bluuebunny/crossref_metadata_2025 huggingface dataset:
EVALUATION OF MEAN WAVE OVERTOPPING AND MAXIMUM INDIVIDUAL WAVE OVERTOPPING ON ROCK REVETMENT
Authors: Ab Razak Mohd Shahrizal , Masri Amirah Afiqah , Mohamad Noor Asiah , Rosdi Nor Syamimi , Khan Abdul Rehman
Published: January 2025

An accurate estimation of wave overtopping discharge on rock revetment is important to protect coastal areas from possible hazards. The mean discharge value is often used in the coastal structural design. However, the anticipated impact of the maximum volume of overtopping by individual waves is expected to be significant in wave overtopping analysis. This research investigates the mean discharge of wave overtopping and maximum volume of overtopping by individual wave using two-dimensional (2D) physical model tests. The rock revetment model consists of armour layer with D50=46 mm, a filter layer with D50=13 mm, and an impermeable core, with a thickness of 2D50 for armour and filter layers. Wave overtopping volumes obtained from physical tests were then compared to EurOtop empirical formulae. The results showed that the variability of wave overtopping increases when the wave height and water level increase. This variation falls within the specified interval boundaries by EurOtop empirical methods, with the exception of the lower maximum volume of overtopping by individual waves. Furthermore, the findings indicate that the maximum volume of overtopping by individual waves can exceed the mean wave overtopping volume by up to 85%.
Circulating neuropeptide Y dynamics and performance during exercise in heart failure patients with contemporary medical and device therapy
Authors: Ayagama Thamali , Green Peregrine G. , Tan Cheryl , Monteiro Cristiana , Holdsworth David A. , Herring Neil
Published: January 2025

High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long‐term prognosis. CHF patients (n = 15) underwent cardiopulmonary exercise testing with venous blood sampling at rest, peak exercise and recovery. These patients had significantly higher resting venous NPY levels compared with an age‐ and sex‐matched control group of patients (n = 16) with normal left ventricular function (40 ± 6.9 vs. 9.0 ± 4.6 pg/mL, respectively; P < 0.0001). In CHF patients, NPY levels increased significantly from baseline to peak exercise (to 93.5 ± 42.1 pg/mL; P = 0.0004) and remained elevated during recovery (86.8 ± 44.6 pg/mL; P = 0.0018). The peak (r = 0.58, P = 0.0222) and recovery (r = 0.56, P = 0.0304) NPY levels and the ability to increase NPY from baseline (r = 0.53, P = 0.0427) showed significant positive correlations with heart rate recovery at 1 min, but not with peak oxygen consumption. In CHF patients, the ability to increase NPY levels on exertion is correlated with heart rate recovery, a known prognostic indicator for mortality. These findings suggest that NPY dynamics during exercise might provide valuable insights into sympathetic responses and prognosis in CHF patients.
Supplemental Material: An integrated structural and GPS study of the Jalpatagua fault, southeastern Guatemala
Authors: Garnier B. , al. et
Published: January 2025

Complete 40Ar/39Ar results.
Trichoptysis: a pathognomonic presentation of anterior mediastinal teratoma
Authors: Varadharajan Vijayakumar , Venkitaraman Balasubramanian , Mahender Banu , Ganesan Srinath
Published: January 2025

Germ cell tumours are usually found in the gonads, while the most common extragonadal site is the anterior mediastinum. When these tumours involve the tracheobronchial tree, patients present with trichoptysis or coughing up of hair. We present a rare case of a woman who presented with trichoptysis and was evaluated and diagnosed with benign mature teratoma of the anterior mediastinum with bronchopulmonary involvement. The patient underwent right anterolateral thoracotomy and complete surgical excision of the mass along with right upper bilobectomy. The patient is on regular follow-up and is asymptomatic.
Ethnic disparities in HbA1c and hypoglycemia among youth with type 1 diabetes: beyond access to technology, social deprivation and mean blood glucose
Authors: Pemberton John Stuart , Fang Zhide , Chalew Stuart A , Uday Suma
Published: January 2025

Introduction

The UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably related to higher mean blood glucose (MBG) due to lower socioeconomic status (SES) and less access to technology. We aimed to determine if HbA1c ethnic disparity persists after accounting for the above variables.

Research design and methods

A retrospective analysis of participants who received structured education in continuous glucose monitoring (CGM) use was conducted at a tertiary center. HbA1c was paired with glucose metrics from 90-day CGM data. The influence of ethnicity, SES determined by Index of Multiple Deprivation (IMD), MBG and other covariates on HbA1c was evaluated using multiple variable regression analysis. Occurrence of hypoglycemia was evaluated.

