bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the Subtypes of Long COVID and Risk Factors for Prolonged Disease
Authors: Resendez Skyler , Brown Steven H. , Ruiz H. Sebastian , Rangan Prahalad , Nebeker Jonathan R. , Montella Diane , Elkin Peter L. 
Published: May 2023

AbstractImportanceThere have been over 759 million confirmed cases of COVID-19 worldwide. A significant portion of these infections will lead to long COVID and its attendant morbidities and costs.ObjectiveTo empirically derive a long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support clinical, public health, research, and policy initiatives related to the pandemic.DesignCase-Crossover Population-based study.SettingVeterans Affairs (VA) medical centers across the United States between January 1, 2020 and August 18, 2022.Participants367,148 individuals with positive COVID-19 tests and preexisting ICD-10-CM codes recorded in the VA electronic health record were enrolled.TriggerSARS-CoV-2 infection documented by positive laboratory test.Case WindowOne to seven months following positive COVID testing.Main Outcomes and MeasuresWe defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of >= 1:1000 and they were significantly increased in our entire cohort after a positive COVID test when compared to case frequencies before COVID testing. We present odds ratios with confidence intervals for long COVID signs, symptoms, and diagnoses, organized by ICD-10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based upon a patient’s demographics, Elixhauser score, vaccination status, and COVID disease severity.ResultsWe developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367,148 patient post-COVID population. We define seventeen medical-specialty long COVID subtypes such as cardiology long COVID. COVID-19 positive patients developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of at least 59.7% (based on all COVID positive patients). Patients with more severe cases of COVID-19 and multiple comorbidities were more likely to develop long COVID.Conclusions and RelevanceAn actionable, empirical definition for long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. An actionable long COVID definition can also support public health, research and policy initiatives. COVID patients with low oxygen saturation levels or multiple co-morbidities should be preferentially watched for the development of long COVID.
The impact of flavored e-cigarette bans on e-cigarette use in three US states
Authors: Yang Yong , Lindblom Eric N. , Ward Kenneth D. , Salloum Ramzi G. 
Published: May 2023

AbstractIntroductionBeginning in 2019, several U.S. states implemented temporary or permanent bans on the sale of flavored e-cigarettes. This study examined the impact of flavor bans on adult e-cigarette use in Washington, New Jersey, and New York.MethodsAdults who used e-cigarettes at least once a week before the flavor bans were recruited online. Respondents reported their e-cigarette use, primarily used flavor, and ways of obtaining ecigarettes before and after the bans. Descriptive statistics and multinomial logistic regression models were applied.ResultsAfter the ban, 8.1% of respondents (N=1624) quit using e-cigarettes, those primarily used banned menthol or other flavors declined from 74.4% to 50.8, those using tobacco-flavored declined from 20.1% to 15.6%, and those using non-flavored increased from 5.4% to 25.4%. More frequent e-cigarette use and smoking cigarettes were associated with being less likely to quit e-cigarettes and more likely to use banned flavors. Of those primarily using banned flavors, 45.1% obtained e-cigarettes from in-state stores, 31.2% from out-of-state stores, 32% from friends, family, or others, 25.5% from Internet/mail sellers, 5.2% from illegal sellers, 4.2% mixed flavored e-liquids themselves, and 6.9% stocked up on e-cigarettes before the ban.ConclusionsMost respondents continued to use e-cigarettes with banned flavors post-ban. Compliance of local retailers with the ban was not high, and many respondents obtained banned-flavor e-cigarettes through legal channels. However, the significant increase in the use of non-flavored e-cigarettes post-ban suggests that these may serve as a viable alternative among those who used previously used banned or tobacco flavors.ImplicationsThis study examined the impact on adult e-cigarette users from the recent e-cigarette-only flavor bans in Washington State, New Jersey, and New York. We found that most respondents continued to use e-cigarettes with banned flavors post-ban and obtain banned-flavor e-cigarettes through legal channels. Our findings indicate that non-flavored e-cigarettes may serve as an acceptable alternative to both non-tobacco and tobacco-flavored e-cigarettes and state e-cigarette flavor bans are unlikely to prompt a significant number of adult e-cigarette users to replace their e-cigarette use with new or increased smoking. Enforcing compliance of retailers to the policy is crucial to control e-cigarette use.
Reciprocal polarization imaging of complex media
Authors: Xie Zhineng , Huang Guowu , Lin Weihao , Jin Xin , Qian Xiafei , Xu Min 
Published: May 2023

