bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies
Authors: Davids Matthew S. , Brander Danielle M. , Alvarado-Valero Yesid , Diefenbach Catherine S. , Egan Daniel N. , Dinner Shira N. , Javidi-Sharifi Nathalie , Al Malki Monzr M. , Begna Kebede H. , Bhatt Vijaya Raj , Abedin Sameem , Cook Rachel J. , Collins Mary C. , Roleder Carly , Dominguez Edward C. , Rajagopalan Prabhu , Wiley Sandra E. , Ghalie Richard G. , Danilov Alexey V.
Published: December 2024

The antiapoptotic protein, myeloid cell leukemia-1 (Mcl-1), contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models. This dose escalation study evaluated voruciclib in patients with previously treated hematologic malignancies. Initially, voruciclib was administered daily, continuously, on a 28-day cycle (group 1). After 2 patients with prior allogeneic stem cell transplantation had a dose-limiting toxicity (DLT) of interstitial pneumonitis at 100 mg, voruciclib administration was changed to days 1 to 14 of a 28-day cycle (group 2). Forty patients, 21 with AML and 19 with B-cell malignancies, were enrolled. Patients had a median of 3 prior lines of therapy (range, 1-8). Dose escalation in group 2 was stopped at 200 mg, a dose that achieved plasma concentrations sufficient for target inhibition, without DLTs observed. The most common adverse events were diarrhea (30%), nausea (25%), anemia (22%), fatigue (22%), constipation (17%), dizziness (15%), and dyspnea (15%). In AML, 1 patient achieved a morphologic leukemia-free state, and 2 had stable disease. Voruciclib treatment led to a decrease in MCL1 messenger RNA expression, downregulation of myelocytomatosis (MYC) and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase 2. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax for patients with previously treated AML. This trial was registered at www.clinicaltrials.gov as #NCT03547115.
CGREF1 modulates osteosarcoma proliferation by regulating the cell cycle through the Wnt/β-catenin signaling pathway
Authors: Wei Zicheng , Xia Kezhou , Liu Wenda , Huang Xinghan , Wei Zhun , Guo Weichun
Published: December 2024

Background

Osteosarcoma, the most prevalent primary bone malignancy in children and adolescents, exhibits high heterogeneity. The CGREF1 gene encodes a novel 301 amino acid classical secreted protein that contains the presumed N-terminal signaling peptide and EF hand motif. However, its role in osteosarcoma remains unclear.

Methods

Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized for bioinformatics analysis. Western blot and immunohistochemistry (IHC) techniques were employed to detect the expression of relevant proteins. siRNA, lentivirus, and plasmid technologies were applied to modulate gene expression. The downstream pathway of CGREF1 was identified through RNA sequencing analysis. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were conducted for in vitro functional experiments. In vivo experiments involved subcutaneous tumor formation in nude mice.

Results

Our analysis of public databases and clinical samples revealed that CGREF1 is highly expressed in osteosarcoma and is associated with poor prognosis. Knockdown of CGREF1 impeded cell cycle progression and suppressed the proliferation of osteosarcoma cells. Conversely, upregulation of CGREF1 exhibited an opposing pattern. The RNA-seq data from 143B cells was subjected to analysis, revealing that the differentially expressed genes were predominantly enriched in the Wnt signaling pathway. Further experimental results demonstrated that CGREF1 affects activation of the Wnt pathway by regulating GSK3/β-catenin signaling, thereby affecting proliferation ability of osteosarcoma cells. Finally, experiments using subcutaneous transplanted tumor models in nude mice showed that CGREF1 knockdown inhibited tumor growth in vivo by inhibiting the Wnt/β-catenin signaling pathway.

Conclusion

The expression of CGREF1 was significantly upregulated in osteosarcoma and correlated with unfavorable prognosis. CGREF1 exerted a regulatory effect on the proliferation of osteosarcoma cells both in vitro and in vivo through modulation of the wnt/β-catenin signaling pathway. In the future, targeting CGREF1 could potentially offer a novel therapeutic strategy for treating osteosarcoma.
CXCL4 deficiency limits M4 macrophage infiltration and attenuates hyperoxia-induced lung injury
Authors: Yu Bingrui , Jia Siyuan , Chen Yu , Guan Rong , Chen Shuyu , Tang Wanwen , Bao Tianping , Tian Zhaofang
Published: December 2024

Background

Bronchopulmonary dysplasia (BPD), a chronic lung disease prevalent among premature infants, significantly impacts lifelong respiratory health. Macrophages, as key components of the innate immune system, play a role in lung tissue inflammation and injury, exhibiting diverse and dynamic functionalities. The M4 macrophage, a distinctive subtype primarily triggered by chemokine (C-X-C motif) ligand 4 (CXCL4), has been implicated in pulmonary inflammatory and fibrotic processes. Nonetheless, its contribution to the pathophysiology of BPD remains uncertain.

Objective

This study aimed to elucidate the involvement of CXCL4 in hyperoxia-induced neonatal lung injury and fibrosis, with a particular focus on its influence on M4 macrophages.

