bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryonic thermal manipulation: a potential strategy to mitigate heat stress in broiler chickens for sustainable poultry production
Authors: Al Amaz Sadid , Mishra Birendra
Published: June 2024

Due to high environmental temperatures and climate change, heat stress is a severe concern for poultry health and production, increasing the propensity for food insecurity. With climate change causing higher temperatures and erratic weather patterns in recent years, poultry are increasingly vulnerable to this environmental stressor. To mitigate heat stress, nutritional, genetic, and managerial strategies have been implemented with some success. However, these strategies did not adequately and sustainably reduce the heat stress. Therefore, it is crucial to take proactive measures to mitigate the effects of heat stress on poultry, ensuring optimal production and promoting poultry well-being. Embryonic thermal manipulation (TM) involves manipulating the embryonic environment’s temperature to enhance broilers’ thermotolerance and growth performance. One of the most significant benefits of this approach is its cost-effectiveness and saving time associated with traditional management practices. Given its numerous advantages, embryonic TM  is a promising strategy for enhancing broiler production and profitability in the poultry industry. TM increases the standard incubation temperature in the mid or late embryonic stage to induce epigenetic thermal adaption and embryonic metabolism. Therefore, this review aims to summarize the available literature and scientific evidence of the beneficial effect of pre-hatch thermal manipulation on broiler health and performance.
Assessing the interplay of contrast, defocus, and resolution in cryo-EM: a benchmark experiment for limited dataset screening
Authors: Lee Hayeon , Lee Yeseul , Lee Jinseok , Jeong Hyeongseop , Yon Dong Keon , Durie Clarissa L. , Ryu Bumhan , Chung Jeong Min
Published: June 2024

The selection of defocus ranges for small datasets in cryo-electron microscopy (cryo-EM) is under-researched. We present a comprehensive benchmark experiment that aimed to evaluate the relationship between contrast, defocus, and resolution, particularly in the context of limited datasets. We conducted a detailed analysis of beta-galactosidase, apo-ferritin, and connexin-46/50 datasets to optimize pre-screening strategies for cryo-EM. Our approach involved classifying micrographs based on image contrast using an artificial intelligence (AI) model without considering the defocus level. This method allowed us to investigate the optimal defocus range for pre-screening in a limited dataset and its impact on the overall image processing. The micrographs were categorized into good, moderate, and bad contrast groups. Subsequent analysis revealed that, contrary to the prevailing assumption that lower contrast (associated with lower defocus) leads to higher resolution, in scenarios with limited datasets higher contrast images yield superior resolution. This finding was consistent across all three protein samples, underscoring the critical role of contrast in determining the quality of 3D reconstructions in limited datasets. This significant finding challenges conventional cryo-EM methodologies. In conclusion, our study provides new benchmarks for selecting appropriate contrast and defocus levels in cryo-EM, particularly for screening approaches that use limited datasets. This strategy promises to enhance the data quality and efficiency in structural biology research, particularly in resource-constrained scenarios.
Gameful strategies in the education of autistic children: a systematic literature review, scientometric analysis, and future research roadmap
Authors: Honorato Noemi , Soltiyeva Aiganym , Oliveira Wilk , Delabrida Saul Emanuel , Hamari Juho , Alimanova Madina
Published: June 2024

The education of autistic children presents significant challenges, compelling various educational stakeholders to seek solutions that can enhance teaching and learning experiences for these individuals. Among the most promising strategies are gameful approaches, including gamification, card games, and simulators. Despite recent efforts, understanding the development and application (i.e., the state of the art) of these approaches in the education of autistic children remains a complex task. To address this issue, we conducted a thorough systematic literature review and scientometric analysis to explore the design and implementation of gameful approaches for the education of children with autism. Our findings highlight the predominant use of 2D games designed for personal computers, focusing on natural, home, and urban settings. Additionally, we observed that the studies were primarily qualitative. Based on these results, we proposed a research agenda. We offer a comprehensive overview and a research agenda for the design, use, and assessment of gameful approaches in the education of children with autism.
Brain age gap estimation using attention-based ResNet method for Alzheimer’s disease detection
Authors: Aghaei Atefe , Ebrahimi Moghaddam Mohsen ,   Alzheimer’s Disease Neuroimaging Initiative
Published: June 2024

This study investigates the correlation between brain age and chronological age in healthy individuals using brain MRI images, aiming to identify potential biomarkers for neurodegenerative diseases like Alzheimer's. To achieve this, a novel attention-based ResNet method, 3D-Attention-Resent-SVR, is proposed to accurately estimate brain age and distinguish between Cognitively Normal (CN) and Alzheimer’s disease (AD) individuals by computing the brain age gap (BAG). Unlike conventional methods, which often rely on single datasets, our approach addresses potential biases by employing four datasets for training and testing. The results, based on a combined dataset from four public sources comprising 3844 data points, demonstrate the model's efficacy with a mean absolute error (MAE) of 2.05 for brain age gap estimation. Moreover, the model's generalizability is showcased by training on three datasets and testing on a separate one, yielding a remarkable MAE of 2.4. Furthermore, leveraging BAG as the sole biomarker, our method achieves an accuracy of 92% and an AUC of 0.87 in Alzheimer's disease detection on the ADNI dataset. These findings underscore the potential of our approach in assisting with early detection and disease monitoring, emphasizing the strong correlation between BAG and AD.
Clinical characteristics and treatment strategies for pituitary adenoma associated with intracranial aneurysm
Authors: Huang Zheng , Yang Zeng , Xu Lixin , Leng Haibin , Yang Kui , Ding Wei , Xie Bo , Chen Fenghua , Liu Zhixiong , Li Zhenyan
Published: June 2024

Background

This study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA).

