bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study of Physical Properties of Laminated Veneer Lumber Made by Three Cameroonian Hardwoods with Two Adhesives
Authors: Tankou Ntahayo Celestin Patrick , Mabekou Takam Jeanne Sandrine , Kouefouet Hervice , Foadieng Emmanuel , Pitti Rostand Moutou , Talla Pierre Kisito
Published: June 2024

This work deals with the determination of some properties of laminated veneer lumber (LVL) made from tropical hardwoods, specifically focusing on Cameroonian woods. The LVL samples are manufactured using veneer from three tropical wood species: Ayous, Ilomba, and Bete. Two types of adhesives are used: a neoprene contact adhesive (Magpow) and a white vinyl adhesive (Nemo). The specimens have undergone multiple drying cycles, and hundreds of samples from each species have been selected with dimensions of 1 cm × 1 cm × 1 cm. These samples are then machined according to the specific wood grain of each species. The experiments conducted aim to determine properties such as moisture content, densities, volume swelling, shrinkage coefficients, and the hygroscopic point of equilibrium of the samples. Swelling and shrinkage measurements allow for the visualization of sample dimensions in relation to humidity levels, and the hysteresis of the adsorption phenomenon of the LVL is also obtained. The results show that regardless of the type of adhesive or veneer used, LVLs are denser than the wood they are made from. For each type of LVL, the ratio between the mass of a sample saturated in water and the mass of the dried sample remains constant. The rule of mixture is investigated, and the density properties of materials and the vacuum rates of LVL samples are compared with experimental data.
Analytical Bayesian Copula‐Based Uncertainty Quantification (A‐BASIC‐UQ) Using Data with Missing Values in Structural Health Monitoring
Authors: Yuen Ka-Veng , Zhao Zi-Tong , Mu He-Qing , Shao Wei
Published: June 2024

The presence of missing values is common in real‐world datasets, so modeling and uncertainty quantification (UQ) of incomplete datasets have gained increasing attention in various research areas, including structural health monitoring (SHM). However, modeling and UQ utilizing incomplete datasets are nontrivial tasks. On the other hand, prediction based on a set of incomplete measured input variables is also an important task, but most existing methods, which are discriminative models, do not possess this capability. Aiming to tackle these two challenges, we propose the two‐stage analytical Bayesian copula‐based uncertainty quantification (A‐BASIC‐UQ) using incomplete SHM data. In the modeling stage, the copula‐based multivariate joint probability density function (PDF) is modeled directly according to an incomplete dataset without imputation or disposal of any data points. For the univariate marginal PDF, using the measured (nonmissing) values of the corresponding random variable (RV), Bayesian model class selection is conducted to select the most suitable model class. For the Gaussian copula PDF, using the bivariate complete data points of entry‐by‐entry pairwise data, the optimal parameter vector is obtained from the estimation of the Pearson correlation coefficient. In the prediction stage, the analytical expressions of the predictive PDF, the predicted value and the credible region of the output variables are derived according to a set of incomplete measured input variables. The analytical expression of the predictive PDF is obtained based on the analytical operations on the auxiliary RVs and that of the predicted value and the credible region are obtained based on the analysis of multivariate Gaussian distribution. Therefore, the proposed method does not require numerical integration nor Monte Carlo simulation and does not suffer from computational burden even when there are many variables (say 4 or above). Examples using simulated data and real SHM data are presented to illustrate the capability of the proposed A‐BASIC‐UQ.
Research on the Damage Characteristics of Ti‐6Al‐4V Simulation Blades Subjected to Foreign Object Damage
Authors: Li Zhongsheng , Zhang Taidou , Zhang Haiyang , Zhao Zhenhua
Published: June 2024

In order to study the influence of different factors on the foreign object damage (FOD) of titanium alloy blades, a Ti‐6Al‐4V simulation blade was taken as the research object, and FOD tests were carried out under different working conditions by using an air cannon. The results show that the type of foreign object has an obvious influence on the impact damage, mainly reflected in the hardness and density of the foreign object materials. The greater the hardness and density of the materials, the greater the damage width and depth. The effects of foreign object size and impact velocity on damage width and depth show a positive correlation due to the impact energy. The widths and depths of FOD damage do not present obvious relationships with the impact angles, but the impact angles show some influences on the forms of damage. FOD with an angle of 0° usually results in semicircular notches, and FOD with a certain angle can cause tearing notches.
Longitudinal Association between Bullying Victimization and Depressive Symptoms in Chinese Early Adolescents: The Effect of Life Satisfaction
Authors: Tong Yingying , Xie Faliang , Wen Xue , Li Yonghan , Yuan Mengyuan , Zhang Xueying , Chen Juan , Wang Gengfu , Su Puyu
Published: June 2024

