bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of tools and algorithms for network motif discovery in biological networks
Authors: Patra Sabyasachi , Mohapatra Anjali
Published: May 2020

Network motifs are recurrent and over‐represented patterns having biological relevance. This is one of the important local properties of biological networks. Network motif discovery finds important applications in many areas such as functional analysis of biological components, the validity of network composition, classification of networks, disease discovery, identification of unique subunits etc. The discovery of network motifs is a computationally challenging task due to the large size of real networks, and the exponential increase of search space with respect to network size and motif size. This problem also includes the subgraph isomorphism check, which is Nondeterministic Polynomial (NP)‐complete. Several tools and algorithms have been designed in the last few years to address this problem with encouraging results. These tools and algorithms can be classified into various categories based on exact census, mapping, pattern growth, and so on. In this study, critical aspects of network motif discovery, design principles of background algorithms, and their functionality have been reviewed with their strengths and limitations. The performances of state‐of‐art algorithms are discussed in terms of runtime efficiency, scalability, and space requirement. The future scope, research direction, and challenges of the existing algorithms are presented at the end of the study.
Variants in HNRNPDL and SETX Not Necessarily Indicate Familial Amyotrophic Lateral Sclerosis or Limb Girdle Muscular Dystrophy 1G in Acute Muscular Respiratory Failure
Authors: Finsterer Josef , Stöllberger Claudia , Keller Hans , Laccone Franco
Published: May 2020

Genetic work-up is useful for the identification of a primary myopathy. However, even sophisticated genetic methods may fail to detect the underlying cause of myopathy as in the following case. The patient is a 52-year-old female with a history of epilepsy, arterial hypertension, atrial flutter requiring cardioversion, ablation, and anticoagulation, coronary heart disease, hyperlipidemia, and hyper-CKemia. At age 52 years, she was referred for heart failure due to ischemic cardiomyopathy requiring appropriate medication and implantation of an ICD. During hospitalization she developed acute muscular respiratory failure requiring mechanical ventilation. Genetic panels for myopathy, neuropathy, and cardiomyopathy revealed variants of unknown significance in the HNRNPDL and SETX genes respectively. Clinical presentation and muscle biopsy, however, suggested metabolic myopathy. Acute muscular respiratory failure may require traditional diagnostic work-up for primary myopathy and long-term invasive and non-invasive ventilation. Panel investigations not necessarily lead to a conclusive diagnosis. The multisystem nature of the condition rather suggests a metabolic defect than LGMD-1G or fALS as genetic findings suggested.
A Comparative Evaluation of Different Chemical Agents and Herbal Products in Disinfecting Gutta-Percha Cones: An In Vitro Study
Authors: Bansal Manu , Bansal Rajinder , Wazir Nikhil Dev , Matta Mandeep Singh , Chaudhary Shalini , Singla Priya
Published: May 2020

Introduction The main aim of this study was to compare and evaluate different chemical agents and herbal products in disinfecting gutta-percha (GP) cones through an in vitro study.

Materials and Methods For this study, 160 GP cones were taken in test tubes, which were contaminated with Enterococcus faecalis inocula, prepared by dissolving it in Brain Heart Infusion (BHI) broth. The GP cones were then taken from the test tubes and dried on Whatman filter paper no. 1 and were divided into four groups according to the decontaminant used for the study—group 1 (5% sodium hypochlorite [NaOCl]), group 2 (2% chlorhexidine), group 3 (propolis), and group 4 (Aloe vera)—which were further subdivided into subgroups on the basis immersion time periods of 1 and 10 minutes. The GP cones were then again dried and taken in the test tubes containing freshly prepared BHI broth to check the turbidity.

Results It was found that 2% chlorhexidine was the most effective disinfectant against E. faecalis, 5% NaOCl was the second best disinfectant followed by propolis, while Aloe vera had not shown any effect as GP disinfectant.

Conclusion Since 2% chlorhexidine showed better disinfection efficacy against E. faecalis than 5% NaOCl, it can be recommended for chairside disinfection of GP. One-minute immersion of GP in 2% chlorhexidine is sufficient for elimination of E. faecalis.
COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach
Authors: Shalish Wissam , Lakshminrusimha Satyanarayana , Manzoni Paolo , Keszler Martin , Sant'Anna Guilherme M.
Published: May 2020

The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject.

