bluuebunny/crossref_metadata_2025 huggingface dataset:
DxPU: Large-scale Disaggregated GPU Pools in the Datacenter
Authors: He Bowen , Zheng Xiao , Chen Yuan , Li Weinan , Zhou Yajin , Long Xin , Zhang Pengcheng , Lu Xiaowei , Jiang Linquan , Liu Qiang , Cai Dennis , Zhang Xiantao
Published: October 2023

The rapid adoption of AI and convenience offered by cloud services have resulted in the growing demands for GPUs in the cloud. Generally, GPUs are physically attached to host servers as PCIe devices. However, the fixed assembly combination of host servers and GPUs is extremely inefficient in resource utilization, upgrade, and maintenance. Due to these issues, the GPU disaggregation technique has been proposed to decouple GPUs from host servers. It aggregates GPUs into a pool and allocates GPU node(s) according to user demands. However, existing GPU disaggregation systems have flaws in software-hardware compatibility, disaggregation scope, and capacity.

In this article, we present a new implementation of
datacenter-scale
GPU disaggregation, named DxPU. DxPU efficiently solves the above problems and can flexibly allocate as many GPU node(s) as users demand. To understand the performance overhead incurred by DxPU, we build up a performance model for AI specific workloads. With the guidance of modeling results, we develop a prototype system, which has been deployed into the datacenter of a leading cloud provider for a test run. We also conduct detailed experiments to evaluate the performance overhead caused by our system. The results show that the overhead of DxPU is less than 10%, compared with native GPU servers, in most of user scenarios.
Hierarchical Learning and Dummy Triplet Loss for Efficient Deepfake Detection
Authors: Beuve Nicolas , Hamidouche Wassim , Déforges Olivier
Published: October 2023

The advancement of generative models has made it easier to create highly realistic Deepfake videos. This accessibility has led to a surge in research on Deepfake detection to mitigate potential misuse. Typically, Deepfake detection models utilize binary backbones, even though the training dataset contains additional exploitable information, such as the Deepfake generation method employed for each video. However, recent findings suggest that inferring a binary class from a multi-class backbone yields superior performance compared to directly employing a binary backbone. Building upon this research, our article introduces two novel methods to infer a binary class from a multi-class backbone. The first method, named
root dummies
, leverages the dummy triplet loss, which employs fixed vectors (i.e., dummies) instead of mined positives and negatives in the triplet loss. By training the multi-class backbone with these dummies, we can easily infer a binary class during testing by adjusting the number of dummies (from six during training to two during inference). Through this approach, we achieve an accuracy improvement of 0.23% compared to the existing inference method, without requiring additional training. The second proposed method is transfer learning. It involves training a classifier, such as a support vector machine, to predict binary classes based on the image embeddings generated by the multi-class backbone. Although this method necessitates additional training, it further enhances the model’s performance, resulting in an accuracy increase of 1.79%. In summary, our proposed methods improve the accuracy of Deepfake detection by simply modifying the number of classes during training, making them suitable for integration into a variety of existing Deepfake training pipelines. Additionally, to foster reproducible research, we have made the source code of our solution publicly available at
https://github.com/beuve/DmyT
.
Practical Design Considerations for Wide Locally Recoverable Codes (LRCs)
Authors: Kadekodi Saurabh , Silas Shashwat , Clausen David , Merchant Arif
Published: October 2023

Most of the data in large-scale storage clusters is erasure coded. At exascale, optimizing erasure codes for low storage overhead, efficient reconstruction, and easy deployment is of critical importance.
Locally recoverable codes (LRCs)
have deservedly gained central importance in this field, because they can balance many of these requirements. In our work, we study wide LRCs; LRCs with large number of blocks per stripe and low storage overhead. These codes are a natural next step for practitioners to unlock higher storage savings, but they come with their own challenges. Of particular interest is their
reliability
, since wider stripes are prone to more simultaneous failures.

We conduct a practically minded analysis of several popular and novel LRCs. We find that wide LRC reliability is a subtle phenomenon that is sensitive to several design choices, some of which are overlooked by theoreticians, and others by practitioners. Based on these insights, we construct novel LRCs called
Uniform Cauchy LRCs
, which show excellent performance in simulations and a 33% improvement in reliability on unavailability events observed by a wide LRC deployed in a Google storage cluster. We also show that these codes are easy to deploy in a manner that improves their robustness to common maintenance events. Along the way, we also give a remarkably simple and novel construction of distance-optimal LRCs (other constructions are also known), which may be of interest to theory-minded readers.
NPU-Accelerated Imitation Learning for Thermal Optimization of QoS-Constrained Heterogeneous Multi-Cores
Authors: Rapp Martin , Khdr Heba , Krohmer Nikita , Henkel Jörg
Published: October 2023

