bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sex and ageing on the human respiratory muscle metaboreflex
Authors: Leahy Michael G. , Kipp Shalaya , Benbaruj Jenna M. , Charkoudian Nisha , Foster Glen E. , Koehle Michael S. , Sheel A. William
Published: December 2022

Intense inspiratory muscle work evokes a sympathetically mediated pressor reflex, termed the respiratory muscle metaboreflex, in which young females demonstrate an attenuated response relative to males. However, the effects of ageing and female sex hormones on the respiratory muscle metaboreflex are unclear. We tested the hypothesis that the pressor response to inspiratory work would be similar between older males and females, and higher relative to their younger counterparts. Healthy, normotensive young (26 ± 3 years) males (YM; n = 10) and females (YF; n = 10), as well as older (64 ± 5 years) males (OM; n = 10) and females (OF; n = 10), performed inspiratory pressure threshold loading (PTL) to task failure. Older adults had a greater mean arterial pressure (MAP) response to PTL than young (P < 0.001). YF had a lower MAP compared to YM (+10 ± 6 vs. +19 ± 15 mmHg, P = 0.026); however, there was no difference observed between OF and OM (+26 ± 11 vs. +27 ± 11 mmHg, P = 0.162). Older adults had a lower heart rate response to PTL than young (P = 0.002). There was no effect of sex between young females and males (+19 ± 9 and +27 ± 11 bpm, P = 0.186) or older females and males (+17 ± 7 and +20 ± 7 bpm, P = 0.753). We conclude the respiratory muscle metaboreflex response is heightened in older adults, and the sex effect between older males and post‐menopause females is absent, suggesting an effect of circulating sex hormones.

image

Key points

The arterial blood pressure response to the respiratory muscle metaboreflex is greater in older males and females.

Compared to sex‐matched young individuals, there is no sex differences in the blood pressure response between older males and post‐menopause females.

Our results suggest the differences between males and females in the cardiovascular response to high levels of inspiratory muscle work is abolished with reduced circulating female sex hormones.
Deeper Integration or Open Regionalism in the Indian Ocean Rim Association (IORA): A CGE Approach
Authors: Akintola Abdallah , Boughanmi Houcine , Antimiani Alessandro , Zaibet Lokman , Kotagama Hemesiri
Published: December 2022

The Indian Ocean Rim Association (IORA) is a regional association based on the principle of open regionalism to promote liberalization through trade and investment facilitation. This study compares two main scenarios with the ingredients of a deeper regional integration compared to the IORA's present open regionalism status. Scenario I evaluates the effects of gradual tariff cuts on IORA, while Scenario II combines the impact of tariff cuts, non-tariff measures (NTM) reduction, and trade facilitation. A recent recursive dynamic model, called Global Trade Analysis Project recursive dynamic model (GTAP-RD), was used to understand the adjustment path. The result shows welfare gain for all IORA countries when a trade liberalization involving tariff cuts is complemented with NTM reduction and trade facilitation. In addition, the "NTM spillover" effect on some non-IORA members (the rest of Gulf Cooperation Council, the rest of Greater Arab Free Trade Agreement, and the United Kingdom) was observed. The results suggest that IORA has more to gain if it involves a deeper regional integration than the present form of open regionalism.
Optical Measurement of Roller Slip, Tilt, and Skew in a Spherical Roller Bearing
Authors: Shafiee Abbas , Russell Thomas , Lorenz Steven J. , Sadeghi Farshid , Wilmer Matthew G.
Published: December 2022

In this study, a novel test rig was designed and developed to investigate roller slip, tilt, and skew in a spherical roller bearing (SRB). The test rig utilized a double-row 22313 SRB and was designed to allow for direct visual access to each row. A high-speed camera was used to capture the motion and angular position of the various rollers as they traversed the bearing. Successive frames captured from the videos were analyzed to determine roller slip and the SRB load zone. Roller tilt and skew angles were also measured by inserting a nearly weightless pin into the center of a roller. In a similar manner, high-speed videography was used to assess the tilt and skew of the roller for a complete revolution of the roller around the inner race of the SRB. The dynamic behavior of the rollers was then corroborated with a previously developed SRB dynamic bearing model (DBM). The experimental and analytical results indicate that the roller tilt angle increases with axial load, remains constant with speed, and decreases with increasing radial load when the roller is located in the load zone. Further, roller skew in the load zone increases with axial load and shaft speed; however, it decreases with the radial load. The results indicate that when the radial-to-axial load ratio is greater than 4, roller tilt and skew are minimized. Due to roller intermittent slip and roller-cage pocket collision in the unload zone, tilt and skew become chaotic. The magnitude of the tilt and skew in the unload zone is directly related to the roller-race and roller-cage pocket clearances, respectively.
Vaccination induces HIV broadly neutralizing antibody precursors in humans
Authors: Leggat David J. , Cohen Kristen W. , Willis Jordan R. , Fulp William J. , deCamp Allan C. , Kalyuzhniy Oleksandr , Cottrell Christopher A. , Menis Sergey , Finak Greg , Ballweber-Fleming Lamar , Srikanth Abhinaya , Plyler Jason R. , Schiffner Torben , Liguori Alessia , Rahaman Farhad , Lombardo Angela , Philiponis Vincent , Whaley Rachael E. , Seese Aaron , Brand Joshua , Ruppel Alexis M. , Hoyland Wesley , Yates Nicole L. , Williams LaTonya D. , Greene Kelli , Gao Hongmei , Mahoney Celia R. , Corcoran Martin M. , Cagigi Alberto , Taylor Alison , Brown David M. , Ambrozak David R. , Sincomb Troy , Hu Xiaozhen , Tingle Ryan , Georgeson Erik , Eskandarzadeh Saman , Alavi Nushin , Lu Danny , Mullen Tina-Marie , Kubitz Michael , Groschel Bettina , Maenza Janine , Kolokythas Orpheus , Khati Nadia , Bethony Jeffrey , Crotty Shane , Roederer Mario , Karlsson Hedestam Gunilla B. , Tomaras Georgia D. , Montefiori David , Diemert David , Koup Richard A. , Laufer Dagna S. , McElrath M. Juliana , McDermott Adrian B. , Schief William R.
Published: December 2022

