bluuebunny/crossref_metadata_2025 huggingface dataset:
A Meta-analysis of Structural and Functional Brain Abnormalities in Early-Onset Schizophrenia
Authors: Ioakeimidis Vasileios , Haenschel Corinna , Yarrow Kielan , Kyriakopoulos Marinos , Dima Danai
Published: March 2020

Early-onset schizophrenia (EOS) patients demonstrate brain changes that are similar to severe cases of adult-onset schizophrenia. Neuroimaging research in EOS is limited due to the rarity of the disorder. The present meta-analysis aims to consolidate MRI and functional MRI findings in EOS. Seven voxel-based morphometry (VBM) and 8 functional MRI studies met the inclusion criteria, reporting whole-brain analyses of EOS vs healthy controls. Activation likelihood estimation (ALE) was conducted to identify aberrant anatomical or functional clusters across the included studies. Separate ALE analyses were performed, first for all task-dependent studies (Cognition ALE) and then only for working memory ones (WM ALE). The VBM ALE revealed no significant clusters for gray matter volume reductions in EOS. Significant hypoactivations peaking in the right anterior cingulate cortex (rACC) and the right temporoparietal junction (rTPJ) were detected in the Cognition ALE. In the WM ALE, consistent hypoactivations were found in the left precuneus (lPreC), the right inferior parietal lobule (rIPL) and the rTPJ. These hypoactivated areas show strong associations with language, memory, attention, spatial, and social cognition. The functional co-activated networks of each suprathreshold ALE cluster, identified using the BrainMap database, revealed a core co-activation network with similar topography to the salience network. Our results add support to posterior parietal, ACC and rTPJ dysfunction in EOS, areas implicated in the cognitive impairments characterizing EOS. The salience network lies at the core of these cognitive processes, co-activating with the hypoactivating regions, and thus highlighting the importance of salience dysfunction in EOS.
Differential activating effects of thyrotropin-releasing hormone and its analog taltirelin on motor output to the tongue musculature in vivo
Authors: Liu Wen-Ying , Liu Hattie , Aggarwal Jasmin , Huang Zhi-Li , Horner Richard L
Published: March 2020

Thyrotropin-releasing hormone (TRH) is produced by the hypothalamus but most brain TRH is located elsewhere where it acts as a neuromodulator. TRH-positive neurons project to the hypoglossal motoneuron pool where TRH receptor RNA shows a high degree of differential expression compared with the rest of the brain. Strategies to modulate hypoglossal motor activity are of physiological and clinical interest given the potential for pharmacotherapy for obstructive sleep apnea (OSA), a common and serious respiratory disorder. Here, we identified the effects on tongue motor activity of TRH and a specific analog (taltirelin) applied locally to the hypoglossal motoneuron pool and systemically in vivo. Studies were performed under isoflurane anesthesia and across sleep–wake states in rats. In anesthetized rats, microperfusion of TRH (n = 8) or taltirelin (n = 9) into the hypoglossal motoneuron pool caused dose-dependent increases in tonic and phasic tongue motor activity (both p < 0.001). However, the motor responses to TRH were biphasic, being significantly larger “early” in the response versus at the end of the intervention (p ≤ 0.022). In contrast, responses to taltirelin were similar “early” versus “late” (p ≥ 0.107); i.e. once elicited, the motor responses to taltirelin were sustained and maintained. In freely behaving conscious rats (n = 10), microperfusion of 10 μM taltirelin into the hypoglossal motoneuron pool increased tonic and phasic tongue motor activity in non-rapid-eye-movement (REM) sleep (p ≤ 0.038). Intraperitoneal injection of taltirelin (1 mg/kg, n = 16 rats) also increased tonic tongue motor activity across sleep–wake states (p = 0.010). These findings inform the studies in humans to identify the potential beneficial effects of taltirelin for breathing during sleep and OSA.
Topiramate reduces nocturnal eating in sleep-related eating disorder
Authors: Winkelman John W , Wipper Benjamin , Purks Julia , Mei Leslie , Schoerning Laura
Published: March 2020

Study Objectives

Sleep-related eating disorder (SRED) is a parasomnia characterized by partial arousals from sleep with compulsive consumption of food with impaired level of awareness and memory for the event. Small case series’ have demonstrated efficacy of topiramate in SRED. We conducted a placebo-controlled randomized clinical trial of topiramate to assess efficacy in SRED.