Methods

A BPD model in neonatal mice was established through continuous exposure to 95% O2 for 7 days. Comparative analyses of lung damage and subsequent regeneration were conducted between wild-type (WT) and CXCL4 knockout (KO) mice. Lung tissue inflammation and fibrosis were assessed using histological and immunofluorescence staining, enzyme-linked immunosorbent assay, Western blot, and real-time quantitative polymerase chain reaction. Differentiation of M0 and M4 macrophages was performed in vitro using macrophage colony-stimulating factor and CXCL4, while expressions of S100A8 and MMP7, along with migration assays, were evaluated.

Results

Elevated CXCL4 levels and M4 macrophage activation were identified in the lung tissue of BPD model mice. CXCL4 deficiency conferred protection to alveolar type 2 epithelial cells, reduced sphingosine-1-phosphate metabolic activity, mitigated pulmonary fibrosis, and limited M4 macrophage progression. This deletion further enhanced lung matrix remodeling during recovery. In vitro, CXCL4 promoted M4 macrophage differentiation and increased macrophage migration via chemokine (C-C motif) receptor 1.

Conclusion

CXCL4 contributes to hyperoxia-induced lung injury and fibrosis through modulation of cytokine release, alveolar cell proliferation, lipid metabolism, and the regulation of macrophage phenotype and function.
Topological Design of a Nanosatellite Structure with Optimal Frequency Responses Filled by Non-Uniform Lattices
Authors: Wang Cunyi , Zhang Bin , Huang Songhua , Dou Weiyuan , Xin Shengzhen , Yan Jiayong
Published: December 2024

Traditional structural forms are difficult to meet the lightweight requirements of subsequent spacecraft for load-bearing structures. In the aerospace industry, filling structure with lattices is a popular approach to reduce the weight of a spacecraft. However, this design strategy has deficiencies in the spatial distribution of lattice cells as well as its affection on the mechanical properties. In this study, a two-step topology optimization technique is proposed to solve the spatial distribution problem of nanosatellite. Firstly, an entire nanosatellite box composed of panels which filled with uniform lattices is sent to the vibration test to obtain the frequency data. Then, a finite element (FE) model of the nanosatellite structure which contains the same uniform lattices is built and validated with the obtained frequency data above. For the subsequent calculation of topology optimization. An equivalent model of the verified FE model is established by replacing the lattice cells in the sandwich layer with equivalent fictional elements. Subsequently, a topology optimization problem under the mass constraints is formulated for maximize the nature frequency, and a new light weighted nanosatellite which filled with non-uniform lattices is established by applying the density mapping method and the previous topology configuration result. By separating the design problem of nanosatellite into two steps, the proposed optimization design method achieves the maximum frequency design under the weight constraint. Furthermore, the frequency is also guaranteed to be around the nature frequency. The results reveal that the mass of the new structure with non-uniform lattices is reduced by 50.32% and the frequency is increased by 1.19%. An important technical importance and application value of this proposed technique is that it improves the performance and design efficiency of the load-bearing structures of a nanosatellite, and this method has significant technical significance and application value.
Anticholinergic burden and frailty in older inpatients: insights from analysis of admission and discharge medicines using four anticholinergic scales
Authors: Mohammed Mohammed Adem , Chan Amy Hai Yan , Wabe Nasir , Ali Ayesha , Harris Louis , West Sianne , Colaabavala Rhea , Aw Justine , Harrison Jeff
Published: December 2024

Background

Exposure to high anticholinergic burden is associated with adverse outcomes in older adults. Older adults with frailty have greater vulnerability to adverse anticholinergic effects. There is limited data on anticholinergic burden in hospitalised older adults with frailty particularly, in New Zealand. This study aimed to (i) examine exposure to anticholinergic medicines in older inpatients using multiple scales, and (ii) describe the association of patient factors such as frailty with anticholinergic exposure.

Methods

We reviewed admission and discharge medicines of 222 older patients (≥ 65 years) in a New Zealand hospital. Sociodemographic, diagnostic and medication data were collected from electronic health records. Anticholinergic burden was quantified using the Anticholinergic Burden Classification (ABC), Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Risk Scale (ARS), and Drug Burden Index (DBI). Frailty was assessed using frailty index (FI) and the Hospital Frailty Risk score (HFRS); higher scores indicate higher frailty. Multivariable logistic regression analysis was used to determine patient factors associated with anticholinergic burden.

Results

Depending on the scale used, the mean anticholinergic burden ranged from 0.65 to 1.83 on admission and 0.59 to 1.40 at discharge, with 32–74% of the patients on admission and 25–65% at discharge prescribed at least one anticholinergic medicine. About 1 in 3 patients had high anticholinergic burden on admission and discharge. On admission, being frail (adjusted odds ratio [AOR] 5.16, 95% confidence interval [95% CI] 1.57, 16.97), having history of readmission (AOR 4.96, CI 1.58, 15.59), and higher number of medicines [AOR range 1.18 CI 1.10, 1.26 (ARS scale) to 1.25 CI 1.15, 1.36 (DBI scale)] were associated with higher odds of anticholinergic exposure. At discharge, pre-frail (DBI scale: AOR = 6.58, CI 1.71–25.32) and frail patients (ACB scale: AOR = 5.73, CI 1.66, 19.70) and those with higher number of medicines [AOR range 1.18 CI 1.09, 1.29 (ARS scale) to 1.33 CI 1.20, 1.49 (DBI scale)] had higher odds of anticholinergic exposure.

