bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiological follow-up of adults hospitalised with pneumonia and SARS-CoV-2 infection, in Bristol UK, during the COVID19 pandemic
Authors: Ruffino Gabriella , Williams Rachel L , Barratt Shaney , Hyams Catherine 
Published: January 2022

ABSTRACTIntroductionRadiological change which may be attributed to infection can also be attributable to lung cancer. Patients with SARS-CoV-2 infection can develop groundglass lung opacification which may result in chronic lung changes. Current British Thoracic Society (BTS) guidelines recommend patients with pneumonia and COVID19 undergo repeat chest radiography.MethodsA single-centre audit of patients hospitalised with community-acquired pneumonia or COVID19 over three time periods during the COVID19 pandemic (Aug-Dec 2020, Jun-Aug 2021, Dec-Jan 2022). We assessed whether patients were eligible for radiological follow-up and if repeat radiological investigation occurred.Results1040 adults were hospitalised with infective radiological change (pneumonia=596, COVID19=444). 831/1040 patients (80%) required radiological follow-up under BTS guideline criteria: there was minimal difference between the first two time periods studied. Patients hospitalised with CAP were less likely to have radiological follow-up planned than those admitted with COVID19 disease (49% versus 59% respectively). Following a change in hospital policy, follow-up rates increased to 69% and 71% for pneumonia and COVID19. Overall, only 47% eligible patients received follow-up in line with current guidelines.ConclusionBTS guideline adherence is important to avoid delay in diagnosing underlying malignancy or chronic lung disease. Radiological follow-up following CAP and COVID19 may be suboptimal, with a paucity of data. Follow-up arranged under the hospital team was more likely to occur than when the GP was responsible for instigating repeat radiological imaging. Further investigation into rates of radiological follow-up should be undertaken, including reasons for non-adherence, to ensure patients receive appropriate treatment following respiratory infection.
Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients
Authors: Yang Lu M. , Costales Cristina , Ramanathan Muthukumar , Bulterys Philip L. , Murugesan Kanagavel , Schroers-Martin Joseph , Alizadeh Ash A. , Boyd Scott D. , Brown Janice M. , Nadeau Kari C. , Nadimpalli Sruti S. , Wang Aileen X. , Busque Stephan , Pinsky Benjamin A. , Banaei Niaz 
Published: January 2022

ABSTRACTImportanceData on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited.ObjectiveTo determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response.DesignRetrospective observational cohort study.SettingLarge healthcare system in Northern California.ParticipantsThis study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection.Exposure(s)Immunosuppressive diseases and therapies.Main Outcome(s) and Measure(s)Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination.Results496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (P<.001), sphingosine 1-phsophate (S1P) receptor modulators (P<.001), mycophenolate (P=.002), and B cell lymphoma (P=.004); those associated with low rates of cellular response included S1P receptor modulators (P<.001) and mycophenolate (P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose.Conclusions and RelevanceCellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.
Cortical and STN spectral changes during limb movements in PD patients with and without dystonia
Authors: Olson Joseph W. , Nakhmani Arie , Irwin Zachary T. , Edwards Lloyd J. , Gonzalez Christopher L. , Wade Melissa H. , Black Sarah D. , Awad Mohammad Z. , Kuhman Daniel J. , Hurt Christopher P. , Guthrie Bart L. , Walker Harrison C. 
Published: January 2022

ABSTRACTBackgroundDystonia is an under-studied motor feature of Parkinson disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear.ObjectivesTo investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in PD patients with and without dystonia.MethodsWe examined the prevalence and distribution of dystonia in PD patients undergoing deep brain stimulation surgery and recorded intracranial electrophysiology from motor cortex and directional electrodes in subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia.ResultsDystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0±3.3 and 4.2±2.9 Hz peak frequencies for hand and foot movements respectively). PD patients with dystonia during DBS surgery displayed greater M1 beta power at rest and STN low frequency power during movements versus those without dystonia.ConclusionsSpectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low frequency synchronization, especially in PD patients with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy.
Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases
Authors: Ota Mineto , Nakano Masahiro , Nagafuchi Yasuo , Kobayashi Satomi , Hatano Hiroaki , Yoshida Ryochi , Akutsu Yuko , Itamiya Takahiro , Ban Nobuhiro , Tsuchida Yumi , Shoda Hirofumi , Yamamoto Kazuhiko , Ishigaki Kazuyoshi , Okamura Tomohisa , Fujio Keishi 
Published: January 2022