Methods

Thirty-four participants with an ICSD-2/ICSD-3 diagnosis of SRED with >6 months of symptoms and ≥3 sleep-related eating episodes per week were randomized to placebo or topiramate with flexible dosing to a maximum dosage of 300 mg for 13 weeks. Primary outcomes were percentage of nights with eating and Clinician Global Impression-Improvement (CGI-I). Intention-to-treat last observation carried forward (ITT LOCF) analysis was conducted.

Results

Mean age was 39.5 years, 74% were female, with mean duration of sleep-related eating of 13.7 years. SRED symptoms were significantly reduced with topiramate (74.7% to 33.2% nights/week; n = 15) compared to placebo (77.0% to 57.4%; n = 17) (p = 0.035). There were significantly more CGI-I responders on topiramate (71%) than placebo (27%) (p = 0.016). Level of wakefulness (r = −0.49) and memory for nighttime eating (r = −0.58) at baseline predicted topiramate response. The topiramate group lost significantly more weight than the placebo group (−8.5 lbs vs. +1.0 lbs, p = 0.001). The most common side effects were paresthesias and cognitive dysfunction.

Conclusions

This first randomized controlled trial demonstrating efficacy for treatment of SRED supports preliminary data on the use of topiramate for SRED. Side effects were prominent for topiramate. Limitations include a small sample size and a high drop-out rate in both study groups.

Clinical Trial Information

NCT00606411
New insights into the cognitive effects of sleep deprivation by decomposition of a cognitive throughput task
Authors: Honn Kimberly A , Halverson T , Jackson M L , Krusmark M , Chavali V P , Gunzelmann G , Van Dongen H P A
Published: March 2020

Study Objectives

A cognitive throughput task known as the Digit Symbol Substitution Test (DSST) (or Symbol Digit Modalities Test) has been used as an assay of general cognitive slowing during sleep deprivation. Here, the effects of total sleep deprivation (TSD) on specific cognitive processes involved in DSST performance, including visual search, spatial memory, paired-associate learning, and motor response, were investigated through targeted task manipulations.

Methods

A total of 12 DSST variants, designed to manipulate the use of specific cognitive processes, were implemented in two laboratory-based TSD studies with N = 59 and N = 26 subjects, respectively. In each study, the Psychomotor Vigilance Test (PVT) was administered alongside the DSST variants.

Results

TSD reduced cognitive throughput on all DSST variants, with response time distributions exhibiting rightward skewing. All DSST variants showed practice effects, which were however minimized by inclusion of a pause between trials. Importantly, TSD-induced impairment on the DSST variants was not uniform, with a principal component analysis revealing three factors. Diffusion model decomposition of cognitive processes revealed that inter-individual differences during TSD on a two-alternative forced choice DSST variant were different from those on the PVT.

Conclusions

While reduced cognitive throughput has been interpreted to reflect general cognitive slowing, such TSD-induced impairment appears to reflect cognitive instability, like on the PVT, rather than general slowing. Further, comparisons between task variants revealed not one, but three distinct underlying processes impacted by sleep deprivation. Moreover, the practice effect on the task was found to be independent of the TSD effect and minimized by a task pacing manipulation.
Effects of low dose radiation on immune cells subsets and cytokines in mice
Authors: Liu Xiaochang , Liu Zheng , Wang Duo , Han Yang , Hu Sai , Xie Ying , Liu Yike , Zhu Maoxiang , Guan Hua , Gu Yongqing , Zhou Ping-Kun
Published: March 2020

Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.
Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)
Authors: Alhazzani Waleed , Møller Morten Hylander , Arabi Yaseen M. , Loeb Mark , Gong Michelle Ng , Fan Eddy , Oczkowski Simon , Levy Mitchell M. , Derde Lennie , Dzierba Amy , Du Bin , Aboodi Michael , Wunsch Hannah , Cecconi Maurizio , Koh Younsuck , Chertow Daniel S. , Maitland Kathryn , Alshamsi Fayez , Belley-Cote Emilie , Greco Massimiliano , Laundy Matthew , Morgan Jill S. , Kesecioglu Jozef , McGeer Allison , Mermel Leonard , Mammen Manoj J. , Alexander Paul E. , Arrington Amy , Centofanti John E. , Citerio Giuseppe , Baw Bandar , Memish Ziad A. , Hammond Naomi , Hayden Frederick G. , Evans Laura , Rhodes Andrew
Published: March 2020

Background:

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.

Methods:

We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using theGrading of Recommendations, Assessment, Development and Evaluation(GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.

Results:

The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy.

