bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies for genetic manipulation of the halotolerant black yeast
Hortaea werneckii
: ectopic DNA integration and marker-free CRISPR/Cas9 transformation
Authors: Hernandez-Rodriguez Yainitza , Bullard A. Makenzie , Busch Rebecca J. , Marshall Aidan , Vargas-Muñiz José M.
Published: December 2024

Hortaea werneckii
is a halotolerant black yeast commonly found in hypersaline environments. This yeast is also the causative agent of tinea nigra, a superficial mycosis of the palm of the hand and soles of the feet of humans. In addition to their remarkable halotolerance, this black yeast exhibits an unconventional cell division cycle, alternating between fission and budding cell division. Cell density and the salt concentration in their environment regulate which cell division cycle
H. werneckii
uses. Although
H. werneckii
have been extensively studied due to their unique physiology and cell biology, deciphering the underlying mechanisms behind these remarkable phenotypes has been limited due to the lack of genetic tools available. Here, we report a new ectopic integration protocol for
H. werneckii
using polyethylene glycol-CaCl
2
mediated protoplast transformation. This approach relies on a drug (hygromycin B) resistance gene to select for successful integration of the genetic construct. The same construct was used to express cytosolic green fluorescent protein. Finally, we developed a marker-free CRISPR/Cas9 protocol for targeted gene deletion using the melanin synthesis pathway as a visual reporter of successful transformation. These transformation strategies will allow testing hypotheses related to
H. werneckii
cell biology and physiology.

IMPORTANCE

Hortaea werneckii
is a remarkable yeast capable of growing in high salt concentration, and its cell division cycle alternates between fission-like and budding. For these unique attributes,
H. werneckii
has gathered interest in research programs studying extremophile fungi and cell division. Most of our understanding of
H. werneckii
biology comes from genomic analyses, the usage of drugs to target a particular pathway, or the heterologous expression of its genes in
S. cerevisiae
. Nonetheless,
H. werneckii
has remained genetically intractable. Here, we report on two strategies to transform
H. werneckii
: ectopic integration of a plasmid and gene deletion using CRISPR/Cas9. These approaches will be fundamental to expanding the experimental techniques available to study
H. werneckii
, including live-cell imaging of cellular processes and reverse genetic approaches.
Comparison of clinical outcomes between different combinations of hybrid multifocal, extended-depth-of-focus and enhanced monofocal intraocular lenses
Authors: Kim Bokyung , Son Hyeck-Soo , Khoramnia Ramin , Auffarth Gerd U , Choi Chul Young
Published: December 2024

Purpose

To compare clinical outcomes of bilateral implantation of hybrid multifocal intraocular lenses (IOLs) versus mix-and-match implantation of hybrid multifocal and extended-depth-of-focus (EDOF) versus mix-and-match implantation of hybrid multifocal and enhanced monofocal IOLs.

Methods

Patients with bilateral age-related cataract were randomised in one of three groups: group 1, bilateral hybrid multifocal IOL; group 2, EDOF in the dominant eye, hybrid multifocal in the non-dominant eye; group 3, enhanced monofocal in the dominant eye, hybrid multifocal in the non-dominant eye. Assessments at 6 months postoperatively included monocular and binocular uncorrected distance visual acuity (UDVA), intermediate (UIVA) and near distance (UNVA) at 40 and 33 cm, defocus curves, contrast sensitivity (CS), reading speed and questionnaires on quality of vision and dysphotopsia.

Results

75 patients (25 per group) were enrolled. There were no statistically significant differences in binocular UDVA and UNVA between groups (p>0.05); binocular UIVA was better for group 1 and 2 versus group 3 (p=0.030). Binocular uncorrected defocus curve showed better performance for group 1 compared with group 3 from −2.00 to −3.50 D. Significantly higher reading speed was measured for Jaeger 1 font in group 1. There were no differences in CS between groups, but higher incidence of starbursts in group 1 and higher need for near spectacles in group 3.

Conclusion

Bilateral hybrid multifocal IOL implantation resulted in better near vision, but higher rates of photic phenomena compared with the mix-and-match groups. Combinations of IOLs may allow surgeons to fine-tune for individual patient’s needs.
Sex differences in the intention and decision to use emergency medical services for acute coronary syndrome in Australia: a retrospective study
Authors: Eastwood Kathryn J , Shi Annie , Howell Stuart , Buttery Amanda , Bray Janet E
Published: December 2024

Background

Sex-based disparities in acute coronary syndrome (ACS) presentations exist and women often have worse outcomes after an ACS event. Calling the emergency medical services (EMS) initiates prehospital diagnosis and treatment and reduces in-hospital time to treatment. This study aims to identify factors affecting the intention to call EMS and EMS usage in Australian women and men.

Methods

A retrospective cross-sectional analysis was conducted to identify sex differences and associated characteristics in the (1) intention to call EMS and (2) EMS use in the setting of ACS. Data sources included national survey data (2018–2020) and the Victorian Emergency Minimum Dataset (2016–2021). Multivariable analysis identified factors associated with intention and EMS use by sex.