Bullying victimization is associated with an increased risk of depression among adolescents. However, few studies have examined the association between bullying victimization and depressive symptoms, the impact of particular dimensions of life satisfaction on this relationship, and whether these associations vary by gender. A multilevel model (MLM) was used to explore the relationship between 1,611 Chinese early adolescents’ incidence of bullying victimization and depression and life satisfaction’s effect on this relationship (60.5% boys, Mage = 12.48, SD = 0.48 at baseline). Bullying victimization was found to predict a high risk of depression in early adolescence. Further, we observed that life satisfaction mitigated the relationship between bullying victimization and depression; the MLM analysis indicated that these associations somewhat differed between genders. This study emphasized—based on ecological theory—four special dimensions of life satisfaction and bullying victimization in relation to depression risk. Additionally, this study provides novel insights into the correlation between bullying victimization and depression among Chinese early adolescents.
An Effective Dataset Preprocessing Method in Tilted Gear Defects Target Detection
Authors: Tu Lifen , Peng Qi , Zhang Aiqun , Yang Xiao , Wang Jiaqi
Published: June 2024

Gear defect detection is a crucial component in power automation systems. Methods based on deep learning have exhibited excellent performance in detecting gears. However, the effect of defect detection for tilted gears is not as good. This is due to the traditional horizontal bounding box annotation method, which inevitably produces many overlapping areas in the annotated bounding box when used in tilted gear targets, and a large part of the areas do not belong to defects. In order to address the issue of low precision in the detection of defects in tilted gears based on deep learning, a dataset preprocessing scheme has been proposed. Initially, the images and annotation files of the training set and validation set are automatically rotated. Subsequently, the rotated data are utilized to train the defect detection model. Finally, the test set is subjected to the same image rotation method as the first step, resulting in the generation of high‐precision defect detection results, which are then input into the defect detection model. In order to facilitate comparison with the ground truth, the JSON file obtained from the detection result is rotated in reverse and the result is mapped to the original test set before rotation. In order to verify the effectiveness of the dataset optimization method proposed in this article, the same configuration file is used to train and evaluate the gear defect detection model with the dataset before and after optimization, respectively. The three detection models with the highest comprehensive indicators were employed to assess the dataset before and after optimization, with the average detection precision mAP serving as a quantitative comparison indicator. The findings demonstrate that the data optimization method proposed in this article has markedly enhanced mAP in tilted gear defect detection. Upon testing the proposed method on the PP‐YOLOE + model, mAP (0.5) exhibited an increase of 18.5%, while mAP (0.5 : 0.95) demonstrated a 29.1% improvement. When the method was tested on the RT‐DETR model, mAP (0.5) exhibited an increase of 24.7%, while mAP (0.5 : 0.95) demonstrated an 18.4% improvement. When tested on the few‐short model, mAP (0.5) increased by 23.3% and mAP (0.5 : 0.95) increased by 19.8%. This validates the effectiveness of the dataset processing method proposed in this article in the detection of tilted gear defects.
Laparoscopy and Laparotomy for Endometrioid Adenocarcinoma: Short‐ and Long‐Term Outcomes’ Comparison
Authors: Hong Lan , Wang Xiuzhen , Wang Shengtan , Li Wei , Zheng Lang , Liu Jun , Gao Haocheng , Liu Xiaohang , Li Guifei , Shen Lifan , Zhuang Hengzhi , Zhu Genhai
Published: June 2024

Aims. To analyze the short‐term and long‐term outcomes of laparoscopy versus laparotomy in treatment of endometrioid adenocarcinoma and examine the benefits of laparoscopy. Methods. From January 2012 to July 2020, 693 endometrioid adenocarcinoma patients undergoing laparoscopy versus laparotomy were retrospectively identified and enrolled in this study. Basic information for the patients, their perioperative indexes, and recurrence rates were reviewed to assess the therapeutic effect of these two approaches for endometrioid adenocarcinoma. Results. A total of 365 endometrioid adenocarcinoma patients underwent laparoscopy, and 328 patients underwent laparotomy. When compared with the laparotomic group, the laparoscopic group had longer operative times, lower intraoperative bleeding volumes, and shorter postoperative hospital stays. The rate of less‐radical hysterectomy and radical hysterectomy performed in the laparoscopic group (59/365, 16.16%) was significantly lower than that in the laparotomic group (162/328, 49.39%). There was no statistically significant difference in the local recurrence rate between the two groups; however, the remote recurrence rate in the laparotomic group (15/308, 4.87%) was significantly higher than that in the laparoscopic group (3/351, 0.85%). A further subgroup analysis revealed a higher survival benefit both in I/II patients (314/314, 100%, vs. 7/242, 28.93%) and III/IV patients (35/37, 94.59%, vs. 51/66, 77.27%) in the laparoscopic group, when compared with the laparotomic group. Conclusion. Patients who received laparoscopic surgery had a faster surgical recovery and a lower postoperative recurrence rate in the short term than patients who received laparotomic surgery. Laparoscopic surgery is a safe and effective treatment for endometrioid adenocarcinoma.
Land Use Contributions to Heavy Metals/Metaloids Pollution in the Tano Basin, Ghana, and Its Associated Health Risks to Dependant Communities
Authors: Adiyiah Nyantakyi Jackson , Wiafe Samuel , Fusen Yong Osman , Akoto Osei
Published: June 2024