Conclusion:

The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
Relationship Between Contact Lens Sensor Output Parameters and Visual Field Progression in Open-angle Glaucoma: Assessment of a Practical Tool to Guide Clinical Risk-assessment
Authors: Gillmann Kevin , Young Cara C. , Stanley Jordan , Seibold Leonard K. , Hoskens Kirsten , Midha Neha , Kahook Malik Y. , Mansouri Kaweh
Published: March 2020

Purpose:

In recent years, new technologies have emerged to better analyze and interpret intraocular pressure (IOP) fluctuations. Among them is the progression report (PR), an algorithm based on continuous contact lens sensor (CLS) readings to estimate the likelihood of fast visual field (VF) glaucomatous progression. The objective of this study is to validate the PR.

Methods:

In this retrospective study, 30 open-angle glaucoma patients were enrolled. Twenty-four hours IOP-related variations were recorded using a CLS. Recordings were used to generate PR. The likelihood of fast VF progression (<−1 dB/y mean deviation) was estimated by 2 masked assessors based on clinical parameters. At least 3 VF were performed over the 2 years following the initial assessment, to determine actual progression.

Results:

Mean age was 65.9±10.45 years, with a mean baseline mean deviation of −5.4±5.1. After a mean follow-up of 29.5±12.9 months, 26.7% of eyes were assessed as fast progressors (−2.9±1.9 dBs/y). The average risk-score attributed by the PR was 42% [41% (slow) vs. 44% (fast); P=0.035]. Correlations between the 2 assessors were good (r=0.59), and identical to that between PR and the averaged assessors’ gradings. Correlations between mean deviation progression rates and PR, Assessor 1 and Assessor 2’s gradings were, r=0.57, 0.31, and 0.43, respectively.

Conclusions:

PR provided comparable predictions of the risk of fast VF progression as did physician estimates based on all available clinical data. With their relationship to the eye’s biomechanical properties and the ocular tissues’ response to pressure variations, CLS recordings may offer new information that complements conventional examinations.
Reversible Corneal Endothelial Abnormalities With Netarsudil
Authors: Tanna Angelo P. , Esfandiari Hamed , Teramoto Kyla
Published: March 2020

Purpose:

To report a case of reversible corneal endothelial abnormalities after treatment with netarsudil.

Observation:

A 68-year-old woman presented with the complaint of blurred vision soon after starting treatment with the fixed-dose combination of netarsudil and latanoprost (FC-netarsudil-latanoprost). She had been receiving the fixed-dose combination of dorzolamide and timolol and latanoprost for primary open-angle glaucoma until her ophthalmologist switched latanoprost to FC-netarsudil-latanoprost 2 months before referral to our center.

Best-corrected visual acuity was 20/20-1 in the right eye and 20/20-3 in the left eye. The slit-lamp biomicroscopic examination was remarkable for a guttata-like abnormality of the corneal endothelium of both eyes. The intraocular pressure was 10 mm Hg in both eyes. Specular microscopy revealed irregularly shaped corneal endothelial cells with indistinct borders between cells. FC-netarsudil-latanoprost was replaced with latanoprost in the left eye but continued in the right eye. Nine weeks later, best-corrected visual acuity remained 20/20-1 in the right eye but it improved to 20/20 in the left eye. Repeat specular microscopy was unchanged in the right eye and was normal in the left eye.

Conclusion and Importance:

Topical therapy with netarsudil can result in guttata-like changes of the corneal endothelium and corneal endothelial cell abnormalities that can be detected with specular microscopy. These abnormalities seem to be transient and resolved upon the cessation of netarsudil. Ophthalmologists should consider the possibility of a corneal endothelial abnormality in patients treated with netarsudil who develop blurred vision.
Food System Sustainability
Authors: Miller Gregory D. , Slimko Michelle , Tricarico Juan , Peerless Dan
Published: March 2020

Sustainability in food systems has often been oversimplified. Many criteria are required to accurately assess the sustainability of foods, including multiple nutrition, economic, environmental, and social concerns. The US dairy industry is working to develop the methods and data needed to understand the benefits and impacts of dairy production and consumption from a food systems perspective to improve sustainability.
Consensus Health and Nutrition Communication
Authors: Rowe Sylvia , Alexander Nick
Published: March 2020