Key Points
Antiepileptic drugs induce subcritical dynamics in human cortical networks
Authors: Meisel Christian
Published: May 2020

Significance

Activity propagation in cortex must be carefully balanced to prevent premature die-out and runaway excitation. In this study, large-scale human electrophysiology data and systematic pharmacological control of cortical network interactions are used to provide evidence that cortical network dynamics is controlled by network interactions according to a branching process. The results provide a missing link to the branching process theory of cortical network function with implications for understanding the foundations of cortical excitability, its monitoring in conditions like epilepsy, and how the balance of excitation and inhibition shapes the capacity of temporal information integration in cortical networks.
Features of the implementation of environmental policies by Russian fuel and energy enterprises
Authors: Tsopanova Zarina , Kharitonova Nataliya
Published: May 2020

The study discovers the problem of combating greenhouse gas emissions, which is most relevant for companies in the fuel and energy complex. The country and industry structure of carbon dioxide emissions was analyzed based on available statistical data. Scenario forecasts of changes in the level of emissions developed by the international energy agency are presented here, possible fiscal measures aimed at preventing further development of the “greenhouse effect are also considered. It was noted that Russian fuel and energy companies need to switch to regular accounting and reporting of actual greenhouse gas emissions, which can ensure that they maintain their achieved level of competitiveness in the world energy markets.
Sulfur-containing emulsions under alternative non-thermal initiation: a way to increase the energy efficiency of chemical processes
Authors: Zanin Alexey , Lopatkin Dmitry , Sobolev Pavel , Sadriddinov Manuchehr , Gibadullin Arthur , Morkovkin Dmitry
Published: May 2020

Currently, there is a tendency to develop chemical and chemical-technological processes that consume as little energy as possible. Recently, ionizing and microwave radiation began to be used for these purposes in the chemical industry, since conventional heating can be slow and inefficient, which increases energy consumption. Polymer sulfur, which is one of the modifications of elemental sulfur, has a number of valuable properties, however, the existing methods for its synthesis are characterized by high energy consumption and therefore are disadvantageous. In order to develop a more efficient method for the synthesis of polymer sulfur, the processes that occur in sulfur-containing emulsions under the influence of ionizing and microwave radiation, and the products formed in these processes are investigated.
Assessment of the level of stability and reliability of the electric power complex
Authors: Gibadullin A A
Published: May 2020

This study is aimed at assessing the level of reliability and uninterrupted power supply to consumers. The concept of the reliability of power supply to consumers, which should contain the properties of persistence, uninterrupted operation, durability and maintainability, was presented. In addition, the study analyzed reliability indicators, as a result of which it was revealed that the number of accidents is reduced, however, qualitative indicators, including the number of disconnected consumers, average power outages of consumers and the time of outages, are increasing. At the end of the study, the authors proposed a causal relationship model that affects the reliability and uninterrupted power supply to consumers.
Digital technologies as a tool for improving production and technological activities and information security in Fuel and energy complex
Authors: Dzhafarov E I , Kharitonova N A
Published: May 2020

The article considers the features of using digital technologies in organizations of the fuel and energy complex (FEC). The characteristic features and main problems in the production and auxiliary processes of the oil and gas industry are identified. A study and analysis of the use of blockchain technology based on a variety of distributed registry in the fuel and energy sector, in particular for the oil and gas industry. The encryption algorithm used in blockchain technology is considered. The most relevant models for the application of projects based on distributed database subtechnology in production, trade in oil and natural gas, document management, logistics, with an assessment of the effect of digital technologies in the degree of influence on information security have been developed.
Deducing the N- and O-glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2
Authors: Shajahan Asif , Supekar Nitin T , Gleinich Anne S , Azadi Parastoo
Published: May 2020

The current emergence of the novel coronavirus pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high-resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor-binding domain of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O-glycosylation are strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research toward the development of a suitable vaccine candidate.
The limits of strong government: attempts to control criminality in thirteenth-century England*
Authors: Duggan Kenneth F
Published: May 2020

This article examines how far centrally-directed structures of peacekeeping influenced communal reactions to criminality in thirteenth-century England, and the extent to which developments in the systems and procedures of criminal justice manifested into tighter control over law and order. It challenges claims for the importance of the frankpledge system, offering an alternative means upon which the central government came to rely for the maintenance of law and order. Nevertheless, it also complicates the matter by demonstrating that the mechanisms designed to bring crime more firmly under the state’s control did not necessarily result in greater central control over criminality, let alone reduce local autonomy over criminal justice practices and procedures.
Relationship between iHOT12 and HOS scores in hip pain patients
Authors: Brand Jeff , Hardy Rich , Tori Aerika , Fuchs Hannah , Sungur Engin , Monroe Emily
Published: May 2020