Increased anthropogenic activities are suspected to have contributed to the Tano basin heavy metal/metalloids water quality. However, data on land use contribution to the basin’s heavy metal/metalloids pollution are limited. The study assessed the contribution of land use to the basin’s heavy metals/metalloids pollution by assessing the levels of heavy metals/metalloids in 36 water samples taken from the source/control and experimental sites along the basin. Atomic absorption spectrophotometer was used to analysis samples. Metals/metalloids concentrations in water samples from the basin’s source and the physicochemical parameters were compared with the corresponding concentrations in samples from the experimental sites. Significantly, higher heavy metal/metalloids concentrations and physicochemical levels were identified in the experimental sites than the source/control site. Heavy metal/metalloids levels at the source were as follows: As (0.001 ± 0.11 mg/L) < Cd (0.003 ± 0.34 mg/L) < Zn (0.011 ± 0.97 mg/L) but Pb, Hg, and Cr were not detected. The corresponding levels in the experimental sites were As (0.014 ± 0.88 mg/L) < Hg (0.051 ± 0.76 mg/L) < Cd (0.056 ± 0.45 mg/L) < Zn (0.166 ± 1.95 mg/L) < Cr (0.299 ± 0.42 mg/L) < Pb (0.428 ± 0.44 mg/L). Control water pH was slightly acidic (5.38 ± 3.4) but the experimental sites were near neutrality (7.35 ± 2.1). Noncarcinogenic and carcinogenic risks were detected for water consumption by children and adults in the experimental but none in the control. Land use activities identified were industrial, agricultural, and commercial. Enforcement of buffer zone protection laws is recommended.
Fixating targets in visual search: The role of dorsal and ventral attention networks in the processing of relevance and rarity
Authors: Ischebeck Anja , Kreilinger Hannah , Peiris Miller Joe , Höfler Margit , Gilchrist Iain D. , Körner Christof
Published: July 2024

The dorsal attention network, often observed to be activated in serial visual search tasks, has been associated with goal-directed attention, responsible for the processing of task relevance. In serial visual search, the moment of target detection constitutes not only a task-relevant event, but also a rare event. In the present fMRI experiment, we disentangled task relevance from item rarity using a fixation-based analysis approach. We used a multiple target search task, and participants had to report the number of targets among distractors in the display. We had also added rare distractors to the displays. We found that rare events (targets and rare distractors) activated the dorsal attention network more strongly than common distractors. More importantly, we observed that the left IPS and the left insula, belonging to the dorsal and ventral attention system, respectively, were more strongly activated for targets compared to rare distractors. Using multi-voxel pattern analysis, we found that activation in the TPJ, bilaterally, an area also associated with the ventral attention system, distinguished between target and rare distractor fixations. These results point to an expanded role of the TPJ that seems to process post-perceptual information which is linked to task relevance.
The dissociative role of bursting and non-bursting neural activity in the oscillatory nature of functional brain networks
Authors: Cordier Alix , Mary Alison , Vander Ghinst Marc , Goldman Serge , De Tiège Xavier , Wens Vincent
Published: July 2024

The oscillatory nature of intrinsic brain networks is largely taken for granted in the systems neuroscience community. However, the hypothesis that brain rhythms—and by extension transient bursting oscillations—underlie functional networks has not been demonstrated per se. Electrophysiological measures of functional connectivity are indeed affected by the power bias, which may lead to artefactual observations of spectrally specific network couplings not genuinely driven by neural oscillations, bursting or not. We investigate this crucial question by introducing a unique combination of a rigorous mathematical analysis of the power bias in frequency-dependent amplitude connectivity with a neurobiologically informed model of cerebral background noise based on hidden Markov modeling of resting-state magnetoencephalography (MEG). We demonstrate that the power bias may be corrected by a suitable renormalization depending nonlinearly on the signal-to-noise ratio, with noise identified as non-bursting oscillations. Applying this correction preserves the spectral content of amplitude connectivity, definitely proving the importance of brain rhythms in intrinsic functional networks. Our demonstration highlights a dichotomy between spontaneous oscillatory bursts underlying network couplings and non-bursting oscillations acting as background noise but whose function remains unsettled.
Integrative taxonomy study of brackish water crabs of the genus Ptychognathus Stimpson, 1858 (Crustacea: Brachyura: Varunidae) from Polynesia, with description of two new species
Authors: MAZANCOURT VALENTIN DE , MAZEL VIRGILE , MARQUET GÉRARD , POUPIN JOSEPH , KEITH PHILIPPE
Published: July 2024

In the present contribution, five species of Ptychognathus Stimpson, 1858 are reported from Polynesia: P. crassimanus Finnegan, 1931, P. easteranus Rathbun, 1907, P. riedelii (A. Milne-Edwards, 1868) and two new species. The first new species named P. ngankeeae sp. nov. is close to P. barbatus (A. Milne-Edwards, 1873) from New Caledonia, which is here redescribed for comparison purposes. The second new species named P. similis sp. nov. is close to P. hachijoensis Sakai, 1955.
Outbreak of equine herpesvirus 4 (EHV-4) in Denmark: tracing patient zero and viral characterization
Authors: Ryt-Hansen Pia , Johansen Victoria Kyhl , Cuicani Marta Maria , Larsen Lars Erik , Hansen Sanni
Published: July 2024

