bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Detection and Quantification of COVID-19 Airspace Disease on Chest Radiographs
Authors: Mortani Barbosa Eduardo J. , Gefter Warren B. , Ghesu Florin C. , Liu Siqi , Mailhe Boris , Mansoor Awais , Grbic Sasa , Vogt Sebastian 
Published: January 2021

Objectives
The aim of this study was to leverage volumetric quantification of airspace disease (AD) derived from a superior modality (computed tomography [CT]) serving as ground truth, projected onto digitally reconstructed radiographs (DRRs) to (1) train a convolutional neural network (CNN) to quantify AD on paired chest radiographs (CXRs) and CTs, and (2) compare the DRR-trained CNN to expert human readers in the CXR evaluation of patients with confirmed COVID-19.

Materials and Methods
We retrospectively selected a cohort of 86 COVID-19 patients (with positive reverse transcriptase-polymerase chain reaction test results) from March to May 2020 at a tertiary hospital in the northeastern United States, who underwent chest CT and CXR within 48 hours. The ground-truth volumetric percentage of COVID-19-related AD (POv) was established by manual AD segmentation on CT. The resulting 3-dimensional masks were projected into 2-dimensional anterior-posterior DRR to compute area-based AD percentage (POa). A CNN was trained with DRR images generated from a larger-scale CT dataset of COVID-19 and non-COVID-19 patients, automatically segmenting lungs, AD, and quantifying POa on CXR. The CNN POa results were compared with POa quantified on CXR by 2 expert readers and to the POv ground truth, by computing correlations and mean absolute errors.

Results
Bootstrap mean absolute error and correlations between POa and POv were 11.98% (11.05%–12.47%) and 0.77 (0.70–0.82) for average of expert readers and 9.56% to 9.78% (8.83%–10.22%) and 0.78 to 0.81 (0.73–0.85) for the CNN, respectively.

Conclusions
Our CNN trained with DRR using CT-derived airspace quantification achieved expert radiologist level of accuracy in the quantification of AD on CXR in patients with positive reverse transcriptase-polymerase chain reaction test results for COVID-19.
Association Between Converting Asystole From Initial Shockable ECG Rhythm Before Extracorporeal Cardiopulmonary Resuscitation and Outcome
Authors: Maeda Keisuke , Inoue Akihiko , Kuroda Yasuhiro , Inoue Fumiya , Suga Masafumi , Ijuin Shinichi , Kai Soichiro , Koga Tokito , Igarashi Nobuaki , Matsuyama Shigenari , Kawase Tetsunori , Ishihara Satoshi , Naitou Hiroshi , Nakayama Shinichi 
Published: January 2021

ABSTRACT

Background:
Initial electrocardiogram (ECG) rhythm is a predictor of outcomes in out-of-hospital cardiac arrest (OHCA) in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). However, ECG rhythm often changes before ECPR, and the consequence of this change remains unclear. This study aimed to assess the relationship between the conversion of ECG rhythm from initial shockable rhythm before ECPR and mortality.

Patients and Methods:
This was a retrospective cohort study of OHCA patients with initial shockable rhythm who underwent ECPR between January 2010 and September 2020. Patients were classified into two groups: asystole (patients whose ECG rhythm converted to asystole at any time before initiating ECPR) and non-asystole (patients whose ECG rhythm did not convert to asystole at any time before initiating ECPR) groups. The primary outcome was in-hospital mortality.

Results:
A total of 102 patients were included in the study; in-hospital mortality rate was 46.1% (n = 47) and 76 (74.5%) patients had unfavorable neurological outcomes (Cerebral Performance Category: 3–5). There were 33 and 69 patients in the asystole and non-asystole groups, respectively. The mortality rates in the asystole and non-asystole groups were 69.7% and 34.8%, respectively (P = 0.001). On multivariable analysis, the asystole group showed a significant association with mortality (odds ratio, 5.42; 95% confidence interval, 2.11–15.36; P < 0.001).

