bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial Intelligence–Driven Ultra-Fast Superresolution MRI
Authors: Lin Dana J. , Walter Sven S. , Fritz Jan 
Published: November 2022

Abstract
Magnetic resonance imaging (MRI) is the keystone of modern musculoskeletal imaging; however, long pulse sequence acquisition times may restrict patient tolerability and access. Advances in MRI scanners, coil technology, and innovative pulse sequence acceleration methods enable 4-fold turbo spin echo pulse sequence acceleration in clinical practice; however, at this speed, conventional image reconstruction approaches the signal-to-noise limits of temporal, spatial, and contrast resolution. Novel deep learning image reconstruction methods can minimize signal-to-noise interdependencies to better advantage than conventional image reconstruction, leading to unparalleled gains in image speed and quality when combined with parallel imaging and simultaneous multislice acquisition. The enormous potential of deep learning–based image reconstruction promises to facilitate the 10-fold acceleration of the turbo spin echo pulse sequence, equating to a total acquisition time of 2–3 minutes for entire MRI examinations of joints without sacrificing spatial resolution or image quality. Current investigations aim for a better understanding of stability and failure modes of image reconstruction networks, validation of network reconstruction performance with external data sets, determination of diagnostic performances with independent reference standards, establishing generalizability to other centers, scanners, field strengths, coils, and anatomy, and building publicly available benchmark data sets to compare methods and foster innovation and collaboration between the clinical and image processing community. In this article, we review basic concepts of deep learning–based acquisition and image reconstruction techniques for accelerating and improving the quality of musculoskeletal MRI, commercially available and developing deep learning–based MRI solutions, superresolution, denoising, generative adversarial networks, and combined strategies for deep learning–driven ultra-fast superresolution musculoskeletal MRI. This article aims to equip radiologists and imaging scientists with the necessary practical knowledge and enthusiasm to meet this exciting new era of musculoskeletal MRI.
Altered Glucose Metabolism Postchemotherapy Precedes PSMA Expression in Poorly Differentiated Prostate Cancer
Authors: Alabed Yazan Z. 
Published: November 2022

Abstract
A 73-year-old man presented with gastric lesion on upper endoscopy, biopsy-proven as poorly differentiated carcinoma. Staging FDG PET/CT scan showed gastric, intraprostatic, nodal, and extensive osseous lesions. Prostate-specific antigen levels were greater than 1000. The patient was treated as metastatic poorly differentiated prostate cancer with chemotherapy. Posttherapy 18F-PSMA-1007 and FDG PET/CT scans were obtained. PSMA PET/CT scan revealed extensive disease similar in appearance as staging FDG PET/CT scan, indicating no apparent treatment response. FDG PET/CT scan showed partial metabolic response, correlating with improved prostate-specific antigen levels. This case indicates that chemotherapy-induced changes in glucose metabolism likely precede change in PSMA expression in poorly differentiated prostate cancer.
Natural History of Stage IV Pancreatic Cancer. Identifying Survival Benchmarks for Curative-intent Resection in Patients With Synchronous Liver-only Metastases
Authors: Kaslow Sarah R. , Sacks Greg D. , Berman Russell S. , Lee Ann Y. , Correa-Gallego Camilo 
Published: November 2022

Objective:
To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients.

Background:
Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups.

Methods:
We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan–Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis.

Results:
We identified 241 patients. Median OS was 7 months (95% CI, 5–9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17–39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR).

Conclusions:
The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.
Sentiments and Emotions for Vaccination in 2021: An International Comparison Study
Authors: Liu Xue-Jing 
Published: November 2022

