bluuebunny/crossref_metadata_2025 huggingface dataset:
PeSTZ1 confers salt stress tolerance by scavenging the accumulation of ROS through regulating the expression of PeZAT12 and PeAPX2 in Populus
Authors: He Fang , Niu Meng-Xue , Feng Cong-Hua , Li Hui-Guang , Su Yanyan , Su Wan-Long , Pang Hongguang , Yang Yanli , Yu Xiao , Wang Hou-Ling , Wang Jie , Liu Chao , Yin Weilun , Xia Xinli
Published: April 2020

ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12) plays an important role in stress responses, but the transcriptional regulation of ZAT12 in response to abiotic stress remains unclear. In this study, we confirmed that a SALT TOLERANCE ZINC FINGER1 transcription factor from Populus euphratica (PeSTZ1) could regulate the expression of PeZAT12 by dual-luciferase reporter (DLR) assay and electrophoretic mobility shift assay. The expression of PeSTZ1 was rapidly induced by NaCl and hydrogen peroxide (H2O2) treatments. Overexpressing PeSTZ1 in poplar 84K (Populus alba × Populus glandulosa) plant was endowed with a strong tolerance to salt stress. Under salt stress, transgenic poplar exhibited higher expression levels of PeZAT12 and accumulated a larger amount of antioxidant than the wild-type plants. Meanwhile, ASCORBATE PEROXIDASE2 (PeAPX2) can be activated by PeZAT12 and PeSTZ1, promoting the accumulation of cytosolic ascorbate peroxidase (APX) to scavenge reactive oxygen species (ROS) under salt stress. This new regulatory model (PeSTZ1–PeZAT12–PeAPX2) was found in poplar, providing a new idea and insight for the interpretation of poplar resistance. Transgenic poplar reduced the accumulation of ROS, restrained the degradation of chlorophyll and guaranteed the photosynthesis and electron transport system. On the other hand, transgenic poplar slickly adjusted K+/Na+ homeostasis to alleviate salt toxicity in photosynthetic organs of plants under salt stress and then increased biomass accumulation. In summary, PeSTZ1 confers salt stress tolerance by scavenging the accumulation of ROS through regulating the expression of PeZAT12 and PeAPX2 in poplar.
No evidence for distinct types in the evolution of SARS-CoV-2
Authors: MacLean Oscar A , Orton Richard J , Singer Joshua B , Robertson David L
Published: April 2020

A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.
Roles of Nitric Oxide and Prostanoid Mediators in the Adaptation of the Cerebrocortical Blood Flow to Carotid Artery Occlusion
Authors: Hricisak Laszlo , Pal Eva , Izsa Gergely Tamas , Polycarpou Andreas , Dobrydnio Laura Simoes , Jabronka Nikolett , Ruisanchez Eva , Fulop Agnes , Benyo Zoltan
Published: April 2020

The understanding of cerebral autoregulation has become of notable importance due to the increased incidence of carotid artery stenosis in the elderly population which entails an increased risk of stroke, the 2nd most common cause of mortality worldwide. Many debates, regarding its exact mechanisms, exist in the scientific literature including the role of endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS) and prostanoid mediators (PMs). According to our previous observations, eNOS, surprisingly, does not seem to play an important role in the autoregulation of the cerebrocortical blood flow (CoBF) to unilateral common carotid artery occlusion (CAO)
(1). In our recent study we aimed to analyze the combined lack of eNOS and nNOS and the role of PMs in cerebrovascular autoregulation by analyzing the changes of CoBF after reducing the cerebral perfusion pressure by unilateral (left) CAO in wild‐type (WT), as well as in eNOS/nNOS double knock‐out (KO) male mice. The role of PMs was tested by indomethacin administration (1 mg/kg, i.p.) and in thromboxane knock‐out (TPR‐KO) male mice. Using the high temporal and spatial resolution of laser‐speckle imaging regional CoBF changes were analyzed after CAO in anesthetized adult male mice. In wild‐type animals CoBF reduction in the left temporal cortex started immediately after CAO, reaching its maximum (−27%) at 6–9 s. Thereafter, CoBF recovered close to the pre‐occlusion level within 30 s indicating the activation of regulatory pathway(s). Interestingly, the frontoparietal cerebrocortical regions also showed CoBF reduction in the left (−17–19%) hemisphere, indicating a stealing effect through pial collateral vessels from the frontoparietal to the more ischemic temporal cortex. Surprisingly, in eNOS/nNOS double KO animals the acute CoBF reduction after CAO was unaltered in all cerebrocortical regions, but the recovery of CoBF was worsened as compared to controls. Indomethacin treatment resulted in a faster recovery in the temporal region, specifically 9–21 s after the occlusion. In TPR‐KO animals, however, the recovery of the CoBF was slightly diminished. These results indicate that (1) the Willis circle alone is not sufficient to provide an immediate compensation for the loss of one carotid artery, (2) the combined lack of eNOS and nNOS impairs only the subacute phase of the recovery after unilateral CAO and (3) indomethacin treatment results in a faster recovery, probably by inhibiting the release of a vasoconstrictor prostanoid, which is not thromboxane A2.