Food, health, and other science communicators have, for years, been concerned about the public's trust in science—especially, with the fierce opposition to some believed-to-be-settled scientific consensus regarding vaccine safety, global climate change, the safety of food biotechnology, and assorted nutrition issues. Experts have struggled to understand why significant segments of the public have continued to resist consensus conclusions. The present article investigates the impact on science communications of a broader, decades-long, societal decline in public trust in most social institutions. The authors investigate the role of trust in the context of a culture-wide loss of confidence in the society's traditional gatekeepers and authority figures. They examine possible causes for the erosion of trust and explore a new heuristic approach, offering possible guidance for food and health communicators in taking account of the ever-more-challenging communication landscape.
Hip fracture care and national systems: Australia and Asia
Authors: Tarrrant Seth M. , Ajgaonkar Amit , Babhulkar Sushrut , Cui Zhiyong , Harris Ian A. , Kulkarni Sunil , Minehara Hiroaki , Miyamoto Takashi , Oppy Andrew , Shigemoto Kenji , Tian Yun , Balogh Zsolt J.
Published: March 2020

The Asia-Pacific region includes countries with diverse cultural, demographic, and socio-political backgrounds. Countries such as Japan have very high life expectancy and an aged population. China and India, with a combined population over 2.7 billion, will experience a huge wave of ageing population with subsequent osteoporotic injuries. Australia will experience a similar increase in the osteoporotic fracture burden, and is leading the region by establishing a national hip fracture registry with governmental guidelines and outcome monitoring. While it is impossible to compare fragility hip fracture care in every Asia-Pacific country, this review of 4 major nations gives insight into the challenges facing diverse systems. They are united by the pursuit of internationally accepted standards of timely surgery, combined orthogeriatric care, and secondary fracture prevention strategies.
Surgical timing for open fractures
Authors: You Daniel Z. , Schneider Prism S.
Published: March 2020

Controversy exists over the optimal management of open fractures as new clinical studies question open fracture management dogma. Open fractures are complex injuries requiring the orthopaedic surgeon to consider both the bone injury as well as associated soft tissue injury. Early intravenous antibiotics and tetanus prophylaxis remain instrumental in infection prevention. However, the “six-hour rule” for initial open fracture debridement and revascularization has come into question. New evidence supports initial debridement within 24 hours with the appropriate surgical team. Additionally, orthopaedic surgeons and vascular surgeons should collaborate on the sequence of management of open fractures with associated vascular injury. Whereas debates on the optimal irrigation pressure and solution have been answered by multicenter randomized controlled trials, further research is required to determine the optimal irrigation volume and timing of wound closure. With advances in management of open fractures, the utility of well-known classification systems including the Gustilo-Anderson classification and Mangled Extremity Severity Score need to be re-evaluated in favor of up-to-date classification systems which better guide management and predict prognosis.
It Is Time to Reconsider Factorial Designs: How Bradford Hill and R. A. Fisher Shaped the Standard of Clinical Evidence
Authors: Neuhauser Duncan , Provost Shannon M. , Provost Lloyd P.
Published: March 2020

Objectives:

Could medical research and quality improvement studies be more productive with greater use of multifactor study designs?

Methods:

Drawing on new primary sources and the literature, we examine the roles of A. Bradford Hill and Ronald A. Fisher in introducing the design of experiments in medicine.

Results:

Hill did not create the randomized controlled trial, but he popularized the idea. His choice to set aside Fisher's advanced study designs shaped the development of clinical research and helped the single-treatment trial to become a methodological standard.

Conclusions:

Multifactor designs are not widely used in medicine despite their potential to make improvement initiatives and health services research more efficient and effective. Quality managers, health system leaders, and directors of research institutes could increase productivity and gain important insights by promoting a broader use of factorial designs to study multiple interventions simultaneously and to learn from interactions.
Timeliness of Care for Injured Patients Initially Seen at Freestanding Emergency Departments: A Pilot Quality Improvement Project
Authors: Birmingham Lauren E. , Richner Gwendolyn , Moran Mary , Hatridge Kindra M. , George Richard L.
Published: March 2020

Background:

The impact of freestanding emergency departments (FSEDs) on timeliness of care for trauma patients is not well understood. This quality improvement project had 2 objectives: (1) to determine whether significant delays in definitive care existed among trauma patients initially seen at FSEDs compared with those initially seen at other outlying sites prior to transfer to a level I trauma center; and (2) to determine the feasibility of identifying differences in time-to-definitive care and emergency department length of stay (ED LOS) based on initial treatment location.

Methods:

Trauma registry data from January 1, 2017, through December 31, 2017, from a verified level I trauma center were analyzed by location of initial presentation. Appropriate statistical tests are used to make comparisons across transport groups.

Results:

Patients initially seen at non-FSEDs experienced ED LOS that were, on average, 24.5 minutes greater than patients seen initially at FSEDs, although the difference was not statistically significant (P = .3112). Several challenges were identified in the feasibility analysis that will inform the design for a larger study including large quantities of missing time stamp data and potential selection bias. Prospective solutions were identified.