Conclusion

A reduction in the anticholinergic burden from admission to discharge was observed in the study population yet, one-third of the study cohort were discharged with high anticholinergic medicines. Enhancing hospital prescribers’ and pharmacists’ awareness about anticholinergic burden and targeted interventions such as in-hospital deprescribing are needed to reduce high anticholinergic exposure in acute setting.
Characterizing sociodemographic disparities and predictors of Gestational Diabetes Mellitus among Asian and Native Hawaiian or other Pacific Islander pregnant people: an analysis of PRAMS data, 2016–2022
Authors: Go Mallory , Sokol Natasha , Ward L. G. , Anderson Micheline , Sun Shufang
Published: December 2024

Background

Gestational Diabetes Mellitus (GDM) affects between 2 and 10% of pregnancies in the United States, with trends of increasing prevalence and a significant amount of variability across race and ethnicity, maternal age, and insurance status. Asian and Native Hawaiian or Other Pacific Islanders (NHOPI) have been documented to have a higher prevalence and risk of developing GDM compared to non-Hispanic white populations and have been under-studied in health disparities research.

Methods

Using data from the Pregnancy Risk Assessment Monitoring System (PRAMS) 2016–2022 surveys, we conducted analyses for the overall PRAMS sample as well as within-group analyses among participants who identify as Asian and NHOPI to identify risk factors for GDM. Descriptive statistics were also collected in the Asian and NHOPI subsample, stratified by Asian and NHOPI ethnicity. Bivariate analyses were performed to explore the relationship between potential GDM risk factors among the overall analytic sample and within the Asian and NHOPI subsample, and multivariable logistic regression was used to investigate potential predictors of GDM.

Results

Asian and NHOPI ethnicities differed by prevalence of GDM at 17.2%, 19.56%, 10.8%, 10.71%, and 18.49% for Chinese, Filipino, Japanese, Native Hawaiian/Other Pacific Islander, and Other Asian, respectively. Compared to White individuals (reference group), the odds of GDM were higher for Asian and Native Hawaiian/Other Pacific Islander individuals in the adjusted model (adjusted odds ratio (aOR) = 2.19, 95% CI: 2.62–2.9). Native mothers also demonstrated significantly elevated odds (aOR = 1.48, 95% CI: 1.4–1.6), while Mixed-race individuals exhibited slightly increased odds (OR = 1.22, 95% CI: 1.14–1.29). The findings revealed notable variability in GDM risk factors across ANHOPI subgroups. Obesity emerged as a consistent and strong predictor of GDM across all groups, while other factors such as interpersonal violence exposure and prenatal depression demonstrated limited or subgroup specific effects.

Conclusion

This analysis of 2016 to 2022 PRAMS data illustrated significant variations of GDM predictors between the general population and the Asian and NHOPI population, as well as differences between Asian and NHOPI ethnicities.
Assessing the impact of critical care training on pharmacy students in Egypt: a pre-post study
Authors: Moustafa Hebatallah Ahmed Mohamed , Hamid Alaa Essawy , Hassoub Gehad , Kassem Amira B.
Published: December 2024

Background

Transition to independent pharmacy practice is challenging. Undergraduate and postgraduate pharmacy students in low-to-middle-income countries (LMICs) currently receive minimal experiential learning in critical care.

Objective

To assess the critical care training course’s impact on pharmacy students’ knowledge, self-efficacy, and self-esteem, as well as their satisfaction with the course.

Method

In a pre-post interventional study, pharmacy students took a 10-day critical care training course with experiential learning. They completed a knowledge questionnaire covering various critical care topics, the 18 questions Pharmacy Self-efficacy and Self-esteem Study Questionnaire, and a satisfaction questionnaire. Data was analyzed using IBM SPSS version 20.0.

Results

A total of 72 trainees participated in the study. The average score for pre-course self-efficacy and self-esteem significantly increased post-course, with a median (IQR) of 3.75 (3.50–3.94) compared to 3.56 (3.28–3.78) pre-course, with a p-value of less than 0.05. Furthermore, their overall knowledge score significantly increased from baseline to post-course, with the median (IQR) rising from 0.53 (0.50–0.61) to 0.98 (0.97–1.0), with a p-value of less than 0.05. Their course satisfaction average total score was 45.08 (SD ± 5.41) (on a scale of 10–50).

Conclusion

The present study provides clear evidence that integrating this critical care training course into a structured curriculum for pharmacy students using experiential learning can act as a facilitator of knowledge enrichment, increase their self-esteem and self-efficacy, and make them satisfied with learning. Larger long duration studies are needed to support this evidence.
Eradication of bovine tuberculosis in Ireland: is it a case of now or never?
Authors: More Simon J.
Published: December 2024