Conclusion:
Conversion to asystole before ECPR at any time in patients with OHCA is associated with mortality in patients with an initial shockable ECG rhythm.
CX3CR1 Depletion Promotes the Formation of Platelet–Neutrophil Complexes and Aggravates Acute Peritonitis
Authors: Ngamsri Kristian-Christos , Böhne Jan , Simelitidis Mariana-Sophie , Gamper-Tsigaras Jutta , Zhang Yi , Ehnert Sabrina , Konrad Franziska M. 
Published: January 2021

ABSTRACT

Background:
Peritonitis is a life-threatening condition on intensive care units. Inflammatory cytokines and their receptors drive inflammation, cause the formation of platelet–neutrophil complexes (PNCs) and therefore the migration of polymorphonuclear neutrophils (PMNs) into the inflamed tissue. CX3CL1 and its receptor CX3CR1 are expressed in various cells, and promote inflammation. The shedding of CX3CL1 is mediated by a disintegrin and metalloprotease (ADAM) 17. The role of the CX3CL1-CX3CR1 axis in acute peritonitis remains elusive.

Methods:
In zymosan-induced peritonitis, we determined the formation of PNCs in the blood and the expression of PNC-related molecules on PNCs. PMN migration into the peritoneal lavage was evaluated in wild-type (WT) and CX3CR1-/- animals by flow cytometry. CX3CL1, ADAM17, and the expression of various inflammatory cytokines were detected. Further, we determined the inflammation-associated activation of the intracellular transcription factor extracellular signal-regulated kinase 1/2 (ERK1/2) by Western blot.

Results:
The PMN accumulation in the peritoneal lavage and the PNC formation in the circulation were significantly raised in CX3CR1-/- compared with WT animals. The expression of PNC-related selectins on PNCs was significantly increased in the blood of CX3CR1-/- animals, as well as cytokine levels. Further, we observed an increased activation of ERK1/2 and elevated ADAM17 expression in CX3CR1-/- during acute inflammation. Selective ERK1/2 inhibition ameliorated inflammation-related increased ADAM17 expression.

Conclusions:
A CX3CR1 deficiency raised the release of inflammatory cytokines and increased the PNC formation respectively PMN migration via an elevated ERK1/2 activation during acute peritonitis. Further, we observed a link between the ERK1/2 activation and an elevated ADAM17 expression on PNC-related platelets and PMNs during inflammation. Our data thus illustrate a crucial role of CX3CR1 on the formation of PNCs and regulating inflammation in acute peritonitis.
Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients
Authors: L'Huillier Arnaud G. , Hirzel Cedric , Ferreira Victor H. , Ierullo Matthew , Ku Terrance , Selzner Nazia , Schiff Jeffrey , Juvet Stephen , Miao Congrong , Schmid D. Scott , Humar Atul , Kumar Deepali 
Published: January 2021

Background.
Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection.

Methods.
VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2–6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines.

Results.
Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes.

Conclusions.
RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.
Evaluating Data-Driven Forecasting Methods for Predicting SARS-CoV2 Cases: Evidence From 173 Countries
Authors: Ahmad Ghufran , Ahmed Furqan , Rizwan Suhail , Muhammad Javed , Fatima Hira , Ikram Aamer , Zeeb Hajo 
Published: January 2021

AbstractThe WHO announced the epidemic of SARS-CoV2 as a public health emergency of international concern on 30th January 2020. To date, it has spread to more than 200 countries, and has been declared as a global pandemic. For appropriate preparedness, containment, and mitigation response, the stakeholders and policymakers require prior guidance on the propagation of SARS-CoV2. This study aims to provide such guidance by forecasting the cumulative COVID-19 cases up to 4 weeks ahead for 173 countries, using four data-driven methodologies; autoregressive integrated moving average (ARIMA), exponential smoothing model (ETS), random walk forecasts (RWF) with and without drift. We also evaluate the accuracy of these forecasts using the Mean Absolute Percentage Error (MAPE). The results show that the ARIMA and ETS methods outperform the other two forecasting methods. Additionally, using these forecasts, we generated heat maps to provide a pictorial representation of the countries at risk of having an increase in cases in the coming 4 weeks for June. Due to limited data availability during the ongoing pandemic, less data-hungry forecasting models like ARIMA and ETS can help in anticipating the future burden of SARS-CoV2 on healthcare systems.
Evaluating the Long-Term Efficacy of COVID-19 Vaccines
Authors: Lin Dan-Yu , Zeng Donglin , Gilbert Peter B. 
Published: January 2021

