immune system development.

This manuscript presents the protocol of the double blinded, randomised, placebo-controlled Protea trial, which will demonstrate whether treatment with immunomodulatory bacterial lysates (OM-85) can reduce lower respiratory tract infections and wheeze in the first year of life. The follow-up Protea-2 trial will identify possible carry-over effects of OM-85 treatment, and investigate the clinical effect of continued treatment in the second year of life. Infants included are otherwise healthy infants born after 30 to 36 week of gestation, excluding those small for gestational age (<3rd percentile). They are recruited shortly after birth in 22 medical centres in the Netherlands.

Participants will take OM-85 or placebo starting from 6–10 weeks of life till age 1 (Protea study) or 2 (Protea-2 study) and are closely monitored regarding respiratory health through e-applications. Biological samples, lung function measurements and detailed information on covariates will be collected at ages 2, 6, 12 and 24 months. Biological samples will aid in estimating the impact of bacterial lysate administration on immune cell composition, activation and maturation, vaccination responses, and microbiome diversity and maturation. Participant recruitment has started in March 2022.
Exploring the roles of airway dipeptidyl peptidase 1 in obstructive airway disease
Authors: Tanabe Naoya , Matsumoto Hisako , Kogo Mariko , Morimoto Chie , Nomura Natsuko , Hayashi Yusuke , Sakamoto Ryo , Oguma Tsuyoshi , Nagasaki Tadao , Sunadome Hironobu , Sato Atsuyasu , Sato Susumu , Ohashi Kai , Tsukahara Takamitsu , Hirai Toyohiro
Published: November 2024

Background

Dipeptidyl peptidase 1 (DPP1) exacerbates airway neutrophilic inflammation in bronchiectasis, which is characterized by airway dysfunction and dilation and chronic bacterial infection. However, little is known about the pathogenetic roles of DPP1 in obstructive airway diseases, including chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap (ACO). Here, we tested the hypothesis that airway DPP1 could enhance neutrophilic inflammation and affect mucus plugging, airway dilation, and the airway microbiome in patients with these diseases.

Methods

The sputum DPP1, cell differential count, and microbiome were cross-sectionally evaluated in patients with COPD, asthma with airflow limitation, and ACO. Sputum high mobility group box 1 (HMGB1) was measured to estimate airway epithelial damage. Chest computed tomography (CT) was also performed to visually assess mucus plugs and airway dilation with the Reiff score and quantify the total airway count and wall area percentage.

Results

Sixty-eight patients were classified into high-DPP1/high-neutrophil, low-DPP1/high-neutrophil, and low-neutrophil groups (n=17, 37, and 14) based on sputum DPP1 levels and neutrophil percentages. The rate of mucus plugging and the relative abundance of the phylum Firmicutes were significantly lower, and the level of sputum HMGB1 was significantly greater in the high-DPP1/high-neutrophil group than in the low-DPP1/high-neutrophil group. Moreover, airway dilation without mucus plugging was observed only in the high-DPP1/high-neutrophil subgroup (prevalence, 29%).

Conclusions

High sputum DPP1 levels may reduce colonization by the phylum Firmicutes and mucus plugging, but increase airway epithelial damage, which could induce airway dilation without mucus plugging in patients with obstructive airway disease with neutrophilic inflammation.
Endobronchial valve treatment improves diaphragm function in severe emphysema patients
Authors: ter Haar Else A.M.D. , Slebos Dirk-Jan , Bakker J.T. , Augustijn Sonja W.S. , Dijkstra Linze J. , Hartman Jorine E.
Published: November 2024

Rationale and aim

Diaphragm dysfunction is common in severe emphysema patients, primarily due to hyperinflation, placing the diaphragm at a mechanical disadvantage. Endobronchial valve (EBV) treatment is a bronchoscopic procedure to reduce hyperinflation, and thus potentially restore diaphragm function in this patient population. Our aim was to investigate the effect of EBV treatment on diaphragm function.

Patients and methods

A prospective cohort study was performed in which diaphragm function was measured at baseline and 6 weeks after EBV treatment by ultrasonic assessment to measure diaphragm motion and diaphragm thickening fraction (dTF), surface electromyography (sEMG) to quantify diaphragm activity, and maximal inspiratory pressure (MIP) to assess diaphragm strength.

