bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring a new method for the assessment of metal exposure by analysis of exhaled breath of welders
Authors: Ljungkvist Göran , Tinnerberg Håkan , Löndahl Jakob , Klang Therese , Viklund Emilia , Kim Jeong-Lim , Schiöler Linus , Forsgard Niklas , Olin Anna-Carin
Published: January 2022

Purpose

Air monitoring has been the accepted exposure assessment of toxic metals from, e.g., welding, but a method characterizing the actual dose delivered to the lungs would be preferable. Sampling of particles in exhaled breath can be used for the biomonitoring of both endogenous biomarkers and markers of exposure. We have explored a new method for the sampling of metals in exhaled breath from the small airways in a study on welders.

Methods

Our method for particle sampling, Particles in Exhaled Air (PExA®), is based on particle counting and inertial impaction. We applied it on 19 stainless steel welders before and after a workday. In parallel, air monitoring of chromium, manganese and nickel was performed as well as blood sampling after work.

Results

Despite substantial exposure to welding fumes, we were unable to show any significant change in the metal content of exhaled particles after, compared with before, exposure. However, the significance might be obscured by a substantial analytical background noise, due to metal background in the sampling media and possible contamination during sampling, as an increase in the median metal contents were indicated.

Conclusions

If efforts to reduce background and contamination are successful, the PExA® method could be an important tool in the investigations of metals in exhaled breath, as the method collects particles from the small airways in contrast to other methods. In this paper, we discuss the discrepancy between our findings and results from studies, using the exhaled breath condensate (EBC) methodology.
Stress memory responses and seed priming correlate with drought tolerance in plants: an overview
Authors: Liu Xun , Quan Wenli , Bartels Dorothea
Published: January 2022

Main conclusion

Environmental-friendly techniques based on plant stress memory, cross-stress tolerance, and seed priming help sustainable agriculture by mitigating negative effects of dehydration stress.

The frequently uneven rainfall distribution caused by global warming will lead to more irregular and multiple abiotic stresses, such as heat stress, dehydration stress, cold stress or the combination of these stresses. Dehydration stress is one of the major environmental factors affecting the survival rate and productivity of plants. Hence, there is an urgent need to develop improved resilient varieties. Presently, technologies based on plant stress memory, cross-stress tolerance and priming of seeds represent fruitful and promising areas of future research and applied agricultural science. In this review, we will provide an overview of plant drought stress memory from physiological, biochemical, molecular and epigenetic perspectives. Drought priming-induced cross-stress tolerance to cold and heat stress will be discussed and the application of seed priming will be illustrated for different species.
Validation of the work ability index—single item and the pain disability index—work item in patients with chronic low back pain
Authors: Boekel Imke , Dutmer Alisa L. , Schiphorst Preuper Henrica R. , Reneman Michiel F.
Published: January 2022

Purpose

A cross-sectional and longitudinal study was conducted to analyse construct validity, responsiveness, and Minimal Clinically Important Change (MCIC) in the Work Ability Score (WAS) and Pain Disability Index Work item (PDI-W) in patients with Chronic Low Back Pain (CLBP).

Method

Construct validity was assessed by testing predefined hypotheses. Responsiveness and MCIC were measured with an anchor-based method. The area under the receiver Operating Characteristic Curve (AUC) and the optimal cut-off point were calculated. Smallest Detectable Change (SDC) was calculated to determine measurement error.

Results

In total, 1502 patients (age 18–65 years) with CLBP were included. For validity of the WAS and PDI-W, respectively, seven and six out of 10 hypotheses were not rejected. The WAS (n = 355) was responsive to change with an AUC of 0.70. MCIC was 1.5 point, SDCindividual 4.9, and SDCgroup 0.3. MCICs were 4.5, 1.5, and − 0.5 points for, respectively, low, middle, and high scoring baseline groups. The PDI-W (n = 297) was responsive to change with an AUC of 0.80. MCIC was − 2.5 points, SDCindividual 5.2, and SDCgroup 0.3. MCICs were − 0.5, − 2.5, and − 4.5 points for, respectively, low, middle, and high scoring baseline groups.

Conclusion

Construct validity of the WAS and PDI-W was insufficient in this patient sample. The WAS and PDI-W are responsive to change. On average, improvements of 1.5 point (WAS) and  − 2.5 points (PDI-W) were interpreted as clinically important. However, MCICs are also baseline dependent. Due to a risk of measurement error, at the individual level change scores should be interpreted with caution.
Line-of-sight path-following control utilizing an extended Kalman filter for estimation of speed and course over ground from GNSS positions
Authors: Fossen Thor I.
Published: January 2022