AbstractObjectivesDespite the involvement of B cells in the pathogenesis of immune-mediated diseases, biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalog of five B cell subsets of immune-mediated disease patients.MethodsWe mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under immune-mediated diseases and health. We characterized the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment.ResultsHeavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed only in naïve B cells and suggested the role for interferon in pre-mature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of systemic lupus erythematosus (SLE) patients. We developed a scoring system for this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extra-follicular pathway. Further, this skewing led to high usage of IGHV4-34 gene in unswitched-memory B cells, whose usage showed prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment.ConclusionsOur multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.
Detection of fecal coliforms and SARS-CoV-2 RNA in sewage and recreational waters in the Ecuadorian Coast: a call for improving water quality regulation
Authors: Cárdenas-Calle Maritza , Patiño Leandro , Pernia Beatríz , Erazo Roberto , Muñoz Carlos , Valencia-Avellan Magaly , Lozada Mariana , Regato-Arrata Mary , Barrera Miguel , Aquino Segundo , Moyano Stalyn , Fuentes Stefania , Duque Javier , Velazquez-Araque Luis , Carpio Bertha , Méndez-Roman Carlos , Calle Carlos , Cárdenas Guillermo , Guizado-Herrera David , Lucía Tello Clara , Bravo-Basantes Veronica , Zambranod Josué , Francis Jhannelle , Uyaguari Miguel 
Published: January 2022

ABSTRACTWastewater surveillance represents an alternative approach for the diagnosis and early detection of infectious agents of public health importance. This study aimed to evaluate SARS-CoV-2 and other quality markers in oxidation lagoons, estuarine areas and seawater at Guayas and Santa Elena in Ecuador. Sample collections were conducted twice at 42 coastal sites and 2 oxidation lagoons during dry and rainy seasons (2020-2021). Physico-chemical and microbiological parameters were evaluated to determine organic pollution. Quantitative reverse transcription PCR was conducted to detect SARS-CoV-2. Results showed high levels of Escherichia coli and low dissolved oxygen concentrations. SARS-CoV-2 was detected in sea-waters and estuaries with salinity levels between 34.2-36.4 PSU and 28.8 °C-31.3 °C. High amounts of fecal coliforms were detected and correlated with the SARS-CoV-2 shedding. We recommend to decentralized autonomous governments in developing countries such as Ecuador to implement corrective actions and establish medium-term mechanisms to minimize a potential contamination route.HIGHLIGHTSSARS-CoV-2 RNA was detected in estuaries, bays and the wastewater treatment systems in Playas and Santa Elena.High levels of fecal coliforms were detected along shorelines.Water quality parameters revealed a negative impact on the beaches studied associated with human activities.
Development of the one-step qualitative RT-PCR assay to detect SARS-CoV-2 Omicron (B.1.1.529) variant in respiratory specimens
Authors: Phan Tung , Boes Stephanie , McCullough Melissa , Gribschaw Jamie , Wells Alan 
Published: January 2022

AbstractA new SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern has been emerging worldwide. We are seeing an unprecedented surge in patients due to Omicron in this COVID-19 pandemic. A rapid and accurate molecular test that effectively differentiates Omicron from other SARS-CoV-2 variants would be important for both epidemiologic value and for directing variant-specific therapies such as monoclonal antibody infusions. In this study, we developed a real-time RT-PCR assay for the qualitative detection of Omicron from routine clinical specimens sampling the upper respiratory tract. The limit of detection of the SARS-CoV-2 Omicron variant RT-PCR assay was 2 copies/μl. Notably, the assay did not show any cross-reactivity with other SARS-CoV-2 variants including Delta (B.1.617.2). This SARS-CoV-2 Omicron variant RT-PCR laboratory-developed assay is sensitive and specific to detect Omicron in nasopharyngeal and nasal swab specimens.
Waning Effectiveness of the BNT162b2 Vaccine Against Infection in Adolescents
Authors: Prunas Ottavia , Weinberger Daniel M. , Pitzer Virginia E. , Gazit Sivan , Patalon Tal 
Published: January 2022

