Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury.

Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain-containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin-mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion-induced AKI in mice. By using genetically engineered mice and transduced Slp76(-/-) primary leukocytes, we demonstrate that ADAP as well as two N-terminal-located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kγ (phosphoinositide 3-kinase-γ)- and PLCγ2 (phospholipase Cγ2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin-mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion-induced AKI in humans

Evolution of complex organic molecules in hot molecular cores: Synthetic spectra at (sub-)mm wavebands

Hot molecular cores (HMCs) are intermediate stages of high-mass star formation and are also known for their rich emission line spectra at (sub-)mm wavebands. The observed spectral feature of HMCs such as total number of emission lines and associated line intensities are also found to vary with evolutionary stages. We developed various 3D models for HMCs guided by the evolutionary scenarios proposed by recent empirical and modeling studies. We then investigated the spatio-temporal variation of temperature and molecular abundances in HMCs by consistently coupling gas-grain chemical evolution with radiative transfer calculations. We explored the effects of varying physical conditions on molecular abundances including density distribution and luminosity evolution of the central protostar(s). The time-dependent temperature structure of the hot core models provides a realistic framework for investigating the spatial variation of ice mantle evaporation as a function of evolutionary timescales. With increasing protostellar luminosity, the water ice evaporation font ($\sim$100K) expands and the spatial distribution of gas phase abundances of these COMs also spreads out. We simulated the synthetic spectra for these models at different evolutionary timescales to compare with observations. A qualitative comparison of the simulated and observed spectra suggests that these self-consistent hot core models can reproduce the notable trends in hot core spectral variation within the typical hot core timescales of 10$^{5}$ year. These models predict that the spatial distribution of various emission line maps will also expand with evolutionary time. The model predictions can be compared with high resolution observation that can probe scales of a few thousand AU in high-mass star forming regions such as from ALMA.[Abridged]Comment: accepted for publication in A&

Including mixed methods research in systematic reviews: Examples from qualitative syntheses in TB and malaria control.

BACKGROUND: Health policy makers now have access to a greater number and variety of systematic reviews to inform different stages in the policy making process, including reviews of qualitative research. The inclusion of mixed methods studies in systematic reviews is increasing, but these studies pose particular challenges to methods of review. This article examines the quality of the reporting of mixed methods and qualitative-only studies. METHODS: We used two completed systematic reviews to generate a sample of qualitative studies and mixed method studies in order to make an assessment of how the quality of reporting and rigor of qualitative-only studies compares with that of mixed-methods studies. RESULTS: Overall, the reporting of qualitative studies in our sample was consistently better when compared with the reporting of mixed methods studies. We found that mixed methods studies are less likely to provide a description of the research conduct or qualitative data analysis procedures and less likely to be judged credible or provide rich data and thick description compared with standalone qualitative studies. Our time-related analysis shows that for both types of study, papers published since 2003 are more likely to report on the study context, describe analysis procedures, and be judged credible and provide rich data. However, the reporting of other aspects of research conduct (i.e. descriptions of the research question, the sampling strategy, and data collection methods) in mixed methods studies does not appear to have improved over time. CONCLUSIONS: Mixed methods research makes an important contribution to health research in general, and could make a more substantial contribution to systematic reviews. Through our careful analysis of the quality of reporting of mixed methods and qualitative-only research, we have identified areas that deserve more attention in the conduct and reporting of mixed methods research

Stability of Feline Coronavirus in aerosols and dried in organic matrices on surfaces at various environmental conditions

Enveloped respiratory viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be transmitted through aerosols and contact with contaminated surfaces. The stability of these viruses outside the host significantly impacts their transmission dynamics and the spread of diseases. In this study, we investigated the tenacity of Feline Coronavirus (FCoV) in aerosols and on surfaces under varying environmental conditions. We found that airborne FCoV showed different stability depending on relative humidity (RH), with higher stability observed at low and high RH. Medium RH conditions (50–60%) were associated with increased loss of infectivity. Furthermore, FCoV remained infectious in the airborne state over 7 h. On stainless-steel surfaces, FCoV remained infectious for several months, with stability influenced by organic material and temperature. The presence of yeast extract and a temperature of 4 °C resulted in the longest maintenance of infectivity, with a 5 log10 reduction of the initial concentration after 167 days. At 20 °C, this reduction was achieved after 19 days. These findings highlight the potential risk of aerosol and contact transmission of respiratory viruses, especially in enclosed environments, over extended periods. Studying surrogate viruses like FCoV provides important insights into the behavior of zoonotic viruses like SARS-CoV-2 in the environment