Path-following control systems for ships can be designed using both heading and course angle autopilots in conjunction with a proportional line-of-sight (LOS) guidance law. Ships are usually equipped with a gyrocompass from a safety perspective since magnetic compasses are susceptible to magnetic disturbances. Unfortunately, the gyrocompass is an expensive device, and smaller vessels and boats cannot afford to use this as the primary device for steering. An alternative solution is to compute the course over ground (COG) and speed over ground (SOG) from global navigation satellite systems (GNSS) and use these signals for feedback control. This article presents course autopilot design for path following and a five-state extended Kalman filter (EKF) to estimate the COG and SOG efficiently. Even though many algorithms exist for computation of the COG and SOG, it is advantageous to design an EKF since a state estimator can be extended to include other sensory systems such as Doppler Velocity Log (DVL), radar, attitude rate sensors, computer vision systems, etc. This is in contrast to proprietary systems that do not allow the user to modify the software. The convergence and accuracy of the EKF are significantly improved by using target-tracking models in combination with kinematic equations. A high-fidelity model of a MARINER class cargo ship is used in the path-following case study. From the simulation study, it can be concluded that the EKF successfully estimates the COG and the SOG from GNSS measurements during path following. The solution is remarkably robust and accurate, and when combined with a course autopilot, the need for a compass is eliminated during path following.
Effects of benzydamine and mouthwashes containing benzydamine on Candida albicans adhesion, biofilm formation, regrowth, and persistence
Authors: Ardizzoni Andrea , Boaretto Giorgia , Pericolini Eva , Pinetti Diego , Capezzone de Joannon Alessandra , Durando Lucia , Ragni Lorella , Blasi Elisabetta
Published: January 2022

Objectives

To assess the effects of benzydamine and mouthwashes (MoWs) containing benzydamine on different stages of Candida albicans biofilm: adhesion, formation, persistence, and regrowth (if perturbed).

Materials and methods

C. albicans CA1398, carrying the bioluminescence ACT1p-gLUC59 fusion product, was employed. Fungal cells were exposed for 1′, 5′, or 15′ to 4 different benzydamine concentrations (0.075 to 0.6%) to 2 mouthwashes (MoWs) containing benzydamine and to a placebo MoW (without benzydamine). Treated cells were tested for adhesion (90 min) and biofilm formation (24-h assay). Next, 24- and 48-h-old biofilms were exposed to benzydamine and MoWs to assess regrowth and persistence, respectively. The effects of benzydamine, MoWs containing benzydamine, and placebo on different biofilm stages were quantified by bioluminescence assay and by the production of quorum sensing (QS) molecules.

Results

Benzydamine and MoWs containing benzydamine impaired C. albicans ability to adhere and form biofilm, counteracted C. albicans persistence and regrowth, and impaired a 48-h-old biofilm. Some of these effects paralleled with alterations in QS molecule secretion.

Conclusions

Our results show for the first time that benzydamine and MoWs containing benzydamine impair C. albicans capacity to form biofilm and counteract biofilm persistence and regrowth.

Clinical relevance

Benzydamine and MoWs containing benzydamine capacity to affect C. albicans biofilm provides an interesting tool to prevent and treat oral candidiasis. Likely, restraining C. albicans colonization through daily oral hygiene may counteract colonization and persistence by other critical oral pathogens, such as Streptococcus mutans, whose increased virulence has been linked to the presence of C. albicans biofilm.
Exploring the relevance of ‘smart city’ approaches to low-income communities in Medellín, Colombia
Authors: Smith Harry , Medero Gabriela M. , Crane De Narváez Stephanie , Castro Mera Wilmar
Published: January 2022

Smart city approaches have tended to be top-down, techno-centric/corporate and expensive approaches which are promoted by large, global companies. Smart city narratives focus on their expected capacity to improve citizens’ quality of life. However, can technology-driven and municipally-led smart city initiatives address the issues faced by poor and vulnerable communities in urban and peri-urban areas? This paper explores key aspects of the implementation of smart city approaches in the Global South taking as a case study the Colombian city of Medellín, which has been recognized internationally for its social innovation and is considered a smart city by the Inter-American Development Bank. The paper draws on a local, national and international literature review; interviews with key local stakeholders involved in smart city initiatives; and an international workshop on smart cities and community data management organized by the authors in Medellín and bringing together three perspectives: academia, government and community. The paper provides a reflection on the concept of smart city, data management and citizen participation in smart city initiatives in Medellín, contrasting each of these with the literature. Our research found gaps between broader conceptualisations and community-oriented intentions in smart city initiatives in Medellín, as well as very low uptake and reported impact of such initiatives. We conclude that a redefinition of smart city approaches that may respond to the needs of the population while improving liveability is still urgently needed, and we set out a series of questions for an international research agenda on low-income community-oriented smart city research.
Phenotyping a diversity panel of quinoa using UAV-retrieved leaf area index, SPAD-based chlorophyll and a random forest approach
Authors: Jiang Jiale , Johansen Kasper , Stanschewski Clara S. , Wellman Gordon , Mousa Magdi A. A. , Fiene Gabriele M. , Asiry Khalid A. , Tester Mark , McCabe Matthew F.
Published: January 2022

Given its high nutritional value and capacity to grow in harsh environments, quinoa has significant potential to address a range of food security concerns. Monitoring the development of phenotypic traits during field trials can provide insights into the varieties best suited to specific environmental conditions and management strategies. Unmanned aerial vehicles (UAVs) provide a promising means for phenotyping and offer the potential for new insights into relative plant performance. During a field trial exploring 141 quinoa accessions, a UAV-based multispectral camera was deployed to retrieve leaf area index (LAI) and SPAD-based chlorophyll across 378 control and 378 saline-irrigated plots using a random forest regression approach based on both individual spectral bands and 25 different vegetation indices (VIs) derived from the multispectral imagery. Results show that most VIs had stronger correlation with the LAI and SPAD-based chlorophyll measurements than individual bands. VIs including the red-edge band had high importance in SPAD-based chlorophyll predictions, while VIs including the near infrared band (but not the red-edge band) improved LAI prediction models. When applied to individual treatments (i.e. control or saline), the models trained using all data (i.e. both control and saline data) achieved high mapping accuracies for LAI (R2 = 0.977–0.980, RMSE = 0.119–0.167) and SPAD-based chlorophyll (R2 = 0.983–0.986, RMSE = 2.535–2.861). Overall, the study demonstrated that UAV-based remote sensing is not only useful for retrieving important phenotypic traits of quinoa, but that machine learning models trained on all available measurements can provide robust predictions for abiotic stress experiments.
Occupational ocular health problems among marble workers at Shaq El Tho’ban industrial area in Egypt
Authors: Khorshed Enjy A. E. , El-Naggar Safaa A. , El-Gohary Samia S. , Awad Ahmed M. B. , Ahmed Amani S.
Published: January 2022

