tbuckley/cabot-search huggingface dataset:
Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging
Authors: Yan-Ran Joyce Wang, Kai Yang, Yi Wen, Pengcheng Wang, Yuepeng Hu, Yongfan Lai, Yufeng Wang, Kankan Zhao, Siyi Tang, Angela Zhang, Huayi Zhan, Minjie Lu, Xiuyu Chen, Shujuan Yang, Zhixiang Dong, Yining Wang, Hui Liu, Lei Zhao, Lu Huang, Yunling Li, Lianming Wu, Zixian Chen, Yi Luo, Dongbo Liu, Pengbo Zhao, Keldon Lin, Joseph C Wu, Shihua Zhao
Journal: Nature Medicine (2024)

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.
Brain clearance is reduced during sleep and anesthesia
Authors: Andawei Miao, Tianyuan Luo, Bryan Hsieh, Christopher J Edge, Morgan Gridley, Ryan Tak Chun Wong, Timothy G Constandinou, William Wisden, Nicholas P Franks
Journal: Nature Neuroscience (2024)

It has been suggested that the function of sleep is to actively clear metabolites and toxins from the brain. Enhanced clearance is also said to occur during anesthesia. Here, we measure clearance and movement of fluorescent molecules in the brains of male mice and show that movement is, in fact, independent of sleep and wake or anesthesia. Moreover, we show that brain clearance is markedly reduced, not increased, during sleep and anesthesia.
Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer
Authors: Yue Zeng, Chun-Hong Hu, Yi-Zheng Li, Jian-Song Zhou, Shu-Xing Wang, Meng-Dong Liu, Zhen-Hua Qiu, Chao Deng, Fang Ma, Chun-Fang Xia, Fei Liang, Yu-Rong Peng, Ao-Xi Liang, Sheng-Hao Shi, Shi-Jiao Yao, Jun-Qi Liu, Wen-Jie Xiao, Xiao-Qiao Lin, Xin-Yu Tian, Ying-Zhe Zhang, Zhuo-Ying Tian, Ji-An Zou, Yun-Shu Li, Chao-Yue Xiao, Tian Xu, Xiao-Jie Zhang, Xiao-Ping Wang, Xian-Ling Liu, Fang Wu
Journal: Nature Medicine (2024)

Abstract Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .
Large-scale lexical and genetic alignment supports a hybrid model of Han Chinese demic and cultural diffusions
Authors: Chengkun Yang, Xiaoxi Zhang, Shi Yan, Sizhe Yang, Baihui Wu, Fengshuo You, Yue Cui, Ni Xie, Zhiyi Wang, Li Jin, Shuhua Xu, Menghan Zhang
Journal: Nature Human Behaviour (2024)
High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response
Authors: Alexander J. Mentzer, Alexander T. Dilthey, Martin Pollard, Deepti Gurdasani, Emre Karakoc, Tommy Carstensen, Allan Muhwezi, Clare Cutland, Amidou Diarra, Ricardo da Silva Antunes, Sinu Paul, Gaby Smits, Susan Wareing, HwaRan Kim, Cristina Pomilla, Amanda Y. Chong, Debora Y. C. Brandt, Rasmus Nielsen, Samuel Neaves, Nicolas Timpson, Austin Crinklaw, Cecilia S. Lindestam Arlehamn, Anna Rautanen, Dennison Kizito, Tom Parks, Kathryn Auckland, Kate E. Elliott, Tara Mills, Katie Ewer, Nick Edwards, Segun Fatumo, Emily Webb, Sarah Peacock, Katie Jeffery, Fiona R. M. van der Klis, Pontiano Kaleebu, Pandurangan Vijayanand, Bjorn Peters, Alessandro Sette, Nezih Cereb, Sodiomon Sirima, Shabir A. Madhi, Alison M. Elliott, Gil McVean, Adrian V. S. Hill, Manjinder S. Sandhu
Journal: Nature Medicine (2024)

