bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pacpaint: a histology-based deep learning model uncovers the extensive intratumor molecular heterogeneity of pancreatic adenocarcinoma
Authors: Saillard Charlie , Delecourt Flore , Schmauch Benoit , Moindrot Olivier , Svrcek Magali , Bardier-Dupas Armelle , Emile Jean Francois , Ayadi Mira , Rebours Vinciane , de Mestier Louis , Hammel Pascal , Neuzillet Cindy , Bachet Jean Baptiste , Iovanna Juan , Dusetti Nelson , Blum Yuna , Richard Magali , Kermezli Yasmina , Paradis Valerie , Zaslavskiy Mikhail , Courtiol Pierre , Kamoun Aurelie , Nicolle Remy , Cros Jerome 
Published: June 2023

AbstractTwo tumor (Classical/Basal) and stroma (Inactive/active) subtypes of Pancreatic adenocarcinoma (PDAC) with prognostic and theragnostic implications have been described. These molecular subtypes were defined by RNAseq, a costly technique sensitive to sample quality and cellularity, not used in routine practice. To allow rapid PDAC molecular subtyping and study PDAC heterogeneity, we develop PACpAInt, a multi-step deep learning model. PACpAInt is trained on a multicentric cohort (n = 202) and validated on 4 independent cohorts including biopsies (surgical cohorts n = 148; 97; 126 / biopsy cohort n = 25), all with transcriptomic data (n = 598) to predict tumor tissue, tumor cells from stroma, and their transcriptomic molecular subtypes, either at the whole slide or tile level (112 µm squares). PACpAInt correctly predicts tumor subtypes at the whole slide level on surgical and biopsies specimens and independently predicts survival. PACpAInt highlights the presence of a minor aggressive Basal contingent that negatively impacts survival in 39% of RNA-defined classical cases. Tile-level analysis ( > 6 millions) redefines PDAC microheterogeneity showing codependencies in the distribution of tumor and stroma subtypes, and demonstrates that, in addition to the Classical and Basal tumors, there are Hybrid tumors that combine the latter subtypes, and Intermediate tumors that may represent a transition state during PDAC evolution.
A heterogeneously integrated lithium niobate-on-silicon nitride photonic platform
Authors: Churaev Mikhail , Wang Rui Ning , Riedhauser Annina , Snigirev Viacheslav , Blésin Terence , Möhl Charles , Anderson Miles H. , Siddharth Anat , Popoff Youri , Drechsler Ute , Caimi Daniele , Hönl Simon , Riemensberger Johann , Liu Junqiu , Seidler Paul , Kippenberg Tobias J. 
Published: June 2023

AbstractThe availability of thin-film lithium niobate on insulator (LNOI) and advances in processing have led to the emergence of fully integrated LiNbO3 electro-optic devices. Yet to date, LiNbO3 photonic integrated circuits have mostly been fabricated using non-standard etching techniques and partially etched waveguides, that lack the reproducibility achieved in silicon photonics. Widespread application of thin-film LiNbO3 requires a reliable solution with precise lithographic control. Here we demonstrate a heterogeneously integrated LiNbO3 photonic platform employing wafer-scale bonding of thin-film LiNbO3 to silicon nitride (Si3N4) photonic integrated circuits. The platform maintains the low propagation loss (<0.1 dB/cm) and efficient fiber-to-chip coupling (<2.5 dB per facet) of the Si3N4 waveguides and provides a link between passive Si3N4 circuits and electro-optic components with adiabatic mode converters experiencing insertion losses below 0.1 dB. Using this approach we demonstrate several key applications, thus providing a scalable, foundry-ready solution to complex LiNbO3 integrated photonic circuits.
Parieto-occipital ERP indicators of gut mechanosensation in humans
Authors: Mayeli Ahmad , Al Zoubi Obada , White Evan J. , Chappelle Sheridan , Kuplicki Rayus , Morton Alexa , Bruce Jaimee , Smith Ryan , Feinstein Justin S. , Bodurka Jerzy , Paulus Martin P. , Khalsa Sahib S. 
Published: June 2023

AbstractUnderstanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the body’s interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with faster stimulation detection and reduced reaction time variability. Capsule stimulation induced late neural responses in parieto-occipital electrodes near the midline. Moreover, these ‘gastric evoked potentials’ showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. Our results replicated in a separate experiment, and abdominal X-ray imaging localized most capsule stimulations to the gastroduodenal segments. Combined with our prior observation that a Bayesian model is capable of estimating computational parameters of gut-brain mechanosensation, these findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut feelings and gut-brain interactions in healthy and clinical populations.
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Authors: Lenza Maria Pia , Egia-Mendikute Leire , Antoñana-Vildosola Asier , Soares Cátia O. , Coelho Helena , Corzana Francisco , Bosch Alexandre , Manisha Prodhi , Quintana Jon Imanol , Oyenarte Iker , Unione Luca , Moure María Jesús , Azkargorta Mikel , Atxabal Unai , Sobczak Klaudia , Elortza Felix , Sutherland James D. , Barrio Rosa , Marcelo Filipa , Jiménez-Barbero Jesús , Palazon Asis , Ereño-Orbea June 
Published: June 2023