Results

A total of 168 (79 White, 61 South Asian, 28 Black) CYP with T1D were included. There were no differences between groups for age, MBG, time in range (3.9–10.0 mmol/L), diabetes duration, gender, insulin delivery method (multiple daily injections vs continuous subcutaneous insulin infusion), or percent sensor use (PSU). In multiple variable analysis, MBG (p<0.0001), ethnicity (p<0.0001), age (p<0.001), duration of diabetes (p<0.01) and PSU (p<0.05) accounted for 81% of the variability in HbA1c. Adjusted HbA1c in the Black group (67 mmol/mol) was higher than both South Asian (63 mmol/mol) and White groups (62 mmol/mol) (p<0.001). Despite significant IMD differences between groups, it did not influence HbA1c. Multiple variable analysis showed that the Black group experienced more hypoglycemia than South Asian and White groups (<3.9 and <3.0 mmol/L, p<0.05).

Conclusions

CYP from Black ethnic backgrounds have a higher HbA1c compared with their South Asian and White counterparts which is clinically significant and independent of MBG, potentially contributing to increased complications risk. Additionally, the Black group experienced a higher incidence of hypoglycemia, possibly due to a treat-to-HbA1c target approach.
Exploring the experiences of cognitive symptoms in Long COVID: a mixed-methods study in the UK
Authors: Miller Amy , Song Ning , Sivan Manoj , Chowdhury Rumana , Burke Melanie Rose
Published: January 2025

Objective

To explore the lived experiences and extent of cognitive symptoms in Long COVID (LC) in a UK-based sample.

Design

This study implemented a mixed-methods design. Eight focus groups were conducted to collect qualitative data, and the Framework Analysis was used to reveal the experiences and impact of cognitive symptoms. A self-report questionnaire was used to collect the quantitative data to assess the perceived change and extent of symptomology post COVID-19.

Setting

Focus groups were conducted in April 2023 online via Zoom and in-person at the University of Leeds, UK.

Participants

25 people with LC living in the UK participated in the study. Participants were aged 19–76 years (M=43.6 years, SD=14.7) and included 17 women and 8 men.

Results

Reduced cognitive ability was among the most prevalent symptoms reported by the study participants. Three key themes were identified from the qualitative data: (1) rich accounts of cognitive symptoms; (2) the impact on physical function and psychological well-being and (3) symptom management. Descriptions of cognitive symptoms included impairments in memory, attention, language, executive function and processing speed. Cognitive symptoms had a profound impact on physical functioning and psychological well-being, including reduced ability to work and complete activities of daily living. Strategies used for symptom management varied in effectiveness.

Conclusion

Cognitive dysfunction in LC appears to be exacerbated by vicious cycle of withdrawal from daily life including loss of employment, physical inactivity and social isolation driving low mood, anxiety and poor cognitive functioning. Previous evidence has revealed the anatomical and physiological biomarkers in the brain affecting cognition in LC. To synthesise these contributing factors, we propose the Long-COVID Interacting Network of factors affecting Cognitive Symptoms. This framework is designed to inform clinicians and researchers to take a comprehensive approach towards LC rehabilitation, targeting the neural, individual and lifestyle factors.
Predicting preventive self-care behaviours among type 2 diabetes based on the health belief model in Bandar Abbas city: a cross-sectional study
Authors: Darvishi Arezu , Hassani Laleh , Mohseni Shokrollah , Shahabi Nahid
Published: January 2025

Objectives

It is essential to manage type 2 diabetes mellitus (T2DM) through self-care behaviours and to ascertain the predictors of correct health training for the control of diabetes. The aim of this study was to determine the predictive role of the constructs of the health belief model in encouraging T2DM to adopt self-care behaviours in Bandar Abbas city.

Design

This cross-sectional study was conducted in 2022 in Bandar Abbas.

Participants

Participants were 246 patients with T2DM referring to six comprehensive healthcare centres in Bandar Abbas city. They were enrolled using the accessible sampling method and were requested to complete a questionnaire.

Results

The results of the present study indicated that the health belief model could explain 50.73% of the variance in patients with T2DM’s self-care behaviours. Among the constructs of the health belief model, the constructs of self-efficacy (52.4%), perceived barriers (38.8%) and perceived susceptibility (34.9%) best predicted the adherence of patients to self-care behaviours, suggesting that these constructs can be considered to improve self-care behaviours in patients with T2DM.

Conclusions

According to the results of this study, the health belief model can be a suitable and effective tool for predicting self-care behaviours in patients with T2DM. There was a statistically significant correlation was found between self-care behaviours and all the constructs except perceived barriers. Considering the positive effects of the health belief model in improving the self-care of patients with type 2 diabetes, it is suggested to use this model in planning interventions to improve self-care in other diseases affected by lifestyle-based behaviour.
Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study
Authors: Inthanachai Thananya , Boonkrai Chatikorn , Phakham Tanapati , Pisitkun Trairak , Thaiwong Rattapoom , Chuthaphakdikun Vichaya , Sakunrangsit Nithidol , Limprasutr Vudhiporn , Chinsuwan Thanyavi , Hirankarn Nattiya , Suppipat Koramit , Watanabe Norihiro , Tawinwung Supannikar
Published: January 2025

Background

B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.