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine–priming candidate eOD-GT8 60mer adjuvanted with AS01
B
had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.
Magma accumulation at depths of prior rhyolite storage beneath Yellowstone Caldera
Authors: Maguire Ross , Schmandt Brandon , Li Jiaqi , Jiang Chengxin , Li Guoliang , Wilgus Justin , Chen Min
Published: December 2022

Seismic tomography has provided key insight into Yellowstone’s crustal magmatic system that includes attempts to understand the melt distribution in the subsurface and the current stage of the volcano’s life cycle. We present new tomographic images of the shear wave speed of the Yellowstone magmatic system based on full waveform inversion of ambient noise correlations, which illuminates shear wave speed reductions of greater than 30% associated with Yellowstone’s silicic magma reservoir. The slowest seismic wave speeds (shear wave speed less than 2.3 kilometers per second) are present at depths between 3 and 8 kilometers, overlapping with petrological estimates of the assembly depth of erupted rhyolite bodies. Assuming that Yellowstone’s magmatic system is a crystal mush with broadly distributed melt, we estimate a partial melt fraction of 16 to 20%.
What lies beneath Yellowstone?
Authors: Cooper Kari M.
Published: December 2022

There is more magma than previously recognized, but it may not be eruptible
In Other Journals
Authors: Hines Pamela J. , Ash Caroline , Ray L. Bryan , Hurtley Stella M. , Suleymanov Yury , Wible Brad , Grocholski Brent
Published: December 2022

Editors’ selections from the current scientific literature
CRUISE, a Tool for the Detection of Iterons in Circular Rep-Encoding Single-Stranded DNA Viruses
Authors: Jones Adam , Kasun George W. , Stover Joel , Stedman Kenneth M. , de la Higuera Ignacio
Published: December 2022

Iterons are short, repeated DNA sequences that are important for the replication of circular single-stranded DNA viruses. No tools that can reliably predict iterons are currently available. The CRUcivirus Iteron SEarch (CRUISE) tool is a computational tool that identifies iteron candidates near stem-loop structures in viral genomes.
The Spatial Features and Temporal Changes in the Gut Microbiota of a Healthy Chinese Population
Authors: Zhang Wen , Han Na , Zhang Tingting , Qiang Yujun , Peng Xianhui , Li Xiuwen , Kan Biao
Published: December 2022

China accounts for approximately 1/5th of the world’s total population. Differences in environment, ethnicity, and living habits could impart unique features to the structure of the gut microbiota of Chinese individuals.
Mycobacterium Fluoroquinolone Resistance Protein D (MfpD), a GTPase-Activating Protein of GTPase MfpB, Is Involved in Fluoroquinolones Potency
Authors: Huang Yu , Yan Shuangquan , Li Yuzhu , Ai Xuefeng , Yu Xi , Ge Yan , Lv Xi , Fan Lin , Xie Jianping
Published: December 2022

Tuberculosis is one of the leading causes of morbidity and mortality worldwide largely due to increasingly prevalent drug-resistant strains. Fluoroquinolones are important antibiotics used for treating multidrug-resistant tuberculosis (MDR-TB).
Infection Patterns of a Liberibacter Associated with Macrohomotoma gladiata, a Psyllid Feeding on Ficus microcarpa
Authors: Lin Fang-Yu , Lee Shin , Liao Yi-Chang , Yang Man-Miao , Chu Chia-Ching
Published: December 2022

Despite the ever-increasing interest in Liberibacter-psyllid interactions, most of the current knowledge on the subject has been established from studies focusing on species associated with crop diseases. To obtain a more holistic understanding of Liberibacter ecology, we investigated the infection patterns of a Liberibacter recently detected in
Macrohomotoma gladiata
, a psyllid pest of
Ficus microcarpa
.
Holospinal epidural abscess caused byStreptococcus anginosus group: a literature review
Authors: Maeda Keisuke , Kikuta Shota , Matsuyama Shigenari , Ishihara Satoshi
Published: December 2022