Eye health of the working population is an essential condition for productivity. Marble industry is processed at large scale at Shaq El Tho’ban area where much dust, crushed pieces of stone, and fluctuating temperatures are endangering employees’ health generally and eye health specifically. The objectives of this study were assessing the prevalence of the most common ocular health problems associated with marble industry and investigating the impact of the working environment and occupational risk factors on the oculo-visual status of marble workers. A cross-sectional study was conducted among 250 workers, working at Shaq El Tho’ban area in Egypt during the period from August 2020 to September 2021, using a semi-structured questionnaire and eye examination comprised of full ocular history, visual acuity testing (unaided/aided), slit lamp examination, ophthalmoscopy, and Schirmer’s type I and tear break up time tests. The current study showed that gritty sensation (65.2%) and eye dryness (51.2%) were the commonest symptoms complained. By examination, conjunctival hyperemia (59.6%) was the most prevalent finding. By performing dry eye tests, dry eye was diagnosed in 60.4% and 51.2% of workers by Schirmer’s test and tear break up time test respectively. The study’s results indicated that age, working category, smoking, and diabetes had significant impact on development of ocular symptoms, while working duration, diabetes, smoking, ocular symptoms, and ocular foreign body had significant impact on development of dry eye disease. Implementation of engineering control measures, proper designing, and supply of eye PPE together with adequate health education to all workers about occupational health risks and preventive measures are recommended.
Prevalence and Correlates of Physical Comorbidities in Alcohol Use Disorder (AUD): a Pilot Study in Treatment-Seeking Population
Authors: AshaRani P. V. , Karuvetil Mohamed Zakir , Brian Tan Yeow Wee , Satghare Pratika , Roystonn Kumarasan , Peizhi Wang , Cetty Laxman , Zainuldin Noor Azizah , Subramaniam Mythily
Published: January 2022

This study aimed to understand the prevalence of physical comorbidities, undiagnosed and inadequately controlled chronic physical conditions and correlates of high cholesterol, hypertension and liver enzyme abnormalities in those with alcohol use disorder (AUD). Participants (n = 101) with AUD were recruited from a tertiary care centre through convenient sampling. The prevalence of physical and psychiatric comorbidities in the sample was 83.17% and 51.49%, respectively. Around 53.47% had two or more chronic physical conditions (multimorbidity). Hypertension (44.55%), asthma (23.76%), high cholesterol (22.77%) and liver enzyme abnormalities (21.78%) were the top four physical comorbidities. The prevalence of undiagnosed and inadequately controlled chronic physical conditions was 61.4% and 32.7%, respectively. Gender, education and body mass index (BMI) were associated with hyperlipidaemia while age and education were associated with hypertension. Higher waist-hip ratio was associated with liver enzyme abnormalities. Routine clinical care must include regular screening and follow-up of the risk groups to monitor their physical and mental health.
A fractional diffusion model of CD8+T cells response to parasitic infection in the brain
Authors: Farhadi Afshin , Hanert Emmanuel
Published: January 2022

Toxoplasma gondii(T. gondii) is a parasitic pathogen that causes serious brain diseases in fetuses and patients with immunodeficiency, particularly AIDS patients. In the field of immunology, a large number of studies have shown that effector CD8+T cells can respond toT. gondiiinfection in the brain tissue through controlling the proliferation of intracellular parasites and killing infected brain cells. These protective mechanisms do not occur without T cell movement and searching for infected cells, as a fundamental feature of the immune system. Following infection with a pathogen in a tissue, in their search for infected cells, CD8+T cells can perform different stochastic searches, including Lévy and Brownian random walks. Statistical analysis of CD8+T cell movement in the brain ofT. gondii-infected mouse has determined that the search strategy of CD8+T cells in response to infected brain cells could be described by a Lévy random walk. In this work, by considering a Lévy distribution for the displacements, we propose a space fractional-order diffusion equation for the T cell density in the infected brain tissue. Furthermore, we derive a mathematical model representing CD8+T cell response to infected brain cells. By solving the model equations numerically, we perform a comparison between Lévy and Brownian search strategies. we demonstrate that the Lévy search pattern enables CD8+T cells to spread over the whole brain tissue and hence they can rapidly destroy infected cells distributed throughout the brain tissue. However, with the Brownian motion assumption, CD8+T cells travel through the brain tissue more slowly, leading to a slower decline of the infected cells faraway from the source of T cells. Our results show that a Lévy search pattern aids CD8+T cells in accelerating the elimination of infected cells distributed broadly within the brain tissue. We suggest that a Lévy search strategy could be the result of natural evolution, as CD8+T cells learn to enhance the immune system efficiency against pathogens.
Kinetic specific features of singlet fission in highly anisotropic organic semiconductors
Authors: Shushin A. I.
Published: January 2022