Background

Equine herpesvirus 4 (EHV-4) causes respiratory disease in horses, and the virus is considered endemic in the global equine population. However, outbreaks can occur when several horses are gathered in relation to shows, competitions, breeding units and at hospitals. In the spring year 2022, an EHV-4 outbreak occurred at the Large Animal Teaching Hospital, University of Copenhagen, Denmark. Nine horses were tested EHV-4 positive during the outbreak, which lasted approx. seven weeks. In addition, a tenth horse “Eq10” tested EHV-4 positive almost three weeks after the last of the outbreak horses tested positive. Detailed clinical registrations were obtained from all ten horses as well as their location and movement during hospitalization. Nasal swabs were obtained throughout the outbreak and tested by qPCR for EHV-4. Additionally, pre- and post-infection sera were tested for the presence of EHV-4 antibodies. Selected samples were characterized by partial and full genome sequencing.

Results

The most common clinical signs of the EHV-4 infected horses during this outbreak were pyrexia, nasal discharge, mandibular lymphadenopathy and increased lung sounds upon auscultation. Based on the locations of the horses, EHV-4 detection and antibody responses the most likely “patient zero” was identified as being “Eq1”. Partial genome sequencing revealed that Eq10 was infected by another wild type EHV-4 strain, suggesting that the hospital was able to eliminate the outbreak by testing and reinforcing biosecurity measures. The complete genome sequence of the outbreak strain was obtained and revealed a closer relation to Australian and Japanese EHV-4 strains rather than to other European EHV-4 strains, however, very limited sequence data are available from Europe.

Conclusion

The study illustrated the transmission of EHV-4 within an equine facility/hospital and provided new insights into the viral shedding, antibody responses and clinical signs related to EHV-4 infections. Finally, sequencing proved a useful tool in understanding the transmission within the hospital, and in characterizing of the outbreak strain.
ZnO NPs induce miR-342-5p mediated ferroptosis of spermatocytes through the NF-κB pathway in mice
Authors: Liu Guangyu , Lv Jing , Wang Yifan , Sun Kaikai , Gao Huimin , Li Yuanyou , Yao Qichun , Ma Lizhu , Kochshugulova Gulzat , Jiang Zhongliang
Published: July 2024

Background

Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated.

Results

We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1.

Conclusions

The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs.

Graphical Abstract
Filarial chylous ascites with chylothorax: challenge of diagnosis and management case report
Authors: Elhadidy Abdelmoneim , Elrefaay Mohamed , Elsheshiny Hamdy , Elnagdy Fathy
Published: July 2024

Background

Chylous ascites (CA), an uncommon clinical condition, is defined as a milky-appearing, triglyceride-rich peritoneal fluid in the abdominal cavity. It may be due to malignancy or cirrhosis in developed countries or infections such as tuberculosis or filariasis in developing countries. This report presents a female patient with chylous ascites with chylothorax secondary to lymphatic filariasis after the exclusion of other etiologies.

Case presentation

A 33-year-old female, from Damietta, Egypt, was referred to us complaining of abdominal distension and easy fatigability for 5 months. The patient was diagnosed to have elephantiasis of both lower limbs caused by filariasis and treated by ant-filarial therapy for 9 years. Aspirated ascitic fluid was milky in appearance and rich in triglyceride. All other causes of chylous ascites were excluded by ascetic fluid analysis (chemical, microbiological, and pathological). The patient was treated with diethylcarbamazine (DEC), albendazole, pheniramine, and hydrocortisone followed by a therapeutic pleural and ascitic tapping but ascites re-accumulate. With the addition of doxycycline and Somatostatin/ocreotide, the ascites gradually decreased. Three months later, the patient came back with a significant increase in ascites, and paracentesis was done.

Conclusion

Despite rarity, filarial chylous ascites remains a challenge, and the only effective treatment is still repeated aspiration of the accumulated fluid. More work and discussion are needed.
Prognostic scores for predicting clinical outcomes in upper gastrointestinal bleeding
Authors: Khatana Gaurav , K Sunil Kumar , Kolassery Sandesh , Sebastian Saji , Joseph Deni , Muraleedharanpillai Ramu , Joseph Tony , V Nithya , Unnikrishnan Lal Krishna , Rony Gino
Published: July 2024

Background and aims

This study aimed to determine the performance of AIMS65, Rockall score, and Glasgow-Blatchford score (GBS) in patients presenting with upper gastrointestinal bleeding (UGIB) and to compare results between patients with nonvariceal UGIB (NVUGIB) and variceal UGIB (VUGIB).

Methods

We conducted a single-center prospective cohort study between December 2021 and December 2022. A total of 400 patients who met the inclusion criteria were included in the study, out of which 232 patients (58%) had NVUGIB and 168 patients (42%) had VUGIB. Receiver operating characteristic curve analysis was performed for all outcomes for comparison.

