bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the interplay between vocational competence and dropout intention: insights and perspectives
Authors: Ma Beifang , Krötz Maximilian , Deutscher Viola , Winther Esther
Published: May 2024

High drop-out rates from Vocational Education and Training (VET) remain a severe problem in VET systems globally. Despite decades of drop-out research revealing numerous influencing factors, the role of trainees’ vocational competence in their drop-out behavior has been neglected. This study aims to define the structure of vocational competence and analyze its effects on drop-out intention. Using longitudinal data from 458 commercial trainees in Germany, vocational competence is measured at three time points using a validated competence test, subdivided into domain-linked and domain-specific dimensions (Gelman and Greeno, 1989). Four different directions of drop-out intentions are considered, enabling a detailed effect inspection of the prevailing research gap. Additionally, factors identified in previous studies, such as educational level, age, language, and the degree of having chosen one’s desired occupation, are controlled for. We conducted 12 rounds of ordinal logistic regression to test three lagged temporal combinations of the effect relationship between vocational competence and dropout intention over different time spans (T0- > T1, T1- > T2, T0- > T2). We find that lower domain-specific competence increases the intention to drop out from VET without qualification over different time spans. Initial lower domain-specific competence also affects trainees’ intention to change their occupation in the final year of training. Furthermore, higher levels of domain-linked competence at the beginning increase the intention to leave VET to pursue higher qualifications in the midterm of training.
Axonal autophagic vesicle transport in the rat optic nerve in vivo under normal conditions and during acute axonal degeneration
Authors: Luo Xiaoyue , Zhang Jiong , Tolö Johan , Kügler Sebastian , Michel Uwe , Bähr Mathias , Koch Jan Christoph
Published: May 2024

Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the axon and transported back to the soma. This transport is essential since the final degradation of the vesicular content occurs only close to or in the soma. Here, we established an in vivo live-imaging model in the rat optic nerve using viral vector mediated LC3-labeling and two-photon-microscopy to analyze axonal transport of AVs. Under basal conditions in vivo, 50% of the AVs are moving with a majority of 85% being transported in the retrograde direction. Transport velocity is higher in the retrograde than in the anterograde direction. A crush lesion of the optic nerve results in a rapid breakdown of retrograde axonal transport while the anterograde transport stays intact over several hours. Close to the lesion site, the formation of AVs is upregulated within the first 6 h after crush, but the clearance of AVs and the levels of lysosomal markers in the adjacent axon are reduced. Expression of p150Glued, an adaptor protein of dynein, is significantly reduced after crush lesion. In vitro, fusion and colocalization of the lysosomal marker cathepsin D with AVs are reduced after axotomy. Taken together, we present here the first in vivo analysis of axonal AV transport in the mammalian CNS using live-imaging. We find that axotomy leads to severe defects of retrograde motility and a decreased clearance of AVs via the lysosomal system.
Human-land relationship in the construction of historical settlements based on Complex Adaptive System (CAS) theory: evidence from Shawan in Guangfu region, China
Authors: Zhang Yang , He Yi
Published: May 2024

The relationship between humans and land environment within historical settlements reflects the intricate interplay between human societies, their construction activities, and the specific geographical contexts. Inadequate research into this relationship hinders a comprehensive understanding of the social spatial intricacies inherent in historical settlements. This paper adopts the theoretical framework of complex adaptive system and takes Shawan Ancient Town in Guangfu area of China as an example. Under the geographical background of sustainable land growth in the coastal zone, this study analyzed the subtle changes in the relationship between people and land during the historical construction, and the key findings of the investigation are threefold: (1) Land resources play a central role in the construction of human-land relationships in historical settlements. The geographical environment and social institutions serve as configuring factors in the formation and evolution of human-land relationships. These factors collectively determine the formation and evolution of human-land relationships. (2) Social space emerges as a pivotal manifestation of the human–environment relationship in historical settlements, transcending mere physical dimensions. Consequently, a holistic study of this relationship necessitates a comprehensive exploration not only of spatial configurations but also of the intricate interconnections among social bonds, structural formations, societal order, and settlement spatiality. (3) Drawing on the framework of complex adaptive systems theory, the study disentangles intricate elements within the human-land relationship of historical settlements. It distills and examines the manifestations of four intricate adaptive capacities—namely aggregation, non-linearity, flow, and diversity—alongside the mechanisms of tags, internal models, and fundamental building blocks. It is believed that the study of historical settlements in coastal areas needs to grasp the invariable social-spatial objects such as geographical environment, land form, local beliefs. Take it as a clue to sort out how other elements of change have iterated and transformed in the process of historical evolution, such as the rise and fall of families, land ownership changes and social class evolution. This paper explores the value connotation of historical settlements from the perspective of dialectic thinking of change and invariance with CAS theory, which has theoretical significance for protection of settlement's human-land relationship from the perspective of "social-spatial".
Definition of a thermal conductivity map for geothermal purposes
Authors: García-Noval Carlota , Álvarez Rodrigo , García-Cortés Silverio , García Carmen , Alberquilla Fernando , Ordóñez Almudena
Published: May 2024