Spinal epidural abscess (SEA) usually extends over three to four vertebrae. We present a case of holospinal epidural abscess (HEA) caused by theStreptococcus anginosusgroup (SAG). A man in his 40s with a 2-week history of fever, back pain, and progressive tetraparesis was referred to us from the local hospital. MRI showed epidural fluid collection from C2 to S1. Blood and pus cultures revealed the presence of SAG. He was treated by emergency laminoplasty, epidural drainage and antibiotic treatment. After the 111st hospital day, his manual muscle test was shown to improve; hence, he was transferred for rehabilitation. According to the previous reports, we identified 12 cases of SEA extending from the cervical spine to the sacrum, including our case. For one-fourth of these cases, SAG was the causative organism of this rare SEA. Therefore, SAG should be considered causative organisms in HEA.
Exclusive determinations of $$\vert V_{cb} \vert $$ and $$R(D^{*})$$ through unitarity
Authors: Martinelli G. , Simula S. , Vittorio L.
Published: December 2022

In this work we apply the Dispersive Matrix (DM) method of Di Carlo et al. (Phys Rev D 104:054502, 2021) and Martinelli et al. (Phys Rev D 105:034503, 2022) to the lattice computations of the Form Factors (FFs) entering the semileptonic $$B \rightarrow D^* \ell \nu _\ell $$

B
→

D
∗

ℓ

ν
ℓ

decays, recently produced by the FNAL/MILC Collaborations (Fermilab Lattice, MILC collaboration, Semileptonic form factors for $$B \rightarrow D^*\ell \nu $$

B
→

D
∗

ℓ
ν

at nonzero recoil from 2 + 1-flavor lattice QCD. arXiv:2105.14019) at small, but non-vanishing values of the recoil variable ($$w-1$$

w
-
1

). Thanks to the DM method we obtain the FFs in the whole kinematical range accessible to the decay in a completely model-independent and non-perturbative way, implementing exactly both unitarity and kinematical constraints. Using our theoretical bands of the FFs we extract $$\vert V_{cb} \vert $$

|

V

cb

|

from the experimental data and compute the theoretical value of $$R(D^*)$$

R
(

D
∗

)

. Our final result for $$\vert V_{cb} \vert $$

|

V

cb

|

reads $$\vert V_{cb} \vert = (41.3 \pm 1.7) \cdot 10^{-3}$$

|

V

cb

|
=

(
41.3
±
1.7
)

·

10

-
3

, compatible with the most recent inclusive estimate at the $$0.5\sigma $$

0.5
σ

level. Moreover, we obtain the pure theoretical value $$R(D^*) = 0.275 \pm 0.008$$

R
(

D
∗

)
=
0.275
±
0.008

, which is compatible with the experimental world average at the $$\sim 1.3 \sigma $$

∼
1.3
σ

level.
Assessing the foundation and applicability of some dark energy fluid models in the Dirac–Born–Infeld framework
Authors: Aljaf Muhsin , Gregoris Daniele , Khurshudyan Martiros
Published: December 2022

In this paper, we will deepen the understanding of some fluid models proposed by other authors for the description of dark energy. Specifically, we will show that the so-called (Modified) Berthelot fluid is the hydrodynamic realization of the free Dirac–Born–Infeld (DBI) theory and that the Dieterici fluid admits a nonrelativistic [Formula: see text]-essence formulation; for the former model the evolution of the scalar field will be written in terms of some cosmographic parameters. The latter model will also be tested using Machine Learning algorithms with respect to cosmic chronometers data, and results about the dynamics at a background level will be compared with those arising when other fluids (Generalized Chaplygin Gas and Anton-Schmidt) are considered. Due to some cosmic opacity effects, the background cosmology of universes filled by these inequivalent fluids, as they arise in physically different theories, may not be enough for discriminating among them. Thus, a perturbation analysis in the long-wavelength limit is carried out revealing a rich variety of possible behaviors. It will also be shown that the free DBI theory cannot account for flat galactic rotation curves, and therefore we derive an appropriate relationship between the scalar field potential and the brane tension for achieving this goal; this provides an estimate for the dark matter adiabatic speed of sound inside the halo consistent with other literature. A certain relationship between the Newtonian gravitational potential within the galaxy and the Lagrangian potential in the nonrelativistic regime for the (Modified) Berthelot fluid will also be enlightened.
DDoS ATTACK DETECTION METHODS BASED ON DEEP LEARNING IN HEALTHCARE
Authors: WANG CHAOYING , ZHU TING
Published: December 2022

Software-defined network (SDN) is a new network structure, which has the characteristics of centralized management and programmable, and is widely used in the field of Internet of things. Distributed denial of service (DDoS) attack is one of the most threatening attacks in SDN network. How to effectively detect DDoS attacks has become a research hotspot in the field of SDN security management. Aiming at the above problems, this paper proposes a DDoS attack detection method based on Deep belief network (DBN) in SDN network architecture. By extracting the characteristics of OpenFlow switch flow table entries, DBN algorithm is trained to detect whether there are DDoS attacks. The experimental results show that the method is better than the other algorithms in accuracy, precision and recall.
DETERMINING MITRAL STENOSIS THROUGH RADIAL ARTERIAL PULSE: A COMPUTATIONAL UNDERSTANDING
Authors: HEMALATHA K. , MANIVANNAN M. , SIKKANDAR MOHAMED YACIN
Published: December 2022

