bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing abdominal aortic aneurysm growth using radiomic features of perivascular adipose tissue after endovascular repair
Authors: Lv Rui , Hu Ge , Zhang Shenbo , Zhang Zhe , Chen Jin , Wang Kefei , Wang Zhiwei , Jin Zhengyu
Published: September 2024

Objectives

The study aimed to investigate the relationship between the radiomic features of perivascular adipose tissue (PVAT) and abdominal aortic aneurysm (AAA) growth after endovascular aneurysm repair (EVAR).

Methods

Patients with sub-renal AAA who underwent regular follow-up after EVAR between March 2014 and March 2024 were retrospectively collected. Two radiologists segmented aneurysms and PVAT. Patients were categorised into growing and non-growing groups based on volumetric changes observed in two follow-up computed tomography examinations. One hundred seven radiomic features were automatically extracted from the PVAT region. Univariable and multivariable logistic regression was performed to analyse radiomic features and clinical characteristics. Furthermore, the performance of the integrated clinico-radiological model was compared with models using only radiomic features or clinical characteristics separately.

Results

A total of 79 patients (68 ± 9 years, 89% men) were enroled in this study, 19 of whom had a growing aneurysm. Compared to the non-growing group, PVAT of growing AAA showed a higher surface area to volume ratio (non-growing vs growing, 0.63 vs 0.70, p = 0.04), and a trend of low dependence and high dispersion manifested by texture features (p < 0.05). The area under the curve of the integrated clinico-radiological model was 0.78 (95% confidence intervals 0.65–0.91), with a specificity of 87%. The integrated model outperformed models using only radiomic or clinical features separately (0.78 vs 0.69 vs 0.69).

Conclusions

Higher surface area to volume ratio and more heterogeneous texture presentation of PVAT were associated with aneurysm dilation after EVAR. Radiomic features of PVAT have the potential to predict AAA progression.

Clinical relevance statement

Radiomic features of PVAT are associated with AAA progression and can be an independent risk factor for aneurysm dilatation to assist clinicians in postoperative patient surveillance and management.

Key Points

After EVAR for AAA, patients require monitoring for progression.

PVAT surrounding growing AAA after EVAR exhibits a more heterogeneous texture.

Integrating PVAT-related features and clinical features results in better predictive performance.

Graphical Abstract
Clonality in black locust (Robinia pseudoacacia L.) and implications for seed production
Authors: Pakull Birte , Schneck Volker , Liesebach Heike
Published: September 2024

Key message

The strong clonal growth of black locust (Robinia pseudoacacia L.) not only influences the stand structure of natural or artificially established stands, but also the genetic composition of seed harvested from such clonal stands. For the commercial production of genetically diverse seeds, the stand structure should be taken into account or, at best, seeds harvested from seed orchards should be used.

Context

Black locust is characterised by intensive asexual reproduction through the formation of root suckers. By this means clonal structures can develop within black locust stands, in which ramets of a single clone can dominate extensive areas.

Aims

We want to analyse to what extent clonal structures within black locust stands negatively influence the genetic composition and diversity in seed harvested in such stands. We discuss how a potential reduction in genetic diversity can be reduced by measures taken during harvesting and whether the harvesting of seed orchards may be a better alternative.

Methods

We compare the genetic composition and diversity of parent trees and seed harvested from a clonal black locust stand with a seed orchard in which multiple ramets of selected clones were arranged in a randomised design.

Results

Within the clonal stand, parent contributions to the seed lot analysed proved to be strongly uneven. Selfing rates were high and large full-sib families dominated within the seed lot. Although the relatively strong pollination from unknown pollen donors, probably located outside of the stand, prevented a massive loss of alleles, high selfing rates and the formation of large full-sib families led to an unequal distribution of alleles within the progeny. Within the seed orchard—even though it had a lower number of clones than expected—the randomised design promoted a more diverse pollination pattern.

Conclusion

We conclude that for black locust, seed orchards have the greater potential to ensure a balanced genetic composition of harvested seed lots. If economic considerations make it necessary to harvest seed stands, this should only be done in a considered manner and, if possible, with knowledge of the clonal structures of the stand.
Expression levels and stoichiometry of Hnf1β, Emx2, Pax8 and Hnf4α influence direct reprogramming of induced renal tubular epithelial cells
Authors: Hu Xueli , Sun Jianjian , Wan Meng , Zhang Bianhong , Wang Linhui , Zhong Tao P.
Published: September 2024

Generation of induced renal epithelial cells (iRECs) from fibroblasts offers great opportunities for renal disease modeling and kidney regeneration. However, the low reprogramming efficiency of the current approach to generate iRECs has hindered potential therapeutic application and regenerative approach. This could be in part attributed to heterogeneous and unbalanced expression of reprogramming factors (RFs) Hnf1β (H1), Emx2 (E), Pax8 (P), and Hnf4α (H4) in transduced fibroblasts. Here, we establish an advanced retroviral vector system that expresses H1, E, P, and H4 in high levels and distinct ratios from bicistronic transcripts separated by P2A. Mouse embryonic fibroblasts (MEFs) harboring Cdh16-Cre; mT/mG allele are utilized to conduct iREC reprogramming via directly monitoring single cell fate conversion. Three sets of bicistronic RF combinations including H1E/H4P, H1H4/EP, and H1P/H4E have been generated to induce iREC reprogramming. Each of the RF combinations gives rise to distinct H1, E, P, and H4 expression levels and different reprogramming efficiencies. The desired H1E/H4P combination that results in high expression levels of RFs with balanced stoichiometry. substantially enhances the efficiency and quality of iRECs compared with transduction of separate H1, E, P, and H4 lentiviruses. We find that H1E/H4P-induced iRECs exhibit the superior features of renal tubular epithelial cells, as evidenced by expressing renal tubular-specific genes, possessing endocytotic arrogation activity and assembling into tubules along decellularized kidney scaffolds. This study establishes H1E/H4P cassette as a valuable platform for future iREC studies and regenerative medicine.
Effect of the combination of Lithospermum erythrorhizon and Lonicera japonica on dexamethasone-induced muscle atrophy in mice
Authors: Yoo Ahyoung , Lee Hyunjung , Kim Jung-In , Hahm Jeong-Hoon , Jung Chang Hwa , Ahn Jiyun
Published: September 2024