AbstractLarge-scale deployment of safe and durably effective vaccines can curtail the COVID-19 pandemic.1−3However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4−5and thus does not pertain to long-term efficacy. To evaluate the duration of protection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the performance of blinded and unblinded crossover designs in estimating long-term VE.Authors’ InformationDan-Yu Lin, Ph.D., is Dennis Gillings Distinguished Professor of Biostatistics, and Donglin Zeng, Ph.D., is Professor of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7420, USA. Peter B. Gilbert, Ph.D., is Member, Vaccine and Infectious Disease Division, Fred Hutch, Seattle, WA 98109-1024, USA.SummaryWe show how to estimate the potentially waning long-term efficacy of COVID-19 vaccines using data from randomized, placebo-controlled clinical trials with staggered enrollment of participants and sequential crossover of placebo recipients.
KSR1- and ERK-dependent Translational Regulation of the Epithelial-to-Mesenchymal Transition
Authors: Rao Chaitra , Frodyma Danielle E. , Southekal Siddesh , Svoboda Robert A. , Black Adrian R. , Guda Chittibabu , Mizutani Tomohiro , Clevers Hans , Johnson Keith R. , Fisher Kurt W. , Lewis Robert E. 
Published: January 2021

AbstractThe epithelial-to-mesenchymal transition (EMT) is considered a transcriptional process that induces a switch in cells from a polarized state to a migratory phenotype. Here we show that KSR1 and ERK promote EMT through the preferential translation of Epithelial-Stromal Interaction 1 (EPSTI1), which is required to induce the switch from E-to N-cadherin and coordinate migratory and invasive behavior. EPSTI1 is overexpressed in human colorectal cancer (CRC) cells. Disruption of KSR1 or EPSTI1 significantly impairs cell migration and invasioninvitro, and reverses EMT, in part, by decreasing the expression of N-cadherin and the transcriptional repressors of E-cadherin expression, ZEB1 and Slug. In CRC cells lacking KSR1, ectopic EPSTI1 expression restored the E-to N-cadherin switch, migration, invasion, and anchorage-independent growth. KSR1-dependent induction of EMT via selective translation of mRNAs reveals its underappreciated role in remodeling the translational landscape of CRC cells to promote their migratory and invasive behavior.
Characterization of influenza vaccination recommendation across spatial scales in the United States
Authors: Kuney Madeline C. , Zipfel Casey M. , Bansal Shweta 
Published: January 2021

AbstractThe US public health system is organized in 3 levels: national, state-level, and county-level. Public health messaging both within and across these scales may not always be consistent, and for transmissible public health threats where cases in one spatial location may impact other areas, this lack of consistency could create problems. Here, we collected and analyzed data on influenza vaccination recommendations across public health administration levels. We assess spatial heterogeneity at the county level, and analyze consistency in recommendations across spatial scales. We also compare information accessibility with influenza vaccine affordability and availability to identify factors that may be most related to vaccine uptake. We find that influenza vaccine recommendations are highly variable in both their priority group specificity and in their ease of access, and there is poor agreement across spatial scales. This lack of consistency results in a lack of clear relationship between vaccination information and vaccine uptake. This work highlights the need for greater consistency in specific, easily accessed public health information from trusted sources.
Luminal nutrients activate distinct patterns in submucosal and myenteric neurons in the mouse small intestine
Authors: Fung C. , Hao M.M. , Obata Y. , Tack J. , Pachnis V. , Boesmans W. , Vanden Berghe P. 
Published: January 2021

