bluuebunny/crossref_metadata_2025 huggingface dataset:
A critical influence of HIF-1 on MMP-9 and Galectin-3 in oral lichen planus
Authors: Hazzaa Hala H. , El Shiekh Marwa A. M. , Elkashty Osama , Magdy Eman , Riad Dalia , khalifa Eman , Elewa Gasser M. , Kamal Naglaa M.
Published: July 2024

Objective

Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease.

Subjects and methods

The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group.

Results

Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252).

Conclusion

These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.
Using community-based participatory research methods to build the foundation for an equitable integrated health data system within a Canadian urban context
Authors: Fierheller Dianne , Chu Casey , D’Silva Chelsea , Krishendeholl Arvind , Arham Abdul , Carter Angela , Dias Keddone , Francis Isaac , Glasgow Marcia , Malhotra Gurpreet , Zenlea Ian , Rosella Laura C.
Published: July 2024

Health inequalities amplified by the COVID-19 pandemic have disproportionately affected racialized and equity-deserving communities across Canada. In the Municipality of Peel, existing data, while limited, illustrates that individuals from racialized and equity-deserving communities continue to suffer, receive delayed care, and die prematurely. In response to these troubling statistics, grassroots community advocacy has called on health systems leaders in Peel to work with community and non-profit organizations to address the critical data and infrastructure gaps that hinder addressing the social determinants of health in the region. To support these advocacy efforts, we used a community-based participatory research approach to understand how we might build a data collection ecosystem across sectors, alongside community residents and service providers, to accurately capture the data about the social determinants of health. This approach involved developing a community engagement council, defining the problem with the community, mapping what data is actively collected and what is excluded, and understanding experiences of sociodemographic data collection from community members and service providers. Guided by community voices, our study focused on sociodemographic data collection in the primary care context and identified which service providers use and collect these data, how data are used in their work, the facilitators and barriers to data use and collection. Additionally, we gained insight into how sociodemographic data collection could be respectful, safe, and properly governed from the perspectives of community members. From this study, we identify a set of eight recommendations for sociodemographic data collection and highlight limitations. This foundational community-based work will inform future research in establishing data governance in partnership with diverse and equity-deserving communities.
Integrated domestic violence and reproductive health interventions in India: a systematic review
Authors: Sabri Bushra , Mani Serena Sloka , Kaduluri Venkata Preetam Sandeep
Published: July 2024

Background

Domestic violence is a leading cause of poor health outcomes during pregnancy and the postpartum period. Therefore, there is a need for integrated domestic violence interventions in reproductive health care settings. India has one of the highest maternal and child mortality rates. This review aimed to identify characteristics of existing evidence-based integrated domestic violence and reproductive healthcare interventions in India to identify gaps and components of interventions that demonstrate effectiveness for addressing domestic violence.

Methods

A systematic review of intervention studies was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three research team members performed independent screening of title, abstracts and full-texts.

Results

The search resulted in 633 articles, of which 13 articles met inclusion criteria for full text screening and analysis. Common components of integrated violence and reproductive health interventions that were effective in addressing domestic violence included: psychoeducation/education (n = 5), skill building (n = 5), counseling (n = 5), engaging stakeholders with use of trained lay peer facilitators (n = 3), and engaging male spouses (n = 3).

Conclusions

Interventions in India for domestic violence that are integrated with reproductive health care remain few, and there are fewer with effective outcomes for domestic violence. Of those with effective outcomes, all of the interventions utilized psychoeducation/education, skill building, and counseling as part of the intervention.
An improved bacterial mRNA enrichment strategy in dual RNA sequencing to unveil the dynamics of plant-bacterial interactions
Authors: Shilpha Jayabalan , Lee Junesung , Kwon Ji-Su , Lee Hyun-Ah , Nam Jae-Young , Jang Hakgi , Kang Won-Hee
Published: July 2024

Background

Dual RNA sequencing is a powerful tool that enables a comprehensive understanding of the molecular dynamics underlying plant-microbe interactions. RNA sequencing (RNA-seq) poses technical hurdles in the transcriptional analysis of plant-bacterial interactions, especially in bacterial transcriptomics, owing to the presence of abundant ribosomal RNA (rRNA), which potentially limits the coverage of essential transcripts. Therefore, to achieve cost-effective and comprehensive sequencing of the bacterial transcriptome, it is imperative to devise efficient methods for eliminating rRNA and enhancing the proportion of bacterial mRNA. In this study, we modified a strand-specific dual RNA-seq method with the goal of enriching the proportion of bacterial mRNA in the bacteria-infected plant samples. The enriched method involved the sequential separation of plant mRNA by poly A selection and rRNA removal for bacterial mRNA enrichment followed by strand specific RNA-seq library preparation steps. We assessed the efficiency of the enriched method in comparison to the conventional method by employing various plant-bacterial interactions, including both host and non-host resistance interactions with pathogenic bacteria, as well as an interaction with a beneficial rhizosphere associated bacteria using pepper and tomato plants respectively.