Skeletal muscle atrophy occurs in several pathological conditions. Among other reasons, high-dose or long-term administration of glucocorticoids increases circulating glucocorticoid levels and causes muscle atrophy. The purpose of this study was to investigate whether Lithospermum erythrorhizon and Lonicera japonica complex extract (LELJ) has a beneficial effect on dexamethasone (Dexa)-induced muscle atrophy. In Dexa-induced myotube atrophy, treatment with LELJ increased myotube diameter, decreased the expression of muscle atrophy markers, and increased the expression of myosin heavy chain (MHC) isoforms. Supplementation with LELJ improved muscle function and performance in mice with Dexa-induced muscle atrophy as demonstrated by grip strength and running tests. Additionally, it increased skeletal muscle mass, size, and expression of MHC isoforms and protein synthesis-related markers. Furthermore, it reduced the upregulated protein levels of skeletal muscle atrophy markers in Dexa-treated mice. Supplementation with LELJ reversed Dexa-induced translocation of the glucocorticoid receptor and forkhead box O3 from the cytosol to the nucleus in skeletal muscles. LELJ also ameliorated age-related muscle loss by extending lifespan and increasing locomotor capacity in Caenorhabditis elegans. We identified loganin and lithospermic acid as bioactive compounds of LELJ and found that treatment with these agents increased myotube diameter, MHC isoform, and puromycin protein levels, and decreased atrophy markers in Dexa-treated myotubes. The current findings underscore how LELJ can prevent Dexa-induced skeletal muscle atrophy, attributing the effects to loganin and lithospermic acid.
High-Strength Self-Compacting Concrete Production Incorporating Supplementary Cementitious Materials: Experimental Evaluations and Machine Learning Modelling
Authors: Sobuz Md. Habibur Rahman , Aditto Fahim Shahriyar , Datta Shuvo Dip , Kabbo Md. Kawsarul Islam , Jabin Jannat Ara , Hasan Noor Md. Sadiqul , Khan Md. Munir Hayet , Rahman S. M. Arifur , Raazi Mehernaz , Zaman Ahmad Akib Uz
Published: September 2024

This study investigates mechanical properties, durability performance, non-destructive testing (NDT) characteristics, environmental impact evaluation, and advanced machine learning (ML) modelling techniques employed in the analysis of high-strength self-compacting concrete (HSSCC) incorporating varying supplementary cementitious materials (SCMs) to develop sustainable building construction. The findings from the fresh characteristics test indicate that mixes’ optimal flowability and passing qualities can be achieved using different concentrations of marble powder (MP) alongside a consistent amount of silica fume (SF) and fly ash (FA). Moreover, the incorporation of 10% MP along with 10% FA and 20% SF in HSSCC significantly improved the compressive strength by 14.68%, while the splitting tensile strength increased by 15.59% compared to the reference mix at 56 days. While random forest (RF), gradient boosting (GB), and their ensemble models exhibit strong coefficient correlation (R2) values, the GB model demonstrates more precision, indicating reliable predicted outcomes of the mechanical properties. Following subsequent testing, it has been demonstrated that incorporating SCMs improves the NDT properties of HSSCC and enhances its durability. The finer MP, SF, and FA particles enhanced microstructural performance by minimizing voids and cracks while improving the C–H–S bond. As noticed by its lower CO2-eq per MPa for SCMs, the HSSCC mix with up to 15% MP inclusion increased mechanical strength while reducing the environmental footprint, making it an eco-friendly concrete alternative.
Further analysis of tuberculosis in eight high-burden countries based on the Global Burden of Disease Study 2021 data
Authors: Lv Hengliang , Wang Longhao , Zhang Xueli , Dang Caixia , Liu Feng , Zhang Xin , Bai Junzhu , You Shumeng , Chen Hui , Zhang Wenyi , Xu Yuanyong
Published: September 2024

Backgrounds

Most significant findings from the Global Tuberculosis (TB) Report 2023 indicate that India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of the Congo (DRC) collectively contribute to approximately two-thirds of global TB cases. This study aims to provide crucial data-driven insights and references to improve TB control measures through a comprehensive analysis of these eight high-burden countries.

Methods

The eight high-burden TB countries analyzed in this study include India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the DRC. Age-standardized incidence rates (ASIR) of TB were derived from the Global Burden of Diseases Study 2021 data. Temporal trends were analyzed using Joinpoint regression. An age-period-cohort model was applied to examine the risk ratios (RR) of TB across diverse age groups, periods, and birth cohorts. A Bayesian age-period-cohort framework was employed to predict the ASIR of TB by 2030.