Conclusion:

This project found that there were not significant differences in ED LOS for injured patients presenting initially to FSEDs or other non-FSED facilities, suggesting that timeliness of care was similar across location types.
Summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation
Authors: Chadban Steven J. , Ahn Curie , Axelrod David A. , Foster Bethany J. , Kasiske Bertram L. , Kher Vijah , Kumar Deepali , Oberbauer Rainer , Pascual Julio , Pilmore Helen L. , Rodrigue James R. , Segev Dorry L. , Sheerin Neil S. , Tinckam Kathryn J. , Wong Germaine , Balk Ethan M. , Gordon Craig E. , Earley Amy , Rofeberg Valerie , Knoll Gregory A.
Published: March 2020

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual’s suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate’s profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence. The strengths of recommendations are provided in the full report. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.
Resources Utilization After Liver Transplantation in Patients With and Without Hepatopulmonary Syndrome: Cleveland Clinic Experience
Authors: Cywinski Jacek B. , Makarova Natalya , Arney Andrea , Liu Qiang , Fujiki Masato , Menon K. V. Narayanan , Quintini Cristiano
Published: March 2020

Background.

Patients with hepatopulmonary syndrome (HPS) reportedly experience posttransplant morbidity and require more resources to care during perioperative period. The exact incremental increase of resources utilization compared with non-HPS population remains unknown.

Methods.

In this single-center retrospective investigation, we compared the perioperative resources utilization of HPS patients undergoing orthotopic liver transplant (n = 28) to cohort without HPS (n = 739). Potential confounding variables were adjusted in the analysis and the multivariable log-linear regression were used.

Results.

The overall hospital costs for HPS patients were about 27% higher compared with non-HPS patients (the ratio of geometric means, 1.27; 98.3% confidence interval, 1.09-1.47;P < 0). HPS diagnosis was independently associated with both longer intensive care unit stay (P < 0.001) and hospital stay (P < 0.001). The odds of being discharged to extended care facility were about 15 times higher for HPS patients comparing to non-HPS patients (odds ratio, 14.9; 97.5% confidence interval, 4.98-44.29;P < 0.001). There were no differences observed in odds of being readmitted to the hospital within 6 mo after the transplant (P = 0.75).

Conclusions.

HPS diagnosis was associated with longer intensive care unit stay, hospital stay, and increased hospital cost, together with higher odds of being discharged to extended care facility compared with non-HPS patients.
The fourth law of thermodynamics: steepest entropy ascent
Authors: Beretta Gian Paolo
Published: March 2020

When thermodynamics is understood as the science (or art) of constructing effective models of natural phenomena by choosing a minimal level of description capable of capturing the essential features of the physical reality of interest, the scientific community has identified a set of general rules that the model must incorporate if it aspires to be consistent with the body of known experimental evidence. Some of these rules are believed to be so general that we think of them as laws of Nature, such as the great conservation principles, whose ‘greatness’ derives from their generality, as masterfully explained by Feynman in one of his legendary lectures. The second law of thermodynamics is universally contemplated among the great laws of Nature. In this paper, we show that in the past four decades, an enormous body of scientific research devoted to modelling the essential features of non-equilibrium natural phenomena has converged from many different directions and frameworks towards the general recognition (albeit still expressed in different but equivalent forms and language) that another rule is also indispensable and reveals another great law of Nature that we propose to call the ‘fourth law of thermodynamics’. We state it as follows: every non-equilibrium state of a system or local subsystem for which entropy is well defined must be equipped with a metric in state space with respect to which the irreversible component of its time evolution is in the direction of steepest entropy ascent compatible with the conservation constraints. To illustrate the power of the fourth law, we derive (nonlinear) extensions of Onsager reciprocity and fluctuation–dissipation relations to the far-non-equilibrium realm within the framework of the rate-controlled constrained-equilibrium approximation (also known as the quasi-equilibrium approximation).