Results

In all cases of plant-bacterial interactions examined, an increase in mapping efficiency was observed with the enriched method although it produced a lower read count. Especially in the compatible interaction with Xanthmonas campestris pv. Vesicatoria race 3 (Xcv3), the enriched method enhanced the mapping ratio of Xcv3-infected pepper samples to its own genome (15.09%; 1.45-fold increase) and the CDS (8.92%; 1.49-fold increase). The enriched method consistently displayed a greater number of differentially expressed genes (DEGs) than the conventional RNA-seq method at all fold change threshold levels investigated, notably during the early stages of Xcv3 infection in peppers. The Gene Ontology (GO) enrichment analysis revealed that the DEGs were predominantly enriched in proteolysis, kinase, serine type endopeptidase and heme binding activities.

Conclusion

The enriched method demonstrated in this study will serve as a suitable alternative to the existing RNA-seq method to enrich bacterial mRNA and provide novel insights into the intricate transcriptomic alterations within the plant-bacterial interplay.
Clinical trial results in context: comparison of baseline characteristics and outcomes of 38,510 RECOVERY trial participants versus a reference population of 346,271 people hospitalised with COVID-19 in England
Authors: Pessoa-Amorim Guilherme , Goldacre Raphael , Crichton Charles , Stevens Will , Nunn Michelle , King Andy , Murray Dave , Welsh Richard , Pinches Heather , Rees Andrew , Morris Eva J. A. , Landray Martin J. , Haynes Richard , Horby Peter , Wallendszus Karl , Peto Leon , Campbell Mark , Harper Charlie , Mafham Marion
Published: July 2024

Background

Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent.

Methods

We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality.

Results

Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3–24.1%]; vs reference 24.8% [24.6–25.0%]), except during the first pandemic wave in the UK (March–May 2020) when adjusted mortality was lower in RECOVERY.

Conclusions

Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates.

Trial registration

ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020.
Random forest and spatial cross-validation performance in predicting species abundance distributions
Authors: Mushagalusa Ciza Arsène , Fandohan Adandé Belarmain , Glèlè Kakaï Romain
Published: July 2024

Random forests (RF) have been widely used to predict spatial variables. Several studies have shown that spatial cross-validation (CV) methods consistently cause RF to yield larger prediction errors compared to standard CV methods. This study examined the impact of species characteristics and data features on the performance of the standard RF and spatial CV approaches for predicting species abundance distribution. It compared the standard 5-fold CV, design-based validation, and three different spatial CV methods, such as spatial buffering, environmental blocking, and spatial blocking. Validation samples were randomly selected for design-based validation without replacement. We evaluated their predictive performance (accuracy and discrimination metrics) using artificial species abundance data generated by a linear function of a constant term ($$\beta _0$$

β
0

) and a random error term following a zero-mean Gaussian process with a covariance matrix determined by an exponential correlation function. The model was tuned over multiple simulations to consider different mean levels of species abundance, spatial autocorrelation variation, and species detection probability. Here we found that the standard RF had poor predictive performance when spatial autocorrelation was high and the species probability of detection was low. Design-based validation and standard K-fold CV were found to be the most effective strategies for evaluating RF performance compared to spatial CV methods, even in the presence of high spatial autocorrelation and imperfect detection for random samples. For weakly or moderately clustered samples, they yielded good modelling efficiency but overestimated RF’s predictive power, while they overestimated modelling efficiency, predictive power, and accuracy for strongly clustered samples with high spatial autocorrelation. Globally, the checkerboard pattern in the allocation of blocks to folds in blocked spatial CV was found to be the most effective CV approach for clustered samples, whatever the degree of clustering, spatial autocorrelation, or species abundance class. The checkerboard pattern in spatial CV was found to be the best method for random or systematic samples with spatial autocorrelation, but less effective than non-spatial CV approaches. Failing to take data features into account when validating models can lead to unrealistic predictions of species abundance and related parameters and, therefore, incorrect interpretations of patterns and conclusions. Further research should explore the benefits of using blocked spatial K-fold CV with checkerboard assignment of blocks to folds for clustered samples with high spatial autocorrelation.
Age- and gender-specific acute poisoning with drugs and medications affecting nervous system
Authors: Mesgarpour Bita , Faridfar Shabnam , Rezaei Mahya , Abdollahiasl Akbar , Shadnia Shahin , Mahdavinejad Arezou , Abdollahi Mohammad
Published: July 2024

Background

We investigated acute poisonings resulting from medications affecting the nervous system and illicit substances at Loghman Hakim Hospital in Tehran.

Methods

We retrospectively reviewed patient records at Iran’s largest tertiary toxicology referral center between January 2010 and December 2015. We analyzed the prevalence, trend, age and gender distribution of acute poisoning caused by nervous system agents.