Methods

Expression of B7-H3 across various solid tumors was evaluated using RNA-seq data from TCGA, TARGET, and GTEx datasets and by flow cytometry staining. B7-H3-specific mAbs were developed by immunizing mice with human B7-H3, screening with ELISA, and analyzing kinetics with surface plasmon resonance. These mAbs were used to create second-generation CAR constructs, which were evaluated in vitro and in vivo for their antitumor function.

Results

We identified four mAb clones from immunized mice, with three demonstrating high specificity and affinity. The second-generation B7-H3 CAR T cells derived from these mAbs exhibited robust cytotoxicity against B7-H3-positive targets and successfully infiltrated and eliminated tumor spheroids in vitro. In a xenograft mouse model of glioblastoma, these CAR T cells, particularly those derived from clone A2H4, eradicated the primary tumor, and effectively controlled rechallenge tumor, resulting in prolonged survival of the xenograft mice. In vivo T cell trafficking revealed high accumulation and persistence of A2H4-derived CAR T cells at the tumor site.

Conclusions

Our results provide novel B7-H3-targeted CAR T cells with high efficacy, paving the way for clinical translation of solid tumor treatment.
Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy
Authors: Kajihara Ryutaro , Long Mark D , Hoki Toshifumi , Chen Hongbin , Yamauchi Takayoshi , Kanemaru Hisashi , Segal Brahm H , Dy Grace K , Ito Fumito
Published: January 2025

Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy. We found frequent circulating CD8+TIL-TCRs with identical complementarity determining region 3 (CDR3)α amino acid sequences but quasi-identical CDR3β and TCR α/β (TRA/TRB) sequences. Despite their sequence similarities, these highly homologous TIL-TCRs responded differently to immunotherapy, and exhibited distinct transcriptional signatures that were uniquely distinguished by the expression ofGZMK. Overall, the expression ofIFNGin CD8+T-cell subsets including highly homologous TIL-TCRs increased when the patient achieved a response, but gradually decreased as the patient developed acquired resistance. Our findings provide insight into the cross-talk between T cells in the tumor microenvironment and those in the blood, and highlight that CD8+T cells with highly homologous TCR sequences might display divergent transcriptional states and kinetics in response to immunotherapy.
Impact of microgeography on communication dynamics in a healthcare environment
Authors: Chown Jillian , Rey-McIntyre Katrina , Kim John , Purdie Thomas G. , Dickie Colleen , Tsang Richard , Tsang Yat , Seuntjens Jan , Liu Fei-Fei , Liu Christopher C.
Published: January 2025

Background

For growing healthcare organisations, anchored resources—assets that are not easily movable—may complicate expansion and distort workflow patterns. We examine work patterns at a radiation oncology department of a major Canadian hospital. As this department doubled its size, healthcare providers remained bound to treatment planning rooms and radiation machines at the original site. This study examines workplace communication and interactions before and after the expansion.

Methods

We conducted regression analyses using a unique dataset merging email communications, badge swipes, office locations and organisation charts for individuals that routinely use the treatment planning room (n=232). We use a difference-in-differences framework to compare individuals’ behaviours before and after the expansion. Our dependent variables were how often individuals accessed the treatment planning room and email volumes between two individuals.

Findings

We find an overall decrease in the use of the treatment planning room, though the effect was larger for those that moved away from it. Further, we find an increase in email communication for dyads of individuals separated in the move, but only if they belonged to different departments.

Practical implications

Our research points to complex interdependencies among healthcare providers, shedding light on how hospital expansion may have unintended consequences. Healthcare leaders should acknowledge that interaction patterns will be affected when healthcare providers are separated from each other or from anchored resources. Shifting to remote interactions may be adequate in some instances; in others, it may negatively affect work outcomes as well as the engagement and satisfaction of providers and patients.
Constructing stellar solutions with spherical symmetry through quadratic anisotropy in f(Q) gravity
Authors: Kumar R. , Maurya S. K. , Errehymy A. , Jaiswal A. , Myrzakulov K. , Sharma S.
Published: January 2025

This article examines anisotropic models to characterize compact stars (CSs) in the context of modified f(Q) gravity theory. To achieve this, we employ the linear functional form

$$f(Q) = \alpha Q + \beta $$

f
(
Q
)
=
α
Q
+
β

. A physically meaningful metric potential

$$g_{rr}$$

g

rr

is considered, and a quadratic form of anisotropy is utilized to solve the Einstein field equations in closed form. This class of solutions is then applied to characterize observed pulsars from various perspectives. In the scope of f(Q) gravity, we address the Darmois–Israel junction requirements to guarantee a smooth matching of the inner metric with the external metric (Schwarzschild (Anti-) de Sitter solution) at the boundary hypersurface. By applying these junction conditions, we determine the model parameters involved in the solutions. Additionally, this study evaluates the physical viability and dynamical stability of the solution for different values of the f(Q)-parameter

$$\alpha $$

α

within the compact star (CS). The mass–radius relationships associated with observational constraints are analyzed for several compact stars, including Vela X-1, PSR J1614-2230, and PSR J0952-0607. The investigation indicates that the estimated radius of the compact object PSR J0952-0607, with mass

$$2.35 \pm 0.17~M_\odot $$

2.35
±
0.17

M
⊙

, is around

$$15.79^{+0.05}_{-0.09}$$

15
.