To determine if scores of the International Hip Outcome Tool-12 (iHOT12) and the Hip Outcome Score (HOS) correlate with one another in hip pain patients. Patients reporting to an orthopedic clinic for their scheduled appointment for hip pain were given a paper survey consisting of the iHOT12 and the HOS. Demographic information [age, weight, height and body mass index (BMI)] was obtained by chart review. Overall, 114 patients were invited to voluntarily complete the surveys of which 23 declined. Our sample consisted of 91 (57 female and 34 male) patients (80% response rate). The HOS (iHOT12) explained 62% of the variation in iHOT12 (HOS) by using a linear model (Pearson’s correlation(r) is 0.79, P < 0.001). Age, weight, BMI, gender and arthritis did not show a statistically significant predictive power explaining HOS. However, only gender had a ‘statistically’ significant predictive power explaining iHOT12 (P = 0.007). The relationship between the two scores are stronger for males (r = 0.81, P < 0.001) compared with females (r = 0.77, P < 0.001). The proportion of variations explained on one of the scores by the other are 0.66 for males and 0.59 for females. HOS score together with gender explained 64% of the variation in iHOT12 by using a linear model. iHOT12 together with the non-statistically significant gender term explained 62% of the variation in HOS by using a linear model. It may not be necessary to collect both the iHOT12 and HOS, since the predictive power of one on the other is high. Collecting HOS together with information on gender is preferable compared with collecting iHOT12. Level of evidence: Level III.
Potential influence of COVID-19/ACE2 on the female reproductive system
Authors: Jing Yan , Run-Qian Li , Hao-Ran Wang , Hao-Ran Chen , Ya-Bin Liu , Yang Gao , Fei Chen
Published: May 2020

The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.
Medical Assistance in Dying in Canada: Implications and Considerations for Music Therapists Around the Globe
Authors: Clements-Cortes Amy , Yip Joyce
Published: May 2020

Physician-assisted suicide and voluntary euthanasia are two procedures of Medical Assistance in Dying (MAiD) that are readily requested by patients internationally. In April 2016, the legalization of these procedures occurred in Canada after the pursuit of many jurisdictional cases. Known as Bill C-14, this legislation aims to balance patient autonomy at end-of-life with revised standardizations for medical and healthcare professionals. Music therapists may be included in the medical and healthcare team that can be recommended by patients considering MAiD. At present, there are no written guidelines that empirically outline the role of music therapists in this area. This paper explores the global history of MAiD as well as MAiD in the Canadian healthcare system and its implications. Information on the legislation Bill C-14 will be explained, along with a discussion on the current practices of music therapy at end-of-life and the potential scope of a music therapist during the MAiD procedure. Ethical issues and future research are also presented as recommendations to healthcare and music therapy professionals.
Fever and Fever of Unknown Origin: Review, Recent Advances, and Lingering Dogma
Authors: Wright William F , Auwaerter Paul G
Published: May 2020

Fever has preoccupied physicians since the earliest days of clinical medicine. It has been the subject of scrutiny in recent decades. Historical convention has mostly determined that 37.0°C (98.6°F) should be regarded as normal body temperature, and more modern evidence suggests that fever is a complex physiological response involving the innate immune system and should not be characterized merely as a temperature above this threshold. Fever of unknown origin (FUO) was first defined in 1961 by Petersdorf and Beeson and continues to be a clinical challenge for physicians. Although clinicians may have some understanding of the history of clinical thermometry, how average body temperatures were established, thermoregulation, and pathophysiology of fever, new concepts are emerging. While FUO subgroups and etiologic classifications have remained unchanged since 1991 revisions, the spectrum of diseases, clinical approach to diagnosis, and management are changing. This review considers how newer data should influence both definitions and lingering dogmatic principles. Despite recent advances and newer imaging techniques such as 18-fluorodeoxyglucose–positron emission tomography, clinical judgment remains an essential component of care.
Decoding Plant–Environment Interactions That Influence Crop Agronomic Traits
Authors: Mochida Keiichi , Nishii Ryuei , Hirayama Takashi
Published: May 2020

To ensure food security in the face of increasing global demand due to population growth and progressive urbanization, it will be crucial to integrate emerging technologies in multiple disciplines to accelerate overall throughput of gene discovery and crop breeding. Plant agronomic traits often appear during the plants’ later growth stages due to the cumulative effects of their lifetime interactions with the environment. Therefore, decoding plant–environment interactions by elucidating plants’ temporal physiological responses to environmental changes throughout their lifespans will facilitate the identification of genetic and environmental factors, timing and pathways that influence complex end-point agronomic traits, such as yield. Here, we discuss the expected role of the life-course approach to monitoring plant and crop health status in improving crop productivity by enhancing the understanding of plant–environment interactions. We review recent advances in analytical technologies for monitoring health status in plants based on multi-omics analyses and strategies for integrating heterogeneous datasets from multiple omics areas to identify informative factors associated with traits of interest. In addition, we showcase emerging phenomics techniques that enable the noninvasive and continuous monitoring of plant growth by various means, including three-dimensional phenotyping, plant root phenotyping, implantable/injectable sensors and affordable phenotyping devices. Finally, we present an integrated review of analytical technologies and applications for monitoring plant growth, developed across disciplines, such as plant science, data science and sensors and Internet-of-things technologies, to improve plant productivity.
Peripheral Nerve Stimulation for Pudendal Neuralgia: A Technical Note
Authors: Gregory Nicholas S , Terkawi Abdullah S , Prabhakar Nitin K , Tran Johnathan V , Salmasi Vafi , Hah Jennifer M
Published: May 2020