Results

Of 34 328 survey participants, fewer men expressed an intention to call EMS if experiencing ACS symptoms than women (62.7% vs 70.4%, p<0.001). Associated factors in men included being of Aboriginal or Torres Strait Islander origin, living in Western Australia, having diabetes or having a lower education level. In both sexes, preferring a non-English language, having cardiovascular risk factors, poor symptom knowledge, living in the Northern territory or no/unclear EMS insurance status were associated with lower intentions to call EMS. Finally, women were less comfortable with calling EMS and more likely to hesitate (69.1 vs 76.7%, p<0.001).

Among 51 165 ACS presentations (33.6% women) to Victorian public hospitals, fewer men presented by EMS (62.5% vs 67.7%, p<0.001), however, no associated male-specific characteristics were identified. Women preferring a non-English language or living in outer regional/remote Victoria were less likely to use EMS. Being born overseas or being referral by a healthcare provider was associated with lower EMS use in both sexes.

Conclusion

Sex differences were identified in the intention and use of EMS during an ACS event based on cultural background, preferred language and residential regionality. These subgroups’ characteristics can be targeted with education to improve EMS use.
Neuropathy with anti-myelin-associated glycoprotein antibodies: update on diagnosis, pathophysiology and management
Authors: Min Young Gi , Visentin Andrea , Briani Chiara , Rajabally Yusuf A
Published: December 2024

Antimyelin-associated glycoprotein (MAG) neuropathy is a rare autoimmune demyelinating peripheral neuropathy caused by IgM autoantibodies targeting MAG. The typical presentation is that of a slowly progressive, distal, length-dependent, predominantly sensory, sometimes ataxic neuropathy, frequently accompanied by upper limb tremor. Distal motor weakness may subsequently occur. The clinical presentation may vary and rarely be consistent with that of typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as well as have an aggressive and rapidly disabling course. The diagnosis of anti-MAG neuropathy is based on the detection of anti-MAG antibodies through ELISA or western blot analysis, primarily in presence of an IgM monoclonal gammopathy. Anti-MAG neuropathy may occur without or with haematological malignancy. Electrophysiology is characteristic of a predominantly distal demyelinating neuropathy. Intravenous immunoglobulins and plasma exchange have unproven benefits, but may provide short-term effects. Cytotoxic therapies are commonly used, although without an evidence base. Rituximab, an anti-B-cell monoclonal antibody was studied in two randomised controlled trials, neither of which achieved their primary outcome. However, a meta-analysis of these two studies demonstrated improvement of disability at 8–12 months. A recent trial with lenalidomide was interrupted prematurely due to a high rate of venous thromboembolism. There are currently two ongoing trials with Bruton’s tyrosine kinase inhibitors. Symptom control is otherwise frequently needed. Outcome measures used for other inflammatory neuropathies present limitations in anti-MAG neuropathy. International registries such as the planned IMAGiNe study may, in future, provide answers to the many remaining questions.
Health Monitoring Technology for Hydraulic Engineering Gates Based on Multi-Sensor Data Fusion
Authors: Ma Xiaoyan , Yang Runxian , Tao Tao , Zhou Feng , Wang Yong , Wang Jun
Published: December 2024

An essential part of the hydraulic engineering systems, hydraulic gates regulate water flow in dams and other structures. To avoid structural problems, they must ensured to be consistent. Multi-sensor data fusion has become a key tool for health monitoring with advances in machine learning (ML) and sensor technologies. This study aims to provide a novel multi-sensor data fusion health monitoring system for hydraulic engineering gates. To provide more effective and precise real-time monitoring of hydraulic engineering gates, a unique Dynamic Satin Bowerbird search-driven Bidirectional Long Short-Term Memory (DSB-BiLSTM) model were proposed. The hydraulic monitoring dataset was collected from Kaggle website, comprising information and some attributes obtained from hydraulic engineering gates. To improve data quality, noise reduction, and data normalization are used. Time-series analysis techniques extract important information such as vibration patterns and pressure variations. The DSB-BiLSTM model leverages bidirectional LSTM to progress time-dependent data, and the Satin Bowerbird search optimizes sensor selection. The method shows better accuracy and efficiency in identifying potential faults compared to traditional models. When compared to four attributes such as pump, cooling, valve and accumulator with the metrics outcomes of 0.9901, 0.9925, 0.9950, and 0.9890 in accuracy, 0.9930, 0.9960, 0.9902, and 0.9889 in precision, 0.9920, 0.9960, 0.9911, and 0.9890 in recall, and 0.9915, 0.9955, 0.9905, and 0.9889 in F1-score, the DSB-BiLSTM model performs better than all other approaches that were examined. This suggests better overall hydraulic engineering gate health monitoring performance. The proposed DSB-BiLSTM model is a show potential solution for real-time health monitoring of hydraulic gates, provided that it enhances accuracy and reduces computational complexity.
A Quality Prediction Method for Optimizing the Teaching Mode of History Courses Based on Multi-Category Data Fusion Analysis
Authors: Na Wang
Published: December 2024