79

-
0.09

+
0.05

km for a particular parameter value of

$$\alpha = 2.0$$

α
=
2.0

, and the moment of inertia for the de Sitter space is determined as

$$4.31 \times 10^{45}~\textrm{g}~\textrm{cm}^2$$

4.31
×

10
45

g

cm
2

. The

$$I-M$$

I
-
M

curve shows greater sensitivity to the stiffness of the equation of state than the

$$M-R$$

M
-
R

curve, reinforcing our conclusion about the

$$I-M$$

I
-
M

framework’s responsiveness. Finally, we predicted the corresponding radii and moments of inertia for various values of

$$\alpha $$

α

based on the

$$M-R$$

M
-
R

and

$$M-I$$

M
-
I

curves.
Phase structure and optical properties of the de Sitter Spacetime with KR field based on the Lyapunov exponent
Authors: Du Yun-Zhi , Li Huai-Fan , Ma Yu-Bo , Gu Qiang
Published: January 2025

Since the spontaneously broken of the Lorentz symmetry in the gravity theory with the non-minimally coupling between the Kalb–Ramond (KR) field (that acquires a nonzero vacuum expectation value) and the Einstein gravity, there exists the exactly static and spherically symmetric black holes solutions related with the Lorentz violating parameter. Based on this, we consider the corresponding black hole solution in the de-Sitter (dS) spacetime with the KR field and investigate the thermodynamic properties in the expanded phase space through introducing the interplay entropy between the black hole and cosmological horizons. Especially we analyze the effect of the Lorentz-violating parameter on the thermodynamic properties. Furthermore, the Lyapunov exponent and the shadow of these static and spherically symmetric black holes in this Lorentz-violating gravity theory are also investigated. These study will open a new perspective to probe the thermodynamics of black holes.
The revival of $$U(1)_{L_e-L_{\mu }}$$: a natural solution for $$(g-2)_{\mu }$$ with a sub-GeV dark matter
Authors: De Bibhabasu
Published: January 2025

The experiments searching for a hidden gauge sector with a leptophilic neutral gauge boson have already ruled out

$$U(1)_{L_e-L_\mu }$$

U

(
1
)

L
e

-

L
μ

as a feasible extension of the Standard Model (SM) gauge group

$$({\mathscr {G}}_{\textrm{SM}})$$

(

G
SM

)

for explaining the observed discrepancy in

$$(g-2)_\mu .$$

(
g
-
2
)

μ

.

The paper proposes a simple extension of the minimal particle content of

$${\mathscr {G}}_{\textrm{SM}}\otimes U(1)_{L_e-L_\mu }$$

G
SM

⊗
U

(
1
)

L
e

-

L
μ

with a TeV-scale scalar leptoquark

$$S_1.$$

S
1

.

Due to the non-trivial transformation of

$$S_1$$

S
1

under

$$U(1)_{L_e-L_\mu },$$

U

(
1
)

L
e

-

L
μ

,

the model generates additional one-loop contributions to

$$(g-2)_\mu ,$$

(
g
-
2
)

μ

,

reviving the considered gauge extension within the experimentally allowed regions of the parameter space. The model can also accommodate a viable Dark Matter (DM) candidate

$$\chi $$

χ

– a vector-like SM-singlet fermion in the sub-GeV mass regime. The theory provides a natural framework to test the proposed DM phenomenology through electron excitation signals. Moreover, the DM-specific observables and

$$(g-2)_\mu $$

(
g
-
2
)

μ

being connected through the New Physics (NP) parameters, the future beam dump experiments hunting for light, feebly interacting particles and the DM direct detection experiments are complementary to each other for constraining/falsifying the model.
Characterization of the triphenylmethane dye (Patent Blue V)-modified Al/p-Si diode
Authors: Ozaydin C. , Sunkur M. , Gullu O.
Published: January 2025

The sol-gel spin coating method, an easily applicable, low-temperature, and inexpensive method, was used to grow Patent Blue V (PBV) organic thin films placed between metal and semiconductor. Atomic force microscope images were taken to reveal the morphological structure of the resulting organic film. FTIR, NMR, and UV-Vis measurements were taken to investigate the chemical features and optical structure of the PBV molecule. Using the traditional I-V, Cheung, and Norde methods of the produced Al/PBV/p-Si diode structure, ideality factor (n), barrier height (Φb), series resistance (R
s), and interfacial density of states (N
ss) parameters were calculated. The differences between the results obtained with these methods arise from calculating the I-V characteristic of the methods from different regions. The ideality value of n for the produced diodes is much greater than one (n >  > 1). Deviating the calculated n value from 1 indicates possible mechanisms, such as generation-recombination effect, organic PBV layer, and interfacial states. It was observed that the electronic parameters of the Al/p-Si conventional junction can be controlled using an organic PBV interlayer.