The use of geothermal energy is spreading globally due to its many advantages, especially for heating and cooling. The correct design of a geothermal system requires knowledge of the parameters of the subsoil rocks, and particularly the thermal conductivity (k), which is the intrinsic ability of a material to transfer thermal energy as a result of a temperature gradient. A thermal conductivity map of the geological formations is time-consuming to produce, but can be of great help when selecting the location of a low-enthalpy geothermal installation, resulting in significant savings and an increase in the efficiency of that installation. The preferred option for determining k is an in situ thermal response test, but laboratory methods may be an alternative if it is not available or affordable. In this work, the needle thermal probe method has been used to measure the k of representative outcropping rocks in Oviedo (NW Spain), since it allows to obtain a rapid determination, its cost is comparatively low and it can be implemented in a portable device. 162 measurements have been carried out on a total of 27 samples, ranging from 0.2 (clay) to 5.4 W m−1 K−1 (quartzite). A relationship has been found between the k of the rocks and their characteristics, such as mineralogy, anisotropy or geological age and a thermal conductivity map was created.
SERS biosensors for liquid biopsy towards cancer diagnosis by detection of various circulating biomarkers: current progress and perspectives
Authors: Lyu Nana , Hassanzadeh-Barforoushi Amin , Rey Gomez Laura M. , Zhang Wei , Wang Yuling
Published: May 2024

Liquid biopsy has emerged as a promising non-invasive strategy for cancer diagnosis, enabling the detection of various circulating biomarkers, including circulating tumor cells (CTCs), circulating tumor nucleic acids (ctNAs), circulating tumor-derived small extracellular vesicles (sEVs), and circulating proteins. Surface-enhanced Raman scattering (SERS) biosensors have revolutionized liquid biopsy by offering sensitive and specific detection methodologies for these biomarkers. This review comprehensively examines the application of SERS-based biosensors for identification and analysis of various circulating biomarkers including CTCs, ctNAs, sEVs and proteins in liquid biopsy for cancer diagnosis. The discussion encompasses a diverse range of SERS biosensor platforms, including label-free SERS assay, magnetic bead-based SERS assay, microfluidic device-based SERS system, and paper-based SERS assay, each demonstrating unique capabilities in enhancing the sensitivity and specificity for detection of liquid biopsy cancer biomarkers. This review critically assesses the strengths, limitations, and future directions of SERS biosensors in liquid biopsy for cancer diagnosis.
An international phantom study of inter-site variability in Technetium-99m image quantification: analyses from the TARGET radioembolization study
Authors: Keane Grace , van Rooij Rob , Lam Marnix , Kappadath S. Cheenu , Kovan Bilal , Leon Stephanie , Dreher Matthew , Fowers Kirk , de Jong Hugo
Published: May 2024

Background

Personalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose–effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom.

Results

Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6–10.1%). A standardised protocol did not improve variation (interquartile range 8.4–9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5–0.7 and 0.6–0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6–0.7).

Conclusion

Eliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy.
Electroacupuncture attenuates neuropathic pain via suppressing BIP-IRE-1α-mediated endoplasmic reticulum stress in the anterior cingulate cortex
Authors: Ma Lin-Wei , Liu Yu-Fan , Zhang Hui , Huang Chang-Jun , Li Ang , Qu Xin-Zhe , Lin Jia-Piao , Yang Yan , Yao Yong-Xing
Published: May 2024

Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.
Efficacy of soybean-derived crude extract in enzyme-induced carbonate precipitation as soil-improvement technique
Authors: Pratama Galih Bhekti Sula , Yasuhara Hideaki , Kinoshita Naoki , Putra Heriansyah , Almajed Abdullah , Fukugaichi Satoru , Ihsani Zalfa Maulida
Published: May 2024

Calcium carbonate precipitation using a urease enzyme, referred to herein as Enzyme-Induced Carbonate Precipitation (EICP) is a technique for soil improvement. In this technique, a mixed solution composed of reagents and the urease enzyme, which produces calcite, is utilized as the grouting material. Recently, alternative materials to the urease enzyme have been examined to resolve the cost issue of using the urease enzyme. In this study, several tests were conducted to compare commercial urease and soybean-derived crude urease. A comparison of their hydrolysis rates was done through urease activity tests. The microscopic structures and mineralogy of the precipitated materials, produced during various loading periods, were investigated through SEM and XRD analyses. Moreover, the reinforcing effect of the grouting solutions on the treated soil specimens was evaluated by measuring the unconfined compressive strength (UCS) of the treated samples. Interestingly, the precipitated CaCO3 was vaterite and calcite when using soybean urease, while it was mostly calcite when using the urease enzyme. Higher UCS values were obtained with the soybean urease samples because the precipitated CaCO3 seemed to be concentrated at the inter-grain contacts. It was concluded that soybean powder shows great efficacy as a replacement for commercially produced enzyme urease in soil-improvement techniques mediated by carbonate precipitation.
Mitochondrial quality control in human health and disease
Authors: Liu Bo-Hao , Xu Chen-Zhen , Liu Yi , Lu Zi-Long , Fu Ting-Lv , Li Guo-Rui , Deng Yu , Luo Guo-Qing , Ding Song , Li Ning , Geng Qing
Published: May 2024

Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.
Asymmetric interactions among cutting-edge technologies and pioneering conventional and Islamic cryptocurrencies: fresh evidence from intra-day-based good and bad volatilities
Authors: Ghaemi Asl Mahdi , Roubaud David
Published: May 2024

This study examines the nexus between the good and bad volatilities of three technological revolutions—financial technology (FinTech), the Internet of Things, and artificial intelligence and technology—as well as the two main conventional and Islamic cryptocurrency platforms, Bitcoin and Stellar, via three approaches: quantile cross-spectral coherence, quantile-VAR connectedness, and quantile-based non-linear causality-in-mean and variance analysis. The results are as follows: (1) under normal market conditions, in long-run horizons there is a significant positive cross-spectral relationship between FinTech's positive volatilities and Stellar’s negative volatilities; (2) Stellar’s negative and positive volatilities exhibit the highest net spillovers at the lower and upper tails, respectively; and (3) the quantile-based causality results indicate that Bitcoin’s good (bad) volatilities can lead to bad (good) volatilities in all three smart technologies operating between normal and bull market conditions. Moreover, the Bitcoin industry’s negative volatilities have a bilateral cause-and-effect relationship with FinTech’s positive volatilities. By analyzing the second moment, we found that Bitcoin's negative volatilities are the only cause variable that generates FinTech's good volatility in a unidirectional manner. As for Stellar, only bad volatilities have the potential to signal good volatilities for cutting-edge technologies in some middle quantiles, whereas good volatilities have no significant effect. Hence, the trade-off between Bitcoin and cutting-edge technologies, especially FinTech-related advancements, appear more broadly and randomly compared with the Stellar-innovative technologies nexus. The findings provide valuable insights for FinTech companies, blockchain developers, crypto-asset regulators, portfolio managers, and high-tech investors.
Stock price index analysis of four OPEC members: a Bayesian approach
Authors: Hatamerad Saman , Asgharpur Hossain , Adrangi Bahram , Haghighat Jafar
Published: May 2024

This study examines the relationship between macroeconomic variables and stock price indices of four prominent OPEC oil-exporting members. Bayesian model averaging (BMA) and regularized linear regression (RLR) are employed to address uncertainties arising from different estimation models and variable selection. Jointness is utilized to determine the nature of relationships among variable pairs. The case study spans macroeconomic variables and stock prices from 1996 to 2018. BMA findings reveal a strong positive association between stock price indices and both consumer price index (CPI) and broad money growth in each analyzed OPEC country. Additionally, the study suggests a weak negative correlation between OPEC oil prices and the stock price index. RLR results align with BMA analysis, offering insights valuable for policymakers and international wealth managers.
TRPV1 nociceptors are required to optimize antigen-specific primary antibody responses to novel antigens
Authors: Tynan Aisling , Tsaava Téa , Gunasekaran Manojkumar , Bravo Iñiguez Carlos E. , Brines Michael , Chavan Sangeeta S. , Tracey Kevin J.
Published: May 2024

Background

Key to the advancement of the field of bioelectronic medicine is the identification of novel pathways of neural regulation of immune function. Sensory neurons (termed nociceptors) recognize harmful stimuli and initiate a protective response by eliciting pain and defensive behavior. Nociceptors also interact with immune cells to regulate host defense and inflammatory responses. However, it is still unclear whether nociceptors participate in regulating primary IgG antibody responses to novel antigens.

Methods

To understand the role of transient receptor potential vanilloid 1 (TRPV1)-expressing neurons in IgG responses, we generated TRPV1-Cre/Rosa-ChannelRhodopsin2 mice for precise optogenetic activation of TRPV1 + neurons and TRPV1-Cre/Lox-diphtheria toxin A mice for targeted ablation of TRPV1-expressing neurons. Antigen-specific antibody responses were longitudinally monitored for 28 days.

Results

Here we show that TRPV1 expressing neurons are required to develop an antigen-specific immune response. We demonstrate that selective optogenetic stimulation of TRPV1+ nociceptors during immunization significantly enhances primary IgG antibody responses to novel antigens. Further, mice rendered deficient in TRPV1- expressing nociceptors fail to develop primary IgG antibody responses to keyhole limpet hemocyanin or haptenated antigen.