Results

The present study included 16,657 (57.27%) males and 12,426 (42.73%) females, resulting in 29,083 patients. The median age of men and women was 29 and 26 years, respectively (p < 0.0001). There were 12,071 (72.47%) men and 10,326 (83.10%) women under the age of 40 (p < 0.001). Most cases were intentional (69.38% in men and 79.00% in women, p < 0.001) and 44.10% had a history of poisoning. The proportions of men and women varied significantly between different age groups and nervous system agents. For women, the most common agent was alprazolam, whereas for men, methadone. The overall trend of acute poisoning with drug used in addictive disorders, opioids and alcohol was increasing but decreasing with benzodiazepines and antidepressants. Acute poisoning by nervous system agents led to more deaths in men (1.95% vs. 0.56%; p < 0.001).

Conclusions

Methadone intoxication was common especially among young men and most of these intoxications were intentional. Women and men aged 20–29 most frequently suffer poisoning from alprazolam and clonazepam, respectively. Women over 60 and men over 30 used opium. Illicit drugs caused more than half of the deaths, and opium dominated. This study may create awareness and develop educational and preventive gender and age-specific local programs.
Biological control of the shot-hole disease in flowering cherry tree using antimicrobial compounds produced by Bacillus velezensis 8–2
Authors: Kim Seulbi , Kim Ho Myeong , Yang Jung Eun , Jeong Seul-Gi , Kim Yeong Yeol , Hwang In Min , Yu Nan Hee , Kim Jin-Cheol , Park Hae Woong
Published: July 2024

Background

Effective control of shot-hole disease in flowering cherries is challenging because of multiple causative pathogens (bacteria and fungi). Bacillus species are well-known for their ability to control plant pathogens; therefore, biological control potential of a Bacillus isolate, B. velezensis 8–2, against SH disease on flowering cherry trees was investigated.

Results

This study revealed strong antimicrobial activity of Bacillus velezensis 8–2 against various plant pathogenic bacteria and fungi, particularly focusing on Xanthomonas arboricola pv. pruni (Xap) and Mycosphaerella cerasella (Mc), which cause shot-hole (SH) disease in flowering cherry trees. In vitro assays showed that the fermentation filtrate of B. velezensis 8–2 inhibited bacterial and fungal growth with minimum inhibitory concentrations of 1.25–10% and 2.5–10%, respectively. UPLC-Q–Orbitrap–MS analysis revealed that B. velezensis 8–2 produced antagonistic compounds, including polyketides (difficidin and oxydifficidin) and cyclic lipopeptides (iturin A, fengycin, and surfatin). To enhance antimicrobial activity, fermentation parameters for optimal production of two antibacterial and three antifungal compounds were investigated in a 5 L jar fermenter. By regulating the agitation speed to sustain the state of vegetative cells, the production period was extended by 20 h at 400 rpm, resulting in maximum yields of 86.6 μg/mL for difficidin and 150.0 μg/mL for oxydifficidin within a 72 h fermentation period. In a field trial, a 500-fold diluted 10% suspension concentrate formulation of B. velezensis 8–2 effectively inhibited the development of SH disease, demonstrating 66.6% disease control and a 90.2% disease symptoms reduction.

Conclusions

This is the first report to assess the disease control efficacy of B. velezensis for the biocontrol of SH disease in the field. These results suggest that the application of B. velezensis 8–2 could serve as a practical alternative for managing various bacterial and fungal diseases, including the management of SH disease in flowering cherry trees.

Graphical Abstract
An empirical study of reflection attacks using NetFlow data
Authors: Chuah Edward , Suri Neeraj
Published: July 2024

Reflection attacks are one of the most intimidating threats organizations face. A reflection attack is a special type of distributed denial-of-service attack that amplifies the amount of malicious traffic by using reflectors and hides the identity of the attacker. Reflection attacks are known to be one of the most common causes of service disruption in large networks. Large networks perform extensive logging of NetFlow data, and parsing this data is an advocated basis for identifying network attacks. We conduct a comprehensive analysis of NetFlow data containing 1.7 billion NetFlow records and identified reflection attacks on the network time protocol (NTP) and NetBIOS servers. We set up three regression models including the Ridge, Elastic Net and LASSO. To the best of our knowledge, there is no work that studied different regression models to understand patterns of reflection attacks in a large network. In this paper, we (a) propose an approach for identifying correlations of reflection attacks, and (b) evaluate the three regression models on real NetFlow data. Our results show that (a) reflection attacks on the NTP servers are not correlated, (b) reflection attacks on the NetBIOS servers are not correlated, (c) the traffic generated by those reflection attacks did not overwhelm the NTP and NetBIOS servers, and (d) the dwell times of reflection attacks on the NTP and NetBIOS servers are too small for predicting reflection attacks on these servers. Our work on reflection attacks identification highlights recommendations that could facilitate better handling of reflection attacks in large networks.
Short-term epileptic seizures prediction based on cepstrum analysis and signal morphology
Authors: Tajadini Bahar , Seydnejad Saeid R. , Rezakhani Soheila
Published: July 2024