Methods

We enrolled patients with lesions in the sellar region and age-matched general population who were confirmed with IA from two hospitals. Four types of treatment strategies were performed, which included Type I (both IA and PA were treated with surgery), Type II (IA was treated with surgery and PA was performed by non-surgical treatment), Type III (PA was performed with surgery and observation was available for IA) and Type IV (both IA and PA were performed with non-surgical treatment).

Results

The incidence of IA was 2.2% in the general population, 6.1% in patients with PA, 4.3% in patients with Rathke cleft cyst, 2.8% in patients with meningioma and none were found with IA in patients with craniopharyngioma. Age over 50 years (OR, 2.69; 95% CI, 1.20–6.04; P = 0.016), female (OR, 3.83, P = 0.003), and invasive tumor (OR, 3.26, P = 0.003) were associated with a higher incidence of IA in patients with PA. During the mean follow-up of 49.2 months, no patients experienced stroke, and recurrence of aneurysms and aneurysms treated with observation were stable. Of four patients with recurrence of PA, three patients were treated for type I and one patient for type III.

Conclusions

Preoperative evaluation for aneurysm screening is necessary due to the high incidence of IA in PA patients. Our current treatment strategies may provide a benefit for these patients.
Debriefer cognitive load during Traditional Reflective Debriefing vs. Rapid Cycle Deliberate Practice interdisciplinary team training
Authors: Wiltrakis Susan , Hwu Ruth , Holmes Sherita , Iyer Srikant , Goodwin Nandranie , Mathai Claire , Gillespie Scott , Hebbar Kiran B. , Colman Nora
Published: June 2024

Background

Cognitive load impacts performance of debriefers and learners during simulations, but limited data exists examining debriefer cognitive load. The aim of this study is to compare the cognitive load of the debriefers during simulation-based team training (SbTT) with Rapid Cycle Deliberate Practice (RCDP) debriefing and Traditional Reflective Debriefing (TRD). We hypothesize that cognitive load will be reduced during RCDP compared to TRD.

Methods

This study was part of a large-scale, interdisciplinary team training program at Children’s Healthcare of Atlanta Egleston Pediatric Emergency Department, with 164 learners (physicians, nurses, medical technicians, paramedics, and respiratory therapists (RTs)). Eight debriefers (main facilitators and discipline-specific coaches) led 28 workshops, which were quasi-randomized to either RCDP or TRD. Each session began with a baseline medical resuscitation scenario and cognitive load measurement using the NASA Task Load Index (TLX), and the NASA TLX was repeated immediately following either TRD or RCDP debriefing. Raw scores of the NASA TLX before and after intervention were compared. ANOVA tests were used to compare differences in NASA TLX scores before and after intervention between the RCDP and TRD groups.

Results

For all debriefers, mean NASA TLX scores for physical demands and frustration significantly decreased (− 0.8, p = 0.004 and − 1.3, p = 0.002) in TRD and mean perceived performance success significantly increased (+ 2.4, p < 0.001). For RCDP, perceived performance success increased post-debriefing (+ 3.6, p < 0.001), time demands decreased (− 1.0, p = 0.04), and frustration decreased (− 2.0, p < 0.001). Comparing TRD directly to RCDP, perceived performance success was greater in RCDP than TRD (3.6 vs. 2.4, p = 0.04). Main facilitators had lower effort and mental demand in RCDP and greater perceived success (p < 0.001).

Conclusion

RCDP had greater perceived success than TRD for debriefers. Main facilitators also report reduced effort and baseline mental demand in RCDP. For less experienced debriefers, newer simulation programs, or large team training sessions such as our study, RCDP may be a less mentally demanding debriefing methodology for facilitators.
Cognitive profile in Egyptian multiple sclerosis patients has no correlation with serum neurofilament level
Authors: Sayed Amira , Ashmawy Ghada Abdelhadi , Ramadan Ismail , Galeel Aya Abdel , Hamed Mervat
Published: June 2024

Background

Grey matter loss is thought to be the primary reason of cognitive disability in MS, with trans-synaptic axonal degeneration acting a supportive role. This research sought to evaluate cognitive profile of Egyptian multiple sclerosis patients and find out if it has a correlation with serum neurofilament or not.

Methods

This was a cross-sectional research performed on a total of 60 patients with MS and 30 healthy controls. BICAMS battery of neuropsychological tests was used which includes SDMT, CVLT and BVMT. Serum NFLs using ELISA technique.

Results

Mean ± SD of NFL in RRMS was 82.25 ± 170.9, in PPMS was 22.08 ± 7.26, in SPMS was 95.82 ± 187.5, and in control group was 56.65 ± 125.4, there was high statistical substantial variations among the different groups while there was non-statistical variation between RRMS and PPMS groups, also there was no variation between PPMS and SPMS with regard to serum level of NFL. There is no significant correlation between the NFL and different cognitive tests.