Conclusion

This functional and genetic evidence indicates a critical role for nociceptor TRPV1 in antigen-specific primary antibody responses to novel antigens. These results also support consideration of potential therapeutic manipulation of nociceptor pathways using bioelectronic devices to enhance immune responses to foreign antigens.
Circular RNA regulates male spermatogenesis: a narrative review
Authors: Peng Li-fan , Yu Hang
Published: May 2024

Spermatogenesis was crucial for adult male animals to achieve reproductive function, and this complex physiological process required timely and moderate expression of related genes. A large number of epigenetic regulatory factors were involved, including cyclic RNA. Circular RNA had various characteristics such as rich expression, evolutionary conservation, cell or tissue specificity, and higher resistance to exonuclease or ribonuclease degradation. It can regulate the expression of parental genes and function as mRNA traps, miRNAs, or proteins in the corpus cavernous; it can also participate in the process of spermatogenesis through RNA-binding proteins, including the formation of reproductive stem cells, sperm formation, seminal plasma composition, and testicular tissue formation.
FaultSeg3D plus: A comprehensive study on evaluating and improving CNN-based seismic fault segmentation
Authors: Li You , Wu Xinming , Zhu Zhenyu , Ding Jicai , Wang Qingzhen
Published: May 2024

Convolutional neural networks (CNNs) have been widely used for seismic fault segmentation and show more powerful performance than conventional attribute-based methods to obtain a fault map with noise-free and continuously trackable fault features. However, CNN-based methods face the potential problem of poor generalization in field seismic images, and factors affecting fault segmentation remain incompletely studied or unexplored. Moreover, the existing pixel-wise metrics, borrowed from the natural image segmentation tasks, cannot fairly or reasonably evaluate the fault segmentation results. We first develop a distance-based metric to provide a geologically more reasonable evaluation on fault interpretation. We then use the most commonly used U-net architecture as an example to study how the CNN-based fault segmentation is affected by some significant factors such as training data, many kinds of network hyperparameters, and scaling and rotation in the inference step. Experimental results show that a training data set with more realistic reflection features and multiple sampling rates can enrich the data set variations in the structure and waveform signatures, thus significantly enhancing the fault segmentation. Moreover, a novel loss function we developed outperforms others with notable margins. Last, but not least, it is necessary to apply a test-time augmentation strategy by merging predictions with multiple scales and rotations in the reference step because the CNN does not preserve transformation invariance. Based on the studies, we optimally train a properly designed CNN and apply it to multiple field examples, where we obtain accurate, clean, continuous fault detections, and quantitatively evaluate them with manual interpretations.
H3B-6545 + palbociclib in patients (pts) with locally advanced/metastatic estrogen receptor-positive (ER+), HER2 negative (–) breast cancer (BC).
Authors: Johnston Stephen R. D. , Pluard Timothy J. , Wang Judy S. , Hamilton Erika P. , Song Tingting , Rong Yuanxin , Yamaguchi Kohei , Juric Dejan
Published: May 2024

1051

Background: H3B-6545 — a novel selective ER covalent antagonist (SERCA) that potently inactivates wild-type and mutant ERα — has shown preliminary antitumor activity and tolerable safety in pts with advanced/metastatic, ER+, HER2– BC. Palbociclib (palbo), an oral CDK4/6 inhibitor, has shown activity in metastatic disease when combined with endocrine therapy. The dose escalation part of this open-label, multicenter, phase 1b study of H3B-6545 + palbo in pts with ER+, HER2– BC aimed to identify the recommended phase 2 dose (RP2D) of H3B-6545 + palbo and characterize safety and efficacy. Methods: Females aged ≥18 years with ER+, HER2–, locally advanced/recurrent/metastatic BC, ECOG PS 0–1, and progression on/after standard therapy were eligible. In the dose escalation phase, pts had to have received ≥2 prior hormonal therapies. Palbo was to be escalated no higher than 125 mg orally QD (days 1–21) and H3B-6545 no higher than 450 mg orally QD (days 1–28). The MTD was the highest dose at which ≤1 of 6 pts had a dose-limiting toxicity (DLT). The primary endpoint was determination of the MTD and/or RP2D. Secondary endpoints included safety and efficacy (by investigator per RECIST v1.1). Results: At data cutoff (16 Sept 22), 31 pts were treated: Cohort (C) 1: H3B-6545 300 mg + palbo 100 mg (n=7); C2: H3B-6545 300 mg + palbo 125 mg (n=8); C3: H3B-6545 450 mg + palbo 125 mg (n=8); C3b: H3B-6545 450 mg + palbo 100 mg (n=8). 3 DLTs (grade 3/4 neutrophil count decreased [n=2] and grade (G) 3 QTcF prolongation [n=1]) were observed in C3 (5 DLTs were observed at C3b); C2 dose was deemed the MTD. Of all pts, 90.3% had G ≥3 TEAEs, 32.3% had serious TEAEs, and 6.5% had TEAEs leading to drug withdrawal. Sinus bradycardia (67.7% [G ≥3, 0%]) and anemia (54.8% [G ≥3, 19.4%]) were the most frequent TEAEs. QT prolongation and rash occurred in 19.4% [G ≥3, 12.9%] and 16.1% [G ≥3, 9.7%] of pts, respectively. ORR in response evaluable pts was 23.1% (95% CI 9.0–43.6). The Table shows additional results. Conclusions: H3B-6545 300 mg + palbo (100/125 mg) had manageable safety and encouraging preliminary antitumor activity. Further studies are warranted to identify the RP2D. Clinical trial information: NCT04288089 . [Table: see text]
Chemotherapy Care Companion: Enhancing cancer care through digital remote monitoring.
Authors: Pierce Erin , Larned Zoe L. , Salup Adam , Slaughter Katie , Alker Peggy-Jo Jones
Published: May 2024

