bluuebunny/crossref_metadata_2025 huggingface dataset:
4D scale-dependent Schwarzschild-AdS/dS black holes: study of shadow and weak deflection angle and greybody bounding
Authors: Övgün Ali , Pantig Reggie C. , Rincón Ángel
Published: March 2023

We investigate the shadow, deflection angle, and the greybody bounding of a Schwarzschild-AdS/dS black hole in scale-dependent gravity. We used the EHT data to constrain the parameter $$\epsilon$$
ϵ
. We have found that within the $$1\sigma$$

1
σ

level of uncertainty, $$\epsilon M_0$$

ϵ

M
0

ranges at $$10^{-11} - 10^{-16}$$

10

-
11

-

10

-
16

orders of magnitude for Sgr. A*, and $$10^{-11} - 10^{-17}$$

10

-
11

-

10

-
17

for M87*. Using these parameters, we explored how the shadow radius behaves as perceived by a static observer. Using the known parameters for Sgr. A* and M87*, we found different shadow cast behavior near the cosmological horizon even if the same scaling parameters were used. We explored the deflection angle $${\hat{\alpha }}$$

α
^

in the weak field limit for both massive and null particles, in addition to the effect of finite distances using the non-asymptotically flat version of the Gauss-Bonnet theorem. We have found that the $${\hat{\alpha }}$$

α
^

strongly depends on massive particles. Tests on $$\epsilon$$
ϵ
’s effect using Sgr. A* is only along points of low impact parameters. For M87*, only the scaled BH in AdS type can be tested at high impact parameters at the expense of very low value for $${\hat{\alpha }}$$

α
^

. We study the rigorous bound on the greybody factor for scalar field emitted from black holes in the theory and show the bound on the transmission probability. The effects of the scale-dependent gravity on the greybody factors are investigated, and the results indicate that the bound on the greybody factor in this case is less than the bound for the Schwarzschild black hole.
FLASH and the FLASH2020+ project—current status and upgrades for the free-electron laser in Hamburg at DESY
Authors: Beye Martin , Gühr Markus , Hartl Ingmar , Plönjes Elke , Schaper Lucas , Schreiber Siegfried , Tiedtke Kai , Treusch Rolf
Published: March 2023

The free-electron laser in Hamburg, FLASH, is the first extreme ultra-violet and soft X-ray free-electron laser (FEL) user facility and has been continuously upgraded since its start in 2005. Further major works are currently underway within the FLASH2020+ project that pioneeringly implements full repetition rate external seeding at a superconducting accelerator facility. With fully tunable undulators providing variable polarization FEL pulses, we expect FLASH to turn into the ideal spectroscopy machine for ultrafast processes within the coming years.
Structural and magnetic properties of manganese ferrite nanoparticles
Authors: Gochuyeva Aynura F.
Published: March 2023

This paper describes the structural and magnetic properties of [Formula: see text], which is currently widely used and is considered to be one of the promising materials. Although these features of our subject of study have been considered before us, we wanted to confirm the accuracy of these characteristics for our future purposes. In the study of the structural feature, the analysis of Raman spectroscopy was considered and the high purity of nanosized particles was revealed. The magnetic properties were analyzed by electron paramagnetic resonance (EPR) and the presence of unpaired electrons was detected, and the linewidth between the peaks ([Formula: see text]) and the [Formula: see text]-factor (2282) was measured.
A Floating Decremental/ Incremental Meminductor Emulator Using Voltage Differencing Inverted Buffered Amplifier and Current Follower
Authors: Aggarwal Bhawna , Rai Shireesh Kumar , Arora Akanksha , Siddiqui Amaan , Das Rupam
Published: March 2023

This paper presents a floating meminductor emulator circuit using a voltage differencing inverted buffered amplifier (VDIBA), current follower (CF), and two grounded capacitors. The parasitic resistance at the input terminal of the current follower has been utilized. The idea of implementing a meminductor emulator is simple and works on the principle of putting memory inside the active inductor circuit. A capacitor (memory element) has been charged by the current flowing through the active inductor circuit. Therefore, the proposed meminductor emulator can be viewed as an active inductor circuit having memory inside it. The proposed floating meminductor emulator works over a significant range of frequencies and satisfies all the characteristics of a meminductor. The meminductor emulator has been realized and simulated in the LTspice simulation tool using TSMC’s 180-nm CMOS technology parameters. A chaotic oscillator circuit has been realized using the proposed meminductor emulator to verify its performance. The results obtained for the chaotic oscillators are found to be satisfactory and thus verify the performance of the proposed meminductor emulator.
Geodiversity estimate of the Arxan–Chaihe Volcanic Field extending across two geoparks in Inner Mongolia, NE China
Authors: Li Bo-xin , Németh Karoly , Zakharovskyi Vladyslav , Palmer Julie , Palmer Alan , Proctor Jonathan
Published: March 2023