AbstractSialic acid-binding Ig-like lectin 15 (Siglec-15) is an immune modulator and emerging cancer immunotherapy target. However, limited understanding of its structure and mechanism of action restrains the development of drug candidates that unleash its full therapeutic potential. In this study, we elucidate the crystal structure of Siglec-15 and its binding epitope via co-crystallization with an anti-Siglec-15 blocking antibody. Using saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy and molecular dynamics simulations, we reveal Siglec-15 binding mode to α(2,3)- and α(2,6)-linked sialic acids and the cancer-associated sialyl-Tn (STn) glycoform. We demonstrate that binding of Siglec-15 to T cells, which lack STn expression, depends on the presence of α(2,3)- and α(2,6)-linked sialoglycans. Furthermore, we identify the leukocyte integrin CD11b as a Siglec-15 binding partner on human T cells. Collectively, our findings provide an integrated understanding of the structural features of Siglec-15 and emphasize glycosylation as a crucial factor in controlling T cell responses.
Omicron subvariant BA.5 efficiently infects lung cells
Authors: Hoffmann Markus , Wong Lok-Yin Roy , Arora Prerna , Zhang Lu , Rocha Cheila , Odle Abby , Nehlmeier Inga , Kempf Amy , Richter Anja , Halwe Nico Joel , Schön Jacob , Ulrich Lorenz , Hoffmann Donata , Beer Martin , Drosten Christian , Perlman Stanley , Pöhlmann Stefan 
Published: June 2023

AbstractThe SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.
A chip-scale atomic beam clock
Authors: Martinez Gabriela D. , Li Chao , Staron Alexander , Kitching John , Raman Chandra , McGehee William R. 
Published: June 2023

AbstractAtomic beams are a longstanding technology for atom-based sensors and clocks with widespread use in commercial frequency standards. Here, we report the demonstration of a chip-scale microwave atomic beam clock using coherent population trapping (CPT) interrogation in a passively pumped atomic beam device. The beam device consists of a hermetically sealed vacuum cell fabricated from an anodically bonded stack of glass and Si wafers in which lithographically defined capillaries produce Rb atomic beams and passive pumps maintain the vacuum environment. A prototype chip-scale clock is realized using Ramsey CPT spectroscopy of the atomic beam over a 10 mm distance and demonstrates a fractional frequency stability of ≈1.2 × 10−9/$$\sqrt{\tau }$$τfor integration times, τ, from 1 s to 250 s, limited by detection noise. Optimized atomic beam clocks based on this approach may exceed the long-term stability of existing chip-scale clocks, and leading long-term systematics are predicted to limit the ultimate fractional frequency stability below 10−12.
Augmented temperature fluctuation aggravates muscular atrophy through the gut microbiota
Authors: Liu Ya , Guo Yifan , Liu Zheyu , Feng Xu , Zhou Rui , He Yue , Zhou Haiyan , Peng Hui , Huang Yan 
Published: June 2023

AbstractLarge temperature difference is reported to be a risk factor for human health. However, little evidence has reported the effects of temperature fluctuation on sarcopenia, a senile disease characterized by loss of muscle mass and function. Here, we demonstrate that higher diurnal temperature range in humans has a positive correlation with the prevalence of sarcopenia. Fluctuated temperature exposure (10–25 °C) accelerates muscle atrophy and dampens exercise performance in mid-aged male mice. Interestingly, fluctuated temperature alters the microbiota composition with increased levels ofParabacteroides_distasonis,Duncaniella_dubosiiand decreased levels ofCandidatus_Amulumruptor,Roseburia,Eubacterium. Transplantation of fluctuated temperature-shaped microbiota replays the adverse effects on muscle function. Mechanically, we find that altered microbiota increases circulating aminoadipic acid, a lysine degradation product. Aminoadipic acid damages mitochondrial function through inhibiting mitophagy in vitro. AndEubacteriumsupplementation alleviates muscle atrophy and dysfunction induced by fluctuated temperature. Our results uncover the detrimental impact of fluctuated temperature on muscle function and provide a new clue for gut-muscle axis.
TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress
Authors: Kucińska Marika K. , Fedry Juliette , Galli Carmela , Morone Diego , Raimondi Andrea , Soldà Tatiana , Förster Friedrich , Molinari Maurizio 
Published: June 2023