This article aims to provide and implement a patient-specific seizure (for Intervention Time (IT) detection) prediction algorithm using non-invasive data to develop warning devices to prevent further patient injury and reduce stress. Employing algorithms with high initial data volume and computations time to increase the accuracy is an important problem in prediction issues. Consequently, reduction of calculations is met by applying only two effective EEG signal channels without manual removal of artifacts by visual inspection as the algorithm’s input. Autoregression (AR) modeling and Cepstrum detect changes due to IT period. We carry out the goal of higher accuracy by increasing sensitivity to interictal epileptiform discharges or artifacts and reduce errors caused by them, taking advantage of the discrete wavelet transform and the comparison of two channels epochs by applying the median filter. Averaging and positive envelope methods are introduced to patient-specific thresholds become more differentiated as soon as possible and can be lead to sooner prediction. We examined this method on a mathematical model of adult epilepsy as well as on 10 patients with EEG data. The results of our experiments confirm that performance of the proposed approach in accuracy and average false prediction rate is superior to other algorithms. Simulation results have been shown the robustness of our proposed method to artifacts and errors, which is a step towards the development of real-time alarm devices by non-invasive techniques.
From tradition to innovation: dadih, the Minangkabau tribe's traditional fermented buffalo milk from Indonesia
Authors: Herlina Vika Tresnadiana , Setiarto R. Haryo Bimo
Published: July 2024

Dadih, also known as dadiah, is a traditional fermented buffalo milk from Minangkabau tribe in West Sumatra. This product is similar to yogurt, with a smooth and shiny surface, thick-bodied, creamy color and pleasant flavor. Microbes that play a dominant role in dadih fermentation are lactic acid bacteria, which possess several functional features, including antimicrobial, antioxidant, antimutagenic, hypocholesterolemic and immunomodulatory properties. However, traditional dadih production faced numerous challenges that impede its development, including the limitation of buffalo milk production, unstandardized dadih production due to the spontaneous fermentation, safety concerns from the absence of heat treatment, as well as limited shelf-life and consumer acceptance of traditional dadih product. Therefore, it is crucial to improve buffalo cultivation, using different types of milk, and apply pasteurization process in dadih production. Furthermore, innovation in dadih product that is more durable and preferred by consumers can be achieved through the application of various processing and packaging technologies.
Correlations of pathomorphological parameters between lesions at the invasive front and lymph node metastases in colorectal cancer: a retrospective clinical study
Authors: Peng Hui , Zhang Zhifa , Wu Yingjun , Zhu Yalan
Published: July 2024

Background

Lymph node (LN) metastasis is one of the most important indicators to evaluate stage, choose treatment strategy, and predict outcome of colorectal cancer (CRC). The morphological correlation between primary tumors and LN metastases can help predict the incidence of LN metastasis in CRC more accurately and assist with more individualized risk-stratification management decisions.

Methods

A retrospective study was devised with paired tissue specimens from the invasive front of primary tumors and LN metastases in 426 patients after a radial surgery for CRC. According to the presence (N +) or absence (N-) of regional LN metastasis and the number of LN metastases (pN1a/1b/1c/2a/2b), comparisons were performed regarding tumor budding (TB) and poorly-differentiated clusters (PDC). In addition, their correlation with the incidence of LN metastasis and the extent were explored.

Results

The TB and PDC in the invasive front of primary tumors presented significant correlations with the incidence of LN metastasis and the number of LN metastases in CRC (P < 0.001). TB2/3 led to a risk of LN metastasis 6.68-fold higher than TB1, while PDC2/3 resulted in a risk of LN metastasis 8.46-fold higher than PDC1. Additionally, the risk of developing 4 or more LN metastases was 3.08-fold and 2.86-fold higher upon TB2/3 and PDC2/3 than that with TB1 and PDC1, respectively. Moderate positive correlations were found between the invasive front of primary tumors and LN metastases in terms of TB and PDC, respectively.

Conclusions

TB and PDC, at the invasive tumor front are important morphological markers to evaluate LN metastasis in CRC, and they can be employed as reference indicators to assess or predict the potential of LN metastasis in CRC in clinical practice.
Evaluation of nanocellulose-based anthraquinone from marine fungi Penicillium flavidorsum as an alternative therapy for skin wound healing: histopathological and immunohistochemical evidences from a rat model
Authors: Reda Reham , Assar Doaa H. , Al-Hawary Ibrahim I. , Atiba Ayman , Abdelatty Alaa , Althobaiti Norah , Elbialy Zizy I.
Published: July 2024

Background

Wound healing represents a complex clinical challenge, necessitating the selection of appropriate wound dressings to facilitate an efficient healing process. This study aims to explore an effective approach to enhance wound healing by investigating the therapeutic potential of a nanocellulose-based anthraquinone derived from marine fungi.

Forty male Wistar rats were divided into five groups, including a control group and various four treatment groups. The wound healing process was assessed by measuring the wound area at different time points.

Results

The results showed promising outcomes in terms of wound healing progression. The group treated with anthraquinone and nanocellulose demonstrated the most favorable results, with normal epidermal architecture, marked hyperkeratosis, and minimal dermal edema. This study provides comprehensive evidence supporting the efficacy of this novel alternative therapy through histopathological and immunohistochemical analyses conducted on a rat model.

