bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion
Authors: Yamashita Kyoko , Baba Satoko , Togashi Yuki , Dobashi Akito , Ae Keisuke , Matsumoto Seiichi , Tanaka Miwa , Nakamura Takuro , Takeuchi Kengo
Published: March 2023

Aims

Angiofibroma of soft tissue (AFST) is a benign tumour characterised by prominent arborizing blood vessels throughout the lesion. Approximately two‐thirds of AFST cases were reported to have AHRR::NCOA2 fusion, and only two cases have been reported to have other gene fusions: GTF2I::NCOA2 or GAB1::ABL1. Although AFST is included in fibroblastic and myofibroblastic tumours in the World Health Organization's 2020 classification, histiocytic markers, especially CD163, have been reported to be positive in almost all examined cases, and it still remains the possibility of a fibrohistiocytic nature of the tumour. Therefore, we aimed to clarify the genetic and pathological spectrum of AFST and identify whether histiocytic marker‐positive cells were true neoplastic cells.

Methods and results

We evaluated 12 AFST cases, which included 10 cases with AHRR::NCOA2 and two with AHRR::NCOA3 fusions. Pathologically, nuclear palisading, which has not been reported in AFST, was detected in two cases. Furthermore, one tumour resected by additional wide resection revealed severe infiltrative growth. Immunohistochemical analysis indicated varying levels of desmin‐positive cells in nine cases, whereas CD163‐ and CD68‐positive cells were diffusely distributed in all 12 cases. We also performed double immunofluorescence staining and immunofluorescence in situ hybridisation in four resected cases with >10% desmin‐positive tumour cells. The results suggested that the CD163‐positive cells differed from desmin‐positive cells with AHRR::NCOA2 fusion in all four cases.

Conclusion

Our findings suggested that AHRR::NCOA3 could be the second most frequent fusion gene, and histiocytic marker‐positive cells are not genuine neoplastic cells in AFST.
Morphophysiological and nitrogen metabolism responses of inoculated peanut cultivars with contrasting drought tolerance
Authors: Furlan Ana Laura , Morla Federico , Bianucci Eliana , Martin Matías , Ojeda Mayco , Marchesi Ana Clara , Navarro Verónica , Castro Stella
Published: March 2023

Legumes grow in temperate and warm climates, being susceptible to unpredictable episodes of water deficit. This study aimed to evaluate (i) morphology and N‐compound contents in roots and nodules, (ii) N and C contents in shoots and (iii) crop yield in two peanut cultivars with contrasting drought tolerance, inoculated with a reference N‐fixing strain and challenged by water deficit conditions. For that, seeds of two peanut cultivars, Granoleico (sensitive, S) and EC‐98 (tolerant, T) were inoculated with Bradyrhizobium sp. SEMIA6144 and 30 days after sowing, plants were separated into the experimental groups: control, drought stress and drought stress and subsequent rehydration. Although the results obtained on root anatomy and histology revealed differential responses between cultivars, they were not associated with tolerance traits in EC‐98 (T). In contrast, nodules of EC‐98 (T) showed invariable diameter and infection zone upon the exposition to drought stress and rehydration compared to nodules of Granoleico (S) plants exposed to the same treatments. EC‐98 (T) showed invariable contents of C in shoots and of nitrates and ureides in roots and nodules of stressed and rehydrated plants, an increase in total amino acids only in nodules of stressed plants and a small reduction in N‐content (compared with the sensitive cultivar). The status of these variables related to C‐ and N‐metabolism could be associated with an efficient biological nitrogen fixation. Besides, EC‐98 (T) yielded better both in a crop cycle with adequate water supply and in a dry year and the inoculation improved yield in both cultivars. Thus, the inoculation with N‐fixing bacteria is recommended for EC‐98 (T) in seasons with expected drought stress cycles in crops.
Memory functioning after hippocampal removal: Does side matter?
Authors: Lambrecq Virginie , Alonso Irene , Hasboun Dominique , Dinkelacker Vera , Davachi Lila , Samson Séverine , Dupont Sophie
Published: March 2023

To address the memory functioning after medial temporal lobe (MTL) surgery for refractory epilepsy and relationships with the side of the hippocampal removal, 22 patients with pharmaco‐resistant epilepsy who had undergone MTL resection (10 right/12 left) at the Salpêtrière Hospital were compared with 21 matched healthy controls. We designed a specific neuropsychological binding memory test that specifically addressed hippocampal cortex functioning, and left–right material‐specific lateralization. Our results showed that both left and right mesial temporal lobe removal cause a severe memory impairment, for both verbal and visual material. The removal of left medial temporal lobe causes worse memory impairment than the right removal regardless of the stimuli type (verbal or visual) questioning the theory of the hippocampal material‐specific lateralization. The present study provided new evidence for the role of both hippocampus and surrounding cortices in memory‐binding whatever the material type and also suggested that a left MTL removal is more deleterious for both verbal and visual episodic memory in comparison with right MTL removal.
A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis
Authors: Jones Anna E. , Wustefeld‐Janssens Brandan G.
Published: March 2023