Results

Of the total of 400 patients with UGIB, 232 patients (58%) had NVUGIB, and 168 patients (42%) had VUGIB. The present study showed that GBS (AUROC 0.729, 95% CI: 0.598–0.859, p = 0.001) and RS (AUROC 0.693, 95% CI: 0.579–0.807, p = 0.005) but not AIMS65 (AUROC, 0.545, 95% CI: 0.412–0.679, p = 0.500) predicted in-hospital and overall 6-week mortality in patients with UGIB. All the three scores predicted need for blood transfusion and poor composite outcomes (p < 0.05). The need for endoscopic intervention was predicted by all the three scores in overall UGIB (OUGIB) patients (p < 0.05), only GBS and RS in NVUGIB patients (p < 0.05). Rebleeding was best predicated by RS in both OUGIB and NVUGIB patients (p < 0.05). None of the scores predicted the need for endoscopic intervention, rebleeding, need for surgical and radiological intervention, and composite outcomes in VUGIB patients (p > 0.05).

Conclusions

GBS and RS were superior to AIMS65 in predicted in-hospital and overall 6-week mortality in all the three categories: OUGIB, NVUGIB, and VUGIB patients.
Efficacy of encorafenib/binimetinib in patients with metastatic melanoma with brain metastases: Results from the nationwide Dutch Melanoma Treatment Registry.
Authors: Bloem Manja , van Not Olivier Jules , Aarts Maureen J.B. , Van Den Berkmortel Franchette , Blank Christian U. , Blokx Willeke , Boers-Sonderen Marye J. , Bonenkamp Han J. , de Groot Jan Willem , Haanen John , Hospers Geke , Kapiteijn Ellen , Piersma Djura , van Rijn Rozemarijn , Stevense - den Boer Marion , Van Der Veldt Astrid Aplonia Maria , Vreugdenhil Gerard , Wouters Michel WJM , Suijkerbuijk Karijn , van den Eertwegh Alfonsus Johannes Maria
Published: July 2024

9528

Background: Data on the effectiveness of encorafenib plus binimetinib in patients with melanoma brain metastases (BMs) are lacking. Therefore, we aimed to investigate the effectiveness of encorafenib/binimetinib treatment in melanoma patients with BMs. Methods: All melanoma patients with BMs treated with encorafenib/binimetinib between 2019 and 2023 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients with prior BRAF/MEK inhibition treatment were excluded. We analyzed overall response rates (ORR), progression-free (PFS), and overall survival (OS) from start of encorafenib/binimetinib. We performed subgroup analysis for symptomatic versus asymptomatic BMs and previous treatment versus no previous treatment. Results: In total, 208 patients were included. Median age was 61 years and 58.2% of the patients was male. Lactate dehydrogenase levels were elevated in 48.1% of the patients and symptomatic BMs were present in 63.5%. Of all patients, 41.8% received prior immunotherapy and for 58.2% encorafenib/binimetinib was the first-line treatment. The median follow-up duration was 23.2 months. The ORR was 67.3%. Median PFS was 5.6 months (95% confidence interval (CI): 4.9-6.2) and median OS was 10.9 months (95% CI: 9.6-14.0). OS was significantly shorter in patients with symptomatic BMs versus asymptomatic BMs (median 9.7 versus 22.9 months, p<0.01), while PFS was similar (median 5.6 versus 5.8 months, p=0.07). Previously untreated patients had worse prognostic characteristics than previously treated patients. PFS was not significantly different between patients with versus without previous systemic treatment (median 8.8 versus 5.2 months, p=0.08), while OS from start of encorafenib/binimetinib was longer for previously treated patients (median 15.9 versus 9.6 months, p<0.01). Conclusions: Encorafenib plus binimetinib has clinical activity in real world melanoma patients with BMs, but PFS and OS are shorter than previously reported for patients without brain metastases. These data may aid physicians in clinical decision-making.
Tolerance and safety of adjuvant metronomic capecitabine in Indian patients with non-metastatic triple negative breast cancer (TNBC): An institutional experience.
Authors: Kate Shruti , Ramesh Yasam Venkata , Vyavahare Rohini , Nagarkar Rajnish Vasant
Published: July 2024

e12530

Background: Triple-negative breast cancer (TNBC) subtype has a high risk of recurrence and overall poorer survival after standard treatment. SYSUCC-001 study presented in ASCO 2020 reported an increased disease-free survival after one year of metronomic capecitabine in operable TNBC patients after completion of local therapy. As per our clinical experience in metastatic breast cancer, many Indian patients are not able to tolerate capecitabine for longer duration. Hence, we wanted to assess the tolerance and safety of one year of daily dosing of capecitabine in our patients with Non-Metastatic TNBC. Methods: We performed a retrospective analysis of non-metastatic TNBC patients receiving adjuvant capecitabine 650 mg /m2 twice daily continuously for one year who took treatment from June 2020 to August 2022. The data extracted included patient socio-demographics, capecitabine information, side effects, and capecitabine treatment changes (dose reductions and dose interruptions). Statistical analysis was conducted using SPSS, version 24. Results: We analyzed 90 patients, out of which majority (62%) were stage II. Median age of the cohort was 48 years. Germline data was available for 64 patients, out which 8 patients were BRCA 1 positive and 8 patients had a variant of undetermined significance. Median duration of capecitabine in our patients was 230 days (IQR: 10 - 360). Twenty-six (28.8%) patients underwent dose reduction and 15 (16.6%) had reported grade 3 toxicity. Mean dose of capecitabine received was 535 mg / m2 twice daily. Treatment was interrupted due to toxicity in 20 (22%) of patients. The most common capecitabine-induced toxicity was hand foot syndrome, which was also the most common reason for dose reduction and treatment interruption. Dihydropyrimidine dehydrogenase (DPD) mutation status was known for 38 patients out of which only one (2.6%) was found to have DPD deficiency. Incidence of grade 3 toxicity was observed to be less in patients with age less than 50 years, ECOG performance status 0-1 and absence of comorbidities. Two-year disease free survival (DFS) and overall survival (OS) was estimated to be 79.3% and 80% respectively. Most common site of metastases was reported to be brain followed by lung. Conclusions: Continuous metronomic dosing of adjuvant capecitabine for 1 year is fairly well tolerated in Indian patients with non-metastatic TNBC, but may still require dose reduction in some patients due to toxicity.
Clinical outcomes in patients with early-stage breast cancer in a racially and ethnically diverse patient population.
Authors: Shin Denny Donggun , Switchenko Jeffrey M. , Marra Angelo , Kalinsky Kevin
Published: July 2024