1636

Background: Oncology patients often encounter preventable acute issues prompting the need for proactive monitoring and management. To manage disease and therapy complications, Ochsner Health developed Chemotherapy Care Companion (CCC) for remote monitoring of treatment patients. This abstract highlights the feasibility of digital remote monitoring (DRM) in managing oncologic patient care, while increasing patient satisfaction and reducing patient events and healthcare costs. Methods: Starting in January 2021, patients initiating an oral or intravenous cancer treatment with an active Ochsner portal account and smartphone became eligible. Providers can manually enroll patients via an order set and receive enrollment reminders within the Epic electronic medical record (EMR). Patients receive a digital WiFi-enabled monitoring scale, blood pressure cuff, and ear thermometer, at no cost. Patients are reminded via phone alerts to take vitals at 9am and 3pm, along with a daily questionnaire. The data is transmitted wirelessly to the EMR, where abnormal vital signs or questionnaire responses trigger escalations sent to an Epic in-basket pool. During clinic hours, advanced practice providers (APPs) review and intervene, utilizing embedded urgent care slots for same-day access. In August 2022, a patient satisfaction survey comprising of nine questions was distributed to all enrolled patients. Results: A retrospective analysis was conducted from September 2022 to August 2023 including 722 participants, 7,360 escalations and 668 interventions. Patient compliance reached 62%, defined as submitting at least 50% of daily vitals. The most common interventions were related to hypertension, hypotension, weight changes, and questionnaire responses. Regarding questionnaire responses, diarrhea, pain, fever, and dizziness were the mostly frequently triaged. Data analytics revealed that CCC led to a 5.9% decrease in emergency room visits, a 41.7% decrease in the rate of inpatient hospital admissions, and a 32.3% improvement in the inpatient length of stay compared to non-enrolled patients. Extrapolating this data across 5,500 oncology patients within our hospital system, CCC could prevent 172 ER visits, 914 inpatient hospital admissions and 2,006 hospital days. The survey (131 responses) revealed high satisfaction with CCC: over 80% felt a sense of security, 90% were overall satisfied, and more than 90% would recommend CCC. Conclusions: Findings highlight the value of integrating DRM in cancer care, showcasing its ability to reduce healthcare costs and optimize resource utilization while enhancing patient care and satisfaction. Moreover, the study underscores the high patient satisfaction and engagement with DRM, bolstering its feasibility and acceptance in oncology care. Further investigation is warranted to explore the financial benefits for hospitals, insurance companies, and pharmaceutical companies.
The impact of adjuvant endocrine therapy (AET) omission in ER-low (1-10%) early-stage breast cancer.
Authors: Choong Grace Mei Yee , Hoskin Tanya L. , Boughey Judy Caroline , Ingle James N. , Goetz Matthew P.
Published: May 2024