Support or Funding Information

EFOP‐3.6.3‐VEKOP‐16‐2017‐00009, OTKA K‐125174, OTKA K‐112964, NVKP‐16‐1‐2016‐0042
High‐throughput proteome analysis using 50 cm long micro pillar array columns (μPAC&[trade])
Authors: Pervez Ali , Van Raemdonck Geert Geert
Published: April 2020

The practice of bottom‐up proteomics relies to a large extent on the separation performance that can be achieved with state‐of‐the art nano LC‐MS/MS equipment. Depending on the sample complexity or the instrument time that can be dedicated to a certain sample, different LC columns and corresponding LC‐MS/MS methods are required. When aiming for comprehensive proteome analysis with deep coverage, relatively long columns (lengths up to 75 cm) are typically operated with long and shallow solvent gradients, delivering the highest chromatographic performance. However, daily routine proteome analysis often deals with much less complex samples or demands increased sample throughput, making total analysis times above 120 min undesirable or even impossible. The LC columns typically used for this type of analyses do not exceed 25 cm in length, with a focus on workflow robustness and efficiency rather than on maximizing chromatographic performance or peak capacity
(1).

In the past few years, micro pillar array column (μPAC™) technology has evolved from a tool to perform fundamental LC research to a powerful alternative for classical nano LC columns. The inherent high permeability and low ‘on‐column’ dispersion obtained by the perfect order of the separation bed makes pillar array based chromatography unique in its kind. The peak dispersion originating from heterogeneous flow paths in the separation bed is drastically reduced and therefore components remain much more concentrated during separation
(2). Apart from an improved efficiency, pillar array columns can also be designed with substantially lower flow resistances compared to packed bed columns. The distance between the pillars can be independently controlled from the pillar size, enabling the fabrication of columns over a range of external porosities.

Using a 50 cm long reversed phase C18 μPAC™ nano LC column in combination with a Thermo Orbitrap Elite mass spectrometer for detection, we demonstrate extremely robust and high‐throughput proteome analysis at capillary flow rates up to 2 μl/min. At these flow rates, sample throughput can be increased to 20, 30, 60 and even 100 samples per day with corresponding peak capacity values (nC) of respectively 300, 250, 200 and 150. When comparing the chromatographic performance that could be obtained for single protein and cell lysate tryptic digest samples to state‐of‐the art packed bed nano LC columns (packed with sub 2 μm silica particles), average peptide peak widths could be reduced by a factor of 1.6. For complex HeLa cell digest samples, this resulted in an increase in peptide and protein group identifications of respectively 60 and 40%.
Inhibition of warm temperature‐sensitive and Ca2+‐permeable TRPV3 channel by a novel compound QDULM‐12 for anti‐pruritus and dermatitis
Authors: Lv Mengqi , Wu Han , Sun Xiaoying , Zhang Zhongyin , Wang KeWei
Published: April 2020

Transient receptor potential vanilloid 3 (TRPV3) channel as a member of thermoTRPV subfamily is primarily expressed in the keratinocytes of the skin and sensory neurons. Genetic gain‐of‐function mutations of TRPV3 gene cause skin‐related diseases such as pruritus and dermatitis, indicating that pharmacological inhibition of overactive TRPV3 may be beneficial for skin health and diseases. However, there is a significant lack of specific tools that can be used to validate TRPV3 channel as therapeutic target for skin diseases or indications yet to be defined. Recently, we made a serial modifications on natural bioactive compound and evaluated their inhibitory activities on human TRPV3 channels expressed in HEK293 cells using whole‐cell patch clamp recordings. We identified a hit compound QDULM‐12 that exhibited a dose‐dependent inhibition of hTRPV3 channel current activated by agonist 2‐APB (50 μM) with an IC50 value in a range of 0.1 μM. The selectivity of QDULM‐12 compound over other thermoTRP channels and its biological effects on in vitro keratinocytes and in vivo pruritus and dermatitis are currently underway.