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3 cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2 cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5‐year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2 cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2 cm. The association between tumour size group (<2 vs. ≥2 cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9–15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2 cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.
More Integrated than Ever? Long-Term Market and Policy Drivers of Intra-Asian Trade
Authors: Ayuso-Díaz Alejandro , Gómez-Plana Antonio G.
Published: March 2023

Since the Doha Round stalemate after 2001, trade liberalization has progressed through regional trade agreements (RTAs) and East and Southeast Asia is not unfamiliar with this. Before assessing the effectiveness of recent trade agreements, the long tradition of trade exchange in this region that has lasted for more than 2,000 years necessitates an understanding of the evolution of intra-Asian trade across history. In this regard, this study contributes to the literature examining whether present intra-Asian trade is more or less intense than before 1938. This research outperforms previous studies using a gravity model that controls for changes in GDP and trade costs in the region across four different time periods (between 1840 and 2018). The results show that contemporary regional trade in East and Southeast Asia is slightly less intense than before World War II. A second question addressed is the relevance of trade agreements after the 1985 Plaza Accord on trade integration, compared with market determinants. A second gravity model for regional imports after 1986 is regressed on both policy and market indicators, indicating that the latest wave of intra-Asian trade is characterized by trade complementarities that are fueled by regional foreign direct investment, and free trade agreements are less effective. This result is validated through a network analysis demonstrating the symbiosis between trade and investment flows in the region, which should be considered in RTAs that are in place or in negotiation to take intra-Asian trade beyond its historical limits.
Perceptual normalization for speaking rate occurs below the level of the syllable
Authors: Cychosz Margaret , Newman Rochelle S.
Published: March 2023

Because speaking rates are highly variable, listeners must use cues like phoneme or sentence duration to normalize speech across different contexts. Scaling speech perception in this way allows listeners to distinguish between temporal contrasts, like voiced and voiceless stops, even at different speech speeds. It has long been assumed that this speaking rate normalization can occur over small units such as phonemes. However, phonemes lack clear boundaries in running speech, so it is not clear that listeners can rely on them for normalization. To evaluate this, we isolate two potential processing levels for speaking rate normalization—syllabic and sub-syllabic—by manipulating phoneme duration in order to cue speaking rate, while also holding syllable duration constant. In doing so, we show that changing the duration of phonemes both with unique spectro-temporal signatures (/kɑ/) and more overlapping spectro-temporal signatures (/wɪ/) results in a speaking rate normalization effect. These results suggest that when acoustic boundaries within syllables are less clear, listeners can normalize for rate differences on the basis of sub-syllabic units.
A Review of Sedentary Behavior Assessment in National Surveillance Systems
Authors: Harvey Danielle L. , Milton Karen , Jones Andy P. , Atkin Andrew J.
Published: March 2023

Background: Temporal changes in sedentary behavior patterns reflect the evolving nature of our built and social environments, particularly the expanding availability of electronic media. It is important to understand what types of sedentary behavior are assessed in national surveillance to determine whether, and to what extent, they reflect contemporary patterns. The aims of this review were to describe the characteristics of questionnaires used for national surveillance of sedentary behavior and to identify the types of sedentary behaviors being measured. Method: We reviewed questionnaires from national surveillance systems listed on the Global Observatory for Physical Activity (GoPA!) country cards to locate items on sedentary behavior. Questionnaire characteristics were categorized using the Taxonomy of Self-reported Sedentary Behavior Tools (TASST). The purpose and type of sedentary behaviors captured were classified using the Sedentary Behavior International Taxonomy (SIT). Results: Overall, 346 surveillance systems were screened for eligibility, of which 93 were included in this review. Most questionnaires used a single-item direct measure of sitting time (n = 78, 84%). Work and domestic were the most frequently captured purposes of sedentary behavior, while television viewing and computer use were the most frequently captured types of behaviors. Conclusion: National surveillance systems should be periodically reviewed in response to evidence on contemporary behavior patterns in the population and the release of updated public health guidelines.
Do no unconscious harm
Authors: Ortega Rodrigo Pérez
Published: March 2023

Implicit bias can degrade health care. Now, researchers are finding new ways to recognize and mitigate it
Ancient DNA upends European prehistory
Authors: Curry Andrew
Published: March 2023

Genes reveal striking diversity within similar ice age cultures
Antibody-based defense may protect plants from disease
Authors: Stokstad Erik
Published: March 2023