Kinetics of singlet fission (SF) in molecular semiconductors, i.e., spontaneous splitting of the excited singlet state into a pair of triplet (T) excitons, is known to be strongly affected by geminate annihilation of created TT-pairs. In our work, we analyze in detail the specific properties of SF-kinetics in highly anisotropic molecular crystals (in which T-excitons undergo strongly anisotropic hopping migration) within the earlier proposed two-state model (TSM). This model allows for accurate treatment of the characteristic effects of anisotropic relative migration of T-excitons and TT-interaction on SF-kinetics, describing these effects within the approximation, that assumes kinetic coupling of two states: the [TT]-state of interacting TT-pairs and the [T + T]-state of freely migrating T-excitons. The TSM makes it possible to represent the TT-migration and interaction effects in terms of lattice-migration Green’s functions, accurate analytical formulas that are obtained in this work. The TSM is applied to the analysis of SF-kinetics in rubrene single crystals, recently measured in a wide range of times (0.1 ns < t < 104 ns). The analysis enables one to obtain important information on specific properties of SF-kinetics in highly anisotropic crystals. In particular, the observed specific “hump” of SF-kinetics at intermediate times can be treated as a manifestation of the TT-coupling in the [TT]-state. It is also found that the characteristic asymptotic time-dependence of SF-kinetics (∼t−3/2) can markedly be distorted by spin relaxation in TT-pairs.
Evaluating quantum alchemy of atoms with thermodynamic cycles: Beyond ground electronic states
Authors: Eikey Emily A. , Maldonado Alex M. , Griego Charles D. , von Rudorff Guido Falk , Keith John A.
Published: January 2022

Due to the sheer size of chemical and materials space, high-throughput computational screening thereof will require the development of new computational methods that are accurate, efficient, and transferable. These methods need to be applicable to electron configurations beyond ground states. To this end, we have systematically studied the applicability of quantum alchemy predictions using a Taylor series expansion on quantum mechanics (QM) calculations for single atoms with different electronic structures arising from different net charges and electron spin multiplicities. We first compare QM method accuracy to experimental quantities, including first and second ionization energies, electron affinities, and spin multiplet energy gaps, for a baseline understanding of QM reference data. Next, we investigate the intrinsic accuracy of “manual” quantum alchemy. This method uses QM calculations involving nuclear charge perturbations of one atom's basis set to model another. We then discuss the reliability of quantum alchemy based on Taylor series approximations at different orders of truncation. Overall, we find that the errors from finite basis set treatments in quantum alchemy are significantly reduced when thermodynamic cycles are employed, which highlights a route to improve quantum alchemy in explorations of chemical space. This work establishes important technical aspects that impact the accuracy of quantum alchemy predictions using a Taylor series and provides a foundation for further quantum alchemy studies.
Critical assessment of machine-learned repulsive potentials for the density functional based tight-binding method: A case study for pure silicon
Authors: Bissuel D. , Albaret T. , Niehaus T. A.
Published: January 2022

We investigate the feasibility of improving the semi-empirical density functional based tight-binding method through a general and transferable many-body repulsive potential for pure silicon using a common machine-learning framework. Atomic environments using atom centered symmetry functions fed into flexible neural-networks allow us to overcome the limited pair potentials used until now with the ability to train simultaneously on a large variety of systems. We achieve an improvement on bulk systems with good performance on energetic, vibrational, and structural properties. Contrarily, there are difficulties for clusters due to surface effects. To deepen the discussion, we also put these results into perspective with two fully machine-learned numerical potentials for silicon from the literature. This allows us to identify both the transferability of such approaches together with the impact of narrowing the role of machine-learning models to reproduce only a part of the total energy.
A Neuropathological Study of Diffuse Vascular Injury in Fatal Motor Vehicle Collisions
Authors: Stewart Michael K G , Shkrum Michael J , McClafferty Kevin J , Mao Haojie , Zhang Qi
Published: January 2022

In Canada, 42 929 people were involved in fatal motor vehicle collisions (MVCs) between 1999 and 2018. Traumatic brain injuries (TBIs), including diffuse vascular injury (DVI), were the most frequent cause of death. The neuroanatomical injury pattern and severity of DVI in relation to data on MVC dynamics and other MVC factors were the focus of the current study. Five cases of fatal MVCs investigated by Western University’s Motor Vehicle Safety (MOVES) Research Team with the neuropathological diagnosis of DVI were reviewed. DVI was seen in single and multiple vehicle collisions, with/without rollover and with/without partial occupant ejection. DVI occurred regardless of seatbelt use and airbag deployment and in vehicles equipped with/without antilock brakes. All DVI cases sustained head impacts and had focal TBIs, including basal skull fractures and subarachnoid hemorrhages. DVI was seen in MVCs that ranged in severity based on the change in velocity (delta-V) during the crash (minimum 31 km/hour) and occupant compartment intrusion (minimum 25 cm). In all cases, DVI in frontal white matter, corpus callosum and pontine tegmentum were common. In cases with more extensive DVI, pronounced vehicle rotation occurred before the final impact. Extensive DVI was seen in drivers who experienced sudden acceleration during vehicle rotation and deceleration.
Risk Factors for 30-day and 90-day Readmission After Lumbar Decompression
Authors: Canseco Jose A. , Karamian Brian A. , Minetos Paul D. , Paziuk Taylor M. , Gabay Alyssa , Reyes Ariana A. , Bechay Joseph , Xiao Kevin B. , Nourie Blake O. , Kaye I. David , Woods Barrett I. , Rihn Jeffrey A. , Kurd Mark F. , Anderson D. Greg , Hilibrand Alan S. , Kepler Christopher K. , Schroeder Gregory D. , Vaccaro Alexander R.
Published: January 2022

Study Design.