Support or Funding Information

This work was supported by research grants awarded to XYS from the National Natural Sciences Foundation of China (81903734), the Natural Science Foundation of Shandong Province (ZR2017BH020), and to WKW from the National Natural Sciences Foundation of China (81573410), the Ministry of Science and Technology of China (2018ZX09711001‐004‐006).
A novel and potent neuronal Kv7 channel opener SCR2682 alleviates chronic pain in rats
Authors: Wang Jing , Liu Yani , Hu Fang , Ju Chuanxia , Wang Kewei
Published: April 2020

Activation of neuronal Kv7/KCNQ/M‐current emerges as an effective intervention for treatment of hyperexcitability‐related neurological diseases including chronic pain that is prevalent and unmet medical need. The aim of this study was to evaluate the anti‐nociceptive effects of a novel and potent Kv7/KCNQ/M channel opener SCR2682 on chronic pain in rats. The pharmacological effects of SCR2682 on native M current and firing of dorsal root ganglia (DRG) neurons were examined using electrophysiological recordings. Two in vivo rat models of complete Freund’s adjuvant (CFA)‐induced inflammatory pain and spared nerve injury (SNI)‐induced neuropathic pain were used to evaluate anti‐nociceptive effects of SCR2682 by measuring the paw withdrawal mechanical threshold (PWMT) and/or thermal latency (PWTL). Locomotor activity in normal rats was tested for safety evaluation. The expression of KCNQ2 in L4 and L5 DRGs of rat SNI model was detected by quantitative RT‐PCR and western blot.

We found that SCR2682 (0.1 μM) or an FDA approved anti‐epileptic drug retigabine (RTG) (10 μM) increased M current in rat DRG neurons approximately 30%, which was blocked by Kv7 channel inhibitor XE991 (3 μM). SCR2682 caused the resting membrane potential (RMP) hyperpolarization to −66.4 ± 3.7 mV from −56.7 ± 2.8 mV. Current clamp recordings revealed that perfusion of SCR2682 abolished the firing spikes of DRG neurons. In rat model of CFA‐induced inflammatory pain, intraperitoneal (i.p.) administration of SCR2682 at doses of 0.5, 1 and 2 mg/kg increased the PWMT and PWTL in a dose‐dependent manner, as compared with RTG (7 mg/kg) that also increased the PWMT and PWTL. In the model of SNI‐induced neuropathic pain, SCR2682 (0.5, 1 and 2 mg/kg) or RTG (7 mg/kg) increased the PWMT, and the anti‐nociceptive effect of SCR2682 (2 mg/kg) could be reversed by the channel specific blocker XE991 (3 mg/kg, i.p.). Furthermore, SCR2682 (2 mg/kg.) or RTG (7 mg/kg) significantly increased the expression of KCNQ2 mRNA and protein in DRG of SNI rats, and co‐injection of XE991 (3 mg/kg) with SCR2682 reduced the expression levels of KCNQ2. In the open field test, there was no significant difference in the travel total distance and mean speed of rats treated with RTG (7 mg/kg) or SCR2682 (0.5, 1 and 2 mg/kg). Taken together, our data show that the novel compound SCR2682 reduces the excitability of DRG sensory neurons by activating Kv7 channel, and intraperitoneal administration of SCR2682 alleviates chronic pain in rats.

Support or Funding Information

This project was supported by grants awarded to K.W. from National Natural Sciences Foundation of China (81573410) and the Ministry of Science and Technology of China (2018ZX09711001‐004‐006) and Science and Technology Program of Guangdong (2018B030334001).
Mesenchymal Stem Cell–Derived Extracellular Vesicles Alleviate Acute Lung Injury Via Transfer of miR-27a-3p*
Authors: Wang Jiangmei , Huang Ruoqiong , Xu Qi , Zheng Guoping , Qiu Guanguan , Ge Menghua , Shu Qiang , Xu Jianguo
Published: April 2020

Objectives:

The goal of this study was to determine the role of microRNA transfer in mediating the effects of mesenchymal stem cell–derived extracellular vesicles in acute lung injury.

Design:

Experimental cell and animal studies.

Setting:

University-based research laboratory.

Subjects:

THP-1 monocytes, bone marrow–derived macrophages, and C57BL/6 mice.

Interventions:

To determine the microRNA transfer in vitro, mesenchymal stem cells and mesenchymal stem cell–derived extracellular vesicles were cultured with THP-1 cells and bone marrow–derived macrophages and then assayed for microRNA expression in the target cells. To examine the role of microRNA transfer in vivo, mesenchymal stem cell–derived extracellular vesicles were administered to mice with lipopolysaccharide-induced lung injury.