In the process of predicting the optimization quality of teaching mode, a single convolutional neural network method is affected by multiple sources of data such as students’ behavioral data and teachers’ evaluations, which is prone to causing modal collapse and affecting the prediction quality. For this reason, we propose a method for predicting the optimization quality of history course teaching mode based on the fusion analysis of multi-class data. After collecting the data of optimizing the quality of teaching mode of historical courses, noise reduction is carried out by the noise reduction self-coder network on the data collection, and the combination of historical data and current data is realized by the dynamic slicing method of multi-feature matrix, after fusing the multi-category data, the data are inputted into the convolutional neural network, and an optimized multi-objective genetic algorithm optimizes the convolutional neural network, stabilizes the convolutional neural network model, and avoids the modal collapse caused by multi-source attributes and categories of the data. The optimized convolutional neural network is used to extract the deep features of the optimized quality of history course teaching mode, and the obtained features are input into the multiple linear regression model as independent variables to obtain the predicted scores of the optimized quality of history course teaching mode. Through experimental verification, the method can realize in-depth cleaning and denoising of the data of each feature of history curriculum teaching mode, and there is a large correlation between the features related to the optimization quality of the five history curriculum teaching modes collected by the method and the final score of the optimization quality of the history curriculum teaching modes, the method predicts that the optimization quality of the history curriculum teaching modes scores and the scores of the expert evaluation are basically consistent.
A Catalog of Data Smells for Coding Tasks
Authors: Vitale Antonio , Oliveto Rocco , Scalabrino Simone
Published: December 2024

Large Language Models (LLMs) are increasingly becoming fundamental in supporting software developers in coding tasks. The massive datasets used for training LLMs are often collected automatically, leading to the introduction of data smells. Previous work addressed this issue by using quality filters to handle some specific smells. Still, the literature lacks a systematic catalog of the data smells for coding tasks currently known. This paper presents a Systematic Literature Review (SLR) focused on articles that introduce LLMs for coding tasks. We first extracted the quality filters adopted for training and testing such LLMs, inferred the root problem behind their adoption (data smells for coding tasks), and defined a taxonomy of such smells. Our results highlight discrepancies in the adoption of quality filters between pre-training and fine-tuning stages and across different coding tasks, shedding light on areas for improvement in LLM-based software development support.
Innovative Integration of Q-learning in BSO Algorithm for Adaptive Community Detection in Social Networks
Authors: BELDI ZOHRA , Bessedik Malika
Published: December 2024

Community detection in social networks remains a challenging yet crucial task in social network analysis, offering insights into the underlying structures and dynamics of social systems. This study introduces QB-COM, a novel integration of reinforcement learning using Q-learning with Brain Storm Optimization algorithm (BSO), tailored for effective community detection. The proposed approach’s design is distinguished by its utilization of diverse data sources, including the network structure, evolving knowledge from BSO, and Q-learning intelligence, all intended to enhance solution generation and guide the search process adeptly. A thorough comparative analysis is carried out to assess the effectiveness of our algorithm, covering a range of meta-heuristics and heuristics used in community detection. This analysis utilizes diverse real-world networks and evaluation techniques. The results demonstrate QB-COM’s superior performance in accurately identifying true community structures within social networks.
Comparing Large Language Model and Human Reader Accuracy with New England Journal of Medicine Image Challenge Case Image Inputs
Authors: Suh Pae Sun , Shim Woo Hyun , Suh Chong Hyun , Heo Hwon , Park Kye Jin , Kim Pyeong Hwa , Choi Se Jin , Ahn Yura , Park Sohee , Park Ho Young , Oh Na Eun , Han Min Woo , Cho Sung Tan , Woo Chang-Yun , Park Hyungjun
Published: December 2024

Large language models accurately answered New England Journal of Medicine Image Challenge cases using radiologic inputs, outperforming a medical student; however, their accuracy decreased with shorter text lengths, regardless of image inputs.
Visualising the Effect of Areal Current Density on the Performance and Degradation of Lithium Sulfur Batteries Using Operando Optical Microscopy
Authors: Owen Rhodri E. , Du Wenjia , Millichamp Jason , Shearing Paul R. , Brett Dan J. L. , Robinson James B.
Published: December 2024

The degradation of lithium sulfur (Li-S) batteries poses significant challenges to their commercial viability and occurs largely due to the complex electrochemical reactions and structural transformations that take place during charge-discharge cycles. This study employs optical microscopy techniques to investigate and quantify the degradation mechanisms in Li-S batteries. By capturing high-resolution, time-lapsed images of both electrodes and the electrolyte-filled interelectrode space, key morphological changes can be identified and analysed, such as the formation and growth of lithium dendrites, sulfur dissolution, and electrode-electrolyte interface degradation. Quantitative image analysis is conducted to measure the extent of these changes, providing insights into their impact on battery performance. Our findings reveal critical correlations between specific morphological features and electrochemical inefficiencies, contributing to a deeper understanding of the degradation pathways in Li-S batteries. This optical microscopy approach offers a non-destructive, cost-effective, real-time method to monitor battery health, potentially guiding the development of more durable and efficient Li-S batteries.
Engineering Testing Protocols for Machine Learning-Based SoH Estimation in Lithium Metal Batteries
Authors: Ma Wenting , Ha Sara , Pozzato Gabriele , Saatchi Alireza , Aliahmad Nojan , Littau Karl , Onori Simona
Published: December 2024