The Arxan–Chaihe Volcanic Field is located SW of the Great Xing'an Range in Inner Mongolia, NE China. This monogenetic volcanic field formed in the Pleistocene, with its latest activity a fissure eruption
c.
2000 years ago. Here we present the first geodiversity estimate for the region, applying a method combining the geomorphological and geological elements into a grading system, weighting their rarity, significance and uniqueness. To outline the geomorphological diversity, the geomorphon concept was used alongside a watershed analysis of the theoretical fluvial network of the region. In addition volcanic geomorphological elements were provided. Available geological maps, field surveys and volcano geology classification were utilized for the geological diversity estimates. Geology and geomorphology are the core parameters of the qualitative–quantitative assessment of geodiversity. Geographical Information Systems (GIS) were used for calculations of geomorphological and geological parameters to provide geodiversity estimates for the Arxan–Chaihe Volcanic Field region. The variables used to estimate the geodiversity include geology (rock rareness from a global perspective) and geomorphology (slope variations). In addition we used channel systems and terrain characterization (geomorphon) to describe the morphodiversity of the study area. Our study assessed recent volcanic features and concluded that they have a high geodiversity and elevated geoheritage value. However, the uplifted and structurally complicated old terrains with mature fluvial networks provide high geomorphological diversity to the region, therefore keeping the overall geodiversity score high.
Around the GLOBE: Numerical Aggregation Question-answering on Heterogeneous Genealogical Knowledge Graphs with Deep Neural Networks
Authors: Suissa Omri , Zhitomirsky-geffet Maayan , Elmalech Avshalom
Published: March 2023

One of the key AI tools for textual corpora exploration is natural language question-answering (QA). Unlike keyword-based search engines, QA algorithms receive and process natural language questions and produce precise answers to these questions, rather than long lists of documents that need to be manually scanned by the users. State-of-the-art QA algorithms based on DNNs were successfully employed in various domains. However, QA in the genealogical domain is still underexplored, and researchers in this field (and other fields in humanities and social sciences) can highly benefit from the ability to ask questions in natural language, receive concrete answers, and gain insights hidden within large corpora. While some research has been recently conducted for factual QA in the genealogical domain, to the best of our knowledge, there is no previous research on the more challenging task of numerical aggregation QA (i.e., answering questions combining aggregation functions, e.g., count, average, max). Numerical aggregation QA is critical for distant reading and analysis for researchers (and the general public) interested in investigating cultural heritage domains. Therefore, in this study, we present a new end-to-end methodology for numerical aggregation QA for genealogical trees that includes (1) an automatic method for training dataset generation, (2) a transformer-based table selection method, and (3) an optimized transformer-based numerical aggregation QA model. The findings indicate that the proposed architecture, GLOBE, outperforms the state-of-the-art models and pipelines by achieving 87% accuracy for this task compared to only 21% by current state-of-the-art models. This study may have practical implications for genealogical information centers and museums, making genealogical data research easy and scalable for experts as well as the general public.
Electrochemical Deposition with Redox Replacement of Lanthanum with Uranium in Molten LiCl-KCl
Authors: Eakin Jeffrey , Molina Daniel , Guo Xiaofeng , Beyenal Haluk , Ivory Cornelius
Published: March 2023

Electrochemical recovery of dilute concentrations of actinides from spent nuclear fuel would reduce the longevity of storing high-level nuclear waste. Electrochemical deposition with redox replacement (EDRR) is used in a molten salt medium for the selective electrochemical recovery of uranium in the presence of excess concentrations of lanthanum. In each EDRR cycle, after a short electrodeposition pulse, the deposited lanthanum is spontaneously replaced by uranium at open circuit. After repeated cycles, uranium metal was obtained on a tungsten electrode immersed in a LiCl-KCl melt that contained 1 wt% lanthanum chloride—0.15 wt% uranium (IV) chloride. Scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM-EDS) analysis revealed uranium particles approximately 0.5−1 μm with well-defined rectangular shapes; and with 20–60 times more uranium recovered on the surface of the electrode than lanthanum.
Detection of Trace Hg(II) in Cosmetics and Aqueous Solution by a Gold Nanospikes Electrochemical Sensor
Authors: Cao Rui , Liu Xin , Yang Cheng , Wu Ju
Published: March 2023

An ultrasensitive and rapid electrochemical detection of trace Hg(II) sensor was developed. The significantly amplified electrochemical signals was caused by the high specific surface area of the electrochemical sensor. Scanning electron microscopy showed that the gold nanospikes were 200 ∼ 300 nm in length and 50 nm in diameter. The electrochemical properties of sensor were characterized by square wave voltammetry. Experimental parameters were optimized using square wave stripping voltammetry. The linear range of sensor for Hg(II) is 3 × 10−10 mol l−1 ∼ 7 × 10−7 mol l−1 and the limit of detection is 1 × 10−10 mol l−1. Hg(II) was successfully quantified in river water and cosmetics. The original Hg(II) in loose powder, Sunblock and whitening lotion using the high ratio surface area electrochemical sensor determination were found to be 2.234, 2.056 and 2.347 mg kg−1 respectively. The results are within the range of standard values, the RSD are 1.7%, 1.5% and 2.1%, respectively. HRSA Au electrode sensor displays high sensitive, excellent stability, reproducibility, especially more convenient than ICP-MS and AFS verification methods. We look forward to the possibility that the HRSA Au electrode sensor can be used for real-time monitoring of Mercury ions in water and cosmetics in the future.
A Mathematical Model on the Dynamics of In-Host Infection Cholera Disease with Vaccination
Authors: Jackob Owade Kennedy , Akinyi Okaka , Tireito Frankline
Published: March 2023