AbstractThe endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuclear envelope (NE), protects the cell genome with two juxtaposed lipid bilayers, the inner and outer nuclear membranes (INM and ONM) separated by the perinuclear space (PNS). Here we report that expansion of the mammalian ER upon homeostatic perturbations results in TMX4 reductase-driven disassembly of the LINC complexes connecting INM and ONM and in ONM swelling. The physiologic distance between ONM and INM is restored, upon resolution of the ER stress, by asymmetric autophagy of the NE, which involves the LC3 lipidation machinery, the autophagy receptor SEC62 and the direct capture of ONM-derived vesicles by degradative LAMP1/RAB7-positive endolysosomes in a catabolic pathway mechanistically defined as micro-ONM-phagy.
Mean-shift exploration in shape assembly of robot swarms
Authors: Sun Guibin , Zhou Rui , Ma Zhao , Li Yongqi , Groß Roderich , Chen Zhang , Zhao Shiyu 
Published: June 2023

AbstractThe fascinating collective behaviors of biological systems have inspired extensive studies on shape assembly of robot swarms. Here, we propose a strategy for shape assembly of robot swarms based on the idea of mean-shift exploration: when a robot is surrounded by neighboring robots and unoccupied locations, it would actively give up its current location by exploring the highest density of nearby unoccupied locations in the desired shape. This idea is realized by adapting the mean-shift algorithm, which is an optimization technique widely used in machine learning for locating the maxima of a density function. The proposed strategy empowers robot swarms to assemble highly complex shapes with strong adaptability, as verified by experiments with swarms of 50 ground robots. The comparison between the proposed strategy and the state-of-the-art demonstrates its high efficiency especially for large-scale swarms. The proposed strategy can also be adapted to generate interesting behaviors including shape regeneration, cooperative cargo transportation, and complex environment exploration.
Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis
Authors: Xie Tian , Liu Peng , Wu Xinyue , Dong Feitong , Zhang Zike , Yue Jian , Mahawar Usha , Farooq Faheem , Vohra Hisham , Fang Qi , Liu Wenchen , Wattenberg Binks W. , Gong Xin 
Published: June 2023

AbstractThe ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.
d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation
Authors: Folorunso Oluwarotimi O. , Brown Stephanie E. , Baruah Jugajyoti , Harvey Theresa L. , Jami Shekib A. , Radzishevsky Inna , Wolosker Herman , McNally James M. , Gray John A. , Vasudevan Anju , Balu Darrick T. 
Published: June 2023

AbstractThe proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation and inhibition (E/I) balance in cortical circuits. Glutamate contributes to cortical interneuron (CIN) development viaN-methyl-d-aspartate receptors (NMDARs). NMDAR activation requires the binding of a co-agonist, either glycine ord-serine.d-serine (co-agonist at many mature forebrain synapses) is racemized by the neuronal enzyme serine racemase (SR) froml-serine. We utilized constitutive SR knockout (SR−/−) mice to investigate the effect ofd-serine availability on the development of CINs and inhibitory synapses in the prelimbic cortex (PrL). We found that most immature Lhx6 + CINs expressed SR and the obligatory NMDAR subunit NR1. At embryonic day 15, SR−/−mice had an accumulation of GABA and increased mitotic proliferation in the ganglionic eminence and fewerGad1 + (glutamic acid decarboxylase 67 kDa; GAD67) cells in the E18 neocortex. Lhx6 + cells develop into parvalbumin (PV+) and somatostatin (Sst+) CINs. In the PrL of postnatal day (PND) 16 SR−/−mice, there was a significant decrease in GAD67+ and PV+, but not SST + CIN density, which was associated with reduced inhibitory postsynaptic potentials in layer 2/3 pyramidal neurons. These results demonstrate that D-serine availability is essential for prenatal CIN development and postnatal cortical circuit maturation.
A multiscale analysis of heatwaves and urban heat islands in the western U.S. during the summer of 2021
Authors: Chen Kaiyu , Boomsma Jacob , Holmes Heather A. 
Published: June 2023