Conclusion

By addressing the limitations associated with conventional wound dressings, our research contributes to the development of innovative strategies for optimizing wound healing outcomes. The findings presented herein underscore the potential of nanocellulose-based anthraquinone as a promising therapeutic option for promoting skin wound healing. Further investigations are warranted to elucidate the underlying mechanisms and establish the clinical viability of this alternative therapy.
Landscape and challenges in economic evaluations of artificial intelligence in healthcare: a systematic review of methodology
Authors: Kastrup Nanna , Holst-Kristensen Annette W. , Valentin Jan B.
Published: July 2024

Background

The potential for artificial intelligence (AI) to transform healthcare cannot be ignored, and the development of AI technologies has increased significantly over the past decade. Furthermore, healthcare systems are under tremendous pressure, and efficient allocation of scarce healthcare resources is vital to ensure value for money. Health economic evaluations (HEEs) can be used to obtain information about cost-effectiveness. The literature acknowledges that the conduct of such evaluations differs between medical technologies (MedTechs) and pharmaceuticals, and poor quality evaluations can provide misleading results. This systematic review seeks to map the evidence on the general methodological quality of HEEs for AI technologies to identify potential areas which can be subject to quality improvements. We used the 35-item checklist by Drummond and Jefferson and four additional checklist domains proposed by Terricone et al. to assess the methodological quality of full HEEs of interventions that include AI.

Results

We identified 29 studies for analysis. The included studies had higher completion scores for items related to study design than for items related to data collection and analysis and interpretation of results. However, none of the studies addressed MedTech-specific items.

Conclusions

There was a concerningly low number of full HEEs relative to the number of AI publications, however the trend is that the number of studies per year is increasing. Mapping the evidence of the methodological quality of HEEs of AI shows a need to improve the quality in particular the use of proxy measures as outcome, reporting, and interpretation of the ICER.
Improving GPR interpretation by applying image-enhancing attributes and machine learning techniques: A case study over Green Hill Cemetery in Frankfort, Kentucky
Authors: Buist C. Bobby , Bedle Heather
Published: July 2024

Ground-penetrating radar (GPR) enables noninvasive imaging in structural mapping applications such as unmarked grave detection. However, burial signatures can be cryptic and require expert analysis. This study investigates attribute enhancement and machine learning to automate identification of variable-signature graves at Green Hill Cemetery in Frankfort, Kentucky. Nine complementary seismic attributes were computed from the GPR envelope reflectivity volume to boost discontinuities and patterns indicative of shafts. Coherent energy, pseudofrequency, and similarity transforms showed optimal visualization enhancement. These volumes were input into unsupervised k-means and self-organizing map (SOM) machine learning models to cluster potential burial sites. Both methods accurately characterized strong anomaly reflections associated with apparent grave boundaries. However, limitations emerged in classifying subtler signatures that are likely linked to deteriorated or deeper interments. SOM clustering provided finer segmentation between noise and targets. Collectively, attributes amplified burial edges for easier recognition, while machine learning clustering expedited identification of most vault structures and unmarked sites. However, edge case discrimination remains a challenge. Results suggest that hybrid human-machine learning analysis can enhance efficiency over purely manual interpretation. With further method refinement, automated attribute and machine learning workflows show strong potential for accelerating GPR-based cemetery and archaeological mapping.
Seismic modeling using pseudo-impedance derived from physical models
Authors: Willacy Chris , Dooley Tim P.
Published: July 2024

Building accurate numerical models of the earth for simulation is both challenging and time consuming. The subsurface complexity must be captured in sufficient detail for the results to be of practical use for geophysical analysis. Physical models provide an efficient way to add realistic detail to numerical models. Physical models, for example, are scaled simulations of large-scale geologic systems that provide great insight into understanding the interplay between sedimentation, salt tectonics, and faulting. The integration of geophysical workflows with sandbox models has been the subject of previous research, primarily to create synthetic data to compare with observed field data. However, capturing the detail from the physical model is challenging. A novel workflow is presented that uses pixel intensity values from photographic images of the analogue model to create a pseudo-impedance perturbation, mimicking the acoustic impedance contrasts that are encountered in the earth. This solution enables the detailed sedimentary architecture from the sandbox to be transferred to the digital earth model. Acoustic wave equation forward modeling and reverse time migration imaging have been applied using the generated pseudo-impedance model for a Gulf of Mexico-style salt canopy model. The images produced show clear definition of the salt/sediment interface and capture the sedimentary stratigraphy and faulting observed in the original sandbox model.
Matched tissue and circulating tumor DNA (ctDNA) analysis in renal cell carcinoma (RCC): Results from a multimodal real-world database.
Authors: McKay Rana R. , Jani Chinmay , Tran Eli , Hockenberry Adam J , Jaeger Ellen B. , Husni Nabil , Stoppler Melissa Conrad , Mercer Jacob , Pal Sumanta Kumar , Agarwal Neeraj , CHOUEIRI Toni K. , Rose Brent S. , Bagrodia Aditya
Published: July 2024