Background

Pudendal neuropathy is a chronic, disabling form of perineal pain that involves the pudendal nerve, a mixed somatic and autonomic nerve that originates from sacral nerve roots. Peripheral nerve stimulation of the pudendal nerve can be useful to decrease symptom burden in patients who have failed initial conservative treatment modalities.

Methods

In this manuscript, we describe an approach to the placement of a peripheral nerve stimulator for the treatment of pudendal neuralgia. We present a case of complex pelvic neuropathy and review the factors that lead to successful placement. Technical aspects of stimulator placement and ultrasound landmarks are reviewed.

Results

A lateral to medial approach with ultrasound guidance at the level of the ischial spine is likely to facilitate proper lead placement along the course of the pudendal nerve. Aftercare and adherence to postimplant activity restrictions–particularly avoiding use of the extremes of hip flexion and extension for four weeks—lead to the absence of lead migration.

Conclusions

Pudendal nerve stimulation is an emerging technique for neuromodulation of refractory pudendal neuralgia. Ultrasound-guided pudendal nerve stimulation is a viable technique for neuromodulation of pudendal neuralgia. Optimization of patient selection, ultrasound guidance, and proper adherence to postimplant activity restrictions may be helpful for long-term therapeutic success.
Rate of BCG Immunization in HIV-Exposed Infants in a Selected Primary Health Centre in Southern Nigeria: Implications of No Vaccine Policy for HIV-Positive Infants
Authors: Ekanem A M , Oloyede I P , Ekrikpo U E , Idung A U , Edward E
Published: May 2020

Background

Maternal and infant HIV status influences the decision of BCG immunization of infants at birth. The objective of this study was to determine the HIV status of HIV-exposed infants (HEIs) by the first HIV DNA PCR test and the rate of BCG uptake among the HEIs who were confirmed HIV negative.

Methods

This was a retrospective descriptive cross-sectional study involving the review of results of 99 dried blood samples (DBS) for the first HIV DNA PCR test of HEIs whose mothers were diagnosed HIV positive on presentation of the infants at first immunization visit at a Primary Health Centre from January 2018 to January 2019.

Results

Of the 99 DBS examined, 86; 86.9% (95% CI 80.1–93.6) were HIV negative, 9; 9.1% (95% CI 3.3–14.8) were positive while the results of 4 (4.0%) infants were not in the register. Only 7; 7.1% (95% CI 1.9–12.2) of the 99 HEIs returned for BCG immunization at the centre. BCG immunization status of the HEIs after first PCR results was not significantly associated with sex of the infants or availability of phone number of the guardians (p = 0.70 and 0.12, respectively).

Conclusion

The majority of HEIs were HIV negative at first HIV DNA PCR test. Few of these HIV negative infants returned for BCG immunization. Hence, all HEIs should be given BCG immunization according to WHO GAVCS committee recommendation on BCG immunization for settings with poor HIV diagnostic and treatment facilities for mothers and infants.
Per- and poly-fluoroalkyl substances and bone mineral density
Authors: Colicino Elena , Pedretti Nicolo Foppa , Busgang Stefanie A. , Gennings Chris
Published: May 2020

Background:

Per- and poly-fluoroalkyl substances (PFAS) are chemicals, detected in 95% of Americans, that induce osteotoxicity and modulate hormones, thereby influencing bone health. Previous studies found associations between individual PFAS and bone mineral density in adults but did not analyze their combined effects.

Objective:

To extend weighted quantile sum (WQS) regression to a Bayesian framework (Bayesian extension of the WQS regression [BWQS]) and determine the association between a mixture of serum PFAS and mineral density in lumbar spine, total, and neck femur in 499 adults from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES).

Methods:

We used BWQS to assess the combined association of eight PFAS, as a mixture, with bone mineral density in adults. As secondary analyses, we focused on vulnerable populations (men over 50 years and postmenopausal women). Analyses were adjusted for sociodemographic factors. Sensitivity analyses included bone mineral density associations with individual compounds and results from WQS regressions.