AbstractComprehending how individuals feel when they discuss the vaccine is important for the immunization campaign and outbreak management during a health emergency. Online conversations provide useful information for assessing sentimental and emotional reactions to the evolutions of the pandemic and immunization program. In this study, we employ a corpus of around 58 million English tweets from users in 17 countries that discuss vaccine-related topics in the year 2021. We apply Soft Dynamic Time Warping algorithm and Time Lag Cross-Correlation approach and find that the evolutions of sentiments closely mirror the pandemic statistics. We also examine five topics connected to vaccination and discover that trust is the most predominate feeling, followed by fear, anger, and joy. Some countries reported higher emotional scores on a theme than others (people in Cuba and the United States exhibit higher levels of trust, Pakistanis and Indians express higher levels of joy, Australians and Chinese express higher levels of fear, and Japanese and British people express higher levels of anger). This study report offers a viewpoint on the public’s response to the epidemic and vaccination and aids policy-makers with preventive strategies for a future crisis.
Immune landscape of isocitrate dehydrogenase stratified human gliomas
Authors: Gupta Pravesh , Dang Minghao , Oberai Shivangi , Peshoff Mekenzie , Milam Nancy , Ahmed Aml , Bojja Krishna , Tran Tuan M. , Cox Kathryn , Shehwana Huma , Kamiya-Matsuoka Carlos , Li Jianzhuo , Gumin Joy , Goldman Alicia , Seth Sameer A. , Maheshwari Atul , Lang Frederick F. , Navin Nicholas E. , Heimberger Amy B. , Clise-Dwyer Karen , Wang Linghua , Bhat Krishna P. 
Published: November 2022

ABSTRACTThe brain tumor immune microenvironment (TIME) continuously evolves during glioma progression, but only a limited view of a highly complex glioma associated immune contexture across isocitrate dehydrogenase mutation (IDH) classified gliomas is known. Herein, we present an unprecedentedly comprehensive view of myeloid and lymphoid cell type diversity based on our single cell RNA sequencing and spectral cytometry-based interrogation of tumor-associated leukocytes from fifty-five IDH stratified primary and recurrent human gliomas and three non-glioma brains. Our analyses revealed twenty-two myeloid and lymphoid cell types within and across glioma subtypes. Glioma severity correlated with microglial attrition concomitant with a continuum of invading monocyte-derived microglia-like and macrophages amongst other infiltrating conventional T and NK lymphocytes and unconventional mucosa associated invariant T (MAIT) cells. Specifically, certain microglial and monocyte-derived subpopulations were associated with antigen presentation gene modules, akin to cross-presenting dendritic cells (DCs). Furthermore, we identified phagocytosis and antigen presentation gene modules enriched in Triggering receptor expressed on myeloid (TREM)-2+cells as a putative anti-glioma axis. Accelerated glioma growth was observed inTrem2deficient mice implanted with CT2A glioma cells affirming the anti-glioma role of TREM2+myeloid cells. In addition to providing a comprehensive landscape of glioma-specific immune contexture, our investigations discover TREM2 as a novel immunotherapy target for brain malignancies.
TREM1+regulatory myeloid cells expand in steatohepatitis-HCC and associate with poor prognosis and therapeutic resistance to immune checkpoint blockade
Authors: Giraud Julie , Chalopin Domitille , Ramel Eloïse , Boyer Thomas , Zouine Atika , Derieppe Marie-Alix , Larmonier Nicolas , Adotevi Olivier , Bail Brigitte Le , Blanc Jean-Frédéric , Chiche Laurence , Nikolski Macha , Saleh Maya 
Published: November 2022

ABSTRACTHepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Immune checkpoint blockade primarily benefits patients with viral HCC. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by the emergence of high entropy myeloid cell states and myeloid-biased NK cell differentiation. We identify a discrete population of tumor-infiltrating myeloid cells, predominant in the steatohepatitis setting, that expresses a variety of myeloid lineage-affiliated genes, including granulocyte, macrophage and dendritic cell features, and can be identified in HCC tumors based on selective dual expression ofTREM1andCD163. Functional characterization reveals that TREM1+CD163+myeloid cells highly express TGFβ and IL-13RA, localize to HCC fibrotic lesions, and potently suppress T cell effector functionsex vivo, a function further potentiated by TREM1 engagement. We refer to this population as TREM1+CD163+regulatory myeloid cells (TREM1+CD163+Mreg). Deconvolution analyses in large cohorts of patients with HCC and other solid tumors reveals that the density of TREM1+CD163+Mregincreases in advanced stages, associates with poor prognosis, and therapeutic resistance to PD-1 blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC and identify TREM1 as a therapeutic target.HIGHLIGHTSAtlas of hepatic innate immune cells (100,000 transcriptomes) from patients with HCCCore signatures to identify, discriminate and localize innate lymphoid and myeloid cellsA population of TREM1+CD163+myeloid cells, referred to as TREM1+CD163+Mreg, expands in steatohepatitis HCCTREM1+CD163+Mregexpress granulocyte- and macrophage/dendritic cell-lineage genesTREM1+CD163+Mregpotently suppress T cell effector functions, which is potentiated by TREM1 engagement by cognate ligandsTREM1+CD163+Mregproduce high levels of TGFβ and populate fibrotic lesionsThe density of TREM1+CD163+Mregincreases in advanced HCC and associate with poor patient survivalThe density of TREM1+CD163+Mregassociates with resistance to immune checkpoint blockade in other solid tumors
Gac is a transcriptional repressor of the Lyme disease spirochete’s OspC virulence-associated surface protein
Authors: Castro-Padovani Tatiana N. , Saylor Timothy C. , Husted Olivia T. , Krusenstjerna Andrew C. , Jusufovic Nerina , Stevenson Brian 
Published: November 2022

AbstractThe OspC outer-surface lipoprotein is essential for the Lyme disease spirochete’s initial phase of vertebrate infection. Bacteria within the midguts of unfed ticks do not express OspC, but produce high levels when ticks begin to ingest blood. Lyme disease spirochetes cease production of OspC within 1-2 weeks of vertebrate infection, and bacteria that fail to downregulate OspC are cleared by host antibodies. Thus, tight regulation of OspC levels is critical for survival of Lyme borreliae, and therefore an attractive target for development of novel treatment strategies. Previous studies determined that a DNA region 5’ of theospCpromoter, theospCoperator, is required for control of OspC production. Hypothesizing that theospCoperator may bind a regulatory factor, DNA affinity pulldown was performed, and identified binding by the Gac protein. Gac is encoded by the C-terminal domain of thegyrAopen reading frame, from an internal promoter, ribosome-binding site, and initiation codon. Our analyses determined that Gac exhibits a greater affinity forospCoperator and promoter DNAs than for other tested borrelial sequences. In vitro and in vivo analyses demonstrated that Gac is a transcriptional repressor ofospC. These results constitute a substantial advance to our understanding the mechanisms by which the Lyme disease spirochete controls production of OspC.ImportanceBorrelia burgdorferi(sensu lato) requires its surface-exposed OspC protein in order to establish infection of humans and other vertebrate hosts. Bacteria that either do not produce OspC during transmission, or fail to repress OspC after infection is established, are rapidly cleared by the host. Herein, we identified a borrelial protein, Gac, that exhibits preferential affinity to theospCpromoter and 5’ adjacent DNA. A combination of biochemical analyses and investigations of genetically-manipulated bacteria demonstrated that Gac is a transcriptional repressor ofospC. This is a substantial advance toward understanding how the Lyme disease spirochete controls production of the essential OspC virulence factor, and identifies a novel target for preventative and curative therapies.
Jointly aligning cells and genomic features of single-cell multi-omics data with co-optimal transport
Authors: Demetci Pinar , Tran Quang Huy , Redko Ievgen , Singh Ritambhara 
Published: November 2022