Lithium metal batteries (LMB) represent one of the most promising battery technologies due to their high energy density. However, the commercial adoption of LMBs has been hindered by their limited lifespan and safety concerns resulting from lithium metal's high electrochemical reactivity. Effective health estimation could enable optimized LMB operation to improve utilization efficiency and reduce failure risks, as well as accelerate LMB development iteration. In this work, we first propose novel diagnostic tests and aging cycling protocols that enable the tracking of LMB degradation from voltage-current measurements through extracting internal resistance, relaxation voltage statistics, and charging impedance descriptors. We present an integrated data-driven health estimation framework for LMBs, using Bagged Gaussian Process Regression (Bagged-GPR). Validation over test cells demonstrates accurate health tracking performance throughout LMB lifetime using one cycle of voltage-current data. The proposed model provides degradation insights for LMBs without the need for additional internal sensors.
Unveiling the Uncommon: A Case Report of Horner’s Syndrome as a Rare Glimpse Into Giant Cell Arteritis
Authors: Barr Emily , Levesque Justine , Badir John , Dunston Randall , Ranasinghe Tamra
Published: December 2024

Giant cell arteritis (GCA) is an inflammatory vasculitis affecting large and medium‐sized arteries, leading to complications such as arterial dissection, blindness, and stroke. Rarely, GCA presents with Horner’s syndrome due to sympathetic neuron involvement from arterial inflammation. This case report discusses an 82‐year‐old female with hypertension, atrial fibrillation, and arthritis who presented with a 24 h history of right eye ptosis, blurred vision, dizziness, and aching eye pain. She had a mild headache and tenderness over the right temporomandibular joint but no temporal artery tenderness. Examination revealed right eye ptosis and miosis, indicative of Horner’s syndrome, with no other neurological deficits. Lab results showed elevated ESR (68 mm/h) and CRP (16 mg/L). MRI with contrast revealed mild to moderate stenosis and enhancement in bilateral MCAs and basilar artery with inflammation in the right distal extracranial ICA, suggesting an inflammatory process. The patient was started on prednisone 40 mg daily. A temporal artery biopsy confirmed GCA with characteristic histopathological findings. Her prednisone dosage was increased to 60 mg/day, and she was started on tocilizumab. This case underscores the need to consider GCA in patients with Horner’s syndrome and the importance of vessel wall imaging, as early corticosteroid treatment can prevent complications like vision loss and stroke.
Semaglutide Inducing Resolution of Proliferative Diabetic Retinopathy: A Case Report
Authors: Cool Daniel , Coventon James , Sharma Abhishek
Published: December 2024

Purpose: To describe a case of regression of proliferative diabetic retinopathy (PDR) following treatment with semaglutide.

Methods: Case report.

Results: The case describes a 47‐year‐old woman with Type 2 diabetes, obesity, hypertension, and dyslipidaemia who had difficulty controlling her blood sugar levels despite oral hypoglycaemic medications. She presented with PDR in her right eye and severe nonproliferative diabetic retinopathy (NPDR) in her left eye. After missing her follow‐up appointment for panretinal photocoagulation (PRP), her general practitioner initiated semaglutide therapy. Despite minimal changes in glycaemic control, the patient exhibited resolution of neovascularisation in her right eye and improved diabetic macular oedema (DMO) within 6 weeks of semaglutide therapy.

Conclusion: This case report suggests a potential independent role for semaglutide in managing PDR.
Characteristics of Children, Youth, and Young Adults With Diabetes: A Cross‐Sectional Study in New Zealand Aotearoa
Authors: Mustafa Sara , Paul Ryan , Keenan Rawiri , Magliano Dianna , Chepulis Lynne
Published: December 2024

Background: The prevalence of diabetes mellitus among children, youth, and young adults is increasing, yet limited information is known about the characteristics and management of these groups with Type 1 (T1D) and Type 2 (T2D) diabetes in primary care. The aim of the study is to explore the characteristics of people with T1D and T2D aged < 25 years across the Auckland and Waikato regions of New Zealand.

Methods: Sociodemographic and clinical data were collected from electronic primary care records (February 2021–July 2022) of four primary healthcare organisations, with medication data sourced from the National Pharmaceutical dataset. Associations between sociodemographic and clinical data were conducted using chi‐square and nonparametric ANOVA.

Results: Of 1198 patients, 72% had T1D and 28% had T2D. People with T1D were evenly distributed by gender but more commonly of European descent (66.7%) compared to other ethnic groups. A higher proportion of T2D was observed in females (58.2%) compared to males (41.6%) and among Māori (38.2% vs. 20.3% European; p < 0.001). Over 95% of individuals with T2D were overweight/obese. Overall, 9.5% and 23.9% of individuals with T1D and T2D, respectively, were at target for HbA1c, though median HbA1c was higher for Māori and Pasifika compared to other ethnicities (p < 0.001). In T1D, 94.7% of individuals were dispensed insulin and 7.5% and 4.4% were dispensed angiotensin‐converting enzyme (ACE) inhibitors and statins, respectively. In T2D, medication use included metformin (84.9%), insulin (76.1%), and SGLT2i/GLP1RA (59.5%).