AbstractBackgroundThe short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, though, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months.MethodsLeveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where two outcomes were evaluated separately: a documented SARS-CoV-2 infection (regardless of symptoms) and a symptomatic infection (COVID-19). Cases were defined as individuals aged 12 to 16 with a positive PCR test occurring between June 15 and December 8, 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously.ResultsWe estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% and 90% effectiveness against SARS-CoV-2 infection and COVID-19, respectively. However, in line with previous findings for adults, waning of vaccine effectiveness was evident in adolescents as well. Long-term protection conferred by the vaccine was reduced to 75-78% against infection and symptomatic infection, respectively, 3 to 5 months after the second dose, and waned to 58% against infection and 65% against COVID-19 after 5 months.ConclusionsLike adults, vaccine-induced protection against both SARS-CoV-2 infection and COVID-19 wanes with time, starting three months after inoculation and continuing for more than five months.
HMGN5 escorts oncogenic STAT3 signaling by regulating chromatin landscape in tumorigenesis of breast cancer
Authors: Mou Jiahui , Huang Meijun , Wang Feifei , Xu Xiaoding , Xie Hanqi , Lu Henglei , Li Mingyang , Li Yu , Kong Weiwen , Chen Jing , Xiao Ying , Chen Yiding , Wang Chaochen , Ren Jin 
Published: January 2022

AbstractEpigenetic alterations are widely linked with carcinogenesis, therefore becoming emerging therapeutic targets in the treatment of cancers, including breast cancer. HMGNs are nucleosome binding proteins, which regulate chromatin structures in a cell type- and disease-specific manner. However, the roles of HMGNs in the tumorigenesis of breast cancer are less known. In this study, we report that HMGNs are highly expressed in 3D-cultured breast cancer cells. HMGN5, a member of HMGNs, controls the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Clinically, HMGN5 is an unfavorable prognostic marker in patients. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape oncogenic chromatin landscape and transcriptional program. Lastly, we provide evidence that interference of HMGN5 by nanoparticle-packaged siRNA is potentially an effective approach in breast cancer treatment. Taken together, our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic-target in STAT3- hyperactive breast cancer.
Evaluation of a predictive method for the H&E-based molecular profiling of breast cancer with deep learning
Authors: Arslan Salim , Li Xiusi , Schmidt Julian , Hense Julius , Geraldes Andre , Bass Cher , Brown Keelan , Marcia Angelica , Dewhirst Tim , Pandya Pahini , Singhal Shikha , Mehrotra Debapriya , Raharja-Liu Pandu 
Published: January 2022

AbstractWe present a public validation of PANProfiler (ER, PR, HER2), an in-vitro medical device (IVD) that predicts the qualitative status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) by analysing the hematoxylin and eosin (H&E)-stained tissue scan. In public validation on 648 (ER), 648 (PR) and 560 (HER2) unseen cases with known biomarker status, the device achieves an accuracy of 87% (ER), 83% (PR) and 87% (HER2). The validation offers early evidence of the ability to predict clinically relevant breast biomarkers from an H&E slide in a relevant clinical setting.
Red blood cells protein profile is modified in breast cancer patients
Authors: Pereira-Veiga Thais , Bravo Susana , Gómez-Tato Antonio , Yáñez-Gómez Celso , Abuín Carmen , Varela Vanesa , Cueva Juan , Palacios Patricia , Dávila-Ibáñez Ana B. , Piñeiro Roberto , Vilar Ana , Chantada-Vázquez María del Pilar , López-López Rafael , Costa Clotilde 
Published: January 2022

AbstractMetastasis is the primary cause of death for most breast cancer patients who succumb to the disease. During the haematogenous dissemination, circulating tumor cells interact with different blood components. Thus, there are micro-environmental and systemic processes contributing to cancer regulation. We have published that Red Blood Cells (RBCs) that accompany circulating tumor cells have prognostic value in metastatic breast cancer patients. Although the principal known role of RBCs is gas transport, it has been recently assigned additional functions as regulatory cells on circulation. Hence, to explore their potential contribution to tumor progression, we characterized the proteomic composition of RBCs from 53 breast cancer patients, compared with 33 healthy donors. RBCs from breast cancer patients showed a different proteomic profile compared to healthy donors. The differential proteins were mainly related to extracellular components, proteasome, and metabolism. Besides, LAMP2 emerge as a new RBCs marker with diagnostic and prognostic potential for metastatic patients. Seemingly, RBCs are acquiring modifications in their proteomic composition that probably represents the systemic cancer disease, conditioned by the tumor microenvironment.
Drosophila Mechanical Nociceptors Preferentially Sense Localized Poking
Authors: Liu Zhen , Wang Qi-Xuan , Wu Meng-Hua , Lin Shao-Zhen , Feng Xi-Qiao , Li Bo , Liang Xin 
Published: January 2022