AbstractThe availability of various single-cell sequencing technologies allows one to jointly study multiple genomic features and understand how they interact to regulate cells. Although there are experimental challenges to simultaneously profile multiple features on the same single cell, recent computational methods can align the cells from unpaired multi-omic datasets. However, studying regulation also requires us to map the genomic features across different measurements. Unfortunately, most single-cell multi-omic alignment tools cannot perform these alignments or need prior knowledge. We introducescootr, a co-optimal transport-based method, which jointly aligns both cells and genomic features of unpaired single-cell multi-omic datasets. We applyscootrto various single-cell multi-omic datasets with different types of measurements. Our results show thatscootrprovides quality alignments for unsupervised cell-level and feature-level integration of datasets with sparse feature correspondences (e.g., one-to-one mappings). For datasets with dense feature correspondences (e.g., many-to-many mappings), our joint framework allows us to provide supervision on one level (e.g., cell types), thus improving alignment performance on the other (e.g., genomic features) or vice-versa. The unique joint alignment framework makesscootra helpful hypothesis-generation tool for the integrative study of unpaired single-cell multi-omic datasets.Available at:https://github.com/rsinghlab/SCOOTR.
Standardization of laboratory practices for the study of the human gut microbiome
Authors: Kool Jolanda , Tymchenko Liza , Shetty Sudarshan , Fuentes Susana 
Published: November 2022

AbstractTechnical advances in next-generation sequencing (NGS) have made it more accessible to study the human microbiome, resulting in more available data and knowledge. As a result of this expansion of data, the need to obtain comparable and reproducible data has become one of the most important challenges facing microbiome research nowadays. In this study, we aim to contribute to existing knowledge to promote high quality microbiome data and minimize bias introduced by technical variation throughout studies, from sample collection, storage, to sequencing strategies. While immediate freezing upon sampling has been the “golden standard” in the field, this method is often logistically difficult and expensive, becoming a limiting factor when conducting large scale studies or in regions where maintenance of the cold-chain presents difficulties. Therefore, we compared the immediately frozen method to storage at room temperature for 3 – 5 days in two commercially available stabilization solutions (Omnigene gut and Zymo Research) as well as without buffer. Other important aspects were tested, such as DNA extraction, bacterial DNA input or number of PCR cycles. Method choice for cell disruption resulted in the biggest difference in compositional profiles. The changes observed in microbiome profiles in samples stored at RT without stabilization solution was prevented by the use of these. For library preparation and sequencing, we found the highest heterogeneity in the DNA extraction step, followed by the use of different Illumina barcodes, indicating that both of these steps have an impact during library preparation. We did not observe a batch effect between the different sequencing runs. Standardized methods are important to allow comparison of results between different research groups worldwide and reliably expand microbiome data to a broad range of diseases, ethnical backgrounds and geographic locations. A more global perspective will increase our understanding of the human microbiome around the world.
Massive proteogenomic reanalysis of publicly available proteomic datasets of human tissues in search for protein recoding via adenosine-to-inosine RNA editing
Authors: Levitsky Lev I. , Ivanov Mark V. , Goncharov Anton O. , Kliuchnikova Anna A. , Bubis Julia A. , Lobas Anna A. , Solovyeva Elizaveta M. , Pyatnitskiy Mikhail A. , Ovchinnikov Ruslan K. , Kukharsky Mikhail S. , Farafonova Tatiana E. , Novikova Svetlana E. , Zgoda Victor G. , Tarasova Irina A. , Gorshkov Mikhail V. , Moshkovskii Sergei A. 
Published: November 2022

AbstractThe proteogenomic search pipeline developed in this work has been applied for re-analysis of 40 publicly available shotgun proteomic datasets from various human tissues comprising more than 8,000 individual LC-MS/MS runs, of which 5442 .raw data files were processed in total. The scope of this re-analysis was focused on searching for ADAR-mediated RNA editing events, their clustering across samples of different origin, and classification. In total, 33 recoded protein sites were identified in 21 datasets. Of those, 18 sites were detected in at least two datasets representing the core human protein editome. In agreement with prior art works, neural and cancer tissues were found being enriched with recoded proteins. Quantitative analysis indicated that recoding of specific sites did not directly depend on the levels of ADAR enzymes or targeted proteins themselves, rather it was provided by differential and yet undescribed regulation of interaction of enzymes with mRNA. Nine recoding sites conservative between human and rodents were validated by targeted proteomics using stable isotope standards in murine brain cortex and cerebellum, and an additional one was validated in human cerebrospinal fluid. In addition to previous data of the same type from cancer proteomes, we provide a comprehensive catalog of recoding events caused by ADAR RNA editing in the human proteome.
High Throughput Chromosome Conformation Capture identifies differential genome organization in virulent and avirulent strains ofMycobacterium tuberculosis
Authors: Mishra Mohit , Arya Ajay , Malik Md. Zubbair , Bhatnagar Rakesh , Hasnain Seyed E. , Ahmad Shandar , Chaturvedi Rupesh 
Published: November 2022