Measurements and Main Results:

Mesenchymal stem cell–derived extracellular vesicles were efficiently taken up by macrophages in vitro and in vivo. miR-27a-3p was one of the most highly expressed microRNAs in THP-1 cells in microarray analysis and was transferred from mesenchymal stem cells and mesenchymal stem cell–derived extracellular vesicles to THP-1/bone marrow–derived macrophages. Mesenchymal stem cell–derived extracellular vesicles promoted M2 polarization in bone marrow–derived macrophages, which was inhibited by lentiviral anti-miR-27a-3p transduction. Mesenchymal stem cell–derived extracellular vesicles administered systemically and intratracheally were as effective as mesenchymal stem cells in alleviating acute lung injury, elevating miR-27a-3p levels in alveolar macrophages, and promoting M2 macrophage polarization. Treatment of mesenchymal stem cell–derived extracellular vesicles concurrently decreased alveolar macrophage expression of nuclear factor kappa B subunit 1, a target of miR-27a-3p. Lentiviral transduction of mesenchymal stem cells with anti-miR-27a-3p or knockdown of miR-27a-3p in vivo abolished the effects of mesenchymal stem cell–derived extracellular vesicles on acute lung injury and M2 macrophage polarization.

Conclusions:

Mesenchymal stem cell–derived extracellular vesicles mitigate acute lung injury at least partially via transferring miR-27a-3p to alveolar macrophages. miR-27a-3p acts to target NFKB1 and is a crucial regulator of M2 macrophage polarization.
Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study*
Authors: Lemiale Virginie , Pons Stéphanie , Mirouse Adrien , Tudesq Jean-Jacques , Hourmant Yannick , Mokart Djamel , Pène Frédéric , Kouatchet Achille , Mayaux Julien , Nyunga Martine , Bruneel Fabrice , Meert Anne-Pascale , Borcoman Edith , Bisbal Magali , Legrand Matthieu , Benoit Dominique , Azoulay Elie , Darmon Michaël , Zafrani Lara
Published: April 2020

Objectives:

Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades.

Data Source:

Seven European ICUs.

Study Selection:

A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality.

Data Extraction:

Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994–2015).

Data Synthesis:

Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48–67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93–0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52–4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10–1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not.

Conclusions:

Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.
Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
Authors: van der Wouden Cathelijne H. , Böhringer Stefan , Cecchin Erika , Cheung Ka-Chun , Dávila-Fajardo Cristina Lucía , Deneer Vera H.M. , Dolžan Vita , Ingelman-Sundberg Magnus , Jönsson Siv , Karlsson Mats O. , Kriek Marjolein , Mitropoulou Christina , Patrinos George P. , Pirmohamed Munir , Rial-Sebbag Emmanuelle , Samwald Matthias , Schwab Matthias , Steinberger Daniela , Stingl Julia , Sunder-Plassmann Gere , Toffoli Giuseppe , Turner Richard M. , van Rhenen Mandy H. , van Zwet Erik , Swen Jesse J. , Guchelaar Henk-Jan
Published: April 2020

Objectives

Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design.

Methods

An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses.

Results

Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene–drug interaction in a gatekeeping analysis.

Conclusion

Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.
Pediatric Procedural Sedation in the Emergency Setting
Authors: Lucich Elizabeth A. , Adams Nicholas S. , Goote Paige C. , Girotto John A. , Ford Ronald D.
Published: April 2020

Background:

Pediatric emergency department (ED) visits are common. Many are due to injury, which require procedural treatments with sedation. There are many well researched independent predictors of adverse events for pediatric procedural sedation. The duration of sedation as a predictor of adverse events has not been well studied. This study aims to determine the complication rate and severity of procedural sedation as well as determine if the duration of sedation is correlated with an increased risk of complications.

Methods:

After Institutional Review Board approval, a retrospective study was performed on all patients seen at Helen Devos Children’s ED who received sedation from August 1, 2011, to August 15, 2016. Study variables included age, weight, type of procedure, American Society of Anesthesiologist (ASA) physical status class, Mallampati score, comorbidities, sedation medication, sedation time, and complication. A logistic regression was performed assessing risk factors for complications. Statistical significance was assessed at P < 0.05.

Results:

There were 1,814 patients included in the study. Median sedation time was 20 minutes. There were 70 (3.9%) total complications. Controlling for age, weight, comorbidities, ASA class, Mallampati score, and total sedation medication, sedation time was a significant predictor of a complication (odds ratio: 1.021; 95% CI, 1.004–1.039).