AbstractMechanical nociception is an evolutionarily conserved sensory process required for the survival of living organisms. Previous studies have revealed much about the neural circuits and key sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device. We find that c4da are sensitive to mN-scale forces and make uniform responses to the forces applied at different dendritic regions. Moreover, c4da showed a greater sensitivity to more localized forces, consistent with them being able to sense the poking of sharp objects, such as wasp ovipositor. Further analysis reveals that high morphological complexity, mechanosensitivity to lateral tension and active signal propagation in the dendrites altogether facilitate the mechanosensitivity and sensory features of c4da. In particular, we discover that Piezo and Ppk1/Ppk26, two key mechanosensory molecules, make differential but additive contributions to the mechanosensation of c4da. In all, our results provide updates into understanding how c4da process mechanical signals at the cellular level and reveal the contributions of key molecules.
Front propagation and arrival times in networks with application to neurodegenerative diseases
Authors: Putra Prama , Oliveri Hadrien , Thompson Travis , Goriely Alain 
Published: January 2022

AbstractMany physical, epidemiological, or physiological dynamical processes on networks support front-like propagation, where an initial localized perturbation grows and systematically invades all nodes in the network. A key question is then to extract estimates for the dynamics. In particular, if a single node is seeded at a small concentration, when will other nodes reach the same initial concentration? Here, motivated by the study of toxic protein propagation in neurodegenerative diseases, we present and compare three different estimates for the arrival time in order of increasing analytical complexity: the linear arrival time, obtained by linearizing the underlying system; the Lambert time, obtained by considering the interaction of two nodes; and the nonlinear arrival time, obtained by asymptotic techniques. We use the classic Fisher-Kolmogorov-Petrovsky-Piskunov equation as a paradigm for the dynamics and show that each method provides different insight and time estimates. Further, we show that the nonlinear asymptotic method also gives an approximate solution valid in the entire domain and the correct ordering of arrival regions over large regions of parameters and initial conditions.
The Metaxin Mitochondrial Import Proteins: Multiple Metaxin-like Proteins in Fungi
Authors: Adolph Kenneth W. 
Published: January 2022

ABSTRACTMultiple metaxin-like proteins are shown to exist in fungi, as also found for the metaxin proteins of vertebrates and invertebrates. In vertebrates, metaxins 1 and 2 are mitochondrial membrane proteins that function in the import of proteins into mitochondria. Fungal metaxin-like proteins were identified by criteria including their homology with human metaxins and the presence of characteristic GST_N_Metaxin, GST_C_Metaxin, and Tom37 protein domains. Fungi in different taxonomic divisions (phyla) were found to possess multiple metaxin-like proteins. These include the Ascomycota, Basidiomycota, Blastocladiomycota, Chytridiomycota, Mucoromycota, Neocallimastigomycota, and Zoopagomycota divisions. Most fungi with multiple metaxin-like proteins contain two proteins, designated MTXa and MTXb. Amino acid sequence alignments show a high degree of homology among MTXa proteins, with over 60% amino acid identities, and also among MTXb proteins of fungi in the same division. But very little homology is observed in aligning MTXa with MTXb proteins of the same or different fungi. Both the MTXa proteins and MTXb proteins have the protein domains that characterize the metaxins and metaxin-like proteins: GST_N_Metaxin, GST_C_Metaxin, and Tom37. The metaxins and metaxin-like proteins of vertebrates, invertebrates, plants, protists, and bacteria all possess these domains. The secondary structures of MTXa and MTXb proteins are both dominated by similar patterns of α-helical segments, but extensive β-strand segments are absent. Nine highly conserved α-helical segments are present, the same as other metaxins and metaxin-like proteins. Phylogenetic analysis reveals that MTXa and MTXb proteins of fungi form two separate and distinct groups. These groups are also separate from the groups of vertebrate metaxins, metaxin-related Sam37 proteins of yeasts, and metaxin-like FAXC proteins.