bluuebunny/crossref_metadata_2025 huggingface dataset:
Irritant asthma and work: cases from the UK SWORD reporting scheme from 1999 to 2018
Authors: Fishwick David , Carder Melanie , Iskandar Ireny , Fishwick Beth Charlotte , van Tongeren Martie
Published: September 2023

Background

Acute irritant asthma is a preventable health consequence of a workplace exposure and has a number of adverse outcomes. While cases and case series are reported, little is known about the causes and incidence of this condition over prolonged periods of time.

Aims

We aimed to estimate the reported incidence of irritant asthma referred to a national reporting scheme, and how this has changed over time.

Methods

Cases of irritant asthma reported to SWORD, the UK-based Surveillance of Work-related Occupational Respiratory Diseases scheme, were grouped into four 5-year time periods from 1999 onwards. Likely causative exposures, job, work sector and incidence rates were analysed over time.

Results

307 actual cases equated to 1066 estimated cases; actual cases had a mean age of 46 years (SD 17.8); 70.7% were male. The annual incidence fell from 1.98 per million employed in the first 5-year period, to 0.56 in the most recent. Eleven occupational codes were associated with six or more attributed cases, and between them accounted for 38% of all cases. Thirteen exposure categories were associated with five or more cases. These were formaldehyde (n=5), cutting oils and coolants (n=6), isocyanates (n=6), pesticides and herbicides (n=6), welding fumes (n=7), paints (n=7), solder and colophony (n=7), solvents (n=9), fuel oil, diesel and ill-defined fumes (n=10), chlorine and hypochlorites (n=15), acids (n=23), smoke (n=25) and cleaning products and sterilising agents (n=39).

Conclusions

While the incidence of irritant asthma may have fallen, cases are persistently attributed to well-described causes. A persistence of cases attributed to cleaning agents was seen.
Occupational differences in the prevalence and severity of long-COVID: analysis of the Coronavirus (COVID-19) Infection Survey
Authors: Kromydas Theocharis , Demou Evangelia , Edge Rhiannon , Gittins Matthew , Katikireddi Srinivasa Vittal , Pearce Neil , van Tongeren Martie , Wilkinson Jack , Rhodes Sarah
Published: September 2023

Objectives

To establish whether prevalence and severity of long-COVID symptoms vary by industry and occupation.

Methods

We used Office for National Statistics COVID-19 Infection Survey (CIS) data (February 2021–April 2022) of working-age participants (16–65 years). Exposures were industry, occupation and major Standard Occupational Classification (SOC) group. Outcomes were self-reported: (1) long-COVID symptoms and (2) reduced function due to long-COVID. Binary (outcome 1) and ordered (outcome 2) logistic regression were used to estimate odds ratios (OR)and prevalence (marginal means).

Results

Public facing industries, including teaching and education, social care, healthcare, civil service, retail and transport industries and occupations, had the highest likelihood of long-COVID. By major SOC group, those in caring, leisure and other services (OR 1.44, 95% CIs 1.38 to 1.52) had substantially elevated odds than average. For almost all exposures, the pattern of ORs for long-COVID symptoms followed SARS-CoV-2 infections, except for professional occupations (eg, some healthcare, education, scientific occupations) (infection: OR<1 ; long-COVID: OR>1). The probability of reporting long-COVID for industry ranged from 7.7% (financial services) to 11.6% (teaching and education); whereas the prevalence of reduced function by ‘a lot’ ranged from 17.1% (arts, entertainment and recreation) to 22%–23% (teaching and education and armed forces) and to 27% (not working).

Conclusions

The risk and prevalence of long-COVID differs across industries and occupations. Generally, it appears that likelihood of developing long-COVID symptoms follows likelihood of SARS-CoV-2 infection, except for professional occupations. These findings highlight sectors and occupations where further research is needed to understand the occupational factors resulting in long-COVID.
Nonlinear finite element investigation on shear behaviour of simply supported and continuous RC T-beams retrofitted with deep embedded CFRP/steel bars
Authors: Dutta Baisali , Nayak Amar Nath , Dirar Samir , Nanda Bharadwaj , Theofanous Marios
Published: September 2023

The shear performances of simply supported (SS) and continuous (CN) reinforced concrete T-beams strengthened with deep embedded (DE) steel or carbon fibre-reinforced polymer bars are compared in this investigation. A nonlinear finite element (NLFE) analysis is performed for this purpose by modelling these beams with the FEM software by validating with the experimental data from the published studies. The experimental and NLFE shear strength values are then compared with those of the available design models to examine the efficacy of these models. Thereafter, the parametric study is conducted to obtain the impact of beam types (SS and CN) on the structural performances. It shows that the DE-strengthened CN beam provides higher shear capacity in comparison to the corresponding SS beam. However, the enhancements of the shear strength of SS beam due to strengthening with DE bars are significantly higher than that of the corresponding CN beam.
Investigating the difference in factors influencing the injury severity between daytime and nighttime speeding-related crashes
Authors: Yuan Renteng , Xiang Qiaojun , Huang Yan , Gu Xin
Published: September 2023

This study investigates the differences in the factors affecting the injury severity of speeding-related crashes occurring in the daytime and nighttime. Two log-likelihood ratio tests are conducted to validate whether speeding-related crashes classified by daytime and nighttime should be modeled separately. The result proves that separate modeling is necessary. Two correlated random parameter order probit models with heterogeneity in means are conducted using the data collected from 2018 to 2020 in the United States. Model estimation results show that urban areas, speed limits, and young and older drivers are temporal instability. Angle crashes, head-on crashes, intersections, downhill, exceeding the speed limit, drunk driving, and motorcycles are statistically significant in both models with an increased crash severity. Interaction and heterogeneity effects between random parameters are also reported. For instance, large trucks driving above the speed limit are more likely to increase the probability of severe injury.
Synthesis and characterization of a β-ketoenamine COF Tp-BD(Me)2 at mild temperatures
Authors: Wan Shuquan , Liu Guanyu , Chen Ying , Leng Senlin , Yao Yuanyong , Zeng Xinjuan , Zhou Cailong
Published: September 2023

