bluuebunny/crossref_metadata_2025 huggingface dataset:
StAC-DA: Structure aware cross-modality domain adaptation framework with image and feature-level adaptation for medical image segmentation
Authors: Baldeon-Calisto Maria , Lai-Yuen Susana K. , Puente-Mejia Bernardo
Published: September 2024

Objective

Convolutional neural networks (CNNs) have achieved state-of-the-art results in various medical image segmentation tasks. However, CNNs often assume that the source and target dataset follow the same probability distribution and when this assumption is not satisfied their performance degrades significantly. This poses a limitation in medical image analysis, where including information from different imaging modalities can bring large clinical benefits. In this work, we present an unsupervised Structure Aware Cross-modality Domain Adaptation (StAC-DA) framework for medical image segmentation.

Methods

StAC-DA implements an image- and feature-level adaptation in a sequential two-step approach. The first step performs an image-level alignment, where images from the source domain are translated to the target domain in pixel space by implementing a CycleGAN-based model. The latter model includes a structure-aware network that preserves the shape of the anatomical structure during translation. The second step consists of a feature-level alignment. A U-Net network with deep supervision is trained with the transformed source domain images and target domain images in an adversarial manner to produce probable segmentations for the target domain.

Results

The framework is evaluated on bidirectional cardiac substructure segmentation. StAC-DA outperforms leading unsupervised domain adaptation approaches, being ranked first in the segmentation of the ascending aorta when adapting from Magnetic Resonance Imaging (MRI) to Computed Tomography (CT) domain and from CT to MRI domain.

Conclusions

The presented framework overcomes the limitations posed by differing distributions in training and testing datasets. Moreover, the experimental results highlight its potential to improve the accuracy of medical image segmentation across diverse imaging modalities.
The Benefits of Social Media Among Children Aged 8 to 17 in Tema Metropolitan Area in Ghana
Authors: Kyei-Gyamfi Sylvester
Published: September 2024

In modern society, children actively engage with social media platforms, and Ghana is not an exception to this trend. People have, however, placed an excessive amount of focus on the negative implications of using social media, which has overshadowed the positive effects that it has on children. This study examines the use of social media by children, including their preferred platforms, as well as the positive and negative consequences associated with their usage. This was a cross-sectional study that employed convenient and snowball sampling procedures for data collection and analysis. The study was conducted on 400 children aged 8 to 17 in Tema. The Uses and Gratifications Theory (UGT) is the study’s underlying theory. The association between demographic characteristics and correlates of social media usage was examined using bivariate analysis, whereas the qualitative data analysis was guided by thematic analysis. The results show that 87.5% of children have ever used social media, with males being more likely than females to have done so (91.7% vs. 83.5%). The main reason social media platforms are used by children (87%) is for entertainment. TikTok has the highest usage percentage, making up 88.7% of all platforms, according to the findings. Some benefits of social media include communication, entertainment, and resources for creativity, research, and academic work. Also, the detrimental consequences of social media usage comprise exposure to sexually explicit material, addiction in children, and diminished academic achievement in children who become too engrossed in its usage. The study demonstrated that social media is widely used among children in Ghana. TikTok is the most popular social media platform among children, and it is their preferred platform. Parents are urged to encourage their children to use social media platforms for beneficial purposes, and media industry stakeholders should develop and implement initiatives to increase the benefits of social media for children. Regulation and supervision are necessary to mitigate the adverse consequences of children’s social media usage.
Reliability of Wearable Technology to Monitor Core Temperature Among Helicopter-Based EMS Crews
Authors: Callihan Michael , Cole Heather , Callihan Amanda , Penn Elizabeth , Peek Lauren , Barrow Mahalia , Lungu Claudiu , Odame Emmanuel Atuahene , Oh Jonghwa , Stokley Holly , Wickliffe Jeffrey , Winchester Lee
Published: September 2024

Background:

Excessive heat stress led to more than 400 deaths in the United States from 2011 to 2021. Common methods for heat injury prevention revolve around measurements of the environment and fail to account for the unique individual response to stressors.

Methods:

An observational approach was utilized with nine helicopter-based emergency medical services personnel during emergency flights to compare core temperature readings obtained from an ingestible temperature monitoring pill and the estimated core temperature reading of the Slate Safety Band V2 wearable device. Comparison of data was conducted within Microsoft Excel programming to determine the mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), mean biased error (MBE), and Bland–Altman plot development.

Findings:

A significant bias ( t = 17.58, p < .001) toward the Slate Safety device reading higher with an average difference of −0.48°C (−0.86°F) was found, meaning the average temperature reading is 0.48°C (−0.86°F) higher with the Slate Safety device. A significant correlation of .26 ( p < .001) was noted between the ingestible pill and the wearable device with a 95% confidence interval of 0.23 to 0.29. Aggregate core temperature data demonstrated an MSE of 0.43, an RMSE of 0.65, an MAE of 0.54, and an MBE of −0.48.