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Formulation of moment equations for rarefied gases within two frameworks of non-equilibrium thermodynamics: RET and GENERIC
Authors: Öttinger Hans Christian , Struchtrup Henning , Torrilhon Manuel
Published: March 2020

In this work, we make a further step in bringing together different approaches to non-equilibrium thermodynamics. The structure of the moment hierarchy derived from the Boltzmann equation is at the heart of rational extended thermodynamics (RET, developed by Ingo Müller and Tommaso Ruggeri). Whereas the full moment hierarchy has the structure expressed in the general equation for the nonequilibrium reversible–irreversible coup- ling (GENERIC), the Poisson bracket structure of reversible dynamics postulated in that approach is a major obstacle for truncating moment hierarchies, which seems to work only in exceptional cases (most importantly, for the five moments associated with conservation laws). The practical importance of truncated moment hierarchies in rarefied gas dynamics and microfluidics motivates us to develop a new strategy for establishing the full GENERIC structure of truncated moment equations, based on non-entropy-producing irreversible processes associated with Casimir symmetry. Detailed results are given for the special case of 10 moments.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
A new continuum model for general relativistic viscous heat-conducting media
Authors: Romenski E. , Peshkov I. , Dumbser M. , Fambri F.
Published: March 2020

The lack of formulation of macroscopic equations for irreversible dynamics of viscous heat-conducting media compatible with the causality principle of Einstein’s special relativity and the Euler–Lagrange structure of general relativity is a long-lasting problem. In this paper, we propose a possible solution to this problem in the framework of SHTC equations. The approach does not rely on postulates of equilibrium irreversible thermodynamics but treats irreversible processes from the non-equilibrium point of view. Thus, each transfer process is characterized by a characteristic velocity of perturbation propagation in the non-equilibrium state, as well as by an intrinsic time/length scale of the dissipative dynamics. The resulting system of governing equations is formulated as a first-order system of hyperbolic equations with relaxation-type irreversible terms. Via a formal asymptotic analysis, we demonstrate that classical transport coefficients such as viscosity, heat conductivity, etc., are recovered in leading terms of our theory as effective transport coefficients. Some numerical examples are presented in order to demonstrate the viability of the approach.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Rational extended thermodynamics of dense polyatomic gases incorporating molecular rotation and vibration
Authors: Arima Takashi , Ruggeri Tommaso , Sugiyama Masaru
Published: March 2020

The paper aims to construct a rational extended thermodynamics (RET) theory of dense polyatomic gases by taking into account the experimental evidence that the relaxation time of molecular rotation and that of molecular vibration are quite different from each other. For simplicity, we focus on gases with only one dissipative process due to bulk viscosity. In fact, in some polyatomic gases, the effect of bulk viscosity is much larger than that of shear viscosity and heat conductivity. The present theory includes the previous RET theory of dense gases with six fields as a particular case, and it also includes the RET theory of rarefied polyatomic gases with seven fields in the rarefied-gas limit. The closure is carried out by using the universal principles, that is, Galilean invariance and objectivity, entropy principle, and thermodynamic stability (convexity of entropy), where the duality principle connecting rarefied gases to dense gases also plays an important role. A detailed discussion is devoted to the expression of the production terms in the system of balance equations. As typical examples, we study a gas with virial equations of state and a van der Waals gas. Lastly the dispersion relation of a linear wave is derived, and its comparison with experimental data is made.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Intrinsic properties of conservation-dissipation formalism of irreversible thermodynamics
Authors: Yong Wen-An
Published: March 2020

This paper proposes four fundamental requirements for establishing PDEs (partial differential equations) modelling irreversible processes. We show that the PDEs derived via the CDF (conservation-dissipation formalism) meet all the requirements. In doing so, we find useful constraints on the freedoms of CDF and point out that a shortcoming of the formalism can be remedied with the help of the Maxwell iteration. It is proved that the iteration preserves the gradient structure and strong dissipativeness of the CDF-based PDEs. A refined formulation of the second law of thermodynamics is given to characterize the strong dissipativeness, while the gradient structure corresponds to nonlinear Onsager relations. Further advantages and limitations of CDF will also be presented.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Variational principles and nonequilibrium thermodynamics
Authors: Ván P. , Kovács R.
Published: March 2020

Variational principles play a fundamental role in deriving the evolution equations of physics. They work well in the case of non-dissipative evolution, but for dissipative systems, the variational principles are not unique and not constructive. With the methods of modern nonequilibrium thermodynamics, one can derive evolution equations for dissipative phenomena and, surprisingly, in several cases, one can also reproduce the Euler–Lagrange form and symplectic structure of the evolution equations for non-dissipative processes. In this work, we examine some demonstrative examples and compare thermodynamic and variational techniques. Then, we argue that, instead of searching for variational principles for dissipative systems, there is another viable programme: the second law alone can be an effective tool to construct evolution equations for both dissipative and non-dissipative processes.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Weak invariants in dissipative systems: action principle and Noether charge for kinetic theory
Authors: Abe Sumiyoshi
Published: March 2020