In this work, we investigated the morphology and crystallinity changes of a [Formula: see text]-ketoenamine COF, Tp-BD(Me)2 (Tp=1,3,5-triformylphloroglucinol, BD(Me)2=3,3′-dimethyl-[1,1′-biphenyl]-4,4′-diamine), with different reaction time and temperatures. Powder X-ray diffraction (PXRD) and Fourier-transform infrared (FTIR) spectra tests confirmed the synthesis of Tp-BD(Me)2, which has a specific [Formula: see text]-ketoenamine linkage and a probable eclipsed stacking mode. At a reaction temperature of 50∘C, the morphology of Tp-BD(Me)2 underwent a progressive process of growing, extending and splitting. The band gaps of the Tp-BD(Me)2 obtained with the reaction time of 18–24 h were calculated near 2.0 eV. The BET surface areas of the Tp-BD(Me)2 were around 400–600 m2/g. It is not an optimal choice if the reaction temperature is below 50∘C, which could cause a low crystallinity and disordered morphology. However, slightly improving the reaction temperature to 60∘C is beneficial for generating high-crystallinity Tp-BD(Me)2.
Minimally Invasive Surgery for Trapezoid Nonunion: Case Report and Review of the Literature
Authors: KOHARA Toshiki , SAITO Taichi , SHIMAMURA Yasunori , OZAKI Toshifumi
Published: September 2023

We report a case of trapezoid nonunion diagnosed 3 months post injury. A 25-year-old male patient felt continuous wrist pain after being injured. His radiograph showed non-union with sclerotic change and bone resorption. He was planned for surgery, and this was done using a minimally invasive technique. Via a dorsal approach, we percutaneously drilled to the nonunion site and freshened the fracture ends. Bone plugs were harvested from the iliac crest using a bone marrow biopsy needle and packed into the nonunion site. The fracture was then fixed with a cannulated headless compression screw. This procedure could be performed without injuring the ligaments around the trapezoid. The patient was immobilised for 4 weeks, and bone union was achieved 6 months after surgery. He had full range of finger and wrist motion and no pain at the final follow-up.

Level of Evidence: Level V (Therapeutic)
The lower Cambrian Cranbrook Lagerstätte of British Columbia
Authors: Caron Jean-Bernard , Webster Mark , Briggs Derek E. G. , Pari Giovanni , Santucci Guy , Mángano M. Gabriela , Izquierdo-López Alejandro , Streng Michael , Gaines Robert R.
Published: September 2023

Discovered over a century ago, the lower Cambrian (Series 2, Stage 4) Cranbrook Lagerstätte of southeastern British Columbia's Eager Formation is one of the oldest Burgess Shale-type deposits in North America. This Konservat-Lagerstätte is rich in olenelloid trilobites, but also yields a very low-diversity soft-bodied fossil assemblage including
Tuzoia
and
Anomalocaris
, and a low-diversity ichnofauna. Its scientific study, however, remains limited. A 2015 field-based investigation by the Royal Ontario Museum has revealed new information about the site's biota, depositional environment and taphonomic conditions. Not only is the Cranbrook Lagerstätte significant for early Cambrian biostratigraphy and comparisons with other Burgess Shale-type deposits, it also reveals some of the little-known diversity of life in a distal outer shelf environment during the Cambrian period.

Supplementary material:
Three supplementary figures (historical map,
Tuzoia
outlines,
Anomalocaris
specimens), supplementary material and methods, and a supplementary data file (generic presence/absence matrix) are available at
https://doi.org/10.6084/m9.figshare.c.6850810
Design and Analysis of High Performance Heterogeneous Block-based Approximate Adders
Authors: Farahmand Ebrahim , Mahani Ali , Hanif Muhammad Abdullah , Shafique Muhammad
Published: September 2023

Approximate computing is an emerging paradigm to improve the power and performance efficiency of error-resilient applications. As adders are one of the key components in almost all processing systems, a significant amount of research has been carried out toward designing approximate adders that can offer better efficiency than conventional designs; however, at the cost of some accuracy loss. In this article, we highlight a new class of energy-efficient approximate adders, namely, Heterogeneous Block-based Approximate Adders (HBAAs), and propose a generic configurable adder model that can be configured to represent a particular HBAA configuration. An HBAA, in general, is composed of heterogeneous sub-adder blocks of equal length, where each sub-adder can be an approximate sub-adder and have a different configuration. The sub-adders are mainly approximated through inexact logic and carry truncation. Compared to the existing design space, HBAAs provide additional design points that fall on the Pareto-front and offer a better quality-efficiency tradeoff in certain scenarios. Furthermore, to enable efficient design space exploration based on user-defined constraints, we propose an analytical model to efficiently evaluate the Probability Mass Function (PMF) of approximation error and other error metrics, such as Mean Error Distance (MED), Normalized Mean Error Distance (NMED), and Error Rate (ER) of HBAAs. The results show that HBAA configurations can provide around 15% reduction in area and up to 17% reduction in energy compared to state-of-the-art approximate adders.
MOEA/D vs. NSGA-II: A Comprehensive Comparison for Multi/Many Objective Analog/RF Circuit Optimization through a Generic Benchmark
Authors: Saǧlican Enes , Afacan Engin
Published: September 2023