There has been a sharp disimprovement in the bovine tuberculosis (bTB) situation in Ireland in recent years. This commentary argues for critical programme change in three overarching themes relevant to the Irish bTB eradication programme, if eradication is to be successful: (1) Limiting infection in cattle. Residual (hidden) infection is an important constraint to eradication, due to the use of imperfect diagnostic tests. This is resolved with a risk-based approach, as is widely used in other national programmes, and would impact herd management, cattle trade and regionalisation. (2) Limiting infection within and from wildlife. Infection in wildlife is a key feature of bTB in many countries, including Ireland. Early research with badger vaccination has been promising. However, wide-scale badger vaccination has proved logistically challenging, and research to monitor progress is underway. It is unlikely that badger vaccination, in addition to current cattle controls, will be sufficient to achieve bTB eradication. (3) Programme leadership, management, governance and cost-sharing. There are a number of substantial, seemingly intractable, issues relating to programme leadership, management, governance and cost-sharing which alone are sufficient to preclude any sustained move to eradication. International examples of success are available, with funding models being critical to progress. In these three themes, most of the constraints are non-technical. If difficult decisions are not taken and the status quo is allowed to continue, there is a risk that infection may establish in further wildlife species, which may make eradication unattainable. Current decisions (including inaction) will impact future generations, including the general public (through the Exchequer) and future farming families.
Shotgun metagenomic sequencing reveals the influence of artisanal dairy environments on the microbiomes, quality, and safety of Idiazabal, a raw ewe milk PDO cheese
Authors: Santamarina-García Gorka , Yap Min , Crispie Fiona , Amores Gustavo , Lordan Cathy , Virto Mailo , Cotter Paul D.
Published: December 2024

Background

Numerous studies have highlighted the impact of bacterial communities on the quality and safety of raw ewe milk-derived cheeses. Despite reported differences in the microbiota among cheese types and even producers, to the best of our knowledge, no study has comprehensively assessed all potential microbial sources and their contributions to any raw ewe milk-derived cheese, which could suppose great potential for benefits from research in this area. Here, using the Protected Designation of Origin Idiazabal cheese as an example, the impact of the environment and practices of artisanal dairies (including herd feed, teat skin, dairy surfaces, and ingredients) on the microbiomes of the associated raw milk, whey, and derived cheeses was examined through shotgun metagenomic sequencing.

Results

The results revealed diverse microbial ecosystems across sample types, comprising more than 1300 bacterial genera and 3400 species. SourceTracker analysis revealed commercial feed and teat skin as major contributors to the raw milk microbiota (45.6% and 33.5%, respectively), being a source of, for example, Lactococcus and Pantoea, along with rennet contributing to the composition of whey and cheese (17.4% and 41.0%, respectively), including taxa such as Streptococcus, Pseudomonas_E or Lactobacillus_H. Functional analysis linked microbial niches to cheese quality- and safety-related metabolic pathways, with brine and food contact surfaces being most relevant, related to genera like Brevibacterium, Methylobacterium, or Halomonas. With respect to the virulome (virulence-associated gene profile), in addition to whey and cheese, commercial feed and grass were the main reservoirs (related to, e.g., Brevibacillus_B or CAG-196). Similarly, grass, teat skin, or rennet were the main contributors of antimicrobial resistance genes (e.g., Bact-11 or Bacteriodes_B). In terms of cheese aroma and texture, apart from the microbiome of the cheese itself, brine, grass, and food contact surfaces were key reservoirs for hydrolase-encoding genes, originating from, for example, Lactococcus, Lactobacillus, Listeria or Chromohalobacter. Furthermore, over 300 metagenomic assembled genomes (MAGs) were generated, including 60 high-quality MAGs, yielding 28 novel putative species from several genera, e.g., Citricoccus, Corynebacterium, or Dietzia.

Conclusion

This study emphasizes the role of the artisanal dairy environments in determining cheese microbiota and, consequently, quality and safety.
Analysis of topical conjunctival microbiotic cultures in patients treated with intravitreal injections using antibiotic prophylaxis with 0.3% ofloxacin eye drops
Authors: de Miranda Gonçalves Luca Bongiovanni , Campos Maria Leticia Lasca Sales , Barros Guilherme Feltrin , da Veiga Glaucia Luciano , Silva Juliana Antoniali , Fonseca Fernando Luiz Affonso , Gascón Thaís Moura , de Carvalho Samantha Sanches , de Carvalho Andrea Karla Ribeiro , Fernandes Greicy Ellen Pinheiro , Lima Vagner Loduca , Lima Tiago Mirco
Published: December 2024

Background

Intravitreal injections, a relatively recent treatment in ophthalmology, is being adopted rapidly worldwide and becoming one of the most common therapies in the field. Numerous complications are associated with this treatment, ranging from minor inflammatory ailments to endophthalmitis. We analyzed the conjunctival flora of patients treated with intravitreal injections and topical antibiotics.

Methods

The study was a longitudinal prospective analysis of cultures and antibiograms collected from patients who underwent intravitreal injections and topical antibiotics afterwards at the retina clinic in ABC’s Medical University.

Results

A total of 148 swabs obtained from 98 patients were cultured and underwent antibiotic sensitivity testing. All bacteria were sensitive to vancomycin, and with the exception of Escherichia coli samples, they were also sensitive to a third-generation cephalosporin (ceftriaxone—same class and generation as ceftazidime), both of which are important antibiotics for the treatment of endophthalmitis. The bacteria species were specifically coagulase-negative Staphylococcus sp. 92% of which was penicillin-resistant and 56.9% was resistant to ciprofloxacin, a second-generation fluoroquinolone. The culture results were similar to that described in the literature and showed the same higher prevalence of coagulase-negative Staphylococcus sp. and S. epidermidis. Regarding the antibiotic resistance profiles, vancomycin, a third-generation cephalosporin, and penicillin showed almost identical results to those reported previously. Regarding fluoroquinolones, the incidence of resistant coagulase-negative Staphylococcus sp. was lower than the findings worldwide, but the resistance rates found were: S. aureus (26.7%), S. epidermidis (61.3%), and Staphylococcus sp. (coagulase negative, 56.9%).