Retrospective cohort study.

Objective.

To assess readmission rates and risk factors for 30-day and 90-day readmission after elective lumbar decompression at a single institution.

Summary of Background Data.

Hospital readmission is an undesirable aspect of interventional treatment. Studies evaluating readmissions after elective lumbar decompression typically analyze national databases, and therefore have several drawbacks inherent to their macroscopic nature that limit their clinical utility.

Methods.

Patients undergoing primary one- to four-level lumbar decompression surgery were retrospectively identified. Demographic, surgical, and readmission data within “30-days” (0–30 days) and “90-days” (31–90 days) postoperatively were extracted from electronic medical records. Patients were categorized into four groups: (1) no readmission, (2) readmission during the 30-day or 90-day postoperative period, (3) complication related to surgery, and (4) Emergency Department (ED)/Observational (OBs)/Urgent (UC) care.

Results.

A total of 2635 patients were included. Seventy-six (2.9%) were readmitted at some point within the 30- (2.3%) or 90-day (0.3%) postoperative periods. Patients in the pooled readmitted group were older (63.1 yr, P 
< 0.001), had a higher American Society of Anesthesiologists (ASA) grade (31.2% with ASA of 3, P = 0.03), and more often had liver disease (8.1%, P = 0.004) or rheumatoid arthritis (12.0%, P = 0.02) than other cohorts. A greater proportion of 90-day readmissions and complications had surgical-related diagnoses or a diagnosis of recurrent disc herniation than 30-day readmissions and complications (66.7% vs. 44.5%, P = 0.04 and 33.3% vs. 5.5%, P < 0.001, respectively). Age (Odds ratio [OR]: 1.02, P = 0.01), current smoking status (OR: 2.38, P < 0.001), longer length of stay (OR: 1.14, P < 0.001), and a history of renal failure (OR: 2.59, P = 0.03) were independently associated with readmission or complication.

Conclusion.

Increased age, current smoking status, hospital length of stay, and a history of renal failure were found to be significant independent predictors of inpatient readmission or complication after lumbar decompression.
The Differences of CPR duration between Shockable and Nonshockable Rhythms in Predicting the Benefit of Target Temperature Management
Authors: Lin Jr-Jiun , Huang Chien-Hua , Chien Yu-San , Hsu Chih-Hsin , Chiu Wei-Ting , Wu Cheng-Hsueh , Wang Chen-Hsu , Tsai Min-Shan
Published: January 2022

Background:

Among cardiac arrest (CA) survivors, whether the combination of duration of cardiopulmonary resuscitation (CPR) and shockable/nonshockable rhythms during resuscitation can help predict the benefit of targeted temperature management (TTM) remains un-investigated.

Materials and methods:

This multicenter retrospective cohort study enrolled 479 nontraumatic adult CA survivors with TTM and CPR duration < 60 min during January 2014 to June 2019 from the Taiwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry. The differences of CPR duration between shockable and nonshockable rhythms in predicting outcomes in the studied population was evaluated.

Results:

We observed that 205 patients (42.8%) survived to hospital discharge and 100 patients (20.9%) presented favorable neurological outcomes at discharge. The enrolled patients were further re-classified into four groups according to shockable/nonshockable rhythms and CPR duration. Patients with shockable rhythms and shorter CPR duration had better survival-to-discharge (adjusted odds ratio [OR] = 2.729, 95% confidence interval [CI] = 1.384–5.383, P = 0.004) and neurological recovery (adjusted OR = 9.029, 95%CI = 3.263–24.983, P 
< 0.001) than did those with nonshockable rhythms and longer CPR duration.

Conclusion:

The CPR duration for predicting outcomes differs between CA patients with shockable and nonshockable rhythms. The combination of shockable/nonshockable rhythms and CPR duration may help predict the prognosis in CA survivors undergoing TTM.
Esmolol to Treat the Hemodynamic Effects of Septic Shock: A Randomized Controlled Trial
Authors: Cocchi Michael N. , Dargin James , Chase Maureen , Patel Parth V. , Grossestreuer Anne , Balaji Lakshman , Liu Xiaowen , Moskowitz Ari , Berg Katherine , Donnino Michael W.
Published: January 2022

Introduction:

Septic shock is often characterized by tachycardia and a hyperdynamic hemodynamic profile. Use of the beta antagonist esmolol has been proposed as a therapy to lower heart rate, thereby improving diastolic filling time and improving cardiac output, resulting in a reduction in vasopressor support.

Methods:

We conducted a two-center, open-label, randomized, Phase II trial comparing esmolol to placebo in septic shock patients with tachycardia. The primary endpoint was improvement in hemodynamics as measured by the difference in norepinephrine equivalent dose (NED) between groups at 6 hours after initiation of study drug. Secondary outcomes included assessing differences in inflammatory biomarkers and oxygen consumption (VO2).