Thanks to the enhanced computational capacity of modern computers, even sophisticated analog/radio frequency (RF) circuit sizing problems can be solved via electronic design automation (EDA) tools. Recently, several analog/RF circuit optimization algorithms have been successfully applied to automatize the analog/RF circuit design process. Conventionally, metaheuristic algorithms are widely used in optimization process. Among various nature-inspired algorithms, evolutionary algorithms (EAs) have been more preferred due to their superiorities (robustness, efficiency, accuracy etc.) over the other algorithms. Furthermore, EAs have been diversified and several distinguished analog/RF circuit optimization approaches for single-, multi-, and many-objective problems have been reported in the literature. However, there are conflicting claims on the performance of these algorithms and no objective performance comparison has been revealed yet. In the previous work, only a few case study circuits have been under test to demonstrate the superiority of the utilized algorithm, so a limited comparison has been made for only these specific circuits. The underlying reason is that the literature lacks a generic benchmark for analog/RF circuit sizing problem. To address these issues, we propose a comprehensive comparison of the most popular two evolutionary computation algorithms, namely Non-Sorting Genetic Algorithm-II and Multi-Objective Evolutionary Algorithm based Decomposition, in this article. For that purpose, we introduce two ad hoc testbenches for analog and RF circuits including the common building blocks. The comparison has been made at both multi- and many-objective domains and the performances of algorithms have been quantitatively revealed through the well-known Pareto-optimal front quality metrics.
Achievement Goals: A Social Influence Cycle
Authors: Butera Fabrizio , Dompnier Benoît , Darnon Céline
Published: September 2023

Achievement goals have been defined as the purpose of competence-relevant behavior. In this respect they connect one of the basic human needs, i.e., competence, to one of society's core values, i.e., achievement. We propose to look at achievement goals through the lens of social influence. We review both the influence that cultural, structural, and contextual factors have on achievement goal endorsement and the influence that endorsing achievement goals allows people to have within their social space. The review allows us to propose a circular model of the influence on and of achievement goals: The culture, social structures, and contexts that are typical of a certain society shape the specific environments in which individuals develop their achievement goals, which in turn has an influence on the expression and circulation of these achievement goals into society, in a social influence cycle.
Deposition and Morphology Control of Carbon Film through Electrochemical Reduction of Carbonate Ions in Molten LiCl
Authors: Zhuang Chongrui , Jin Weiliang , Xiao Jiusan , Lu Xin , Takeda Osamu , Zhu Hongmin
Published: September 2023

Synthesis of a compact, uniform and thick carbon film on nickel substrate were conducted by electrochemical reduction of carbonate ions in LiCl-Li2CO3 molten salt. It was found that the carbon is consistently formed into structure of wire and sphere particle. The uniformity and compactness of the carbon film were found to be dependent on the applied current density, electricity, and the electrolysis method. At lower current densities, the carbon tended to grow locally, resulting in larger-sized wires and particles. At higher current density, a relatively uniform and thin carbon film can be synthesized at the beginning but soon changed to a cluster-like structure. The contradiction between current density and carbonate ions‘ diffusion limit make it is impossible to obtain a compact and uniform film by using constant current electrolysis. By applying pulsed current electrolysis with an average current density of 10 mA cm−2 and a peak current density of 200 mA cm−2, a compact and uniform carbon film with a thickness of approximately 10 μm was successfully prepared.
Mild dehydration effects on the murine kidney single-nucleus transcriptome and chromatin accessibility
Authors: Huynh Nha Van , Rehage Cassidy , Hyndman Kelly A.
Published: September 2023

The kidney consists of >30 cell types that work collectively to maintain fluid-electrolyte balance. Kidney single-nucleus transcriptomes and chromatin accessibility profiles from male and female control (ad libitum water and food) or mildly dehydrated mice (ad libitum food, water deprivation) were determined. Mild dehydration caused hundreds of cell- and sex-specific transcriptomic changes, even though the kidney function to conserve water was the same.
Muscle blood flow and vasodilation are blunted at the onset of exercise following an acute bout of ischemia-reperfusion
Authors: Hanson Brady E. , Feider Andrew J. , Hanada Satoshi , Aldrich Aric W. , Casey Darren P.
Published: September 2023

Ischemia-reperfusion can impair endothelial function; however, it remains unknown whether exercise hyperemia and vasodilation are also impaired. This study presents novel findings that ischemia-reperfusion blunts the hyperemic and vasodilatory responses at the onset of muscle contractions but not during steady-state exercise. Plasma [nitrite] was also blunted at baseline and during steady-state exercise following ischemia-reperfusion compared with time control. These attenuated responses at the onset of exercise may be associated with ischemia-reperfusion reductions in NO bioavailability.
Establishment and Performance Evaluation of Multiplex PCR-Dipstick DNA Chromatography for Mycoplasma pneumoniae and Chlamydia pneumoniae Rapid Detection
Authors: Hu Liuyang , Wang Xiuri , Cao Donglin , Cheng Qiuchen , Li Qiong
Published: September 2023