Results

The study found that the Philippines (average annual percentage change = 3.1%, P < 0.001) exhibited an upward trend from 1990 to 2021. In India, the Philippines, Pakistan, and Bangladesh, the RR of TB incidence exceeded 1 after individuals reached 25 years old. Notably, the RR has shown a consistent upward trend since 2001, peaking during the period of 2017–2021 with an estimated RR of 1.5 (P < 0.001) in the Philippines. Similarly, the highest RR was observed during the period of 2017–2021 reaching 1.1 (P < 0.001) in the DRC. In the Philippines, the markedly increasing RR values for TB have been observed among individuals born after 1997–2001. Projections suggest that the ASIR of TB is expected to follow a continued upward trajectory, with an estimated rate of 392.9 per 100,000 by 2030 in the Philippines; India and Indonesia are projected to achieve less than 20.0% of the target set by the World Health Organization (WHO).

Conclusions

Among the eight high-burden countries, the Philippines, India and Indonesia are diverging from the goals set by the WHO, and the risk of TB in the Philippines and the DRC shows a trend toward affecting younger populations, which suggests that the management strategies for TB patients need to be further strengthened.

Graphical Abstract
“The only way that they can access help quickly”: a qualitative exploration of key stakeholders’ perspectives on guided self-help interventions for children and young people with eating disorders
Authors: Davey Emily , Micali Nadia , Bryant-Waugh Rachel , Bennett Sophie D , Lau Charmayne , Shafran Roz
Published: September 2024

Background

There is a significant unmet treatment need for children and young people (CYP) with eating disorders. Guided self-help interventions have the potential to expand access to evidence-based treatments. Guided self-help is a type of low intensity psychological intervention where individuals engage with a workbook or online programme, with the support of a health professional. Its primary aim is to equip patients and/or their caregivers with self-management skills. However, little is currently known about the acceptability and suitability of guided self-help interventions for CYP with eating disorders. This study aimed to explore the perspectives of three key stakeholder groups – CYP with lived experience of eating disorders, parents/carers, and healthcare professionals – on guided self-help for this population.

Methods

Qualitative focus groups and semi-structured interviews were conducted with 11 CYP (aged 13–19 years) with lived experience of eating disorders, 12 parents/carers, and 10 healthcare professionals. The study comprised a total of seven focus groups (including 2 with CYP, 3 with parent/carers, and 2 with healthcare professionals), as well as four semi-structured interviews (including 3 with CYP and 1 with a parent/carer). Discussion topics included past experiences of using/delivering guided self-help, the suitability of guided self-help for CYP with eating disorders, and preferences towards the content, structure and modes of guided self-help. Data were analysed using reflexive thematic analysis.

Results

Three themes were generated across all three stakeholder groups. Theme one, Bridging the gap, highlighted the role of guided self-help in increasing access to psychological support for CYP with eating disorders. Theme two, Timing matters, considered the suitability of guided self-help for CYP with eating disorders at different stages of illness and the care pathway. Theme three, One size does not fit all, emphasised the heterogeneity of eating disorders and the need for a personalised and flexible approach in guided self-help.

Conclusions

Findings from this study lay a foundation for the future design and delivery of guided self-help interventions for CYP with eating disorders. Future work must consider these findings in the context of best available research evidence to optimise the potential utility of guided self-help for this population.
The statistical building blocks of animal movement simulations
Authors: Getz Wayne M. , Salter Richard , Sethi Varun , Cain Shlomo , Spiegel Orr , Toledo Sivan
Published: September 2024

Animal movement plays a key role in many ecological processes and has a direct influence on an individual’s fitness at several scales of analysis (i.e., next-step, subdiel, day-by-day, seasonal). This highlights the need to dissect movement behavior at different spatio-temporal scales and develop hierarchical movement tools for generating realistic tracks to supplement existing single-temporal-scale simulators. In reality, animal movement paths are a concatenation of fundamental movement elements (FuMEs: e.g., a step or wing flap), but these are not generally extractable from a relocation time-series track (e.g., sequential GPS fixes) from which step-length (SL, aka velocity) and turning-angle (TA) time series can be extracted. For short, fixed-length segments of track, we generate their SL and TA statistics (e.g., means, standard deviations, correlations) to obtain segment-specific vectors that can be cluster into different types. We use the centroids of these clusters to obtain a set of statistical movement elements (StaMEs; e.g.,directed fast movement versus random slow movement elements) that we use as a basis for analyzing and simulating movement tracks. Our novel concept is that sequences of StaMEs provide a basis for constructing and fitting step-selection kernels at the scale of fixed-length canonical activity modes: short fixed-length sequences of interpretable activity such as dithering, ambling, directed walking, or running. Beyond this, variable length pure or characteristic mixtures of CAMs can be interpreted as behavioral activity modes (BAMs), such as gathering resources (a sequence of dithering and walking StaMEs) or beelining (a sequence of fast directed-walk StaMEs interspersed with vigilance and navigation stops). Here we formulate a multi-modal, step-selection kernel simulation framework, and construct a 2-mode movement simulator (Numerus ANIMOVER_1), using Numerus RAMP technology. These RAMPs run as stand alone applications: they require no coding but only the input of selected parameter values. They can also be used in R programming environments as virtual R packages. We illustrate our methods for extracting StaMEs from both ANIMOVER_1 simulated data and empirical data from two barn owls (Tyto alba) in the Harod Valley, Israel. Overall, our new bottom-up approach to path segmentation allows us to both dissect real movement tracks and generate realistic synthetic ones, thereby providing a general tool for testing hypothesis in movement ecology and simulating animal movement in diverse contexts such as evaluating an individual’s response to landscape changes, release of an individual into a novel environment, or identifying when individuals are sick or unusually stressed.
Mechanism of initiation and regeneration of convective cell in Bandung Basin, Indonesia
Authors: Firdaus Irfans Maulana , Trilaksono Nurjanna Joko , Yamazaki Takeshi
Published: September 2024