Conclusions: The increasing burden of diabetes among young individuals in New Zealand underscores the urgent need for comprehensive strategies to address obesity and socioeconomic disparities, especially among marginalised communities. Addressing socioeconomic factors such as affordable housing, living wages, and healthcare access may be important for improving diabetes outcomes, as these factors significantly influence overall childhood health and well‐being.
Association between Locoregional Failure and NFE2L2/KEAP1/CUL3 Mutations in NRG/RTOG 9512: A Randomized Trial of Radiation Fractionation in T2N0 Glottic Cancer
Authors: Guan Li , Torres-Saavedra Pedro A. , Zhao Xiaobei , Major Michael B. , Holmes Brittany J. , Nguyen Ngan K. , Kumaravelu Parasakthy , Hodge Tim , Diehn Maximilian , Zevallos Jose , Holsinger F. Christopher , Emami Bahman , Jordan Richard C. , Hayward Michele C. , Sagar Stephen M. , Morrison William , Schultz Christopher , Caudell Jimmy J. , Jones Christopher U. , Bratman Scott V. , Galloway Thomas J. , Ma Daniel J. , Yom Sue S. , Kudrimoti Mahesh , Kim Harold E. , Harris Jonathan , Le Quynh-Thu , Hayes D. Neil
Published: December 2024

Purpose:

NFE2L2/KEAP1/CUL3 mutations have been validated for radioresistance in cell-based assays and animal models. However, clinical validation of these biomarkers has been challenging because of multimodality treatment regimens. This study aims to investigate the association between NFE2L2/KEAP1/CUL3 mutations and patient outcomes, including local failure, locoregional failure, disease-free survival (DFS), and overall survival, using samples from a phase III trial in which patients were treated with radiation monotherapy at two controlled doses.

Patients and Methods:

We investigated NFE2L2/KEAP1/CUL3 mutations in 250 randomized patients with T2N0 glottic squamous cell carcinoma receiving definitive radiotherapy in the NRG/RTOG 9512 trial. A total of 119 patients had available biospecimens that were subjected to amplicon-based next-generation sequencing to assess for the presence of NFE2L2/KEAP1/CUL3 mutations without regard to outcomes. Mutations in NFE2L2/KEAP1/CUL3 were assessed blinded to clinical outcomes. Cox models (two-sided α = 0.05) were used to evaluate the association with clinical outcomes, performed by an independent statistical team.

Results:

Nineteen of 119 patients (16.0%) had NFE2L2/KEAP1/CUL3 mutations. Patient, treatment, and tumor characteristics were similar between those with and without mutations. Patients with mutation compared with those without had significantly more local failure [HR = 3.50; 95% confidence interval (CI), 1.56–7.89; P = 0.0025] and locoregional failure (HR = 3.80; 95% CI, 1.80–8.03; P = 0.0005). DFS was significantly worse for the mutated compared with the nonmutated group in the first 2 years (HR = 2.88; 95% CI, 1.46–5.66; P = 0.0022). The median DFS was shorter in the mutation group (10.3 months) versus those with intact NFE2L2/KEAP1/CUL3 (4.2 years).

Conclusions:

NFE2L2/KEAP1/CUL3 mutations may predict radiation treatment failure in T2N0 glottic cancer.
Data from Multiomic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target
Authors: Vanner Robert J. , Dobson Stephanie M. , Gan Olga I. , McLeod Jessica , Schoof Erwin M. , Grandal Ildiko , Wintersinger Jeff A. , Garcia-Prat Laura , Hosseini Mohsen , Xie Stephanie Z. , Jin Liqing , Mbong Nathan , Voisin Veronique , Chan-Seng-Yue Michelle , Kennedy James A. , Waanders Esmé , Morris Quaid , Porse Bo , Chan Steven M. , Guidos Cynthia J. , Danska Jayne S. , Minden Mark D. , Mullighan Charles G. , Dick John E.
Published: December 2024

Abstract
Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease.
Significance:
Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition.

This article is highlighted in the In This Issue feature, p. 1
De triunfo a fiasco: o Monumento à Independência do Brasil nas comemorações do centenário em São Paulo
Authors: Monteiro Michelli Cristine Scapol
Published: December 2024

The Monument to the Independence is one of the largest sculptures in Brazil, located on the banks of the Ipiranga river and idealized to be a central element of the São Paulo celebrations of the centennial of Brazilian emancipation in 1922. The proposal to erect a monument of unprecedented proportions in the country came from the political elite of São Paulo, who intended to use the work to definitively link September 7th to the Ipiranga hill and highlight the city's leading role in the event that had taken place a hundred years earlier. Therefore, the largest international competition ever held in Brazil took place to choose the project that best suited São Paulo's memorialistic intentions. The winners were sculptor Ettore Ximenes and architect Manfredo Manfredi, both of Italian origin. This article is dedicated to analyzing the Monument to the Independence, investigating its conception and construction. The competition is examined, highlighting both the intentions of the promoters of the work and the artistic projects that were awarded and their reception by the São Paulo press. The reasons that led to the victory of Ettore Ximenes and Manfredo Manfredi are identified, as well as the adaptations that the work underwent at the request of the members of the Judging Committee. The construction process of the work is observed, focusing on the adversities faced in its completion, which impacted the centennial celebrations in São Paulo, since the work was unfinished in 1922.
Por uma própria independência: assentos e moradas do Ipiranga aos Jafet
Authors: Cristofi Renato Brancaglione
Published: December 2024