Conclusion

Since sNfL did not strongly connect with cognitive function in MS patients, it is possible that it cannot be used as a substitute indicator for neuropsychological state in these groups.
Enhancing fairness of trading environment: discovering overlapping spammer groups with dynamic co-review graph optimization
Authors: Wang Chaoqun , Li Ning , Ji Shujuan , Fang Xianwen , Wang Zhen
Published: June 2024

Within the thriving e-commerce landscape, some unscrupulous merchants hire spammer groups to post misleading reviews or ratings, aiming to manipulate public perception and disrupt fair market competition. This phenomenon has prompted a heightened research focus on spammer groups detection. In the e-commerce domain, current spammer group detection algorithms can be classified into three categories, i.e., Frequent Item Mining-based, graph-based, and burst-based algorithms. However, existing graph-based algorithms have limitations in that they did not adequately consider the redundant relationships within co-review graphs and neglected to detect overlapping members within spammer groups. To address these issues, we introduce an overlapping spammer group detection algorithm based on deep reinforcement learning named DRL-OSG. First, the algorithm filters out highly suspicious products and gets the set of reviewers who have reviewed these products. Secondly, taking these reviewers as nodes and their co-reviewing relationships as edges, we construct a homogeneous co-reviewing graph. Thirdly, to efficiently identify and handle the redundant relationships that are accidentally formed between ordinary users and spammer group members, we propose the Auto-Sim algorithm, which is a specifically tailored algorithm for dynamic optimization of the co-reviewing graph, allowing for adjustments to the reviewers’ relationship network within the graph. Finally, candidate spammer groups are discovered by using the Ego-Splitting overlapping clustering algorithm, allowing overlapping members to exist in these groups. Then, these groups are refined and ranked to derive the final list of spammer groups. Experimental results based on real-life datasets show that our proposed DRL-OSG algorithm performs better than the baseline algorithms in Precision.
Procoagulant activity of red blood cell microparticles in stored packed red blood cell units and its relation to ABO blood grouping
Authors: Hassan Ayat Salaheldin Mohamed , ElKhafif Nagwa Abdelkhalek , Amin Noha Abdelal , Yassin Rabab Fouad
Published: June 2024

Background

Throughout the storage of blood, the red cells undergo alterations known as “storage lesions,” which involve shape changes and the formation of microparticles (MPs). Studies of the formation of red cell microparticles (RMPs) emphasize the prospective application of RMPs as a quality control measure in the preparation and storage of blood components in the future. In the present study, twenty packed RBC units in citrate phosphate dextrose adenine-1 (CPDA1) were collected from volunteers and stored for 35 days. Over 35 days of storage, samples were collected at six distinct time points weekly and evaluated for the presence of RMPs. MPs were separated by the ultracentrifugation method. Electron microscopy was used to characterize the morphology and size of the isolated microparticles, and flow cytometry was performed to determine the percentage of RMPs that expressed glycophorin A (CD235a) and Annexin V antigens. RMPs' procoagulant activity (PCA) was assessed using a plasma recalcification test. RMP concentration in accordance with ABO blood grouping was assessed by using various types of donated blood groups.

Results

RMPs progressively increased over storage. The procoagulant activity (PCA) exhibited a significant increase during storage, as evidenced by a shorter plasma recalcification time (P value = 0.001). A significant negative correlation (P value = 0.001) between plasma recalcification time and Annexin V-positive microparticles, as well as a dual-positive Annexin V/CD235a population, was identified, indicating a strong correlation between the direct quantitative assay by flowcytometry and the functional assay through the PCA.

Conclusion

RMPs increase on storage with increased PCA. Finding ways to reduce these microparticles in packed RBC units is crucial for reducing the risk of transfusion-related coagulopathy.
An improved method for evaluating fracture density using pulsed neutron capture logging
Authors: Zhang Feng , Xie Bing , Chen Qian , Zhang Xiaoyang , ABuLaHai YiMula , Lu Baoping , Zhang Hui , Fan Jilin
Published: June 2024

Fracture density is a critical fracture evaluation parameter for the optimization and production prediction of hydraulic fracturing models. Nonradioactive tracer (NRT) techniques have successfully used a quantitative fracture density method based on neutron-induced gamma rays from formation elements. Furthermore, fracture density can be calculated using the formation capture cross section before and after hydraulic fracturing based on pulsed neutron capture logging. However, the response sensitivity of the macroscopic scattering cross section to the fractures decreases when the fracture density is high due to the neutron self-shielding phenomenon. Therefore, an improved fracture density evaluation method is applied, which combines the macroscopic capture cross section and the neutron self-shielding correction factor. In the new method, the peak area of titanium from the captured gamma spectrum is used to obtain a neutron self-shielding correction factor to improve the sensitivity of fracture density determination. Furthermore, the response of capture cross-section variation to fracture density at various tagged proppant concentrations and formation backgrounds is investigated. The findings indicate that the tagged proppant concentration influences the detection limit of fracture density and the sensitivity of fracture density identification. The accurate calculation range of fracture density using the new method has been extended from 5% to 10% under the condition that the tagged proppant concentration is 0.2%. Meanwhile, whereas water salinity significantly impacts capture cross-section variation, the effects of porosity, lithology, and fluid type on capture cross-section variation are negligible. A simulated fracturing example demonstrates the method’s applicability in various measurement environments. The results show that fracture density and height are consistent with the model settings after correcting for water salinity, and the fracture density calculation error is less than 3%. Therefore, our evaluation method for fracture density corrected for the neutron self-shielding effect improves response sensitivity and fracture density calculation accuracy.
Crustal stress buildup/relaxation and pore pressure in preparation and sequential brittle-shear fault rupture — Implications for a general theory of earthquake nucleation
Authors: Kurison Clay
Published: June 2024