513

Background: Adjuvant endocrine therapy (AET) improves overall survival (OS) in patients (pts) with hormone receptor (HR) positive early-stage breast cancer (BC). For pts with estrogen receptor (ER)-low BC (defined as ER 1-10%), there is controversy regarding AET benefit, given tumor heterogeneity (>40% basal; (1)), and similar chemotherapy response and prognosis to ER-negative (neg) BC. Current guidelines categorize ER-low BC as a separate entity and suggest equipoise regarding AET benefit. We previously determined that AET omission in chemotherapy-treated pts with ER+ BC resulted in a nearly 2-fold increase in death (2). However, the impact of AET omission in patients with ER-low BC is unknown. Methods: Beginning in 2018, the National Cancer Database (NCDB) began to abstract ER as a continuous variable, allowing classification of ER+ tumors as 1-10% or >10%. Therefore, we queried the NCDB 2018-2020 for patients with stage I-III ER+BC treated with neoadjuvant or adjuvant chemotherapy, as these pts have the highest risk of recurrence. ER was assessed as ER-neg (0%), low (1-10%) and ER >10%. OS was analyzed with AET as a time-dependent covariate using Cox proportional hazards regression. Results: 357,085 pts with stage I-III ER+BC were identified, with 10,396 (3%) classified as ER-low. Among pts with ER-low disease, 69% had PR-neg BC and 67% had HER2-neg BC. The majority (77%) were treated with chemotherapy (32% neoadjuvant, 44% adjuvant, 1% unknown timing) and formed our analysis cohort. Among these 7,956 pts, AET was omitted in 3,233 (41%). AET omission was more common for pts with tumors that were PR-neg vs positive (46% vs 30%, p<0.001), HER2-neg vs positive (44% vs 37%, p<0.001), and Ki67≥20% (44% vs 35%, p<0.001). With median follow-up of 3 years, 648 deaths were observed. OS was 94.3% (95% CI: 93.8-94.9%) at 2 years and 87.6% (95% CI: 86.5-88.7%) at 4 years. In unadjusted analysis, omission of AET was associated with worse OS (HR 1.40, 95% CI: 1.19-1.65, p<0.001), with similar effects regardless of PR, HER2, or Ki67 (each interaction test p>0.3). When controlling for age, comorbidity score, year of diagnosis, PR, HER2, and pathologic stage, the adjusted effect of AET omission on OS was HR 1.22 (95% CI: 1.00-1.48, p=0.05). Given assessment of OS was performed during pandemic years, with 1/3 of deaths occurring during the first year of follow-up, we performed a sensitivity analysis to analyze pts who survived to one year after definitive surgery. In this analysis, the adjusted effect of AET omission on OS was 1.24 (95% CI: 1.02-1.51, p=0.03). Conclusions: Omission of AET in pts treated with chemotherapy for ER-low, early-stage BC is associated with significantly worse OS. These data strongly suggest that pts with ER low BC should be counseled regarding the benefit of AET and practice guidelines should recommend AET in this setting. 1. Benefield JNCI 2020. 2. Choong SABCS 2022.
Benefit of perioperative chemotherapy in the patients with loco-regional recurrence of HR-positive HER2-negative breast cancer: A multi-institutional retrospective cohort study.
Authors: Ozaki Yukinori , Tokuda Emi , Hara Fumikata , Sasada Shinsuke , Sagara Yasuaki , Sawaki Masataka , Kanbayashi Chizuko , Yamanaka Takashi , Onishi Tatsuya , Fujiki Yoshitaka , Suto Akihiko , Takahashi Yuko , Tokunaga Eriko , Aruga Tomoyuki , Nakamura Rikiya , Fujisawa Tomomi , Saji Shigehira , Iwata Hiroji , Shien Tadahiko
Published: May 2024

526

Background: Loco-regional recurrence (LRR) in breast cancer (BC) is addressed with multimodal treatment, yet the prognosis remains unfavorable. The benefit of adjuvant chemotherapy for the hormone receptor-positive, HER2-negative (HR+HER2-) subtype of BC is controversial. Methods: We performed a multi-institutional retrospective cohort study under the Japan Clinical Oncology Group. This study focused on patients without distant metastasis who developed HR+HER2- ipsilateral breast tumor recurrence (IBTR) or other LRR (oLRR) including recurrence in skin, chest wall, or regional lymph nodes. The patients received curative surgery for LRR between 2014 and 2018. Patients were divided into two groups: the chemotherapy group and no chemotherapy group before/after LRR. We performed a Cox proportional hazards model to evaluate invasive disease-free survival (iDFS) between the two groups. Sensitivity analysis was conducted using propensity score (PS) matching and IPTW. Results: A total of 967 patients were registered from 41 institutions, and 958 patients concordant with inclusion criteria were analyzed. There were 509 patients (53%) of only IBTR and 449 patients (47%) of oLRR. Neoadjuvant/Adjuvant chemotherapy was administered to 235 patients (25%), while 722 (75%) did not receive it. Compared to the no-chemotherapy group, the chemotherapy group included a higher number of patients aged 41-60, oLRR, and recurrences during adjuvant endocrine therapy. At a median follow-up of 5.2 years (Interquartile range: 4.1-6.5), the 5-year iDFS rate was 75.4% (95% CI: 72.4-78.2). Multivariate analysis showed an improvement in iDFS for the chemotherapy group (HR: 0.70, 95% CI: 0.49-0.99, p = 0.045). Sensitivity analysis also consistently suggested the effectiveness of chemotherapy (PS matching HR 0.76, IPTW HR 0.75). In the subgroup analysis, the chemotherapy group showed more significant iDFS improvement in cases with oLRR, recurrences during adjuvant endocrine therapy for primary BC, and those without perioperative chemotherapy for primary BC. Conclusions: Our study showed improvement in iDFS in patients who received perioperative chemotherapy for HR+HER2- LRR. This improvement was particularly notable in patients with oLRR, recurrences during adjuvant endocrine therapy, and those without perioperative chemotherapy for primary BC. [Table: see text]
Updated SEER database study of 21-gene assay to assess breast cancer–specific mortality and benefit of chemotherapy by race and ethnicity.
Authors: Diego Emilia , Bennett John P. , Tang Gong , Geyer Charles E. , Racz Jennifer M. , Russell Christy A , Baehner Frederick , Shak Steven , Petkov Valentina I.
Published: May 2024