Results

Twenty-five patients were included, with a mean age of 64±7 years. Residual volume (−0.85±0.49 Liter, p<0.001) decreased significantly post EBV treatment, with a significant increase in MIP (+0.6 kPa, range −1.2–2.8, p=0.001). Diaphragm motion on the treated side during tidal breathing significantly decreased (−3.3 mm, range −24.7–14.6, p=0.023). There were no significant changes in dTF on the treated side. Diaphragm activity (sEMG) for tidal breathing (−1.7 µV, p=0.004, range −8.8–5.8), maximal inspiration (−4.1 µV, p=0.004, range −42.3–16.0), and sniff manoeuvre (−6.1 µV, p=0.027, range −42.2–24.2) all significantly decreased.

Conclusion

Our results show that diaphragm function significantly improves after EBV treatment in severe emphysema patients. This emphasizes the physiological interaction between hyperinflation and diaphragm function, suggesting that reducing hyperinflation can at least partially reverse diaphragm dysfunction.
Comparison of commonly used software pipelines for analyzing fungal metabarcoding data
Authors: Rzehak Theresa , Praeg Nadine , Galla Giulio , Seeber Julia , Hauffe Heidi Christine , Illmer Paul
Published: November 2024

Background

Metabarcoding targeting the internal transcribed spacer (ITS) region is commonly used to characterize fungal communities of various environments. Given their size and complexity, raw ITS sequences are necessarily processed and quality-filtered with bioinformatic pipelines. However, such pipelines are not yet standardized, especially for fungal communities, and those available may produce contrasting results. While some pipelines cluster sequences based on a specified percentage of base pair similarity into operational taxonomic units (OTUs), others utilize denoising techniques to infer amplicon sequencing variants (ASVs). While ASVs are now considered a more accurate representation of taxonomic diversity for prokaryote communities based on 16S rRNA amplicon sequencing, the applicability of this method for fungal ITS sequences is still debated.

Results

Here we compared the performance of two commonly used pipelines DADA2 (inferring ASVs) and mothur (clustering OTUs) on fungal metabarcoding sequences originating from two different environmental sample types (fresh bovine feces and pasture soil). At a 99% OTU similarity threshold, mothur consistently identified a higher fungal richness compared to DADA2. In addition, mothur generated homogenous relative abundances across multiple technical replicates (n = 18), while DADA2 results for the same replicates were highly heterogeneous.

Conclusions

Our study highlights a potential pipeline-associated bias in fungal metabarcoding data analysis of environmental samples. Based on the homogeneity of relative abundances across replicates and the capacity to detect OTUs/ASVs, we suggest using OTU clustering with a similarity of 97% as the most appropriate option for processing fungal metabarcoding data.
Housing conditions and COVID-19 in Barcelona: do they change by gender?
Authors: Perez Gloria , Forcadell-Diez Lluís , Reyes Alexia , Perez Catherine , Bartoll Xavier , Borrell Carme
Published: November 2024

Background

Evidence has linked poor housing conditions to negative health outcomes. However, in urban contexts characterized by social vulnerability and population-level inequalities, the gender perspective is often overlooked, despite evidence showing that housing conditions impact men and women differently in terms of health. This study aimed to describe the association between housing conditions and the prevalence of COVID-19 among men and women in Barcelona, Spain.

Methods

An observational cross-sectional study was conducted using the 2021 Barcelona Health Survey. The study population consisted of non-institutionalized residents over 14 years of age in Barcelona. The survey was administered to a sample of 3,545 participants during the COVID-19 pandemic, between February 2021 and February 2022. Crude and adjusted prevalence ratios of COVID-19 (aPR), along with 95% confidence intervals (95% CI), were estimated using multivariate Poisson regression models with robust variance. The analysis was stratified by gender.