e12532

Background: Despite the growing evidence that substantial disparities exist in breast cancer care per socioeconomic status, the racial and ethnic disparities that contribute to clinical outcomes in patients with early breast cancer are not well understood. This analysis attempts to better characterize these differences in a diverse group of patients with early breast cancer. Methods: Patients were identified from an institutional database from the Winship Cancer Institute, which included those with pathologic stage I-III breast cancer with varying hormone receptors (HR) and HER2 receptor status who received care between 1999-2023. Patients with ductal carcinoma in-situ (DCIS) and with metastatic breast cancer at diagnosis were excluded from this retrospective analysis. Using variables such as race, treatment received, pathological stage, tumor grade, and histology, we performed univariate and multivariate analysis for IDFS, defined as pts who are alive and free of any breast or other cancer. Results: 449 patients were included, which comprised of 148 non-Hispanic African American (33%) and 301 (66%) Caucasian women. Mean age at diagnosis was 60; 77.3% of patients were post-menopausal, and 79.1% received operable endocrine therapy. 76.4% of patients had invasive ductal carcinoma (IDC) and 13.1% invasive lobular carcinoma (ILC). Only 9.8% received chemotherapy. In univariate analysis, patients who were triple negative (n=30, 6.8%) had worse IDFS compared to those who were HR+/HER2- (n=351) (Hazard Ratio=2.49, p=0.036) Additional patients with larger tumors with pT2-pT4 (n=133, 30.4%) had worse IDFS compared to those with pT0-pT1 (p=297, 67.8%) tumors (HR=2.04, p=0.014). There were no significant differences in clinical outcomes by patient race or by lymph node involvement. Conclusions: In our lower-risk, racially diverse cohort, our findings demonstrate that patients with HR-/HER2- breast cancer and larger tumors have worse IDFS. More analyses should be performed on a population with higher-risk patients and larger cohort. Future studies should continue to focus on early screening, as well as novel therapeutics to treat HR-/HER2- disease.
Characterizing vaginal stenosis in female cancer survivors.
Authors: Mihulka Olivia , Curran Melissa , Wolde Tizeta M. , Moore Jessica Firdman , Rojas Kristin E.
Published: July 2024

e13800

Background: Vaginal stenosis is an underreported and undertreated sequelae of cancer treatment that leads to pain with sexual activity and inability to tolerate pelvic exams. We sought to describe a population of female cancer survivors presenting with sexual health concerns and identify factors associated with presence of vaginal stenosis on genitourinary exam (GU). Methods: A retrospective analysis included 134 female cancer survivors presenting to a sexual health after cancer program in South Florida (2020-2023). Sexual function and GU anatomy disruptions were evaluated using the Female Sexual Function Index (FSFI) and Adapted Vulvovaginal Exam Score (AVES), respectively. Vaginal stenosis was defined as presence of vaginal agglutination, shortening, or scarring/adhesions on GU exam. Patients who did and did not present with vaginal stenosis were compared using Chi-squared analysis, while independent t-test analyzed FSFI and AVES scores. Results: Of 134 patients, 116 met criteria for inclusion and underwent a GU examination. Median age was 45 (23-75). Race, ethnicity, menopausal status, cancer type, and treatment type were similar between groups. The rate of vaginal stenosis in patients with breast cancer was 13.4%, gynecologic cancer was 27.2%, and 28.6% with other cancer types (including gastrointestinal, hematologic, sarcoma). Higher median AVES scores, which denote more severe GU exam disruptions, were found in patients with vaginal stenosis compared to those without (13 vs 5; p<.001). While overall FSFI scores were similar between groups, median FSFI pain domain scores were lower in those with vaginal stenosis compared to those without stenosis (7.8 vs 11; p=0.037). Conclusions: Factors associated with the development of vaginal stenosis in female cancer survivors are not well-described. Our analysis reveals that vaginal stenosis develops in women treated for a variety of cancer types across the age continuum. Identifying and treating this severe sequela of treatment is a critical step in improving the sexual health of female cancer survivors. Ongoing work seeks to evaluate the safety and efficacy of treatments to reverse GU exam disruptions after cancer treatment. [Table: see text]
Transcriptional mechanisms of phenotypic plasticity in glioblastoma.
Authors: Mukherjee Ishita , Park James H. , Patel Anoop P. , Baliga Nitin S.
Published: July 2024