533

Background: In randomized studies (NSABP B-20, SWOG 8814, TAILORx, RxPONDER), the predictive effect of the 21-gene Breast Recurrence Score assay (RS) on chemotherapy (CT) benefit has been evaluated in patients with node-negative (N0) and node-positive (N+) breast cancer. Retrospective analyses of TAILORx and RxPONDER demonstrated differences in outcome by racial/ethnic groups (RG); however, there were no differences in CT benefit for any of the clinical outcome measures. In this study we characterized the association between the RS result and breast cancer-specific mortality (BCSM) and chemotherapy benefit in BCSM in RG in the recently updated, population-based SEER registries. Methods: Eligible patients were from the SEER 17 registries, November 2022 submission, and had non-metastatic, hormone receptor-positive, HER2-negative, node negative (N0) breast cancer diagnosed between 2006 and 2019 with a RS result. Analyses were weighted using the inverse of estimated propensity of using CT (yes vs. none/unknown). Prognosis was ascertained by estimating breast cancer specific survival (BCSS) at 9 years among patients with CT recorded as none/unknown by RG. The log-rank test was used to compare BCSM by RG. Multivariable Cox models, including RS result (26-100 vs. 0-25) x CT interaction, were used to assess whether RS result was predictive of CT benefit. Analyses were performed in the overall cohort and in Hispanic (H), non-Hispanic Asian and Pacific Islander (NHAPI), non-Hispanic Black (NHB), and non-Hispanic White (NHW) RGs. Results: There were 145,642 eligible patients and 3,212 breast cancer deaths. Median follow-up was 68 months. NHB patients had higher median RS result and CT usage than other groups (p < .001). In N0 patients, higher RS result was associated with lower 9-year BCSS, both overall and by race/ethnicity (p < .001). In Cox multivariable models (Table), the interaction between RS result by CT was significant among all N0 patients (p < .001) and in NHB patients (p = 0.005), NHW patients (p = 0.002), and H patients (p = 0.019), but not in NHAPI patients (p = 0.766). Analyses of patients with N+ disease and more detailed analysis of CT benefit according to RS results by RG are underway and will also be presented. Conclusions: Real-world evidence from the SEER registries in over 145,000 patients confirms the 21-gene assay is prognostic for BCSS in all groups by race and ethnicity. The RS result was predictive of CT benefit in N0 patients overall and in Hispanic, NHB, and NHW patients, but not in NHAPI patients in this analysis. [Table: see text]
Cost consequence model of the MammaPrint (70-gene signature) and 21-gene signature in patients with primary HR+HER2-, N1 early-stage breast cancer in Germany.
Authors: Lux Michael Patrick , Sandor Mariana Felicia , Hofman Viktoria , Fischer Lotta Ada , Kuemmel Sherko , Pronin Darina , Klinkhamer Jelle , Mueller-Huesmann Harald
Published: May 2024

534

Background: The MammaPrint 70-gene and Oncotype DX 21-gene signatures serve to stratify breast cancer tumors, distinguishing between those with low or high risk of distant metastasis. Patients with a low genomic risk tumor have the option to avoid overtreatment by omitting chemotherapy and minimize associated toxicities. This analysis evaluates the economic impact of implementing MammaPrint, Oncotype DX (ODx), or no gene signature testing for patients with HR+ HER2- early breast cancer with 1 to 3 positive lymph nodes (N1) in Germany. Methods: We constructed a cost-consequence model to assess the budget implications of MammaPrint, ODx, and not employing a gene signature, considering both the healthcare payers and societal perspective. The model focuses on patients with HR+/HER2-/N1 breast tumors who, in the absence of a gene expression analysis, would receive chemotherapy in 63% of cases according to the data of the certified breast cancers in Germany. Input data were sourced from MINDACT, RxPONDER, literature, the EBM, the DRG system. The healthcare payer perspective covers testing, direct/indirect costs of chemotherapy, and disease recurrence costs. The societal perspective adds transport costs and productivity losses to these. Results: A projected 9,207 HR+/HER2-/N1 breast cancer patients were candidates for genomic testing. In MINDACT, patients were classified as MammaPrint Low Risk in 73% of cases, and in RxPONDER 83% of patients were categorized as ODx Low Risk (RS 0-25). The model demonstrated per patient savings from a healthcare payer perspective of €3.766 for MammaPrint and €900 for ODx compared to not using any gene signature for N1 breast cancer patients in Germany. Importantly, the savings are even more substantial from a societal perspective, reaching €11.815 for MammaPrint and €11.243 for ODx. When limiting the population to women >50 years, similar results were observed with per patient savings from a payer perspective of €3.766 and €1.549, and from a societal perspective of €9.826 and €9.349, for MammaPrint and ODx, respectively. Conclusions: These data demonstrate that personalized treatment planning with genomic testing for breast cancer with HR+/HER2-/LN1 breast cancer, leads to a reduction in chemotherapy use and associated costs in Germany. Although MammaPrint designates a smaller proportion of genomically high risk patients compared to ODx, MammaPrint Low Risk patients without chemotherapy demonstrate higher survival outcomes. Consequently, any increased chemotherapy costs are offset by lower testing and distant recurrence expenses, making MammaPrint a cost-conscious option.
Impact of CYP2D6 polymorphisms on adverse events in patients with breast cancer treated with tamoxifen: Insights from an early dose escalation trial in CYP2D6 poor metabolizers.
Authors: Blancas Isabel , Martínez-De Dueñas Eduardo , Rodríguez-Serrano Fernando
Published: May 2024