Conclusions

The current results showed that the typical conjunctival bacteria had higher resistance to fluoroquinolones (although they were not tested specifically to ofloxacin), suggesting a possible selection of resistant bacteria that should not be taken for granted in clinic. However, the same bacteria did not exhibit cross-resistance in the analysis of vancomycin and third-generation cephalosporins. This real-world, longitudinal, prospective study on conjunctival flora analyzed bacterial resistance profiles and contemporary antibiotic use, offering deeper insights into this subject.
Is nitrogen-modified atmosphere packaging a tool for retention of volatile terpenes and cannabinoids in stored Cannabis sativa inflorescence?
Authors: MacLaughlin Luke L. , MacDonald Mason T.
Published: December 2024

Modified atmosphere packaging (MAP) alters the gaseous composition of air surrounding packaged goods to prevent deleterious oxidation associated reactions. MAP has been adopted for the storage of cannabis, though a recent study revealed little difference in terpene content under MAP conditions. Questions regarding its efficacy for preservation of high value compounds like terpenes and cannabinoids lost during postharvest storage remain. The goal of this research is to determine weather N2 MAP preserves high value compounds of cannabis during its postharvest storage. This experiment followed a completed randomized block design. There were two factors of interest. The first was storage atmosphere (atmospheric or N2 MAP). The second was storage duration (18, 46, or 74 days). The experiment was then blocked by cannabis chemovar using 5 different chemovars. The concentration of 17 cannabinoids was evaluated through UPLC-UV and 61 volatile terpene compounds through GC–MS. Concentrations were compared over time and between storage treatments. There were no significant differences in total cannabinoids and volatile terpene compounds over time or between storage treatments. Individual cannabinoids Δ9-THC, CBG, CBNA, CBC, THCV, and THCVA all increased during storage time while THCA decreased. CBG and THCV only increased under MAP storage. Individual aromatics limonene, β-pinene, α-pinene, camphene, and terpinolene all only decreased during storage under N2 MAP. Only caryophyllene oxide and α-humulene increased under N2 MAP storage. β-Myrcene decreased under atmospheric storage, but not under N2 MAP. While N2 MAP had no effect on the preservation of total cannabinoids and aromatics during storage, it did influence several individual compounds. CBG, THCV, and α-humulene all increased under N2 MAP. N2 MAP also maintained the concentration β-myrcene over time, though the preservation of β-myrcene was offset by a decrease limonene. Overall, N2 MAP was not needed for preservation of most high value compounds but did have an effect of some compounds with reputed therapeutic benefits.
Designated confirmer threshold signature and its applications in blockchains
Authors: Ji Yunfeng , Zhang Rui , Tao Yang , Gao Birou
Published: December 2024

The non-transferability of a designated confirmer signature scheme allows a signer to control the verification ability of a signature, hence protecting the signer’s privacy. However, a designated confirmer signature is insufficient when the secret keys are damaged and incapable of collaborative signature generation. In this paper, we circumvent these limitations by introducing the notion of designated confirmer threshold signature. First, we present a formal security model, then give a generic construction, which utilizes threshold signature schemes, encryption schemes and $$\Sigma$$
Σ
-protocols. Instantiating this generic construction, we have two specific schemes, based on threshold Schnorr and threshold ECDSA, respectively. We further design two efficient $$\Sigma$$
Σ
-protocols for efficient proofs. We also implement these schemes, and the experiment results show that our schemes are practical with rich functionalities. Finally, we demonstrate interesting applications for blockchains, such as verifiable asset auctions in blockchain and traditional electronic bidding.
Clinical evaluation of primary endoscopic frontal sinus surgery grade 6 (Draf III) in patients with moderate to severe eosinophilic chronic rhinosinusitis with polyps: a randomized study
Authors: Elshamy Ibrahim Talal , Askar Mohammed Hamed , Khalifa Mohammed Adel , Tomoum Mohammed Osama , Hamad Mohammed Hesham Ali
Published: December 2024

Background

Endoscopic sinus surgery (ESS) is an effective treatment for chronic rhinosinusitis (CRS) that does not respond to proper conventional treatment. The Draf 2A frontal sinusotomy is the most used procedure for this purpose and Draf III is classically reserved for revision cases. The aim of this study was to assess the impact of primary endoscopic frontal sinus surgeries grade 6 (Draf III) on the clinical results of individuals with moderate to severe eosinophilic CRS with Nasal Polyps (CRS w NP).

Methods

This double-blinded, pilot randomized, prospective, controlled, work included 50 individuals who had moderate to severe eosinophilic CRS w NP. These individuals were separated into two groups. Group A: 25 individuals underwent wide corridor paranasal sinus surgery including endoscopic frontal sinus surgery grade 6 (Draf III). Group B: 25 patients received wide corridor paranasal sinus surgery including endoscopic frontal sinus surgery grade 1–3 (Draf I or IIa).

Results

Rhinologic symptom score, extra-nasal rhinologic score, psychological dysfunction score, facial/ear symptoms, sleep score, and total of SNOT 22 were significantly lower in follow-up at 1 year than preoperative in group Draf III and group Draf I or IIa (P value < 0.001) and were insignificantly different at preoperative among group A and group B while were significantly lower at 1 year in group A contrasted to group B (P value < 0.05). There were no substantial variations observed among both groups in terms of age, sex, or total follow-up time. The number of corticosteroid courses needed and total dose of systemic corticosteroids through 1 year postoperatively were significantly lower in group A than in group B (P value = 0.003 and 0.02, respectively). % of cohort exceeding minimal clinically important difference (MCID) improvement at 1 year was substantially greater in group A than group B (P value = 0.039).