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
Correction: Targeting KRASG12C in Non-Small-Cell Lung Cancer: Current Standards and Developments
Authors: Javier Torres-Jiménez, Javier Baena Espinar, Helena Bote de Cabo, María Zurera Berjaga, Jorge Esteban-Villarrubia, Jon Zugazagoitia Fraile, Luis Paz-Ares
Journal: Drugs (2024)
Genetic mapping across autoimmune diseases reveals shared associations and mechanisms
Authors: Matthew R. Lincoln, Noah Connally, Pierre-Paul Axisa, Christiane Gasperi, Mitja Mitrovic, David van Heel, Cisca Wijmenga, Sebo Withoff, Iris H. Jonkers, Leonid Padyukov, Ashley H. Beecham, Nikolaos A. Patsopoulos, Chris Cotsapas, David Booth, An Goris, Annette Oturai, Janna Saarela, Betrand Fontaine, Bertrand Hemmer, Martin Claes, Frauke Zipp, Sandra D’Alfonso, Filippo Martinelli-Boneschi, Bruce Taylor, Hanne F. Harbo, Ingrid Kockum, Jan Hillert, Tomas Olsson, Jorge R. Oksenberg, Rogier Hintzen, Lisa F. Barcellos, Lars Alfredsson, Federica Esposito, Roland Martin, Jonathan L. Haines, Margaret A. Pericak-Vance, Adrian J. Ivinson, Graeme Stewart, David Hafler, Stephen L. Hauser, Alastair Compston, Gil McVean, Philip De Jager, Stephen J. Sawcer, Jakob L. McCauley, Stephen S. Rich, Robert R. Graham, Patrick M. Gaffney, Carl D. Langefeld, Timothy J. Vyse, David A. Hafler, Sung Chun, Shamil R. Sunyaev, Chris Cotsapas
Journal: Nature Genetics (2024)
Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes
Authors: Minsoo Kim, Alexander N. Gorelick, Ignacio Vàzquez-García, Marc J. Williams, Sohrab Salehi, Hongyu Shi, Adam C. Weiner, Nick Ceglia, Tyler Funnell, Tricia Park, Sonia Boscenco, Ciara H. O’Flanagan, Hui Jiang, Diljot Grewal, Cerise Tang, Nicole Rusk, Payam A. Gammage, Andrew McPherson, Sam Aparicio, Sohrab P. Shah, Ed Reznik
Journal: Nature Genetics (2024)

The extent of cell-to-cell variation in tumor mitochondrial DNA (mtDNA) copy number and genotype, and the phenotypic and evolutionary consequences of such variation, are poorly characterized. Here we use amplification-free single-cell whole-genome sequencing (Direct Library Prep (DLP+)) to simultaneously assay mtDNA copy number and nuclear DNA (nuDNA) in 72,275 single cells derived from immortalized cell lines, patient-derived xenografts and primary human tumors. Cells typically contained thousands of mtDNA copies, but variation in mtDNA copy number was extensive and strongly associated with cell size. Pervasive whole-genome doubling events in nuDNA associated with stoichiometrically balanced adaptations in mtDNA copy number, implying that mtDNA-to-nuDNA ratio, rather than mtDNA copy number itself, mediated downstream phenotypes. Finally, multimodal analysis of DLP+ and single-cell RNA sequencing identified both somatic loss-of-function and germline noncoding variants in mtDNA linked to heteroplasmy-dependent changes in mtDNA copy number and mitochondrial transcription, revealing phenotypic adaptations to disrupted nuclear/mitochondrial balance.
Changing the incentive structure of social media may reduce online proxy failure and proliferation of negativity
Authors: Claire E. Robertson, Kareena del Rosario, Steve Rathje, Jay J. Van Bavel
Journal: Behavioral and Brain Sciences (2024)

Abstract Social media takes advantage of people's predisposition to attend to threatening stimuli by promoting content in algorithms that capture attention. However, this content is often not what people expressly state they would like to see. We propose that social media companies should weigh users’ expressed preferences more heavily in algorithms. We propose modest changes to user interfaces that could reduce the abundance of threatening content in the online environment.
Animal welfare science, performance metrics, and proxy failure
Authors: Heather Browning, Walter Veit
Journal: Behavioral and Brain Sciences (2024)