AbstractThe vectorial evolution of polarized light interaction with a medium can reveal its microstructure and anisotropy beyond what can be obtained from scalar light interaction. Anisotropic properties (diattenuation, retardance, and depolarization) of a complex medium can be quantified by polarization imaging by measuring the Mueller matrix. However, polarization imaging in the reflection geometry, ubiquitous and often preferred in diverse applications, has suffered a poor recovery of the medium’s anisotropic properties due to the lack of suitable decomposition of the Mueller matrices measured inside a backward geometry. Here, we present reciprocal polarization imaging of complex media after introducing reciprocal polar decomposition for backscattering Mueller matrices. Based on the reciprocity of the optical wave in its forward and backward scattering paths, the anisotropic diattenuation, retardance, and depolarization of a complex medium are determined by measuring the backscattering Mueller matrix. We demonstrate reciprocal polarization imaging in various applications for quantifying complex non-chiral and chiral media, uncovering their anisotropic microstructures with remarkable clarity and accuracy. Reciprocal polarization imaging will be instrumental in imaging complex media from remote sensing to biomedicine and will open up new applications of polarization optics in reflection geometry.
WebAtlas pipeline for integrated single cell and spatial transcriptomic data
Authors: Li Tong , Horsfall David , Basurto-Lozada Daniela , Roberts Kenny , Prete Martin , Lawrence John E G , He Peng , Tuck Elisabeth , Moore Josh , Ghazanfar Shila , Teichmann Sarah , Haniffa Muzlifah , Bayraktar Omer Ali 
Published: May 2023

AbstractSingle cell and spatial transcriptomics illuminate complementary features of tissues. However, online dissemination and exploration of integrated datasets is challenging due to the heterogeneity and scale of data. We introduce the WebAtlas pipeline for user-friendly sharing and interactive navigation of integrated datasets. WebAtlas unifies commonly used atlassing technologies into the cloud-optimised Zarr format and builds on Vitessce to enable remote data navigation. We showcase WebAtlas on the developing human lower limb to cross-query cell types and genes across single cell, sequencing- and imaging-based spatial transcriptomic data.
The spatially resolved tumor microenvironment predicts treatment outcome in relapsed/refractory Hodgkin lymphoma
Authors: Aoki Tomohiro , Jiang Aixiang , Xu Alexander , Yin Yifan , Gamboa Alicia , Milne Katy , Takata Katsuyoshi , Miyata-Takata Tomoko , Wu Shaocheng , Warren Mary , Strong Celia , Goodyear Talia , Morris Kayleigh , Chong Lauren C. , Hav Monirath , Colombo Anthony R. , Telenius Adele , Boyle Merrill , Ben-Neriah Susana , Power Maryse , Gerrie Alina S. , Weng Andrew P. , Karsan Aly , Roth Andrew , Farinha Pedro , Scott David W. , Savage Kerry J. , Nelson Brad H. , Merchant Akil , Steidl Christian 
Published: May 2023

AbstractPURPOSEAbout a third of relapsed or refractory classic Hodgkin lymphoma (r/r CHL) patients succumb to their disease after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Here, we aimed to describe spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL.METHODSWe performed imaging mass cytometry (IMC) on 169 paired primary diagnostic and relapse biopsies using a marker panel specific for CHL biology. For each cell type in the TME, we calculated a ’spatial score’ measuring the distance of nearest neighbor cells to the malignant Hodgkin Reed Sternberg cells within close interaction range. ‘Spatial scores’ were used as features in prognostic model development for post-ASCT outcomes.RESULTSHighly multiplexed IMC data revealed shared TME patterns in paired diagnostic and early relapse/refractory CHL samples, whereas TME patterns were more divergent in pairs of diagnostic and late relapse samples. Integrated analysis of IMC and single cell RNA sequencing data identified unique architecture defined by CXCR5+HRS cells and their strong spatial relationship with CXCL13+ macrophages in the TME. We developed a prognostic assay (‘RHL4S’) using four spatially resolved parameters, CXCR5+ HRS cells, PD1+CD4+ T cells, tumor-associated macrophages, and CXCR5+ B cells, which effectively separated patients into high-risk vs low-risk groups with significantly different post-ASCT outcomes. The RHL4S assay was validated in an independent r/r CHL cohort using a multicolor immunofluorescence assay.CONCLUSIONSWe identified the interaction of CXCR5+ HRS cells with ligand-expressing CXCL13+ macrophages as a prominent crosstalk axis in relapsed CHL. Harnessing this TME biology, we developed a novel prognostic model applicable to r/r CHL biopsies, RHL4S, opening new avenues for spatial biomarker development.
A Scalable High Throughput Fully Automated Pipeline for the Quantification of Amyloid Pathology in Alzheimer’s Disease using Deep Learning Algorithms
Authors: Gopal Ramaswamy Vivek , Ahirwar Monika , Ryan Genadi , Signaevsky Maxim , Haroutunian Vahram , Finkbeiner Steven 
Published: May 2023