The mechanism of convective cell initiation and regeneration in the Bandung Basin ($$107.35^\circ \text{E}-107.95^\circ \text{E};6.75^\circ \text{S}-7.25^\circ \text{S}$$

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), Indonesia, is investigated using a Weather Research and Forecasting model. Based on the Cumulative Distribution Function and Regeneration Index, model simulations were conducted using case studies in February–March 2019. Upslope wind flows to the mountain peak in north and south of the basin due to solar heating, carrying water vapor from the bottom of the basin. Therefore, low-level convergence is formed due to the convergence of winds from the bottom of the basin and from outside the basin. The low-level convergence causes the developing updraft, makes atmosphere unstable, and generates convective initiation. The convective system will be developed in the mountains region, produced precipitation, and formed cold pools on the surface. The cold pool will fall down the slopes and convective activity from the mountains will continue to the bottom of the basin. The convective system’s outflow causes the cold pool to move in the west–east direction. The cold pool will collide with warmer air from the opposite direction, resulting in an updraft at the cold pool leading edge, and convection will be re-initiated (convective regeneration) in the Bandung Basin, with the new convective system tending to move eastward.
Personalized prediction of immunotherapy response in lung cancer patients using advanced radiomics and deep learning
Authors: Liao Chien-Yi , Chen Yuh-Min , Wu Yu-Te , Chao Heng-Sheng , Chiu Hwa-Yen , Wang Ting-Wei , Chen Jyun-Ru , Shiao Tsu-Hui , Lu Chia-Feng
Published: September 2024

Background

Lung cancer (LC) is a leading cause of cancer-related mortality, and immunotherapy (IO) has shown promise in treating advanced-stage LC. However, identifying patients likely to benefit from IO and monitoring treatment response remains challenging. This study aims to develop a predictive model for progression-free survival (PFS) in LC patients with IO based on clinical features and advanced imaging biomarkers.

Materials and methods

A retrospective analysis was conducted on a cohort of 206 LC patients receiving IO treatment. Pre-treatment computed tomography images were used to extract advanced imaging biomarkers, including intratumoral and peritumoral-vasculature radiomics. Clinical features, including age, gene status, hematology, and staging, were also collected. Key radiomic and clinical features for predicting IO outcomes were identified using a two-step feature selection process, including univariate Cox regression and chi-squared test, followed by sequential forward selection. The DeepSurv model was constructed to predict PFS based on clinical and radiomic features. Model performance was evaluated using the area under the time-dependent receiver operating characteristic curve (AUC) and concordance index (C-index).

Results

Combining radiomics of intratumoral heterogeneity and peritumoral-vasculature with clinical features demonstrated a significant enhancement (p < 0.001) in predicting IO response. The proposed DeepSurv model exhibited a prediction performance with AUCs ranging from 0.76 to 0.80 and a C-index of 0.83. Furthermore, the predicted personalized PFS curves revealed a significant difference (p < 0.05) between patients with favorable and unfavorable prognoses.

Conclusions

Integrating intratumoral and peritumoral-vasculature radiomics with clinical features enabled the development of a predictive model for PFS in LC patients with IO. The proposed model’s capability to estimate individualized PFS probability and differentiate the prognosis status held promise to facilitate personalized medicine and improve patient outcomes in LC.
Revisiting the Person-relative-to-Event (PrE) model of coping with threat: a study in the Azores (Portugal)
Authors: Pereira Sofia Morgado , Rego Isabel Estrela , Mónico Lisete dos Santos Mendes
Published: September 2024

Background

Approximately 20 years have passed since the Person-relative-to-Event (PrE) Model of Coping with Threat was conceptualized. Despite its familiar name, this model has been under-researched. This study investigates the main assumptions of the PrE, identifies predictors of actual household earthquake adjustments in the absence of fear appeals using a non-experimental design, and proposes an alternative model: the Sequential Person-relative-to-Event Model of Coping with Threat (SPrE).

Methods

A survey methodology was employed with self-completed questionnaires from 822 residents of the Azores, an earthquake-vulnerable location. The associations between variables were examined. Structural Equation Modeling was applied to test the PrE and SPrE models.

Results

Actual household earthquake adjustment was associated with person, event, and person-relative-to-event appraisals, responsibility attributions, age, and educational level. There was a non-significant association with gender. Person-relative-to-event appraisal was a non-significant predictor of actual household earthquake adjustments and responsibility attributions did not moderate this relationship. We found that event appraisal predicted person appraisal and that its relationship with actual household earthquake adjustments was moderated by the responsibility attributions. Thus, a new hypothesis is proposed regarding the relationship between risk perception (equivalent to event appraisal) and actual household earthquake adjustments.