In their target article, John et al. make a convincing case that there is a unified phenomenon behind the common finding that measures become worse targets over time. Here, we will apply their framework to the domain of animal welfare science and present a pragmatic solution to reduce its impact that might also be applicable in other domains.
Proxies, heuristics, and goal alignment
Authors: Bruce D. Burns
Journal: Behavioral and Brain Sciences (2024)

Abstract Decision-making heuristics rely on proxies so the elements of heuristics appear to map well to the elements of proxies identified by John et al. However, unlike proxy failure, heuristics do not fail because of feedback. This may be because for successful heuristics the goals of regulators and agents are aligned, but this is not the case for proxy failure.
Proxy failure in social policies as one of the main causes of persistent sexism and racism
Authors: Konrad Szocik
Journal: Behavioral and Brain Sciences (2024)

Abstract One example of proxy failure is current antisexist and antiracist policies. One of the most popular proxy in them is the number of representatives of marginalized groups – women and nonwhite people – in power structures. Here I show that such measures do not lead to combating sexism and racism, which flourish despite their application.
The cost of success or failure for proxy signals in ecological problems
Authors: Peter Nonacs
Journal: Behavioral and Brain Sciences (2024)

Abstract Two of John et al.'s examples of proxy failures in ecological situations are not failures: Runaway sexual selection and marsupial neonate competition. Instead, more appropriate ecological examples may be paternal genetic kin recognition and warning coloration. These differ in proxy effectiveness and failure in ways that illustrate the importance of “costs” in the evolution of ecological proxy traits.
It's the biology, stupid! Proxy failures in economic decision making
Authors: Pier Luigi Sacco
Journal: Behavioral and Brain Sciences (2024)

Abstract Utilitarian characterizations of economic decision making fail to capture the complex, conditional, and heterogeneous motivations underlying human behavior as shaped by the predictive, multicriterial drivers of biological regulation. Unless economic models start to acknowledge that humans have bodies and a biology with its own adaptive logic and tradeoffs, economic policies will be systematically exposed to, and systematic generators of, proxy failures.
Behavioral proxies compete by the time courses of their rewards, including endogenous rewards
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2024)

Abstract Natural selection is slow, so behavioral goals must be based on patterns of reward. Addictions are rewarded in the same way as adaptive choice, so they can be distinguished only by their time course. In addition, the reward process is more plastic than is generally recognized, so abstract goals are shaped by the “legibility” of their proxies.
Genies, lawyers, and smart-asses: Extending proxy failures to intentional misunderstandings
Authors: Tomer D. Ullman, Sophie Bridgers
Journal: Behavioral and Brain Sciences (2024)

Abstract We propose that the logic of a genie – an agent that exploits an ambiguous request to intentionally misunderstand a stated goal – underlies a common and consequential phenomenon, well within what is currently called proxy failures. We argue that such intentional misunderstandings are not covered by the current proposed framework for proxy failures, and suggest to expand it.
Navigating proxy failures in education: Learning from human and animal play
Authors: Robin Samuelsson
Journal: Behavioral and Brain Sciences (2024)

Abstract The notion of proxy failure provides considerable insight into educational processes, and in childhood education has the potential to elucidate known problems stemming from the early implementation of overly regulated educational regimes. This commentary expands on play and how its relation to learning provides a useful perspective on how activities based on nongoal-oriented interactions can lead to desired outcomes.
Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma‐associated oncogene homolog 1 and chemokine CCL2
Authors: Yiming Luo, Zhi Li, He Zhu, Junli Lu, Zhen Lei, Chen Su, Furong Liu, Hongwei Zhang, Qibo Huang, Shenqi Han, Dean Rao, Tiantian Wang, Xiaoping Chen, Hong Cao, Zhiwei Zhang, Wenjie Huang, Huifang Liang
Journal: MedComm (2024)