Compelling geoscience evidence has heightened the appreciation of abnormal (suprahydrostatic, sub/quasi/supralithostatic) pore pressure and multimode (brittle-shear) fault rupture leading to seismicity. However, preparation and rupture nucleation are yet to be adequately constrained and quantitatively modeled. This challenges crucial schemes, notably physics-based earthquake forecasting/prediction. In this multidisciplinary study, the transitions and associated critical points linking the preexisting fluid overpressure in the fault patches, temporal crustal stress, and sequential brittle-shear fault failure were considered. In preparation, tectonic loading was accompanied by processes such as off-fault yielding, permeability enhancement, and foreshocks that facilitate local/regional stress relaxation. Subsequent equalization of stress and the preexisting local overpressure triggers hydraulic fracturing that destabilizes major asperities. Almost instant shear failure follows with the spatially varying rupture velocity/intensity of the frictional slip because of localized asperity stress and syn-slip fluid-/melt-driven fracturing/dilation and lubrication. Based on the aforementioned critical points, quantitative modeling associated stress drop with the evolution of the stress and pore pressure. Equations for the time to onset of stress relaxation and time to rupture were derived using fluid flow and viscoelastic models. The seismic moment was estimated with classical seismological relations after modifications accounting for the smaller surface area during frictional slip. For retrospective testing, two cases of induced seismicity (2016 Fairview, Oklahoma, USA, and 2017 Pohang, South Korea) and multiple cases of natural seismicity (including the 2024 Noto Peninsula earthquake, Japan) were considered. The replication of triggering mechanisms, source properties, and time to rupture suggested that stress temporal relaxation and triggered anomalies (STRATA) encompass fundamental hydromechanical processes in seismogenesis. The setting and scale invariance of STRATA suggest it might be a general theory of earthquake nucleation. Based on the identified preparatory processes/retrospective validations, a physics-based earthquake forecasting/prediction scheme was developed. The nurseries/hypocenters of impending earthquakes are identified through the simultaneous consideration of locally preexisting fluid overpressure and spatiotemporal analysis of stress relaxation. Event size and rupture timing are estimated with the derived relations herein.
Comparison of antitumor efficacy of first-line palbociclib, ribociclib, or abemaciclib in patients with HR+/HER2- aBC: Results of the multicenter, real-world, Italian study PALMARES-2.
Authors: Vernieri Claudio , Provenzano Leonardo , Giuliano Mario , Rizzo Gianpiero , Toss Angela , Piras Marta , Sirico Marianna , Tagliaferri Barbara , Giordano Monica , Miliziano Daniela , Generali Daniele Giulio , Sartori Donata , Zambelli Alberto , Gennari Alessandra , La Verde Nicla Maria , Pedersini Rebecca , Lambertini Matteo , Botticelli Andrea , Curigliano Giuseppe , Dieci Maria Vittoria ,   PALMARES-2 Study Group
Published: June 2024

1014

Background: The Cyclin Dependent Kinase 4/6 inhibitors (CDK4/6i) Palbociclib, Ribociclib and Abemaciclib in combination with Endocrine Therapy (ET) represent the standard-of-care, 1st line treatment for patients with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative, advanced Breast Cancer (HR+/HER2- aBC). So far, no large real-world studies have compared the efficacy of the three CDK4/6i in this clinical setting. Methods: The multicenter, population-based study PALMARES-2 evaluated the antitumor efficacy of 1st line Palbociclib, Ribociclib or Abemaciclib in combination with ET in consecutive HR+/HER2- aBC patients treated in 18 Italian cancer centers between 1st January 2016 and 1st September 2023. The primary study endpoint was real-world Progression-Free Survival (rwPFS), as defined as the time interval between ET plus CDK4/6i initiation and disease progression. Multivariate Cox regression model was used to adjust the association between individual CDK4/6i and rwPFS for clinically relevant variables. Results: With a data cut-off date of January 1st, 2024, we enrolled 1850 patients, 750 (40.6%), 676 (36.5%) and 424 (22.9%) of whom received Palbociclib, Ribociclib and Abemaciclib, respectively. Among 1226 (66.3%) patients with endocrine-sensitive disease, 1087 (89%) received concomitant Aromatase Inhibitors, whereas 441 (70.7%) out of 624 (33.7%) patients with endocrine-resistant disease received concomitant Fulvestrant. Patients treated with Abemaciclib were more likely to have endocrine-resistant disease, liver metastases, lobular tumor histology and lower PgR tumor expression, and less likely to have de novometastatic disease (p<0.001). Median rwPFS in the whole study cohort was 34.9 months (95% CI 32.0-37.4). Abemaciclib and Ribociclib were independently associated with better rwPFS when compared to Palbociclib (Table), whereas Abemaciclib and Ribociclib showed no significantly different efficacy (aHR 0.91, 95% CI 0.70-1.19; p=0.505). Other covariates independently associated with rwPFS are shown (Table). Conclusions: The real-world study PALMARES-2 revealed different antitumor efficacy of individual CDK4/6i in HR+/HER2- aBC patients. Longer follow-up is required to study if Palbociclib, Ribociclib and Abemaciclib are associated with different overall survival. [Table: see text]
Genomic alterations (GA) in ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) patients (pts) with metastatic breast cancer (MBC): Co-occurrence and prevalence along treatment course.
Authors: Bhave Manali A. , Quintanilha Julia , Ross Jeffrey S. , Graf Ryon P , Levy Mia Alyce , Kalinsky Kevin
Published: June 2024