Conclusions

These results contribute to the literature, practice and cumulative scientific knowledge.
The remarkable larval morphology of Rhaebo nasicus (Werner, 1903) (Amphibia: Anura: Bufonidae) with the erection of a new bufonid genus and insights into the evolution of suctorial tadpoles
Authors: Dias Pedro Henrique dos Santos , Phillips Jackson R. , Pereyra Martín O. , Means D. Bruce , Haas Alexander , Kok Philippe J. R.
Published: September 2024

Tadpoles serve as crucial evidence for testing systematic and taxonomic hypotheses. Suctorial tadpoles collected in Guyana were initially assigned to Rhaebo nasicus through molecular phylogeny. Subsequent analysis of larval and adult morphological traits revealed synapomorphies within the clade encompassing R. nasicus and R. ceratophrys, prompting the recognition of a new genus described herein as Adhaerobufo. The new genus is distinguished from other bufonids by specific phenotypic traits including an enlarged, suctorial oral disc with distinct papillae arrangements, and the presence of certain muscles and narial vacuities at the larval stage. However, only a few adult external characteristics (e.g., enlarged eyelids, infraocular cream spot), seem to be reliably discriminative from related genera. This study underscores the significance of larval morphology in anuran systematics and offers new insights into the evolution of suctorial and gastromyzophorous larvae within bufonids.
A review of gut microbial metabolites and therapeutic approaches in hypertension
Authors: Olalekan Samuel Oluwadare , Bakare Olalekan Olanrewaju , Faponle Abayomi Samson , Okwute Patrick Godwin
Published: September 2024

Background

Hypertension is a prevalent and complex disease that is increasingly recognized to be influenced by the gut microbiome and its metabolites. Understanding the relationship between gut microbial metabolites and blood pressure regulation could provide new therapeutic avenues.

Main body

This review examines the role of key microbial metabolites—short-chain fatty acids, trimethylamine N-oxide, tryptophan derivatives, polyamines, bile acids, and phenylacetylglutamine—in blood pressure regulation. Short-chain fatty acids, produced through dietary fiber fermentation, can lower blood pressure by modulating immune responses and reducing inflammation. Elevated trimethylamine N-oxide levels are associated with increased cardiovascular risk and hypertension, influencing cholesterol metabolism and promoting atherosclerosis. Tryptophan derivatives interact with vascular and renal functions to modulate blood pressure. Polyamines affect blood pressure regulation through their impact on nitric oxide synthesis and vascular tone. Bile acids influence blood pressure via gut microbiota modulation and activation of metabolic receptors. Phenylacetylglutamine has been linked to hypertension through its effects on platelet hyperactivity and thrombosis. Therapeutic approaches targeting these metabolites, including probiotics, prebiotics, fecal microbiota transplantation, dietary interventions, and polyphenols, have shown varying degrees of success. Probiotics and prebiotics promote the growth of beneficial gut bacteria and may lower blood pressure. Dietary interventions, such as the Mediterranean diet, positively affect blood pressure and cardiovascular health by modulating the gut microbiota. Polyphenols, known for their antioxidant properties, are associated with blood pressure reductions and improved vascular function. Fecal microbiota transplantation shows promise in restoring gut microbial balance and improving metabolic health, potentially influencing blood pressure regulation.

Conclusion

The review highlights the significant role of gut microbial metabolites in regulating blood pressure, offering new avenues for hypertension management. Key metabolites, including short-chain fatty acids, trimethylamine N-oxide, and bile acids, play critical roles in blood pressure modulation. Therapeutic strategies targeting these metabolites, such as probiotics, prebiotics, and dietary interventions, hold promise, though further research is needed to fully understand their mechanisms and optimize their use. Advancing microbiota-based interventions through large-scale studies and exploring personalized therapies will be essential for developing effective treatments in hypertension management.
Retro-maxillary nasal recess: a case report with a new finding
Authors: El-Anwar Mohammad Waheed
Published: September 2024

Background

Retro-maxillary recess of the nasal cavity is an area that has not yet described in the literature.

Objective

To report, present, and describe a previously non-reported case which has bilateral retro-maxillary nasal recess by multi-slices computed tomography (MSCT).

Case presentation

A CT of a 22-year-old male showed bilateral retro-maxillary nasal recess extends beyond the posterior maxillary sinus wall and anterior to the pterygopalatine fossa as an extension of the middle meatus laterally and bounded by the maxillary sinus anterior, the orbital floor superior, the inferior turbinates lateral attachment inferior, and the pterygopalatine fossa anterior. The retro-maxillary nasal recess anteroposterior, lateral, and vertical dimensions were 11.53, 8.24, and 11.6 mm respectively at the left side and 5.6, 4.61, and 6.16 mm respectively at the right side.

Conclusion

This study reports and describes a new retro-maxillary nasal recess that could represent a new hidden challenging area for ESS.
Prescription predicament: Unveiling the financial fallout of drug shortages.
Authors: Indurlal Puneeth , Garey Jody S. , Albaugh John , Standring Arran , White Jessica , Busby Leslie T. , Wilfong Lalan S.
Published: September 2024