Conclusion

The use of endoscopic modified Lothrop procedure (EMLP) as a primary surgery for patients with moderate to severe eosinophilic CRSwNP improved outcomes in those patients. The technique is well-tolerated and has a low rate of complications. It also helps in effectively managing medical conditions for individuals with AERD.
Cross-sectional study on skin prick test reactivity to common aeroallergens among allergic rhinitis patients in Southern India
Authors: Pratap Deepika , Parbat Abhishek Narayan , G. Ravikeerthi , K. G. Somashekara , Balakrishna Vibha , Suresh Shaalini
Published: December 2024

Background

Allergic rhinitis (AR) is the most common cause of rhinitis impairing quality of life. The prevalence of allergic rhinitis varies considerably across countries and regions. Our cross-sectional study aims to identify the common aero-allergens in a tertiary care hospital in Southern India.

Methods

A cross-sectional study of 50 patients with allergic rhinitis was done over a period of 6 months in a tertiary care center in Southern India. Skin prick test was performed on the eligible candidates and correlated with their symptoms.

Results

The most common presentation was sneezing (96%). The majority were found to be sensitized to more than one set of allergens. The most common allergen was found to be house dust mite (D. Farinae 58%, D. pteronyssinus 54%, Blomia 48%), followed by Parthenium (38%) and Cockroach (32%).

Conclusion

Our results explore the clinical profile of allergic rhinitis patients and its correlation with skin prick tests. The most common aero-allergen found was house dust mite.
Surgical explantation of an infected Lotus Edge valve: a case report
Authors: Yanagino Yusuke , Kainuma Satoshi , Kawamoto Naonori , Tadokoro Naoki , Kakuta Takashi , Ikuta Ayumi , Tonai Kohei , Fujita Tomoyuki , Fukushima Satsuki
Published: December 2024

Background

With the rapid expansion of transcatheter aortic valve replacement (TAVR), TAVR valve explantation is also increasing. Nevertheless, previous reports on Lotus Edge valve explantation are limited to only two reports, none of which include intraoperative videos. Therefore, we report the case of an older adult who underwent a 2-year-old Lotus Edge valve explantation, after developing prosthetic valve endocarditis (PVE) and aortic annular abscess, with a strong indication for a TAVR explantation and surgical aortic valve replacement (AVR).

Case presentation

An 85-year-old male patient, who underwent TAVR with a 25-mm Lotus Edge valve for severe aortic stenosis 2 years ago, was referred to our hospital. He presented with a 1-month history of high-grade fever, refractory to oral antimicrobials and trifascicular heart block. Two sets of blood cultures were positive for Streptococcus dysgalactiae subspecies equisimilis, and transesophageal echocardiography revealed vegetation on the valve leaflets. Enhanced computed tomography scan showed thickening and enhancement of the aortic root and aorto-mitral continuity, with a small low-density area. Therefore, we diagnosed PVE. Subsequently, we planned AVR re-intervention and pacemaker implantation. The vegetation mass was attached to the aortic valve leaflet. We attempted to explant the valve while deforming it using forceps. The areas with abscess formation were easily dissected; however, the other areas were difficult to separate. Cold-saline irrigation softened the nitinol stent and enabled to dissect the prosthetic valve from the aortic wall. The infected aortic annulus was irrigated and then repaired. AVR using a 21-mm Avalus bioprosthetic valve and epicardial pacemaker lead implantation were simultaneously performed. Postoperative echocardiography confirmed that the prosthetic valve function was favorable, and the patient was transferred to a rehabilitation hospital after 6 weeks of intravenous antimicrobial therapy.

Conclusion

The Lotus Edge valve is difficult to remove due to its fixation after deployment and strong adhesion, but the use of cold water may be effective in facilitating its removal.
Valve-sparing procedure for acute aortic regurgitation due to intimal intussusception in a minimally localized aortic root dissection
Authors: Matsushiro Takuya , Tamura Tomoki , Ishiwaki Daiki , Umibe Takumi , Inoue Nobuyuki
Published: December 2024

Background

Acute heart failure due to aortic regurgitation (AR) is a severe comorbidity of type A acute aortic dissection (AAD). Valve-sparing aortic root replacement is typically performed when the aortic valve remains intact.

Case presentation

A 33-year-old male presented to our hospital with chest pain. Initial computed tomography (CT) scans did not clearly identify an aortic dissection. However, subsequent evaluations suggested acute coronary syndrome. Catheter angiography revealed difficulties in catheterizing the coronary arteries, and echocardiography detected aortic insufficiency. Electrocardiogram-gated CT angiography ultimately confirmed a localized aortic root dissection, necessitating urgent surgical intervention. The patient underwent valve reimplantation to preserve the aortic valve. The postoperative course was uneventful, with follow-up echocardiography and CT showing no residual dissection or regurgitation.