Results

A significant gradient was observed across age groups for both men and women, with higher COVID-19 prevalence in younger categories. The prevalence was notably higher among individuals born in low-income countries, particularly for women (aPR 1.62). We also identified a significant association between housing conditions, vulnerability factors, and COVID-19 prevalence in both men and women. Living with four or more cohabitants was associated with higher prevalence (aPR 1.96 for women and 1.89 for men), as was the presence of dampness in the home (aPR 1.34 for women and 1.27 for men). Additionally, energy poverty was significantly associated with higher COVID-19 prevalence in women (aPR 1.36), but not in men.

Conclusion

This study highlights the association between housing conditions and COVID-19 in Barcelona, with a pronounced impact on young people, women from low-income countries, and women experiencing energy poverty.
A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases
Authors: Furuta Yutaka , Tinker Rory J. , Hamid Rizwan , Cogan Joy D. , Ezell Kimberly M. , Oglesbee Devin , DeBerardinis Ralph J. , Phillips John A. ,   the Undiagnosed Diseases Network
Published: November 2024

Background

The number of known inherited metabolic diseases (IMDs) has been expanding, and the rate of diagnosis is improving with the development of innovative approaches including next generation sequencing (NGS). However, a substantial proportion of IMDs remain undetected by traditional diagnostic approaches. We aim to highlight the spectrum of IMDs diagnosed by the Undiagnosed Diseases Network (UDN) and to learn from the UDN diagnostic processes that were able to detect IMDs.

Methods

We conducted a retrospective analysis of 757 UDN participants diagnosed from 2015 until 2023 using the cohort database, which were divided into a cohort with IMDs (n = 194; 27%) and a cohort whose phenotypes were not explained by an IMD (n = 563; 73%), based on the International Classification of Inherited Metabolic Disorders (ICIMD). Then, we divided the causes of the metabolic 194 diagnoses into seven groups that included all the ICIMD categories. We inspected which clinical and laboratory approaches contributed to a final UDN diagnosis. We also present a UDN case example from each group to highlight the diagnostic yields that resulted from combining newer diagnostic approaches in the UDN and illustrate potential pitfalls of current NGS methods.

Results

These 194 cases of IMDs included examples from 21/25 (84%) of the ICIMD categories. Of the UDN subjects 164/194 (85%) were diagnosed with IMDs through NGS.

Conclusion

The spectrum of IMDs detected in the UDN cohort is large and growing and appropriate use of newer multiple diagnostic approaches should further increase diagnosis of IMDs that are presently missed by the traditional laboratory screening methods.
How does emotional insecurity affect non-suicidal self-injury among Chinese early adolescents: a longitudinal study
Authors: Ni Xingcan , Liang Qiao , Liao Xiaoyan , Wang Huahua , Yu Chengfu
Published: November 2024

Background

Non-suicidal self-injury (NSSI) is a serious public health concern. Emotional insecurity is a crucial predictor of NSSI among adolescents. However, few studies have elucidated the specific mechanisms between emotional insecurity and NSSI.

Methods

This study employed a longitudinal research design, using a sample of 886 Chinese early adolescents (Mage at T1 = 10.62 years, SD = 0.77 years; 47.40% females), and conducted two surveys six months apart to examine the mediating role of peer exclusion between emotional insecurity and NSSI, as well as the moderating effect of school climate.

Results

The results indicated that peer exclusion significantly mediated the connection between emotional insecurity and adolescent NSSI. Moreover, school climate significantly moderated the connection between emotional insecurity and peer exclusion. Specifically, the impact of emotional insecurity on peer exclusion was significant only in adolescents who reported a negative school climate, but non-significant in those who reported a positive school climate.

Conclusions

These findings provide a robust theoretical foundation and practical insights to help inform the prevention of and interventions for NSSI in adolescents.
The BrEasT cancer afTER-CARE (BETTER-CARE) programme to improve breast cancer follow-up: design and feasibility study results of a cluster-randomised complex intervention trial
Authors: Horn Anna , Wendel Julia , Franke Isabella , Bauer Armin , Baumeister Harald , Bendig Eileen , Brucker Sara Y. , Deutsch Thomas M. , Garatva Patricia , Haas Kirsten , Heil Lorenz , Hügen Klemens , Manger Helena , Pryss Rüdiger , Rücker Viktoria , Salmen Jessica , Szczesny Andrea , Vogel Carsten , Wallwiener Markus , Wöckel Achim , Heuschmann Peter U. ,   the BETTER-CARE Study Group, Ast Alexander , Belke Kerstin , Beurer Björn , Bolkenius Petra , Freese Kristina , Frumkin Nora , Gnauert Karsten , Graf Heiko , Hackmann John , Hartmann Corinna , Hesse Tobias , Hopp Melanie , Keil Elke , Lehnert Antje , Müller Cordula , Mundhenke Christoph , Niestroj Hue Phan , Nixdorf Antje , Pankert Kilian , Perez Sibylle , Radosa Julia , Rezek Daniela , Seldte Jens-Paul , Stalzer Gabriele , Sykorova Zuzana , Tenger Martin , Volmer Léa , Würfel Katharina , Zorr Andreas
Published: November 2024