AbstractExtreme heat events are occurring more frequently and with greater intensity due to climate change. They result in increased heat stress to populations causing human health impacts and heat-related deaths. The urban environment can also exacerbate heat stress because of man-made materials and increased population density. Here we investigate the extreme heatwaves in the western U.S. during the summer of 2021. We show the atmospheric scale interactions and spatiotemporal dynamics that contribute to increased temperatures across the region for both urban and rural environments. In 2021, daytime maximum temperatures during heat events in eight major cities were 10–20 °C higher than the 10-year average maximum temperature. We discuss the temperature impacts associated with processes across scales: climate or long-term change, the El Niño–Southern Oscillation, synoptic high-pressure systems, mesoscale ocean/lake breezes, and urban climate (i.e., urban heat islands). Our findings demonstrate the importance of scale interactions impacting extreme heat and the need for holistic approaches in heat mitigation strategies.
Patient-reported distress at a cancer center during the COVID-19 pandemic
Authors: Shah Manan P. , Rosenthal Sarah W. , Roy Mohana , Khaki Ali Raza , Hernandez-Boussard Tina , Ramchandran Kavitha 
Published: June 2023

AbstractAssessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019–3/15/2020, surge1: 6/17/2020–9/7/2020, valley1: 9/8/2020–11/16/2020, surge2: 11/17/2020–3/2/2021, and valley2: 3/3/2021–6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.
Influence of ecological traits on spatio-temporal dynamics of an elasmobranch community in a heavily exploited basin
Authors: Maioli Federico , Weigel Benjamin , Chiarabelli Elettra , Manfredi Chiara , Anibaldi Alessandra , Isailović Igor , Vrgoč Nedo , Casini Michele 
Published: June 2023

AbstractElasmobranchs, which include sharks and batoids, play critical roles in maintaining the integrity and stability of marine food webs. However, these cartilaginous fish are among the most threatened vertebrate lineages due to their widespread depletion. Consequently, understanding dynamics and predicting changes of elasmobranch communities are major research topics in conservation ecology. Here, we leverage long-term catch data from a standardized bottom trawl survey conducted from 1996 to 2019, to evaluate the spatio-temporal dynamics of the elasmobranch community in the heavily exploited Adriatic Sea, where these fish have historically been depleted. We use joint species distribution modeling to quantify the responses of the species to environmental variation while also including important traits such as species age at first maturity, reproductive mode, trophic level, and phylogenetic information. We present spatio-temporal changes in the species community and associated modification of the trait composition, highlighting strong spatial and depth-mediated patterning. We observed an overall increase in the abundance of the dominant elasmobranch species, except for spurdog, which has shown a continued decline. However, our results showed that the present community displays lower age at first maturity and a smaller fraction of viviparous species compared to the earlier observed community due to changes in species’ relative abundance. The selected traits contributed considerably to explaining community patterns, suggesting that the integration of trait-based approaches in elasmobranch community analyses can aid efforts to conserve this important lineage of fish.
Reference-based cell type matching of in situ image-based spatial transcriptomics data on primary visual cortex of mouse brain
Authors: Zhang Yun , Miller Jeremy A. , Park Jeongbin , Lelieveldt Boudewijn P. , Long Brian , Abdelaal Tamim , Aevermann Brian D. , Biancalani Tommaso , Comiter Charles , Dzyubachyk Oleh , Eggermont Jeroen , Langseth Christoffer Mattsson , Petukhov Viktor , Scalia Gabriele , Vaishnav Eeshit Dhaval , Zhao Yilin , Lein Ed S. , Scheuermann Richard H. 
Published: June 2023

AbstractWith the advent of multiplex fluorescence in situ hybridization (FISH) and in situ RNA sequencing technologies, spatial transcriptomics analysis is advancing rapidly, providing spatial location and gene expression information about cells in tissue sections at single cell resolution. Cell type classification of these spatially-resolved cells can be inferred by matching the spatial transcriptomics data to reference atlases derived from single cell RNA-sequencing (scRNA-seq) in which cell types are defined by differences in their gene expression profiles. However, robust cell type matching of the spatially-resolved cells to reference scRNA-seq atlases is challenging due to the intrinsic differences in resolution between the spatial and scRNA-seq data. In this study, we systematically evaluated six computational algorithms for cell type matching across four image-based spatial transcriptomics experimental protocols (MERFISH, smFISH, BaristaSeq, and ExSeq) conducted on the same mouse primary visual cortex (VISp) brain region. We find that many cells are assigned as the same type by multiple cell type matching algorithms and are present in spatial patterns previously reported from scRNA-seq studies in VISp. Furthermore, by combining the results of individual matching strategies into consensus cell type assignments, we see even greater alignment with biological expectations. We present two ensemble meta-analysis strategies used in this study and share the consensus cell type matching results in the Cytosplore Viewer (https://viewer.cytosplore.org) for interactive visualization and data exploration. The consensus matching can also guide spatial data analysis using SSAM, allowing segmentation-free cell type assignment.