O presente artigo procura compreender a construção da relação representativa entre os Jafet e o Ipiranga. Como ponto de partida, procuramos entender como o lugar de memória do Ipiranga e as comemorações do Primeiro Centenário da Independência foram elencados por aquela família de imigrantes levantinos, entre as possibilidades de inserção social, representação de dignidades e superação de desconfianças. Estratégias engendradas para se colocar “ao lado” das elites políticas locais, por meio de seus símbolos nacionais na cidade, tendo em vista sua presença como industriais no bairro. Observa-se, também, como essa representação foi pautada por ideais de progresso material e honras próprias de uma ética do trabalho, que pudessem simbolizar os sócios da Nami Jafet & Irmãos. Discorre-se sobre um processo contínuo de reinvenção de identidades, pelo qual os Jafet buscaram ser reconhecidos por meio de feitos para com um singular Ipiranga, como um “antes e depois”, portanto, em símbolos próprios. Por fim, analisamos o processo de construção dos Palacetes dos Jafet no bairro, por meio de uma vizinhança coerente e não cindida, entre o Edifício-Monumento e a Fábrica. Da mesma forma, oferecem-se compreensões sobre a historicidade desses palacetes – em seus contextos e momentos de produção – diante das próprias tensões, dos rearranjos políticos e das identidades públicas dos Jafet no Brasil.
Machine Learning–Based Prediction for In‐Hospital Mortality After Acute Intracerebral Hemorrhage Using Real‐World Clinical and Image Data
Authors: Matsumoto Koutarou , Ishihara Kazuaki , Matsuda Katsuhiko , Tokunaga Koki , Yamashiro Shigeo , Soejima Hidehisa , Nakashima Naoki , Kamouchi Masahiro
Published: December 2024

BACKGROUND

Machine learning (ML) techniques are widely employed across various domains to achieve accurate predictions. This study assessed the effectiveness of ML in predicting early mortality risk among patients with acute intracerebral hemorrhage (ICH) in real‐world settings.

METHODS AND RESULTS

ML‐based models were developed to predict in‐hospital mortality in 527 patients with ICH using raw brain imaging data from brain computed tomography and clinical data. The models' performances were evaluated using the area under the receiver operating characteristic curves and calibration plots, comparing them with traditional risk scores such as the ICH score and ICH grading scale. Kaplan–Meier curves were used to examine the post‐ICH survival rates, stratified by ML‐based risk assessment. The net benefit of ML‐based models was evaluated using decision curve analysis. The area under the receiver operating characteristic curves were 0.91 (95% CI, 0.86–0.95) for the ICH score, 0.93 (95% CI, 0.89–0.97) for the ICH grading scale, 0.83 (95% CI, 0.71–0.91) for the ML‐based model fitted with raw image data only, and 0.87 (95% CI, 0.76–0.93) for the ML‐based model fitted using clinical data without specialist expertise. The area under the receiver operating characteristic curve increased significantly to 0.97 (95% CI, 0.94–0.99) when the ML model was fitted using clinical and image data assessed by specialists. All ML‐based models demonstrated good calibration, and the survival rates showed significant differences between risk groups. Decision curve analysis indicated the highest net benefit when utilizing the findings assessed by specialists.

CONCLUSIONS

ML‐based prediction models exhibit satisfactory performance in predicting post‐ICH in‐hospital mortality when utilizing raw imaging data or nonspecialist input. Nevertheless, incorporating specialist expertise notably improves performance.
When a Dispute Exists: the Emerging Evidentiary Practice of the ICJ in Common Interests Proceedings
Authors: Lo Giacco Letizia
Published: December 2024

This contribution considers the practice of determining the existence of a dispute in proceedings before the International Court of Justice and explores the extent to which such assessment varies – or should vary – in relation to the legal interest protected. This question appears increasingly relevant in the context of common interests proceedings before the ICJ, that is, in cases in which the legal standing of the applicant(s) is based on a common interest in the compliance with erga omnes (partes) obligations. Zooming in on the requirements elaborated by the Court’s case law to date, the article argues that diverging theoretical postures – termed dialogic vs. systemic – inform the evidentiary approaches that have so far emerged and that are essentially discretionary. This contribution aims to shed light on how the Court’s evidentiary approach has adjusted to common interests proceedings to stand the test of time, while cautiously preserving the performance of the Court’s judicial function.
Angiotensin-Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) Use are Associated With Increased Readmission After Ileostomy Creation
Authors: Gan Connie Y. , Rahman Shahrose , Flerchinger Shaun R. , Barton Jeffrey S.
Published: December 2024

Background

High output is a common cause for readmission after new ileostomy creation. The loss of sodium leads to compensatory activation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are first-line therapy for hypertension in the United States. We hypothesized that concurrent use of ACEI/ARB increases the risk of readmission following new ileostomy creation due to the loss of this compensatory mechanism.

Methods

Patients undergoing ileostomy creation between 2009-2022 at an integrated managed health care system were included in this retrospective study. Primary outcomes were hospital readmission and ED visit within 30-days. Additional variables included ACEI/ARB use, ileostomy type, Charlson Comorbidity Index, additional antihypertensives at discharge (furosemide, hydrochlorothiazide, spironolactone, amlodipine, nifedipine, and diltiazem), and readmission diagnosis. Descriptive and advanced statistical analysis was completed with SPSS.