1060

Background: The standard of care for HR(+) HER2(-) MBC is evolving with new biomarker-guided drugs, including novel selective estrogen receptor degraders (SERDs) for pts with ESR1 mutations (mut) and PIK3CA and AKT inhibitors for pts with alterations in the PI3K pathway (PIK3CA, AKT1, and PTEN). This study aimed to evaluate the co-occurrence and the prevalence of these GA in different metastatic lines of therapy in real-world practice for MBC. Methods: This study included pts with HR(+) HER2(-) MBC who underwent genomic testing using Foundation Medicine tissue or liquid comprehensive genomic profiling assays, with specimens collected within 60 days of therapy initiation. Clinical data were obtained by the nationwide (US-based) de-identified Flatiron Health and Foundation Medicine real-world clinicogenomic breast cancer database (FH-FMI CGDB), originated from ~280 US cancer clinics (~800 sites of care) between 01/2011-06/2023. The prevalence of ESR1mut, PIK3CAmut, AKT1, PTENmut, and PTEN copy loss were calculated in tissue (TBx) and liquid biopsies (LBx) collected at time of 1st, 2nd, and 3rd lines of therapy. The co-occurrence of GA in TBx was evaluated. Results: Among patients with a TBx collected around therapy initiation (n=2,536), 81.5% (2,066) was collected at 1st, 10.2% (258) at 2nd, and 8.3% (212) at 3rd line. Among patients with a LBx collected around therapy initiation (n=545), 47% (256) was collected at 1st, 33.2% (181) at 2nd, and 19.8% (108) at 3rd line. In TBx, the prevalence of GA detected in 1st, 2nd, and 3rd lines were 58.6% (1,210), 67.4% (174), and 71.2% (151), respectively. In LBx, the prevalence was 42.7% (121), 65.7% (119), and 60.1% (65), respectively. Among LBx with tumor fraction ³1%, the prevalence was 67.9% (74/109), 89.1% (81/91), and 84.3% (43/51). Among patients with a GA detected in TBx 1st (n=1,210), 2nd (n=174), and 3rd (n=151) lines, both ESR1mut and a PIK3 pathway GA was detected in 7.4% (90), 12.1% (21), and 23.8% (36), respectively. Conclusions: In our dataset, 42-59% of patients with HR(+) HER2(-) MBC have at least one GA detected by TBx or LBx in 1st line, with prevalence increasing in later lines of therapy to 60-71% due to acquisition of an ESR1mut. PTEN copy loss is detected at much higher rates in TBx than LBx, consistent with the known inherent limitations of ctDNA testing. Serial genomic testing with LBx with reflex TBx if alterations are not identified should strongly be considered with the recent approvals of several molecularly targeted agents for HR(+) HER2(-) MBC. [Table: see text]
Geriatric assessment-directed supportive care intervention (GAIN-S)-implementation via telehealth in a lower-resourced community.
Authors: Phillips Tanyanika , Sun Can-Lan , Cabrera Chien Leana , Kim Heeyoung , Celis Ashley , Lee Ty , Robison Africa , Eastman Boryana , Merla Amartej , Player Heather , Kim Ji-Hyun , Asghari Hannah , Cuevas Claudia , Hite Sherry , Wei Kayla , Katheria Vani , Dale William
Published: June 2024

1510

Background: Based on randomized controlled trials,ASCO guidelines recommend use of geriatric assessment (GA)-directed interventions for older adults with cancer. The translation of these models to lower resourced settings has been limited. We assessed the feasibility of implementing GA-directed supportive care (GAIN-S) via telehealth in a lower resourced community setting. Methods: A quality improvement study was conducted in a high poverty, limited access, and low resourced community oncology practice (City of Hope - Antelope Valley [COH-AV]). Eligible participants were 65+ years with a new diagnosis of a malignant neoplasm under evaluation for cancer therapy. Before starting therapy, patients completed: baseline GA, SupportScreen, and the Fulmer SPICES assessment. A geriatric nurse practitioner (GNP) reviewed GA results and implemented multidisciplinary supportive care interventions (GAIN-S) via telehealth between April 2020 and January 2023. Key evaluation measures included: number of patients who completed GAIN-S; number of referrals to multidisciplinary supportive care services and completion rate; advance directives (ADs); and patient satisfaction with telehealth visits. Participants’ demographics, including distance traveled for care, type of cancer, stage, treatment, and telehealth satisfaction items, were summarized using descriptive statistics. To analyze and visualize the implementation process, run charts were utilized. Results: 251 patients (mean age 74, 62% Non-Hispanic White, 22% live 60+ miles from COH-AV, 56% stage II or less, 30% received chemotherapy) completed baseline assessments. 242 had initial visits with GNP, 197 via televideo and 45 via telephone. GNP reviewed vulnerabilities with 209 patients and generated 460 referrals for supportive care services, with 85% of services implemented. Highest numbers of referrals were to pharmacy (177), social work (142), occupational therapy (76), and physical therapy (48). GNP discussed GA-guided care plans with all patients and 43 patients completed AD after discussion with GNP. Over 92% of patients were satisfied with telehealth-based GAIN-S in terms of both ease of visit and access to care with their provider and with telehealth. Conclusions: Telehealth-based GAIN-S has proven to be feasible in providing accessible healthcare to older patients with cancer in a lower resourced community setting. This approach, well-received by most patients, highlights the potential of telehealth in delivering GAIN-S effectively in such settings.
Activating HR+/HER2- and triple-negative breast cancer care teams and their patients in shared decision-making.
Authors: McKinnon Kelly E. , Dewald Ilona , Storey Janet , Dooyema Samuel , Carter Jeffrey D. , Heggen Cherilyn , Mahtani Reshma L.
Published: June 2024