Conclusions:

Pediatric patients can safely undergo procedural sedation in the ED. This study demonstrates a high safety profile for long procedural sedations with slight increases in risk as sedation time increases. There is no identifiable time where the duration of sedation significantly increases the risk of complication.
Locoregional Flap Closure for High-risk Multilevel Spine Surgery
Authors: Rinkinen Jacob R. , Weitzman Rachel E. , Clain Jason B. , Lans Jonathan , Shin John H. , Eberlin Kyle R.
Published: April 2020

Background:

Postoperative wound complications pose a challenge to patients undergoing complex spine surgery. Long-term sequelae can be devastating including decreased quality of life, meningitis, prolonged hospital stay, and need for reoperation. Among high-risk patients, postoperative wound complications have been shown to approach 40% in the literature. The aim of this study was to identify predictive factors for postoperative complications following soft-tissue reconstruction after high-risk spine surgery with the hypothesis that it would result in significantly fewer postoperative wound complications.

Methods:

A retrospective review of 67 consecutive spine operations at an academic, tertiary care center was performed, evaluating outcomes with a single plastic surgeon in conjunction with the spine surgery team. Data regarding patient demographics, perioperative risk variables, flap type, location of defect, and postoperative outcomes were obtained through retrospective chart review. Complications included soft-tissue complications and a number of reoperations. A bivariate analysis was used to identify predictors of postoperative complication. These data were compared to literature-reported averages.

Results:

A total of 67 consecutive spinal reconstructive operations were included with a mean follow-up of 11.8 months. Thirty-seven patients (55.2%) underwent immediate reconstruction at the time of the index operation, and 30 (44.8%) underwent delayed reconstruction for secondary wound healing problems following the index operation (in which plastic surgery was not involved). The majority of both immediate (95%, n = 35) and delayed (100%, n = 30) patients was defined as high risk based on literature standards. Patients in this series demonstrated a 7.5% complication rate, compared to 18.7% complication rate in the literature. We did not find a difference between major wound complications in the immediate (8.1%) or delayed (6.7%) reconstructive setting (P > 0.99). There were no specific variables identified that predicted postoperative complications.

Conclusion:

This study illustrates a postoperative complication rate of 7.5% among patients undergoing paraspinous or locoregional muscle flap closure by plastic surgery, which is significantly lower than that reported in contemporary literature for these high-risk patients.
Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices
Authors: Rossini Lorenzo , Braun Oscar Ö. , Brambatti Michela , Benito Yolanda , Mizeracki Adam , Miramontes Marissa , Nguyen Cathleen , Martinez-Legazpi Pablo , Almeida Shone , Kraushaar Megan , Vu Vi , May-Newman Karen , Bermejo Javier , Adler Eric D. , Kahn Andrew M. , Del Alamo Juan C.
Published: April 2020

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.
Extracorporeal Membrane Oxygenation in the Treatment of Severe Pulmonary and Cardiac Compromise in Coronavirus Disease 2019: Experience with 32 Patients
Authors: Jacobs Jeffrey P. , Stammers Alfred H. , St. Louis James , Hayanga J. W. Awori , Firstenberg Michael S. , Mongero Linda B. , Tesdahl Eric A. , Rajagopal Keshava , Cheema Faisal H. , Coley Tom , Badhwar Vinay , Sestokas Anthony K. , Slepian Marvin J.
Published: April 2020