A “creative” strategy to keep crops healthy borrows key pathogen detectors from the animal immune system
Chromosomal Position of Ribosomal Protein Genes Affects Long-Term Evolution of Vibrio cholerae
Authors: Larotonda Leticia , Mornico Damien , Khanna Varun , Bernal-Bayard Joaquín , Ghigo Jean-Marc , Val Marie-Eve , Comerci Diego , Mazel Didier , Soler-Bistué Alfonso
Published: March 2023

The bacterial chromosome harbors several entangled processes such as replication, transcription, DNA repair, and segregation. Replication begins bidirectionally at the replication origin (
oriC
) until the terminal region (
ter
) organizing the genome along the
ori-ter
axis gene order along this axis could link genome structure to cell physiology.
Metatranscriptomics Reveals Sequential Expression of Genes Involved in the Production of Melanogenesis Inhibitors by the Defined Microbial Species in Fermented Unpolished Black Rice
Authors: Sangkaew Orrarat , Prombutara Pinidphon , Roytrakul Sittiruk , Yompakdee Chulee
Published: March 2023

Fermentation of food is a metabolic process through the action of enzymes from certain microorganisms. Although roles of the microbial community in the fermented food were investigated using metatranscriptomic approach in terms of flavors, but no study has been reported so far on the function of the microorganisms on producing compounds with a melanogenesis inhibition activity.
Insights into the Biocontrol Function of a Burkholderia gladioli Strain against Botrytis cinerea
Authors: Wang Dan , Luo Wan-Zhen , Zhang Dan-Dan , Li Ran , Kong Zhi-Qiang , Song Jian , Dai Xiao-Feng , Alkan Noam , Chen Jie-Yin
Published: March 2023

Searching the economical, eco-friendly and efficient biological control measures is the key to protecting crops from pathogenic fungi. The species of
Burkholderia
genus are widespread in the natural environment, of which nonpathogenic members have been reported to have great potential for biological control agents and biofertilizers for agricultural application.
Burkholderia gladioli
strains, however, need more study and application in the control of pathogenic fungi, plant growth promotion, and induced systemic resistance (ISR).
Supplemental Material: The life and death of a subglacial lake in West Antarctica
Authors: Siegfried Matthew J. , al. et
Published: March 2023

Supplemental Figures S1–S3 and Table S1, and extended information about our GPS, satellite altimetry, ApRES, distributed temperature sensing, and sediment core statistical methods. 
An Efficient Fully Automated Lung Cancer Classification Model Using GoogLeNet Classifier
Authors: Samundeeswari P. , Gunasundari R.
Published: March 2023

Lung cancer (LC) causes the most superior mortality rate globally. Medical experts diagnose the disease and stage with prolonged procedures. Early diagnosis is only a promising way to improve the survival rate. Previously, an enormous investigation was executed to detect LC by different artificial intelligence systems. Still, detection accuracy has to be improved as equal to expert diagnosis. They were not majorly focused on LC type and TNM stage prediction. However, the treatment planning is strictly based on one cancer cell type and the survival rate is closely related to the stage. Hence in this work, a new Fully Automated Lung Cancer Classification System (FALCCS) using GoogLeNet classifier is proposed to detect non-small cell LC along with its types and stages. Initially, our previous segmentation work is adapted to automatically extract tumor regions from CT images. Then, a new post-processing technique is introduced to enhance image features and create required training databases. Using deep learning techniques, the proposed system used GoogLeNet to create five new automatic classifiers to perform LC detection, type, T state, N state and M state prediction. Finally, TNM state classifier’s outputs were gathered and combined to find the LC stage by referring TNM staging system eighth edition. The proposed system successfully put a novel step towards TNM stage classification as equal to expert’s diagnosis. Experimental results show that the proposed system achieved the superior cancer detection accuracy of 99.2% simultaneously with the type and final TNM stage categorizer resulting in 96.5% and 90.5% of accuracy. These results illustrate the proposed classifier’s efficacy more than the existing methods.
Gacha Game Analysis and Design
Authors: Chen Canhui , Fang Zhixuan
Published: March 2023

Gacha game is a special opaque selling approach, where the seller is selling gacha pulls to the buyer. Each gacha pull provides a certain probability for the buyer to win the gacha game reward. The gacha game has been enthusiastically embraced in numerous online video games and has a wide range of potential applications.In this work, we model the complex interaction between the seller and the buyer as a Stackelberg game, where the sequential decision of the buyer is modeled as a Markov Decision Process (MDP). We define the whale property in the context of gacha games. Then, we show that this is the necessary condition to achieve optimal revenue. Moreover, we provide the revenue-optimal gacha game design and show that it is equivalent to the single-item single-bidder Myerson auction.We further explore two popular multi-item gacha games, namely, the sequential multi-item gacha game and the banner-based multi-item gacha game. We also discuss the subsidies in the gacha game and demonstrate how subsidies may encourage the buyer to engage in grinding behavior. Finally, we provide a case study on blockchain systems as gacha games.
Detecting and Measuring Security Risks of Hosting-Based Dangling Domains
Authors: Zhang Mingming , Li Xiang , Liu Baojun , Lu Jianyu , Zhang Yiming , Chen Jianjun , Duan Haixin , Hao Shuang , Zheng Xiaofeng
Published: March 2023