1547

Background: In the rapidly evolving treatment landscape of metastatic breast cancer (MBC), shared decision-making (SDM) is critical to individualize care and improve patient outcomes. To help facilitate improved SDM, we developed an educational toolkit for health care providers (HCPs) to use with HR+/HER2- and triple negative breast cancer (TNBC) patients (pts) and evaluated the implementation of this toolkit at 5 community oncology clinics. Methods: In May-June 2022, pts (N=94) and HCPs (N=18) completed surveys assessing attitudes, confidence, goals, and barriers to SDM in MBC care. HCPs then led collaborative learning sessions with their pts using the SDM toolkit to provide education regarding treatment options and side effects, and to better align on shared goals and treatment plans. Results: In surveys, only 50% of pts reported that they decide on a treatment plan together with their HCPs , 38% reported being asked about treatment preferences, and 34% reported discussing supportive care, such as mental health care or pain relief. Additionally, very few pts reported high knowledge of BC treatments and side effects. HCPs and pts were misaligned on patient goals and barriers to SDM. For example, 56% of HCPs thought pts were too overwhelmed/anxious/fatigued to make treatment decisions, but only 21% of pts agreed that was a top challenge. While pts and HCPs were aligned on top treatment decision factors of effectiveness and quality-of-life, HCPs underestimated the importance of concerns about side effects (HCPs 11% vs pts 32%), and the cost and duration of treatment (17% vs 30%, and 22% vs 30%, respectively). HCPs correctly identified survival (56%) as a top goal for pts but were less likely to identify progression/recurrence as important to pts (39%). Additionally, 28% of pts reported their top challenge was worrying about being unable to work or meet responsibilities at home; however, only 19% of HCPs recognized this as a top challenge. Following pt-HCPs collaborative education sessions, in which HCPs used the SDM toolkit to facilitate pt education and SDM, HCPs and pts reported improved confidence in pt-HCP communication. Additionally, 46% of pts reported discussing treatment goals with their HCPs and 46% reported taking a more active role in their care following the learning session. Conclusions: These findings reveal misalignments between HCPs and patients with BC regarding treatment decision-making. The gaps identified are critical to address as they are pre-requisites for SDM. The downloadable shared decision-making toolkit developed as part of this implementation science initiative can be adopted by breast cancer clinical teams to help facilitate patient education and SDM, empowering patients to be active participants in their care.
Integrating 4 Methods (In4M) to evaluate physical function in patients with cancer: Results of a comprehensive digital health study.
Authors: Thanarajasingam Gita , Dueck Amylou C. , Bhatnagar Vishal , Brown Abbie , Cathcart-Rake Elizabeth Jane , Diamond Matthew , Faust Louis , Fiero Mallorie , Huntington Scott F. , Jeffery Molly , Jones Lee , Paludo Jonas , Power Bradford , Ross Joseph S. , Ruddy Kathryn Jean , Schellhorn Sarah , Tarver Michelle , Wood William Allen , Gross Cary Philip , Kluetz Paul Gustav
Published: June 2024

1564

Background: Physical function (PF) is a core outcome in cancer trials that can inform treatment tolerability. PF can be assessed across modalities including by patient (pt) report, clinician (clin) report, performance tests and digital sensors. The optimal approach for PF measurement has not been defined. Methods: In4M is a prospective observational study evaluating PF in pts initiating chemotherapy for breast cancer or lymphoma followed over 9 months. We used an electronic platform (Hugo) to aggregate serially assessed pt-reported PF, clin- and pt-reported ECOG performance status (PS), 6-minute walk test (6MWT) and wearable (Fitbit) data. We evaluated feasibility in all pts; associations among PF measures and the ability of PF measures to detect change were evaluated in pts with both baseline (BL) and 3-month (3M) data. We used Pearson correlations to assess the relationship of average daily steps with measures of PF. To assess change, we compared each PF measure from BL to 3M using a 2-sided α=.05 paired t-test. Results: Of the208 pts enrolled, 193 (93%) and 159 (76%) completed surveys, and 121 (58%) and 124 (60%) provided wearable data (evaluable: ≥1 day data) at BL and 3M, respectively. When requiring a stringent BL with 4+ days of data with ≥1 weekend day to be evaluable, 88 (42%) and 120 (58%) provided wearable data at BL and 3M. At both BL and 3M, pt-reported PF was generally more highly correlated with wearable-derived daily steps than clin-reported PF and 6MWT were (Table). Significant declines in PF were observed for pt- and clin-reported PF (all p<0.05), but not other modalities. Conclusions: Longitudinalassessment of multi-modal PF data including pragmatic wearable data collection was feasible in pts receiving chemotherapy. Pt-reported PF was the only modality that was both correlated with step count and able to detect change. Additional wearable metrics, correlations among PF measurements and outcomes, and clinically meaningful change scores will be reported. Optimal PF measurement may improve future reporting of treatment tolerability. Clinical trial information: NCT05214144 . [Table: see text]
Interim report of a phase 2 study of sonodynamic therapy (SDT) using SONALA-001 together with MR-guided low-intensity focused ultrasound (MRgFUS) in children with diffuse intrinsic pontine glioma (DIPG).
Authors: Kilburn Lindsay Baker , Packer Roger J. , Fonseca Adriana , Keating Robert F , Mueller Sabine , Narsinh Kazim , Ho Winson S , Niazi Toba , Fenn Peter , Clanton Ryan , Henry Lenora , Potter Wyatt , Andresen Corina , Marcus Stuart , Benaim Ely , Syed Hasan R
Published: June 2024