In this paper, a within-host cholera mathematical model has been developed using a system of ordinary differential equations incorporating vaccine efficacy. The formulated model considers cells in an already vaccinated individual with a vaccine whose efficacy is

γ

. The solutions of the model have been shown to be both positive and bounded hence well-posed. The vaccine basic reproduction number has been carried out using the next generation matrix approach and is given by

R

0
V

=

γ
/

d
+

μ

2

and

R

0
V

<
1

if

γ
<

d
+

μ

2

. Analysis of the model shows that

i
n
f
e
c
t
i
o
n
 
f
r
e
e
 
e
q
u
i
l
i
b
r
i
u
m

I
F
E

point is both locally and globally asymptotically stable when

R

0
V

<
1

and

i
n
f
e
c
t
i
o
n
 
e
q
u
i
l
i
b
r
i
u
m

I
E

point is locally asymptotically stable when

R

0
V

>
1

. Furthermore, analysis of the model shows that

R

0
V

<
1

is not sufficient enough to eradicate in-host cholera disease, hence the existence of backward bifurcation which is an indication as to why cholera disease is persistent. To highlight the relevance of vaccine efficacy, a numerical simulation of the model with respect to vaccination is carried out and shows that when the vaccine efficacy

γ

is high, there will be a lower infection rate of cells, hence the need to improve cholera vaccine efficacy.
Monitoring a Mandatory Nonmedical Switching Policy from Originator to Biosimilar Infliximab in Patients with Inflammatory Bowel Diseases: A Population-Based Cohort Study
Authors: Fisher Anat , Kim Jason D. , Dormuth Colin R.
Published: March 2023

Background. On September 5, 2019, British Columbia announced a new policy (the Biosimilars Initiative) to switch from originator to biosimilar infliximab for patients with inflammatory bowel diseases. Objective. To monitor the impacts of the policy on the use of medications and health services during the first year of the policy. Methods. In this population-based cohort study, we used administrative health data to construct three historical cohorts and one policy cohort of patients with inflammatory bowel diseases who used the originator infliximab. We then monitored the cumulative incidence of medications and health services. Log-likelihood ratios were used to quantify differences between the policy cohort and the average of the historical cohorts. Results. The cohorts included 1839–2368 users of the originator infliximab, ages 4–90 years, mean age 43 years. During the first year of follow-up, we found: (1) a 0.9% increase in the first dispensation of infliximab, biosimilar, or originator; (2) a 16.2% increase in infliximab dose escalation; (3) a decrease of 2.4% in the dispensation of antibiotics and a 2.6% decrease in new use of prednison; (4) an anticipated increase in visits to physicians and gastroenterologists to manage switching to biosimilars (24.0%); (5) a 4.0% decrease in discharges from hospital; and (6) a 2.9% decrease in emergency admissions to hospital. Conclusion. British Columbia’s Biosimilars Initiative for nonmedical switching from originator to biosimilar infliximab for inflammatory bowel diseases was not associated with harmful impacts on medications and health services use. An increase in dose escalation was accompanied by an improvement in health status proxies.
The Path Planning and Location Method of Inspection Robot in a Large Storage Tank Bottom
Authors: Wang Yinchu , Zhu Haijiang , Yu Yue , Hu Bin
Published: March 2023

With the development of robot technology, inspection robots have been applied to the defect detection of large tanks. However, the existing path planning algorithm of the tank bottom detection robot is easy to fall into the local minimum, and the path is not smooth. Besides, the positioning of the tank bottom detection robot is not accurate. This article proposes a path planning and location algorithm for the large tank bottom detection robot. Specifically, we design a preset spiral path according to the shape of the tank bottom, and a rotating potential field (RPF) near the obstacle is added to avoid the problem of path planning falling into a local minimum. We obtained accurate and smooth planning results. Compared with the state‐of‐the‐art, the RPF method reduced the average RMSE by 9.49%. In addition, by measuring the acoustic emission distance, the three‐point positioning algorithm can be used to achieve the calculation of the robot position detection in the proposed method, and the average positioning error on the spiral path is only 0.0748 ± 0.0032.
The Behavior of RC Beams Strengthened with Steel Fiber Concrete Layer by ANSYS Simulation
Authors: Lam Thanh Quang Khai , Do Thi My Dung
Published: March 2023

In this study, a double-layer reinforced concrete beam structure was created for the purpose of repairing reinforced concrete beams by pouring a layer of concrete on top of the reinforced concrete beam and then adding fibers to the concrete. Take into consideration the bearing capacity of these double-layer concrete beams as well as the effects that the input parameters have on the stress strain, the propagation of cracks in reinforced concrete beams. The study looks at double-layered reinforced concrete beams, with the steel fiber concrete placed on top of the one containing the normal concrete. This investigation led to the following relationships: load-compressive stress, tensile stress, and vertical displacement at the midpoint of the beam span, as well as a diagram showing how cracks spread in the beams. After getting the experimental results and comparing them with an ANSYS simulation, the diagram was used to figure out the loads at which the beams start to look cracked and the loads at which the beams are damaged. This study investigated the following six cases: how the addition of SFs affects the properties of concrete, the spacing of the stirrups at the ends of the beam should be looked into to see what effects it might have, how the number of tensile steel bars in the beam affects its properties, how the diameter of tensile steel bars affects their properties, how the diameter of compressed steel bars affects the results, and how the thickness of the SFC layer affects the properties of the material. Also, the things that were mentioned would have a big effect on how these double-layer beams in the design work.
A Numerical Study of CO2 Decoupled Effects on Extinction Limit and Flame Microstructure in CH4/Air Counterflow Diffusion Flame with Various Pressures
Authors: Chen Ying , Wang Jingfu , Li Jianrong , Zhang Jian
Published: March 2023