Public hosting services provide convenience for domain owners to build web applications with better scalability and security. However, if a domain name points to released service endpoints (e.g., nameservers allocated by a provider), adversaries can take over the domain by applying the same endpoints. Such a security threat is called "hosting-based domain takeover''. In recent years, a large number of domain takeover incidents have occurred; even well-known websites like the subdomains of microsoft.com have been impacted. However, until now, there has been no effective detection system to identify these vulnerable domains on a large scale. In this paper, we fill this research gap by presenting a novel framework, HostingChecker, for detecting domain takeovers. Compared with previous work, HostingChecker expands the detection scope and improves the detection efficiency by: (i) systematically identifying vulnerable hosting services using a semi-automated method; and (ii) effectively detecting vulnerable domains through passive reconstruction of domain dependency chains. The framework enables us to detect the subdomains of Tranco sites on a daily basis. We evaluate the effectiveness of HostingChecker and eventually detect 10,351 subdomains from Tranco Top-1M apex domains vulnerable to domain takeover, which are over 8× more than previous findings. Furthermore, we conduct an in-depth security analysis on the affected vendors, like Amazon and Alibaba, and gain a suite of new insights, including flawed implementation of domain ownership validation. Following responsible disclosure processes, we have reported issues to the security response centers of affected vendors, and some (e.g., Baidu and Tencent) have adopted our mitigation.
Detecting and Measuring Aggressive Location Harvesting in Mobile Apps via Data-flow Path Embedding
Authors: Lu Haoran , Zhao Qingchuan , Chen Yongliang , Liao Xiaojing , Lin Zhiqiang
Published: March 2023

Today, location-based services have become prevalent in the mobile platform, where mobile apps provide specific services to a user based on his or her location. Unfortunately, mobile apps can aggressively harvest location data with much higher accuracy and frequency than they need because the coarse-grained access control mechanism currently implemented in mobile operating systems (e.g., Android) cannot regulate such behavior. This unnecessary data collection violates the data minimization policy, yet no previous studies have investigated privacy violations from this perspective, and existing techniques are insufficient to address this violation. To fill this knowledge gap, we take the first step toward detecting and measuring this privacy risk in mobile apps at scale. Particularly, we annotate and release thefirst dataset to characterize those aggressive location harvesting apps and understand the challenges of automatic detection and classification. Next, we present a novel system, LocationScope, to address these challenges by(i) uncovering how an app collects locations and how to use such data through a fine-tuned value set analysis technique,(ii) recognizing the fine-grained location-based services an app provides via embedding data-flow paths, which is a combination of program analysis and machine learning techniques, extracted from its location data usages, and(iii) identifying aggressive apps with an outlier detection technique achieving a precision of 97% in aggressive app detection. Our technique has further been applied to millions of free Android apps from Google Play as of 2019 and 2021. Highlights of our measurements on detected aggressive apps include their growing trend from 2019 to 2021 and the app generators' significant contribution of aggressive location harvesting apps.
PEACH: Proactive and Environment-Aware Channel State Information Prediction with Depth Images
Authors: Ayvasik Serkut , Mehmeti Fidan , Babaians Edwin , Kellerer Wolfgang
Published: March 2023