Results:

A total of 1,122 patients were assessed for eligibility and met inclusion criteria; 42 underwent randomization, and 40 received study interventions (18 in the esmolol arm and 22 in the usual care arm). The mean NED at 6 h was 0.30 ± 0.17 mcg/kg/min in the esmolol arm compared to 0.21 ± 0.19 in the standard care arm (P = 0.15). There was no difference in number of shock free days between the esmolol (2, IQR 0, 5) and control groups (2.5, IQR 0, 6) (P = 0.32). There were lower levels of C-reactive protein at 12 and 24 h in the esmolol arm, as well as a statistically significant difference in trend over time between groups. There were no differences in terms of IL-4, IL-6, IL-10, and TNFα. Among a subset who underwent VO2 monitoring, there was decreased oxygen consumption in the esmolol patients; the mean difference between groups at 24 h was −2.07 mL/kg/min (95% CI −3.82, −0.31) (P = 0.02), with a significant difference for the trend over time (P < 0.01).

Conclusion:

Among patients with septic shock, infusion of esmolol did not improve vasopressor requirements or time to shock reversal. Esmolol was associated with decreased levels of C-reactive protein over 24 h.

Trial Registration:

www.clinicaltrials.gov. Registered February 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02369900
Temperature Trajectory Sub-phenotypes and the Immuno-Inflammatory Response in Pediatric Sepsis
Authors: Yehya Nadir , Fitzgerald Julie C. , Hayes Katie , Zhang Donglan , Bush Jenny , Koterba Natalka , Chen Fang , Tuluc Florin , Teachey David T. , Balamuth Fran , Lacey Simon F. , Melenhorst Jan Joseph , Weiss Scott L.
Published: January 2022

Objective:

Heterogeneity has hampered sepsis trials, and sub-phenotyping may assist with enrichment strategies. However, biomarker-based strategies are difficult to operationalize. Four sub-phenotypes defined by distinct temperature trajectories in the first 72 h have been reported in adult sepsis. Given the distinct epidemiology of pediatric sepsis, the existence and relevance of temperature trajectory-defined sub-phenotypes in children is unknown. We aimed to classify septic children into de novo sub-phenotypes derived from temperature trajectories in the first 72 h, and compare cytokine, immune function, and immunometabolic markers across subgroups.

Methods:

This was a secondary analysis of a prospective cohort of 191 critically ill septic children recruited from a single academic pediatric intensive care unit. We performed group-based trajectory modeling using temperatures over the first 72 h of sepsis to identify latent profiles. We then used mixed effects regression to determine if temperature trajectory-defined sub-phenotypes were associated with cytokine levels, immune function, and mitochondrial respiration.

Results:

We identified four temperature trajectory-defined sub-phenotypes: hypothermic, normothermic, hyperthermic fast-resolvers, and hyperthermic slow-resolvers. Hypothermic patients were less often previously healthy and exhibited lower levels of pro- and anti-inflammatory cytokines and chemokines. Hospital mortality did not differ between hypothermic children (17%) and other sub-phenotypes (3–11%; P = 0.26).

Conclusions:

Critically ill septic children can be categorized into temperature trajectory-defined sub-phenotypes that parallel adult sepsis. Hypothermic children exhibit a blunted cytokine and chemokine profile. Group-based trajectory modeling has utility for identifying subtypes of clinical syndromes by incorporating readily available longitudinal data, rather than relying on inputs from a single timepoint.
Systemic Review of Animal Models Used in the Study of Crush Syndrome
Authors: Liu Yahua , Yu Mengyang , Chen Li , Liu Jing , Li Xin , Zhang Chengying , Xiang Xueyuan , Li Xiaoxue , Lv Qi
Published: January 2022

Crush syndrome (CS), also known as traumatic rhabdomyolysis, is the leading cause of death following extrication from structural collapse due to earthquakes. Due to the unfeasibility of human studies, animal models are used to study crush syndrome pathophysiology, including biochemistry and treatment regimes. The aim of this systematic literature review was to identify the differences and benefits of various animal models used in the study of CS and provide valuable information for design of future research. A systematic search was conducted in two methods: with the filters “(crush syndrome) AND (crush muscle injury)” and with the keywords “(crush syndrome) AND (animal model)” covering all articles in the PubMed databases. The search generated 378 articles. After screening abstracts, 91 articles were retrieved and read, then 11 repeated articles were removed and 2 reference papers were included. We finally reviewed 82 original articles. There appear to be two primary methods employed for inducing crush syndrome in animal models, which are chemically induced injury and physically induced injury. Chemical method mainly includes intramuscular (IM) injection of tissue extract solution and IM injection of 50% glycerine. Physical method can be classified into invasive and non-invasive physical compression by elasticated material, inflatable band and heavy load. Various species of animals have been used to study CS, including mice (13.4%), rats (68.3%), rabbits (11.0%), canines (4.9%), goats (1.2%), and pigs (1.2%). Small animals are suitable for researches exploring the mechanism of disease or drug efficacy while large animals can work better with clinical application-related researches. In regard to the choice of modeling method, compressing the certain muscle of animals by heavy things is superior to others to cause systemic trauma-related rhabdomyolysis signs. In addition, due to the significant burden of crush injuries on animals, further attention shall be paid to the selection of the most suitable anesthetics and appropriate analgesics.
CIGARETTE SMOKING IS ASSOCIATED WITH DECREASED MORTALITY IN CRITICALLY ILL TRAUMA PATIENTS
Authors: Grigorian Areg , Kuza Catherine M. , Delaplain Patrick T. , Singh Mandeep , Dominguez Oscar Hernandez , Vu Trung , Kim Michael P. , Nahmias Jeffry
Published: January 2022