Mitral Stenosis (MS) is an abnormal condition of the heart mitral valve in which the valve orifice area is reduced leading to many complications in heart function. Noninvasive and less expensive procedures for diagnosis are not currently available. The aim of this work was to explore the use of the radial artery pulse (RAP) to diagnose MS. This paper analyzed the effect of the development and growth of MS on possible radial artery noninvasive assessment parameters. For this, MS was introduced to ex vivo by varying the orifice area to either 1, 2, 3, 4 or 5[Formula: see text]cm2 in a hybrid cardiopulmonary electrical analogous model based on clinically obtained healthy controls with an orifice area of 6[Formula: see text]cm2. Results showed that a mitral valve area less than 2[Formula: see text]cm2 significantly influenced the pulse magnitude and time parameters. A strong correlation was observed in pulse height (PH), mean pulse height (MPH), and time occurrence of the dichotic notch. This may be due to increased blood remaining in the left atrium and hence decreased stoke volume (SV). SV is proportional to arterial pulse pressure which is evident from the decrease in the PH and MPH in MS. In summary, this study provides the first evidence that MS may be diagnosed by examining peripheral pulses which thus, needs further investigation to use RAP as a noninvasive and less expensive MS diagnostic tool.
ACADEMICS IN THE BOARDROOM: THE EFFECT OF A GENDER QUOTA REGULATION
Authors: DE VINCENTIIS PAOLA , OGGERO NOEMI
Published: December 2022

In the framework of literature devoted to corporate governance and board composition, we take a peculiar viewpoint and focus on the presence of university professors in the governing body of Italian banks. In particular, we test whether the gender quota regulation increased the presence of female professors as directors. We find evidence of a relevant increase in the probability of designating women from the academia in the years immediately following the entry into force of the gender quota regulation in Italy, whereas no significant increase is in place for male professors over the same period. Our results suggest the need to enhance the career opportunities for women up the C-levels in order to fuel diversity in the boardrooms, not only in independent but also in executive roles. In light of the empirical evidence provided, a re-thinking of gender quota regulations would also be advisable in order to better pursue the desired outcomes.
Stochastic Estimator Based Adaptive Sliding Mode Control for a Quadrotor in Rainy Flight Conditions
Authors: Hamdadou Nabil , Bouadi Hakim , Hebablia Nacir , Yazid Mounir
Published: December 2022

Novel modeling of the raindrops impact forces on a quadrotor has been developed and implemented in this work. These forces are meant to generate dispersed displacement disturbances in the vertical axis [Formula: see text] and dispersed rotation disturbances around roll and pitch axis. The proposed model is derived using the stochastic characteristics of the raindrops combined with classical quadrotor dynamics to address the issue of the adopted sliding mode controller, which shows lack of robustness while tracking the desired path, resulting in sensitive fluctuations. These fluctuations are increasingly visible for disturbances generated by raindrops with an average diameter greater than 2 mm. To deal with these types of disturbances, a novel control law based on an adaptive sliding mode approach and the estimated parameters of the stochastic disturbances (average and variance) was employed. This control law has been synthesized based on the sliding mode approach and Lyapunov principle to ensure quadrotor stability and robustness purposes. The adopted estimation of the average and variance of the disturbances was carried out by filtering the difference between the system state and a reference model state. The adopted control law has been implemented on MATLAB/SIMULINK, yielding satisfactory results and minimizing the fluctuations.
Straits and seaways: controls, processes and implications in modern and ancient systems
Authors: Rossi Valentina Marzia , Longhitano Sergio G. , Olariu Cornel , Chiocci Francesco L.
Published: December 2022

Straits and seaways are connections between basins, key areas for exchange and transfer of water, heat, biota and sediments, and they can influence regional and global climate. A better understanding of strait/seaway dynamics, their evolution and preserved deposits is, therefore, fundamental to reconstructing the palaeoecology, palaeogeography and stratigraphy of interconnected basins. Straits and seaways are also important for understanding climate dynamics in Earth's past, and for safely exploiting energy resources (fossil and renewable). This volume aims at improving the knowledge on this topic, and at providing a comprehensive collection of state-of-the-art works bringing together complementary disciplines. Even though studies on modern and ancient straits and seaways exist, they are not necessarily conceived towards a better geological understanding of these features as depositional systems in their own right. In this introduction, we emphasize the geological importance of straits and seaways, summarizing the content and key findings of the contributions on this topic. The articles included in this volume explore four main research themes related to straits and seaways: (1) occurrence and classification; (2) morphological features, facies and stratigraphic variability, sedimentary processes and dynamics; (3) tectonic and climatic controls, their feedback with climate changes; and (4) palaeogeographical reconstructions and preservation of associated deposits.
Joint Augmented and Compressed Dictionaries for Robust Image Classification
Authors: Zeng Shaoning , Rao Yunbo , Zhang Bob , Xu Yong
Published: December 2022