In non-equilibrium classical thermostatistics, the state of a system may be described by not only dynamical/thermodynamical variables but also a kinetic distribution function. This ‘double structure’ bears some analogy with that in quantum thermodynamics, where both dynamical variables and the Hilbert space are involved. Recently, the concept of weak invariants has repeatedly been discussed in the context of quantum thermodynamics. A weak invariant is defined in such a way that its value changes in time but its expectation value is conserved under time evolution prescribed by a kinetic equation. Here, a new aspect of a weak invariant is revealed for the classical Fokker–Planck equation as an example of classical kinetic equations. The auxiliary field formalism is applied to the construction of the action for the kinetic equation. Then, it is shown that the auxiliary field is a weak invariant and is the Noether charge. The action is invariant under the transformation generated by the weak invariant. The result may shed light on possible roles of the symmetry principle in the kinetic descriptions of non-equilibrium systems.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Gradient and GENERIC time evolution towards reduced dynamics
Authors: Grmela M. , Klika V. , Pavelka M.
Published: March 2020

Reduction of a mesoscopic dynamical theory to equilibrium thermodynamics brings to the latter theory the fundamental thermodynamic relation (i.e. entropy as a function of the thermodynamic state variables). The reduction is made by following the mesoscopic time evolution to its conclusion, i.e. to fixed points at which the time evolution ceases to continue. The approach to fixed points is driven by entropy, that, if evaluated at the fixed points, becomes the thermodynamic entropy. Since the fixed points are parametrized by the thermodynamic state variables (by constants of motion), the thermodynamic entropy arises as a function of the thermodynamic state variables and thus the final outcome of the reduction is the fundamental thermodynamic relation. This reduction process extends also to reductions in which the reduced theory still involves the time evolution (e.g. reduction of kinetic theory to hydrodynamics). The essence of the extension is the replacement of the mesoscopic time evolution of the state variables with the corresponding mesoscopic time evolution of the vector field (i.e. of the fluxes). The fixed point in this flux time evolution is the vector field generating the reduced mesoscopic time evolution. The flux-entropy driving the flux time evolution becomes, if evaluated at the fixed point, the flux fundamental thermodynamic relation in the reduced dynamical theory. We show that the flux-entropy is a potential related to the entropy production.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Re-validation and update of an extended-specificity multiplex assay for detection of Streptococcus pneumoniae capsular serotype/serogroup-specific antigen and cell-wall polysaccharide in urine specimens
Authors: Eletu Seyi D. , Sheppard Carmen L. , Rose Samuel , Smith Kenneth , Andrews Nick , Lim Wei Shen , Litt David J. , Fry Norman K.
Published: March 2020

National surveillance of pneumococcal disease at the serotype level is essential to assess the effectiveness of vaccination programmes. We previously developed a highly sensitive extended-specificity multiplex immunoassay for detection of

Streptococcus pneumoniae

serotype-specific antigen in urine in the absence of isolates. The assay uses human mAbs that detect the 24 pneumococcal serotype/groups targeted by the pneumococcal conjugate vaccines (PCVs) and pneumococcal polysaccharide vaccine (PPV-23) plus some cross-reactive types and the pneumococcal cell-wall polysaccharide. However, the previous assay had some limitations, namely the reduced specificity of the serotype 7F, 20 and 22F assays, for which non-specific binding in urine samples was observed. Here we report on the further development and re-validation of a new version of the assay (version 2.1), which offers improved sensitivity towards serotypes 7F, 18C and 19F and increased specificity for serotypes 7F, 20 and 22F by replacement of some of the antibody clones with new clones. Using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease, the overall clinical sensitivity of this version of the assay based on isolation of

S. pneumoniae

from a normally sterile site is 94.3 % and the clinical specificity is 93.6 %, in comparison with clinical sensitivity and specificity values of 96.2 % and 89.9 % in the previous assay.
Phylogenetic evaluation of the genus Nostoc and description of Nostoc neudorfense sp. nov., from the Czech Republic
Authors: Singh Prashant , Šnokhousová Jana , Saraf Aniket , Suradkar Archana , Elster Josef
Published: March 2020

Cyanobacterial strain ARC8 was isolated from seepage coming into the river Dračice, Františkov, Czech Republic, and was characterized using a polyphasic approach. Strain ARC8 showed a typical

Nostoc

-like morphology and in-depth morphological characterization indicated that it is a member of the genus