Thermal optimization of a heterogeneous clustered multi-core processor under user-defined QoS targets requires application migration and DVFS. However, selecting the core to execute each application and the VF levels of each cluster is a complex problem because (1) the diverse characteristics and QoS targets of applications require different optimizations, and (2) per-cluster DVFS requires a global optimization considering all running applications. State-of-the-art resource management for power or temperature minimization either relies on measurements that are commonly not available (such as power) or fails to consider all the dimensions of the optimization (e.g., by using simplified analytical models). To solve this, ML methods can be employed. In particular, IL leverages the optimality of an oracle policy, yet at low run-time overhead, by training a model from oracle demonstrations. We are the first to employ IL for temperature minimization under QoS targets. We tackle the complexity by training NN at design time and accelerate the run-time NN inference using NPU. While such NN accelerators are becoming increasingly widespread, they are so far only used to accelerate user applications. In contrast, we use for the first time an existing accelerator on a real platform to accelerate NN-based resource management. To show the superiority of IL compared to RL in our targeted problem, we also develop multi-agent RL-based management. Our evaluation on a
HiKey 970
board with an
Arm big.LITTLE
CPU and NPU shows that IL achieves significant temperature reductions at a negligible run-time overhead. We compare
TOP-IL
against several techniques. Compared to
ondemand
Linux governor,
TOP-IL
reduces the average temperature by up to 17 ˆC at minimal QoS violations for both techniques. Compared to the RL policy, our
TOP-IL
achieves 63 % to 89 % fewer QoS violations while resulting similar average temperatures. Moreover,
TOP-IL
outperforms the RL policy in terms of stability. We additionally show that our IL-based technique also generalizes to different software (unseen applications) and even hardware (different cooling) than used for training.
Unbiased Identification of Broadly Appealing Content Using a Pure Exploration Infinitely Armed Bandit Strategy
Authors: Aziz Maryam , Anderton Jesse , Jamieson Kevin , Wang Alice , Bouchard Hugues , Aslam Javed
Published: October 2023

Podcasting is an increasingly popular medium for entertainment and discourse around the world, with tens of thousands of new podcasts released on a monthly basis. We consider the problem of identifying from these newly released podcasts those with the largest potential audiences so they can be considered for personalized recommendation to users. We first study and then discard a supervised approach due to the inadequacy of either content or consumption features for this task and instead propose a novel non-contextual bandit algorithm in the fixed-budget infinitely armed pure-exploration setting. We demonstrate that our algorithm is well suited to the best-arm identification task for a broad class of arm reservoir distributions, out-competing a large number of state-of-the-art algorithms. We then apply the algorithm to identifying podcasts with broad appeal in a simulated study and show that it efficiently sorts podcasts into groups by increasing appeal while avoiding the popularity bias inherent in supervised approaches. Finally, we study a setting in which users are more likely to stream more-streamed podcasts independent of their general appeal and find that our proposed algorithm is robust to this type of popularity bias.

1
Shortest Cycles with Monotone Submodular Costs
Authors: Fomin Fedor V. , Golovach Petr A. , Korhonen Tuukka , Lokshtanov Daniel , Stamoulis Giannos
Published: October 2023

We introduce the following submodular generalization of the
Shortest Cycle
problem. For a nonnegative monotone submodular cost function
f
defined on the edges (or the vertices) of an undirected graph
G
, we seek for a cycle
C
in
G
of minimum cost 𝖮𝖯𝖳 =
f(C)
. We give an algorithm that given an
n
-vertex graph
G
, parameter ɛ > 0, and the function
f
represented by an oracle, in time
n
𝒪
(log 1/ɛ) finds a cycle
C
in
G
with
f(C)
≤ (1+ɛ). 𝖮𝖯𝖳. This is in sharp contrast with the non-approximability of the closely related

Monotone Submodular Shortest (
s,t
-Path

problem, which requires exponentially many queries to the oracle for finding an
n
2/3-ɛ
-approximation Goel et al. [
7
], FOCS 2009. We complement our algorithm with a matching lower bound. We show that for every ɛ > 0, obtaining a (1+ɛ)-approximation requires at least
n
Ω (log 1/ ɛ)
queries to the oracle.

When the function
f
is integer-valued, our algorithm yields that a cycle of cost 𝖮𝖯𝖳 can be found in time
n
𝒪(log 𝖮𝖯𝖳)
. In particular, for 𝖮𝖯𝖳 =
n
𝒪(1)
this gives a quasipolynomial-time algorithm computing a cycle of minimum submodular cost. Interestingly, while a quasipolynomial-time algorithm often serves as a good indication that a polynomial time complexity could be achieved, we show a lower bound that
n

𝒪(log
n
)

queries are required even when 𝖮𝖯𝖳= 𝒪(
n
).

We also consider special cases of monotone submodular functions, corresponding to the number of different color classes needed to cover a cycle in an edge-colored multigraph
G
. For special cases of the corresponding minimization problem, we obtain fixed-parameter tractable algorithms and polynomial-time algorithms, when restricted to certain classes of inputs.
Effect of Ni on Electroless Cu Plating Rates in the Presence of 2,2′-Bipyridyl and 2-Mercaptobenzothiazole
Authors: Lindsay Gavin S. , Rohde Dirk , Bernhard Tobias , Zarwell Sebastian , Schmidt Ralf , Bandas Christopher D. , Gewirth Andrew A.
Published: October 2023

Electrochemical measurements and Surface Enhanced Raman Spectroscopy (SERS) are used to evaluate the effect of Ni addition on the rate of Cu electroless deposition in the presence of 2,2′-bipyridyl (BP) and 2-mercaptobenzothiazole (MBT). Ni addition is found to increase the rate of electroless Cu deposition in the presence of BP but had no effect on the rate in the presence of MBT. In situ SERS obtained at the potential of electroless deposition shows that BP is destabilized from the Cu surface in the presence of Ni, likely due to the increased positive charge present with Ni-incorporated Cu. The BP deficient surface exhibits a higher electroless deposition rate relative to a surface with substantial BP. In contrast, SERS shows that Ni addition does not alter MBT adsorption to Cu, due to the increased affinity of MBT to the electrode surface relative to BP.
Pathways and parameters of sacral neuromodulation in rats
Authors: Hokanson James A. , Langdale Christopher L. , Grill Warren M.
Published: October 2023

Acute low-amplitude electrical stimulation of sacral nerve (sacral neuromodulation) did not increase bladder capacity in anesthetized CD, obese-prone, or obese-resistant rats. Increasing stimulation amplitude correlated with increases in bladder capacity and pudendal sensory nerve recruitment. It is unclear how the high-amplitude acute stimulation that is commonly used in animal experiments to generate immediate effects compares mechanistically to the chronic low-amplitude stimulation used clinically.
Delayed metabolic disturbances in the myocardium after exertional heat stroke: contrasting effects of exertion and thermal load
Authors: Garcia Christian K. , Gambino Bryce J. , Robinson Gerard P. , Rua Michael T. , Alzahrani Jamal M. , Clanton Thomas L.
Published: October 2023

Epidemiological data demonstrate greater cardiovascular risk in patients with previous heat stroke exposure. Using a preclinical mouse model of exertional heat stroke, male mice were exposed to one of three environmental temperatures (Te) during exercise. Paradoxically, after 2 wk, the mice in the lowest Te, exhibiting the largest exercise response and lowest heat load, had the greatest ventricular metabolic disturbances. Metabolic outcomes resemble developing left ventricular hypertrophy or stress-induced heart disease.
Microgravity-induced skeletal muscle atrophy in women and men: implications for long-duration spaceflights to the Moon and Mars
Authors: Trappe Todd A. , Tesch Per , Alkner Björn , Trappe Scott
Published: October 2023

This study adds to the limited evidence regarding sex-specific responses to real or simulated microgravity exposure, which collectively suggests a sex-specific muscle atrophy profile, with women losing more than men at least through the first 4 mo of weightlessness. Considering the increase in women being selected for space missions, including the first women to travel to the Moon, more physiological data on women in response to microgravity are needed.
Cardiovascular responses to combined mechanoreflex and metaboreflex activation in healthy adults: effects of sex and low- versus high-hormone phases in females
Authors: Lee Jordan B. , Thompson Kyle M. A. , Teixeira André L. , Burr Jamie F. , Millar Philip J.
Published: October 2023

The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.
Simulated Annealing Method for the Automated Simulation of DNA Dynamics in the HhaI Protein Binding Site
Authors: Pederson Kari , Groves Michael , Drobny Gary P.
Published: October 2023

Solid-state deuterium NMR is well suited to the study of the conformational dynamics of DNA. Deuterium quadrupole echo spectra for a particular motional model can be calculated and matched to the experimental spectrum to extract information on the DNA dynamics; however, doing so can be very time-intensive. The two-axis motion used to model the dynamics of either 2″ or 5′/5″ furanose ring deuteron is particularly complex with up to ten independent variables that can be optimized. Here, we present a program which automates both the input script generation and searches the parameter space for the best fit using a simulated annealing algorithm. The parameter,

χ

red

2

, provides a relative measure of goodness of fit. This method reduces the overall time to determine the best fit of a line shape to a few days, in most cases, when running on a low-power desktop PC. The automated fitting program presented here can be easily modified to generate input scripts for new models, incorporate a weighting factor to the

χ

red

2

calculation to emphasize key line shape features, or fit nonsymmetrized data. This adaptable program will make simulation of solid-state deuterium spectra accessible to a broader audience.
A Prospective Study Exploring the Safety and Efficacy of Lenvatinib for Patients with Advanced Hepatocellular Carcinoma and High Tumor Burden: The LAUNCH Study
Authors: Kobayashi Kazufumi , Ogasawara Sadahisa , Maruta Susumu , Okubo Tomomi , Itokawa Norio , Haga Yuki , Seko Yuya , Moriguchi Michihisa , Watanabe Shunji , Shiko Yuki , Takatsuka Hirokazu , Kanzaki Hiroaki , Koroki Keisuke , Inoue Masanori , Nakamura Masato , Kiyono Soichiro , Kanogawa Naoya , Kondo Takayuki , Suzuki Eiichiro , Ooka Yoshihiko , Nakamoto Shingo , Inaba Yosuke , Ikeda Masafumi , Okabe Shinichiro , Morimoto Naoki , Itoh Yoshito , Nakamura Kazuyoshi , Ito Kenji , Azemoto Ryosaku , Atsukawa Masanori , Itobayashi Ei , Kato Naoya
Published: October 2023

Purpose:

This study aimed to investigate the safety and efficacy of lenvatinib in real-world settings, including patients excluded from the REFLECT trial, a phase III trial that compared lenvatinib with sorafenib.

Patients and Methods:

This multicenter, nonrandomized, open-label prospective study was conducted at 10 medical facilities in Japan (jRCTs031190017). Eligible patients had advanced hepatocellular carcinoma (HCC) and were suitable for lenvatinib therapy. The study included patients with high tumor burden (with >50% intrahepatic tumor volume, main portal vein invasion, or bile duct invasion), Child-Pugh B status, and receiving lenvatinib as second-line therapy following atezolizumab plus bevacizumab.

Results:

From December 2019 to September 2021, 59 patients were analyzed (47 and 12 patients with Child-Pugh A and B, respectively). In patients with Child-Pugh A, the frequency of aspartate aminotransferase elevation was high (72.7%) in the high-burden group. No other significant ad verse events (AE) were observed even in second-line treatment. However, patients with Child-Pugh B had high incidence of grade ≥3 AE (100.0%) and high discontinuation rates caused by AE (33.3%) compared with patients with Child-Pugh A (80.9% and 17.0%, respectively). Median progression-free survival was 6.4 and 2.5 months and median overall survival was 19.7 and 4.1 months in Child-Pugh A and B, respectively. Lenvatinib plasma concentration was higher in patients with Child-Pugh B on days 8 and 15 and correlated with dose modifications and lower relative dose intensity.

Conclusions:

Lenvatinib is safe and effective for advanced HCC in patients with Child-Pugh A, even with high tumor burden. However, it carries a higher risk of AE and may not provide adequate efficacy for patients with Child-Pugh B status.
Supplementary Notes 1-5 from The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer
Authors: Mattox Austin K. , Douville Christopher , Wang Yuxuan , Popoli Maria , Ptak Janine , Silliman Natalie , Dobbyn Lisa , Schaefer Joy , Lu Steve , Pearlman Alexander H. , Cohen Joshua D. , Tie Jeanne , Gibbs Peter , Lahouel Kamel , Bettegowda Chetan , Hruban Ralph H. , Tomasetti Cristian , Jiang Peiyong , Chan K.C. Allen , Lo Yuk Ming Dennis , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert
Published: October 2023

Supplementary Notes 1-5. Supplementary Note 1: Origins of cell-free DNA. Supplementary Note 2: Leukocyte Lysis. Supplementary Note 3: Reference datasets and deconvolution algorithms used to interpret whole genome bisulfite sequencing data. Supplementary Note 4: Turnover rates. Supplementary Note 5: Relationships between ctDNA and tissue specific cfDNA in cancer patients.
Figure S8 from The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer
Authors: Mattox Austin K. , Douville Christopher , Wang Yuxuan , Popoli Maria , Ptak Janine , Silliman Natalie , Dobbyn Lisa , Schaefer Joy , Lu Steve , Pearlman Alexander H. , Cohen Joshua D. , Tie Jeanne , Gibbs Peter , Lahouel Kamel , Bettegowda Chetan , Hruban Ralph H. , Tomasetti Cristian , Jiang Peiyong , Chan K.C. Allen , Lo Yuk Ming Dennis , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert
Published: October 2023

Supplemental Figure 8. The relative contribution of cfDNA from various tissues before and ~24 hours after surgery for pancreatic cancer. * p < 0.05, ** p < 0.01, *** p < 0.001
Figure S7 from The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer
Authors: Mattox Austin K. , Douville Christopher , Wang Yuxuan , Popoli Maria , Ptak Janine , Silliman Natalie , Dobbyn Lisa , Schaefer Joy , Lu Steve , Pearlman Alexander H. , Cohen Joshua D. , Tie Jeanne , Gibbs Peter , Lahouel Kamel , Bettegowda Chetan , Hruban Ralph H. , Tomasetti Cristian , Jiang Peiyong , Chan K.C. Allen , Lo Yuk Ming Dennis , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert
Published: October 2023

Supplemental Figure 7. The amount of total cfDNA before and after surgery in patients with pancreatic cancer.
Table S8 from Early-Stage Breast Cancer Detection in Breast Milk
Authors: Saura Cristina , Ortiz Carolina , Matito Judit , Arenas Enrique J. , Suñol Anna , Martín Ágatha , Córdoba Octavi , Martínez-Sabadell Alex , García-Ruiz Itziar , Miranda Ignacio , Morales-Comas Clara , Carrasco Estela , Viaplana Cristina , Peg Vicente , Nuciforo Paolo , Bayó-Puxan Neus , Gonzalez-Medina Alberto , Miquel Josep M. , Gómez-Rey Marina , Villacampa Guillermo , Arévalo Silvia , Espinosa-Bravo Martín , Balmaña Judith , Dienstmann Rodrigo , Arribas Joaquin , Tabernero Josep , Vivancos Ana , Sansó Miriam
Published: October 2023

List of oligos and probes for each ddPCR assay
Table S2 from Early-Stage Breast Cancer Detection in Breast Milk
Authors: Saura Cristina , Ortiz Carolina , Matito Judit , Arenas Enrique J. , Suñol Anna , Martín Ágatha , Córdoba Octavi , Martínez-Sabadell Alex , García-Ruiz Itziar , Miranda Ignacio , Morales-Comas Clara , Carrasco Estela , Viaplana Cristina , Peg Vicente , Nuciforo Paolo , Bayó-Puxan Neus , Gonzalez-Medina Alberto , Miquel Josep M. , Gómez-Rey Marina , Villacampa Guillermo , Arévalo Silvia , Espinosa-Bravo Martín , Balmaña Judith , Dienstmann Rodrigo , Arribas Joaquin , Tabernero Josep , Vivancos Ana , Sansó Miriam
Published: October 2023

AURORA NGS panel gene list.
Table S6 from Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity
Authors: Guirguis Andrew A. , Ofir-Rosenfeld Yaara , Knezevic Kathy , Blackaby Wesley , Hardick David , Chan Yih-Chih , Motazedian Ali , Gillespie Andrea , Vassiliadis Dane , Lam Enid Y.N. , Tran Kevin , Andrews Byron , Harbour Michael E. , Vasiliauskaite Lina , Saunders Claire J. , Tsagkogeorga Georgia , Azevedo Aleksandra , Obacz Joanna , Pilka Ewa S. , Carkill Marie , MacPherson Laura , Wainwright Elanor N. , Liddicoat Brian , Blyth Benjamin J. , Albertella Mark R. , Rausch Oliver , Dawson Mark A.
Published: October 2023

LMOs for sc-RNA sequencing
Table S3 from Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity
Authors: Guirguis Andrew A. , Ofir-Rosenfeld Yaara , Knezevic Kathy , Blackaby Wesley , Hardick David , Chan Yih-Chih , Motazedian Ali , Gillespie Andrea , Vassiliadis Dane , Lam Enid Y.N. , Tran Kevin , Andrews Byron , Harbour Michael E. , Vasiliauskaite Lina , Saunders Claire J. , Tsagkogeorga Georgia , Azevedo Aleksandra , Obacz Joanna , Pilka Ewa S. , Carkill Marie , MacPherson Laura , Wainwright Elanor N. , Liddicoat Brian , Blyth Benjamin J. , Albertella Mark R. , Rausch Oliver , Dawson Mark A.
Published: October 2023

WB + other antibodies
Figure S3 from Early-Stage Breast Cancer Detection in Breast Milk
Authors: Saura Cristina , Ortiz Carolina , Matito Judit , Arenas Enrique J. , Suñol Anna , Martín Ágatha , Córdoba Octavi , Martínez-Sabadell Alex , García-Ruiz Itziar , Miranda Ignacio , Morales-Comas Clara , Carrasco Estela , Viaplana Cristina , Peg Vicente , Nuciforo Paolo , Bayó-Puxan Neus , Gonzalez-Medina Alberto , Miquel Josep M. , Gómez-Rey Marina , Villacampa Guillermo , Arévalo Silvia , Espinosa-Bravo Martín , Balmaña Judith , Dienstmann Rodrigo , Arribas Joaquin , Tabernero Josep , Vivancos Ana , Sansó Miriam
Published: October 2023

Diagnostic images of the PPBC from case #15 right breast
Table S1 from Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity
Authors: Guirguis Andrew A. , Ofir-Rosenfeld Yaara , Knezevic Kathy , Blackaby Wesley , Hardick David , Chan Yih-Chih , Motazedian Ali , Gillespie Andrea , Vassiliadis Dane , Lam Enid Y.N. , Tran Kevin , Andrews Byron , Harbour Michael E. , Vasiliauskaite Lina , Saunders Claire J. , Tsagkogeorga Georgia , Azevedo Aleksandra , Obacz Joanna , Pilka Ewa S. , Carkill Marie , MacPherson Laura , Wainwright Elanor N. , Liddicoat Brian , Blyth Benjamin J. , Albertella Mark R. , Rausch Oliver , Dawson Mark A.
Published: October 2023

STM3006 properties
Figure S1 from Early-Stage Breast Cancer Detection in Breast Milk
Authors: Saura Cristina , Ortiz Carolina , Matito Judit , Arenas Enrique J. , Suñol Anna , Martín Ágatha , Córdoba Octavi , Martínez-Sabadell Alex , García-Ruiz Itziar , Miranda Ignacio , Morales-Comas Clara , Carrasco Estela , Viaplana Cristina , Peg Vicente , Nuciforo Paolo , Bayó-Puxan Neus , Gonzalez-Medina Alberto , Miquel Josep M. , Gómez-Rey Marina , Villacampa Guillermo , Arévalo Silvia , Espinosa-Bravo Martín , Balmaña Judith , Dienstmann Rodrigo , Arribas Joaquin , Tabernero Josep , Vivancos Ana , Sansó Miriam
Published: October 2023

Breast milk charactherization as liquid biopsy specim and comparison to plasma
Figure S5 from Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity
Authors: Guirguis Andrew A. , Ofir-Rosenfeld Yaara , Knezevic Kathy , Blackaby Wesley , Hardick David , Chan Yih-Chih , Motazedian Ali , Gillespie Andrea , Vassiliadis Dane , Lam Enid Y.N. , Tran Kevin , Andrews Byron , Harbour Michael E. , Vasiliauskaite Lina , Saunders Claire J. , Tsagkogeorga Georgia , Azevedo Aleksandra , Obacz Joanna , Pilka Ewa S. , Carkill Marie , MacPherson Laura , Wainwright Elanor N. , Liddicoat Brian , Blyth Benjamin J. , Albertella Mark R. , Rausch Oliver , Dawson Mark A.
Published: October 2023

Co-culture assays + human PBMC data
Figure S3 from Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity
Authors: Guirguis Andrew A. , Ofir-Rosenfeld Yaara , Knezevic Kathy , Blackaby Wesley , Hardick David , Chan Yih-Chih , Motazedian Ali , Gillespie Andrea , Vassiliadis Dane , Lam Enid Y.N. , Tran Kevin , Andrews Byron , Harbour Michael E. , Vasiliauskaite Lina , Saunders Claire J. , Tsagkogeorga Georgia , Azevedo Aleksandra , Obacz Joanna , Pilka Ewa S. , Carkill Marie , MacPherson Laura , Wainwright Elanor N. , Liddicoat Brian , Blyth Benjamin J. , Albertella Mark R. , Rausch Oliver , Dawson Mark A.
Published: October 2023

METTL3 KD in B16 cell line
Supplementary Table S6 from An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma
Authors: Zhang Mao , Huang Yingying , Pan Jiaomeng , Sang Chen , Lin Youpei , Dong Liangqing , Shen Xia , Wu Yingcheng , Song Guohe , Ji Shuyi , Liu Fen , Wang Mengcheng , Zheng Yuyan , Zhang Sirui , Wang Zefeng , Ren Jianke , Gao Daming , Zhou Jian , Fan Jia , Wei Wu , Lin Jian , Gao Qiang
Published: October 2023

Supplementary Table S6. GO term and KEGG pathway information in Gzmb+ Cd8+ T cells.
Supplementary Table S1 from An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma
Authors: Zhang Mao , Huang Yingying , Pan Jiaomeng , Sang Chen , Lin Youpei , Dong Liangqing , Shen Xia , Wu Yingcheng , Song Guohe , Ji Shuyi , Liu Fen , Wang Mengcheng , Zheng Yuyan , Zhang Sirui , Wang Zefeng , Ren Jianke , Gao Daming , Zhou Jian , Fan Jia , Wei Wu , Lin Jian , Gao Qiang
Published: October 2023

Supplementary Table S1. Samples and transcriptomics information.
Data from Early-Stage Breast Cancer Detection in Breast Milk
Authors: Saura Cristina , Ortiz Carolina , Matito Judit , Arenas Enrique J. , Suñol Anna , Martín Ágatha , Córdoba Octavi , Martínez-Sabadell Alex , García-Ruiz Itziar , Miranda Ignacio , Morales-Comas Clara , Carrasco Estela , Viaplana Cristina , Peg Vicente , Nuciforo Paolo , Bayó-Puxan Neus , Gonzalez-Medina Alberto , Miquel Josep M. , Gómez-Rey Marina , Villacampa Guillermo , Arévalo Silvia , Espinosa-Bravo Martín , Balmaña Judith , Dienstmann Rodrigo , Arribas Joaquin , Tabernero Josep , Vivancos Ana , Sansó Miriam
Published: October 2023

Abstract
Breast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection.
Significance:
For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image.

See related commentary by Cunningham and Turner, p. 2125.

This article is featured in Selected Articles from This Issue, p. 2109
A New Paradigm of the Origins of Circulating DNA in Patients with Cancer
Authors: Thierry Alain R. , Pisareva Ekaterina
Published: October 2023

By shedding light on the cellular origins of circulating DNA (cirDNA), this research provides important insights into the mechanisms of cirDNA production in cancer. Contrary to expectations, the increased cirDNA in patients with cancer was not derived predominantly from neoplastic cells or surrounding nonneoplastic epithelial cells; rather, the excess cirDNA originated primarily from leukocytes, implying a systemic impact of cancer on cell turnover or DNA clearance.

See related article by Mattox et al., p. 2166 (1).
Liquid Biopsies in Breast Milk for the Early Detection of Breast Cancer
Authors: Cunningham Niamh , Turner Nicholas C
Published: October 2023

Cell-free tumor DNA has previously been detected in nonblood sources, including urine, saliva, stool, cerebrospinal fluid, and pleural fluid. In this issue, Saura and colleagues present a novel proof-of-concept study demonstrating that detection of tumor DNA in breast milk is feasible and may be a potential future strategy to screen for postpartum breast cancer.

See related article by Saura et al., p. 2180 (14).
Supplementary Table 8 from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry
Authors: Harris Alexandra R. , Panigrahi Gatikrushna , Liu Huaitian , Koparde Vishal N. , Bailey-Whyte Maeve , Dorsey Tiffany H. , Yates Clayton C. , Ambs Stefan
Published: October 2023

Supplementary table 8 displaying data output from differential ATAC signal analysis performed on ATAC-seq data from TNBC cell lines cultured under hypoxia.
Supplementary Table 3 from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry
Authors: Harris Alexandra R. , Panigrahi Gatikrushna , Liu Huaitian , Koparde Vishal N. , Bailey-Whyte Maeve , Dorsey Tiffany H. , Yates Clayton C. , Ambs Stefan
Published: October 2023

Supplementary table 3 displaying data output from gene set enrichment analysis for transcriptional regulators performed on RNA-seq data from TNBC cell lines.
Supplementary Figure 1 from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry
Authors: Harris Alexandra R. , Panigrahi Gatikrushna , Liu Huaitian , Koparde Vishal N. , Bailey-Whyte Maeve , Dorsey Tiffany H. , Yates Clayton C. , Ambs Stefan
Published: October 2023

Supplemental Figure 1. Quantified genetic ancestry in TCGA participants by self-reported race. Using published ancestry annotations from Carrot-Zhang et al1, quantified genetic ancestry was compared to self-reported race (SRR). For 111/112 TCGA samples used in our study, genetic ancestry consensus was concordant with SRR. Genetic ancestry consensus classification of African or admixed African ancestry captured 100% of TCGA participants who self-identified as “Black or African American”. Genetic ancestry consensus classification of EUR ancestry captured 98.7% of TCGA participants who self-identified as “White”; in one case, a participant that self-identified as White demonstrated a higher proportion of admixed American genetic ancestry. Among TCGA participants who self-identified as Black or African American, the average percentage of African ancestry was 83.2%, which is comparable to the quantified genetic ancestry estimates for the human cell lines used in this study that were classified as African American-derived (average African ancestry of 79.5%). Among TCGA participants who self-identified as White, the average percentage of European ancestry was 96.7%, which is comparable to the quantified genetic ancestry estimates for the human cell lines used in this study that were classified as European American-derived (average European ancestry of 93.0%).
FIGURE 3 from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry
Authors: Harris Alexandra R. , Panigrahi Gatikrushna , Liu Huaitian , Koparde Vishal N. , Bailey-Whyte Maeve , Dorsey Tiffany H. , Yates Clayton C. , Ambs Stefan
Published: October 2023

Differential ATAC signal analysis of human TNBC cell lines identified ancestry-associated genes within differentially accessible chromatin regions across all genomic elements. Genes are displayed on a volcano plot, where the y-axis shows statistical significance (plotted as −log10 FDR) and the x-axis shows the differences between each ancestry group (plotted as log2 fold change). The horizontal dashed lines depict our specified significance cut-off points, with genes that showed an FDR < 0.05 and a |log2FC| > 1 shown in red. Negative log2 fold change values show genes differentially open or up in AA donor cell lines, while positive log2 fold change values show genes differentially open or up in EA donor cell lines.
FIGURE 1 from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry
Authors: Harris Alexandra R. , Panigrahi Gatikrushna , Liu Huaitian , Koparde Vishal N. , Bailey-Whyte Maeve , Dorsey Tiffany H. , Yates Clayton C. , Ambs Stefan
Published: October 2023

Genome-wide landscape of chromatin accessibility in TNBC cell lines derived from EA and AA women. A, Fragment length distribution plot for TNBC cell lines. Peak < 150 bp indicates a nucleosome-free peak; peak between 150 and 300 bp indicates a mononucleosome peak. FRiP scores greater than 0.3 indicate high quality of the data. Technical replicates (n = 2) were averaged for each cell line. B, Summary of peak distribution across all samples. C, Number of peaks by TNBC cell line. All samples had high peak numbers (∼75,000) covering promoters and intergenic regions. D, Principal component analysis showing separation of the chromosome accessibility landscape by ancestry for the nine TNBC cell lines. Technical replicates (n = 2) were averaged for each line. E, Chromosome map showing the distribution of DARs between EA and AA TNBC cells (FC > 2, FDR < 0.01).
Data from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry
Authors: Harris Alexandra R. , Panigrahi Gatikrushna , Liu Huaitian , Koparde Vishal N. , Bailey-Whyte Maeve , Dorsey Tiffany H. , Yates Clayton C. , Ambs Stefan
Published: October 2023

Abstract
African American (AA) women have an excessive risk of developing triple-negative breast cancer (TNBC). We employed Assay for Transposase-Accessible Chromatin using sequencing to characterize differences in chromatin accessibility between nine commonly used TNBC cell lines derived from patients of European and African ancestry. Principal component and chromosome mapping analyses of accessibility peaks with the most variance revealed separation of chromatin profiles by patient group. Motif enrichment and footprinting analyses of disparate open chromatin regions revealed differences in transcription factor activity, identifying 79 with ancestry-associated binding patterns (FDR < 0.01). AA TNBC cell lines exhibited increased accessibility for 62 transcription factors associated with epithelial-to-mesenchymal transition, cancer stemness/chemotherapeutic resistance, proliferation, and aberrant p53 regulation, as well as KAISO, which has been previously linked to aggressive tumor characteristics in AA patients with cancer. Differential Assay for Transposase-Accessible Chromatin signal analysis identified 1,596 genes located within promoters of differentially open chromatin regions in AA-derived TNBC, identifying DNA methyltransferase 1 as the top upregulated gene associated with African ancestry. Pathway analyses with these genes revealed enrichment in several pathways, including hypoxia. Culturing cells under hypoxia showed ancestry-specific stress responses that led to the identification of a core set of AA-associated transcription factors, which included members of the Kruppel-like factor and Sp subfamilies, as well as KAISO, and identified ZDHHC1, a gene previously implicated in immunity and STING activation, as the top upregulated AA-specific gene under hypoxia. Together, these data reveal a differential chromatin landscape in TNBC associated with donor ancestry. The open chromatin structure of AA TNBC may contribute to a more lethal disease.
Significance:
We identify an ancestry-associated open chromatin landscape and related transcription factors that may contribute to aggressive TNBC in AA women. Furthermore, this study advocates for the inclusion of diversely sourced cell lines in experimental in vitro studies to advance health equity at all levels of scientific research.
Feminist Pragmatist Design: Evolutionary Systems Change
Authors: Lake Danielle , Whipps Judy
Published: October 2023

What might feminist pragmatist methods of engagement have to offer to design efforts aimed at catalyzing and sustaining change in complex systems? This article examines two systemic social design initiatives emerging from classical feminist pragmatists that illustrate their core commitments and social change methods. These initiatives highlight four strategies found to be critical to feminist pragmatist social design inquiry: 1) situated and relational exploration across diverse communities, 2) iterative and experimental prototyping, 3) a willingness to accept incremental change, and 4) a commitment to deep and sustained engagement within communities.
Striatal response to negative feedback in a stop signal task operates as a multi-value learning signal
Authors: Smith Benjamin J. , Lipsett Megan , Cosme Danielle , Braun Victoria A. , Browning O’Hagan Anastasia M. , Berkman Elliot T.
Published: October 2023

Background and aim: We examined error-driven learning in fMRI activity of 217 subjects in a stop signal task to obtain a more robust characterization of the relation between behavioral measures of learning and corresponding neural learning signals than previously possible.

Methods: The stop signal task is a two-alternative forced choice in which participants respond to an arrow by pressing a left or right button but must inhibit that response on 1 in 7 trials when cued by an auditory “stop signal.” We examined post-error learning by comparing brain activity (BOLD signal) and behavioral responses on trials preceded by successful (correct stop) vs. failed (failed stop) inhibition.

Results: There was strong evidence of greater bilateral striatal activity in the period immediately following correct (vs. failed) stop trials (most evident in the putamen; peak MNI coordinates [-26 8 -2], 430 voxels, p < 0.001; [24 14 0], 527 voxels, p < 0.001). We measured median activity in the bilateral striatal cluster following every failed stop and correct stop trial and correlated it with learning signals for (a) probability and (b) latency of the stop signal. In a mixed-effects model predicting activity 5-10 s after the stop signal, both reaction time (RT) change (B = -0.05, t = 3.0, χ2 = 11.3, p < 0.001) and probability of stop trial change (B = 1.53, t = 6.0, χ2 = 43.0, p < 0.001) had significant within-subjects effects on median activity. In a similar mixed model predicting activity 1-5 s after the stop signal, only probability of stop trial change was predictive.