As coronavirus disease 2019 (COVID-19) cases surge worldwide, an urgent need exists to enhance our understanding of the role of extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with COVID-19 who develop acute respiratory and cardiac compromise refractory to conventional therapy. The purpose of this manuscript is to review our initial clinical experience in 32 patients with confirmed COVID-19 treated with ECMO. A multi-institutional registry and database was created and utilized to assess all patients who were supported with ECMO provided by SpecialtyCare. Data captured included patient characteristics, pre-COVID-19 risk factors and comorbidities, confirmation of COVID-19 diagnosis, features of ECMO support, specific medications utilized to treat COVID-19, and short-term outcomes through hospital discharge. This analysis includes all of our patients with COVID-19 supported with ECMO, with an analytic window starting March 17, 2020, when our first COVID-19 patient was placed on ECMO, and ending April 9, 2020. During the 24 days of this study, 32 consecutive patients with COVID-19 were placed on ECMO at nine different hospitals. As of the time of analysis, 17 remain on ECMO, 10 died before or shortly after decannulation, and five are alive and extubated after removal from ECMO, with one of these five discharged from the hospital. Adjunctive medication in the surviving patients while on ECMO was as follows: four of five survivors received intravenous steroids, three of five survivors received antiviral medications (Remdesivir), two of five survivors were treated with anti-interleukin-6-receptor monoclonal antibodies (Tocilizumab or Sarilumab), and one of five survivors received hydroxychloroquine. Analysis of these 32 COVID-19 patients with severe pulmonary compromise supported with ECMO suggests that ECMO may play a useful role in salvaging select critically ill patients with COVID-19. Additional patient experience and associated clinical and laboratory data must be obtained to further define the optimal role of ECMO in patients with COVID-19 and acute respiratory distress syndrome (ARDS). These initial data may provide useful information to help define the best strategies to care for these challenging patients and may also provide a framework for much-needed future research about the use of ECMO to treat patients with COVID-19.
De-novo nonalcoholic fatty liver disease at 5 years after liver transplantation: prevalence and predictive factors
Authors: Tejedor-Tejada Javier , Valenzuela Esteban Fuentes , Muñoz Rodrigo Nájera , Gómez Laura Hernandez , García-Pajares Félix , Álvarez Carolina Almohalla , Sánchez-Martín Fátima , Alonso-Martín Carmen , Sánchez-Antolín Gloria
Published: April 2020

Background and aims:

Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors.

Methods:

This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan–Meier method.

Results:

A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P < 0.001) and de-novo diabetes (OR, 2.79; P = 0.018), were predictive. Significant fibrosis (≥F2) was presented in 58–86%. The mean survival in NAFLD and control group was 166.3 and 173.6 months, respectively (P = 0 0.50).

Conclusion:

De-novo NAFLD at fifth-year post-liver transplantation is frequently and associated with cardiovascular comorbidity. Male sex, obesity, de-novo diabetes and metabolic syndrome were factors associated with de-novo NAFLD. A significant proportion of patients had advanced fibrosis. This group trends toward worse patients’ survival.
Repetitive peripheral magnetic stimulation combined with intensive physical therapy for gait disturbance after hemorrhagic stroke: an open-label case series
Authors: Kinoshita Shoji , Ikeda Kumi , Hama Midori , Suzuki Shin , Abo Masahiro
Published: April 2020

In this pilot study, we aimed to determine the safety and feasibility of a 15-day protocol consisting of in-hospital repetitive peripheral magnetic stimulation (rPMS) combined with intensive physical therapy for the recovery of the gait disturbance in chronic stroke patients with lower limb hemiparesis. Seven hemorrhagic stroke patients with lower limb hemiparesis and gait disturbance (age: 50–78; time from onset of stroke: 7–107 months) were enrolled. rPMS was applied to the muscles of the paretic lower limb with a parabolic coil. A train of stimuli at a frequency of 20 Hz was applied for 3 s followed by a 27-s rest interval. Therapy with rPMS was performed with eighty such trains of stimuli (total 4800 pulses). Following rPMS therapy, 120 min of physical therapy was administrated daily. Each patient received this combination treatment over fifteen consecutive days, with the walking function of all participants assessed before and after the intervention. The proposed treatment protocol resulted in significant improvements in the walking speed, ambulation ability, and balance ability, but showed no significant effects on the endurance capacity, step length, and spasticity. No rPMS-related side effects were noted. Our protocol consisting of rPMS and intensive physical therapy appears well tolerated and feasible for therapy in hemorrhagic stroke patients with gait disturbance. Further large-scale studies are required to confirm its efficacy.
Nursing Work Environment and Patient Outcomes in a Hospital Context
Authors: Nascimento Ana , Jesus Élvio
Published: April 2020

OBJECTIVE

The aims of this study were to summarize the current state of knowledge regarding the relationship between nursing work environment (NWE) and patient outcomes and to identify gaps in the literature.

BACKGROUND

There was an increased awareness of the impact of NWE on patient outcomes, in particular, related to safety and quality of care.

METHOD

Scoping review was conducted. Studies published between 2002 and the 1st quarter of 2018 were included to provide an overview of the research on the associations between NWE and patient outcomes.

RESULTS

Of 2238 titles and abstracts identified, 35 studies were included, and publication ranged from 2005 to 2018. All studies included were observational, 4 had a longitudinal design, and the remaining studies were cross-sectional. Evidence indicates that better NWE decreases the risk of patient adverse events and increases the quality of care.