Graphical abstract
PUF-Dilithium: Design of a PUF-Based Dilithium Architecture Benchmarked on ARM Processors
Authors: Aghapour Saeed , Ahmadi Kasra , Anastasova Mila , Azarderakhsh Reza , Mozaffari Kermani Mehran
Published: January 2025

Addressing the looming threat posed by quantum computers capable of breaching current public key cryptography schemes has become imperative. To this end, the National Institute of Standards and Technology (NIST) initiated a competition in Post-Quantum Cryptography, resulting in the selection of four schemes as the new standardized replacements, while a fourth round and an additional signature round is still ongoing. Notably, CRYSTALS-Dilithium, a lattice-based signature scheme, has exhibited promising resilience due to its efficiency and simplicity. Despite the finalization of standardization for these new four schemes, transitioning from classical cryptography to these alternatives necessitates further investigation and analysis. Comprehensive scrutiny of these newly standardized schemes is imperative, including considerations of implementation efficiency across various platforms and side-channel vulnerability analysis. This article introduces a novel design leveraging physical unclonable functions to bolster the physical security of CRYSTALS-Dilithium. Physical security is paramount in scenarios where network nodes are exposed to public scrutiny, potentially making them targets for adversaries. After discussing the advantages of our design compared to the original design, we implemented it on two different architectures, ARMv7 and ARMv8. Our results indicate substantial improvements in both security and performance compared to existing references. Moreover, noting the new competition initiated by the NIST in 2023 for new signatures (first round finalized in October 2024), potentially the proposed schemes can be adopted to the new standards set to be finalized in the coming years. These make our scheme not solely confined to the current standards and would be an important merit of the presented approaches.
Multiframe Target Localization With Strapdown Seeker Based on Self‐Adaptive L‐SHADE
Authors: Wu Jiayang , Yang Huabo , Yang Hao , Zhou Jiexin , Zhang Shifeng
Published: January 2025

Strapdown seekers are increasingly used in the terminal guidance for the advantages of small size and low cost. However, due to the coupling of the seeker with the missile and its limited field of view, there is a risk of losing the target. This paper proposes a multiframe fusion target localization method for missiles with strapdown seekers, which can still obtain the target location through the recorded state data even when the target is lost. First, some preprocessing approaches are applied to ensure the accuracy of target location estimation with the linear success history–based adaptive differential evolution (L‐SHADE) algorithm. Second, L‐SHADE is extended into the self‐adaptive linear success history–based adaptive differential evolution (SL‐SHADE) algorithm to speed up the calculation of the target location to be applied onboard for actual flight use. Third, the simulation verifies its efficiency and further investigates the effect of parameter settings on the algorithm performance.
Systematic Review of Methods for Individual Prediction of Postoperative Pain
Authors: Mogianos Krister , Åkeson Jonas , Persson Anna K. M.
Published: January 2025

Background: Acute postoperative pain is a common problem in clinical practice and merits attention considering its potential long‐term adverse effects. This systematic review covers current knowledge on methods for individual prediction of postoperative pain.

Methods: A systematic literature search was conducted using the PubMed, EMBASE, and CINAHL databases for original studies with adult patients published in English between 2016 and 2022. Inclusion required assessment of risk factors preoperatively and assessment of postoperative pain. No reviews, meta‐analyses, or study protocols were included, nor studies with outcomes other than pain or where risk factor analysis was not performed preoperatively. A two peer‐reviewed system was utilized using the screening and data collection tool Covidence, with a focus on new tools for preoperative pain prediction. The results were only analyzed qualitatively.

Results: The search yielded 1950 abstracts to be screened. In total, 208 articles were subjected to full‐text review, and 107 articles were included in the data synthesis of this review. The evaluated scientific methods were grouped and analyzed separately. Psychometric questionnaires and methods for quantitative sensory testing are still being studied. New methods proposed include the evaluation of pain induced by tourniquet inflation, venous cannulation, or pin‐prick stimulation, the analgesia/nociception index, electroencephalographic recording, and other new equipment developed for this purpose.

Conclusion: Various screening methods have been proposed to identify patients prone to postoperative pain. The focus has shifted from procedure‐specific to individualized strategies to improve early management of pain. However, many traditional predictive methods still have a questionable role in clinical practice.