Results:

The mean age was 55 years old (SD = 1) with average spine, total, and neck femur mineral densities of 1.01 (SD = 0.01), 0.95 (SD = 0.01), and 0.78 (SD = 0.01) gm/cm2, respectively. PFAS mixture levels showed no evidence of association with mineral density (spine: β = −0.004; 95% credible interval [CrI] = −0.04, 0.04; total femur: β = 0.002; 95% CrI = −0.04, 0.05; femur neck: β = 0.005; 95%CrI = −0.03, 0.04) in the overall population. Results were also null in vulnerable populations. Findings were consistent across sensitivity analyses.

Conclusions:

We introduced a Bayesian extension of WQS and found no evidence of the association between PFAS mixture and bone mineral density.
Identification of distinct clinical phenotypes in mechanically ventilated patients with acute brain dysfunction using cluster analysis
Authors: Souza-Dantas Vicente Cés , Dal-Pizzol Felipe , Tomasi Cristiane D. , Spector Nelson , Soares Márcio , Bozza Fernando A. , Póvoa Pedro , Salluh Jorge I. F.
Published: May 2020

Acute brain dysfunction (ABD) is a frequent and severe syndrome occurring in critically ill patients and early identification of high-risk patients is paramount. In the present analysis, we propose a clinically applicable model for early phenotype identification of ABD at the bedside in mechanically ventilated patients, improving the recognition of patients with prolonged ABD.

Prospective cohort with 629 mechanically ventilated patients in two medical-surgical intensive care units at academic centers. We applied cluster analysis to identify phenotypes using clinical and biological data. We then tested the association of phenotypes and its respective clinical outcomes. We performed a validation on a new cohort of patients select on subsequent patients admitted to the participants intensive care units.

A model with 3 phenotypes best described the study population. A 4-variable model including medical admission, sepsis diagnosis, simplified acute physiologic score II and basal serum C-reactive protein (CRP) accurately classified each phenotype (area under curve 0.82; 95% CI, 0.79–0.86). Phenotype A had the shorter duration of ABD (median, 1 day), while phenotypes B and C had progressively longer duration of ABD (median, 3 and 6 days, respectively; P < .0001). There was an association between the duration of ABD and the baseline CRP levels and simplified acute physiology score II score (sensitivity and specificity of 80%). To increase the sensitivity of the model, we added CRP kinetics. By day 1, a CRP < 1.0 times the initial level was associated with a shorter duration of ABD (specificity 0.98).

A model based on widely available clinical variables could provide phenotypes associated with the duration of ABD. Phenotypes with longer duration of ABD (phenotypes B and C) are characterized by more severe inflammation and by significantly worse clinical outcomes.
Impact of Advanced Practice Prehospital Programs on Health Care Costs and ED Overcrowding
Authors: Green Darcia , Ruel Jennifer
Published: May 2020

Health care costs in the United States continue to increase, requiring solutions that permit safe, quality care with a lower financial investment. Utilization of the emergency department for nonemergent care is considered to be one of the costliest, and most preventable methods of health care delivery. This review seeks to demonstrate how advanced practice prehospital programs can potentially decrease the cost of health care without sacrificing quality or safety. Utilization of the emergency department for nonemergent care contributes to the escalating cost of health care as well as to emergency department overcrowding. Advanced practice prehospital programs are a novel approach to potentially decreasing health care costs and emergency department overcrowding. This review introduces the current state of health care costs, emergency department overcrowding, and advanced practice prehospital programs. Further research is needed to determine the actual fiscal impact of these programs.
Allopurinol-Induced Drug Reaction With Eosinophilia and Systemic Symptoms
Authors: Myers Charlene M. , Miller Jennifer J. , Davis Wesley D.
Published: May 2020

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon yet serious adverse cutaneous drug reaction that results from a hypersensitivity reaction. Drug reaction with eosinophilia and systemic symptoms is often misdiagnosed because of vague and confounding signs and symptoms. The most common clinical manifestations of DRESS are shared with many other diseases and include rash, lymphadenopathy, and fever. Because the syndrome can be difficult to diagnose, patients are often in the late stages of the disease process before treatment is initiated. The mainstay of treatment is stopping the culprit medication. Drug reaction with eosinophilia and systemic symptoms is associated with a high mortality rate, most often from liver failure and failure to diagnose. Emergency providers should be able to recognize the clinical manifestations of DRESS, know what diagnostic studies are indicated, and be familiar with the appropriate treatment.
Respiratory Neurophysiology in Intensive Care Unit
Authors: Swash Michael , de Carvalho Mamede
Published: May 2020