Background and Objective. Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) infections are becoming increasingly prominent in respiratory infections. This study established a rapid, simple, sensitive, accurate multiplex PCR-dipstick DNA chromatography assay for Mycoplasma pneumoniae and Chlamydia pneumoniae detection. Methods. Nasopharyngeal swab samples of 300 children with an acute respiratory tract infection were detected by a multiplex PCR-dipstick chromatography assay, and the results were compared with the DNA sequencing and serum IgM antibody assay. Results. A multiplex PCR-dipstick DNA assay can specifically detect Mycoplasma pneumoniae and Chlamydia pneumoniae and shows a good specificity, with a minimum detection limit of 10 CFU/mL, respectively. Using DNA sequencing results as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of the multiplex PCR-dipstick DNA chromatography assay for the diagnosis of Mycoplasma pneumoniae were 96.61%, 100%, 100%, and 99.18% respectively, and those of Chlamydia pneumoniae were 95.24%, 100%, 100%, and 99.64% respectively. There was no statistical significance MP and CP diagnosis by the multiplex PCR-dipstick DNA assay and DNA sequencing (MP:

P
=
0.5

; CP:

P
=
1.0

), and the two assays had very high statistical consistency (MP: kappa = 0.979; CP: kappa = 0.974). The positive rate of the multiplex PCR-dipstick chromatography assay was significantly higher than that of the serum IgM antibody assay, with MP (17.7% vs. 13.3%), CP (5.7% vs. 3.3%), and mixed infection of MP and CP (1.3% vs. 0.67%). Conclusions. A multiplex PCR-dipstick chromatography assay was successfully established for the joint detection of Mycoplasma pneumoniae and Chlamydia pneumoniae within 2 hours. It is simple, fast, sensitive, accurate, cost-effective with good diagnostic performance, which can be used for small laboratories and point-of-care diagnosis.
On the Convergence Result of the Fractional Pseudoparabolic Equation
Authors: Van Tien Nguyen , Saadati Reza
Published: September 2023

In this paper, we consider the nonlinear fractional Laplacian pseudoparabolic equation (NFLPPE). We mainly focus on the convergence of mild solutions with respect to the order of fractional Laplacian. By using many techniques, we obtain the result that the mild solution will converge when the fractional order of the Laplacian tends to

1

−

. The proof of convergent result relies on sharp techniques of evaluating the exponential terms, the Sobolev embeddings, and weakly singular Gronwall inequalities.
Relationship between Self-Compassion and Uneasiness about the Professional Future among Dental Hygiene Students: A Cross-Sectional Study
Authors: Izumi Maya , Akifusa Sumio
Published: September 2023

Purpose. To examine the self-compassion of dental hygiene students in Japan and the correlation between their self-compassion and uneasiness about their professional future. Methods. This study was conducted from May to September 2021. Students were invited from three colleges and one university in Fukuoka Prefecture to take the survey. Participants provided information regarding demographic variables (e.g., gender and year of study) and answered six questions regarding feeling uneasy about one’s future, matters of learning, and what might happen after graduation. Self-compassion was assessed using the Japanese short version of the self-compassion scale (SCS), with the positive- and negative-SCS subdomains. Resilience was measured using the bidimensional resilience scale with the subdomains of innate and acquired resilience. For the statistical analysis, participants were divided into the “yes” group, where members felt uneasy and the “no” group, where members did not feel uneasy. Results. Data were obtained from 464 participants (response rate: 96.3%). The scores of total-, positive-, and negative-SCS were 36 (12–56), 18 (6–29), and 19 (6–30), respectively; 55.2% of students felt uneasy about their professional future. There was a statistically significant difference in scores for positive- and negative-SCS and innate resilience between the “yes” and “no” groups. Binomial logistic regression analysis revealed that when negative-SCS increased by one point, the risk of feeling uneasy about one’s professional future was 1.12 times higher (95% confidence interval: 1.07–1.17) after adjusting for resilience and the answers to the remaining five questions. Conclusion. Our findings suggest that the negative factor of self-compassion is related to increasing the risk of feeling uneasy about one’s professional future as a dental hygienist.
Fractured Zone Detection Using Petrophysical Logs by Rescaled Windowed R/S Analyses and Discrete Fracture Network (DFN) of Yanchang Formation in Mahuangshan-Hongliugou Area, Ordos Basin, China
Authors: Gao Jindong , Li Lirong , Gao Gaorun , Ma Shuwei , Li Meng
Published: September 2023

Structural fractures generally develop in the upper crust strata and are usually distributed in a convergent pattern, forming structural fracture zones with a specific strike. Fracture zones control the reservoir seepage system and seriously affect the migration and accumulation of oil and gas in tight sandstone reservoirs. Therefore, characterizing the characteristics of the fracture zones for tight oil exploration and development effectively is essential. In this paper, the variable scale fractal method is introduced to calculate the petrophysical log, and a new curve

H

is built. An intensity log is to characterize the intensity of structural fracture development. The

H

curve is in a good linear relationship with the intensity curve after the comparison of the

H

curve and intensity curve in 32 wells. A quantitative relationship between

H

and the intensity curve is established. Based on the parameters obtained from the core and image logs, the discrete fracture network model was established using

H

curves from more than 300 wells, and the structural fracture zone was analyzed. The model shows that the fracture zones formed by structural fractures are in S-N and NW-SE directions in the study area. The orientation of the structural fracture zone is consistent with that of the fractured fault zone and fault, and the development of the fractured zone is consistent with the regional tectonic evolution characteristics. The characteristics of the fracture zone explain the distribution law of oil accumulation and groundwater salinity in the study area.
Estratificación de riesgo del dolor torácico en el servicio de urgencia.
Authors: Navea Carrasco Oscar Gonzalo , Tapia Valeria , Miguel Alonso , Maluenda Felipe
Published: September 2023