1

Background:
Managing drug shortages has become a part of care delivery in oncology. Shortages have been reported to result in missed/delayed treatment, substitution of alternative therapy, increased costs, and significant administrative burden. A national shortage of cisplatin caused by manufacturing disruptions was reported by the Food and Drug Administration in the United States from February until August 2023 (shortage period). We assessed the effects of cisplatin shortage on the treatment of head and neck cancer (HNC) at practices in The US Oncology Network (The Network).
Methods:
Using drug administration data from medical records and claims for 26 practices in The Network prior to (July 2022 to January 2023), during, and after (September 2023 to March 2024) the shortage period, we assessed the utilization trends and financial impact (using Medicare average sale price (ASP)) of cisplatin and other anti-cancer drugs for HNC patients.
Results:
During the shortage period, cisplatin utilization for HNC decreased by 15% compared to pre-shortage levels. The lowest utilization occurred in June and July 2023, with a 60% decrease. Practices initially obtained supplies through an allocation model and fair-share utilization guidance from The Network Pharmacy & Therapeutics Committee. During the shortage period, alternative chemotherapy drugs for HNC saw increased use: carboplatin by 40%, paclitaxel by 24%, 5-fluorouracil by 5.3%, and cetuximab by 15%. The increased use of alternative drugs corresponded to the decrease in cisplatin usage, with new starts shifting to carboplatin (with or without paclitaxel), cetuximab and 5-fluorouracil. Ten percent of existing cisplatin recipients were shifted to an alternative drug during the shortage period. Interestingly, 5-fluorouracil was also in short supply, albeit less acutely than cisplatin. After the shortage, cisplatin volumes rebounded by 8% of pre-shortage use, while carboplatin use dropped below pre-shortage levels. Cetuximab use remained consistently 12% higher. The average cost per administration was $18 for cisplatin, $14 for carboplatin, $16 for paclitaxel, $22 for 5-fluorouracil, and $2,607 for cetuximab, based on the ASP. The increased use of cetuximab instead of cisplatin resulted in a 16% total cost increase, leading to a 144-fold increase in costs at the administration level, impacting payer costs and patient cost-sharing amounts.
Conclusions:
Cisplatin shortage led to a shift in utilization to alternative therapies for HNC, resulting in significant cost increases for both payers and patients. These consequences may not be limited to specific cancer types or drugs and may have other undesirable effects. Even temporary shortages of drugs can lead to lasting utilization changes and have long-term financial implications. The impacts of drug shortages on treatment decisions, guideline concordance, costs, and patient outcomes are apt for further investigation.
Characterizing access for oral oncolytics used to treat breast cancer at an academic medical center.
Authors: Kraft Shawna , Cheung Annie , Westover Mary , Widmer Gina , Pichla Nichole , Venera Hanna , Kidwell Kelley M. , Henry Norah Lynn
Published: September 2024

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Background:
Everolimus, CDK 4/6, PIK3CA, Her2 tyrosine kinase, and PARP inhibitors are commonly used oral oncolytic agents for breast cancer patients. However, oral oncolytics are tiered differently for insurance cost coverage than IV therapies. We characterized the financial toxicity associated with breast cancer oral oncolytics, investigated the prevalence of financial assistance mechanisms utilized, and explored the association of these mechanisms with timing of treatment initiation in adult breast cancer patients.
Methods:
Patients 18 years or older with a primary breast cancer diagnosis who received care at the outpatient breast cancer clinic and were prescribed an oral oncolytic by a Michigan Medicine provider were included. Using the electronic medical record, we identified initial prescriptions for everolimus, CDK 4/6 inhibitors (palbociclib, ribociclib, abemaciclib), PIK3CA inhibitor (alpelisib), HER2 tyrosine kinase inhibitors (lapatinib, neratinib, tucatinib), and PARP inhibitors (olaparib, talazoparib) dated between January 1, 2014 and November 30, 2022. Patient demographics, adjuvant versus metastatic status, insurance coverage, monthly out-of-pocket costs, financial assistance obtained, prescribed date, planned medication start date, pill-to-mouth date, duration of treatment and reason for treatment discontinuation were collected.
Results:
There were 418 unique patients in our final cohort. Almost one third of all prescriptions were filled with financial assistance (n=126, 31.2%). The three most common assistance mechanisms were copay cards (n=55, 43.6%), grants (n=34, 26.9%) and patient assistance programs (n=31, 24.6%). For monthly out-of-pocket costs before any financial assistance was obtained, the three most common cost groups were $0-$15 (n=155, 36%), $15-$100 (n=101, 23.7%) and >$500 (n=91, 21%). Among the 48 prescriptions that were never filled, almost one third were due to prohibitive cost (n=15, 28.3%). For insurance coverage, the three most common types were commercial (n=224, 54%), Medicare Part D (n=108, 26%), and Medicaid (n=57, 14%). The median number of days treatment was delayed was 10 days (range 0-495 days). Insurance approval/denial delays accounted for 33.9% of delays (n=120).
Conclusions:
One third of breast cancer oral oncolytic prescriptions were filled with financial assistance. In the instances in which patients were not able to receive timely treatment for their cancer, one out of three times it was due to insurance delay.
State opioid prescribing laws and associations with radiotherapy delays and radiotherapy completion.
Authors: Barnes Justin Michael , Chino Fumiko , Yang Joanna Chensi
Published: September 2024