Patients with intensive care unit-acquired weakness have an increased risk of prolonged mechanical ventilation, which is a risk factor for prolonged stay and mortality. The most common cause of this problem is weakness of the diaphragm, which can derive from phrenic nerve injury associated with critical neuropathy, or with the complex multiorgan failure/systemic respiratory response syndrome causing muscle fiber lesion. Two conventional neurophysiological techniques are useful to investigate the respiratory muscles, phrenic nerve conduction, and needle electromyography of the accessory respiratory muscles and diaphragm. Phrenic nerve stimulation is a standard noninvasive technique; amplitude of the motor response can be reduced because of muscle fiber inexcitability or axonal loss. Electromyography of the diaphragm is an invasive method but is safe if performed as indicated. It can reveal neurogenic or myopathic motor units. Although these neurophysiological methods have limitations in the investigation of intensive care unit patients with severe respiratory involvement, normal phrenic nerve responses should exclude marked axonal loss and indicate a better prognosis.
Race, Socioeconomic Deprivation, and Hospitalization for COVID-19 in English participants of a National Biobank
Authors: Patel Aniruddh P. , Paranjpe Manish D. , Kathiresan Nina P. , Rivas Manuel A. , Khera Amit V.
Published: May 2020

Preliminary reports suggest that the Coronavirus Disease 2019 (COVIDâ^’19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. The extent to which these disparities are related to socioeconomic versus biologic factors is largely unknown. We investigate the racial and socioeconomic associations of COVIDâ^’19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both black participants (odds ratio 3.4; 95%CI 2.4â^’4.9) and Asian participants (odds ratio 2.1; 95%CI 1.5â^’3.2) were at substantially increased risk as compared to white participants. We further observed a striking gradient in COVIDâ^’19 hospitalization rates according to the Townsend Deprivation Index â^’ a composite measure of socioeconomic deprivation â^’ and household income. Adjusting for such factors led to only modest attenuation of the increased risk in black participants, adjusted odds ratio 3.1 (95%CI 2.0â^’4.8). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-white individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.
Characterization of the Diffusion Signal of Breast Tissues using Multi-exponential Models
Authors: Rodríguez-Soto Ana E. , Andreassen Maren M. Sjaastad , Conlin Christopher C. , Park Helen H. , Ahn Grace S. , Bartsch Hauke , Kuperman Joshua , Vidić Igor , Ojeda-Fournier Haydee , Wallace Anne M. , Hahn Michael , Seibert Tyler M. , Jerome Neil Peter , Østlie Agnes , Bathen Tone Frost , Goa Pål Erik , Rakow-Penner Rebecca , Dale Anders M.
Published: May 2020

Background

Diffusion-weighted magnetic resonance imaging (DW-MRI) has demonstrated potential as an exogenous contrast-free diagnostic tool for breast cancer screening. Advanced non-Gaussian models of the DW-MRI signal provide insight into the tissue microstructure. Restriction spectrum imaging (RSI) is a mathematical framework that improves tumor conspicuity by decomposing the DW-MRI signal into separate diffusion components. The number of diffusion components and corresponding apparent diffusion coefficients (ADCs) optimal for RSI are organ-specific and determined empirically. The outputs of RSI are the signal contributions of each separable diffusion component.

Purpose

To understand the diffusion-weighted MRI signal of cancerous and healthy breast tissues in the context of RSI.

Study Type

Prospective.

Populations

74 women, from two sites, with pathology-proven breast cancer.

Field Strength/Sequence

3.0T

Assessment

The DW-MRI signal was described using a linear combination of a variable number of exponential components. The ADC for each component was estimated across all voxels from control and cancer regions of interest (ROIs), patients and sites. Once ADCs were determined, the signal contributions of each diffusion component were estimated using these fixed ADC values. Conventional ADC (mono-exponential) values were also estimated.

Statistical Tests

The relative fitting residual and relative Bayesian information criterion (BIC) were assessed. The signal contributions of each diffusion component were compared using analysis of variance (ANOVA) and post-hoc tests.

Results

Estimated ADCs for the bi-exponential model were D1,2 = 2.0 × 10−5 and D2,2 = 2.2 × 10−3 mm2/s, and D1,3=0, D2,3 = 1.4 × 10−3 and D3,3=10.2 × 10−3 mm2/s for tri-exponential model, which in practice is reduced to a bi-exponential model with an offset, or a three-component model. The relative fitting residuals of conventional ADC, bi-exponential and three-component models in control ROIs were 2.1%, 1.62%, and 1.03%, and 3.3%, 1.0%, and 0.3% for cancer ROIs. BIC was smaller for the three-component model, indicating an improved fitting of breast DW-MRI data compared to the bi-exponential model.