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Background: Next generation sequencing (NGS) of ctDNA can complement tissue NGS and is a non-invasive test that can be conducted serially, with the potential to enhance assessment of spatial and temporal molecular tumor heterogeneity. Here, we investigated mutations in RCC patients from ctDNA and matched tissue genomic profiling. Methods: From the Tempus multimodal database, we retrospectively analyzed de-identified NGS data from patients (pts) with RCC that had dual tissue (Tempus xT, 648 genes) and ctDNA testing (Tempus xF, 105 genes). Pts with matched samples (collected +/- 90 days of one another) were included. Clinical characteristics and select pathogenic somatic short variants (PSSV) and copy number variants [(amplifications and deletions, two copy number losses (CNL)] were evaluated. Concordance analyses were restricted to the 105 genes tested on the ctDNA panel and further restricted to short variants, with the exception of amplifications and CNL detected by both xF and xT. Results: Among all pts (n=393), the median age was 61 years and 71% were male. Median time from tissue to blood collection was 21 days (IQR, 7, 39). 67% (n=265) and 68% (n=266) had metastatic disease at the time of tissue and blood collection, respectively. The most common tissue sites were kidney (49%, n=189), bone (11%, n=43), lung (9%, n=34), lymph node (8%, n=29), liver (6%, n=23), and brain/CNS (4%, n=17). Genes harboring the most common PSSV in tissue included VHL (59% n=232), PBRM1 (31%, n=123), SETD2 (23%, n=91), and TP53 (14%, n=54). Genes with common PSSV in ctDNA included TP53 (23%, n=91), VHL (18%, n=69), BAP1 (6%, n=23), and PBRM1 (5%, n=21). The combination of tissue and ctDNA testing increased detection of mutations (Table). There was higher concordance between somatic alterations in select genes among patients with metastases. Conclusions: This analysis shows that ctDNA profiling is complementary to tissue based NGS in RCC and can increase the detection of mutations. Concordance between ctDNA and tissue profiling increased in individuals with metastatic disease. Future research is warranted to understand how longitudinal ctDNA analysis can define biomarkers of response and resistance at the mutation and ctDNA fraction levels. [Table: see text]
Belzutifan in patients with advanced clear cell renal cellcarcinoma (ccRCC): Subgroup analysis of the phase 2 LITESPARK-013 study.
Authors: Atkins Michael B. , Ghatalia Pooja , Merchan Jaime R. , George Saby , Haanen John , Gurney Howard , Ravilla Rahul , Van Der Veldt Astrid Aplonia Maria , Beuselinck Benoit , Pokataev Ilya , Suelmann Britt , Tuthill Mark H. , Vaena Daniel A. , Zagouri Flora , Lin Jianxin , Perini Rodolfo F. , Liu Yanfang , Brugarolas James , Agarwal Neeraj
Published: July 2024

4534

Background: In the randomized phase 2 LITESPARK-013 study (NCT04489771), the first-in-class HIF-2α inhibitor belzutifan showed comparable antitumor activity in patients with pretreated advanced ccRCC at 200 mg and 120 mg doses (objective response rate [ORR]: 23.1% vs 23.7%; 1-sided P= 0.5312). We present results of a post hoc analysis of the pooled population (200 mg and 120 mg arms) across patient subgroups based on prior therapy and IMDC risk group. Methods: Patients with advanced ccRCC, measurable disease per RECIST v1.1, a Karnofsky Performance Scale score of ≥70%, ≤3 prior systemic regimens for advanced ccRCC (including an anti–PD-(L)1 regimen), and disease progression during or after an anti–PD-(L)1 regimen were randomly assigned 1:1 to receive belzutifan 200 mg or 120 mg QD. End points in the pooled population and subgroups were ORR and duration of response per RECIST v1.1 by blinded independent central review. Data cutoff was February 10, 2023. Results: A total of 154 patients were enrolled (200 mg, n = 78; 120 mg, n = 76). In the pooled population, the median age was 64.0 years, 127 patients (82.5%) had intermediate/poor risk per IMDC criteria, 110 patients (71.4%) received 1-3 prior tyrosine kinase inhibitor (TKI) regimens, and 81 patients (52.6%) received 2 or 3 prior lines of therapy. As of the data cutoff date, 39 patients (25.3%) in the pooled population remained on treatment. Median follow-up was 20.1 months (range, 14.8-28.4). In the pooled population, ORR was 23.4% (95% CI, 16.9-30.9; 4 complete responses [CRs], 32 partial responses [PRs]) and median duration of response (DOR) was 16.1 months (range, 2.1+ to 23.5+). Additional efficacy analyses for subgroups are presented in the table. Conclusions: This post hoc analysis from the LITESPARK-013 study of patients with pretreated advanced ccRCC suggests that belzutifan has antitumor activity regardless of prior lines of therapies and prognostic risk category. These results further support belzutifan as a treatment option for advanced RCC. Clinical trial information: NCT04489771 . [Table: see text]
Age and other criteria influencing nontreatment of patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a physician survey in five European countries (Eu5).
Authors: Gupta Shilpa , Powles Thomas , Kearney Mairead , Panattoni Laura , Land Natalie , Flottemesch Thomas , Sullivan Patrick , Kirker Melissa , Bharmal Murtuza , Guenther Silke , Costa Nuno , Grande Enrique
Published: July 2024