Conclusion

This report highlights a case of acute aortic root dissection resulting in acute AR. The primary cause of AR in this case was the intussusception of the disrupted aortic intima. The dissection was confined solely to the aortic root. The patient underwent successful valve reimplantation, with no postoperative complications. Electrocardiogram-gated CT angiography and transesophageal echocardiography proved valuable in identifying localized aortic abnormalities with precision.
Surgical management of a huge mediastinal mature teratoma in a 2-year-old girl: a case report
Authors: Matsui Yusuke , Shiono Satoshi , Mizumoto Masahiro , Nakamura Megumi , Suzuki Jun , Watanabe Hikaru , Uchida Tetsuro
Published: December 2024

Background

Mature teratomas are benign cystic tumors that are most commonly asymptomatic. However, in some cases, mediastinal teratomas rupture the lungs and mediastinum with potentially fatal outcomes. Herein, we report a case of a large mediastinal mature teratoma that expanded to the entire left hemithorax in a child with common cold-like symptoms.

Case presentation.

A 2-year-7-month old girl visited a family doctor because of cough and rhinorrhea. Chest radiography revealed a large tumor occupying the left hemithorax, necessitating transfer to our institution. Chest computed tomography (CT) revealed a large tumor with calcifications and an encapsulated surface. The lesion was 10.5 cm in size and covered the entire left hemithorax, deviating significantly from the heart. CT suggested a mature mediastinal teratoma. Considering the risk of tumor dissemination, we did not perform a diagnostic biopsy; however, surgery was performed as an oncological emergency. As ventilation and circulation were difficult to maintain during the surgery, extracorporeal membrane oxygenation was performed. During surgery, although the large tumor tightly adhered to the sternum and innominate vein, it could be safely removed from these structures, and the tumor was completely removed through median sternotomy. The pathological diagnosis revealed a benign mature mediastinal teratoma. The patient’s postoperative course was uneventful.

Conclusion

As the clinical course of child-specific problems in mature teratomas tends to be severe, a surgical strategy should be meticulously planned to ensure safety.
Building Communities of Practice among Undergraduate STEM Departments to Foster Emergent Transformation: A Report on the Impact of Multiple-year Engagement within the PULSE Midwest and Great Plains Regional Network
Authors: Allen Taylor , Arriola Paul E. , Breitenberger Caroline , Klyczek Karen , Marrs Kathleen A. , Matzner Steven , Miller Kathryn G. , Powell-Coffman Jo Anne , Thatcher Mikayla
Published: December 2024

We describe and evaluate via mixed methods an effective community of practice focused on transforming undergraduate biology programs' organizational practices, behaviors, and beliefs. The approach drew on Community of Practice, Participatory Organizational Change, and Organizational Justice change theories.
Alone and Together: Exploring the Relationship Between Individual and Social Metacognition in College Biology Students During Problem Solving
Authors: Bremers Emily K. , McKay Olive K. , Stanton Julie Dangremond
Published: December 2024

This qualitative study of metacognition in upper-level biology undergraduates used in-the-moment data to reveal complexity in the relationship between students's individual and social metacognition while problem solving. Interestingly, students more readily corrected and evaluated their group members' ideas compared to their own ideas.
Implementation Strategy for Artificial Intelligence in Radiotherapy: Can Implementation Science Help?
Authors: Swart Rachelle , Boersma Liesbeth , Fijten Rianne , van Elmpt Wouter , Cremers Paul , Jacobs Maria J.G.
Published: December 2024

PURPOSE

Artificial intelligence (AI) applications in radiotherapy (RT) are expected to save time and improve quality, but implementation remains limited. Therefore, we used implementation science to develop a format for designing an implementation strategy for AI. This study aimed to (1) apply this format to develop an AI implementation strategy for our center; (2) identify insights gained to enhance AI implementation using this format; and (3) assess the feasibility and acceptability of this format to design a center-specific implementation strategy for departments aiming to implement AI.

METHODS

We created an AI-implementation strategy for our own center using implementation science methods. This included a stakeholder analysis, literature review, and interviews to identify facilitators and barriers, and designed strategies to overcome the barriers. These methods were subsequently used in a workshop with teams from seven Dutch RT centers to develop their own AI-implementation plans. The applicability, appropriateness, and feasibility were evaluated by the workshop participants, and relevant insights for AI implementation were summarized.

RESULTS

The stakeholder analysis identified internal (physicians, physicists, RT technicians, information technology, and education) and external (patients and representatives) stakeholders. Barriers and facilitators included concerns about opacity, privacy, data quality, legal aspects, knowledge, trust, stakeholder involvement, ethics, and multidisciplinary collaboration, all integrated into our implementation strategy. The workshop evaluation showed high acceptability (18 participants [90%]), appropriateness (17 participants [85%]), and feasibility (15 participants [75%]) of the implementation strategy. Sixteen participants fully agreed with the format.

CONCLUSION

Our study highlights the need for a collaborative approach to implement AI in RT. We designed a strategy to overcome organizational challenges, improve AI integration, and enhance patient care. Workshop feedback indicates the proposed methods are useful for multiple RT centers. Insights gained by applying the methods highlight the importance of multidisciplinary collaboration in the development and implementation of AI.
Prospective Observational Study on Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer in Rwanda: Acute Toxicity in Patients
Authors: Sinzabakira Felix , Heemsbergen W.D. , Mugenzi Pacifique , Ndoli A. Diane , Maniragaba Theoneste , Umubyeyi Claire , Rubagumya Fidel , Mutabazi Emmanuel , Incrocci Luca
Published: December 2024

PURPOSE

Moderate hypofractionation (MHF) offers logistical and financial advantages, and has become standard in Western countries but not yet in Africa. This study assessed GI and genitourinary (GU) acute toxicity in Rwandan men undergoing MHF (20 × 3 Gy) treatment.