AbstractNutrient signals sensed by enteroendocrine cells are conveyed to the enteric nervous system (ENS) to initiate intestinal reflexes. We addressed whether there are specific enteric pathways dedicated to detecting different luminal nutrients. Calcium imaging was performed on intact jejunal preparations from Wnt1-cre;R26R-GCaMP3 and Villin-cre;R26R-GCaMP3 mice which express a fluorescent calcium indicator in their ENS or intestinal epithelium, respectively. Glucose, acetate, and L-phenylalanine were perfused onto the mucosa whilst imaging underlying enteric neurons. Nutrient transport or diffusion across the mucosa was mimicked by applying nutrients onto sensory nerve endings in a villus, or onto myenteric ganglia. The nutrients perfused onto the mucosa each elicited Ca2+transients in submucosal neurons and in distinct patterns of myenteric neurons. Notably, the neurochemical subtypes of myenteric neurons that responded differed between the nutrients, while submucosal responders were predominantly cholinergic. Nutrients applied into villi or onto ganglia did not elicit specific neuronal responses but did stimulate Ca2+signaling in the mucosal epithelium. These data suggest that nutrients are first detected at the level of the epithelium and that the ENS is capable of discriminating between different compositions of luminal content. Furthermore, our data show that responses to mucosal stimulation are primarily in the myenteric plexus and submucosal neurons respond secondarily.
Neuropsychological assessment and virtual reality training of social prediction in patients with cerebellar malformation
Authors: Urgesi Cosimo , Butti Niccolò , Finisguerra Alessandra , Biffi Emilia , Valente Enza Maria , Romaniello Romina , Borgatti Renato 
Published: January 2021

AbstractIt has been proposed that impairments of the predictive function exerted by the cerebellum may account for social cognition deficits. Here, we integrated cerebellar functions in a predictive coding framework to elucidate how cerebellar alterations could affect the predictive processing of others’ behavior. Experiment 1 demonstrated that cerebellar patients were impaired in relying on contextual information during action prediction, and this impairment was significantly associated with social cognition abilities. Experiment 2 indicated that patients with cerebellar malformation showed a domain-general deficit in using contextual information to predict both social and physical events. Experiment 3 provided first evidence that a social-prediction training in virtual reality could boost the ability to use context-based predictions to understand others’ intentions. These findings shed new light on the predictive role of the cerebellum and its contribution to social cognition, paving the way for new approaches to the rehabilitation of the Cerebellar Cognitive Affective Syndrome.
Modeling Brain Connectivity Dynamics in Functional Magnetic Resonance Imaging via Particle Filtering
Authors: Ambrosi Pierfrancesco , Costagli Mauro , Kuruoğlu Ercan E , Biagi Laura , Buonincontri Guido , Tosetti Michela 
Published: January 2021

AbstractInterest in the studying of functional connections in the brain has grown considerably in the last decades, as many studies have pointed out that these interactions can play a role as markers of neurological diseases. Most studies in this field treat the brain network as a system of connections stationary in time, but dynamic features of brain connectivity can provide useful information, both on physiology and pathological conditions of the brain. In this paper, we propose the application of a computational methodology, named Particle Filter (PF), to study non-stationarities in brain connectivity in functional Magnetic Resonance Imaging (fMRI). The PF algorithm estimates time-varying hidden parameters of a first-order linear time-varying Vector Autoregressive model (VAR) through a Sequential Monte Carlo strategy. On simulated time series, the PF approach effectively detected and enabled to follow time-varying hidden parameters and it captured causal relationships among signals. The method was also applied to real fMRI data, acquired in presence of periodic tactile or visual stimulations, in different sessions. On these data, the PF estimates were consistent with current knowledge on brain functioning. Most importantly, the approach enabled to detect statistically significant modulations in the cause-effect relationship between brain areas, which correlated with the underlying visual stimulation pattern presented during the acquisition.
PEBP regulates balance between apoptosis and autophagy, enabling coexistence of arbovirus and insect vector
Authors: Wang Shifan , Guo Huijuan , Zhu-Salzman Keyan , Ge Feng , Sun Yucheng 
Published: January 2021