Trial Registration: ClinicalTrials.gov identifier: CRD42022298479
Abstract A002: Flash proton re-irradiation and hypofractionation alleviate radiation-induced toxicity of the head and neck tissues in mice
Authors: Chowdhury Priyanka , Morcos George , Kim Michele , Lin Yuewei , Qin Ling , Metz James , Lin Alexander , Koumenis Costas
Published: January 2025

The effect of FLASH Proton Radiation therapy (F-PRT) in decreasing normal tissue toxicity while maintaining equal tumor control compared to Standard Proton Radiation therapy (S-PRT) has been previously investigated for head and neck tissues in mice using a single dose of either S-PRT/F-PRT. Here, we studied the effect of F-PRT following a hypo-fractionated regimen and in a re-irradiation setting. The head and neck area of C57Bl/6 mice was irradiated with a single dose of 12 Gy of F-PRT (128Gy/s) or S-PRT (0.95 Gy/s) and was followed with a hypo-fractionated re-irradiation scheme (6 Gy x 3). Mice with orthotopic tongue tumors were also irradiated with two different hypo-fractionated regimes of 8 Gy x 3 and 9 Gy x 3 respectively. Compared to the re-irradiation with S-PRT, F-PRT re-irradiated mice mitigate xerostomia by improving salivary flow. Histopathological analysis of the salivary gland showed increased acinar cell atrophy and individual cell death in the submandibular gland in mice re-irradiated with S-PRT compared to the ones re-irradiated with F-PRT. Re-irradiation with hypo-fractionated S-PRT showed a significant increase in the alveolar bone loss compared to F-PRT. Following irradiation with hypo-fractionated F-PRT mice with orthotopic tongue tumors significantly increases the overall survival compared to the ones irradiated with hypo-fractionated S-PRT. This study provides evidence of the sparing effect of F-PRT in minimizing radiation-induced head and neck tissue toxicity in a hypo-fractionated re-irradiation setting. The results support the efficacy of F-PRT for clinical application.

Citation Format: Priyanka Chowdhury, George Morcos, Michele Kim, Yuewei Lin, Ling Qin, James Metz, Alexander Lin, Costas Koumenis. Flash proton re-irradiation and hypofractionation alleviate radiation-induced toxicity of the head and neck tissues in mice. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A002.
Abstract B004: TIGIT blockade synergizes with PD-1 blockade and radiation therapy to enhance antitumor T-cell responses in breast cancer
Authors: Kim Seongmin , Jeon Seung Hyuck , Kim Yoomin , Park Nawon , Kim In Ah
Published: January 2025

Background: The study aims to investigate the role of TIGIT in immunosuppressive environment and evaluates the potential of TIGIT blockade (αTIGIT) to improve antitumor immune responses. Methods: We analyzed public transcriptomic data to identify the expression patterns of TIGIT on T cells in breast cancer and its prognostic impact. In addition, a murine TNBC model was utilized to evaluate the effects of PD-1 blockade (αPD-1), local RT, and αTIGIT. T cells in tumors, tumor-draining lymph nodes (TdLNs), and the spleen were analyzed to assess the antitumor immune responses upon the treatments. Results: The analysis revealed that TIGIT is predominantly expressed on T cells within breast cancer, and the expression of TIGIT was associated with poor outcomes in TNBC patients. In the murine model, the combination of αPD-1 and RT increased TIGIT+CD226+CD8+ TILs, which are crucial for the efficacy of αTIGIT. Adding αTIGIT to αPD-1 and RT (αPD-1/RT) resulted in a synergistic antitumor effect, characterized by increased infiltration of CD8+ TILs in both irradiated and nonirradiated tumors. The triple combination therapy (TCT) also resulted in a less exhausted phenotype among CD8+ TILs and increased the proliferation of splenic CD8+ T cells. Moreover, αTIGIT significantly reduced Tregs in tumors, TdLNs, and the spleen when combined with αPD-1/RT. Conclusion: αTIGIT exhibits synergistic effects when added to αPD-1/RT by increasing the infiltration and activation of CD8+ TILs while reducing Tregs. The study suggests that αTIGIT could be an effective strategy to enhance the antitumor efficacy of αPD-1 and RT in TNBC.

Citation Format: Seongmin Kim, Seung Hyuck Jeon, Yoomin Kim, Nawon Park, In Ah Kim. TIGIT blockade synergizes with PD-1 blockade and radiation therapy to enhance antitumor T-cell responses in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B004.
Abstract B009: Abscopal effect in metastatic melanoma: generating clinical insights from radiation-induced immune response
Authors: Phan Baovy N.
Published: January 2025

Despite modern advancements in systemic therapies, melanoma remains a highly malignant cancer, with persistent resistance to therapies such as checkpoint inhibitors and inhibitors of mutated BRAF V600E. Current therapy for targeting metastatic melanoma remains palliative radiation therapy, particularly directly at symptomatic sites. Extraordinarily, few case studies have reported locally targeted radiation resulting in regression of distal non-targeted lesions. This rare phenomenon was coined as the abscopal effect and presents with increasing frequency due to the advancement of systemic therapy. This narrative review attempts to understand the underlying mechanisms behind the abscopal effect through clinical data from 21 melanoma patients reported in 19 case studies. Case identification focused on patients who had progressed on systemic therapy before receiving radiation. Our study observed a mean total Gy of 34 (median total 30 Gy) and mean fractionation Gy of 8 (median fractionation 7.5 Gy) with increased frequency of reported abscopal effects with incorporation of modern systemic immunotherapies. The reviewed cases suggest that combining radiation with immunotherapy may enhance systemic tumor control, though further research is required to better understand the underlying mechanisms and improve treatment outcomes.