Background

The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany.

Methods

We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence.

Results

The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach.

Discussion

BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care.

Trial registration

German Clinical Trial Register DRKS00028840. Registered on April 2022.
Bio-inspired one-pot synthesis of luminescent silver nanoparticles and its significant utility as a fluorescence nano sensor for analysis of two adjunctive COVID-19 drugs
Authors: Mostafa Yasmeen E. , Elsebaei Fawzi , Metwally Mohammed El-Sayed
Published: November 2024

This study reveals one-step green synthesis of plant inspired silver nanoparticles (Ag-NPs). The synthesis procedure relies on the bio-reduction of Ag+ to Ag0 using orange waste (orange peel) extract as cheap, readily available, sustainable, biocompatible feedstocks as a reducing and stabilizing agent. The prepared Ag-NPs passed through a full characterization procedure for better confirmation and elucidation of optical and structural properties. The fluorescence of the prepared Ag-NPs has a quantum yield of 17.15% enabling its potential use in chemical sensing of drugs. Ag-NPs are conceived to be used as a fluorescent nano sensor for sensitive, ecofriendly, rapid spectrofluorimetric determination of two recent direct oral anticoagulants, namely, rivaroxaban (RIV) and edoxaban tosylate monohydrate (EDT); COVID-19 adjunctive drugs in their raw materials and pharmaceutical tablets. The fluorescence of the prepared Ag-NPs at 333 nm $${(\uplambda }_{\text{ex}}=258 \text{nm})$$

(
λ

ex

=
258
nm
)

was found to be substantially quenched in existence of increasing concentrations of each drug. The quenching mechanisms were studied and explained. The validation of the method revealed linear correlation over the ranges of 0.5–10 µg/ml with an excellent regression correlation (r = 0.9999) for both drugs with minimum detection limits of 0.14 and 0.16 µg/ml for rivaroxaban and edoxaban tosylate monohydrate, correspondingly. Three different metrics were employed for verifying the greenness profile of the presented study. The findings of the greenness assessment were congruent and compatible with the green synthesis procedure, ecofriendly analysis, and the exclusion of using organic solvents and noxious materials opening an avenue for green synthesis of nanoparticles instead of chemical and physical methods.
Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients
Authors: Zhang Xiuli , Goedegebuure S. Peter , Chen Michael Y. , Mishra Rashmi , Zhang Felicia , Yu Yik Yeung , Singhal Kartik , Li Lijin , Gao Feng , Myers Nancy B. , Vickery Tammi , Hundal Jasreet , McLellan Michael D. , Sturmoski Mark A. , Kim Samuel W. , Chen Ina , Davidson Jesse T. , Sankpal Narendra V. , Myles Stephanie , Suresh Rama , Ma Cynthia X. , Foluso Ademuyiwa , Wang-Gillam Andrea , Davies Sherri , Hagemann Ian S. , Mardis Elaine R. , Griffith Obi , Griffith Malachi , Miller Christopher A. , Hansen Ted H. , Fleming Timothy P. , Schreiber Robert D. , Gillanders William E.
Published: November 2024

Background

Neoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence.

Methods

Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite of neoantigen prediction algorithms was used to identify and prioritize cancer neoantigens and facilitate vaccine design for manufacture in an academic GMP facility. Neoantigen DNA vaccines were administered via electroporation in the adjuvant setting (i.e., following surgical removal of the primary tumor and completion of standard of care therapy). Vaccines were monitored for safety and immune responses via ELISpot, intracellular cytokine production via flow cytometry, and TCR sequencing.