AbstractApoptosis and autophagy are two most prominent forms of programmed cell deaths (PCD) that have been implicated in antiviral immunity in vertebrate and plant hosts. Arboviruses are able to coexist with its arthropod vectors by coordinating the PCD immunity, but the regulatory mechanism involved is largely unknown. We found that the coat protein (CP) of an insect-borne plant virus TYLCV directly interacted with a phosphatidylethanolamine-binding protein (PEBP) of its insect vector whitefly to negatively influence the MAPK signaling cascade. As a result, the apoptosis was activated in whitefly which increased viral loading. Simultaneously, the PEBP4-CP interaction liberated ATG8, the hallmark of autophagy initiation, and eliminates arbovirus. Furthermore, apoptosis-promoted virus loading was compromised by agonist-induced autophagy, but autophagy-associated suppression on virus loading was unaffected by apoptosis agonist or inhibitor, suggesting that virus loading was predominantly determined by autophagy rather than by apoptosis. Our results demonstrated that maintaining a mild immune response by coordinating apoptosis and autophagy processes presumably could facilitate coexistence of the arbovirus and its insect vector. Taken together, immune homeostasis shaped by two types of PCD may facilitate the arbovirus preservation within the insect vector.Graphical abstractHighlightsInteraction between whitefly PEBP4 and TYLCV CP suppresses phosphorylation of MAPK cascade, activating apoptosisTYLCV CP liberates PEBP4-bound ATG8, resulting in lipidation of ATG8 and initiation of autophagy.PEBP4 balances apoptosis and autophagy in viruliferous whitefly to optimize virus loading without obvious fitness cost.
Phosphoproteomics reveals new insights into the role of PknG during the persistence of pathogenic mycobacteria in host macrophages
Authors: Baros-Steyl Seanantha S. , Nakedi Kehilwe C. , Ganief Tariq A. , Okendo Javan O. , Tabb David L. , Soares Nelson C. , Blackburn Jonathan M. 
Published: January 2021

AbstractPathogenic mycobacteria, such asMycobacterium tuberculosis, modulate the host immune system to evade clearance and promote long-term persistence, resulting in disease progression or latent infection. Understanding the mechanisms pathogenic mycobacteria use to escape elimination by the host immune system is critical to better understanding the molecular mechanisms of mycobacterial infection. Protein kinase G (PknG) in pathogenic mycobacteria has been shown to play an important role in avoiding clearance by macrophages through blocking phagosome-lysosome fusion; however, the exact mechanism is not completely understood. Here, to further investigate the role of mycobacterial PknG during early events of macrophage infection, RAW 264.7 macrophage cell lines were infected withM. bovisBCG wild-type and PknG knock-out mutant strains. After proteolysis, phosphopeptides were enriched via TiO2 columns and subjected to LC-MS/MS to identify differentially phosphorylated peptides between the wild-type and PknG mutant infected macrophages. A total of 1401 phosphosites on 914 unique proteins were identified. Following phosphoproteome normalisation and differential expression analysis, a total of 149 phosphosites were differentially phosphorylated in the wild-type infected RAW 264.7 macrophages versus the PknG knock-out mutant. A subset of 95 phosphosites was differentially up-regulated in the presence of PknG. Functional analysis of our data revealed that PknG kinase activity reprograms normal macrophage function through interfering with host cytoskeletal organisation, spliceosomal machinery, translational initiation, and programmed cell death. Differentially phosphorylated proteins in this study serve as a foundation for further validation and PknG host substrate assignment.ImportanceTuberculosis (TB) remains one of the leading causes of death from infection worldwide, due to the ability ofMycobacterium tuberculosis(Mtb) to survive and replicate within the host, establishing reservoirs of live bacteria that promote persistence and recurrence of disease. Understanding the mechanisms thatMtbuses to evade the host immune system is thus a major goal in the TB field. Protein kinase G is thought to play an important role inMtbavoiding clearance by the host through disruption of macrophage function, but the underlying molecular mechanisms of this are not well understood. Here, our new phosphoproteomic data reveals that mycobacterial PknG substantially reprograms normal macrophage function through extensive PknG-mediated post-translational control of critical host cellular processes. These novel findings therefore considerably increase our knowledge of mycobacterial pathogenicity, including specific host cellular pathways that might be re-activatable through host-directed therapy, thereby restoring macrophage ability to eliminateMtb.