Citation Format: Baovy N. Phan. Abscopal effect in metastatic melanoma: generating clinical insights from radiation-induced immune response. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B009.
Abstract B018: GSK3β inhibition synergizes with radiation therapy to stimulate type-I interferon and anti-tumor effects in lung cancer
Authors: Braun Chen , Li Nan , Lin Steven H.
Published: January 2025

Radiation therapy (RT) is widely used to treat various tumor types to minimize the risk of recurrence. However, only a subset of patients experiences significant responses to RT, primarily due to inadequate immune responses within lung tumors. Therefore, there is a pressing need to develop innovative strategies to overcome tumor immunosuppression following RT. In this study, we investigated alternative mediators that could mitigate the effects of immunosuppression in lung cancer cells. We screened over 700 pharmacological inhibitors using an interferon beta-1(IFNβ1)-luciferase reporter system, identifying a group of glycogen synthase kinase 3 beta inhibitors (GSK3βi) that enhanced IFNβ1 expression. Notably, one GSK3βi agent, Kenpaullone, significantly induced IFNβ1 in multiple lung cancer cell lines. Compared to other GSK3β inhibitors, it exhibited superior synergy (over 20-fold) without inducing cellular cytotoxicity, even at high doses (30 µM). Furthermore, our syngeneic mouse models showed that GSK3βi and RT reduced tumor size more effectively than monotherapy and enhanced immunologic response in these tumors. This pharmacological-RT combination approach holds promise for improving the immunologic response to RT in lung cancer patients, potentially reducing tumor burden in those that already exhausted standard of care treatment options.

Citation Format: Chen Braun Nan Li, Steven H. Lin. GSK3β inhibition synergizes with radiation therapy to stimulate type-I interferon and anti-tumor effects in lung cancer. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B018
Abstract B032: Concurrent mutant KRAS inhibition and Stereotactic Body Radiation Therapy (SBRT) for preclinical KRASG12D-Driven Pancreatic Ductal Adenocarcinoma (PDAC) treatment
Authors: Wang Tianyu , Chen Jasper R , Pagan Vincent Bernard , Wang Liang , Guo Youming , Xia Ling , Singh Pankaj K. , Jiang Dadi , Koong Albert
Published: January 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is known for its extensive intrinsic and acquired resistance to standard of care therapies. With the KRASG12D mutation being a key driver, MRTX1133, a selective small molecule KRASG12D inhibitor, has demonstrated superior anti-tumor efficacy in preclinical PDAC models. However, tumor resistance to MRTX1133 is expected to occur inevitably. We hypothesize that combining MRTX1133 with stereotactic body radiation therapy (SBRT) can enhance local tumor control and minimize tumor recurrence after treatment. Methods: C57Bl/6J mice orthotopically transplanted with luciferase-tagged mouse KPC PDAC cells (KrasG12D; Trp53R172H; Pdx1-Cre) were assigned to 4 treatment groups: (1) vehicle, (2) SBRT (8 Gy x 5), (3) MRTX1133 (30 mg/kg I.P. BID), and (4) SBRT + MRTX1133. Tumor progression was monitored with IVIS luciferase imaging, and survival data were collected and analyzed using a Log-rank test. At the study endpoint, tumors as well as normal tissues were collected for histological analysis to evaluate immune cell infiltration, tumor proliferation and differentiation, and normal tissue toxicity. Results: SBRT + MRTX1133 combination therapy significantly enhanced local tumor control and prolonged mouse survival when compared to either MRTX1133 or SBRT alone. The median survival in the combination group exceeded 120 days, with significantly reduced tumor burden, suggesting a synergistic effect between SBRT and MRTX1133 in suppressing KPC tumor progress in vivo. Conclusion: Our findings demonstrate that MRTX1133 combined with SBRT improves tumor control and overall survival in a preclinical KRASG12D-driven PDAC tumor model. This combination strategy has the potential for clinical translation, offering a promising therapeutic approach to overcome resistance and improve outcomes in PDAC patients.

Citation Format: Tianyu Wang, Jasper R Chen, Vincent Bernard Pagan, Liang Wang, Youming Guo, Ling Xia, Pankaj K. Singh, Dadi Jiang, Albert Koong. Concurrent mutant KRAS inhibition and Stereotactic Body Radiation Therapy (SBRT) for preclinical KRASG12D-Driven Pancreatic Ductal Adenocarcinoma (PDAC) treatment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B032.
Abstract B033: Long-Term quality of life and hearing preservation after stereotactic radiosurgery for vestibular schwannoma
Authors: Siddiqui Shayzal , Lee Joseph S. , Abbo Julia , Cummings Jessica , Desai Avi , Grills Inga S. , Chen Peter Y. , Jacob Jeffrey , Lee Kuei C.
Published: January 2025