Background: Smoking may offer pathophysiologic adaptations that increase survivability in certain patients with cardiovascular disease. We sought to identify if smoking increases survivability in trauma patients, hypothesizing that critically ill trauma patients who smoke have a decreased risk of mortality compared with non-smokers. Methods: The Trauma Quality Improvement Program (2010-2016) database was queried for trauma patients with intensive care unit admissions. A multivariable logistic regression model was performed. Results: From the 630,278 critically ill trauma patients identified, 116,068 (18.4%) were current cigarette smokers. Critically ill trauma smokers, compared with non-smokers, had a higher rate of pneumonia (7.8% vs. 6.9%, P< 0.001) and lower mortality rate (4.0% vs. 8.0%, P< 0.001). After controlling for covariates, smokers had a decreased associated risk of mortality compared with non-smokers (OR = 0.55, CI = 0.51-0.60, P< 0.001), and no difference in the risk of major complications (OR = 0.98, CI = 0.931.03, P = 0.44). The same analysis was performed using age as a continuous variable with associated decreased risk of mortality (OR 0.57 (CI 0.53–0.62), P< 0.001). Conclusion: Critically ill trauma smokers had a decreased associated mortality risk compared with non-smokers possibly due to biologic adaptations such as increased oxygen delivery developed from smoking. Future basic science and translational studies are needed to pursue potential novel therapeutic benefits without the deleterious long-term side effects of smoking.
Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance in Early Human Sepsis
Authors: Leligdowicz Aleksandra , Kamm Jack , Kalantar Katrina , Jauregui Alejandra , Vessel Kathryn , Caldera Saharai , Serpa Paula Hayakawa , Abbott Jason , Fang Xiaohui , Tian Xiaoli , Prakash Arun , Kangelaris Kirsten Neudoerffer , Liu Kathleen D. , Calfee Carolyn S. , Langelier Charles , Matthay Michael A.
Published: January 2022

Background:

Limited studies have functionally evaluated the heterogeneity in early ex vivo immune responses during sepsis. Our aim was to characterize early sepsis ex vivo functional immune response heterogeneity by studying whole blood endotoxin responses and derive a transcriptional metric of ex vivo endotoxin response.

Methods:

Blood collected within 24 h of hospital presentation from 40 septic patients was divided into two fractions and incubated with media (unstimulated) or endotoxin. Supernatants and cells were isolated, and responses measured using: supernatant cytokines, lung endothelial permeability after supernatant exposure, and RNA expression. A transcriptomic signature was derived in unstimulated cells to predict the ex vivo endotoxin response. The signature was tested in a separate cohort of 191 septic patients to evaluate for association with clinical outcome. Plasma biomarkers were quantified to measure in vivo host inflammation.

Results:

Ex vivo response to endotoxin varied and was unrelated to immunosuppression, white blood cell count, or the causative pathogen. Thirty-five percent of patients demonstrated a minimal response to endotoxin, suggesting early immunosuppression. High ex vivo cytokine production by stimulated blood cells correlated with increased in vitro pulmonary endothelial cell permeability and was associated with attenuated in vivo host inflammation. A four-gene signature of endotoxin response detectable without the need for a functional assay was identified. When tested in a separate cohort of septic patients, its expression was inversely associated with hospital mortality.

Conclusions:

An attenuated ex vivo endotoxin response in early sepsis is associated with greater host in vivo inflammation and a worse clinical outcome.
Conserved Structural Motifs in the Hammerhead Ribozyme of a Chloroplast Viroid Mimic tRNA Anticodon Structure to Hijack tRNA Ligase for Viroid Circularization
Authors: Ortolá Beltrán , Daròs José-Antonio
Published: January 2022

Viroids belonging to the family Avsunviroidae contain hammerhead ribozymes that process to unit length the oligomeric RNAs of both polarities generated during the rolling-circle replication that occurs in chloroplasts of host plants. Linear products, with 5’-hydroxyl and 2’,3’-phosphodiester termini, are then recognized and circularized by the host chloroplastic isoform of the tRNA ligase. Here we analyze the circularization process of eggplant latent viroid (ELVd), an asymptomatic viroid that infects eggplants (Solanum melongena L.), using an Escherichia coli co-expression system in which longer-than-unit linear ELVd (+) precursors are expressed along with the eggplant chloroplastic tRNA ligase. The RNA precursor contains two copies of the hammerhead ribozyme and yields the appropriate termini for the tRNA ligase-mediated ligation in bacteria. We have determined that the ligation efficiency is highly dependent on the presence of ribozyme sequences in the ligatable termini, since the circularization of a series of viroid variants in which the ligation position was rearranged increased substantially in the presence of these sequences. Further in silico analysis showed sequence and structure similarity between the hammerhead ribozyme catalytic pocket and the anticodon loop of tRNAs, both of which harbor a characteristic U-turn of the phosphodiester backbone. Directed mutagenesis in the ribozyme domain supports the role of this U-turn loop in the ligation process. We propose that, in addition to its self-cleavage function, the viroid ribozymes have evolved to mimic the structure of the tRNA anticodon loop to recruit host tRNA ligase for the circularization of the monomeric linear replication intermediates.