Influence of Measurement Depth and Acquisition Parameters on Shear Wave Speed and Shear Wave Dispersion in Certified Phantoms Using a Canon Aplio Clinical Ultrasound Scanner

OBJECTIVE The aim of the work described here was to investigate the relative contribution of confounding factors on liver shear wave speed (SWS) and shear wave dispersion slope (SWDS) measurements in three certified phantoms using a Canon Aplio clinical ultrasound scanner. METHODS A Canon Aplio i800 i-series ultrasound system (Canon Medical Systems Corporation, Otawara, Tochigi, Japan) with i8CX1 convex array (center frequency = 4 MHz) was used to examine dependencies caused by the depth, width and height of the acquisition box (AQB), the depth and size of the region of interest (ROI), the AQB angle and the pressure of the ultrasound probe on the surface of the phantom. RESULTS Results revealed that depth is the most significant confounder in both SWS and SWDS measurements. AQB angle, height and width and ROI size exhibited minimal confounding effects on measurements. For SWS, the most consistent measurement depth is when the top of the AQB is placed between 2 and 4 cm, and the ROI is located between 3 and 7 cm deep. For SWDS, results indicate that measurement values significantly decrease with depth from the surface of the phantom until approximately 7 cm deep, and consequently no stable area of AQB placement or ROI depth exists. CONCLUSION In contrast to SWS, the same ideal acquisition depth range cannot necessarily be applied to SWDS measurements because of a significant depth dependency

Impact of air humidity on the tenacity of different agents in bioaerosols

Despite the variety of pathogens that are transmitted via the airborne route, few data are available on factors that influence the tenacity of airborne pathogens. In order to better understand and thus control airborne infections, knowledge of these factors is important. In this study, three agents, S. aureus, G. stearothermophilus spores and the MS2 bacteriophage, were aerosolized at relative humidities (RH) varying between 30% and 70%. Air samples were then analyzed to determine the concentration of the agents. S. aureus was found to have significantly lower survival rate in the aerosol at RH above 60%. It showed the lowest recovery rates of the three agents, ranging from 0.13% at approximately 70% RH to 4.39% at 30% RH. G. stearothermophilus spores showed the highest tenacity with recovery rates ranging from 41.85% to 61.73% with little effect of RH. For the MS2 bacteriophage, a significantly lower tenacity in the aerosol was observed with a recovery rate of 4.24% for intermediate RH of approximately 50%. The results of this study confirm the significant influence of the RH on the tenacity of airborne microorganisms depending on the specific agent. These data show that the behavior of microorganism in bioaerosols is varies under different environmental conditions

Steering a Historical Disease Forecasting Model Under a Pandemic: Case of Flu and COVID-19

Forecasting influenza in a timely manner aids health organizations and policymakers in adequate preparation and decision making. However, effective influenza forecasting still remains a challenge despite increasing research interest. It is even more challenging amidst the COVID pandemic, when the influenza-like illness (ILI) counts are affected by various factors such as symptomatic similarities with COVID-19 and shift in healthcare seeking patterns of the general population. Under the current pandemic, historical influenza models carry valuable expertise about the disease dynamics but face difficulties adapting. Therefore, we propose CALI-Net, a neural transfer learning architecture which allows us to 'steer' a historical disease forecasting model to new scenarios where flu and COVID co-exist. Our framework enables this adaptation by automatically learning when it should emphasize learning from COVID-related signals and when it should learn from the historical model. Thus, we exploit representations learned from historical ILI data as well as the limited COVID-related signals. Our experiments demonstrate that our approach is successful in adapting a historical forecasting model to the current pandemic. In addition, we show that success in our primary goal, adaptation, does not sacrifice overall performance as compared with state-of-the-art influenza forecasting approaches.Comment: Appears in AAAI-2

Negative enrichment by immunomagnetic nanobeads for unbiased characterization of circulating tumor cells from peripheral blood of cancer patients