Conclusion

Breast DW-MRI signal was best described using a tri-exponential model. The signal contributions of the slower component in bi- or tri-exponential models were larger in tumor lesions. These data may be used as differential features between healthy and malignant breast tissues.
Effectiveness of the strategies implemented in Sri Lanka for controlling the COVID–19 outbreak
Authors: Erandi K.K.W.H. , Mahasinghe A.C. , Perera S.S.N. , Jayasinghe S.
Published: May 2020

In order to bring the new coronavirus pandemic in the country under control, the government of Sri Lanka implemented a set of control strategies including social distancing, quarantine, lockdowns, travel restrictions and isolation of villages. The aim of this study is to investigate the effectiveness of the overall control process with the aid of classical compartment models and network models. Our results indicate that the prevailing control strategies are effective with at least 50% contact rate reduction or with at least 40% isolation of the contact history of infected population.
Altered substance P signaling underlies perivascular sensory nerve dysfunction in inflammatory bowel disease
Authors: Norton Charles E. , Borgmann Elizabeth A. , Hart Marcia L. , Jones Benjamin W. , Franklin Craig , Boerman Erika M
Published: May 2020

Objective

Inflammatory Bowel Disease (IBD) is associated with cardiovascular disease risk and impaired intestinal blood flow, but the functional role of perivascular nerves that control vasomotor function of mesenteric arteries (MAs) perfusing the intestine is unknown in IBD. Because perivascular sensory nerves and their transmitters calcitonin gene-related peptide (CGRP) and substance P (SP) are important mediators of both vasodilation and inflammatory responses, our objective was to identify IBD-related deficits in perivascular sensory nerve function and vascular neurotransmitter signaling.

Approach and Results

In MAs from an IL-10−/−mouse model, we found that IBD significantly impairs EFS-mediated sensory vasodilation and sensory inhibition of sympathetic vasoconstriction, despite decreased sympathetic nerve density and vasoconstriction. The MA content and EFS-mediated release of both CGRP and SP are slightly decreased with IBD, but IBD has different effects on each transmitter. CGRP nerve density, receptor expression, hyperpolarization and vasodilation are preserved with IBD. In contrast, SP nerve density and receptor expression are increased, and SP hyperpolarization and vasodilation are impaired with IBD. A critical finding is that blocking neurokinin 1 (SP) receptors restored EFS-mediated sensory vasodilation and enhanced CGRP-mediated vasodilation in MAs from IBD but not Control mice.

Conclusions

An aberrant role for the perivascular sensory neurotransmitter SP and its downstream signaling in MAs underlies vascular dysfunction with IBD. With IBD, SP signaling impedes CGRP-mediated sensory vasodilation, contributing to impaired blood flow. Substance P and NK1 receptors may represent an important target for treating vascular dysfunction in IBD.
Synergistic Material-Topography Combinations to Achieve Immunomodulatory Osteogenic Biomaterials
Authors: Burroughs Laurence , Amer Mahetab H. , Vassey Matthew , Koch Britta , Figueredo Grazziela P , Mukonoweshuro Blessing , Mikulskis Paulius , Vasilevich Aliaksei , Vermeulen Steven , Dryden Ian L. , Winkler David A. , Ghaemmaghami Amir M. , Rose Felicity R. A. J. , de Boer Jan , Alexander Morgan R.
Published: May 2020

Human mesenchymal stem cells (hMSCs) are widely represented in ongoing regenerative medicine clinical trials due to their ease of autologous implantation. In bone regeneration, crosstalk between macrophages and hMSCs is critical with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to both direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-microtopography screening platform, theChemoTopoChip, is used to identify materials suitable for bone regeneration by screening with human immortalized mesenchymal stem cells (hiMSCs) and human macrophages. The osteoinduction achieved in hiMSCs cultured on the “hit” materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative in bone-regenerative applications. These also exhibit immunomodulatory effects, concurrently polarizing macrophages towards a pro-healing phenotype. Control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large library of materials reveals that the relative roles of microtopography and material chemistry are similar, and machine learning identifies key material and topographical features for cell-instruction.
Reducing Sanger Confirmation Testing through False Positive Prediction Algorithms
Authors: Holt James M. , Wilk Melissa , Sundlof Brett , Nakouzi Ghunwa , Bick David , Lyon Elaine
Published: May 2020

Purpose

Clinical genome sequencing (cGS) followed by orthogonal confirmatory testing is standard practice. While orthogonal testing significantly improves specificity it also results in increased turn-around-time and cost of testing. The purpose of this study is to evaluate machine learning models trained to identify false positive variants in cGS data to reduce the need for orthogonal testing.

Methods

We sequenced five reference human genome samples characterized by the Genome in a Bottle Consortium (GIAB) and compared the results to an established set of variants for each genome referred to as a ‘truth-set’. We then trained machine learning models to identify variants that were labeled as false positives.