2067

Background: Children with DIPG have limited treatment options and a poor prognosis, with median survival of 9-12 months. Preclinical studies reveal that sonodynamic therapy (SDT) with MR-guided focused ultrasound (MRgFUS) activates ALA metabolite, protoporphyrin IX (PpIX), leading to tumor cell death and extending survival in glioma models. Methods: SDT-201 (NCT05123534) is a multi-center, first-in-child dose escalation trial of SDT with SONALA-001 and MRgFUS administered in children aged ≥ 5 years with DIPG, enrolled 4-20 weeks post-radiation therapy and prior to disease progression. The trial evaluates the safety and preliminary efficacy of SDT and pharmacokinetics (PK) of intravenous ALA (SONALA-001) at 5mg/kg, administered 6-12 hours before MRgFUS to the pons (delivered to half the pons 30 days apart for the first patient in each cohort of 3, with subsequent patients receiving entire pons treatment). The trial was subsequently amended to allow up to 12 monthly treatments. Results: Six patients in 2 cohorts were treated (4 male:2 female, range 5-12 years) between August 2022 and December 2023. No DLTs or related AE grade ≥ 3 were observed. For SONALA-001, the Cmax occurred at the end of infusion, followed by rapid clearance (15.7 mL/min/kg) with plasma half-life of < 1 hour, indicating rapid distribution. The PpIX Cmax occurred 4-6 hours post-dose and declined with a longer mean half-life than SONALA-001 of 6 hours. Both Cmax and AUCall demonstrate circulating-PpIX and systemic exposure were significantly lower than for SONALA-001. Two of the first 6 patients achieved a partial response per RAPNO central-review, and 2 subjects continuing treatment are 11 to 15 months from start of study therapy. Conclusions: SDT is a well-tolerated strategy for patients with DIPG after initial radiotherapy. SONALA-001 shows rapid distribution and clearance, and PpIX PK align with metabolite formation. Following dose escalation completion, dose-expansion will be initiated at RP2D offering further insights into safety, PK, and efficacy. Clinical trial information: NCT05123534 .
Pathological complete response to predict long term outcomes in the I-SPY2 TRIAL.
Authors: Yee Douglas , Esserman Laura , Yau Christina ,   I-SPY investigators
Published: June 2024

597

Background: The I-SPY2 platform trial uses pathologic complete response (pCR) to identify active agents in patients with stage 2/3 breast cancer. Only patients with HR+ HER2- tumors, and low risk 70-gene assay results are excluded. 2118 patients were enrolled from March 2010 through June 2022 with follow-up data from 2005 patients as of January 2024. We have reported the improved event-free (EFS) and distant-recurrence free (DRFS) survival for 950 patients (1) who achieved a pathological complete response (pCR). Here we report the outcomes for the additional 1055 patients not included in our initial report. Methods: Patients have been randomized to one of 25 arms. Residual Cancer Burden (RCB) assessment was performed by site pathologists who were trained to ensure uniform response classification; RCB 0 = pCR. EFS is defined as time to local or distant recurrence or death. DRFS is defined as time to distant recurrence or death. Patients without events were censored at time to last follow-up. Association between pCR and EFS/DRFS was assessed using Cox proportional hazard modeling with significance assessment using the log rank test. EFS and DRFS at 3 years are estimated using the Kaplan Meier method. Results: Median follow up was 3.3 years (0.05-10.2 y). There were 144 EFS and 123 DRFS events. pCR rates varied by subtype, but achieving pCR was associated with an EFS of 96% and DRFS of 96%. For patients without pCR the EFS was 82% and DRFS was 84% at 3 years. The relationship between pCR and EFS was significant and clinically impactful within each subtype. Conclusions: pCR continues to have a strong positive association with EFS and DRFS as in our initial report. It is notable that EFS for non-pCR patients improved to 82% from our initial report of 78%. Initially few patients received additional adjuvant therapy except for standard of care endocrine and HER2-targeted therapy. Increased adoption of post neoadjuvant therapy with the approval of several agents for patients with non-pCR likely contributed to this improvement. I-SPY also reported a shift in residual cancer burden for patients receiving investigational therapies, which also may improve outcome for non-pCR patients. Taken together, these data demonstrate the value of pCR as an early endpoint regardless of tumor type or drugs delivered. These findings emphasize the need for new agents that will allow all patients to achieve pCR and potentially avoid the need for additional therapy after surgery. 1. Yee, et al. JAMA Oncol 2020. 2. Symmans, et al. JAMA Oncol 2021. Clinical trial information: NCT01042379 . [Table: see text]
Pilot evaluation of allostatic load and breast cancer characteristics in a predominantly Han Chinese population.
Authors: Gou Wenjing , Zou Qin , Carlos Ruth C.
Published: June 2024