AbstractThe most common approach to characterize neuropathology in Alzheimer’s disease (AD) involves a manual survey and inspection by an expert neuropathologist of postmortem tissue that has been immunolabeled to visualize the presence of amyloid β in plaques and around blood vessels and neurofibrillary tangles of the tau protein. In the case of amyloid β pathology, a semiquantitative score is given that is based on areas of densest pathology. The approach has been well-validated but the process is laborious and time consuming, and inherently susceptible to intra- and inter-observer variability. Moreover, the tremendous growth in genetic, transcriptomic and proteomic data from AD patients has created new opportunities to link clinical features of AD to molecular pathogenesis through pathology, but the lack of high throughput quantitative and comprehensive approaches to assess neuropathology limits the associations that can be discovered. To address these limitations, we designed a computational pipeline to analyze postmortem tissue from AD patients in a fully automated, unbiased and high throughput manner. We used deep learning to train algorithms with a Mask Regional-Convolutional Neural Network to detect and classify different types of amyloid pathology with human level accuracy. After training on pathology slides from a Mt Sinai cohort, our algorithms identified amyloid pathology in samples made at an independent brain bank and from an unrelated cohort of patients, indicating that the algorithms were detecting reproducible and generalizable pathology features. We designed the pipeline to retain the position of the pathology it detects, making it possible to reconstruct a map of pathology across the entire whole slide image, facilitating neuropathological analyses at multiple scales. Quantitative measurements of amyloid pathology correlated positively and significantly with the severity of AD as measured by standard approaches. We conclude that we have developed a computational pipeline to analyze digitized images of neuropathology in high throughput and algorithms to detect types of amyloid pathology with human level accuracy that should enable neuropathological analysis of large tissue collections and integration of those results with orthogonal clinical and multiomic measurements.
Genome-wide neighbor effects predict genotype pairs that reduce herbivory in mixed planting
Authors: Sato Yasuhiro , Shimizu-Inatsugi Rie , Takeda Kazuya , Schmid Bernhard , Nagano Atsushi J. , Shimizu Kentaro K. 
Published: May 2023

SummaryGenetically diverse populations can increase plant resistance to natural enemies. Yet, beneficial genotype pairs remain elusive due to the occurrence of both positive and negative effects of mixed planting on plant resistance, called associational resistance and susceptibility. We used genome-wide polymorphisms of the plant speciesArabidopsis thalianato identify genotype pairs that enhance associational resistance to herbivory. By quantifying neighbor interactions among 199 genotypes grown in a randomized block design, we predicted that 823 of the 19,701 candidate pairs could reduce herbivory through associational resistance. We planted such pairs with predicted associational resistance in mixtures and monocultures and found a significant reduction in herbivore damage in the mixtures. Our study highlights the potential application to assemble genotype mixtures with positive biodiversity effects.
RPM: an open-source rotation platform for open- and closed-loop vestibular stimulation in head-fixed mice
Authors: Cano-Ferrer Xavier , Tran-Van-Minh Alexandra , Rancz Ede 
Published: May 2023

AbstractHead fixation allows the recording and presentation of controlled stimuli and is used to study neural processes underlying spatial navigation. However, it disrupts the head direction system because of the lack of vestibular stimulation.To overcome this limitation, we developed a novel rotation platform which can be driven by the experimenter (open-loop) or by animal movement (closed-loop). The platform is modular, affordable, easy to build and open source. Additional modules presented here include cameras for monitoring eye movements, visual virtual reality and a micro-manipulator for positioning various probes for recording or optical interference.We demonstrate the utility of the platform by recording eye movements and showing the robust activation of head-direction cells. This novel experimental apparatus combines the advantages of head fixation and intact vestibular activity in the horizontal plane. The open-loop mode can be used to study e.g. vestibular sensory representation and processing, while the closed-loop mode allows animals to navigate in rotational space, providing a better substrate for 2-D navigation in virtual environments. Documentation is available at (https://ranczlab.github.io/RPM/).
Epigenetic age acceleration in frontotemporal lobar degeneration: a comprehensive analysis in the blood and brain
Authors: Murthy Megha , Rizzu Patrizia , Heutink Peter , Mill Jonathan , Lashley Tammaryn , Bettencourt Conceição 
Published: May 2023