El dolor torácico es un motivo de consulta frecuente en los servicios de urgencia. Su espectro de presentaciones y su diagnóstico diferencial es amplio, con patologías de elevada morbilidad y mortalidad asociadas. Es el síntoma principal en pacientes con un síndrome coronario agudo y, ante su sospecha es mandatorio realizar una evaluación inicial centrada en la estratificación de riesgo de sufrir eventos adversos en cada paciente, para así definir su tratamiento y disposición posterior de forma correcta. Objetivo: presentar los elementos que componen la evaluación inicial del dolor torácico ante una sospecha de síndrome coronario agudo y las herramientas disponibles para realizar la estratificación de riesgo y así guiar la disposición desde el servicio de urgencia. Método: Se realizó una revisión bibliográfica de la literatura sobre la estratificación de riesgo del dolor torácico, buscando la evidencia actual respecto a las herramientas diagnósticas utilizadas habitualmente en el servicio de urgencia. Resultados: Se presenta una revisión con generalidades del dolor torácico, sus diagnósticos diferenciales, los elementos de la evaluación inicial y las herramientas clínicas para la evaluación de riesgo de pacientes con dolor torácico y sospecha de síndrome coronario agudo en el servicio de urgencia. Discusión y conclusiones: La presentación del síndrome coronario agudo es variable en la población. Ante la presencia de un cuadro de dolor atípico y/o un electrocardiograma no diagnóstico, recomendamos el uso de un sistema de puntaje validado como el HEART / HEART pathway para reducir la posibilidad de una inadecuada estratificación de riesgo en el servicio de urgencia.
Evaluación de residentes de pediatría con una modalidad virtual durante la pandemia COVID 19: presentación de una experiencia.
Authors: Torres Fernando , Domínguez Paula , Labanca Vanesa , Urtasun Marcela , Giacomossi Pedro , Grisolía Nicolás , Yulita Horacio , Ossorio María Fabiana , Ferrero Fernando
Published: September 2023

El examen clínico objetivo estructurado (ECOE) es una herramienta válida para medir competencias clínicas. En el contexto de la pandemia por COVID-19 se debieron adaptar las evaluaciones, habitualmente presenciales, a un formato virtual. El objetivo de este artículo es comunicar la experiencia de utilizar una modalidad virtual del ECOE para residentes de primer año de pediatría durante la pandemia por COVID-19. El ECOE comprendió 12 estaciones utilizando casos simulados en línea y consultas virtuales a distancia. Participaron del ECOE 115 residentes, aprobaron 110 (95,7%) y solo 17 participantes aprobaron el 100% de las estaciones. Las estaciones con mejor rendimiento fueron las referidas a alimentación complementaria, abordaje del traumatismo encéfalo craneano, interpretación de resultados de laboratorio y de imágenes radiológicas. El menor rendimiento se observó en uso de equipo de protección personal y vacunas. La encuesta de satisfacción fue respondida por 80/115 participantes (69,5%). El 91% de los participantes encontró fácil de utilizar la plataforma virtual. La mayoría (73/80) consideró que los temas fueron acordes al nivel de formación. La estación de pautas madurativas fue identificada como la más difícil. El 57% refirió que el ECOE les resultó útil para identificar puntos débiles en su formación. La implementación de una modalidad virtual del ECOE fue posible y presentó buena aceptación de los participantes.
Suppl. Data 1 from Whole Slide Imaging-Based Prediction of TP53 Mutations Identifies an Aggressive Disease Phenotype in Prostate Cancer
Authors: Pizurica Marija , Larmuseau Maarten , Van der Eecken Kim , de Schaetzen van Brienen Louise , Carrillo-Perez Francisco , Isphording Simon , Lumen Nicolaas , Van Dorpe Jo , Ost Piet , Verbeke Sofie , Gevaert Olivier , Marchal Kathleen
Published: September 2023

Contains
1. significantly differentially expressed genes between eTN and eFP ("FP_TN"),
2. significantly differentially expressed genes between eTN and eTP ("TP_TN"),
3. the pathway overrepresentations for 2-3. ("Reactome_table_FP_TN", "Reactome_table_TP_TN", "MSIGDBHALLMARK_TP_TN", "MSIGDBHALLMARK_FP_TN")
Data from Whole Slide Imaging-Based Prediction of TP53 Mutations Identifies an Aggressive Disease Phenotype in Prostate Cancer
Authors: Pizurica Marija , Larmuseau Maarten , Van der Eecken Kim , de Schaetzen van Brienen Louise , Carrillo-Perez Francisco , Isphording Simon , Lumen Nicolaas , Van Dorpe Jo , Ost Piet , Verbeke Sofie , Gevaert Olivier , Marchal Kathleen
Published: September 2023

Abstract
In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify the metastatic potential of a tumor at an early stage. While recent analyses indicated TP53 mutations as candidate biomarkers, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in whole slide images (WSI) offer the potential to mitigate this issue. To assess the potential of WSIs as proxies for spatially resolved profiling and as biomarkers for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. In an independent multifocal cohort, the model showed successful generalization at both the patient and lesion level. Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions, suggesting that some FP carry an alteration that leads to the same histological phenotype as TP53 mutations. Comparative expression and histologic cell type analyses identified a TP53-like cellular phenotype triggered by expression of pathways affecting stromal composition. Together, these findings indicate that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations but they have the potential to elucidate the prognosis of a tumor by depicting a downstream phenotype associated with aggressive disease biomarkers.
Significance:
Deep learning models predicting TP53 mutations from whole slide images of prostate cancer capture histologic phenotypes associated with stromal composition, lymph node metastasis, and biochemical recurrence, indicating their potential as in silico prognostic biomarkers.