Conclusions/Application to Practice:

The ability to monitor the physiological parameters of a worker remotely adds safety tools relative to the risks of heat stress. The slightly higher reading associated with the Slate Safety wearable device provides an added safety margin to protect our workers.
A Comprehensive Examination of Entrepreneurial Networking Within the Indian Entrepreneurial Ecosystem
Authors: Khokhawala Shirin M. , Iyer Radha
Published: September 2024

Entrepreneurial networking is critical for early-stage entrepreneurs to sustain their ideas, gather knowledge, and innovate, especially in emerging economies. This qualitative study explores entrepreneurial networking within the Indian entrepreneurial ecosystem, with primary data collected through interviews with 20 entrepreneurship experts, that include educators, government policymakers, investors, mentors and incubation managers. Theoretical bounding provides a clear understanding of the phenomenon. The research employs a grounded theory approach to develop clarity on the factors influencing entrepreneurial networking. The findings suggest that motivation, driven by the entrepreneur’s desire to create impact and other key motivational factors, significantly affects networking behaviour. Trust, encompassing both being trusting and trustworthy, positively influences networking, while networking impacts innovation and venture performance. Entrepreneurial networking facilitates social capital creation within and outside the ecosystem, enabling entrepreneurs to fulfil various early-stage venture needs, such as team formation, securing capital and finding customers and suppliers. This study contributes to the literature by addressing the gap in understanding the entrepreneurial networking phenomenon for early-stage entrepreneurs within the Indian context. The implications of these findings for industry, academia, research and policy are discussed, highlighting the importance of fostering a supportive entrepreneurial ecosystem that encourages networking and collaboration among the various stakeholders.
Comparison of Bond Strength of Soft Denture Liner on the Denture Base Materials Produced by Different Methods and Effect of Thermocycling
Authors: Tugut Faik , Koyu Tug˘çe , Turkyilmaz Orhun
Published: September 2024

Aim:

This study set out to determine the tensile bond strength between denture bases (produced by 3D printing technology, conventional technique, and computer-aided design and computer-aided manufacturing [CAD/CAM] milled) and silicone-based soft lining material. The consequence of thermocycling on the bonding strength was also investigated.

Materials and Methods:

The bonding between denture foundation materials produced through three distinct techniques (conventional, CAD/CAM milled, and 3D printed) and silicone-based soft lining material was examined. Before tensile testing, half of the samples underwent thermocycling (5–55°C, 5,000 cycles) in 37°C distilled water for 48 hours. A universal testing apparatus employed a crosshead speed of 5 mm/min. The failure type was identified visually, and the maximum tensile strength was noted. The Shapiro-Wilk test and analysis of variances ( P = .05) were used to assess the statistics.

Results:

CAD/CAM milled denture base material (1.56 ± 0.62/1.36 ± 0.16 MPa) showed higher bond strength values than the other denture bases in the tensile test conducted before and after thermocycling ( P < .001). The denture base material made conventionally had the lowest bond strength (1.02 ± 0.24/0.77 ± 0.1 MPa) ( P < .001). The tensile bond strength values of the conventional and 3D printing groups showed a statistically significant drop before and after thermocycling ( P = .001). Regardless of thermocycling, adhesive failure was primarily seen in all groups (76.6%).

Conclusion:

Compared to conventionally produced denture bases, the bond strength of soft relining materials to CAD/CAM milled and 3D printed denture base is different. In denture base materials that are conventionally, CAD/CAM and 3D printed, the thermocycling method reduced bonding strength values.
Lower PrEP Retention among Young and Black Clients Accessing PrEP at a Cluster of Safety Net Clinics for Gay and Bisexual Men
Authors: Agarwal Harsh , Erwin Mark , Lyles Scott , Esposito Maria , Ahsan Zunaid
Published: September 2024

Young men of color who have sex with men are vulnerable to HIV and experience poor PrEP uptake and retention. We conducted a secondary data analysis and calculated adjusted Prevalence Odds Ratios (aPORs) for PrEP retention along with 95% CIs at 90, 180, and 360 days at an organization running safety net clinics in Texas for gay and bisexual men. We found statistically significant association with age, race, in-clinic versus telehealth appointments, and having healthcare insurance. White clients had an aPOR of 1.29 [1.00, 1.67] as compared to Black clients at 90 days. Age group of 18–24 had a lower aPOR than all other age groups except 55 or older at all three time periods. Clients who met providers in person had an aPOR of 2.6 [2.14, 3.19] at 90, 2.6 [2.2, 3.30] at 180 days and 2.84 [2.27, 3.54] at 360 days. Our findings highlight the need for population-specific targeted interventions.
Measuring the Efficacy of Zearn Math in Louisiana
Authors: Hashim Shirin
Published: September 2024