547

Background: Tamoxifen is widely used in treating hormone receptor-positive breast cancer. It is primarily metabolized by the CYP2D6 enzyme to yield active metabolites. However, CYP2D6 polymorphisms have been associated with a differential response to tamoxifen. In a clinical trial involving an early dose escalation of tamoxifen in poor metabolizers, we found endoxifen concentration levels similar to those of patients with extensive phenotype, and no long-term survival differences among CYP2D6 phenotypes. However, the impact of that dose escalation on side effect incidence was not addressed. Methods: In this study, we analyzed the incidence of specific side effects - osteoarticular pain, hot flashes, asthenia, and uterine alterations - in 86 breast cancer patients, differentiated by their CYP2D6 phenotype estimated according to the Clinical Pharmacogenetics Implementation Consortium. In poor metabolizers, the tamoxifen standard dose of 20 mg/day was escalated to 40 mg/day and 60 mg/day for 4 months each, and then treated with 20 mg/day until completing the treatment. Kaplan-Meier analysis and Cox proportional hazards regression model were employed to assess the relationship between the CYP2D6 phenotype and the incidence of these side effects. Results: The median follow-up time was 139.5 months. The analyses revealed that only uterine changes showed significant differences between CYP2D6 phenotypes, with a lower incidence in extensive metabolizers (P-value < 0.001 in Kaplan-Meier; HR in Cox of 0.195, 95% CI 0.073 - 0.521, P = 0.001). This finding persisted after adjustment for the covariates tumor grade, size, nodal status, chemotherapy, and radiotherapy in multivariate Cox regression (HR 0.098, 95% CI 0.020 - 0.466, P = 0.004). Selection of a subgroup through Propensity Score Matching (21 vs 21) corroborated these results. The spectrum of uterine changes and pathologies included endometrial hyperplasia, polyps, adenocarcinoma, myometrial or endometrial thickening, and the presence of multiple myomas. Conclusions: Our study indicates that an early increase in tamoxifen dose in poor metabolizer patients according to CYP2D6 polymorphisms may significantly affect the incidence of uterine changes, but not the incidence of osteoarticular pain, hot flashes, or asthenia. Clinical trial information: 2007-002942-40/ES .
Patient-reported outcomes in N1 breast cancer: A phase III trial comparing whole-breast to whole-breast plus regional irradiation after taxane-based chemotherapy (KROG 1701).
Authors: Kim Nalee , Park Won , Kim Haeyoung , Cho Won Kyung , Park Yeon Hee , Ahn Sung Ja , Jung Jinhong , Jo In Young , Lee Kyu Chan , Kim Tae Hyun , Kim Tae Gyu , Shin Kyung Hwan , Kim Jin Hee , Lee Jong Hoon , Lee Hyung-Sik , Park Hae Jin , Lee Ju Hye , Koh Minji , Kim Yong Bae , Lee Ik Jae ,   Korean Radiation Oncology Group 17-01 Study Committee
Published: May 2024

577

Background: Recent randomized trials have highlighted the benefits of regional node irradiation (RNI) in high-risk node-positive or pN1 breast cancer, yet its impact in the context of modern taxane-based adjuvant chemotherapy remains unclear. In this multi-center phase III trial, we study to prove the hypothesis that there is no difference in terms of disease-free survival between standard whole-breast irradiation (WBI) with RNI and WBI alone in pN1 breast cancer patients receiving taxane-based adjuvant chemotherapy. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are now reported. Methods: The KROG 17-01 trial (NCT03269981), a prospective, multicenter, non-inferiority study, randomized patients with pN1 breast cancer after breast-conserving surgery and adjuvant taxane-containing chemotherapy to WBI or WBI+RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. PROs were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at follow-up intervals of 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. Linear mixed models were used to compare PROs between treatment arms. Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI). Overall, PRO domains improved over time (p<0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (p<0.05), and reported lower global health (p=0.090) and physical functioning (p=0.049) with borderline significance compared to the WBI group. At 3-6 months post-RT, WBI+RNI group also showed higher arm symptom scores (p=0.030). Apart from these specific timepoints, no significant differences were observed in other PRO domain scores, including arm and breast symptoms, between treatment arms. In addition, there was no significant differences in PRO domains according to RT techniques and fractionation, except for breast symptoms during RT, favoring hypofractionation and intensity-modulated RT. Conclusions: In patients with pN1 breast cancer treated with taxane-based adjuvant chemotherapy, adding RNI was associated with minor, transient declines in specific PRO domains. However, these differences were not clinically significant, indicating comparable overall patient experiences between the two treatment arms. Clinical trial information: NCT03269981 .