CONCLUSIONS

The associations between different dimensions of NWE and patient outcomes should be explored.
Machine Learning/Deep Neuronal Network
Authors: Fischer Andreas M. , Yacoub Basel , Savage Rock H. , Martinez John D. , Wichmann Julian L. , Sahbaee Pooyan , Grbic Sasa , Varga-Szemes Akos , Schoepf U. Joseph
Published: April 2020

The constantly increasing number of computed tomography (CT) examinations poses major challenges for radiologists. In this article, the additional benefits and potential of an artificial intelligence (AI) analysis platform for chest CT examinations in routine clinical practice will be examined. Specific application examples include AI-based, fully automatic lung segmentation with emphysema quantification, aortic measurements, detection of pulmonary nodules, and bone mineral density measurement. This contribution aims to appraise this AI-based application for value-added diagnosis during routine chest CT examinations and explore future development perspectives.
Buckling instabilities and spatio-temporal dynamics of active elastic filaments
Authors: Fily Yaouen , Subramanian Priya , Schneider Tobias M. , Chelakkot Raghunath , Gopinath Arvind
Published: April 2020

Biological filaments driven by molecular motors tend to experience tangential propulsive forces also known as active follower forces. When such a filament encounters an obstacle, it deforms, which reorients its follower forces and alters its entire motion. If the filament pushes a cargo, the friction on the cargo can be enough to deform the filament, thus affecting the transport properties of the cargo. Motivated by cytoskeletal filament motility assays, we study the dynamic buckling instabilities of a two-dimensional slender elastic filament driven through a dissipative medium by tangential propulsive forces in the presence of obstacles or cargo. We observe two distinct instabilities. When the filament’s head is pinned or experiences significant translational but little rotational drag from its cargo, it buckles into a steadily rotating coiled state. When it is clamped or experiences both significant translational and rotational drag from its cargo, it buckles into a periodically beating, overall translating state. Using minimal analytically tractable models, linear stability theory and fully nonlinear computations, we study the onset of each buckling instability, characterize each buckled state, and map out the phase diagram of the system. Finally, we use particle-based Brownian dynamics simulations to show our main results are robust to moderate noise and steric repulsion. Overall, our results provide a unified framework to understand the dynamics of tangentially propelled filaments and filament-cargo assemblies.
MicroCT analysis of connectivity in porous structures: optimizing data acquisition and analytical methods in the context of tissue engineering
Authors: Nair Malavika , Shepherd Jennifer H. , Best Serena M. , Cameron Ruth E.
Published: April 2020

Micro-computed X-ray tomography (MicroCT) is one of the most powerful techniques available for the three-dimensional characterization of complex multi-phase or porous microarchitectures. The imaging and analysis of porous networks are of particular interest in tissue engineering due to the ability to predict various large-scale cellular phenomena through the micro-scale characterization of the structure. However, optimizing the parameters for MicroCT data capture and analyses requires a careful balance of feature resolution and computational constraints while ensuring that a structurally representative section is imaged and analysed. In this work, artificial datasets were used to evaluate the validity of current analytical methods by considering the effect of noise and pixel size arising from the data capture, and intrinsic structural anisotropy and heterogeneity. A novel ‘segmented percolation method’ was developed to exclude the effect of anomalous, non-representative features within the datasets, allowing for scale-invariant structural parameters to be obtained consistently and without manual intervention for the first time. Finally, an in-depth assessment of the imaging and analytical procedures are presented by considering percolation events such as micro-particle filtration and cell sieving within the context of tissue engineering. Along with the novel guidelines established for general pixel size selection for MicroCT, we also report our determination of 3 μm as the definitive pixel size for use in analysing connectivity for tissue engineering applications.
Self-reported COVID-19 symptoms on Twitter: An analysis and a research resource
Authors: Sarker Abeed , Lakamana Sahithi , Hogg-Bremer Whitney , Xie Angel , Al-Garadi Mohammed Ali , Yang Yuan-Chi
Published: April 2020

Objective

To mine Twitter to quantitatively analyze COVID-19 symptoms self-reported by users, compare symptom distributions against clinical studies, and create a symptom lexicon for the research community.

Materials and methods

We retrieved tweets using COVID-19-related keywords, and performed semi-automatic filtering to curate self-reports of positive-tested users. We extracted COVID-19-related symptoms mentioned by the users, mapped them to standard concept IDs (UMLS), and compared the distributions to those reported in early studies from clinical settings.

Results

We identified 203 positive-tested users who reported 1002 symptoms using 668 unique expressions. The most frequently-reported symptoms were fever/pyrexia (66.1%), cough (57.9%), body ache/pain (42.7%), fatigue (42.1%), headache (37.4%), and dyspnea (36.3%) amongst users who reported at least 1 symptom. Mild symptoms, such as anosmia (28.7%) and ageusia (28.1%) were frequently reported on Twitter, but not in clinical studies.