MATERIALS AND METHODS

Since 2021, patients with prostate cancer at the Rwanda Cancer Centre have been informed about the study on MHF treatment and could participate by signing an informed consent. The study included patients with confirmed prostate adenocarcinoma (any T, any prostate-specific antigen any Gleason score, N0M0), excluding those with inflammatory bowel disease, previous pelvic irradiation, or previous prostatectomy. Participants received 20 fractions of 3 Gy over 4 weeks using the volumetric modulated arc radiotherapy (RT) technique with a 6 megavoltage linear accelerator. GI and GU acute toxicity was evaluated at week 2, at the end of RT, and 3 months after treatment using the Radiation Therapy Oncology Group (RTOG) acute toxicity grading system.

RESULTS

Fifty consecutive patients with localized prostate cancer were included. The median patient age was 70 years. Most patients (86%) had high-risk disease and 94% received androgen-deprivation therapy. The cost and treatment time were reduced by 50%. The distribution of maximum acute RTOG toxicity scores were for GI 10% grade 0, 70% grade 1, 20% grade 2, 0% grade 3, and for GU scores were 0%, 40%, 54%, and 6%, respectively. By 3 months, RT symptoms had returned to baseline levels for most patients.

CONCLUSION

MHF (20 × 3 Gy) was well tolerated in men treated for prostate cancer in Rwanda, showing that MHF is feasible in an African setting. However, further research on acute and late toxicity for more patients is warranted.
Cell-Based Assays to Detect Innate Immune Response Modulating Impurities: Application to Biosimilar Insulin
Authors: Her Cheng , Thacker Seth , Balsamo Joseph , Kelley Baker Logan , Ireland Derek DC , Pang Eric , Verthelyi Daniela
Published: December 2024

Characterizing and mitigating factors that impact product immunogenicity can aid in risk assessment and/or managing risk following manufacturing changes. For follow-on products that have the same indication, patient population, and active product ingredient, the residual immunogenicity risk resides predominantly on differences in product and process related impurities. Characterizing differences in innate immune modulating impurities (IIRMI), which could act as adjuvants by activating local antigen presenting cells (APCs), can inform the immunogenicity risk assessment potentially reducing the need for clinical trials. To date, assays to detect trace levels of IIRMI are being used to support regulatory decisions by FDA for selected synthetic peptide drug products that refer to reference listed drugs of rDNA origin but not recombinant protein or peptide products where more complex mixtures of trace impurities including host cell proteins are expected. Here we describe an exercise to explore whether or not there are differences in the innate immune response elicited by an insulin glargine (produced in E. coli) and its interchangeable biosimilar insulin (produced in P. pastoris) that could indicate differences in IIRMI. Our results suggest the two products elicit comparable innate immune responses as determined by the expression of 90 immune-related genes, including IL-1α, IL-1β, IL-6, CCL3, CCL2, and CXCL8. The data suggest that these assays can provide useful information when assessing recombinant proteins for the presence of IIRMI.

Graphical Abstract
Introduction
Authors: Celermajer Danielle , Otjen Nathaniel
Published: December 2024

Narratives form one dimension of the institutional ecology that shapes what can happen for different types of beings, the modes of relationships available to them, and the possibilities of their lives. This introduction considers the limitations and possibilities that narrative poses for multispecies justice. It sets out four ways in which narrative strategies impede multispecies justice, by (1) presenting (certain) humans as the sole subjects of justice; (2) naturalizing the association between putatively exclusive human capacities and being a subject of justice; (3) normalizing the background conditions that produce humans as the privileged subjects of justice; and (4) positioning humans as the sole agents capable of producing story. It then considers three ways that narrative might help theorize and develop multispecies justice, by (1) imagining, depicting, and evoking the lives of more-than-human others; (2) recognizing storytelling itself as a more-than-human practice; and (3) elaborating the narrative form as a multispecies practice unfolding through more-than-human relationships.
“By Eel's Verve”
Authors: Dunn Kirsty
Published: December 2024

This essay elucidates how the experiences of the tuna (eels) endemic to Aotearoa, New Zealand, and the many ways they have been represented in narrative form exemplify the dynamism of whakapapa (origins, relationships, genealogical knowledge, and layer-making) in Te Ao Māori (the Māori world). Tuna are at once treasured whanaunga (relations), valued sources of sustenance, indicators of the health of the country's waterways, mysterious boundary-breakers, and slippery subjects who often feature in Māori art and literature. Considering tuna and their lifeways can provide multiple ara (passageways or routes) for critically reflecting on their multispecies relations and on how those relations may be made more just. Through the discussion of ancestral narrative, as well as poetry, prose, and visual artworks that center the perspectives and characteristics of tuna, the essay explores the ways Māori worldviews, knowledges, and te reo Māori (the Māori language) draw to, from, and with tuna and help us as Māori understand and maintain our relationships with, and obligations to all our other-thanhuman relations. In doing so, the essay gestures to the ways in which wider multispecies justice initiatives might find alignments within these representations and relationships too