Extinction limits and flame microstructures of CH4 versus air (N2/O2) counterflow diffusion flames with additional CO2 to oxidizer stream under various pressure conditions were numerically investigated by a proposed decoupled strategy. The chemical and thermal effects of CO2 addition were isolated from the synergistic effect on extinction limits and flame microstructures. The results show that the extinction limits were decreased due to the CO2 addition and extended caused by the enhanced pressure, respectively. The changes of flame microstructures from far away from extinction to near extinction mainly are reflected in a narrower combustion zone and thinner flame thickness, while there is no visible displacement of the flame front location. Quantitative analyses manifest the thermal effect of CO2 addition on extinction limit is greater than chemical effect, and elevated pressure can enhance both thermal and chemical effects. An interesting phenomenon occurred between the thermal and chemical effects resulting from increasing CO2 mole fraction in an oxidizer on extinction limit; the former monotonically increase along with CO2 mole fraction, while the latter represents a kind of approximate quadratic-parabola tend along with CO2 mole fraction. The distributions of the production and consumption rate of hydroxyl (OH) radicals were presented to clarify the contribution of the kinetic term in the asymptotic solution to the extinction limits with increasing CO2 molar fraction and various pressures.
Assessment of the Conventional Acid-Clay Method in Reclaiming Waste Crankcase Lubricating Oil
Authors: Opoku-Mensah Patrick , Gyamfi James Nana , Domfeh Adjei , Awarikabey Emmanuel , Kwao-Boateng Emmanuela
Published: March 2023

In this study, the conventional acid-clay method was used to evaluate its potential for recycling waste crankcase lubricating oil (WCLO). The results showed that the acid-clay method was effective in re-refining the WCLO and returning the oil to a quality comparable to oils produced from fresh lube oil stocks. This method has been reported to account for around 90% of the global waste crankcase lubricating oil treatment and is considered to be an inexpensive process. The results revealed that the acid-clay method improved the viscosity of the oil at 40°C from 104 cSt to 105.6 cSt. The flash point of the oil was also increased from 192°C in the WCLO to 204°C in the re-refined crankcase lubricating oil (RCLO). The water content reduced from 0.01% in the WCLO to 0% in the RCLO, indicating the effectiveness of the acid-clay method in removing water traces from the WCLO. Additionally, the contaminants present in the WCLO were reduced drastically, with iron and aluminum content reduced from 23.0% and 21.0% to 0.0% and 0.0%, respectively. The fuel ingress in the WCLO reduced from 4.0% to 1.0%. However, it was observed that the acid-clay method did not significantly impact the viscosity index, TBN, and density of the oil. The re-refined base oil produced by the acid-clay method can be fortified with appropriate additives and reused in vehicles, reducing environmental pollution, depleting fossil resources, and saving the country’s foreign exchange used in importing fresh lubricating oil.
The Approximation of a Modified Baskakov Operator
Authors: Yingdian Ma , Weimeng Wang
Published: March 2023

Because of their simple form and high quality, linear arithmetical operators, particularly linear positive operators, are very popular. The number of in-depth studies on linear operator approximation is extensive, and the majority of the published material falls into four categories: types and structures of operators, approximation of operators, order of approximation and the converse theorem of operators, and operator saturation. The Baskakov operator will be transformed in the same way to explore its approximation characteristics as well as the approximation theorem and converse theorem.
Is Homocysteine Associated with the Prognosis of Covid-19 Pneumonia
Authors: Kalan Sarı Işılay , Keskin Olgun , Seremet Keskin Ayşegül , Elli̇dağ Hamit Yaşar , Harmandar Orbay
Published: March 2023

Background/Aim. Coronavirus disease 2019 (COVID-19) is a life-threatening disease characterized by a prothrombotic state. Because homocysteine (Hcy) is a potential biomarker in thrombotic disease, this article aims to highlight the role of Hcy in the prognosis of COVID-19 pneumonia. Methods. This prospective study was conducted between April 2021 and December 2021 at the University of Health Sciences, Antalya Training and Research Hospital. 162 patients admitted to the emergency department for COVID-19 pneumonia and scheduled for hospitalization in the intensive care unit (ICU) or COVID-19 ward of the chest disease department were included in the study. Hcy levels and other necessary laboratory parameters were analyzed. Results. 134 patients were admitted to the COVID-19 ward and 28 to the ICU. Hcy levels were significantly higher in ICU patients than in ward patients (

p
:
0.001

). Of the 134 patients, 55 later required ICU treatment for various reasons and were transferred to the ICU. Hcy (

p
:
0.010

), ferritin (

p
:
0.041

), and LDH (

p
:
0.010

) were significantly higher in patients who were transferred to the ICU than in patients who remained in the ward. The Hcy level was associated with a poor prognosis. It was found that each unit increase in the Hcy level approximately doubled the risk of death in patients with COVID-19 (odds ratio: 1.753). Discussion. There are few studies examining the association between high Hcy levels and disease severity in COVID-19. Our study supports previous studies and shows the association between the need for intensive care and high Hcy levels. Conclusion. A high Hcy value is a helpful marker in determining the need for critical care on admission to the emergency department and a marker of poor prognosis in COVID-19 pneumonia.
Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: March 2023

Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and redox metabolism. The intracellular cysteine pool can be sustained by cystine uptake or de novo synthesis from serine and homocysteine. Demand for cysteine is increased during tumorigenesis for generating glutathione to deal with oxidative stress. While cultured cells have been shown to be highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and cancers that arise from them using stable isotope 13C1-serine and 13C6-cystine tracing. De novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue, while cysteine synthesis was either inactive or downregulated during tumorigenesis. In contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. However, differences in glutathione labeling from cysteine were evident across tumor types. Thus, cystine is a major contributor to the cysteine pool in tumors, and glutathione metabolism is differentially active across tumor types.

Significance:

Stable isotope 13C1-serine and 13C6-cystine tracing characterizes cysteine metabolism in normal murine tissues and its rewiring in tumors using genetically engineered mouse models of liver, pancreas, and lung cancers.
Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach
Authors: Doe-Tetteh Seyram A. , Camp Sabrina Y. , Reales Dalicia , Crowdis Jett , Noronha Anne Marie , Wolff Bernadette , Alano Tina , Galle Jesse , Selcuklu S. Duygu , Viale Agnes , Socci Nicholas D. , Liu Ying L. , Tew William P. , Aghajanian Carol , Ladanyi Marc , He Meng Xiao , AlDubayan Saud H. , Mazor Roei David , Shpilberg Ofer , Hershkovitz-Rokah Oshrat , Riancho Jose A. , Hernandez Jose L. , Gonzalez-Vela M. Carmen , Buthorn Justin J. , Wilson Manda , Webber Amy E. , Yabe Mariko , Petrova-Drus Kseniya , Rosenblum Marc , Durham Benjamin H. , Abdel-Wahab Omar , Berger Michael F. , Donoghue Mark T.A. , Kung Andrew L. , Glade Bender Julia , Shukla Neerav N. , Funt Samuel A. , Dogan Ahmet , Soslow Robert A. , Al-Ahmadie Hikmat , Feldman Darren R. , Van Allen Eliezer M. , Diamond Eli L. , Solit David B.
Published: March 2023

Purpose:

To overcome barriers to genomic testing for patients with rare cancers, we initiated a program to offer free clinical tumor genomic testing worldwide to patients with select rare cancer subtypes.

Experimental Design:

Patients were recruited through social media outreach and engagement with disease-specific advocacy groups, with a focus on patients with histiocytosis, germ cell tumors (GCT), and pediatric cancers. Tumors were analyzed using the MSK-IMPACT next-generation sequencing assay with the return of results to patients and their local physicians. Whole-exome recapture was performed for female patients with GCTs to define the genomic landscape of this rare cancer subtype.

Results:

A total of 333 patients were enrolled, and tumor tissue was received for 288 (86.4%), with 250 (86.8%) having tumor DNA of sufficient quality for MSK-IMPACT testing. Eighteen patients with histiocytosis have received genomically guided therapy to date, of whom 17 (94%) have had clinical benefit with a mean treatment duration of 21.7 months (range, 6–40+). Whole-exome sequencing of ovarian GCTs identified a subset with haploid genotypes, a phenotype rarely observed in other cancer types. Actionable genomic alterations were rare in ovarian GCT (28%); however, 2 patients with ovarian GCTs with squamous transformation had high tumor mutational burden, one of whom had a complete response to pembrolizumab.

Conclusions:

Direct-to-patient outreach can facilitate the assembly of cohorts of rare cancers of sufficient size to define their genomic landscape. By profiling tumors in a clinical laboratory, results could be reported to patients and their local physicians to guide treatment.

See related commentary by Desai and Subbiah, p. 2339
Abstract ED11-2: HER2 positive breast cancer
Authors: Gianni Luca , Bianchini Giampaolo
Published: March 2023

Neoadjuvant therapy of HER2+ breast cancer has been groundbreaking. It showed the superior results in terms of pathologic complete response (pCR) and event free survival (EFS) of adding trastuzumab to chemotherapy in women with locally advanced breast cancer (NOAH trial) that led to the first regulatory approval of a neoadjuvant approach in the field of breast cancer. In addition, neoadjuvant studies (NeoSphere, neoALLTO) clearly showed the improved antitumor activity of dual blockade of the HER2 receptor, paved the way to the Aphinity adjuvant study and justified the current worldwide use of dual black of HER2 in high/moderate risk HER2+ early breast cancer.