IMPORTANCE

Viroids are a very particular class of infectious agents because they only consist of a small RNA that, to our current knowledge, does not encode for proteins. Consequently, viroids parasite host factors and structures to mediate all processes in the infectious cycle. How these small infectious RNAs are able to hijack host resources is currently a mystery. In this work, we shed some light on the functionality of hammerhead ribozymes during replication of viroids that belong to the family Avsunviroidae, which replicate in the chloroplasts. Our findings suggest that, in addition to mediate self-cleavage of replication intermediates, hammerhead ribozymes also recruit tRNA ligase for monomer circularization, likely mimicking a common host tRNA structural motif.
Iron Deficiency Induces Heart Failure with Ectopic Cardiac Calcification in Mice with Metabolic Syndrome
Authors: Naito Yoshiro , Sawada Hisashi , Yasumura Seiki , Horimatsu Tetsuo , Okuno Keisuke , Tahara Saki , Nishimura Koichi , Asakura Masanori , Tsujino Takeshi , Masuyama Tohru , Ishihara Masaharu
Published: January 2022

Iron deficiency is linked to worse clinical status and outcomes in heart failure. Although metabolic syndrome contributes to the development of heart failure, the impact of iron deficiency in heart failure complicated with metabolic syndrome remains obscure. KKAy mice were used as a model of metabolic syndrome. Four-week-old male C57BL/6J and KKAy mice were fed either a normal diet or iron-restricted (IR) diet for 12 weeks. During the experiment, 40% of mice died due to pulmonary congestion in KKAy mice with IR diet (KKAy-IR), while no mice died in other groups. Necropsy showed the presence of multiple white lesions on the cardiac surface in those KKAy-IR mice. Echocardiography and histological analyses revealed that KKAy-IR mice exhibited cardiac hypertrophy and cardiac dysfunction with cardiac calcification. Cardiac mRNA of ectonucleotide pyrophosphatase/phosphodiesterase-1 (Enpp1), a key enzyme for bone mineralization, was highly abundant in KKAy-IR mice. Of note, iron restriction-induced cardiac calcification and dysfunction were attenuated by etidronate, an inhibitor of bone mineralization, with decreased cardiac Enpp1 mRNA abundance in KKAy-IR mice. In conclusion, iron deficiency leads to ectopic cardiac calcification and dysfunction with the increase of Enpp1 in metabolic syndrome model mice.
Predicting evolution in experimental range expansions of an aquatic model system
Authors: Zilio Giacomo , Krenek Sascha , Gougat-Barbera Claire , Fronhofer Emanuel A. , Kaltz Oliver
Published: January 2022

Predicting range expansion dynamics is a challenge for both fundamental and applied research in conservation and global change biology. However, if ecological and evolutionary processes occur on the same time scale, predictions are challenging to make. Combining experimental evolution and mathematical modelling, we assessed the predictability of independent realisations of range expansions in a laboratory model system, the freshwater protozoan Paramecium caudatum. We followed ecological dynamics and evolutionary change in range core and front populations in the experiment. These settings were recreated in a predictive mathematical model, parametrized with dispersal and growth data of the of the 20 founder strains in the experiment. We find that short-term evolution was driven by selection for increased dispersal at the front and general selection for higher growth rates in all treatments. There was a good quantitative match of predicted and observed trait changes. Phenotypic divergence was mirrored by a complete genotypic divergence, indicating the highly repeatable fixation of strains that also were the most likely winners in our model. Long-term evolution in the experimental range front lines resulted in the emergence of a dispersal syndrome, namely a competition - colonisation trade-off. Altogether, both model and experiment highlight the importance of dispersal evolution as a driver of range expansions. Our study suggests that evolution at range fronts may follow predictable trajectories, at least for simple scenarios, and that predicting these dynamics may be possible from knowledge of few key parameters.
Proteomic deconvolution reveals distinct immune cell fractions in different body sites in SARS-Cov-2 positive individuals
Authors: Okendo Javan , Okanda David , Mwangi Peter , Nyaga Martin
Published: January 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a significant public health challenge globally. SARS-CoV-2 is a novel virus, and what constitutes immunological responses in different human body sites in infected individuals is yet to be presented. We set to determine the various immune cell fractions in gargle solution, bronchoalveolar lavage fluid, nasopharyngeal, and urine samples post-SARS-CoV-2 infection in humans.

Materials and methods

We downloaded proteomics data from (https://www.ebi.ac.uk/pride/) with the following identifiers: PXD019423, n=3 (gargle solution), PXD018970, n=15 (urine), PXD022085, n=5 (Bronchoalveolar lavage fluid), PXD022889, n=18 (nasopharyngeal). MaxQuant was used for the peptide spectral matching using humans, and SARS-CoV-2 was downloaded from the UniProt database (Access date 9th January 2022). The protein count matrix was extracted from the proteins group file and used as an input for the cibersort for the immune cells fraction determination.

Results

The body of individuals infected with the SARS-CoV-2 virus is characterized by different fractions of immune cells in Bronchoalveolar lavage fluid (BALF), nasopharyngeal, urine, and gargle solution. BALF has more abundant memory B cells, CD8, activated mast cells, and resting macrophages than urine, nasopharyngeal, and gargle solution. Our analysis also demonstrates that each body site comprises different immune cell fractions post-SARS-CoV-2 infection in humans.

Conclusion

Different body sites are characterized by different immune cells fractions in SARS-CoV-2 infected individuals. The findings in this study can inform public health policies and health professionals on treatment strategies and drive SARS-CoV-2 diagnosis procedures.