Purpose/Objective(s): The aim of this study is to evaluate the long-term quality of life (QOL) and hearing preservation outcomes following definitive single-fraction Gamma Knife stereotactic radiosurgery (GKSRS) for vestibular schwannoma (VS). Materials/Methods: Baseline and follow-up QOL and audiogram data were collected from our prospectively maintained institutional database of VS patients treated with single-fraction GKSRS from 2006 to 2023. QOL metrics included the Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), and the 36-Item Short-Form Survey (SF-36). Serviceable hearing preservation was classified according to the Gardner-Robertson scale using pure-tone average (PTA) and speech discrimination (SD). Linear mixed-effects models were constructed for each QOL metric over time. Results: A total of 388 patients (median age 61 years) were included with a median follow-up of 48 months. Median tumor size was 1.6 cm (interquartile range [IQR] 1.1-2.1 cm), with a median tumor volume of 0.6 cc (IQR 0.2-1.6 cc). Most patients received a prescription marginal dose of 12.5 Gy with a median cochlear mean dose of 2.7 Gy (IQR 1.9-3.8 Gy). Baseline median HHI, DHI, THI, and SF-36 scores were 28, 12, 12, and 73 respectively. Linear mixed-effects analyses indicated no statistically significant decline in any of these QOL metrics up to 7 years after GKSRS. Of patients with serviceable hearing at baseline, hearing preservation was maintained in 79% at 12 months, 67% at 2 years, and 68% at 3 years. Conclusion: GKSRS preserves long-term patient quality of life and serviceable hearing in the definitive management of VS.

Citation Format: Shayzal Siddiqui, Joseph S. Lee, Julia Abbo, Jessica Cummings, Avi Desai, Inga S. Grills, Peter Y. Chen, Jeffrey Jacob, Kuei C. Lee. Long-Term quality of life and hearing preservation after stereotactic radiosurgery for vestibular schwannoma. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B033.
Abstract IA02: Preserving tumor-draining lymph nodes in the era of immuno-oncology: Opportunities for precision chemo-radio-immunotherapy
Authors: Gutkind J. Silvio
Published: January 2025

The advent of the current cancer immunotherapy era based on the success of immune checkpoint blockade (ICB) inhibiting programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has revolutionized the standard of care for cancer treatment. However, the limited response rates to ICB across multiple cancer types suggest that new approaches and treatment strategies are needed in order to achieve durable cancer remission. This includes re-examining the possibility that standard of care treatments, including surgery and chemo-radiation, may compromise the tumor response when delivered in concert with ICB. In particular, many cancer types, including head and neck squamous cell carcinoma (HNSCC), have a propensity to metastasize to locoregional lymph nodes, and standard oncologic management often involves elective ablation of tumor draining lymph nodes (tdLN). In a recent study, we have used tobacco-signature HSNCC syngeneic mouse models and showed that tdLN ablation by surgery or radiation therapy limits the tumor ICB response, thereby worsening overall survival and repolarizing the tumor- and peripheral-immune compartments. Mechanistically, we provided evidence that cDC1 dendritic cells in the tumor lesions and tdLN are required for an effective anti-tumor immune response. Recently, we have cross-integrated large single-cell RNA-sequencing datasets from intratumoral immune cells and identified a novel mechanism by which antigen-specific CD8+ T cells promote intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. As a multipronged approach, we have also built on this computational pipeline to identify druggable oncogenic signaling networks that override cancer immune surveillance. Evidence will be presented that disruption of specific HNSCC driving signaling axes is sufficient to sculp the tumor immune microenvironment and disable their immune evasive mechanisms, thereby providing opportunities for the development of new precision therapies increasing the response ICB. The emerging information also provided a rationale for investigating the use of a new generation of radiation-sensitizing antibody drug conjugates targeting cancer-specific oncosignaling drivers, in combination with radiotherapy and ICB in the neoadjuvant setting, when tdLN are still intact. Ultimately, evidence will be presented supporting the future evaluation of spatially precise radiosensitizing antibody drug conjugate-directed chemo-radio-immunotherapy for precision cancer care in HNSCC and other malignancies.

Citation Format: J. Silvio Gutkind. Preserving tumor-draining lymph nodes in the era of immuno-oncology: Opportunities for precision chemo-radio-immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA02
Abstract IA05: Toward multi-modal foundation AI for precision oncology
Authors: Li Ruijiang
Published: January 2025

Clinical decision-making is a complex process that involves information obtained from multiple data modalities. Artificial intelligence (AI) approaches that can effectively integrate multi-modal data hold significant promise to advance clinical care. Two areas of success are imaging and digital pathology, where AI has shown great potential to improve cancer diagnosis and treatment. This talk will provide an overview on how AI can be used to extract information from imaging and pathology and identify prognostic and predictive biomarkers for personalized cancer treatment. In particular, I will present our recent work on building multi-modal foundation models for precision oncology.

Citation Format: Ruijiang Li. Toward multi-modal foundation AI for precision oncology. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA05