bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adversarial attacks and adversarial robustness in computational pathology
Authors: Ghaffari Laleh Narmin , Truhn Daniel , Veldhuizen Gregory Patrick , Han Tianyu , van Treeck Marko , Buelow Roman D. , Langer Rupert , Dislich Bastian , Boor Peter , Schulz Volkmar , Kather Jakob Nikolas 
Published: September 2022

AbstractArtificial Intelligence (AI) can support diagnostic workflows in oncology by aiding diagnosis and providing biomarkers directly from routine pathology slides. However, AI applications are vulnerable to adversarial attacks. Hence, it is essential to quantify and mitigate this risk before widespread clinical use. Here, we show that convolutional neural networks (CNNs) are highly susceptible to white- and black-box adversarial attacks in clinically relevant weakly-supervised classification tasks. Adversarially robust training and dual batch normalization (DBN) are possible mitigation strategies but require precise knowledge of the type of attack used in the inference. We demonstrate that vision transformers (ViTs) perform equally well compared to CNNs at baseline, but are orders of magnitude more robust to white- and black-box attacks. At a mechanistic level, we show that this is associated with a more robust latent representation of clinically relevant categories in ViTs compared to CNNs. Our results are in line with previous theoretical studies and provide empirical evidence that ViTs are robust learners in computational pathology. This implies that large-scale rollout of AI models in computational pathology should rely on ViTs rather than CNN-based classifiers to provide inherent protection against perturbation of the input data, especially adversarial attacks.
TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
Authors: Meng Zhaoyue , Li Zhichao , Xie Mingxu , Yu Hongyan , Jiang Liwen , Yao Xiaoqiang 
Published: September 2022

AbstractF-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF4 in regulating actin dynamics and controlling cancer cell motility and metastasis. We show that an N-terminal fragment (NTF) cleaved from TM9SF4 can directly bind to F-actin to induce actin oxidation at Cys374, consequently enhancing cofilin-mediated F-actin disassembly. Knockdown of TM9SF4 reduces cell migration and invasion in ovarian cancer cells A2780, SKOV3 and several high grade serous ovarian cancer lines (HGSOCs). In vivo, knockdown of TM9SF4 completely abolishes the tumor growth and metastasis in athymic nude mice. These data provide mechanistic insights into TM9SF4-mediated regulation of actin dynamics in ovarian cancer cells.
Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
Authors: Li Yan , Xu Chen , Wang Bing , Xu Fujiang , Ma Fahan , Qu Yuanyuan , Jiang Dongxian , Li Kai , Feng Jinwen , Tian Sha , Wu Xiaohui , Wang Yunzhi , Liu Yang , Qin Zhaoyu , Liu Yalan , Qin Jing , Song Qi , Zhang Xiaolei , Sujie Akesu , Huang Jie , Liu Tianshu , Shen Kuntang , Zhao Jian-Yuan , Hou Yingyong , Ding Chen 
Published: September 2022

AbstractChemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals four subtypes (G-I–G-IV) related to different clinical and molecular features. MSI-sig high GC patients benefit from docetaxel combination treatment, accompanied by anticancer immune response. Further study reveals patients with high T cell receptor signaling respond to anti-HER2-based therapy; while activation of extracellular matrix/PI3K-AKT pathway impair anti-tumor effect of trastuzumab. We observe CTSE functions as a cell intrinsic enhancer of chemosensitivity of docetaxel, whereas TKTL1 functions as an attenuator. Finally, we develop prognostic models with high accuracy to predict therapeutic response, further validated in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemotherapy and targeted therapy in GC.
Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler
Authors: Van Nieuwenhuyse Brieuc , Van der Linden Dimitri , Chatzis Olga , Lood Cédric , Wagemans Jeroen , Lavigne Rob , Schroven Kaat , Paeshuyse Jan , de Magnée Catherine , Sokal Etienne , Stéphenne Xavier , Scheers Isabelle , Rodriguez-Villalobos Hector , Djebara Sarah , Merabishvili Maya , Soentjens Patrick , Pirnay Jean-Paul 
Published: September 2022

AbstractPost-operative bacterial infections are a leading cause of mortality and morbidity after ongoing liver transplantation. Bacteria causing these infections in the hospital setting can exhibit high degrees of resistance to multiple types of antibiotics, which leads to major therapeutic hurdles. Alternate ways of treating these antibiotic-resistant infections are thus urgently needed. Phage therapy is one of them and consists in using selected bacteriophage viruses – viruses who specifically prey on bacteria, naturally found in various environmental samples – as bactericidal agents in replacement or in combination with antibiotics. The use of phage therapy raises various research questions to further characterize what determines therapeutic success or failure. In this work, we report the story of a toddler who suffered from extensively drug-resistant Pseudomonas aeruginosa sepsis after liver transplantation. He was treated by a bacteriophage-antibiotic intravenous combination therapy for 86 days. This salvage therapy was well tolerated, without antibody-mediated phage neutralization. It was associated with objective clinical and microbiological improvement, eventually allowing for liver retransplantation and complete resolution of all infections. Clear in vitro phage-antibiotic synergies were observed. The occurrence of bacterial phage resistance did not result in therapeutic failure, possibly due to phage-induced virulence tradeoffs, which we investigated in different experimental models.
Genome-wide association study identifies a gene responsible for temperature-dependent rice germination
Authors: Yoshida Hideki , Hirano Ko , Yano Kenji , Wang Fanmiao , Mori Masaki , Kawamura Mayuko , Koketsu Eriko , Hattori Masako , Ordonio Reynante Lacsamana , Huang Peng , Yamamoto Eiji , Matsuoka Makoto 
Published: September 2022

AbstractEnvironment is an important determinant of agricultural productivity; therefore, crops have been bred with traits adapted to their environment. It is assumed that the physiology of seed germination is optimised for various climatic conditions. Here, to understand the genetic basis underlying seed germination, we conduct a genome-wide association study considering genotype-by-environment interactions on the germination rate of Japanese rice cultivars under different temperature conditions. We find that a 4 bp InDel in one of the 14-3-3 family genes, GF14h, preferentially changes the germination rate of rice under optimum temperature conditions. The GF14h protein constitutes a transcriptional regulatory module with a bZIP-type transcription factor, OREB1, and a florigen-like protein, MOTHER OF FT AND TFL 2, to control the germination rate by regulating abscisic acid (ABA)-responsive genes. The GF14h loss-of-function allele enhances ABA signalling and reduces the germination rate. This allele is found in rice varieties grown in the northern area and in modern cultivars of Japan and China, suggesting that it contributes to the geographical adaptation of rice. This study demonstrates the complicated molecular system involved in the regulation of seed germination in response to temperature, which has allowed rice to be grown in various geographical locations.
Regain flood adaptation in rice through a 14-3-3 protein OsGF14h
Authors: Sun Jian , Zhang Guangchen , Cui Zhibo , Kong Ximan , Yu Xiaoyu , Gui Rui , Han Yuqing , Li Zhuan , Lang Hong , Hua Yuchen , Zhang Xuemin , Xu Quan , Tang Liang , Xu Zhengjin , Ma Dianrong , Chen Wenfu 
Published: September 2022

AbstractContemporary climatic stress seriously affects rice production. Unfortunately, long-term domestication and improvement modified the phytohormones network to achieve the production needs of cultivated rice, thus leading to a decrease in adaptation. Here, we identify a 14-3-3 protein-coding gene OsGF14h in weedy rice that confers anaerobic germination and anaerobic seedling development tolerance. OsGF14h acts as a signal switch to balance ABA signaling and GA biosynthesis by interacting with the transcription factors OsHOX3 and OsVP1, thereby boosting the seeding rate from 13.5% to 60.5% for anaerobic sensitive variety under flooded direct-seeded conditions. Meanwhile, OsGF14h co-inheritance with the Rc (red pericarp gene) promotes divergence between temperate japonica cultivated rice and temperate japonica weedy rice through artificial and natural selection. Our study retrieves a superior allele that has been lost during modern japonica rice improvement and provides a fine-tuning tool to improve flood adaptation for elite rice varieties.
MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis
Authors: LaPierre Mary P. , Lawler Katherine , Godbersen Svenja , Farooqi I. Sadaf , Stoffel Markus 
Published: September 2022

AbstractMicroRNAs (miRNAs) modulate physiological responses by repressing the expression of gene networks. We found that global deletion of microRNA-7 (miR-7), the most enriched miRNA in the hypothalamus, causes obesity in mice. Targeted deletion of miR-7 in Single-minded homolog 1 (Sim1) neurons, a critical component of the hypothalamic melanocortin pathway, causes hyperphagia, obesity and increased linear growth, mirroring Sim1 and Melanocortin-4 receptor (MC4R) haplo-insufficiency in mice and humans. We identified Snca (α-Synuclein) and Igsf8 (Immunoglobulin Superfamily Member 8) as miR-7 target genes that act in Sim1 neurons to regulate body weight and endocrine axes. In humans, MIR-7-1 is located in the last intron of HNRNPK, whose promoter drives the expression of both genes. Genetic variants at the HNRNPK locus that reduce its expression are associated with increased height and truncal fat mass. These findings demonstrate that miR-7 suppresses gene networks involved in the hypothalamic melanocortin pathway to regulate mammalian energy homeostasis.
Deciphering microbial gene function using natural language processing
Authors: Miller Danielle , Stern Adi , Burstein David 
Published: September 2022

AbstractRevealing the function of uncharacterized genes is a fundamental challenge in an era of ever-increasing volumes of sequencing data. Here, we present a concept for tackling this challenge using deep learning methodologies adopted from natural language processing (NLP). We repurpose NLP algorithms to model “gene semantics” based on a biological corpus of more than 360 million microbial genes within their genomic context. We use the language models to predict functional categories for 56,617 genes and find that out of 1369 genes associated with recently discovered defense systems, 98% are inferred correctly. We then systematically evaluate the “discovery potential” of different functional categories, pinpointing those with the most genes yet to be characterized. Finally, we demonstrate our method’s ability to discover systems associated with microbial interaction and defense. Our results highlight that combining microbial genomics and language models is a promising avenue for revealing gene functions in microbes.
Coherent dynamics of multi-spin V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ center in hexagonal boron nitride
Authors: Liu Wei , Ivády Viktor , Li Zhi-Peng , Yang Yuan-Ze , Yu Shang , Meng Yu , Wang Zhao-An , Guo Nai-Jie , Yan Fei-Fei , Li Qiang , Wang Jun-Feng , Xu Jin-Shi , Liu Xiao , Zhou Zong-Quan , Dong Yang , Chen Xiang-Dong , Sun Fang-Wen , Wang Yi-Tao , Tang Jian-Shun , Gali Adam , Li Chuan-Feng , Guo Guang-Can 
Published: September 2022

AbstractHexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in nanolayered-devices. Understanding the coherent dynamics of microwave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$

B

−

) spin ensemble in hBN. We report on different dynamics of the V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$

B

−

spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$

B

−

and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$

B

−

center, which can be modulated by the magnetic field and microwave field.
Spatiotemporal organisation of protein processing in the kidney
Authors: Polesel Marcello , Kaminska Monika , Haenni Dominik , Bugarski Milica , Schuh Claus , Jankovic Nevena , Kaech Andres , Mateos Jose M. , Berquez Marine , Hall Andrew M. 
Published: September 2022

AbstractThe kidney regulates plasma protein levels by eliminating them from the circulation. Proteins filtered by glomeruli are endocytosed and degraded in the proximal tubule and defects in this process result in tubular proteinuria, an important clinical biomarker. However, the spatiotemporal organization of renal protein metabolism in vivo was previously unclear. Here, using functional probes and intravital microscopy, we track the fate of filtered proteins in real time in living mice, and map specialized processing to tubular structures with singular value decomposition analysis and three-dimensional electron microscopy. We reveal that degradation of proteins requires sequential, coordinated activity of distinct tubular sub-segments, each adapted to specific tasks. Moreover, we leverage this approach to pinpoint the nature of endo-lysosomal disorders in disease models, and show that compensatory uptake in later regions of the proximal tubule limits urinary protein loss. This means that measurement of proteinuria likely underestimates severity of endocytotic defects in patients.
Association between formal thought disorder and cannabis use: a systematic review and meta-analysis
Authors: Argote Mathilde , Sescousse Guillaume , Brunelin Jérôme , Fakra Eric , Nourredine Mikail , Rolland Benjamin 
Published: September 2022

AbstractFormal thought disorder (FTD) is a multidimensional syndrome mainly occurring along the psychosis continuum. Cannabis use is known to increase symptoms of psychosis, particularly positive symptoms. However, the impact of cannabis use on FTD in individuals presenting symptoms along the psychosis continuum remains unclear. To address this knowledge gap, we conducted a meta-analysis examining the association between cannabis use and FTD in those individuals. We hypothesized that cannabis would worsen FTD. We conducted a systematic search of the PubMed, ScienceDirect, PsycINFO, Web of Science, Embase and Google Scholar databases up to July 2022. The results were collated through a random-effects model using the statistical software R. Reference lists of included studies were searched for additional relevant publications. Nineteen studies were included, totalling 1840 cannabis users and 3351 non-cannabis users. The severity of FTD was found to be higher in cannabis users (SMD = 0.21, 95%CI [0.12–0.29], p = 0.00009). Subgroup analyses revealed that FTD severity was increased among cannabis users, regardless of the disorder severity: healthy individuals (SMD = 0.19, 95%CI [0.05–0.33], p = 0.02); patients with first-episode psychosis (SMD = 0.21, 95%CI [0.01–0.41], p = 0.04); patients with schizophrenia (SMD = 0.25, 95%CI [0.11–0.38], p = 0.005). Between-group differences were not significant. In line with its already known effect on positive symptoms in psychosis, cannabis use appears to be associated with increased FTD severity all along the psychosis continuum. Future research should consider potential confounding variables such as other substance use disorders and explore how FTD dimensions are impacted by cannabis use.
Analysis of the Human Protein Atlas Weakly Supervised Single-Cell Classification competition
Authors: Le Trang , Winsnes Casper F. , Axelsson Ulrika , Xu Hao , Mohanakrishnan Kaimal Jayasankar , Mahdessian Diana , Dai Shubin , Makarov Ilya S. , Ostankovich Vladislav , Xu Yang , Benhamou Eric , Henkel Christof , Solovyev Roman A. , Banić Nikola , Bošnjak Vito , Bošnjak Ana , Miličević Andrija , Ouyang Wei , Lundberg Emma 
Published: September 2022

AbstractWhile spatial proteomics by fluorescence imaging has quickly become an essential discovery tool for researchers, fast and scalable methods to classify and embed single-cell protein distributions in such images are lacking. Here, we present the design and analysis of the results from the competition Human Protein Atlas – Single-Cell Classification hosted on the Kaggle platform. This represents a crowd-sourced competition to develop machine learning models trained on limited annotations to label single-cell protein patterns in fluorescent images. The particular challenges of this competition include class imbalance, weak labels and multi-label classification, prompting competitors to apply a wide range of approaches in their solutions. The winning models serve as the first subcellular omics tools that can annotate single-cell locations, extract single-cell features and capture cellular dynamics.
Economic estimation of Bitcoin mining’s climate damages demonstrates closer resemblance to digital crude than digital gold
Authors: Jones Benjamin A. , Goodkind Andrew L. , Berrens Robert P. 
Published: September 2022

AbstractThis paper provides economic estimates of the energy-related climate damages of mining Bitcoin (BTC), the dominant proof-of-work cryptocurrency. We provide three sustainability criteria for signaling when the climate damages may be unsustainable. BTC mining fails all three. We find that for 2016–2021: (i) per coin climate damages from BTC were increasing, rather than decreasing with industry maturation; (ii) during certain time periods, BTC climate damages exceed the price of each coin created; (iii) on average, each $1 in BTC market value created was responsible for $0.35 in global climate damages, which as a share of market value is in the range between beef production and crude oil burned as gasoline, and an order-of-magnitude higher than wind and solar power. Taken together, these results represent a set of sustainability red flags. While proponents have offered BTC as representing “digital gold,” from a climate damages perspective it operates more like “digital crude”.
Identification of novel differentially expressed genes in type 1 diabetes mellitus complications using transcriptomic profiling of UAE patients: a multicenter study
Authors: Mussa Bashair M. , Venkatachalam Thenmozhi , Srivastava Ankita , Al-Habshi Abeer , Abdelgadir Elamin , Bashier Alaaeldin , Al Awadi Fatheya , Hafidh Khadija , Hamoudi Rifat , Abusnana Salah 
Published: September 2022

AbstractType 1 diabetes mellitus (T1DM) is a chronic metabolic disorder that mainly affects children and young adults. It is associated with debilitating and long-life complications. Therefore, understanding the factors that lead to the onset and development of these complications is crucial. To our knowledge this is the first study that attempts to identify the common differentially expressed genes (DEGs) in T1DM complications using whole transcriptomic profiling in United Arab Emirates (UAE) patients. The present multicenter study was conducted in different hospitals in UAE including University Hospital Sharjah, Dubai Hospital and Rashid Hospital. A total of fifty-eight Emirati participants aged above 18 years and with a BMI < 25 kg/m2 were recruited and forty-five of these participants had a confirmed diagnosis of T1DM. Five groups of complications associated with the latter were identified including hyperlipidemia, neuropathy, ketoacidosis, hypothyroidism and polycystic ovary syndrome (PCOS). A comprehensive whole transcriptomic analysis using NGS was conducted. The outcomes of the study revealed the common DEGs between T1DM without complications and T1DM with different complications. The results revealed seven common candidate DEGs, SPINK9, TRDN, PVRL4, MYO3A, PDLIM1, KIAA1614 and GRP were upregulated in T1DM complications with significant increase in expression of SPINK9 (Fold change: 5.28, 3.79, 5.20, 3.79, 5.20) and MYO3A (Fold change: 4.14, 6.11, 2.60, 4.33, 4.49) in hyperlipidemia, neuropathy, ketoacidosis, hypothyroidism and PCOS, respectively. In addition, functional pathways of ion transport, mineral absorption and cytosolic calcium concentration were involved in regulation of candidate upregulated genes related to neuropathy, ketoacidosis and PCOS, respectively. The findings of this study represent a novel reference warranting further studies to shed light on the causative genetic factors that are involved in the onset and development of T1DM complications.
Weak-keys and key-recovery attack for $$\text{ TinyJAMBU }$$
Authors: Dutta Pranjal , Rajasree Mahesh Sreekumar , Sarkar Santanu 
Published: September 2022

AbstractIn this paper, we study NIST lightweight 3rd round candidate $$\text{ TinyJAMBU }$$

TinyJAMBU

. The core component of $$\text{ TinyJAMBU }$$

TinyJAMBU

is the keyed permutation $$\mathcal {P}_n$$

P
n

, which is based on a non-linear feedback shift register. By analysing this permutation carefully, we are able to find good cubes that are used to build distinguishers in the weak-key setting. In particular, we show that there are at least $$2^{108}$$

2
108

keys for which TinyJAMBU can be distinguished from a random source for up to 476 rounds. These distinguishers outperform the best-known distinguishers, which were proposed in ‘Scientific Reports - Nature’ by Teng et al. We are the first to study the exact degree of the feedback polynomial $$\mathcal {P}_n$$

P
n

in the nonce variables. This helped us in concluding that $$\text{ TinyJAMBU }$$

TinyJAMBU

with more than 445 rounds is secure against distinguishers using 32 sized cubes in the normal setting. Finally, we give new key-recovery attacks against $$\text{ TinyJAMBU }$$

TinyJAMBU

using the concepts of monomial trail presented by Hu et al. at ASIACRYPT 2020. Our attacks are unlikely to jeopardise the security of the entire 640 rounds $$\text{ TinyJAMBU }$$

TinyJAMBU

, but we strongly anticipate that they will shed new lights on the cipher’s security.