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Background:
In July 2018, Missouri introduced a 7-day limit for initial opioid prescriptions, though there was an exemption for cancer-related pain. However, some worry that the exemptions may be inadequate for patients with cancer who experience cancer-related pain. Since some courses of radiotherapy can cause pain (eg, mucositis, esophagitis), appropriate opioid access is important for helping patients complete radiotherapy in a timely manner, which is associated with oncologic outcomes.
Methods:
Patients with cancer of all ages treated with radiotherapy from 2018-2019 at a large academic institution in Missouri were identified. More recent data were excluded due to the COVID-19 pandemic and Missouri Medicaid expansion. Trends over time in the proportion of missed/delayed radiotherapy fractions, incomplete radiotherapy courses, and a composite measure of excessive delays (≥5 days) or incomplete course were evaluated in linear and linear probability models. Additional analyses included patients from Illinois, an adjacent state without opioid prescribing legislation, and we subsequently performed difference-in-differences analyses comparing the outcomes from pre- to post- Missouri opioid legislation between the states. We conducted unadjusted analyses as well as analyses adjusted for age, sex, site, radiotherapy modality and fractions, as well as other covariates that could impact access to radiotherapy (ZIP code deprivation, distance from the facility, insurance status, and social work referral for unmet needs). Subgroup analyses focused on patients with head and neck cancer and lung cancer receiving definitive radiotherapy, who are at high risk of radiotherapy-related pain.
Results:
A total of 2613 and 1518 patients from Missouri and Illinois were identified, respectively. 4.7% of fractions were missed/delayed, 3.7% of patients did not complete treatment, and 8.1% of patients had either an incomplete course or excessive delays. There were no statistically significant increases (ie, worsening) in any outcome in any quarter after opioid policy implementation, and there were significant decreases in the composite outcome in multiple post-policy quarters in both unadjusted and adjusted analyses. In difference-in-differences analyses comparing trends over time with patients from Illinois, there were no significant associations of policy implementation with any of the outcomes. Results were similar in subgroup analyses for patients with head and neck and lung cancers.
Conclusions:
Missouri legislation limiting opioid prescribing for non-cancer-related pain was not associated with significant changes in a patient’s ability to undergo radiotherapy. Limitations of the study include evaluation of a single center in a single state and the lack of other intermediate outcomes important to patients including access to opioid medication itself, which we will examine in future work.
Changes in cancer diagnoses and stage distribution during the second year of the COVID-19 pandemic in the US.
Authors: Yang Nova Nova , Fan Qinjin , Nogueira Leticia M , Jiang Changchuan , Yabroff Robin , Han Xuesong
Published: September 2024

130

Background:
During 2020, the first year of the COVID-19 pandemic, cancer diagnoses decreased, especially early-stage disease, with largest decreases in medically underserved populations. It is unknown whether this pattern continued during 2021, the second year of the COVID-19 pandemic. With newly released cancer surveillance data, this study examined nationwide changes in adult cancer diagnoses and stage distribution from 2019 to 2021 in the US.
Methods:
Adults aged ≥18 years who were newly diagnosed with first primary malignant cancers between 2019 and 2021 from 50 US states and the District of Colombia were identified from the National Cancer Database. We calculated monthly cases, stage distribution, and adjusted odds ratios (aOR) of stage I vs. stage II–IV cancer and stage IV vs. stage I–III cancer diagnoses in 2021 compared with 2019, controlling for sociodemographic and clinical factors and stratified by cancer type.
Results:
We identified 864,430 individuals diagnosed in 2019, 780,478 diagnosed in 2020, and 819,791 diagnosed in 2021. The proportion of diagnoses at stage I decreased from 39.6% in 2019 to 31.1% in April 2020, and were 39.2% overall in 2021. The decrease in stage I diagnoses was mirrored by an increase in stage IV diagnoses. The pattern was most prominent for female breast, lung, colorectal, and prostate cancers, and melanoma. Overall, compared to 2019, we found a 5.98% decrease in stage I diagnoses and a 4.55% decrease in stage IV diagnoses in 2021 (Table). Lower odds of diagnosis at stage I were most prominent among individuals who were male, aged 18-44, Hispanic, from Mid-Atlantic region, and for the cancers of melanoma, non-Hodgkin lymphoma, prostate, esophagus, and cervical cancer. Higher odds of diagnosis at stage IV in 2021 vs. 2019 were most prominent among individuals who were Hispanic, diagnosed with cancers of prostate, thyroid, liver, esophagus and cervix.
Conclusions:
Decreases in cancer diagnoses and proportion of early-stage diagnoses continued in 2021 in the US. The proportion of late-stage diagnoses were lower in 2021 than 2020 but have not returned to pre-pandemic levels.

Changes in stage I distribution among major cancer sites 2021 vs. 2019.

2019
2021
2021 vs. 2019

Cases

Cases

Percent Change

AdjustedOR* (95%CI)

All Cancers
341971
321514
-5.98%
0.978 (0.972-0.985)

Female breast
116828
116780
-0.04%
1.023 (1.007-1.038)

Prostate
26323
21012
-20.18%
0.826 (0.809-0.843)

Lung cancer and bronchus
28258
25966
-8.11%
1.033 (1.012-1.053)

Colon and rectum
14258
12992
-8.88%
0.942 (0.918-0.968)

Melanoma
21005
19542
-6.97%
0.936 (0.907-0.966)

Data source: National Cancer Database 2019-2021.

*Stage I vs. II-IV, models adjusted for age group, sex, race/ethnicity, zip-code level social deprivation index, comorbidity score, state-level COVID-19 age adjusted mortality rate, MSA, state, insurance status.
Racial disparities in hepatocellular carcinoma (HCC) treatment and survival: A SEER-Medicare analysis.
Authors: Iheanacho Franklin , Tramontano Angela , Manz Christopher
Published: September 2024