Conclusion

The spectrum of COVID-19 symptoms identified from Twitter may complement those identified in clinical settings.
Increased PCR screening capacity using a multi-replicate pooling scheme
Authors: Viehweger A. , Kühnl F. , Brandt C. , König B. , Rodloff A. C.
Published: April 2020

Effective public health response to viral outbreaks such as SARS-CoV-2 require reliable information about the spread of the infecting agent. Often real-time PCR screening of large populations is a feasible method to generate this information. Since test capacities are usually limited, pooling of test specimens is often necessary to increase screening capacity, provided that the test sensitivity is not significantly compromised. However, when a traditional pool is tested positive, all samples in the pool need individual retesting, which becomes ineffective at a higher proportion of positive samples. Here, we report a new pooling protocol that mitigates this problem by replicating samples across multiple pools. The resulting pool set allows the sample status to be resolved more often than with traditional pooling. At 2% prevalence and 20 samples per pool, our protocol increases screening capacity by factors of 5 and 2 compared to individual testing and traditional pooling, respectively. The corresponding software to layout and resolve samples is freely available under a BSD license (https://github.com/phiweger/clonepool).
Spatial variability of nitrogen dioxide and formaldehyde and residential exposure of children in the industrial area of Viadana, Northern Italy
Authors: Marcon Alessandro , Panunzi Silvia , Stafoggia Massimo , Badaloni Chiara , de Hoogh Kees , Guarda Linda , Locatelli Francesca , Silocchi Caterina , Ricci Paolo , Marchetti Pierpaolo
Published: April 2020

Chipboard production is a source of ambient air pollution. We assessed the spatial variability of outdoor pollutants and residential exposure of children living in proximity to the largest industry for chipboard production in Italy, aiming at evaluating the reliability of exposure estimates obtained from passive sampling for an ongoing epidemiological study.

We obtained data on NO2 and formaldehyde, collected by the environmental protection agency of Lombardia region, at 25 passive sampling sites in the municipality of Viadana during 10 weeks (2017-18), and compared NO2 measurements with average weekly concentrations from continuous monitors. We compared interpolated surfaces of NO2 and formaldehyde for 2017-18 with previous maps for 2010. We assessed the relationship between residential proximity to the industry and pollutant exposures, assigned both using our maps and available countrywide/continental models based on routine monitoring data on NO2, PM10, and PM2.5.

The correlation between weekly NO2 concentrations from a continuous monitor and a co-located passive sampler was high (Pearson’s r = 0.89), although passive sampling underestimated NO2 during the cold season. For both 2010 and 2017-18, we observed higher NO2 and formaldehyde concentrations in the southern part of Viadana, with hot-spots in proximity to the industry. PM10 and PM2.5 exposures were higher for children at <1km to the industry and NO2 exposure was higher at 1-1.7 km, compared to the children living at >3.5 km. The density of roads and population was also higher in proximity to the industry.

Findings from a variety of exposure models suggest that children living in proximity to the chipboard industry in Viadana are more exposed to air pollution and that exposure gradients are relatively stable over time.
Is “no test is better than a bad test”? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19
Authors: Gray Nicholas , Calleja Dominic , Wimbush Alexander , Miralles-Dolz Enrique , Gray Ander , De-Angelis Marco , Derrer-Merk Elfriede , Oparaji Bright Uchenna , Stepanov Vladimir , Clearkin Louis , Ferson Scott
Published: April 2020

Testing is viewed as a critical aspect of any strategy to tackle epidemics. Much of the dialogue around testing has concentrated on how countries can scale up capacity, but the uncertainty in testing has not received nearly as much attention beyond asking if a test is accurate enough to be used. Even for highly accurate tests, false positives and false negatives will accumulate as mass testing strategies are employed under pressure, and these misdiagnoses could have major implications on the ability of governments to suppress the virus. The present analysis uses a modified SIR model to understand the implication and magnitude of misdiagnosis in the context of ending lockdown measures. The results indicate that increased testing capacity alone will not provide a solution to lockdown measures. The progression of the epidemic and peak infections is shown to depend heavily on test characteristics, test targeting, and prevalence of the infection. Antibody based immunity passports are rejected as a solution to ending lockdown, as they can put the population at risk if poorly targeted. Similarly, mass screening for active viral infection may only be beneficial if it can be sufficiently well targeted, otherwise reliance on this approach for protection of the population can again put them at risk. A well targeted active viral test combined with a slow release rate is a viable strategy for continuous suppression of the virus.