Up-to-date and accurate prediction of Channel State Information (CSI) is of paramount importance in Ultra-Reliable Low-Latency Communications (URLLC), specifically in dynamic environments where unpredictable mobility is inherent. CSI can be meticulously tracked by means of frequent pilot transmissions, which on the downside lead to an increase in metadata (overhead signaling) and latency, which are both detrimental for URLLC. To overcome these issues, in this paper, we take a fundamentally different approach and propose PEACH, a machine learning system which utilizes environmental information with depth images to predict CSI amplitude in beyond 5G systems, without requiring metadata radio resources, such as pilot overheads or any feedback mechanism. PEACH exploits depth images by employing a convolutional neural network to predict the current and the next 100 ms CSI amplitudes. The proposed system is experimentally validated with extensive measurements conducted in an indoor environment, involving two static receivers and two transmitters, one of which is placed on top of a mobile robot. We prove that environmental information can be instrumental towards proactive CSI amplitude acquisition of both static and mobile users on base stations, while providing an almost similar performance as pilot-based methods, and completely avoiding the dependency on feedback and pilot transmission for both downlink and uplink CSI information. Furthermore, compared to demodulation reference signal based traditional pilot estimation in ideal conditions without interference, our experimental results show that PEACH yields the same performance in terms of average bit error rate when channel conditions are poor (using low order modulation), while not being much worse when using higher modulation orders, like 16-QAM or 64-QAM. More importantly, in the realistic cases with interference taken into account, our experiments demonstrate considerable improvements introduced by PEACH in terms of normalized mean square error of CSI amplitude estimation, up to 6 dB, when compared to traditional approaches.
A Novel Electrochemical Immunosensor Based on Anti-IgY and PLA/PEG Nanofibrous Mats Used for Allergens Detection in Farinaceous Products
Authors: Alves C. F. , Notário A. F. O. , Correia L. I. V. , Ferreira K. N. , Araujo K. C. L. , Taketomi E. A. , Souza G. R. L. , Medeiros E. S. , Cunha-Júnior J. P. , Alves R. P. , Goulart L. R.
Published: March 2023

The present study focuses on the first electrochemical immunosensor built with polymeric mats enriched with nanomaterials, targeting the dust mite protein, for the detection of allergens in flour sources with important implications in allergic reactions. As a proof-of-concept, we have used the Blo t 5 allergen from Blomia tropicalis (target) and established electrochemical parameters to recognize and detect the specific allergen using a polyclonal immunoglobulin (Ig) Y (probe). Detection was performed in a portable potentiostat (EmStat) using a graphite screen-printed electrode. For that, the nanofibrous mats of poly(lactic acid)/poly(ethylene glycol) (PLA/PEG), and carbon nanotubes (CNTs) were placed in contact with the surface of the electrodes. The functionalization that occurs through the deposition of the polymer was induced through the passage of current. Subsequently, the modification was validated by cyclic voltammetry (CV) readings and ferri/ferrocyanide was used as a redox indicator in CV analyses. The novel immunosensor was able to discriminate between allergen-contaminated and uncontaminated farinaceous samples. The immunosensor displays high sensitivity detecting up to 50 μg ml−1 in the calibration curve with a linear response between 5 and 500 μg ml−1. The new biosensor shows great potential in the detection of farinaceous contaminants in laboratories, food factories and in the field.
Integration of respiratory physiology and clinical reasoning in the early years of a medical curriculum: engaging with students in a large classroom setting
Authors: Hakim Amir , Ricketts William , Pfeffer Paul , Ashworth Rachel
Published: March 2023

The development of teaching methods that support integrated learning and build student confidence is a priority. An audience response system was used to engage early year medical students in large classes in preparation for teaching within a hospital setting. Results showed high levels of student engagement and a greater appreciation for the link between theory and practice. This study describes a simple, active, and integrated method of learning that improves student confidence in clinical reasoning.
Effects of biological sex and oral contraceptive pill use on cutaneous microvascular endothelial function and nitric oxide-dependent vasodilation in humans
Authors: Turner Casey G. , Stanhewicz Anna E. , Nielsen Karen E. , Otis Jeffrey S. , Feresin Rafaela G. , Wong Brett J.
Published: March 2023

This study supports differences in microvascular endothelial function and nitric oxide (NO)-dependent vasodilation between women in low hormone phases of two hormonal exposures and men. However, when separated into subgroups of hormonal exposure, women during placebo pills of oral contraceptive pill (OCP) use have greater NO-dependent vasodilation than naturally cycling women in their menstrual phase and men. These data improve knowledge of sex differences and the effect of OCP use on microvascular endothelial function.
An Improved Topology of Isolated Bidirectional Resonant DC-DC Converter Based on Wide Bandgap Transistors for Electric Vehicle Onboard Chargers
Authors: Shahed Md. Tanvir , Rashid A. B. M. Harun-Ur
Published: March 2023