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Background: Real-world studies have shown that a majority of pts with la/mUC do not receive first-line (1L) systemic therapy (tx), despite guideline recommendations. This cross-sectional study assessed the criteria that Eu5 physicians consider when making decisions about 1L tx for pts with la/mUC. Methods: A quantitative online survey of Eu5 physicians was performed in Aug-Sep 2022. Respondents answered questions related to demographics, practice patterns, and criteria considered in 1L decision-making. Descriptive statistics were used to analyze demographics and responses. Logistic regression was used to analyze physician characteristics associated with reporting no age threshold vs any age threshold when defining platinum ineligibility. Results: 503 physicians (69% oncologists and 31% urologists) completed the quota-based survey. Most respondents had been in practice for >10 years (69%) and treated 5-19 pts with la/mUC per month (58%) in public teaching hospitals (40%), public nonteaching hospitals (24%), and private hospitals (20%). Physicians estimated that they do not prescribe 1L tx for ≈25% of their pts. The majority of physicians selected advanced age (62.0%) and poor performance status (PS; 54.7%) as their top reasons for not prescribing 1L tx, followed by pt refusal (45.9%) and poor renal function (43.1%). Most physicians (78.1%) reported having an age threshold above which they recommend against 1L systemic tx (mean, 74.7 years old [Table]). After adjusting for baseline characteristics, physicians were more likely to have an age threshold if they were from Italy vs Germany (odds ratio [OR] 0.22 [95% CI 0.06-0.73]), practiced in a public nonteaching hospital (OR 0.28 [95% CI 0.10-0.73]) or public/private office settings (OR 0.14 [95% CI 0.03-0.57]) vs private hospital, and if they treated <20 pts/month (2-10 pts: OR 0.36 [95% CI, 0.17-0.74]; 11-19 pts: OR 0.25 [95% CI 0.09-0.62]). Conclusions: 1L systemic tx rates self-reported by Eu5 physicians were higher than those previously published. Many physicians reported having an age threshold for not offering systemic tx, which was relatively low compared with the senior age profile of the la/mUC population. Physicians who reported an explicit age threshold may be inappropriately excluding pts from tx; this could be a driver for systemic tx underutilization in la/mUC. [Table: see text]
Quantum delocalization, structural order, and density response of the strongly coupled electron liquid
Authors: Dornheim Tobias , Tolias Panagiotis , Vorberger Jan , Moldabekov Zhandos A.
Published: July 2024

We investigate the impact of electronic correlations and quantum delocalization onto the static structure factor and static density response function of the strongly coupled electron liquid. In contrast to a classical system, the density response of the electron liquid vanishes on small length scales due to quantum delocalization effects, which we rigorously quantify in terms of imaginary-time correlation functions and dynamic Matsubara response functions. This allows us to analyze the interplay of structural order and dynamic quantum effects as it manifests itself in the dynamic Matsubara local field correction. Finally, we identify an effective electronic attraction in the spin-offdiagonal static density response when the wavelength of the perturbation is commensurate with the average interparticle distance.
Secondary Hirata Syndrome in a Neonate: Practical Approach and Management
Authors: Perri Alessandro , Fattore Simona , Sbordone Annamaria , Viti Luca , Pitocco Dario , Vento Giovanni
Published: July 2024

Hirata disease, also known as insulin autoimmune syndrome (IAS), is a rare cause of hypoglycemia, due to the presence of insulin autoantibodies (IAA) in the circulating blood. These antibodies are immunoglobulin G (IgG), making placental transfer to the fetus possible. To our knowledge, no reports of IAS have been previously described in the neonatal population. We present a case report of hypoglycemia due to a secondary IAS in a neonate and discuss the management and treatment of the disease.
Lumbar Sympathetic Block for Treatment of Knee Pain From Synovial Plica Syndrome: A Case Report
Authors: deBettencourt Coreylyn , Zhu Xiaoying
Published: July 2024

Lumbar sympathetic blocks (LSBs) are used to treat sympathetically mediated pain in the lower extremities, kidneys, ureters, and genitals. LSBs use local anesthetic to block the sympathetic system to modulate pain response. In this case report, an avid runner was diagnosed with synovial plica syndrome. His pain was refractory to arthroscopic plica excision, physical therapy, nonsteroidal anti-inflammatory drugs, and intraarticular steroid injections. He received 3 rounds of LSB resulting in significant and sustained pain relief. This case suggests that LSB successfully treated knee pain from synovial plica syndrome and there may be a sympathetic component to this disease state.
Association of Global Ultraviolet Radiation With the Incidence of Aneurysmal Subarachnoid Hemorrhage
Authors: Mirbagheri Andia , Rinkel Gabriel J. E. , Berneburg Mark , Etminan Nima
Published: July 2024

BACKGROUND AND OBJECTIVES:

Inflammation is a key pathomechanism for growth and rupture of intracranial aneurysms. Anti-inflammatory mechanisms may reduce rupture of intracranial aneurysms and the incidence of aneurysmal subarachnoid hemorrhage (SAH). Ultraviolet (UV) radiation from sunlight exposure induces systemic anti-inflammatory responses through immunosuppressive mechanisms. We studied whether SAH incidence is associated with UV radiation.