144

Background:
Between 2017-2022, approved systemic therapies for HCC increased from 1 to 10. Studies have shown racial disparities in overall survival (OS), but no studies have evaluated disparities in new systemic treatments.
Methods:
We identified patients in SEER-Medicare data diagnosed with HCC in 2014-2019 with claims through 2020. We identified demographics, liver disease type, cirrhosis complications (e.g, jaundice), diagnosis stage, receipt of local therapies (e.g, resection) and receipt of systemic therapies (e.g, sorafenib). We described cohort characteristics by race. OS and receipt of treatment were analyzed using Cox and logistical regression models adjusted for the above covariates.
Results:
The study included 8,257 patients (77.7% White, 11.9% Asian, 9.1% Black, 0.9% American Indian). Median OS for all patients was 9.1 months. Compared to White patients, Black patients had worse OS (hazard ratio [HR] 1.36, p= <.0001). Black patients receiving no treatment (HR 1.24, p=0.002) and local therapy first (HR 1.29, p=0.003) also had worse survival, while Black patients receiving systemic therapy first had similar OS (HR 1.08, p=0.62) to White patients. Black patients were less likely than White patients to receive any treatment (odds ratio [OR]: 0.64, p=<.0001) or curative treatment if they had early stage-HCC (OR 0.49, p=0.013), but had no difference in receipt of a new systemic therapy if receiving any systemic therapy (OR 0.72, p=0.19) (Table). Compared to White patients, Asian patients had better OS among all patients (HR 0.91, p=0.04) and among patients receiving local therapy first (HR 0.89), but similar OS among patients receiving no treatment (HR 0.90, p=0.13) or systemic therapy first (HR 1.07, p=0.60). Asian patients were as likely as White patients to receive any treatment (OR 1.07, p=0.43), curative treatment for early-stage HCC (OR 0.94, p=0.70) and novel therapies if receiving systemic therapy (OR 1.10, p=0.70).
Conclusions:
As new HCC therapies emerged, there were racial disparities in OS and receipt of any treatment or local therapies, but not in receipt of new systemic treatments. Targeted interventions are essential to address these disparities and ensure equitable access to care.

Treatment and survival disparities, by race.

All PatientsN=8,218
White N=6412
Black N=747
Asian or Pacific Islander N=983
American Indian/Alaskan Native* N=76

Median Overall survival, months
9.1
9.5
5.6
10.1
8.3

No treatment, n (%)
3213 (39.1)
2510 (39.2)
348 (46.6)
330 (33.6)
25 (32.9)

Systemic first, n (%)
894 (10.9)
693 (10.8)
85 (11.4)
103 (10.5)
13 (17.1)

Local first, n (%)
4111 (50.0)
3209 (50.0)
314 (42.0)
550 (56.0)
38 (50.0)

Of patients with early-stage HCC, those who received curative treatment, n (%)
749 (41.7)
>542 (>41.5)
43 (29.3)
147 (45.2)
<11 (<40.0)

Of patients receiving systemic therapy, those who got a novel therapy, n (%)
763 (44.3)
>581 (>43.9)
63 (40.9)
103 (46.0)
<11 (<50.0)
Country and continent-wise trends in mortality rates of ovarian cancer from 1980-2021: An analysis of GBD study 2021.
Authors: Ahmad Shahzaib , Rehman Wania Ur , Shaukat Muhammad Talha , Rehman Aqeeb Ur , Mohsin Aleenah , Dizon Don S.
Published: September 2024

148

Background:
Ovarian cancer is one of the major causes of cancer related deaths in women worldwide. Early detection, primarily via ultrasound
,
can result in lower mortality and morbidity. We present a comprehensive evaluation derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, depicting the ovarian cancer associated mortality pattern from 1980 to 2021.
Methods:
Data were methodically retrieved from the Global Burden of Diseases (GBD) study, which included age-standardized death rates, Years of Lost Life (YLL), and disability-adjusted life years (DALYs). The dataset was stratified globally and categorized by continent, with Africa divided into Northern, Southern, Eastern, Western, and Central regions, and by World Bank income levels. Joinpoint Regression was employed to determine average annual percentage changes (AAPC).
Results:
Globally, the Age standardized death rates (ASDR) for ovarian cancer had an overall decline from 1980 to 2021. In 1980, the ASDR was 4.64 (95% UI: 4.3-5.14), and it declined to 4.05 (AAPC: -0.315; 95% CI: -0.35 to -0.27) in 2021. Globally, the disability-adjusted life-years (DALYs) rate was 132.4 (95% UI: 121.3–145.6) per 100,000 people in 1990, and it decreased to 115.14 (AAPC: -0.44; 95% CI: -0.52 to -0.36) in 2021. From 1990 to 2021, the age-standardized years of life lost (YLL) showed a uniform drop with an AAPC of -0.36 (95% CI: -0.40 to -0.31). However, in continent wise analysis, while the Americas and Europe had continuously declining ASDRs, Asia and Africa had an increasing trend throughout the predetermined time frame. From 1980 to 2021, America had an AAPC of -0.67 (95% CI: -0.69 to -0.65). Similarly, Europe also had a decreasing trend from 1980 to 2021 with an AAPC of -0.48 (95% CI: -0.50 to -0.45). The AAPC for Africa was 1.203 (95% CI: 1.19 to 1.21), showing a greater incline compared to the other continents. The AAPC for Asia was 0.54 (95% CI: 0.527 to 0.563). During further analysis of the African region, we observed that southern and eastern Africa had the highest ASDRs. According to World Bank income levels, low-income and lower-middle-income countries had increasing death rates, while high and upper-middle income countries had decreasing death rates from 1980 to 2021.
Conclusions:
The study disclosed a global decline in ovarian cancer fatality rates from 1980 to 2021. Although significant progress has been made in the Americas and Europe, mortality rates have risen in Asia and Africa, with southern and eastern Africa exhibiting particularly high rates. An increase in death rates is also observed in low- and lower-middle-income countries, contrasting with an overall decrease globally and in high-income nations.