Results

Of 540 patients, 41.9% were readmitted or visited an ED within 30 days. There was no difference in readmission or ED visit based on age, gender, or ileostomy type. Patients discharged with ACEI/ARB (37.4% vs 25.5%, P = .005) and additional antihypertensives (37.2% vs 17.3%, P = .006) were at a higher risk for readmission.

Conclusions

Inhibition of RAAS is associated with increased risk for hospital readmission. In patients with hypertension undergoing ileostomy creation, individualized care plans are needed with earlier antimotility agent use or intravenous rehydration plans.
Understanding the current provisions of support for people with an intellectual disabilities and/or autism in crisis: A mixed methods study
Authors: Tromans Samuel , Summers Ian , Abdullah Shahbaz , Ledger Joanne , Lennard Sarah , Bassett Paul , Colledge Remie , Bilkey Danielle , Staples Chloe , Edwards Samuel , Carr Grahame , Laugharne Richard , Shankar Rohit
Published: December 2024

Background:

There has been significant reduction in inpatient beds for people with intellectual disability and/or autism (PwID/A) in the UK in the last decade following high profile national scandals in specialist psychiatric hospitals. To reduce inappropriate admissions a new strategy (Blue-Light, an emergency multi-disciplinary meeting to prevent admission to hospital) was introduced. However, there is no research on the influence of Blue-Light on crisis management for PwID/A.

Aim:

To assess Blue-Light’s impact on PwID/A’s crisis presentations

Methods:

Co-produced with experts-by-experience, a mixed methods approach using a 13 question Likert based survey of health and social-care professionals along with semi-structured interviews of carers involved with consecutive Blue-Light patient reviews was undertaken in Cornwall UK (population: 538,000). Patient data was accessed to understand the patient journey. All data analysis was descriptive in nature. Semi-structured interviews were transcribed and thematically analysed using Braun and Clarke’s six-step process.

Results:

Ten patient journeys were examined. Staff interviewed had a good understanding of the Blue-Light process, Blue-Light activation practical challenges and considered Blue-Light reactive. Nearly half wanted ID/A specialist beds recommissioned. A majority wanted improved supervision and standards for third sector providers. Semi-structured interviews of 10 patient-carers identified a lack of consistency from professionals, limited infrastructure provision, the prolongation of crises and a lack of definition of crisis as carers did not feel supported by services.

Conclusions:

Current crisis support systems are not standardised and often leave carers feeling unsupported in crises. An evidence-based debate of crisis support and the inpatient role for PwID/A is required.
The diverse technical choices during the implantation of the totally implantable venous access ports: A review
Authors: Wu Jingjin , Zhang Li , Jia Xiaojian , Mu Yunchuan , Ding Caiyou , Lou Yanbo
Published: December 2024

Although the implantation of the totally implantable venous access ports globally is increasingly sophisticated, there is still a dearth of absolute standardization in the technical choice of each surgical step, with numerous technologies demonstrating significant applicability. This review comprehensively summarizes the diverse choices of implantation procedural techniques related to the pocket location, vein access, port specification, catheterization method, puncture guidance, single-incision technique, catheter tip positioning method, port fixation, skin closure, and first-use period. The aim is to provide surgeons with alternative options when they encounter different problems in each procedure due to the diverse clinical characteristics of patients during venous port implantation.
Pricing efficiency of European carbon futures market during the COVID-19 pandemic
Authors: Tripathi Abhinava , Vadhava Charu , Jha Ravi Raushan
Published: December 2024

We investigate the effects of the COVID-19 pandemic on the efficiency of the European Union Emission Trading Scheme (EU-ETS). This study provides one of the first accounts of the pricing efficiency of EU-ETS around the final leg of its Phase (III) implementation. The study documents that the EU-ETS futures prices become informationally efficient at extremely short horizons (5–30 minutes) that are comparable to mature conventional markets. These results are robust to three methods, namely, ordinary least squares (OLS) autoregression, quantile autoregression, and variance ratio tests. Moreover, the EU-ETS futures prices impound the information content of economic activity in the major European markets at an extremely fast pace (5–30 minutes). The dynamic correlations obtained from the DCC-GARCH method suggest that the linkages between EU-ETS and economic activity remain intact, even when the effect of the pandemic is most severe. Overall, these results indicate that EU-ETS has substantially attained its stated objectives related to pricing efficiency.

JEL classification: Q51, Q54, G14, G01, G10
Statistical analysis on influence of groove patterns on the mechanical strength of friction-welded SAE1018 steel
Authors: A Pradeep , Rao Vittel , Anusha P. , Naga Swapna Sri M. , M Vignesh , G Anbuchezhiyan
Published: December 2024