Dictionary-based Classification (DC) has been a promising learning theory in multimedia computing. Previous studies focused on learning a discriminative dictionary as well as the sparsest representation based on the dictionary, to cope with the complex conditions in real-world applications. However, robustness by learning only one single dictionary is far from the optimal level. What is worse, it cannot take advantage of the available techniques proven in modern machine learning, like data augmentation, to mitigate the same problem. In this work, we propose a novel method that utilizes joint Augmented and Compressed Dictionaries for Robust Dictionary-based Classification (ACD-RDC). For optimization under the noise model introduced by real-world conditions, the objective function of ACD-RDC incorporates only two simple, but well-designed constraints, including one enhanced sparsity constraint by the general data augmentation, which requires less case-by-case and sophisticated tuning, and another discriminative constraint solved by a jointly learned dictionary. The optimization of the objective function is then deduced theoretically to an approximate linear problem. The sparsity and discrimination enhanced by data augmentation guarantees the robustness for image classification under various conditions, which constructs the first positive case using data augmentation to obtain robust dictionary-based classification. Numerous experiments have been conducted on popular facial and object image datasets. The results demonstrate that ACD-RDC obtains more promising classification on diversely collected images than the current dictionary-based classification methods. ACD-RDC is also confirmed to be a state-of-the-art classification method when using deep features as inputs.
AMSA: Adaptive Multimodal Learning for Sentiment Analysis
Authors: Wang Jingyao , Mou Luntian , Ma Lei , Huang Tiejun , Gao Wen
Published: December 2022

Efficient recognition of emotions has attracted extensive research interest, which makes new applications in many fields possible, such as human-computer interaction, disease diagnosis, service robots, and so forth. Although existing work on sentiment analysis relying on sensors or unimodal methods performs well for simple contexts like business recommendation and facial expression recognition, it does far below expectations for complex scenes, such as sarcasm, disdain, and metaphors. In this article, we propose a novel two-stage multimodal learning framework, called AMSA, to adaptively learn correlation and complementarity between modalities for dynamic fusion, achieving more stable and precise sentiment analysis results. Specifically, a multiscale attention model with a slice positioning scheme is proposed to get stable quintuplets of sentiment in images, texts, and speeches in the first stage. Then a Transformer-based self-adaptive network is proposed to assign weights flexibly for multimodal fusion in the second stage and update the parameters of the loss function through compensation iteration. To quickly locate key areas for efficient affective computing, a patch-based selection scheme is proposed to iteratively remove redundant information through a novel loss function before fusion. Extensive experiments have been conducted on both machine weakly labeled and manually annotated datasets of self-made Video-SA, CMU-MOSEI, and CMU-MOSI. The results demonstrate the superiority of our approach through comparison with baselines.
Context Sensing Attention Network for Video-based Person Re-identification
Authors: Wang Kan , Ding Changxing , Pang Jianxin , Xu Xiangmin
Published: December 2022

Video-based person re-identification (ReID) is challenging due to the presence of various interferences in video frames. Recent approaches handle this problem using temporal aggregation strategies. In this work, we propose a novel Context Sensing Attention Network (CSA-Net), which improves both the frame feature extraction and temporal aggregation steps. First, we introduce the Context Sensing Channel Attention (CSCA) module, which emphasizes responses from informative channels for each frame. These informative channels are identified with reference not only to each individual frame, but also to the content of the entire sequence. Therefore, CSCA explores both the individuality of each frame and the global context of the sequence. Second, we propose the Contrastive Feature Aggregation (CFA) module, which predicts frame weights for temporal aggregation. Here, the weight for each frame is determined in a contrastive manner: i.e., not only by the quality of each individual frame, but also by the average quality of the other frames in a sequence. Therefore, it effectively promotes the contribution of relatively good frames. Extensive experimental results on four datasets show that CSA-Net consistently achieves state-of-the-art performance.
Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women
Authors: Kan Hui , He Yining , Li Qing , Mu Yutong , Dong Yao , Fan Wei , Zhang Miao , Wang Tianlei , Li Yaxin , Liu Haiyan , Hu Anqun , Zheng Yingjie
Published: December 2022

Objective. The effect of vaginal microbiota on spontaneous preterm birth (sPTB) has not been fully addressed, and few studies have explored the associations between vaginal taxa and sPTB in the gestational diabetes mellitus (GDM) and non‐GDM groups, respectively. Study Design. To minimize external interference, a total of 41 pregnant women with sPTB and 308 controls (pregnant women without sPTB) from same regain were enrolled in this case‐cohort study. Controls were randomly selected at baseline. With the exception of GDM, other characteristics were not significantly different between the two groups. Vaginal swabs were collected at early second trimester. Using 16S amplicon sequencing, the main bioinformatics analysis was performed on the platform of QIIME 2. Vaginal microbiota traits of the sPTB group were compared with controls. Finally, the effects of binary taxa on sPTB in the GDM group and the non‐GDM group were analyzed, respectively. Results. The proportion of GDM in the sPTB (19.51%) was higher than the controls (7.47%, P = 0.018). The vaginal microbiota of pregnant women with sPTB exhibited higher alpha diversity metrics (observed features, P = 0.001; Faith’s phylogenetic diversity, P = 0.013) and different beta diversity metrics (unweighted UniFrac, P = 0.006; Jaccard’s distance, P = 0.004), compared with controls. The presence of Lactobacillus paragasseri/gasseri (aOR: 3.12, 95% CI: 1.24‐7.84), Streptococcus (aOR: 3.58, 95% CI: 1.68‐7.65), or Proteobacteria (aOR: 3.39, 95% CI: 1.55‐7.39) was associated with an increased risk of sPTB in the non‐GDM group (P < 0.05). However, the relative abundance of novel L. mulieris (a new species of the L. delbrueckii group) was associated with a decreased risk of sPTB (false discovery rate, 0.10) in all pregnant women. Conclusion. GDM may modify the association of vaginal taxa with sPTB, suggesting that maternal GDM should be considered when using vaginal taxa to identify pregnant women at high risk of sPTB.
Influence of Machine Parameters and Coagulant on the Textural Properties of Paneer (Indian Cottage Cheese)
Authors: Sivaranjani S. , Pandian N. Karpoora Sundara , Parveen S. , Baskaran D. , Prasath V. Arun , Nambi V. Eyarkai , Pandiselvam R.
Published: December 2022