e14027

Background: Primary glioblastoma (GBM) tumor cells exhibit plasticity and can adopt different cellular states that exhibit dynamic transitions between states. This could be one of the mechanisms for treatment escape and leads to poor prognosis in GBM. In this regard, we sought to uncover transcriptional regulatory mechanisms responsible for this phenotypic plasticity in GBM. Methods: Standard of care (SOC) treatment (radiation and temozolomide) modulates transcriptional regulatory networks (TRNs) of the tumor cells and drives treatment resistance. Since TRNs could be key mechanistic drivers for state transitions, integrated single-cell RNA sequencing (scRNAseq) data of primary and relapse patient samples (11) were analyzed with scMINER. Our method uses a systems biology framework to identify cell states (St_1 to St_n) in terms of regulatory networks and their activities. Clustering of co-regulated gene modules (regulons), enabled the identification of transcriptional programs and regulatory mechanisms that specify tumor cell states. Results: Activity patterns of 38 transcriptional programs clustered tumor cells from the patients into 21 states. Preliminarily, we observed common regulatory network cell states (St_1, St_2, St_5, St_6) across patient tumors. Additionally, primary tumor cells of a patient (UW14) transitioned from initial cell state(s) observed across multiple patients (e.g., St_1) to a recurrent state (e.g., St_9) through a trajectory driven by transcription factors (TFs). Herein, scMINER regulatory network inference method also defines master TFs (TFs that regulate the majority of the other TFs in the network) that were used to characterize initial (St_1) or recurrent (St_9) cell states. Moreover, certain transcription factors (22) and their co-expressed target genes (regulons) also exhibit variation in expression across the pseudotime trajectory (from St_1 to St_9) including masterTFs such as SOX9 and MECOM. Conclusions: Therefore, we observed that shared cell states may exist across patients (primary and relapse) although in different proportions. Our analysis suggests a de-differentiation trajectory from neuronal cells to developing GBM stem cells and predicts transcription factors that could be playing an important role therein. Moreover, similar transcriptional regulatory mechanisms may promote transitions between primary and recurrent tumor cell states that exhibit phenotypic plasticity.
Correlation of therapy-induced neutropenia with survival in patients with metastatic pancreatic cancer treated with GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.
Authors: Ugolkov Andrey , Koukol Austin , Kellinger Caroline , Smith Sheri Lynn , Gallipoli Susan , Gagnon Suzanne , Seifarth Chris , Reich Steven D. , Mazar Andrew Paul
Published: July 2024

e16311

Background: Previously, elraglusib (9-ING-41), an inhibitor of Glycogen Synthase Kinase-3 (GSK-3), was shown to potentiate the anticancer effects of chemotherapeutic drugs in preclinical models of cancer. The combination of elraglusib and gemcitabine/nab-paclitaxel (GnP) is currently being investigated in a randomized, open-label 1801 phase 2 study as a first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Chemotherapy-induced neutropenia is a common dose-limiting toxicity resulting in dose reductions and/or treatment interruptions. Present evidence shows that therapy-induced neutropenia (TIN) grade 3-4 correlates with survival and is a potential marker for improved clinical outcome in elraglusib/GnP-treated patients. Methods: We correlated overall survival (OS) and time-to-treatment discontinuation (TTD) with TIN grade 3-4 in 72 (GnP arm) and 155 (elraglusib/GnP arm) mPDAC patients previously untreated for advanced disease (1801 Part 3 Arm B study; NCT03678883). TTD was defined as the date of first dose to the date of treatment discontinuation or death. The Kaplan-Meier log-rank test was used for statistical analysis. A p-value < 0.05 was considered statistically significant. Results: The rate of grade 3-4 TIN was 22% (16/72 patients) and 47% (72/155 patients) in the GnP and elraglusib/GnP groups, respectively. Based on 28% of all recorded death events in elraglusib/GnP group and 36% in GnP group, we found that grade 3-4 TIN was significantly associated with improved OS in patients treated with elraglusib/GnP (median OS: 14.4 vs 5.9 months; P < 0.05) but not in patients treated with GnP (median OS: 7.6 vs 7.2 months). In the elraglusib/GnP group, patients with grade 3-4 TIN stayed on treatment significantly longer (median TTD: 7.9 months; P < 0.05) as compared to the patients who did not develop TIN grade 3-4 (median TTD: 1.7 months). Conclusions: Our preliminary results identified grade 3-4 TIN as a potential marker of improved clinical outcome for elraglusib/GnP therapy in previously untreated patients with mPDAC. Recruitment for the 1801 Part 3 Arm B phase 2 trial has been completed. Another interim analysis of OS and its correlation to grade 3-4 TIN will be available by April 2024 and will be included in the final presentation. Clinical trial information: NCT03678883 .
Longitudinal tissue-based evaluation of TIGIT expression in patients with pancreatic cancer: Effect of expression with advancing clinical stages and across racial groups.
Authors: George Madison , Clark Julie , Hartway Kailee , Zwernik Samuel , Gartrelle Kendyll , Sålas-Escabillas Daniel , Long Daniel , Nassif Georges , Pichardo Thais , Wombwell Allison , Wen Hui-Ju , Benitz Simone , Philip Philip A. , Khan Gazala , Shah Rupen A. , Park Hakmin , Crawford Howard , Kwon David S. , Theisen Brian , Steele Nina
Published: July 2024