This research work focuses on the impact of various groove pattern, groove depth, and their combination on SAE 1018 mild steel rod friction welded mechanical properties. SAE 1018 steel was used, with a modified vertical milling machine with parameters of the Taguchi's L9 Orthogonal array used in the welding process. The groove pattern and groove depth which provides maximum UTS were determined with the help of ‘Minitab 17 software analysis’. The parameters with the best characteristics of measurement system were grooves made on the stationary and rotating specimens, equal to 1.5 mm groove depth, and hash pattern. The initial optimization predicted the UTS to be 542 MPa however the experimental analysis resulted in a value of 564 MPa which is greater than the base material UTS of 436 MPa. It was also observed from ANOVA that the groove on both specimens had the greatest effect on the UTS percent contribution of 58.65% followed by the depth and pattern percent contribution of 20.42% and 13.55% respectively. Hardness analysis pointed to the maximum microhardness value of 300 HV at the weld center and the minimum value of 200 HV at 15 mm from the center. The difference in hardness between the two rotating and the two stationary discs was ascribed to increased frictional and plastic flow on the rotating side. XRD characterization of the samples supported the findings of the presence of both α-Fe and FeO phases for all the samples and MnO was detected primarily in the Z Groove pattern.
An assessment of seven closed system transfer devices in accordance with the 2015 NIOSH vapor containment performance protocol
Authors: Armistead Lori T. , Stepanovic Michael , Earnhart Megan A. , Eckel Stephen F.
Published: December 2024

Introduction

The purpose of this study was to assess and compare the effectiveness of seven different closed system transfer device (CSTD) product lines following the 2015 NIOSH Vapor Containment Performance Protocol, using a Gasmet™ DX5000 Terra multigas FTIR analyzer.

Methods

Seven different CSTD systems were assessed using a two-task evaluation on their capacity to contain the NIOSH-specified challenge agent, 70% isopropyl alcohol (IPA). Task 1 simulated reconstitution and compounding steps while Task 2 simulated compounding and administration steps. Vial adapters, syringe adapters, IV bag adapters, and y-site adapters from each CSTD product line were tested. All tasks were performed in a custom-built environmental test chamber as outlined in the 2015 NIOSH protocol, with isopropyl alcohol (IPA) release detected and measured by a Gasmet™ analyzer.

Results

The BD PhaSeal™ CSTD product line effectively contained IPA vapor during both tasks with a task performance metric of 0.00 ppm for each task. BD PhaSeal™ Optima, Equashield®, Yukon Medical Arisure®, ICU Medical ChemoLock™, BD Texium™, and ICU Medical ChemoClave™ non-vented CSTDs demonstrated detectable and quantifiable IPA leakage during each task. The leaks occurred at different steps within the protocol, and the amount of IPA vapor detected varied.

Conclusion

In this study, one CSTD product line (i.e., PhaSeal™) successfully contained IPA vapor below the Gasmet™ analyzer's limit of quantification (LOQ) for IPA of 0.04 ppm for both Tasks 1 and 2, demonstrating it to be a validated closed system per the study protocol. All other CSTD product lines demonstrated some level of IPA leakage with task performance metrics above the analyzer's LOQ. However, these results tell us little about how well CSTDs contain hazardous drugs (HDs), as a universal HD surrogate for effectively assessing the closedness of all types of CSTDs has yet to be identified.
4-year clinical outcomes of anterior acetabular wall reconstruction and cup revision for treatment of anterior acetabular wall defects with iliopsoas tendinopathy following total hip arthroplasty
Authors: Nogier Alexis , Tourabaly Idriss , Ramos-Pascual Sonia , Debiesse Jean-Louis , Chen Antonia F , Saffarini Mo , Courtin Cyril
Published: December 2024

Purpose:

To assess clinical and radiographic outcomes of anterior acetabular wall reconstruction and cup revision in patients with anterior acetabular wall defects and associated iliopsoas tendinopathy (IPT) following total hip arthroplasty (THA).

Methods:

7 patients with IPT (defined as groin pain that increased with active hip flexion) and pre-revision computed tomography (CT) scans showing anterior acetabular wall defects and cup-iliopsoas impingement were included. During cup revision, an autologous biconvex iliac crest graft was harvested and placed over the anterior acetabular wall defect before press-fitting a revision cup. Cup inclination and anteversion, axial and sagittal cup overhang, and iliopsoas muscle strength (0–5) were evaluated pre- and post-revision. Forgotten joint score (FJS; 0–100), Oxford hip score (OHS; 0–48), hip pain (0–10), satisfaction (0–10), graft osseointegration and resorption were evaluated post-revision.

Results:

Pre-revision cup inclination was 43.7 ± 9.4°, anteversion was 30.4 ± 10.5°, axial overhang was 6.6 ± 7.9 mm, and sagittal overhang was 14.2 ± 4.8 mm. Immediate post-revision cup anteversion was 33.0 ± 7.9°, inclination was 45.3 ± 5.1°, while there was no axial or sagittal overhang. At 60.3 ± 5.6 (52–70) months follow-up, 6 of 7 patients were available for assessment (1 patient had died). Iliopsoas muscle strength increased from 3.9 ± 0.7 to 4.6 ± 0.9, FJS was 77.5 ± 32.8, OHS was 40.3 ± 12.8, hip pain on VAS was 0.2 ± 0.4 at rest and 2.3 ± 2.6 during activities. Patient satisfaction with surgery was 8.3 ± 2.3, but 1 patient was dissatisfied and reported persistent hip pain. Last follow-up CT scans were available for 4 of 7 patients, with 3 showing osseointegrated grafts and no graft resorption.

Conclusions:

Anterior acetabular wall reconstruction and cup revision resulted in satisfactory clinical outcomes at a minimum follow-up of 4 years in 5 of 7 cases. Most patients fully recovered their iliopsoas muscle strength, had minimal to no pain, excellent FJS, and an osseointegrated acetabular wall graft.