In the above scenario the design and results of the Katherine study were a landmark achievement. By proving the clinical value of shifting treatment from trastuzumab to trastuzumab-DM1 in women with residual disease after neoadjuvant therapy the study provided firm clinical evidence that residual disease can be used as a surrogate of relative resistance that per se justifies the adoption of alternative non cross resistant regimens/therapies at the individual level.

The clinical success of neoadjuvant trials in HER2+ early breast cancer went hand-to-hand with translational studies that that are identifying markers predicting for pCR and EFS that are and will be used to fine tuning a more individually tailored approach to treatment, and eventually effective and safe de-escalation strategies.

The rich collection of neoadjuvant studies that shaped the modern approach to treatment of women with early HER2+ breast cancer will be enriched of studies with new drugs, trastuzumab deruxtecan and tucatinib to name some of the front runners. All current and future treatments will greatly depend on the neoadjuvant approach as a tool for a quick assessment of the clinical value of new therapies. Such approach has so far been used as basis or supporting evidence for regulatory approvals worldwide, based on the concept that pCR can be viewed as surrogate of long-term benefit. Individual trials and meta-analyses are challenging the dependability of pCR to predict EFS at trial level. However, the benefits of tumor eradication (pCR) at individual level continue to support the simple clinical concept that more pCR is better and that regimens leading to it deserve full credit.

Acknowledgment: The work of Luca Gianni is supported by grants of the BCRF

Citation Format: Luca Gianni, Giampaolo Bianchini. HER2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED11-2.
Abstract ED13-2: Radiation therapy and cardiovascular disease in breast cancer
Authors: Bergom Carmen
Published: March 2023

This presentation will review the topic of radiation-induced cardiac dysfunction in patients with breast cancer. Specific areas of discussion include the a review of the cardiac-sparing techniques available for radiation therapy in breast cancer treatment; guidelines for the prevention, diagnosis, and treatment of cardiac dysfunction after radiation exposure in patients with breast cancer; and new areas of research in the field of radiation-induced cardiac disease in breast cancer. Emerging knowledge of how concurrent systemic therapies may interact with radiation to affect heart function will also be discussed. In addition, future directions in the field of radiation-induced heart dysfunction will be reviewed.

Citation Format: Carmen Bergom. Radiation therapy and cardiovascular disease in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED13-2.
Abstract ED3-3: Oncofertility and other quality of life issues
Authors: Lambertini Matteo
Published: March 2023

The current availability of effective systemic treatment strategies has significantly improved the prognosis of patients with early breast cancer. However, this survival gain is often obtained at the cost of higher toxicity. The increase in life span among breast cancer survivors calls for the need to address both early and late potential adverse effects of anticancer therapies to maximize their quality of life. Among them, the potential gonadotoxicity of anticancer therapies and its implications on fertility and ovarian function need to be discussed with all young patients. According to available guidelines, oncofertility counseling should now be considered mandatory in the care of young women with newly diagnosed cancer. This counselling should focus on the risk of developing treatment-induced premature ovarian insufficiency and on the available techniques to preserve fertility and/or ovarian function. Oocyte/embryo cryopreservation, or ovarian tissue cryopreservation in those not eligible for gamete cryopreservation, are standard strategies to be offered to young patients interested in preserving fertility, i.e. to increase their chances of post-treatment pregnancies. Ovarian suppression with gonadotrophin-releasing hormone agonists (GnRHa) during chemotherapy can be offered to premenopausal patients interested in ovarian function preservation, i.e. to decrease their risk of developing chemotherapy-induced early menopause.

Current available data confirm that pregnancy occurring following proper treatment for breast cancer and period of follow-up is safe, both in terms of long-term clinical outcomes for the patients and safety for the babies. However, there is a slightly higher incidence of obstetric and birth complications that require the need for a closer monitoring of these pregnancies.

Beyond fertility and pregnancy-related issues, a long-term follow-up of young women with breast cancer by the oncofertility unit is recommended for improving the management of other additional gynecological-related issues faced by these women. Among them, contraception should be considered during active treatment and in the follow-up of women who do not wish to get pregnant. Moreover, in the current era of more complex endocrine therapy approaches with a major negative impact on the quality of life of premenopausal patients with breast cancer, it is essential to properly and proactively care about their treatment-related side effects. Among them, menopause related-symptoms and sexual dysfunction may be better managed by implementing a close collaboration between oncologists and gynecologists within the oncofertility unit.

Citation Format: Matteo Lambertini. Oncofertility and other quality of life issues [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED3-3.
Abstract ED5-1: Early palliative care
Authors: Kaufmann Tara
Published: March 2023

This education session will review early palliative care in oncology and applications in patients with metastatic breast cancer. This presentation provides an overview of the field of research in early palliative care for patients with advanced solid tumors and discusses considerations specific to breast cancer. The speaker will present current challenges that we face in integrating palliative care into our practice and future areas for clinical innovation and research in palliative care. The speaker will present practical tips for how breast oncologists can deliver early palliative care to patients. The speaker will present guiding principles on when to consider referral to interdisciplinary, specialty palliative care.