This article proposes an improved topology for an isolated bidirectional resonant DC-DC converter for electric vehicle (EV) onboard chargers. As opposed to the conventional capacitor-inductor-inductor-inductor-capacitor (CLLLC) resonant converter, the proposed converter’s resonant circuit is composed of a capacitor-inductor-inductor-inductor (CLLL) structure, whose inductances, except the capacitor, can be fully integrated with the leakage and mutual inductances of the high-frequency transformer (HF). Therefore, this offers a smaller size, lower costs, minimal power loss, and eventually higher efficiency. Again, the proposed converter design is based on wide bandgap (WBG) transistor switches that operate at MHz-level switching frequency to achieve high power density, high efficiency, and high compactness. A discrete-time proportional integral derivative (PID) controller has been designed using the phase-shifted pulse width modulation (PSPWM) technique to assure closed-loop control of the proposed CLLL converter. The PID controller parameters have been optimized using both the genetic algorithm (GA) and particle swarm optimization (PSO) algorithm and a comparative analysis has been presented between the two algorithms. To achieve fast switching with very little switching loss, the converter is simulated with several wide bandgap (WBG) switching devices. A performance comparison with conventional Si-based switching devices is also provided. A precise power loss model of the semiconductor switches has been devised from the manufacturer’s datasheet to achieve a perfect thermal design for the converter. A 5 kW CLLL converter with an input range of 400–460 V direct current (DC) and an output range of 530–610 V DC, and a switching frequency of 1 MHz has been designed and investigated under various loading scenarios. Gallium nitride (GaN) switching device-based designs achieved the highest levels of efficiency among the switching devices. The efficiency of this device is 97.40 percent in charging mode and 96.67 percent in discharging mode.
Serum Protein Electrophoretic in Children
Authors: Hadrach Safaa , Benazzouz Imane
Published: March 2023

Serum protein electrophoresis is a simple, reliable, and specific method used for separation of serum proteins. This study consisted to detect, at pediatric cases, pathological profiles of serum proteins by capillary electrophoresis and interpret any anomalies. The study was performed on 81 sera collected from pediatric subjects admitted at the Abderrahim Harouchi Children’s Hospital in Casablanca. Study results revealed 72 specific pathological electrophoretic patterns for acute and chronic inflammatory response (35 children), hypogammaglobulinemia (3), polyclonal hypergammaglobulinemia (23), hypoalbuminemia (5), agammaglobulinemia (1), and other medical conditions (2). No cases of alpha-1-antitrypsin deficiency and nephrotic syndrome by electrophoresis were highlighted. Serum protein electrophoresis in children is recommended as a diagnostic technique for increasing the accuracy of the diagnosis in acute, subacute, and chronic inflammatory diseases, liver disease, and cases of immunodeficiency.
Abstract CC1-1-2: To clip or not to clip (Part 2)
Authors: Galimberti Viviana
Published: March 2023

Neoadjuvant chemotherapy (NAC) changed the breast surgery approach and increased indications in recent years. NAC allows to downstage the primary tumor and also may clear the axilla of lymph node metastases in some patients. In fact, NAC allows de-escalation of surgery: not only resulted in an increase in conservative surgery in 40%, which was the initial goal of chemotherapy, but in particular it allows for a reduction in axillary surgery. Furthermore, in relation to the molecular characteristics of the tumors we can have a pathological complete response (pCR) ranging from 20 to 80%. In node-positive patients who converted to cN0 different prospective studies ACOSOG Z1071, SENTINA, SN FNAC and GANEA 2, have demonstrated that the FNR of the SNB was high, more than the acceptable 10%. Therefore, strategies to reduce the FNR treatment in cN+ patients are being investigated: is to remove more than three negative axillary lymph nodes or marking of positive axillary nodes with a tattoo or clip, the so-called target axillary dissection (TAD), to document their removal. But all the effort to reduce the FNR rate do not have clinical prognostic significance. This has already been demonstrated in the literature in different randomized trials with long term follow up. The 10-year follow-up of our study confirmed our preliminary data that the use of standard sentinel node biopsy (SNB) without the use of clip is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome. In fact, the axillary recurrences found were less than 2% in particular in the group that started from a positive axilla were 1.8 %, if we considered that 2 of them had a micrometastatic SN and refused the AD, but if we considered only those with a negative SN the percentage drops to 0.9% Similar positive data with different follow up were also confirmed by other studies that used SNB alone without TAD. All these studies data, with now comforting results on the follow up, confirm that SN surgery alone for selected patients who have an excellent response to NAC is not oncologically inferior to AD during a short- and long-term follow-up.

Citation Format: Viviana Galimberti. To clip or not to clip (Part 2) [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 CC1-1-2.
Abstract ED1-1: What are PROs and evidence for benefit?
Authors: Rosenberg Shoshana
Published: March 2023

Patient-reported outcomes (PROs) are self-reported assessments provided directly by patients. PROs can be used for research, to tailor and improve clinical and supportive care, and for quality assessment purposes. It is well-established that PROs, rather than clinician evaluations, better capture the patient experience. Additionally, there is growing evidence supporting the routine incorporation of PROs into clinical practice. In particular, the use of PRO-based interventions is associated with improved symptom management, enhanced patient-provider communication, and better outcomes, including quality of life and survival, in patients with advanced cancer. Among patients in the post-active treatment and survivorship phase of care, PROs are critical in identifying and understanding late and long-term effects of treatment, identifying unmet needs, and determining if survivors are receiving appropriate follow-up care. There are also data in the survivorship setting demonstrating how PROs can predict other outcomes, such as adherence to aromatase inhibitors in breast cancer survivors. Careful consideration of age (e.g., pediatric vs. adult measures), race and ethnicity (e.g., was the measure validated in a diverse and representative population), language (e.g., was the measure validated in other languages), literacy level (e.g., was the measure written for individuals with low literacy levels), mode of delivery (e.g., paper vs. tablet), and participant burden (e.g., does the assessment take a reasonable amount of time) when selecting PROs is critical to ensure that the information learned is generalizable and that the benefit patients can gain through the incorporation of PROs into cancer care is equitable.