Results

Eighteen subjects received three doses of a neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4–20). The vaccinations were well tolerated with relatively few adverse events. Neoantigen-specific T cell responses were induced in 14/18 patients as measured by ELISpot and flow cytometry. At a median follow-up of 36 months, recurrence-free survival was 87.5% (95% CI: 72.7–100%) in the cohort of vaccinated patients.

Conclusion

Our study demonstrates neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses.

Clinical trial registration number

NCT02348320.
Early continuous glucose monitoring-derived glycemic patterns are associated with subsequent insulin resistance and gestational diabetes mellitus development during pregnancy
Authors: Ku Chee Wai , Zheng Ruther Teo , Tan Hong Ying , Lim Jamie Yong Qi , Chen Ling-Wei , Cheung Yin Bun , Godfrey Keith M. , Chan Jerry Kok Yen , Yap Fabian , Lek Ngee , Loy See Ling
Published: November 2024

Background

Gestational diabetes mellitus (GDM) and insulin resistance (IR) increase the risk of adverse pregnancy outcomes. We aimed to examine the relationship of interstitial glucose assessed by continuous glucose monitoring (CGM) at early gestation, and the subsequent development of IR and GDM, and to determine 24-h interstitial glucose centile distributions in women with normal (non-IR and non-GDM) and suboptimal glycemic status (IR and/or GDM).

Methods

CGM measurements were taken for 3–10 days at 18–24 weeks’ gestation, followed by fasting serum insulin and oral glucose tolerance testing at 24–28 weeks’ gestation. IR and GDM were determined by the updated Homeostasis Model Assessment of IR score of ≥ 1.22 and 2013 World Health Organization criteria, respectively. Risks of IR and GDM were estimated using modified Poisson models, and hourly interstitial glucose centiles determined using Generalized Additive Models for Location, Scale and Shape.

Results

This prospective cohort study involved 167 pregnant women in Singapore, with a mean age of 31.7 years, body mass index of 22.9 kg/m2, and gestation of 20.3 weeks. 25% of women exhibited IR and 18% developed GDM. After confounders adjustment, women with suboptimal glycemic control, indicated by higher mean daily glucose (risk ratio 1.42; 95% confidence interval 1.16, 1.73), glucose management indicator (1.08; 1.03, 1.12), and J-index (1.04; 1.02, 1.06), as well as those with greater glycemic variability, indicated by higher standard deviation (1.69; 1.37, 2.09), coefficient of variation (1.03; 1.00, 1.06), and mean amplitude of glycemic excursions (1.4; 1.14, 1.35) derived from CGM in early gestation were associated with higher risks of developing IR in later gestation. These associations were similarly observed for the development of GDM. Centile curves showed that, compared to those with normal glycemic status, women with suboptimal glycemic status had higher glucose levels, with greater fluctuations throughout 24 h.

Conclusions

In pregnant women who subsequently developed IR and GDM, interstitial glucose levels assessed by CGM were elevated and varied greatly. This supports the potential use of CGM to screen for glycemic changes early in pregnancy.
Accelerated hit identification with target evaluation, deep learning and automated labs: prospective validation in IRAK1
Authors: Kamuntavičius Gintautas , Prat Alvaro , Paquet Tanya , Bastas Orestis , Aty Hisham Abdel , Sun Qing , Andersen Carsten B. , Harman John , Siladi Marc E. , Rines Daniel R. , Flatters Sarah J. L. , Tal Roy , Norvaišas Povilas
Published: November 2024

Background

Target identification and hit identification can be transformed through the application of biomedical knowledge analysis, AI-driven virtual screening and robotic cloud lab systems. However there are few prospective studies that evaluate the efficacy of such integrated approaches.