This study examines the impact of an online math learning program on third through fifth grade math achievement in Louisiana. Employing Zearn Math usage metrics and administrative data from the Louisiana Department of Education, the results indicate that grade levels that programmatically used Zearn Math scored, on average, about .03 standard deviation units higher on Louisiana’s statewide math assessment. A placebo test using English-language arts scores and several robustness checks suggests that this may be an underestimate of the true effect. These findings come at a crucial time because pandemic-related school closures have led to a 20-fold increase in public school spending on Zearn-related materials between July 2019 and July 2021, and its presence continues to expand across the nation.
Hydro-Political Dynamics Between China–India–Pakistan: Dams and Transboundary River Governance Amidst Geopolitical Contestations
Authors: Godara Hari , Pathania Jyoti M. , Kumar Gaurav
Published: September 2024

Transboundary rivers raise critical concerns for state security amidst contemporary ecological strain and regional geopolitics in South Asia. The challenge of ‘water security’ is underscored by the substantial reliance on transboundary rivers, compounded by the multifaceted impacts of climate change and the simmering geopolitical tensions among riparian nations, especially in the complex dynamics between India–China and India–Pakistan. This study endeavours to illuminate distinctive characteristics of the South Asian transboundary governance framework, wherein rivers are subjected to intensive damming aimed at (a) harnessing hydroelectric potential and (b) leveraging water resources as geopolitical bargaining chips, thereby exerting pressure; however, order is not specified, particularly. In this intricate milieu, international conventions often fail to reconcile internal contradictions inherent within the transboundary governance paradigm. Consequently, transboundary water resources have metamorphosed into an extension of geopolitical realities, embodying intricate interplay between hydrology, geopolitics and state security within the region, especially between China, India and Pakistan.
Enhancement of Photoelectric Conversion Efficiency in Dye-Sensitized Solar Cells Using SnO2–TiO2 Composite Nanofibers
Authors: Xu Jun , Wen Yuhang , Chang Qiqi , Hao Tianxu , He Tianhong , Zhang Jian , He Lei , Zhang Chenxu , Liu Yuanjun
Published: September 2024

SnO2 is a wide-band gap N-type semiconductor material with a higher electron transfer rate than TiO2. Therefore, SnO2 has broad application prospects in the photoanode composite materials of dye-sensitized solar cells (DSSC). In this study, SnO2–TiO2 composite nanofibers with different molar ratios (5%, 10%, 15%, and 20%) were prepared by double-needle electrospinning technology, and the nanofibers were characterized after adjusting the solution composition. Different molar ratios of TiO2 and SnO2–TiO2 composite nanofiber photoanodes were fabricated by spin-coating, and the adsorption behavior of dyes on the photoanodes was investigated. Moreover, the electrochemical impedance of the photoanodes and DSSC and their photoelectric performance were also tested. The experimental results showed that SnO2–TiO2 composite nanofibers with a molar ratio of 10% exhibited excellent properties, including a peak specific surface area of 93.01 m2/g, strong dye adsorption capacity, small interfacial resistance, and fast electron transfer rate. These outstanding properties significantly promoted the generation of photoelectrons and improved the photoelectric conversion efficiency of DSSC. Compared with single-component TiO2, the photoelectric conversion efficiency of SnO2–TiO2 nanofiber photoanode composite material improved by 85.65%.
Mandatory Corporate Carbon Disclosures and the Path to Net Zero
Authors: Bolton Patrick , Reichelstein Stefan J. , Kacperczyk Marcin T. , Leuz Christian , Ormazabal Gaizka , Schoenmaker Dirk
Published: September 2024

To advance the world’s progress toward a net zero carbon economy, Patrick Bolton, Stefan Reichelstein, Marcin Kacperczyk, Christian Leuz, Gaizka Ormazabal, and Dirk Schoenmaker recommend that governments impose a mandate on corporations requiring them to report their annual direct carbon emissions.1
Using Business Analytics to Upgrade Sales Promotions
Authors: Baardman Lennart , Cohen Maxime C. , Panchamgam Kiran , Perakis Georgia
Published: September 2024

Lennart Baardman, Maxime Cohen, Kiran Panchamgam, and Georgia Perakis present a detailed case study of how business analytics, prediction models, and optimization methods can be used to improve promotion planning. They describe the entire process, from collecting data to computing promotion recommendations for retailers.
How to Choose the Right Strategy for Digital Transformation
Authors: Mithas Sunil , Rust Roland T.
Published: September 2024

Many executives believe that, in digital transformation, they must pursue either revenue growth or cost reduction, but not both. Sunil Mithas and Roland Rust explain how companies can invest in information technology to pursue both goals.
PUTTING SUPPLY CHAIN RESILIENCE THEORY INTO PRACTICE
Authors: Cohen Morris A. , Cui Shiliang , Doetsch Sebastian , Ernst Ricardo , Huchzermeier Arnd , Kouvelis Panos , Lee Hau , Matsuo Hirofumi , Tsay Andy A.
Published: September 2024

Morris Cohen et al. find that while managers generally understand the basics of supply chain resilience, putting them to work remains challenging. Drawing on interviews with executives, they describe these challenges and share their recommendations for how to overcome them.
How Brands Can Leverage Their Social Media Marketing
Authors: Colicev Anatoli , Malshe Ashwin , Pauwels Koen
Published: September 2024

Anatoli Colicev, Ashwin Malshe, and Koen Pauwels find that both earned and owned social media increase consumers’ awareness, purchase intent, and satisfaction. However, firms can only increase purchase intent with owned social media if they have their house in order.
Unlocking Innovative Selling
Authors: Li Qing , Tang Christopher
Published: September 2024

Online sellers have used several innovative strategies to find out how much customers are willing to pay and to encourage them to pay different prices accordingly. Yet name your own price, pay what you want, and opaque selling did not work as planned. Qing Li and Christopher Tang suggest ways that sellers can unlock the value of these strategies.
Evaluating the impact of urban traffic patterns on air pollution emissions in Dublin: a regression model using google project air view data and traffic data
Authors: Tafidis Pavlos , Gholamnia Mehdi , Sajadi Payam , Krishnan Vijayakrishnan Sruthi , Pilla Francesco
Published: September 2024

Air pollution is a significant and pressing environmental and public health concern in urban areas, primarily driven by road transport. By gaining a deeper understanding of how traffic dynamics influence air pollution, policymakers and experts can design targeted interventions to tackle these critical issues. In order to analyse this relationship, a series of regression algorithms were developed utilizing the Google Project Air View (GPAV) and Dublin City’s SCATS data, taking into account various spatiotemporal characteristics such as distance and weather. The analysis showed that Gaussian Process Regression (GPR) mostly outperformed Support Vector Regression (SVR) for air quality prediction, emphasizing its suitability and the importance of considering spatial variability in modelling. The model describes the data best for particulate matter (PM2.5) emissions, with R-squared (R2) values ranging from 0.40 to 0.55 at specific distances from the centre of the study area based on the GPR model. The visualization of pollutant concentrations in the study area also revealed an association with the distance between intersections. While the anticipated direct correlation between vehicular traffic and air pollution was not as pronounced, it underscores the complexity of urban emissions and the multitude of factors influencing air quality. This revelation highlights the need for a multifaceted approach to policymaking, ensuring that interventions address a broader spectrum of emission sources beyond just traffic. This study advances the current knowledge on the dynamic relationship between urban traffic and air pollution, and its findings could provide theoretical support for traffic planning and traffic control applicable to urban centres globally.
Evaluation of the invasiveness of pure ground-glass nodules based on dual-head ResNet technique
Authors: Yang Dengfa , Yang Yang , Zhao MinYi , Ji Hongli , Niu Zhongfeng , Hong Bo , Shi Hengfeng , He Linyang , Shao Meihua , Wang Jian
Published: September 2024

Objective

To intelligently evaluate the invasiveness of pure ground-glass nodules with multiple classifications using deep learning.

Methods

pGGNs in 1136 patients were pathologically confirmed as lung precursor lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Four different models [EfficientNet-b0 2D, dual-head ResNet_3D, a 3D model combining three features (3D_3F), and a 3D model combining 19 features (3D_19F)] were constructed to evaluate the invasiveness of pGGNs using the EfficientNet and ResNet networks. The Obuchowski index was used to evaluate the differences in diagnostic efficiency among the four models.

Results

The patients with pGGNs (360 men, 776 women; mean age, 54.63 ± 12.36 years) included 235 cases of AAH + AIS, 332 cases of MIA, and 569 cases of IAC. In the validation group, the areas under the curve in detecting the invasiveness of pGGNs as a three-category classification (AAH + AIS, MIA, IAC) were 0.8008, 0.8090, 0.8165, and 0.8158 for EfficientNet-b0 2D, dual-head ResNet_3D, 3D_3F, and 3D_19F, respectively, whereas the accuracies were 0.6422, 0.6158, 0.651, and 0.6364, respectively. The Obuchowski index revealed no significant differences in the diagnostic performance of the four models.

Conclusions

The dual-head ResNet_3D_3F model had the highest diagnostic efficiency for evaluating the invasiveness of pGGNs in the four models.
Implementation of health-promoting retail initiatives in the Healthier Choices in Supermarkets Study—qualitative perspectives from a feasibility study
Authors: Duus Katrine Sidenius , Tjørnhøj-Thomsen Tine , Krølner Rikke Fredenslund
Published: September 2024

Background

Improving food environments like supermarkets has the potential to affect customers’ health positively. Scholars suggest researchers and retailers collaborate closely on implementing and testing such health-promoting interventions, but knowledge of the implementation of such interventions is limited. We explore the implementation of four health-promoting food retail initiatives selected and developed by a partnership between a research institution, a large retail group, and a non-governmental organisation.

Methods

The four initiatives included downsizing of bags for pick’n’ mix sweets and soda bottles at the check-out registers, shelf tags promoting healthier breakfast cereal options, and replacing a complimentary bun with a banana offered to children. The initiatives were implemented for 6 weeks (or longer if the store manager allowed it) in one store in Copenhagen, Denmark. Data were collected through observations, informal interviews with customers, and semi-structured interviews with retailers. We conducted a thematic analysis of transcripts and field notes inspired by process evaluation concepts and included quantitative summaries of selected data.

Results

Two out of four initiatives were not implemented as intended. The implementation was delayed due to delivery issues, which also resulted in soda bottles not being downsized as intended. The maintenance of the shelf tags decreased over time. Retailers expressed different levels of acceptability towards the initiatives, with a preference for the complimentary banana for children. This was also the only initiative noticed by customers with both positive and negative responses. Barriers and facilitators of implementation fell into three themes: Health is not the number one priority, general capacity of retailers, and influence of customers and other stakeholders on store operation.

Conclusions

The retailers’ interests, priorities, and general capacity influenced the initiative implementation. Retailers’ acceptability of the initiatives was mixed despite their involvement in the pre-intervention phase. Our study also suggests that customer responses towards health-promoting initiatives, as well as cooperation with suppliers and manufacturers in the development phase, may be determining to successful implementation. Future studies should explore strategies to facilitate implementation, which can be applied prior to and during the intervention.
Integrating machine learning and artificial intelligence in life-course epidemiology: pathways to innovative public health solutions
Authors: Chen Shanquan , Yu Jiazhou , Chamouni Sarah , Wang Yuqi , Li Yunfei
Published: September 2024

The integration of machine learning (ML) and artificial intelligence (AI) techniques in life-course epidemiology offers remarkable opportunities to advance our understanding of the complex interplay between biological, social, and environmental factors that shape health trajectories across the lifespan. This perspective summarizes the current applications, discusses future potential and challenges, and provides recommendations for harnessing ML and AI technologies to develop innovative public health solutions. ML and AI have been increasingly applied in epidemiological studies, demonstrating their ability to handle large, complex datasets, identify intricate patterns and associations, integrate multiple and multimodal data types, improve predictive accuracy, and enhance causal inference methods. In life-course epidemiology, these techniques can help identify sensitive periods and critical windows for intervention, model complex interactions between risk factors, predict individual and population-level disease risk trajectories, and strengthen causal inference in observational studies. By leveraging the five principles of life-course research proposed by Elder and Shanahan—lifespan development, agency, time and place, timing, and linked lives—we discuss a framework for applying ML and AI to uncover novel insights and inform targeted interventions. However, the successful integration of these technologies faces challenges related to data quality, model interpretability, bias, privacy, and equity. To fully realize the potential of ML and AI in life-course epidemiology, fostering interdisciplinary collaborations, developing standardized guidelines, advocating for their integration in public health decision-making, prioritizing fairness, and investing in training and capacity building are essential. By responsibly harnessing the power of ML and AI, we can take significant steps towards creating healthier and more equitable futures across the life course.
Cruciferous vegetables lower blood pressure in adults with mildly elevated blood pressure in a randomized, controlled, crossover trial: the VEgetableS for vaScular hEaLth (VESSEL) study
Authors: Connolly Emma L. , Liu Alex H. , Radavelli-Bagatini Simone , Shafaei Armaghan , Boyce Mary C. , Wood Lisa G. , McCahon Lyn , Koch Henrietta , Sim Marc , Hill Caroline R. , Parmenter Benjamin H. , Bondonno Nicola P. , Devine Amanda , Croft Kevin D. , Mithen Richard , Gan Seng Khee , Schultz Carl J. , Woodman Richard J. , Bondonno Catherine P. , Lewis Joshua R. , Hodgson Jonathan M. , Blekkenhorst Lauren C.
Published: September 2024

Background

Higher cruciferous vegetable intake is associated with lower cardiovascular disease risk in observational studies. The pathways involved remain uncertain. We aimed to determine whether cruciferous vegetable intake (active) lowers 24-h brachial systolic blood pressure (SBP; primary outcome) compared to root and squash vegetables (control) in Australian adults with mildly elevated BP (SBP 120–160 mmHg inclusive).

Methods

In this randomized, controlled, crossover trial, participants completed two 2-week dietary interventions separated by a 2-week washout. Cruciferous vegetables were compared to root and squash vegetables (~ 300 g/day) consumed with lunch and dinner meals. Participants were blinded to which interventions were the active and control. Adherence was assessed using food diaries and biomarkers (S-methyl cysteine sulfoxide (SMCSO, active) and carotenoids (control)). Twenty-four-hour brachial ambulatory SBP and secondary outcomes were assessed pre- and post each intervention. Differences were tested using linear mixed effects regression.

Results

Eighteen participants were recruited (median (IQR) age: 68 (66–70); female: n = 16/18; mean ± SD clinic SBP: 135.9 ± 10.0 mmHg). For both interventions, 72% participants had 100% adherence (IQR: 96.4–100%). SMCSO and carotenoids were significantly different between interventions (mean difference active vs. control SMCSO: 22.93 mg/mL, 95%CI 15.62, 30.23, P < 0.0001; carotenoids: − 0.974 mg/mL, 95%CI − 1.525, − 0.423, P = 0.001). Twenty-four-hour brachial SBP was significantly reduced following the active vs. control (mean difference − 2.5 mmHg, 95%CI − 4.2, − 0.9, P = 0.002; active pre: 126.8 ± 12.6 mmHg, post: 124.4 ± 11.8 mmHg; control pre: 125.5 ± 12.1 mmHg, post: 124.8 ± 13.1 mmHg, n = 17), driven by daytime SBP (mean difference − 3.6 mmHg, 95%CI − 5.4, − 1.7, P < 0.001). Serum triglycerides were significantly lower following the active vs. control (mean difference − 0.2 mmol/L, 95%CI − 0.4, − 0.0, P = 0.047).

Conclusions

Increased intake of cruciferous vegetables resulted in reduced SBP compared to root and squash vegetables. Future research is needed to determine whether targeted recommendations for increasing cruciferous vegetable intake benefits population health.

Trial registration

Clinical trial registry ACTRN12619001294145. https://www.anzctr.org.au
Efficacy and safety of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pancreatic cancer peritoneal metastasis
Authors: Yan Guojun , Zhang Kai , Yan Lijun , Zhang Yanbin
Published: September 2024

Objectives

Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group.

Methods

A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS).

Results

A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified.

Conclusions

The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.
Developmental trends in young children’s device-measured physical activity and sedentary behaviour
Authors: Christian Hayley E. , Adams Emma K. , Moore Hannah L. , Nathan Andrea , Murray Kevin , Schipperijn Jasper , Trost Stewart G.
Published: September 2024

Background

Knowledge of developmental trends in meeting age-specific 24-hour movement behaviour guidelines is lacking. This study describes developmental trends in device-measured physical activity and sedentary time over a three-year period among Western Australian children aged two to seven years, including differences between boys and girls. The proportion of children meeting age-specific physical activity guidelines before and after they transition to full-time school was also examined.

Methods

Data from waves 1 and 2 of the Play Spaces and Environments for Children’s Physical Activity (PLAYCE) cohort study were used (analysis n = 1217). Physical activity and sedentary time were measured by accelerometry at ages two to five (preschool, wave 1) and ages five to seven (commenced full-time school, wave 2). Accelerometer data were processed using a validated machine-learning physical activity classification model. Daily time spent in sedentary behaviour, energetic play (moderate-to-vigorous physical activity (MVPA)), total physical activity, and meeting physical activity guidelines were analysed using linear and generalised linear mixed-effects models with age by sex interaction terms.

Results

All movement behaviours changed significantly with increasing age, and trends were similar in boys and girls. Total daily physical activity increased from age two to five then declined to age seven. Mean daily total physical activity exceeded 180 min/day from ages two to five. Daily energetic play increased significantly from age two to seven, however, was below 60 min/day at all ages except for seven-year-old boys. Daily sedentary time decreased to age five then increased to age seven but remained lower than at age two. All two-year-olds met their age-specific physical activity guideline, decreasing to 5% of girls and 6% of boys at age four. At age seven, 46% of boys and 35% of girls met their age-specific physical activity guideline.

Conclusions

Young children’s energetic play and total physical activity increased with age, but few children aged three to seven met the energetic play (MVPA) guideline. Interventions should focus on increasing children’s energetic play in early childhood. Clearer guidance and strategies are needed to support young children as they change developmentally and as they transition from one age-specific movement guideline to the next.
Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model
Authors: Zhang Qi , Liu Meng , Xu Yue , Lee Juhyung , Jones Brothely , Li Bing , Huang Wenwei , Ye Yihong , Zheng Wei
Published: September 2024

Background

Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons and the accumulation of Lewy-body protein aggregates containing misfolded α-synuclein (α-syn) in a phosphorylated form. The lack of effective models for drug screens has hindered drug development studies for PD. However, the recent development of in vitro brain-like organoids provides a new opportunity for evaluating therapeutic agents to slow the progression of this chronic disease.

Methods

In this study, we used a 3D brain-like organoid model to investigate the potential of repurposing Tilorone, an anti-viral drug, for impeding the propagation of α-synucleinopathy. We assessed the effect of Tilorone on the uptake of fluorescently labeled α-syn preformed fibrils (sPFF) and sPFF-induced apoptosis using confocal microscopy. We also examined Tilorone’s impact on the phosphorylation of endogenous α-syn induced by pathogenic sPFF by immunoblotting midbrain-like organoid extracts. Additionally, quantitative RT-PCR and proteomic profiling of sPFF-treated organoids were conducted to evaluate the global impact of Tilorone treatment on tissue homeostasis in the 3D organoid model.