Citation Format: Shoshana Rosenberg. What are PROs and evidence for benefit? [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 ED1-1.
Abstract ED12-2: Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond
Authors: Lord Christopher
Published: March 2023

Although PARP inhibitors (PARPi) deliver significant and sustained anti-tumour responses in those with HR defective cancers, PARPi resistance is a common clinical phenomenon and limits the overall effectiveness of these agents. I will discuss how reversion mutations in BRCA1 and BRCA2 cause PARPi resistance and how the emergence of reversions might be targeted by immune responses against the neopeptides caused by reversion mutations. I will also discuss how other mechanisms of PARPi resistance such as 53BP1/Shieldin complex dysfunction could be targeted by evolutionary “double binds” using drugs such as Pol-theta inhibitors that exploit new vulnerabilities put in place by emerging PARPi resistance mechanisms

Citation Format: Christopher Lord. Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond [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 ED12-2.
Abstract ED2-1: Cancer risks in patients with moderate penetrance gene mutations
Authors: Shah Payal
Published: March 2023

The genetic landscape of inherited breast cancer is broad, spanning from high and moderate penetrance pathogenic variants in breast cancer susceptibility genes, to polygenic risk associated with the cumulative impact of single nucleotide polymorphisms (SNPs). This educational session will review the landscape of inherited breast cancer. The discussion will then focus on breast cancer susceptibility genes associated with moderately elevated risks of breast cancer including PALB2, ATM, CHEK2 and others. Recent data informing quantitative and qualitative cancer risk estimates, management recommendations, therapeutic implications, and reproductive considerations will be reviewed. Emerging issues and treatment strategies under investigation will also be discussed.

Citation Format: Payal Shah. Cancer risks in patients with moderate penetrance gene mutations [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 ED2-1.
Abstract ED3-1: Updates in the pathology of PABC
Authors: Siziopikou Kalliopi
Published: March 2023

Updates in the Pathology of Pregnancy Associated Breast Cancer (PABC)

Pregnancy associated breast cancer is defined as a breast cancer diagnosed during gestation, lactation and within 1 to 5 years postpartum. While the development of malignancy during pregnancy is rare, the incidence is increasing; breast cancer is one of the most common cancers diagnosed during pregnancy and the postpartum period occurring in up to 1 in 3000 deliveries. Of interest, breast cancer is the leading cause of cancer death in US women age 15-29. Pregnancy has a dual effect on breast cancer development: on one hand cancer protective and on the other cancer promoting. While a number of hypotheses have been proposed over the years to explain these effects, the most likely hypothesis for the development of PABC is the involution hypothesis. This hypothesis proposes that the involution pathways activated during pregnancy and the immediate postpartum period are remodeling programs similar to wound healing and inflammation that may be associated with tumor development and progression. Although PABCs can be any subtype of breast carcinomas, they are usually invasive ductal carcinomas of high tumor grade and large tumor size with higher stage at presentation and higher rates of lymph node involvement. Most PABCs are hormone receptor negative tumors with high Ki-67 proliferation rates; most frequently, they are either triple negative or HER2-positive carcinomas. A number of studies have shown that PABCs have different genomic signatures than the non-PABC tumors with PABCs having an increased expression of immune response mediators. Better understanding of the molecular pathways of tumor initiation and progression and prompt diagnosis and state-of-art treatment protocols in PABC is expected to lead to better outcomes for these young breast cancer patients.

Citation Format: Kalliopi Siziopikou. Updates in the pathology of PABC [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 ED3-1.
Abstract ED4-3: Inflammatory Breast Cancer
Authors: Lynce Filipa
Published: March 2023

Inflammatory Breast Cancer (IBC) has an incidence of 1-5% among all breast cancers diagnosed within the USA, yet it accounts for a disproportionately high rate of mortality, leading to up to 10% of all breast cancer related deaths. Although IBC can present with any receptor status in terms of estrogen, progesterone, and human epidermal growth factor 2 (HER2), there is a higher proportion of HER2 positive cases compared to non-IBC. Given the distinct difference in outcome, it is important to differentiate IBC from more indolent locally advanced non-IBC with secondary inflammatory features. Despite ongoing efforts to identify molecular markers specific for IBC, the underlying tumor biology and genomic drivers of progression remain largely unknown. In this session we will review tumor-intrinsic signaling pathways, the role of the tumor microenvironment and clinical trials with combination therapies to inform future biomarkers of disease progression in IBC.