Results

After training, the models identified 99.5% of the false positive heterozygous single nucleotide variants (SNVs) and heterozygous insertions/deletions variants (indels) while reducing confirmatory testing of true positive SNVs to 1.67% and indels to 20.29%. Employing the algorithm in clinical practice reduced orthogonal testing using dideoxynucleotide (Sanger) sequencing by 78.22%.

Conclusion

Our results indicate that a low false positive call rate can be maintained while significantly reducing the need for confirmatory testing. The framework that generated our models and results is publicly available athttps://github.com/HudsonAlpha/STEVE.
Bt cotton sustainability needs integration of complementary technologies for the cotton farmers in India
Authors: Gujar GT , Mayee CD , Choudhary B , Suresh A
Published: May 2020

Biased conclusions of long-term impact of Bt cotton published in Nature Plants March 2020 threatens to derail technological development. We therefore advocate integrating available technologies for sustainability of Bt adoption in India and prospecting for all including biotechnological developments.
Epigenetic therapy remodels the immune synaptic cytoskeleton to potentiate cancer susceptibility to γδ T cells
Authors: Weng Rueyhung R. , Lu Hsuan-Hsuan , Lin Chien-Ting , Fan Chia-Chi , Lin Rong-Shan , Huang Tai-Chung , Lin Shu-Yung , Huang Yi-Jhen , Juan Yi-Hsiu , Wu Yi-Chieh , Hung Zheng-Ci , Liu Chi , Lin Xuan-Hui , Hsieh Wan-Chen , Chiu Tzu-Yuan , Liao Jung-Chi , Chiu Yen-Ling , Chen Shih-Yu , Yu Chong-Jen , Tsai Hsing-Chen
Published: May 2020

γδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune systems and can attack cancer or virus-infected cells in an MHC-unrestricted manner. Despite its antitumor ability in both autologous and allogeneic settings, earlier trials of adoptive γδ T cell transfer in solid tumors had limited success due to limitations in cell expansion and the lack of a strategy to modulate tumor lytic interactions between γδ T and cancer cells. Here, we show through quantitative surface proteomics and gene enrichment analyses that DNA methyltransferase inhibitors (DNMTis) upregulate multiple surface molecules related to γδ T cell activation in cancer cells. DNMTi treatment of human lung cancer potentiates tumor lysis byex vivo-expanded γδ T cells using a clinical-grade expansion protocol developed by our team to enrich for the Vδ1 subset while preserving their antitumor effector functions. Mechanistically, DNMTis enhance immune synapse formation and stabilize the synaptic cleft to facilitate γδ T-mediated tumor lysis. Through integrated analysis of RNA-seq, DNA methylation, and ATAC-seq, we demonstrate that depletion of DNMTs induces coordinated pattern alterations of immune synaptic-cytoskeletal networks at the cancer side of the immune synapse. In addition, single-cell mass cytometry reveals enrichment of polyfunctional γδ T subsets by DNMTis. Combined DNMTi and adoptive γδ T transfer in a mouse lung cancer model offers a significant survival benefit. Consistently, the DNMTi-associated cytoskeleton signature identifies a subset of lung cancer patients with improved survival. Our results demonstrate that epigenetic mechanisms are crucial for cytoskeletal remodeling in cancer to potentiate immune attack and support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.

One Sentence Summary

DNA methyltransferase inhibitors potentiate the killing of lung cancer by γδ T cells through remodeling cytoskeletal-immune synaptic networks.
Detecting neural state transitions underlying event segmentation
Authors: Geerligs Linda , van Gerven Marcel , Güçlü Umut
Published: May 2020

Segmenting perceptual experience into meaningful events is a key cognitive process that helps us make sense of what is happening around us in the moment, as well as helping us recall past events. Nevertheless, little is known about the underlying neural mechanisms of the event segmentation process. Recent work has suggested that event segmentation can be linked to regional changes in neural activity patterns. Accurate methods for identifying such activity changes are important to allow further investigation of the neural basis of event segmentation and its link to the temporal processing hierarchy of the brain. In this study, we introduce a new set of elegant and simple methods to study these mechanisms. We introduce a method for identifying the boundaries between neural states in a brain area and a complementary one for identifying the number of neural states. Furthermore, we present the results of a comprehensive set of simulations and analyses of empirical fMRI data to provide guidelines for reliable estimation of neural states and show that our proposed methods outperform the current state-of-the-art in the literature. This methodological innovation will allow researchers to make headway in investigating the neural basis of event segmentation and information processing during naturalistic stimulation.

Highlights

Boundaries between meaningful events are related to neural state transitions.

Neural states are temporarily stable regional brain activity patterns.

We introduce novel methods for data-driven detection of neural state boundaries.

These methods can identify the location and the number of neural state boundaries.

Simulations and empirical data support the reliability and validity of our methods.