Results

Tilorone inhibits the uptake of sPFF in both mouse primary neurons and human midbrain-like organoids. Tilorone also reduces the phosphorylation of endogenous α-syn induced by pathogenic α-syn fibrils and mitigates α-syn fibril-induced apoptosis in midbrain-like organoids. Proteomic profiling of fibril-treated organoids reveals substantial alterations in lipid homeostasis by α-syn fibrils, which are reversed by Tilorone treatment. Given its safety profile in clinics, Tilorone may be further developed as a therapeutic intervention to alleviate the propagation of synucleinopathy in PD patients.
Genomic-inferred cross-selection methods for multi-trait improvement in a recurrent selection breeding program
Authors: Atanda Sikiru Adeniyi , Bandillo Nonoy
Published: September 2024

The major drawback to the implementation of genomic selection in a breeding program lies in long-term decrease in additive genetic variance, which is a trade-off for rapid genetic improvement in short term. Balancing increase in genetic gain with retention of additive genetic variance necessitates careful optimization of this trade-off. In this study, we proposed an integrated index selection approach within the genomic inferred cross-selection (GCS) framework to maximize genetic gain across multiple traits. With this method, we identified optimal crosses that simultaneously maximize progeny performance and maintain genetic variance for multiple traits. Using a stochastic simulated recurrent breeding program over a 40-years period, we evaluated different GCS methods along with other factors, such as the number of parents, crosses, and progeny per cross, that influence genetic gain in a pulse crop breeding program. Across all breeding scenarios, the posterior mean variance consistently enhances genetic gain when compared to other methods, such as the usefulness criterion, optimal haploid value, mean genomic estimated breeding value, and mean index selection value of the superior parents. In addition, we provide a detailed strategy to optimize the number of parents, crosses, and progeny per cross that can potentially maximize short- and long-term genetic gain in a public breeding program.
Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy
Authors: He Kewen , Puebla-Osorio Nahum , Barsoumian Hampartsoum B. , Sezen Duygu , Rafiq Zahid , Riad Thomas S. , Hu Yun , Huang Ailing , Voss Tiffany A. , Leyton Claudia S. Kettlun , Schuda Lily Jae , Hsu Ethan , Heiber Joshua , Cortez Maria-Angelica , Welsh James W.
Published: September 2024

Background

Combining interleukin-2 (IL-2) with radiotherapy (RT) and immune checkpoint blockade (ICB) has emerged as a promising approach to address ICB resistance. However, conventional IL-2 cytokine therapy faces constraints owing to its brief half-life and adverse effects. RDB 1462, the mouse ortholog of Nemvaleukin alfa, is an engineered IL-2 with an intermediate affinity that selectively stimulates antitumor CD8 T and NK cells while limiting regulatory T cell expansion. This study aimed to evaluate the antitumor activity and mechanism of action of the combination of RDB 1462, RT, and anti-PD1 in mouse tumor models.

Methods

Two bilateral lung adenocarcinoma murine models were established using 344SQ-Parental and 344SQ anti-PD1-resistant cell lines. Primary tumors were treated with RT, and secondary tumors were observed for evidence of abscopal effects. We performed immune phenotyping by flow cytometry, analyzed 770 immune-related genes using NanoString, and performed T cell receptor (TCR) repertoire analysis. Serum pro-inflammatory cytokine markers were analyzed by 23-plex kit.

Results

Compared to native IL-2 (RDB 1475), RDB 1462 demonstrated superior systemic antitumoral responses, attributable, at least in part, to augmented levels of CD4 and CD8 T cells with the latter. Our findings reveal substantial reductions in primary and secondary tumor volumes compared to monotherapy controls, with some variability observed among different dosing schedules of RDB 1462 combined with RT. Blood and tumor tissue-based flow cytometric phenotyping reveals an increase in effector memory CD8 and CD4 T cells and a decrease in immunosuppressive cells accompanied by a significant increase in IL-2, IFN-γ, and GM-CSF levels in the combination group. Transcriptomic profiling and TCR sequencing reveal favorable gene expression and T cell repertoire patterns with the dual combination. Furthermore, integrating anti-PD1 therapy with RT and RDB 1462 further reduced primary and secondary tumor volumes, prolonged survival, and decreased lung metastasis. Observations of immune cell profiles indicated that RT with escalating doses of RDB 1462 significantly reduced tumor growth and increased tumor-specific immune cell populations.

Conclusion

The addition of Nemvaleukin therapy may enhance responses to RT alone and in combination with anti-PD1.