Citation Format: Filipa Lynce. Inflammatory 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 ED4-3.
Abstract ED7-2: Multiplex spatial proteomic profiling
Authors: Rimm David
Published: March 2023

Multiplex spatial analysis is touted as a potential solution for tissue biomarkers for prognostic and companion diagnostic applications. Spatial analysis infers maintaining the location of a biomolecule so that both its amount and context can contribute to the information obtained. Immunohistochemistry (IHC) is the archetypal method of spatial profiling and the only application that has made it to the clinic. In this session, we will discuss technologies based on IHC, but that allow assessment of at least two, and as many as 100 or more proteins within the cell or molecular compartment that maintains spatial context. The simplest and most common approach is multiplex immunofluorescence, followed by a number of next generation techniques that use alternative labeling of the antibodies or cycling strategies or both to generate spatially informed data. Excluding Mass spectrometry-based methods, still in early stages, the highest “plex” method for protein is digital spatial profiling. Digital spatial profiling (DSP) uses a molecular method to define spatial compartments which is different from other high-plex methods that use cell segmentation, an image analysis method that largely depends on the presence of a cell nucleus in the image. As a result, the DSP method allows assessment of both cellular and non-cellular stromal compartments. DSP and other high-plex methods that will be discussed are thought to be best used as biomarker discovery tools, that might find biomarkers that can be measured with a more traditional approach for assessment in the clinic.

Citation Format: David Rimm. Multiplex spatial proteomic profiling [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 ED7-2.
Abstract ED9-3: Effects of age on the tumor microenvironment
Authors: McAllister Sandra
Published: March 2023

Dr. McAllister’s translational research group studies breast cancer as a systemic disease with an emphasis on the role of immune fitness in disease control and response to therapy. In this education session, Dr. McAllister will introduce the concept of “immunological age”. She will discuss her team’s ongoing efforts to understand how age sets the stage for triple-negative breast cancer (TNBC) progression and response to immune checkpoint blockade therapy.

Her team was the first to report that bone marrow derived immune cells from 8–10-week-old young mice promote more aggressive TNBC growth when transferred to 12–15-month-old aged mice (Marsh, et al., Cancer Research, 2016). They subsequently identified cellular and molecular mechanisms that promote aggressive disease, as typically observed in younger individuals. Likewise, her group was the first to report that immune checkpoint blockade therapy is less effective in older mice with TNBC and discovered a treatment strategy that improved outcomes in pre-clinical TNBC models (Sceneay, et al., Cancer Discovery, 2019). The same tumor cellular and molecular pathways that stratified by age in their pre-clinical models also defined age-stratified differences between younger (under 40) and older (over 65) TNBC patients in the METABRIC dataset.

She will present her team’s new work on functional aspects of immunological age in TNBC and the ongoing efforts of the Older Women with Breast Cancer Research and Treatment Team at the Dana-Farber/Brigham Cancer Center. Ultimately, she and her team wish to eliminate age- and race-based disparities in breast cancer outcomes.

Citation Format: Sandra McAllister. Effects of age on the tumor microenvironment [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 ED9-3.
Abstract F3-2: Fasting and caloric restriction mimetics stimulate anticancer immunosurveillance
Authors: Kroemer Guido
Published: March 2023

Fasting and caloric restriction induce metabolic and neuroendocrine changes that have major anti-inflammatory and immunostimulatory effects. Some of these effects are mediated by a raise of ketone bodies (such as 3-hydroxybutyrate) and a decrease in circulating insulin-like growth factor-1 (IGF1), meaning that administration of 3-hydroxybutyrate and pharmacological inhibition of IGF1 receptor can mimic some of the beneficial effects of fasting on anticancer immunosurveillance. "Caloric restriction mimetics" (CRMs) are small molecules that induce autophagy through the same pathways that are activated by fasting, including the reduction of cytoplasmic protein acetylation. We have accumulated evidence that CRMs can stimulate anticancer immunosurveillance either as single agents (for the prevention of malignant disease) or in combination with chemotherapy and/or immune checkpoint blockade (for the treatment of established cancers). In preclinical experiments, fasting and CRMs have also been used for the prevention or treatment of hormone-induced breast cancer, and these effects are coupled to an increase in the T lymphocyte-mediated anticancer immune response. We have developed an in vitro screening assay to identify novel pharmacological agents that act as CRMs. Such neo-CRMs can be successfully employed to improve anticancer immunosurveillance in preclinical experiments.

Citation Format: Guido Kroemer. Fasting and caloric restriction mimetics stimulate anticancer immunosurveillance [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 F3-2.