Results

We synergistically integrate our in-house-developed target evaluation (SpectraView) and deep-learning-driven virtual screening (HydraScreen) tools with an automated robotic cloud lab designed explicitly for ultra-high-throughput screening, enabling us to validate these platforms experimentally. By employing our target evaluation tool to select IRAK1 as the focal point of our investigation, we prospectively validate our structure-based deep learning model. We can identify 23.8% of all IRAK1 hits within the top 1% of ranked compounds. The model outperforms traditional virtual screening techniques and offers advanced features such as ligand pose confidence scoring. Simultaneously, we identify three potent (nanomolar) scaffolds from our compound library, 2 of which represent novel candidates for IRAK1 and hold promise for future development.

Conclusion

This study provides compelling evidence for SpectraView and HydraScreen to provide a significant acceleration in the processes of target identification and hit discovery. By leveraging Ro5’s HydraScreen and Strateos’ automated labs in hit identification for IRAK1, we show how AI-driven virtual screening with HydraScreen could offer high hit discovery rates and reduce experimental costs.

Scientific contribution

We present an innovative platform that leverages Knowledge graph-based biomedical data analytics and AI-driven virtual screening integrated with robotic cloud labs. Through an unbiased, prospective evaluation we show the reliability and robustness of HydraScreen in virtual and high-throughput screening for hit identification in IRAK1. Our platforms and innovative tools can expedite the early stages of drug discovery.
Bactericidal activities and biochemical features of 16 antimicrobial peptides against bovine-mastitis causative pathogens
Authors: Cho Hye-sun , Kim Dohun , Jeon Hyoim , Somasundaram Prathap , Soundrarajan Nagasundarapandian , Park Chankyu
Published: November 2024

Mastitis, often caused by bacterial infection, is an inflammatory condition affecting the mammary glands. The condition is particularly prevalent in dairy cattle. Current treatment of bovine mastitis heavily relies on the use of antibiotics. To identify alternative solutions to antibiotic use, we evaluated the antimicrobial activity of 14 cathelicidins reported from 10 animal species. In conjunction, we assessed two bacteriocins against the bovine-mastitis causative bacterial panel, consisting of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis, Streptococcus agalactiae, Streptococcus dysgalactiae, and Streptococcus equi. Among the antimicrobial peptides (AMPs), cc-CATH3, ML-CATH, and PD-CATH proved to be highly active (minimum inhibitory concentration of 2–41 μg/mL, 0.2–10.3 μM) against all bacterial strains in the panel and field isolates from milk, with elevated somatic cell counts (≥ 500,000 cells/mL). Of the AMPs tested in this study, ML-CATH presented the highest level of effectiveness in controlling mastitis-associated bacterial strains while also possessing minimal cytotoxicity and functional stability against pH change and a high salt condition. The results of in silico analyses on the biochemical features of 12 helical cathelicidins revealed that the charge of AMPs appears to be a major determinant in killing Gram-negative bacteria. Furthermore, we observed a unique motif, “N(n≥3)-P(n≥1)-N(n≥3)”, from the sequences of PMAP-36, cc-CATH3, ML-CATH, and PD-CATH that exhibits potent antimicrobial activity against a broad spectrum of bacteria compared to others. Our findings support the proposition that AMPs could serve as effective antimicrobial alternatives to conventional antibiotics in treating complex animal diseases caused by microbial infection, such as bovine mastitis.
Stearoyl-CoA desaturase in CD4+ T cells suppresses tumor growth through activation of the CXCR3/CXCL11 axis in CD8+ T cells
Authors: Hwang Sung-Hyun , Yang Yeseul , Jung Jae-Ha , Kim Jin Won , Kim Yongbaek
Published: November 2024

Background

Within the tumor microenvironment, altered lipid metabolism promotes cancer cell malignancy by activating oncogenic cascades; however, impact of lipid metabolism in CD4+ tumor-infiltrating lymphocytes (TILs) remains poorly understood. Here, we elucidated that role of stearoyl-CoA desaturase (SCD) increased by treatment with cancer-associated fibroblast (CAF) supernatant in CD4+ T cells on their subset differentiation and activity of CD8+ T cells.