METHODS:

Global SAH incidence, time trends, and regional differences from 32 countries were linked to UV radiation data from the Tropospheric Emission Monitoring Internet Service. Odds between low vs high UV exposure and SAH incidence were calculated. Correlation analysis was performed using R (R 4.1.2).

RESULTS:

SAH incidences ranged from 1.3 to 27 per 100 000 patient-years (p-y) and UV index from 1.76 to 11.27. The correlation coefficient (rho) between SAH incidence and UV index was −0.48 (P = .012). SAH incidence was highest in Japan (13.7-27.9 p-y) with an UV index 6.28. UV index was highest in Chile 11.27 with a lower SAH incidence (3.8-4.8 p-y). The lowest UV index 1.76 was seen in Iceland with higher SAH incidence (9.8 p-y).Within Europe, regions with higher UV indices reported lower SAH incidences (Northwest Europe: SAH incidence p-y 8.61/UV index 2.85; Southeast Europe: SAH incidence p-y 7.37/UV index 4.65) with a significant inverse correlation (rho = −0.68, P = .004) and not a significant correlation between non-European countries (rho = −0.43, P = .19). Low exposure of UV radiation in global regions predicted higher than median incidences of SAH with an odds ratio 5.13 (95% CIs 1.02-31.5).

CONCLUSION:

The incidence of SAH is inversely associated with UV radiation. Further studies should assess the actual UV exposure in relation to SAH incidence and potential biological explanations for the relation we found.
Distinct TORC1 signalling branches regulate Adc17 proteasome assembly chaperone expression
Authors: Williams Thomas D. , Joshua Ifeoluwapo , Soubigou Flavie , Dublanska Sylwia M. , Bergquist Rebecka , Rousseau Adrien
Published: July 2024

When stressed, cells need to adapt their proteome to maintain protein homeostasis. This requires increased proteasome assembly. Increased proteasome assembly is dependent on increased production of proteasome assembly chaperones. In Saccharomyces cerevisiae, inhibition of the growth-promoting kinase complex TORC1 causes increased proteasome assembly chaperone translation, including that of Adc17. This is dependent upon activation of the mitogen-activated protein kinase (MAPK) Mpk1 and relocalisation of assembly chaperone mRNA to patches of dense actin. We show here that TORC1 inhibition alters cell wall properties to induce these changes by activating the cell wall integrity pathway through the Wsc1, Wsc3 and Wsc4 sensor proteins. We demonstrate that, in isolation, these signals are insufficient to drive protein expression. We identify that the TORC1-activated S6 kinase Sch9 must be inhibited as well. This work expands our knowledge on the signalling pathways that regulate proteasome assembly chaperone production.
Przyszłość Unii Europejskiej: możliwe kierunki zmian
Authors: Kabat-Rudnicka Danuta
Published: July 2024

THE FUTURE OF THE EUROPEAN UNION: POSSIBLE DIRECTIONS FOR CHANGE
The crises of recent years have revealed the weakness of the European Union in many areas. This, in turn, contributed to the debate on its current state and necessary changes, inter alia, at the Conference on the Future of Europe. And although there are many arguments for the need for reforms, among other things, in order for the Union to better cope with challenges both internally and in its external environment, no Intergovernmental Conference has been convened so far. However, this does not mean that reform is impossible or unlikely, nor does it mean that there are no changes taking place in the European Union. The article will present the positions of institutions, member states and civil society regarding the necessary changes, and, above all, it will outline the directions of necessary and possible changes. The article will be descriptive, analytical, and comparative in nature.
Poland’s Raison d’etat in the European Union: Enlargement Policy as a Case Study
Authors: Zheltovskyy Vadym
Published: July 2024

The different views on EU–Polish relations articulated by different political actors in Poland illustrate two opposite approaches toward the shape of the integration process. The ongoing political debate on Poland’s raison d’état (reason of state) in the European Union calls for the necessity to define this notion in the current geopolitical context. In light of recent challenges and declared plans of the European Commission to transform the EU’s foreign policy it seems particularly reasonable to analyze Poland’s raison d’état in reference to the EU’s enlargement policy. Therefore, the major purpose of the article is to define and explain the essence and evolution of Poland’s position on the issue of EU enlargement. To be precise, the case study is concentrated on the developments caused by Russia’s full-scale invasion of Ukraine as a trigger for the reconsideration of the EU’s foreign policy. By doing so, the author makes an attempt to answer the research question on the essence of Poland’s raison d’état as regards further EU enlargement and Polish structural potential to promote its interests and shape the EU’s foreign policy overall.