Conclusions: A mixed-effects model indicates the striatal activity might be a learning signal that encodes reaction time change and the current expected probability of a stop trial occuring. This extends existing evidence that the striatum encodes a reward prediction error signal for learning within the stop signal task, and demonstrates for the first time that this signal seems to encode both change in stop signal probability and in stop signal delay.
The Othering and Resilience of Jehovah’s Witnesses in Soviet and Contemporary Lithuania
Authors: Ališauskienė Milda
Published: October 2023

Social research data shows that Jehovah’s Witnesses experience social ostracism, distancing, marginalization, and labeling in contemporary Lithuania. This article searches for an explanation for these public attitudes by applying a sociohistorical approach to the analysis of the processes of othering and resilience of Jehovah’s Witnesses in Lithuania from the organization’s arrival at the beginning of the twentieth century to today, focusing on its relations with society and state. It is based on the document and literature analysis of organization and academic sources as well as interviews with Jehovah’s Witnesses conducted in 2020–2021. The article argues that the social history of Jehovah’s Witnesses in Lithuania illustrates the processes of othering and resilience since the arrival of the organization in Lithuania throughout the Soviet period and in the Republic of Lithuania, as since 1990 both society and state have been contributing to the process of othering, while Witnesses continue persistently to exemplify resilient religion.
Faith in Self
Authors: Tanaka Yasuyo
Published: October 2023

In 1994, I migrated to New York City to pursue my art, freedom, and potential. Over the last 27 years, I learned to understand and respect the differences of people with different values, genders, religions, and races. I continued self-transforming by looking at issues from different angles with flexible thinking. Living far away from Japan, I reaffirmed my roots and rediscovered myself objectively. It’s especially interesting to me that the relationship between Japan and the United States has been strengthened through the atomic bomb. Behind this is the influence of Shinto and Buddhism on the Japanese way of thinking. Their teachings play a major role in peace operations. In addition, the power of faith is sometimes abused, and serious social problems are occurring. “Kusudama” means medicine ball. In my Peace and Harmony Workshop, many individual participants, who all experienced the same pandemic disaster, created medicine balls while sharing our common wishes for health, long life, and peace. Faith is, to me, the power to believe in ourselves. The symbolic work of a sphere, connecting faith and art, opens up a world full of charity, not division. Looking back on what I learned through my life and artwork, I consider and write about what kind of future we hope for, and what role religion and art can play.
The “Phenomenon” in Mamardashvili’s Phenomenology of Ontological Maturation
Authors: Kuravsky Erik
Published: October 2023

In the essay, I present the basic principles of Merab Mamardashvili’s phenomenology of ontological maturation. Though Mamardashvili’s thinking has been recently introduced to the West, there is still very little awareness of the uniqueness of his phenomenological insights, allowing him to illuminate contemporary philosophy’s central ontological and existential matters in a novel light. The essay addresses Mamardashvili’s interpretation of the “phenomenon,” which he exemplifies on rich experiential material from Proust’s novel In Search of Lost Time. The “phenomenon” is shown to differ radically from its traditional phenomenological interpretation as something that gives/shows itself in/for experience. Instead, the phenomenon is interpreted as an event that shocks one unexpectedly and offers a momentary opportunity to let oneself be appropriated by that truth, constituting the event of being human. I explicate the relations between Mamardashvili’s notion of the phenomenon, human transformation, and ontology. The central theme of these discussions is a new sense of human agency and autonomy revealed as the goal of transformation and requiring that one walks a path of ontological maturation.
A Moral Success and a Profitable One
Authors: Fleming Catherine
Published: October 2023

In the early years of the twentieth century, U.S. relationships with the East were shaped by influential men and women bent on modernising and Christianising other countries. Sidney Gulick, whose 1915 Working Women of Japan is part of a larger effort to support Japan’s modernisation, writes about a charitable institution as an exemplar for future projects. Although the project successfully attracted many young textile workers and assisted them by providing education, healthy living, and new opportunities, it also reveals a darker underside to western charitable impulses. Gulick conflates morality with industry, happiness with production, and success with profit, reducing a laudable attempt to interest fellow Americans in charitable efforts to an attempt to gain buy-in for a commercial project. By working in close partnership with exploitative factories and their owners, these would-be reformers end by supporting the very conditions which they set out to reform.
International Mediation, Identity Construction, and Normative Change
Authors: Clowry Sarah
Published: October 2023

In this article, I argue the following: mediation can operate as an arena in which identities are reconstructed while the very occurrence of mediation can trigger and fuel processes of identity reconstruction. More precisely, the norms promoted through mediation can serve to reconstruct the identities of the conflict parties. I will make this claim by examining two contemporary instances of mediation in Syria and Yemen, cases which diverge in the third-party peacemaking approach taken. I investigate these cases by gathering and thematically analyzing an original qualitative dataset comprising 74 semi-structured interviews, 50 press conferences, and 110 official documents. My analysis challenges existing literature concerning the intertwinement of norms, identity, and mediation; contributes to our understanding of how identities in Syria and Yemen were transformed following the revolutions of 2011; and interrogates traditional understandings of the purpose and effects of mediation.