e12570

Background: To determine the effects of allostatic load (AL), a measure of cumulative physiological effects of chronic stress due to adverse social determinants of health, on breast cancer (BC) characteristics in Chinese individuals. Methods: A pilot sample of185 women with newly diagnosed BC at Sichuan People’s hospital from 2018 to 2023 and complete AL data were included. AL used 10 markers (total cholesterol, low-density lipoprotein, albumin, glomerular filtration rate, white blood cell count, C-reactive protein, systolic and diastolic blood pressure, body mass index and heart rate). AL was assigned 1 point for each marker value in the worst quartile. The sum of the points represented the AL composite measure. Using linear and logistic regression, we determined the association of AL with age and educational attainment and with tumor ER+ and PR+ status. Results: Participants were 98.37% Han Chinese, mean age 51 (range 27-78). 23.24% attained college-level education or above. Higher AL trended to correlate with less than college-level educational attainment (coefficient=-0.60, p=0.058). In a univariable model, AL correlated with ER+ (OR=0.80, P=0.039) and PR+ (OR=0.81, P<0.001) BC. Adjusting for age and educational attainment, AL trends remained positive but not significant with ER+ BC (OR =0.82, P=0.092). Conclusions: Similar to US patients, AL may represent a physiologic correlate of adverse social conditions and worse BC characteristics. Results remain to be confirmed in a larger population.
Ipsilateral recurrence and breast cancer outcomes in carriers of BRCA1/2 pathogenic variants according to locoregional treatments.
Authors: Bernstein-Molho Rinat , Haisraely Ory , Galper Shira , Gal-Yam Einav Nili , Kaidar-Person Orit
Published: June 2024

e12584

Background: Our previous study of 255 breast cancer (BC) patients, carriers of BRCA1/2 pathogenic variants (PV), showed that patients who underwent mastectomy without post-mastectomy radiotherapy (PMRT) had higher rates of local recurrence (LR) than those who underwent PMRT or breast-conserving therapy (BCT). Our aim was to verify our previous findings in a larger cohort. Methods: Clinical data was extracted from the medical records of BRCA1/2 mutation carriers with BC, treated at a single institution between 1/2006-12/2022. Data extracted included demographics, tumor characteristics, disease stage, surgical and oncological treatment, use of RT and disease outcomes. Results: Overall, 481 BC patients with BRCA1/2 germline mutations were identified, 20 of them presented with synchronous bilateral disease. Median follow-up time was 75.3 months (range 12.5-211). After excluding 16 patients with metastatic de novo disease and 1 patient not operated for medical reasons, 464 patients with 484 primary tumors were analyzed. Of these, 234 (48.3%) mastectomies (84% were skin- or nipple-sparing, SSM/NSM, 16% total mastectomy) and 250 (51.7%) BCT were performed. In the non-PMRT group (n=153) there was earlier disease stage at diagnosis (77.6% of tumors were Tis and T1N0) compared to the PMRT group (n=81) and BCT group (4.9% and 45%, respectively, p<0.001). All had free surgical margins. LR rate in the study cohorts was 20/153 breasts (13.1%) in the non-PMRT group compared with 1/81 breasts (1.2%) in the PMRT group (p=0.003), and 16/250 (6.4%) in the BCS group (p=0.024). All but one recurrence were invasive. Cumulative incidence of LR at 5 and 10 years was 14.1% and 15.9% in the non-PMRT, compared to 4.4% and 9.4% in BCT group, respectively (p=0.034). No significant difference in overall survival was observed (p=0.39). Conclusions: BRCA1/2 PV carriers treated with mastectomy without PMRT had higher rates of LR than those who underwent mastectomy and PMRT or BCT, despite earlier stage disease. Further studies are needed to compare these outcomes to non- BRCA1/2 carriers and find means to improve local control in these patients.
Analysis of risk factors for recurrence within 12 months after surgery in patients with breast cancer receiving neoadjuvant therapy at a Brazilian cancer center.
Authors: Rossato de Almeida Guilherme , Cesca Marcelle Goldner , de Albuquerque e Rodrigues de Sousa Débora Guilherme , Cavalcanti Balint Flavia , Leite Luciana de Moura , Lima Vladmir Cordeiro , Moraes Sanches Solange , Celeste Tavares Monique
Published: June 2024

e13039

Background: Early recurrence following treatment for localized breast cancer typically occurs within 5 years, and is commonly linked to high-risk clinicopathologic factors. However, literature focusing on risk factors for earlier recurrence timeframes is scarce, particularly within the neoadjuvant treatment population. Therefore, this study aims to investigate potential predictors for recurrence within 12 months post-surgery in breast cancer patients submitted to neoadjuvant therapy. Methods: This is an observational, descriptive, retrospective study involving 310 patients with recurrent breast cancer who received neoadjuvant therapy between January 2007 and March 2022, at AC Camargo Cancer Center in São Paulo, Brazil. Patients were compared based on relapse time after surgery (<12 months or ≥12 months), and risk factors were analyzed using the Chi-Square test or Fisher’s Exact test. Results: From 310 patients analyzed, 108 relapsed within 12 months and 202 after this period. Factors predicting recurrence in less than 12 months included: Histologic grade (HG) III ( p < 0.01); nuclear grade (NG) III ( p < 0.001); mitotic counts >20/mm2 ( p = 0.02); Ki67 > 20% ( p = 0.010); triple negative breast cancer (TNBC) and HER2+/HR- subtypes ( p < 0.001); interruption of neoadjuvant therapy due to disease progression or toxicity ( p < 0.001); chemotherapy dose reduction or delay ( p = 0.001); omission of adjuvant radiotherapy ( p < 0.001) and interruption of adjuvant HER2 targeted therapy ( p < 0.001). Menopausal status, Residual Cancer Burden (RCB) index, type of surgery and clinical stage showed no significant correlation with the outcome. Conclusions: Recurrence in less than 12 months was associated with intrinsic factors, such as HG III, NG III, high mitotic counts, Ki67 > 20%, TNBC, as well as interruption or delay of neoadjuvant therapy, omission of adjuvant radiotherapy and interruption or delay of HER2 targeted therapy, pointing out potential risk factors in this population.