Abstract Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation‐specific homologous factor (EHF), a member of the E26 transformation‐specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma‐associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor‐associated macrophages (TAMs) through the C‐C motif chemokine 2/C‐C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co‐expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF‐mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2‐TAMs to inhibit EHF‐driven CCA development.
Single-cell 3D genome structure reveals distinct human pluripotent states
Authors: Niannian Li, Kairang Jin, Bin Liu, Mingzhu Yang, PanPan Shi, Dai Heng, Jichang Wang, Lin Liu
Journal: Genome biology (2024)

Abstract Background Pluripotent states of embryonic stem cells (ESCs) with distinct transcriptional profiles affect ESC differentiative capacity and therapeutic potential. Although single-cell RNA sequencing has revealed additional subpopulations and specific features of naive and primed human pluripotent stem cells (hPSCs), the underlying mechanisms that regulate their specific transcription and that control their pluripotent states remain elusive. Results By single-cell analysis of high-resolution, three-dimensional (3D) genomic structure, we herein demonstrate that remodeling of genomic structure is highly associated with the pluripotent states of human ESCs (hESCs). The naive pluripotent state is featured with specialized 3D genomic structures and clear chromatin compartmentalization that is distinct from the primed state. The naive pluripotent state is achieved by remodeling the active euchromatin compartment and reducing chromatin interactions at the nuclear center. This unique genomic organization is linked to enhanced chromatin accessibility on enhancers and elevated expression levels of naive pluripotent genes localized to this region. In contradistinction, the primed state exhibits intermingled genomic organization. Moreover, active euchromatin and primed pluripotent genes are distributed at the nuclear periphery, while repressive heterochromatin is densely concentrated at the nuclear center, reducing chromatin accessibility and the transcription of naive genes. Conclusions Our data provide insights into the chromatin structure of ESCs in their naive and primed states, and we identify specific patterns of modifications in transcription and chromatin structure that might explain the genes that are differentially expressed between naive and primed hESCs. Thus, the inversion or relocation of heterochromatin to euchromatin via compartmentalization is related to the regulation of chromatin accessibility, thereby defining pluripotent states and cellular identity.
Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial
Authors: Morgan T Rose, Natasha E Holmes, Glenn M Eastwood, Sara Vogrin, Fiona James, Joseph F De Luca, Rinaldo Bellomo, Stephen J Warrillow, Michelle Phung, Sara L Barnes, Brendan Murfin, Ben Rogers, Belinda Lambros, Brennan Collis, Trisha N Peel, Monica A Slavin, Jason A Trubiano
Journal: Intensive Care Medicine (2024)

Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.
Sodium Zirconium Cyclosilicate in HFrEF and Hyperkalemia
Authors: Mikhail N. Kosiborod, David Cherney, Kim Connelly, Akshay S. Desai, Patrícia O. Guimarães, Luca Kuthi, Anuradha Lala, Vagner Madrini, Bela Merkely, Julio Nuñez Villota, Iain Squire, Jeffrey M. Testani, Jan Vaclavik, Subodh Verma, Jerzy Wranicz, Magnus Dahl, James M. Eudicone, Lovisa Friberg, Mark C. Petrie
Journal: JACC Heart Failure (2024)

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns.
EmptyDropsMultiome discriminates real cells from background in single-cell multiomics assays
Authors: Stathis Megas, Valentina Lorenzi, John C Marioni
Journal: Genome biology (2024)

Multiomic droplet-based technologies allow different molecular modalities, such as chromatin accessibility and gene expression (scATAC-seq and scRNA-seq), to be probed in the same nucleus. We develop EmptyDropsMultiome, an approach that distinguishes true nuclei-containing droplets from background. Using simulations, we show that EmptyDropsMultiome has higher statistical power and accuracy than existing approaches, including CellRanger-arc and EmptyDrops. On real datasets, we observe that CellRanger-arc misses more than half of the nuclei identified by EmptyDropsMultiome and, moreover, is biased against certain cell types, some of which have a retrieval rate lower than 20%.
Corrigendum to “KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis.” Kidney International 2024;105(3S):S71–S116
Authors: Jürgen Floege, David R.W. Jayne, Jan-Stephan F. Sanders, Vladimír Tesar, Brad H. Rovin
Journal: Kidney International (2024)