Paneer is an acid coagulated concentrated indigenous Indian dairy product. The texture of paneer manufactured from a developed automatic machine was studied with respect to the processing parameters such as coagulation temperature (70–90°C), pressure (0.3–0.6 MPa), types of coagulant (vinegar and citric acid), and milk (cow, buffalo, and full cream milk). The paneer samples were analysed for texture profile analysis of hardness, adhesiveness, springiness, gumminess, chewiness, and cohesiveness. An inscribed central composite design was used to optimize the desired textural characteristics of paneer such as minimum hardness and maximum springiness of paneer. The optimization result concluded that the full cream milk at the coagulation temperature of 88°C with citric acid at pneumatic pressure of 0.3 MPa would result on minimum hardness of 105.84 N and the springiness value of 0.6073, and the result was validated.
Hierarchical Identity-Based Online/Offline Encryption Scheme with Leakage Resilience
Authors: Yu Qihong , Li Jiguo , Ji Sai
Published: December 2022

The adversary is able to obtain some secret information from side channel attacks, which further damages the security for the system. To resolve this issue, we provide a hierarchical identity-based online/offline encryption scheme which resists side channel attacks. In our scheme, most encryption operations are preprocessed in the offline stage and only a small amount of lightweight calculation needs to be performed in the online stage for generating ciphertext. The presented scheme greatly reduces the workload of online encryption and is suitable for the resource-constrained device. The security of the proposed scheme is proved by the dual system technique. The leakage performance analysis shows that the presented scheme is resilient to leakage for almost the whole symmetric key.
Abstract B022: The adaptor protein FRS2beta fashions a cytokine-rich inflammatory microenvironment that is associated with DCIS and promotes breast cancer carcinogenesis
Authors: Gotoh Noriko
Published: December 2022

Although it is commonly held that pro-inflammatory changes precede the onset of breast cancer, the underlying mechanisms remain obscure. Here, we report that FRS2beta, an adaptor protein with a highly restricted epithelial expression pattern, mediates the pro-inflammatory changes that alter the stroma in premalignant mammary tissues. We posit that these changes, which include lesions of ductal carcinoma in situ (DCIS), precede disease onset. In the MMTV-ErbB2 mouse model of mammary carcinoma, FRS2beta-deficiency markedly attenuated tumorigenesis. Importantly, tumor cells derived from MMTV-ErbB2 mice failed to generate tumors when grafted in the FRS2beta-deficient premalignant tissues. We found that the co-localization of FRS2beta and the NEMO subunit of the IkappaB kinase (IKK) complex in early endosomes activated nuclear factor-kappaB (NFkappaB), a master regulator of inflammation. Moreover, the inhibition of NFkappaB-induced cytokines CXC chemokine ligand (CXCL)12 and insulin-like growth factor (IGF1) abrogated tumorigenesis. In line with this, human breast cancer tissues that express higher levels of FRS2beta contain more stroma. The elucidation of the FRS2beta-NFkappaB axis uncovers a hitherto unknown molecular link between the pro-inflammatory changes in the DCIS and the disease onset.

Citation Format: Noriko Gotoh. The adaptor protein FRS2beta fashions a cytokine-rich inflammatory microenvironment that is associated with DCIS and promotes breast cancer carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B022.
Abstract IA011: Patient-derived organoids as models for breast cancer prevention and interception
Authors: Rosenbluth Jennifer M.
Published: December 2022

Organoid culture technology can be an efficient means for propagating breast tissues from patients, and we have previously generated organoid biobanks derived from normal and malignant human breast samples. Non-cancerous organoids, which are grown in a hydrogel that mimics the basement membrane and are bathed in a cocktail of growth factors, vitamins, and substances that substitute for stroma, grow in a polarized fashion to re-form acinar- and duct-like structures, and differentiate into the major mammary epithelial lineages, and we have found that all the major mammary epithelial lineages can be propagated in vitro. We have utilized mass cytometry and single-cell RNA sequencing to identify specific cell subtypes that are associated with breast cancer risk factors in organoids. In parallel, in malignant organoid cultures we have utilized RNA sequencing and compound screening approaches to identify potential strategies to overcome therapeutic resistance. We now present our initial efforts to establish a DCIS organoid biobank. Similar to the normal breast, organoids can be propagated from DCIS cases that are resistant to endocrine therapy with the goal of identifying strategies to overcome the resistant state.