BACKGROUND: A limitation of positive selection strategies to enrich for circulating tumor cells (CTCs) is that there might be CTCs with insufficient expression of the surface target marker which may be missed by the procedure. We optimized a method for enrichment, subsequent detection and characterization of CTCs based on depletion of the leukocyte fraction. METHODS: The 2-step protocol was developed for processing 20 mL blood and based on red blood cell lysis followed by leukocyte depletion. The remaining material was stained with the epithelial markers EpCAM and cytokeratin (CK) 7/8 or for the melanoma marker HMW-MAA/MCSP. CTCs were detected by flow cytometry. CTCs enriched from blood of patients with carcinoma were defined as EpCAM+CK+CD45-. CTCs enriched from blood of patients with melanoma were defined as MCSP+CD45-. One-hundred-sixteen consecutive blood samples from 70 patients with metastatic carcinomas (n = 48) or metastatic melanoma (n = 22) were analyzed. RESULTS: CTCs were detected in 47 of 84 blood samples (56%) drawn from carcinoma patients, and in 17 of 32 samples (53%) from melanoma patients. CD45-EpCAM-CK+ was detected in pleural effusion specimens, as well as in peripheral blood samples of patients with NSCLC. EpCAM-CK+ cells have been successfully cultured and passaged longer than six months suggesting their neoplastic origin. This was confirmed by CGH. By defining CTCs in carcinoma patients as CD45-CK+ and/or EpCAM+, the detection rate increased to 73% (61/84). CONCLUSION: Enriching CTCs using CD45 depletion allowed for detection of epithelial cancer cells not displaying the classical phenotype. This potentially leads to a more accurate estimation of the number of CTCs. If detection of CTCs without a classical epithelial phenotype has clinical relevance need to be determined

Head-Down Tilt Position, but Not the Duration of Bed Rest Affects Resting State Electrocortical Activity

Adverse cognitive and behavioral conditions and psychiatric disorders are considered a critical and unmitigated risk during future long-duration space missions (LDSM). Monitoring and mitigating crew health and performance risks during these missions will require tools and technologies that allow to reliably assess cognitive performance and mental well-being. Electroencephalography (EEG) has the potential to meet the technical requirements for the non-invasive and objective monitoring of neurobehavioral conditions during LDSM. Weightlessness is associated with fluid and brain shifts, and these effects could potentially challenge the interpretation of resting state EEG recordings. Head-down tilt bed rest (HDBR) provides a unique spaceflight analog to study these effects on Earth. Here, we present data from two long-duration HDBR experiments, which were used to systematically investigate the time course of resting state electrocortical activity during prolonged HDBR. EEG spectral power significantly reduced within the delta, theta, alpha, and beta frequency bands. Likewise, EEG source localization revealed significantly lower activity in a broad range of centroparietal and occipital areas within the alpha and beta frequency domains. These changes were observed shortly after the onset of HDBR, did not change throughout HDBR, and returned to baseline after the cessation of bed rest. EEG resting state functional connectivity was not affected by HDBR. The results provide evidence for a postural effect on resting state brain activity that persists throughout long-duration HDBR, indicating that immobilization and inactivity per se do not affect resting state electrocortical activity during HDBR. Our findings raise an important issue on the validity of EEG to identify the time course of changes in brain function during prolonged HBDR, and highlight the importance to maintain a consistent body posture during all testing sessions, including data collections at baseline and recovery

Electrocortical Evidence for Impaired Affective Picture Processing after Long-Term Immobilization

The neurobehavioral risks associated with spaceflight are not well understood. In particular, little attention has been paid on the role of resilience, social processes and emotion regulation during long-duration spaceflight. Bed rest is a well-established spaceflight analogue that combines the adaptations associated with physical inactivity and semi-isolation and confinement. We here investigated the effects of 30 days of 6 degrees head-down tilt bed rest on affective picture processing using event-related potentials (ERP) in healthy men. Compared to a control group, bed rest participants showed significantly decreased P300 and LPP amplitudes to pleasant and unpleasant stimuli, especially in centroparietal regions, after 30 days of bed rest. Source localization revealed a bilateral lower activity in the posterior cingulate gyrus, insula and precuneus in the bed rest group in both ERP time frames for emotional, but not neutral stimuli