AbstractFrontotemporal lobar degeneration (FTLD) includes a heterogeneous group of disorders pathologically characterized by the degeneration of the frontal and temporal lobes. In addition to major genetic contributors of FTLD such as mutations inMAPT, GRN, andC9orf72, recent work has identified several epigenetic modifications including significant differential DNA methylation inDLX1, andOTUD4loci. As aging remains to be one of the major risk factors for FTLD, we investigated the presence of accelerated epigenetic aging in FTLD compared to controls. We calculated epigenetic age in both peripheral blood and brain tissues of multiple FTLD subtypes using several DNA methylation clocks, i.e., DNAmClockMulti, DNAmClockHannum, DNAmClockCortical, GrimAge and PhenoAge, and determined age acceleration and its association with different cellular proportions and clinical traits. Significant epigenetic age acceleration was observed in the peripheral blood of both frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) patients compared to controls with DNAmClockHannum, even after accounting for confounding factors. A similar trend was observed with both DNAmClockMultiand DNAmClockCorticalin post-mortem frontal cortex tissue of PSP patients and in FTLD cases harboringGRNmutations. Our findings support that increased epigenetic age acceleration in the peripheral blood could be an indicator for PSP and to a smaller extent, FTD.
An RNA origami robot that traps and releases a fluorescent aptamer
Authors: Sampedro Vallina Néstor , McRae Ewan K.S. , Geary Cody , Andersen Ebbe Sloth 
Published: May 2023

ABSTRACTRNA nanotechnology aims at using RNA as a programmable material to create self-assembling nanodevices for application in medicine and synthetic biology. RNA devices have been developed by adopting mechanisms such as allosteric binding and toehold-mediated strand displacement. There are, however, no examples of RNA “robotic” devices that sense, compute, and actuate through mechanical reconfiguration as has been demonstrated in DNA nanotechnology. Here we use the RNA origami method to prototype an RNA robotic device, named the “Traptamer”, that senses two RNA key strands, acts as a Boolean AND gate, and activates the fluorescent aptamer iSpinach through release from a mechanical trap. The Traptamer depends on binding of two different RNA key strands to achieve full activation and can be reversed by addition of two complementary RNA anti-key strands. Cryo-EM of the closed Traptamer structure at 5.45 Å resolution reveals a hinge-like mechanical distortion of the iSpinach motif. Our RNA robot prototype opens the door to build more sophisticated RNA machines that use sensing, computing, and acting modules to precisely control RNA functionalities.
Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells
Authors: Naigles Beverly , Narla Avaneesh V , Soroczynski Jan , Tsimring Lev S , Hao Nan 
Published: May 2023

AbstractMacrophages must respond appropriately to pathogens and other pro-inflammatory stimuli in order to perform their roles in fighting infection. One way in which inflammatory stimuli can vary is in their dynamics – that is, the amplitude and duration of stimulus experienced by the cell. In this study, we performed long-term live cell imaging in a microfluidic device to investigate how the pro-inflammatory genes IRF1, CXCL10, and CXCL9 respond to dynamic interferon-gamma (IFNγ) stimulation. We found that IRF1 responds to low concentration or short duration IFNγ stimulation, whereas CXCL10 and CXCL9 require longer or higher-concentration stimulation to be expressed. We also investigated the heterogeneity in the expression of each gene and found that CXCL10 and CXCL9 have substantial cell-to-cell variability. In particular, the expression of CXCL10 appears to be largely stochastic with a subpopulation of non-responding cells across all the stimulation conditions tested. We developed both deterministic and stochastic models for the expression of each gene. Our modeling analysis revealed that the heterogeneity in CXCL10 can be attributed to a slow chromatin-opening step that is on a similar timescale to that of adaptation of the upstream signal. In this way, CXCL10 expression in individual cells can remain stochastic in response to each pulse of repeated simulations, as validated by experiments. Together, we conclude that pro-inflammatory genes in the same signaling pathway can respond to dynamic IFNγ stimulus with very different response features and that upstream signal adaptation can contribute to shaping the features of heterogeneous gene expression.
Frequency-dependent Distribution of Different Subtypes of Spiral Ganglion Neurons in the Cochlea and the Changes During Aging
Authors: Wang Meijian , Lin Shengyin , Xie Ruili 
Published: May 2023

AbstractSound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and how the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2-5 months (young), 17-19 months (middle-age), and 28-32 months (old). Mouse cochleae were cryo-sectioned and triple-stained using antibodies against Tuj1, calretinin (CR) and calbindin (CB), which are reportedly expressed in all type I, subtype Ia, and subtype IbSGNs, respectively. Labeled SGNs were classified into four groups based on the expression pattern of stained markers, including CR+(subtype Ia), CB+(subtype Ib), CR+CB+(dual-labeled Ia/Ib), and CR-CB-(subtype Ic) neurons. The distribution of these SGN groups was analyzed in the apex, middle, and base regions of the cochleae. It showed that the prevalence of subtype Ia, Iband dual-labeled Ia/IbSGNs are high in the apex and low in the base. In contrast, the distribution pattern is reversed in IcSGNs. Such frequency-dependent distribution is largely maintained during aging except for a preferential reduction of IcSGNs, especially in the base. These findings suggest that sound processing of different frequencies involves distinct combinations of SGN subtypes, and the age-dependent loss of IcSGNs in the base may especially impact high-frequency hearing during ARHL.