Results

In our study, we observed that CD4+ TILs had higher lipid droplet content than CD4+ splenic T cells. In tumor tissue, CAF-derived supernatant provided fatty acids to CD4+ TILs, which increased the expression of SCD and oleic acid (OA) content. Increased SCD expression by OA treatment enhanced the levels of Th1 cell markers TBX21, interleukin-2, and interferon-γ. However, SCD inhibition upregulated the expression of regulatory T (Treg) cell markers, FOXP3 and transforming growth factor-β. Comparative fatty acid analysis of genetically engineered Jurkat cells revealed that OA level was significantly higher in SCD-overexpressing cells. Overexpression of SCD increased expression of Th1 cell markers, while treatment with OA enhanced the transcriptional level of TBX21 in Jurkat cells. In contrast, palmitic acid which is higher in SCD-KO cells than other subclones enhanced the expression of Treg cell markers through upregulation of mitochondrial superoxide. Furthermore, SCD increased the secretion of the C–X–C motif chemokine ligand 11 (CXCL11) from CD4+ T cells. The binding of CXCL11 to CXCR3 on CD8+ T cells augmented their cytotoxic activity. In a mouse tumor model, the suppressive effect of CD8+ T cells on tumor growth was dependent on CXCR3 expression.

Conclusion

These findings illustrate that SCD not only orchestrates the differentiation of T helper cells, but also promotes the antitumor activity of CD8+ T cells, suggesting its function in adverse tumor microenvironments.

Graphical abstract
A novel function for α-synuclein as a regulator of NCK2 in olfactory bulb: implications for its role in olfaction
Authors: Ren Jing , Wu Chao , Zeng Mengxia , Qu Mingqin , Gao Ge , Chen Ning , Yue Jingjing , Jiang Yuwen , Zhao Tongfei , Xiang Na , Meng Fangang , Lu Ling-ling
Published: November 2024

To investigate physiological function of α-synuclein is important for understanding its pathophysiological mechanism in synucleinopathies including Parkinson’s disease. Employing knockout mice, we found that Snac/α-synuclein deletion induced aberrant projection of olfactory sensory neurons and hyposmia. We identified 9 axon guidance associated differentially expressed proteins using iTRAQ based Liquid Chromatograph Mass Spectrometer. NCK2 is most significantly down-regulated protein among them. We further found that either α-synuclein deletion or NCK2 deficiency induced Eph A4 inactivation. Re-expressing Snac/α-synuclein in its knockout neurons reversed the down-regulation of NCK2, as well as the inactivation of EphA4. Overexpression of Snac/α-synuclein in α-synuclein deleted mice reversed the down-regulation of NCK2 and pEphA4, and improved the olfactory impairment of mice. Correlation analysis showed that there is a significant correlation between the protein level of α-synuclein, NCK2, and pEphA4, respectively. Nonetheless, immunoprecipitation analysis showed that NCK2 was associated with both EphA4 and Rho A, suggesting that NCK2 as a scaffolding protein to modulate Eph A4/Rho A pathway. Moreover, Rho A activity was significantly lower in α-synuclein deficient mice. Thus, α-synuclein regulates olfactory neurons projection through NCK2 dependent EphA4/Rho A pathway. Malfunction of α-synuclein because of deletion may cause aberrant olfactory neurons projection. This extended our knowledge of α-synuclein functions, which may explain why olfaction is usually impaired in some synucleinopathies.
Learned scalable video coding for humans and machines
Authors: Hadizadeh Hadi , Bajić Ivan V.
Published: November 2024

Video coding has traditionally been developed to support services such as video streaming, videoconferencing, digital TV, and so on. The main intent was to enable human viewing of the encoded content. However, with the advances in deep neural networks (DNNs), encoded video is increasingly being used for automatic video analytics performed by machines. In applications such as automatic traffic monitoring, analytics such as vehicle detection, tracking and counting, would run continuously, while human viewing could be required occasionally to review potential incidents. To support such applications, a new paradigm for video coding is needed that will facilitate efficient representation and compression of video for both machine and human use in a scalable manner. In this manuscript, we introduce an end-to-end learnable video codec that supports a machine vision task in its base layer, while its enhancement layer, together with the base layer, supports input reconstruction for human viewing. The proposed system is constructed based on the concept of conditional coding to achieve better compression gains. Comprehensive experimental evaluations conducted on four standard video datasets demonstrate that our framework outperforms both state-of-the-art learned and conventional video codecs in its base layer, while maintaining comparable performance on the human vision task in its enhancement layer.