See related commentary by Bordeleau, p. 2809
Data from NR1D1 Stimulates Antitumor Immune Responses in Breast Cancer by Activating cGAS-STING Signaling
Authors: Ka Na-Lee , Park Mi Kyung , Kim Seung-Su , Jeon Yoon , Hwang Sewon , Kim Sun Mi , Lim Ga Young , Lee Ho , Lee Mi-Ock
Published: September 2023

Abstract
Potentiating antitumor immunity is a promising therapeutic approach for treating a variety of cancers, including breast cancer. One potential strategy to promote antitumor immunity is targeting DNA damage response. Given that the nuclear receptor NR1D1 (also known as REV-ERBα) inhibits DNA repair in breast cancer cells, we explored the role of NR1D1 in antitumor CD8+ T-cell responses. First, deletion of Nr1d1 in MMTV-PyMT transgenic mice resulted in increased tumor growth and lung metastasis. Orthotopic allograft experiments suggested that loss of Nr1d1 in tumor cells rather than in stromal cells played a prominent role in increasing tumor progression. Comprehensive transcriptome analyses revealed that biological processes including type I IFN signaling and T cell–mediated immune responses were associated with NR1D1. Indeed, the expression of type I IFNs and infiltration of CD8+ T cells and natural killer cells in tumors were suppressed in Nr1d1−/−;MMTV-PyMT mice. Mechanistically, NR1D1 promoted DNA damage–induced accumulation of cytosolic DNA fragments and activated cGAS-STING signaling, which increased the production of type I IFNs and downstream chemokines CCL5 and CXCL10. Pharmacologic activation of NR1D1 by its ligand, SR9009, enhanced type I IFN–mediated antitumor immunity accompanied by the suppression of tumor progression and lung metastasis. Taken together, these findings reveal the critical role of NR1D1 in enhancing antitumor CD8+ T-cell responses, suggesting that NR1D1 may be a good therapeutic target for breast cancer.
Significance:
NR1D1 suppresses breast cancer progression and lung metastasis by enhancing antitumor immunity via cGAS-STING pathway activation, which provides potential immunotherapeutic strategies for breast cancer.
FGFR3 Alterations in Bladder Cancer Stimulate Serine Synthesis to Induce Immune-Inert Macrophages That Suppress T-cell Recruitment and Activation
Authors: Ouyang Yi , Ou Ziwei , Zhong Wenlong , Yang Jin , Fu Sha , Ouyang Nengtai , Chen Junyu , Xu Longhao , Wu Daqin , Qian Junan , Lin Yi , Lin Tianxin , Huang Jian
Published: September 2023

FGFR3 alterations are common in patients with bladder cancer. While the FGFR tyrosine kinase inhibitor erdafitinib has been approved as a targeted therapy for patients with FGFR3-altered (aFGFR3) bladder cancer, the response rate remains suboptimal, prompting development of strategies to improve treatment response. Here, we observed an immune-desert tumor microenvironment (TME) phenotype in human aFGFR3 bladder cancer and demonstrated that mutant FGFR3 indirectly induces a “cold” TME in mouse bladder cancer models. Single-cell RNA sequencing revealed the central role of macrophages in inducing the cold TME of aFGFR3 tumors. Macrophages in aFGFR3 tumors exhibited reduced T-cell recruitment and antigen presentation capabilities. Increased serine synthesis in bladder cancer cells that was induced by mutant FGFR3 activated the PI3K/Akt pathway in macrophages, shifting them to an immune-inert phenotype. Targeting PI3K in aFGFR3 tumors with duvelisib achieved promising efficacy by reversing the macrophage phenotype, and combination therapy with duvelisib and erdafitinib demonstrated increased antitumor activity. Overall, these findings reveal the critical role of enhanced serine synthesis efflux from cancer cells with mutant FGFR3 in shifting macrophages to an immune-inert phenotype. Reversing the macrophage phenotype holds promise for enhancing erdafitinib efficacy.

Significance:

Metabolic reprogramming of bladder cancer cells driven by mutant FGFR3 increases serine synthesis that suppresses macrophage immunostimulatory functions to generate an immunosuppressive TME, which can be overcome by targeting PI3K.
Supplementary Material from Association of Menopausal Hormone Therapy with Risk of Pancreatic Cancer: A Systematic Review and Meta-analysis of Cohort Studies
Authors: Jang Yeu-Chai , Leung Chi Yan , Huang Hsi-Lan
Published: September 2023

Supplement: Table S1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the reporting of meta-analyses. Table S2. Search strategies on the PubMed. Table S3. Search strategies on the Ovid Embase. Table S4. Search strategies on the Cochrane Library. Table S5. Details of combined risk estimates used in Figure 2. Table S6. Details of combined risk estimates used in Figure 4. Table S7. Details of combined risk estimates used in Figure 5. Table S8. List of references with final exclusion reasons. Table S9. Newcastle-Ottawa Quality Assessment Scale for cohort studies. Figure S1. Prediction interval of pancreatic cancer risk for the use of menopausal hormone therapy, using random-effects model. Figure S2. Funnel plot of pancreatic cancer risk
Data from Association of Menopausal Hormone Therapy with Risk of Pancreatic Cancer: A Systematic Review and Meta-analysis of Cohort Studies
Authors: Jang Yeu-Chai , Leung Chi Yan , Huang Hsi-Lan
Published: September 2023