Citation Format: Tara Kaufmann. Early palliative care [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED5-1.
Abstract ED8-2: The role of advanced radiation technology in reducing toxicity
Authors: Mitchell Melissa
Published: March 2023

Over the past decade, breast cancer radiotherapy has increasingly focused on techniques to improve treatment precision and limit toxicity. Surface guided radiotherapy and respiratory gating has allowed for improved cardiac sparing and the elimination of permanent skin tattoos in women receiving breast radiation, while rapid developments in the technological delivery of radiation via both volumetric arc therapy and proton beam radiation have shown promise in further improving target coverage and normal tissue sparing for breast cancer patients. Cutting edge innovations, including MR-guided radiotherapy and FLASH technology are now being explored as means to further improve treatment precision and decrease toxicity. The purpose of this talk is to highlight and discuss these advances in radiotherapy, review the existing evidence to support their use in the treatment of breast cancer, and detail specific patient populations that are most likely to benefit. Discussion will also focus on ongoing and future research aimed at improving our understanding and utilization of these novel advances in care.

Citation Format: Melissa Mitchell. The role of advanced radiation technology in reducing toxicity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED8-2.
Abstract F1-1: Tumor stroma in DCIS progression
Authors: West Robert
Published: March 2023

The interaction between cancer cells and the surrounding stroma plays a significant role in tumor growth and progression. The rapidly growing field of study involving the tumor microenvironment is discovering stromal-specific genes and cells that participate in this process. In invasive breast cancer, transcriptional analysis of stroma derived samples has identified stromal gene expression features that are correlated with clinical outcome with features characteristic of angiogenesis, hypoxia, and inflammation. The role of the microenvironment in DCIS is less well studied and has significant variation across and within DCIS. The basement membrane and myoepithelial cell layers provide a barrier for the interaction between neoplastic cells and the tumor microenvironment. DCIS tumor cells may be variably exposed to the immune environment. An immune infiltration is common in some DCIS, including high grade DCIS with necrosis. How this influences the transition from DCIS to IBC is complex.

Citation Format: Robert West. Tumor stroma in DCIS progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr F1-1.
Abstract OT1-12-04: MRO PMS study - Intraoperative Specimen Magnetic Resonance Imaging System for Intraoperative Margin Assessment for Invasive Breast Cancer Using the ClearCoast™ System in Breast Conserving Surgery
Authors: Thill Marc , Kelling Katharina , van Haasteren Viviane , Schnitzbauer Tina , Kiene Petia , Levin Anna , Kolka Eyal , Peles Zachi , Aulmann Sebastian
Published: March 2023

Background Re-operation for involved margins in breast conserving surgery is associated with worse cosmetic outcome, increased medical costs, and patient anxiety. Therefore, obtaining negative margins during primary BCS is essential. In our prior non-interventional study, published in October 2021 (Thill M et al., J Surg Oncol 2021) the re-operation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% re-operations, if results had not been blinded for the surgeon. The results suggested a potential reduction of the re-operation rate by up to 80% for patients undergoing BCS. Aim of the study Aim of our current study is to evaluate the interventional performance of the ClearCoast™ system (ClearCut Medical, Ltd.) in assessing surgical margins for IBC in breast conserving surgery (BCS) and reducing the re-excision rates. Material and Methods The ClearCoast™ system utilizes a diffusion-weighted-imaging (DWI) protocol to create 2D surface maps showing T2*, a MR parameter related to the tissue’s apparent diffusion coefficient (ADC), with a depth penetration of 1mm. ADC is a highly accurate differentiator for irregular versus normal tissue. From May 2021 till to date a prospective, non- blinded post marketing study (N=93), evaluating the performance of the ClearCoast™ system is currently ongoing in the Breast Centre at the AGAPLESION MARKUS KRANKENHAUS, Frankfurt, Germany. After standard evaluation with ultrasound and/or X-ray with or without wire or clip marking, the specimens are intraoperatively scanned with the ClearCoast™ system, and positive margins will lead to a direct re-resection by decision of the surgeon applying a simple T2* threshold to flag irregular tissue. The final histopathology results will be compared with the scan results on a margin per margin bases. In addition, the rates of recurrent surgery of the interventional group will be compared with those of a historical group on the bases of matched pairs. Primary endpoint of the study is the re-excision rates in both the interventional and the historical standard of care group. To date, 64 patients are enrolled in the trial, therefore, results of the trial may be presented at the SABCS 2022.

Citation Format: Marc Thill, Katharina Kelling, Viviane van Haasteren, Tina Schnitzbauer, Petia Kiene, Anna Levin, Eyal Kolka, Zachi Peles, Sebastian Aulmann. MRO PMS study - Intraoperative Specimen Magnetic Resonance Imaging System for Intraoperative Margin Assessment for Invasive Breast Cancer Using the ClearCoast™ System in Breast Conserving Surgery [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-04.
Abstract OT1-20-01: SentiNot 2.0: Avoid unnecessary Sentinel Lymph Node Biopsies in women with DCIS
Authors: Pantiora Eirini , Eriksson Staffan , Pistiolis Lida , Bagge Roger Olofsson , Nagy Gyula , Thompson Alastair M. , Man Vivian , Kwong Ava , Karakatsanis Andreas , Wärnberg Fredrik
Published: March 2023