Graphical Abstract
Saving lives with statistics
Authors: Røislien Jo
Published: September 2024

Healthcare is awash with numbers, and figuring out what knowledge these numbers might hold is worthwhile in order to improve patient care. Numbers allow for objective mathematical analysis of the information at hand, but while mathematics is objective by design, our choice of mathematical approach in a given situation is not. In prehospital and critical care, numbers stem from a wide range of different sources and situations, be it experimental setups, observational data or data registries, and what constitutes a “good” statistical analysis can be unclear. A well-crafted statistical analysis can help us see things our eyes cannot, and find patterns where our brains come short, ultimately contributing to changing clinical practice and improving patient outcome. With increasingly more advanced research questions and research designs, traditional statistical approaches are often inadequate, and being able to properly merge statistical competence with clinical knowhow is essential in order to arrive at not only correct, but also valuable and usable research results. By marrying clinical knowhow with rigorous statistical analysis we can accelerate the field of prehospital and critical care.
SMSs as an alternative to provider-delivered care for unhealthy alcohol use: study protocol for Leseli, an open-label randomised controlled trial of mhGAP-Remote vs mhGAP-Standard in Lesotho
Authors: Belus Jennifer M. , Johnson Natalie E. , Yoon Grace H. , Tschumi Nadine , Lerotholi Malebanye , Falgas-Bague Irene , Lee Tristan T. , Letsoela Pearl , Magidson Jessica F. , Amstutz Alain , Labhardt Niklaus D.
Published: September 2024

Background

The World Health Organization’s (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below).

Methods

This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (Nplanned = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs < 50 years old). Follow-up assessments occur at 8, 20, and 32 weeks post-randomisation. The primary outcome is change in self-reported alcohol use (continuous AUDIT score), from baseline to 8 weeks follow-up. Change in the AUDIT from baseline to 20 and 32 weeks follow-up is a secondary outcome. Change in the biomarker phosphatidylethanol (secondary), liver enzyme values in serum (exploratory), and HIV viral load (for people with HIV only; exploratory) are also evaluated from baseline throughout the entire follow-up period. A linear regression model will be conducted for the primary analysis, adjusted for the stratification factors. Three a priori sensitivity analyses for the primary outcome are planned based on per protocol treatment attendance, recovery from unhealthy alcohol use, and clinically significant and reliable change.

Discussion

This trial will provide insight into feasibility and effectiveness of a shortened and primarily SMS supported version of mhGAP, which is especially relevant for settings where regular clinic attendance is a major barrier.

Trial registration

clinicaltrials.gov NCT05925270. Approved on June 29th, 2023.
Cleavage and polyadenylation factors are potential regulators of adipogenesis
Authors: Mostafa Salwa Mohd , Moore Claire
Published: September 2024

Objective

Alternative polyadenylation (APA) is a co-transcriptional process that leads to isoform diversity in the 3’ ends of mRNAs. APA is known to occur during differentiation, and its dysregulation is observed in diseases like cancer and autoimmune disorders. It has been previously reported that differentiation of 3T3-L1 cells to adipocytes leads to an overall lengthening of mRNAs, but the proteins involved in this regulation have not been identified. The expression levels of subunits of the cleavage and polyadenylation (C/P) complex can regulate the choice of poly(A) site, which in turn can affect different cellular activities. In this paper, we studied the change in levels of C/P proteins during 3T3-L1 differentiation.

Results

We observed that while the RNA expression of these proteins is unchanged during differentiation, the protein levels of some subunits do change, including a decrease in levels of CPSF73, the nuclease that cuts at the poly(A) site. However, overexpression of CPSF73 alone does not affect the efficiency and rate of differentiation.
Prostatic lineage differentiation from human embryonic stem cells through inducible expression of NKX3-1
Authors: Wang Songwei , Yu Yangyang , Li Yinglei , Zhang Tianzhe , Jiang Wei , Wang Xinghuan , Liu Ran
Published: September 2024

Background

Understanding the lineage differentiation of human prostate not only is crucial for basic research on human developmental biology but also significantly contributes to the management of prostate-related disorders. Current knowledge mainly relies on studies on rodent models, lacking human-derived alternatives despite clinical samples may provide a snapshot at certain stage. Human embryonic stem cells can generate all the embryonic lineages including the prostate, and indeed a few studies demonstrate such possibility based on co-culture or co-transplantation with urogenital mesenchyme into mouse renal capsule.

Methods

To establish a stepwise protocol to obtain prostatic organoids in vitro from human embryonic stem cells, we apply chemicals and growth factors by mimicking the regulation network of transcription factors and signal transduction pathways, and construct cell lines carrying an inducible NKX3-1 expressing cassette, together with three-dimensional culture system. Unpaired t test was applied for statistical analyses.

Results

We first successfully generate the definitive endoderm, hindgut, and urogenital sinus cells. The embryonic stem cell-derived urogenital sinus cells express prostatic key transcription factors AR and FOXA1, but fail to express NKX3-1. Therefore, we construct NKX3-1-inducible cell line by homologous recombination, which is eventually able to yield AR, FOXA1, and NKX3-1 triple-positive urogenital prostatic lineage cells through stepwise differentiation. Finally, combined with 3D culture we successfully derive prostate-like organoids with certain structures and prostatic cell populations.

Conclusions

This study reveals the crucial role of NKX3-1 in prostatic differentiation and offers the inducible NKX3-1 cell line, as well as provides a stepwise differentiation protocol to generate human prostate-like organoids, which should facilitate the studies on prostate development and disease pathogenesis.