AbstractBackground:
Although menopausal hormone therapy (MHT) is commonly prescribed, little is known about the association between MHT use and risk of pancreatic cancer.
Methods:
We searched PubMed, Embase, and Cochrane Library, from inception until April 20, 2022. The risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale. Pooled relative risks (RR) for pancreatic cancer risk were calculated using random-effects models. We computed prediction intervals (PI) and performed subgroup meta-analyses. Meta-regression was performed to investigate the sources of heterogeneity.
Results:
This study included 2,712,313 women from 11 cohort studies. There was no association between MHT and pancreatic cancer risk (RR, 0.92; 95% confidence interval (CI), 0.83–1.02; I2, 64%; 95% PI, 0.68–1.25). Subgroup meta-analyses of four studies stratified by MHT formulations showed inverse associations with the risk of pancreatic cancer (women receiving estrogen-only MHT: RR, 0.77; 95% CI, 0.64–0.94; I2, 57%; estrogen plus progestin MHT: RR, 0.85; 95% CI, 0.75–0.96; I2, 0%). Subgroup analysis defined by recency and duration of treatment did not reveal evidence of associations between MHT and pancreatic cancer risk.
Conclusions:
This study found no association between the overall use of MHT and risk of pancreatic cancer. However, among four studies with data on MHT formulations, subgroup analysis showed a decreased risk of pancreatic cancer among users of estrogen-only and combined estrogen-progestin therapy. Owing to the inconsistent findings between our main and subgroup analyses, future studies stratified by MHT formulations are warranted.
Impact:
The findings of this study indicate that future investigation should focus on MHT formulations.
Mean plasma SRA737 concentration over time from A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer
Authors: Jones Robert , Plummer Ruth , Moreno Victor , Carter Louise , Roda Desamparados , Garralda Elena , Kristeleit Rebecca , Sarker Debashis , Arkenau Tobias , Roxburgh Patricia , Walter Harriet S. , Blagden Sarah , Anthoney Alan , Klencke Barbara J. , Kowalski Mark M. , Banerji Udai
Published: September 2023

This figure displays the mean SRA737 plasma concentration at each assessment timepoint by dose level. The dotted lines indicates a plasma concentration of 40-500 ng/mL, the range corresponding to the minimal effective dose extrapolated from preclinical models. Error bars represent standard deviation.
Knowledge Mediates the Effects of Game Changers for Cervical Cancer Prevention (GC-CCP) Intervention on Increased VIA Screening Advocacy in Uganda
Authors: Wagner Glenn J. , Matovu Joseph K.B. , Juncker Margrethe , Namisango Eve , Beyeza-Kashesya Jolly , Wanyenze Rhoda K.
Published: September 2023

Game Changers for Cervical Cancer Prevention (GC-CCP), a group advocacy training intervention, has been shown to increase cervical cancer prevention and screening advocacy. In this secondary analysis, we examined mediators and moderators of this effect. A randomized controlled trial of GC-CCP—a 7-session, peer led intervention designed to empower women to engage in cervical cancer prevention advocacy—was conducted with women who had recently been screened by visual inspection of the cervix with acetic acid for cervical cancer. Participants were assessed at baseline and month 6 follow-up. Cervical cancer–related constructs targeted by the intervention were examined as mediators using multivariate linear regression analysis. Individual and social network characteristics were examined as moderators. Change in cervical cancer knowledge fully mediated the intervention effect on increased cervical cancer prevention advocacy; change in cervical cancer risk management self-efficacy was a partial mediator. Moderators of the effect included no secondary education, having a main sex partner, and having trustworthy, supportive, non-stigmatizing peers. The effect of GC-CCP on cervical cancer prevention advocacy seems largely driven by its impact on cervical cancer knowledge, and the intervention may be most effective among women who are partnered, less educated, and have trusting, supportive social networks.

Prevention Relevance:

Enhancing cervical cancer knowledge among women who have screened for cervical cancer is key to empowering these women to engage in cervical cancer prevention advocacy and acting as change agents for encouraging other women to screen.
Supplementary Table S5 from Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Authors: Marin Ines , Boix Olga , Garcia-Garijo Andrea , Sirois Isabelle , Caballe Adrià , Zarzuela Eduardo , Ruano Irene , Attolini Camille Stephan-Otto , Prats Neus , López-Domínguez José A , Kovatcheva Marta , Garralda Elena , Muñoz Javier , Caron Etienne , Abad María , Gros Alena , Pietrocola Federico , Serrano Manuel
Published: September 2023

Supplementary materials
Supplementary Fig. S5 from Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Authors: Marin Ines , Boix Olga , Garcia-Garijo Andrea , Sirois Isabelle , Caballe Adrià , Zarzuela Eduardo , Ruano Irene , Attolini Camille Stephan-Otto , Prats Neus , López-Domínguez José A , Kovatcheva Marta , Garralda Elena , Muñoz Javier , Caron Etienne , Abad María , Gros Alena , Pietrocola Federico , Serrano Manuel
Published: September 2023

Senescent cancer cells from human patients hyperstimulate autologous reactive TILs
Supplementary Fig. S2 from Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Authors: Marin Ines , Boix Olga , Garcia-Garijo Andrea , Sirois Isabelle , Caballe Adrià , Zarzuela Eduardo , Ruano Irene , Attolini Camille Stephan-Otto , Prats Neus , López-Domínguez José A , Kovatcheva Marta , Garralda Elena , Muñoz Javier , Caron Etienne , Abad María , Gros Alena , Pietrocola Federico , Serrano Manuel
Published: September 2023

Noncancer senescent cells induce an adaptive immune response in vivo and present unique immunogenic peptides
TABLE 2 from Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation
Authors: Vaidya Riha , Unger Joseph M. , Loomba Rohit , Hwang Jessica P. , Chugh Rashmi , Tincopa Monica A. , Arnold Kathryn B. , Hershman Dawn L. , Ramsey Scott D.
Published: September 2023