e16314

Background: While ground has been gained, pancreatic ductal adenocarcinoma (PDAC) continues to have a low 5-year survival of 13%. This is owed partially to a lack of early detection biomarkers and resistance to standard therapeutic options. TIGIT, an immune checkpoint receptor, is a marker of T-cell exhaustion and plays a key role in the inhibition of anti-tumor immune responses. TIGIT inhibitors are being explored in clinical trials in PDAC. Here we evaluate TIGIT expression in a cohort of PDAC patients and correlate level and intensity of expression with clinical parameters. We also examine changes in expression as the disease progresses from primary to metastatic disease. Methods: We performed RNAscope in situ hybridization (ISH) with a probe specific for human TIGIT mRNA on 82 formalin-fixed paraffin-embedded (FFPE) tissue samples. The cohort of tissue samples included 9 biopsies, 67 primary resections and 6 metastatic lesions. We evaluated the total TIGIT expression (%) as well as the intensity of TIGIT expression (% of cells with 3+ punctae, signifying putative immune cells), and compared these values between samples. Utilizing linear regression for continuous outcomes and logistic regression for binary outcomes, we tested for associations between TIGIT expression and clinical covariates. Results: Staining analysis showed that TIGIT expression did not differ significantly between racial groups. The mean percentage of TIGIT positive cells was 64.0%. High expression of TIGIT was associated with more advanced clinical stage (p < 0.05). Evaluation of three longitudinal samples from the same patient revealed decreased TIGIT expression from the initial biopsy (41.6%) to resection (33.4%) and metastasis (2.8%). In these specimens, 3+ TIGIT expression also declined (2.1%, 1.2% and 0.02%, respectively). Conclusions: Anti-TIGIT therapy has potential to reverse immune suppression and, with other therapeutic modalities, may provide survival benefit. Here we demonstrate that increased TIGIT expression correlates with more advanced stage at diagnosis and also present data demonstrating that overall TIGIT expression, as detected by RNAscope ISH, may decrease as PDAC progresses to metastasis. As such, anti-TIGIT therapy may have important implications for evading an important mechanism of cancer progression.
Demographic and socioeconomic analysis of patients with glucagonoma: Insights from the National Cancer Database.
Authors: Diagne Yaye Fatou , Alban Sierra , Reddy Nisha , Loomer Michael , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: July 2024

e16319

Background: Glucagonoma is a rare glucagon-producing alpha islet cell tumor primarily of the pancreas, and a type of pancreatic neuroendocrine tumor. These types of cancers have a 10-year survival rate of about 38%. Metastasis may be found in approximately 50% of glucagonoma cases. As a result of the low incidence of glucagonoma, analysis of the diagnostic patterns may provide more insight into the disease’s epidemiology. This study analyzed the National Cancer Database (NCDB) to examine demographic factors of individuals diagnosed with glucagonoma. Methods: ICD-8152-3 Data from the NCDB between 2004-2020 was gathered to perform a retrospective cohort analysis on patients diagnosed with glucagonoma (N = 88). Descriptive statistics were used to investigate demographic factors such as age, sex, race, Hispanic status, years of education, insurance, facility type, distance from facility, and Charlson-Deyo score. Regression analysis was utilized to evaluate incidence trends. Results: We found that patients had an average age of 61 years (SD = 13, range = 23-90), with an average tumor size of 53 mm (SD = 39, range = 12-140), and the majority were male (61%) and White (90%). The majority of patients (97%) did not receive palliative care, with surgery (57%) and chemotherapy (28%) being the primary treatments. Post-surgery, 90% had no residual tumor, and survival rates were 98% after thirty days and 96% after ninety days. Most were treated in academic/research facilities (43%) and had private insurance (59%) or Medicare (34%). The largest median household income quartile of these patients was $74,063 or more (39%).The study noted a 2-year survival rate of 74%, a 5-year rate of 54%, and a 10-year rate of 31%, with a mean survival of 89.3 months. The primary disease sites were the tail of the pancreas (32%) and pancreas, NOS (22%). The distribution across NCDB Analytic Stage Groups was 19% for Stage I, 11% for Stage II, 2% for Stage III, and 23% for Stage IV. Conclusions: This study represents the first analysis of glucagonoma patients using the National Cancer Database, filling a gap in our understanding of the disease. The findings indicate that the majority of glucagonoma patients were non-Hispanic, White, and had tumors primarily located in the tail of the pancreas, aligning with earlier case report descriptions. Socioeconomically, patients most likely had earnings above the median income quartile, resided in densely populated metropolitan areas, and received treatment in academic facilities. Further investigation is necessary to have a more thorough grasp of the impact of demographic and socioeconomic characteristics on glucagonoma patients' diagnosis, course of treatment, and overall survival rates.