Nostoc

. Furthermore, in the 16S rRNA gene phylogeny inferred using Bayesian inference, maximum likelihood and neighbour joining methods, strain ARC8 clustered within the Nostoc sensu stricto clade. The phylogenetic distance and the positioning of strain ARC8 also indicated that it is a member of the genus

Nostoc

. Furthermore, the rbcL gene phylogeny along with the 16S–23S ITS secondary structure analysis also supported the findings from the 16S rRNA gene tree. In accordance with the International Code of Nomenclature for Algae, Fungi and Plants we describe a novel species of

Nostoc

with the name Nostoc neudorfense sp. nov.
Oceanivirga miroungae sp. nov., isolated from oral cavity of northern elephant seal (Mirounga angustirostris)
Authors: Volokhov Dmitriy V. , Blom Jochen , Amselle Megan , Delmonte Pierluigi , Gao Yamei , Shen Zhenyu , Zhang Shuping , Gulland Frances M. , Chizhikov Vladimir E. , Eisenberg Tobias
Published: March 2020

Two independent strains of a

Leptotrichia

species (ES3154-GLUT and ES2714_GLU) were isolated from the oral cavity of northern elephant seals (Mirounga angustirostris) that were admitted to The Marine Mammal Centre facilities in California, USA. The strains were isolated from oral swabs by cultivation in PPLO broth supplemented with serum, penicillin and colistin in anaerobic conditions. The strains were Gram-negative, pleomorphic, indole-, oxidase- and catalase-negative, non-spore-forming, non-motile rods/coccobacilli in short chains. The 16S rRNA gene sequence of these strains shared 94.42 % nucleotide similarity with

Oceanivirga salmonicida

AVG 2115T but demonstrated ≤86.00–92.50 % nucleotide similarity to the 16S rRNA genes of other species of the family

Leptotrichiaceae

. The genome was sequenced for strain ES3154-GLUT. Average nucleotide identity values between strain ES3154-GLUT and 15 type strain genomes from the family

Leptotrichiaceae

ranged from 66.74 % vs.

Sebaldella termitidis

to 73.35 % vs.

O. salmonicida

. The whole genome phylogeny revealed that the novel species was most closely related to

O. salmonicida

AVG 2115T. This relationship was also confirmed by nucleotide similarity and multilocus phylogenetic analyses employing various housekeeping genes (partial 23S rRNA, rpoB, rpoC, rpoD, polC, adh, gyrA and gyrB genes). Chemotaxonomic and phenotypical features of strain ES3154-GLUT were in congruence with closely related members of the family

Leptotrichiaceae

, represented by similar enzyme profiles and fatty acid patterns. MALDI-TOF MS analysis was capable to clearly discriminate strain ES3154-GLUT from all currently described taxa of the family

Leptotrichiaceae

. Based on these data, we propose a novel species of the genus

Oceanivirga

, for which the name Oceanivirga miroungae sp. nov. is proposed with the type strain ES3154-GLUT (=DSM 109740T=CCUG 73653T=ATCC TSD-189T=NCTC 14411T) and one representative strain ES2714_GLU. The G+C content is 26.82 %, genome size is 1 356 983 bp.
Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
Authors: Chen Zhaowei , Hu Jijia , Zhang Zongwei , Jiang Shan , Han Shoumeng , Yan Dandan , Zhuang Ruhong , Hu Ben , Zhang Zhan
Published: March 2020

Aims

Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19.

Main methods

From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ.

Key findings

For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.

Significance

Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.

Trial registration

URL: https://www.clinicaltrials.gov/. The unique identifier: ChiCTR2000029559.
Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors
Authors: Venkatakrishnan AJ , Puranik Arjun , Anand Akash , Zemmour David , Yao Xiang , Wu Xiaoying , Chilaka Ramakrishna , Murakowski Dariusz K. , Standish Kristopher , Raghunathan Bharathwaj , Wagner Tyler , Garcia-Rivera Enrique , Solomon Hugo , Garg Abhinav , Barve Rakesh , Anyanwu-Ofili Anuli , Khan Najat , Soundararajan Venky
Published: March 2020

The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes, airway club cells, and ciliated cells are likely underappreciated targets of SARS-CoV-2 infection, in addition to type II pneumocytes and olfactory epithelial cells. We further identify mature small intestinal enterocytes as a possible hotspot of COVID-19 fecal-oral transmission, where an intriguing maturation-correlated transcriptional signature is shared between ACE2 and the other coronavirus receptors DPP4 (MERS-CoV) and ANPEP (α-coronavirus). This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses.

The nferX Platform Single-cell resource -https://academia.nferx.com/