Base case results
TABLE 1 from Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation
Authors: Vaidya Riha , Unger Joseph M. , Loomba Rohit , Hwang Jessica P. , Chugh Rashmi , Tincopa Monica A. , Arnold Kathryn B. , Hershman Dawn L. , Ramsey Scott D.
Published: September 2023

Model input parameters
Long Noncoding RNA Gpr137b-ps Promotes Advanced Atherosclerosis via the Regulation of Autophagy in Macrophages
Authors: Qu Wenbo , Zhou Xin , Jiang Xinjian , Xie Xianwei , Xu Kaijian , Gu Xia , Na Ruisi , Piao Minghui , Xi Xiangwen , Sun Na , Wang Xueyu , Peng Xiang , Xu Junyan , Tian Jiangtian , Zhang Jian , Guo Junli , Zhang Maomao , Zhang Yao , Pan Zhenwei , Wang Kun , Yu Bo , Sun Bin , Li Shuijie , Tian Jinwei
Published: September 2023

BACKGROUND:

Current therapies cannot completely reverse advanced atherosclerosis. High levels of amino acids, induced by Western diet, stimulate mTORC1 (mammalian target of rapamycin complex 1)-autophagy defects in macrophages, accelerating atherosclerotic plaque progression. In addition, autophagy-lysosomal dysfunction contributes to plaque necrotic core enlargement and lipid accumulation. Therefore, it is essential to investigate the novel mechanism and molecules to reverse amino acid–mTORC1–autophagy signaling dysfunction in macrophages of patients with advanced atherosclerosis.

METHODS:

We observed that Gpr137b-ps (G-protein–coupled receptor 137B, pseudogene) was upregulated in advanced atherosclerotic plaques. The effect of Gpr137b-ps on the progression of atherosclerosis was studied by generating advanced plaques in
ApoE

−/−

mice with cardiac-specific knockout of Gpr137b-ps. Bone marrow–derived macrophages and mouse mononuclear macrophage cell line RAW264.7 cells were subjected to starvation or amino acid stimulation to study amino acid–mTORC1–autophagy signaling. Using both gain- and loss-of-function approaches, we explored the mechanism of Gpr137b-ps–regulated autophagy.

RESULTS:

Our results demonstrated that Gpr137b-ps deficiency led to enhanced autophagy in macrophages and reduced atherosclerotic lesions, characterized by fewer necrotic cores and less lipid accumulation. Knockdown of Gpr137b-ps increased autophagy and prevented amino acid–induced mTORC1 signaling activation. As the downstream binding protein of Gpr137b-ps, HSC70 (heat shock cognate 70) rescued the impaired autophagy induced by Gpr137b-ps. Furthermore, Gpr137b-ps interfered with the HSC70 binding to G3BP (Ras GTPase-activating protein-binding protein), which tethers the TSC (tuberous sclerosis complex) complex to lysosomes and suppresses mTORC1 signaling. In addition to verifying that the NTF2 (nuclear transport factor 2) domain of G3BP binds to HSC70 by in vitro protein synthesis, we further demonstrated that HSC70 binds to the NTF2 domain of G3BP through its W90-F92 motif by using computational modeling.

CONCLUSIONS:

These findings reveal that Gpr137b-ps plays an essential role in the regulation of macrophage autophagy, which is crucial for the progression of advanced atherosclerosis. Gpr137b-ps impairs the interaction of HSC70 with G3BP to regulate amino acid–mTORC1–autophagy signaling, and these results provide a new potential therapeutic direction for the treatment of advanced atherosclerosis.
Retrieval of Chronically Implanted Dual-chamber Leadless Pacemakers in an Ovine Model
Authors: Banker Rajesh S. , Rippy Marian K. , Cooper Nicole , Neužil Petr , Exner Derek V. , Nair Devi G. , Booth Daniel F. , Ligon David , Badie Nima , Krans Mark , Ando Kenji , Knops Reinoud E. , Ip James E. , Doshi Rahul N. , Rashtian Mayer , Reddy Vivek Y.
Published: September 2023

BACKGROUND:

The clinical utilization of leadless pacemakers (LPs) as an alternative to traditional transvenous pacemakers is likely to increase with the advent of dual-chamber LP systems. Since device retrieval to allow LP upgrade or replacement will become an important capability, the first such dual-chamber, helix-fixation LP system (Aveir DR; Abbott, Abbott Park, IL) was specifically designed to allow catheter-based retrieval. In this study, the preclinical performance and safety of retrieving chronically implanted dual-chamber LPs was evaluated.

METHODS:

Atrial and ventricular LPs were implanted in the right atrial appendage and right ventricular apex of 9 healthy ovine subjects. After ≈2 years, the LPs were retrieved using a dedicated transvenous retrieval catheter (Aveir Retrieval Catheter; Abbott) by snaring, docking, and unscrewing from the myocardium. Comprehensive necropsy/histopathology studies were conducted to evaluate device- and procedure-related outcomes.

RESULTS:

At a median of 1.9 years postimplant (range, 1.8–2.6), all 18 of 18 (100%) LPs were retrieved from 9 ovine subjects without complications. The median retrieval procedure duration for both LPs, from first-catheter-in to last-catheter-out, was 13.3 minutes (range, 2.5–36.4). Postretrieval, all right atrial, and right ventricular implant sites demonstrated minimal tissue disruption, with intact fibrous tissue limited to the distal device body. No significant device-related trauma, perforation, pericardial effusion, right heart or tricuspid valve injury, or chronic pulmonary thromboembolism were observed at necropsy.

CONCLUSIONS:

This preclinical study demonstrated the safe and effective retrieval of chronically implanted, helix-fixation, dual-chamber LP systems, paving the way for clinical studies of LP retrieval.