Citation Format: Jennifer M. Rosenbluth. Patient-derived organoids as models for breast cancer prevention and interception [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA011.
Abstract IA013: A single-cell and spatial investigation of tumor and TME for DCIS
Authors: Wei Runmin , He Siyuan , Bai Shanshan , Sei Emi , Hu Min , Nagi Chandandeep , Menegaz Brian , Javaid Huma , Wesseling Jelle , Futreal Andrew , Thompson Alastair , Krishnamurthy Savitri , Navin Nicholas
Published: December 2022

Ductal carcinoma in situ (DCIS) is early-stage non-malignant breast cancer that tumor cells are confined to the lumens of ducts. Over 50,000 DCIS patients are diagnosed each year in the United States, however, less than half of DCIS will develop into invasive breast cancer (IBC), suggesting a risk of overtreatment for some DCIS patients. A comprehensive investigation of the molecular mechanisms of DCIS initiation and progression is urgently needed that can facilitate us stratifying the risk of DCIS invasion and design better intervention approaches. In this study, we conducted single-cell RNA-seq and spatial transcriptomics (ST) on DCIS and IBC samples (most estrogen receptor positive). We first inferred copy number aberrations (CNA) in these samples and found that DCIS and IBC shared the most copy number events while only marginal differences were identified. Tumor CNA subclones colocalized in different ductal regions from the ST data. Further, we applied a sample-wise non-negative matrix factorization (NMF) to identify robust gene expression metaprograms across tumor samples. On the ST data, we found these metaprograms also displayed distinct spatial patterns. For non-tumor cells in the TME, we sub-clustering them into cell states and identified that some cell states showed a gradual change along breast cancer initiation and progression. To recapitulate the tumor ecosystems, we also conducted an ecotype analysis in DCIS samples and identified that some ecotypes showed an increasing/decreasing trend in IBC patients. Further, tumor and TME ecotypes also showed spatially colocalizations based on our ST data. In summary, these results demonstrated that genomic signatures could hardly predict the DCIS progression while tumor metaprograms and TME ecotypes might serve as a potential risk stratification approach for DCIS patients.

Citation Format: Runmin Wei, Siyuan He, Shanshan Bai, Emi Sei, Min Hu, Chandandeep Nagi, Brian Menegaz, Huma Javaid, Jelle Wesseling, Andrew Futreal, Alastair Thompson, Savitri Krishnamurthy, Nicholas Navin. A single-cell and spatial investigation of tumor and TME for DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA013.
Abstract IA022: Imaging tools for DCIS: Past, present and future
Authors: Lehman Connie
Published: December 2022

In the past, mammography was considered the imaging test of choice to identify DCIS. More recent studies clarified breast MRI is more sensitive than mammography to identify DCIS overall and higher grade DCIS specifically. Techniques to support Fast or Abbreviated MRI were developed to try to support greater access, lower costs, increased patient acceptance of breast MRI in both the screening and the diagnostic setting. In the future, contrast enhanced mammography may provide greater access to more patients to the benefits of vascular imaging of DCIS, benefits previously limited to contrast enhanced breast MRI. Deep learning models in the domain of Artificial Intelligence may support more accurate triage of DCIS lesions more and less likely to progress, supporting more effective triage of low risk DCIS lesions to surveillance.

Citation Format: Connie Lehman. Imaging tools for DCIS: Past, present and future [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA022.
Abstract IA030: Molecular subtypes and spatial heterogeneity in DCIS
Authors: Sørlie Therese
Published: December 2022

The large heterogeneity of DCIS complicates the identification of markers for risk of progression to invasive breast cancer. Molecular and cellular heterogeneity is observed across DCIS, between multiple foci of DCIS within a lesion and within mixed lesions of invasive tumors with DCIS foci. The intrinsic breast cancer subtypes represent fundamental biological properties of the disease and are also found at the DCIS stage. However, their frequency and relevance as prognostic markers in pre-invasive stage is still not clear. Novel technologies for spatial characterization of tumors allow detailed mapping of DCIS and the microenvironment and may give us clues to which DCIS have the propensity to invade surrounding stroma. In the presentation, we will discuss results from our ongoing genomic characterization of DCIS and invasive breast carcinomas that illustrate the need for stratification when searching for prognostic markers. We have found disproportionate distribution and characteristics of the intrinsic subtypes in DCIS compared with invasive breast cancer and the dominance of Luminal A and HER2 subtypes. Bona-fide basal-like tumors may rarely be found at the DCIS stage and HER2-enriched DCIS are associated with specific immune cell profiles.