Background Approximately 15-30% of women with a preoperative diagnosis of ductal carcinoma in situ (DCIS) will be diagnosed with invasive cancer (IBC) on specimen pathology. Risk of upgrade, and impairment of lymphatic outflow after breast surgery, mainly mastectomy, are drivers for upfront sentinel lymph node dissection (SLND). In the SentiNot feasibility study, marking the SLN by superparamagnetic iron oxide nanoparticles (SPIO) injection during primary surgery minimized unnecessary SLNDs, allowing for delayed SLND (d-SLND) only in those with IBC up to 50 days after primary surgery. This policy resulted in that 78.3% study participants avoided upfront SLND. In the d-SLND setting, SPIO detection outperformed the isotope (98.5 vs 60.6%), regardless of type of breast procedure. Incremental healthcare costs were reduced by 8.5% (485 USD per patient) for the entire trial population (ref 1). Prospective Clinical Trial Design SentiNot 2.0 (ClinicalTrials.gov Identifier: NCT04722692), is currently accruing data, powered to examine the detection rate of SPIO over isotope±blue dye during d-SLND. Trial candidates are: patients with a diagnosis of high-risk DCIS/pLCIS (mass-lesions, microinvasion, grade 3, grade 2 >20mm) regardless of type of breast surgery, and patients with planned breast surgery that precludes safe and accurate axillary mapping at a d-SLND (extensive oncoplastic breast conservation, tumors of the axillary tail and mastectomy). In d-SLND, study patients receive isotope±blue dye and within-patient-randomization is performed for which detection method to start with (SPIO-first vs. isotope-first). The trial is stratified for mastectomy and breast conservation. Secondary outcomes are nodal concordance (SPIO vs. isotope) at d-SLND, quality-of-life and health-economy outcomes. Present and Planned Accrual Total target accrual is 500 d-SLNDs. Insofar, 360 women have been included at six different sites in Sweden, Hong Kong, and the USA. Currently, data accrual and institution recruitment is active and expanding. For more information about the trial please refer to ClinicalTrials.gov Identifier: NCT04722692. For discussion regarding potential participation contact dr Andreas Karakatsanis (andreas.karakatsanis@surgsci.uu.se).

Citation Format: Eirini Pantiora, Staffan Eriksson, Lida Pistiolis, Roger Olofsson Bagge, Gyula Nagy, Alastair M. Thompson, Vivian Man, Ava Kwong, Andreas Karakatsanis, Fredrik Wärnberg. SentiNot 2.0: Avoid unnecessary Sentinel Lymph Node Biopsies in women with DCIS [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-20-01.
Abstract OT2-16-03: Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, trial in progress)
Authors: Hamilton Erika , Tsurutani Junji , Curigliano Giuseppe , Martín Miguel , O’Sullivan Ciara C. , Sohn Joo Hyuk , Tryfonidis Konstantinos , Santarpia Libero , Yang Shan , Diéras Véronique
Published: March 2023

Background: The current first-line (1L) standard of care (SOC) for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is trastuzumab (T) plus pertuzumab (P) and a taxane. Despite advances in 1L SOC, most patients (pts) progress during maintenance therapy with T+P. Tucatinib is a tyrosine kinase inhibitor (TKI) approved in combination with T and capecitabine for adults with HER2+ MBC, with and without brain metastases (BM). In HER2CLIMB, the addition of tucatinib significantly prolonged progression-free survival (PFS) and overall survival (OS) in pts with HER2+ MBC and was well tolerated. Adding tucatinib also reduced the risk of disease progression or death in pts with untreated and/or active BM (Murthy et al. 2020, Curigliano et al. 2021). HER2CLIMB-05 investigates whether adding tucatinib to 1L SOC as maintenance therapy will extend PFS while maintaining quality of life (QOL). Methods: HER2CLIMB-05 (NCT05132582) is a phase 3, randomized, double-blind study evaluating tucatinib plus T+P as maintenance therapy for HER2+ MBC. Approximately 650 pts will be enrolled. Eligible pts will have advanced HER2+ disease, no progression on 4–8 cycles of prior 1L SOC, ECOG Performance Status of 0 or 1, and no or asymptomatic BM. Exclusion criteria include prior treatment with anti-HER2 and/or anti-epidermal growth factor receptor TKI (prior SOC for early BC is permitted) or inability to undergo contrast magnetic resonance imaging of the brain. Pts will be randomized 1:1 to receive either tucatinib or placebo twice daily, with T+P once every 21 days. Pts with HR+ disease may receive endocrine therapy. The primary endpoint is investigator-assessed PFS. Secondary endpoints include OS (key endpoint), time to deterioration of health-related QOL, central nervous system PFS, safety, and pharmacokinetic (PK) parameters. PFS and OS will be compared using a 2-sided stratified log-rank test between treatment groups. Time-to-event endpoints will be summarized using the Kaplan–Meier method. PK and safety data will be summarized using descriptive statistics. Enrollment is ongoing in the US, with additional sites planned.

Citation Format: Erika Hamilton, Junji Tsurutani, Giuseppe Curigliano, Miguel Martín, Ciara C. O’Sullivan, Joo Hyuk Sohn, Konstantinos Tryfonidis, Libero Santarpia, Shan Yang, Véronique Diéras. Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, trial in progress) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-16-03.