AbstractRecent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization inMycobacterium tuberculosis (M. tuberculosis), the etiologic agent of tuberculosis, remains unknown. On the other hand, exact mechanism of differential pathogenesis in the canonical strains ofM. tuberculosisH37Rv and H37Ra remains poorly understood in terms of their raw sequences. In this context, a detailed contact map from a Hi-C experiment is a candidate for what bridges the gap. Here we present the first comprehensive report on genome-wide contact maps between regions of H37Rv and H37Ra genomes. We tracked differences between the genome architectures of H37Rv and H37Ra, which could possibly explain the virulence attenuation in H37Ra. We confirm the existence of a differential organization between the two strains most significantly a higher Chromosome Interacting Domain (CID) size in attenuated H37Ra strain. CID boundaries are also found enriched with highly expressed genes and with higher operon density in H37Rv. Furthermore, most of the differentially expressed PE/PPE genes were present near the CID boundaries in H37Rv and not in H37Ra. Collectively our study proposes a differential genomic topological pattern between H37Rv and H37Ra, which could explain the virulence attenuation in H37Ra.
Establishing the Median Infectious Dose (ID50) and Characterizing the Clinical Manifestations of Mouse, Rat, Cow, and HumanCorynebacterium bovisIsolates in Select Immunocompromised Mouse Strains
Authors: Mendoza Gerardo , Cheleuitte-Nieves Christopher , Lertpiriyapong Kvin , Wipf Juliette R.K. , Arbona Rodolfo J. Ricart , Miranda Ileana C. , Lipman Neil S. 
Published: November 2022

ABSTRACTCorynebacterium bovis(Cb), the etiology of hyperkeratotic dermatitis in various immunocompromised mouse strains, significantly impacts research in which infected mice are used. Although Cb has been isolated from a variety of species, including mice, rats, cows, and humans, little is known about the differences in the infectivity and clinical disease in mice associated with unique isolates. The infectious dose yielding colonization of 50% of the exposed population (ID50) and any associated clinical disease was determined for mouse (n=3), rat (n=1), cow (n=1), and human (n=2) Cb isolates in athymic nude mice (Hsd:Athymic Nude-Foxn1nu). The same investigations were undertaken comparing 2 of these murine isolates in 2 furred immunocompromised mouse strains (NSG [NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz] and NSG-S [NOD.Cg-PrkdcscidIl2rgtm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ]). To determine the ID50, mice (n=6/dose; 3 of each sex) were inoculated topically with 1 to 108bacteria (10-fold increments) of each Cb isolate. Mice were scored (0 to 5) daily based on the severity of clinical signs for 14 days. On day 7 and 14 post-inoculation (PI), buccal and dorsal skin swabs were evaluated by aerobic culture to determine infection status. The mouse isolates yielded a lower ID50(58 to 1,000 bacteria) as compared to the bovine (6,460 to 7,498 bacteria) and rat (10,000 bacteria) Cb isolates. Mice were not colonized and disease did not result when inoculated with human isolates. Mouse isolates produced varying clinical disease severity in nude mice (max score/isolate: 0 to 5). Despite significant immunodeficiency, furred NSG and NSG-S mice required a considerably higher (1,000- to 3,000-fold) inoculum to become colonized as compared to athymic nude mice. Once colonized, clinically detectable hyperkeratosis did not develop in these strains until 18 to 22 days PI. In contrast, in athymic nude mice that developed clinically detectable disease, hyperkeratosis was observed 6 to 14 days PI. In conclusion, there are significant differences in Cb’s ID50, disease course, and severity between Cb isolates and among immunodeficient mouse strains.