Citation Format: Therese Sørlie. Molecular subtypes and spatial heterogeneity in DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA030.
Abstract PR001: Spatial proximity between CD8+ T cells and tumor cells correlates with invasive recurrence in DCIS
Authors: Campbell Michael J. , Schindler Nicole , Glencer Alexa , Bolen Jennifer , Mori Hidetoshi , Loveday Tristan , Rothschild Harriet , Hirst Gillian , Vandenberg Scott , Borowsky Alexander , Esserman Laura
Published: December 2022

Purpose: The immune microenvironment in ductal carcinoma in situ (DCIS) and its significance are not well established. In this study, we characterized the immune microenvironment of DCIS to determine if immune cell densities, or their spatial relationships with tumor cells, are predictive of recurrence with invasive breast cancer. Methods: One hundred thirty-two cases of DCIS were included in this study. Seventy (53%) cases were high grade, 72 (54%) were HER2+, and 91 (69%) were HR+. Twenty cases recurred with invasive breast cancer. Immune infiltrates were characterized by multiplex immunofluorescence staining of FFPE sections using two 6-plex panels. Panel IP1.2 included markers for CD3, CD20, Foxp3, pan-cytokeratins, Ki67, and HLADR. Panel IP2.2 included markers for CD3, CD8, CD68, pan-cytokeratins, PD-1, and PD-L1. Staining was performed on a Leica Bond autostainer and images were acquired on a Vectra Polaris imaging system. Image analysis was performed utilizing inForm and QuPath software packages, as well as R scripts. Counts for each cell population were determined and spatial point pattern analyses were performed to quantitate the spatial relationships between tumor cells and various immune cell types. Results: High infiltrates of T cells, CD8+ T cells (Tc), Foxp3+ T cells, and B cells were associated with high grade, hormone receptor (HR) negativity, HER2 positivity, and the presence of comedonecrosis. PD-1+ T cells and PD-1+ Tc were associated with high grade, HR negativity, and HER2 positivity. PD-L1+ immune cells, but not PD-L1+ tumor cells, were also associated with high grade, HR negativity, and HER2 positivity. None of the cell populations were associated with invasive recurrence. However, the spatial proximity of tumor cells with T cells, in particular Tc, was significantly associated with a subsequent invasive event. Patients whose DCIS had a high tumor-to-Tc proximity score (indicating close proximity of tumor and Tc) were less likely to have an invasive recurrence. Conclusion: These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases at risk for invasive recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression.

Citation Format: Michael J. Campbell, Nicole Schindler, Alexa Glencer, Jennifer Bolen, Hidetoshi Mori, Tristan Loveday, Harriet Rothschild, Gillian Hirst, Scott Vandenberg, Alexander Borowsky, Laura Esserman. Spatial proximity between CD8+ T cells and tumor cells correlates with invasive recurrence in DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR001.
Abstract PR008: Duration of endocrine treatment for DCIS impacts second events: Insights from a large registry of cases at two academic medical centers
Authors: O'Keefe Thomas , Yau Christina , Iaconetti Emma , Jeong Eliza , Brabham Case , Kim Paul , McGuire Joseph , Griffin Ann , Esserman Laura , Harismendy Olivier , Hirst Gillian
Published: December 2022

Background: Ductal carcinoma in situ (DCIS) incidence has risen with increasing use of screening mammography. It is unclear who benefits from both the amount and type of adjuvant treatment (radiation therapy, (RT), endocrine therapy (ET)) versus what constitutes over-treatment. Our goal was to identify the effects of adjuvant RT, or ET+/- RT versus breast conservation surgery (BCS) alone in a large multi-center DCIS registry of retrospective patients with long follow up. Methods: Data was extracted on women with a primary diagnosis of DCIS (N=2979) between 1985 - 2017 treated in 2 University of California (UC) medical centers. ET treatment and duration was confirmed by chart review for 1916 patients for this analysis. Receipt of ET (N=404) was stratified to > 2 years or < 2 years. Association between treatment type and second events was assessed using Cox regression. Competing risks models were used to assess effect of treatment type on different type of second events (ipsilateral DCIS or invasive, or contralateral combined). Time-varying coefficients were used as appropriate. Results: Median follow up time was 8.2 years for the 1916 patients analyzed. The cumulative second event (any type) rate was 25% at 15 years. In univariate and multivariate analysis adjusting for clinical variables, all treatments reduced the risk of second events compared to BCS only. Further stratifying ET receipt by duration demonstrated significant risk reduction (HR=0.12, P=0.04) only in women taking >2 years of ET, but not in women in the <2year ET group (HR=1.3, P=0.55). In the competing risk model, RT significantly reduces the risk of both ipsilateral DCIS and invasive cancer, and ET > 2 years significantly reduces the risk of ipsilateral invasive cancer. Conclusions: In our registry we show that women with DCIS who took less than 2 years of adjuvant endocrine therapy have a similar second event rate as BCS. In contrast, women who took more than 2 years of ET show a significantly reduced second event rate, similar to those who received either RT or combined ET+RT, which was independent of age, tumor size, grade, or period of diagnosis. This highlights the importance of ET duration for risk reduction of second events following surgery for newly diagnosed DCIS.

Citation Format: Thomas O'Keefe, Christina Yau, Emma Iaconetti, Eliza Jeong, Case Brabham, Paul Kim, Joseph McGuire, Ann Griffin, Laura Esserman, Olivier Harismendy, Gillian Hirst. Duration of endocrine treatment for DCIS impacts second events: Insights from a large registry of cases at two academic medical centers [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR008.