bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the Efficacy and Safety of Intralesional Verapamil With Intralesional Triamcinolone Acetonide in Treatment of Hypertrophic Scars and Keloids: A Meta-Analysis of Randomized Controlled Trials
Authors: Wang Pu , Gu Luosha , Bi Hongsen , Wang Qifei , Qin Zelian
Published: December 2020

Background

Clinical treatment of hypertrophic scars (HSs) and keloids is often unsatisfactory. Intralesional injections of triamcinolone acetonide (TAC) and verapamil are widely used to treat HSs and keloids, but their efficacy and safety are controversial.

Objectives

The aim of this study was to conduct a meta-analysis of the effectiveness and safety of verapamil and TAC in the treatment of HSs and keloids.

Methods

Embase, Google Scholar, and PubMed were searched for randomized controlled trials (RCTs) from inception to February 2020. RCTs that evaluated treatment effects with the Vancouver Scar Scale or reported adverse effects were included. The continuous data and the dichotomous variables were analyzed as mean difference (MD) and relative risk (RR), respectively.

Results

Seven RCTs (461 patients) were included. Compared with verapamil, TAC rapidly changed the ∆height (MD = 0.07; P < 0.05) and ∆pliability (MD = 0.23; P < 0.05) after the first session, but subsequent treatments resulted in no significant differences in the ∆height, ∆pigmentation, ∆vascularity, and ∆pliability. Although total adverse effects (RR = 0.42; P = 0.1) were not significantly different, in the subgroup analysis the incidence of telangiectasia (RR = 0.04; P < 0.05) and skin atrophy (RR = 0.10; P < 0.05), but not pain (RR = 1.27; P = 0.77), was significantly lower with verapamil than with TAC.

Conclusions

Verapamil may be an effective substitute for TAC. Although total adverse effects did not change, the incidence of telangiectasia and skin atrophy was lower with verapamil than with TAC.

Level of Evidence: 4
Prediction of histone post-translational modifications using deep learning
Authors: Baisya Dipankar Ranjan , Lonardi Stefano
Published: December 2020

Motivation

Histone post-translational modifications (PTMs) are involved in a variety of essential regulatory processes in the cell, including transcription control. Recent studies have shown that histone PTMs can be accurately predicted from the knowledge of transcription factor binding or DNase hypersensitivity data. Similarly, it has been shown that one can predict PTMs from the underlying DNA primary sequence.

Results

In this study, we introduce a deep learning architecture called DeepPTM for predicting histone PTMs from transcription factor binding data and the primary DNA sequence. Extensive experimental results show that our deep learning model outperforms the prediction accuracy of the model proposed in Benveniste et al. (PNAS 2014) and DeepHistone (BMC Genomics 2019). The competitive advantage of our framework lies in the synergistic use of deep learning combined with an effective pre-processing step. Our classification framework has also enabled the discovery that the knowledge of a small subset of transcription factors (which are histone-PTM and cell-type-specific) can provide almost the same prediction accuracy that can be obtained using all the transcription factors data.

Availabilityand implementation

https://github.com/dDipankar/DeepPTM.

Supplementary information

Supplementary data are available at Bioinformatics online.
The State Theory of Grotius
Authors: Bhuta Nehal
Published: December 2020

This article argues that Grotius has a modern theory of the state that can take its place alongside Bodin and Hobbes as one of the ways in which early modern civil philosophy sought to solve the problem of the authority and validity of political order. This is interesting because Grotius’s account of the state draws a picture of the relationship between political and legal ordering, and history, in which the interrelationship of the political and the legal allows a range of adaptive and adaptable state-forms. State authority is made possible and accountable under a system of natural legal right, even as its constitution is a historical achievement that should not readily be disturbed and in which a large range of freedom and unfreedom is lawful and should be accepted. I argue that, understood in this way, the State Theory of Grotius is not only modern, but provides in its methods and insights, a potential answer to one of the key conceptual dead ends of modern theories of sovereignty: the idea that sovereign power must be perpetually concentrated in one organ or entity if it is to retain what makes it sovereign. Along the way, I highlight the significance of state theory for contemporary discussions of international, transnational and global law.
A Random Forest Classification Algorithm Based Personal Thermal Sensation Model for Personalized Conditioning System in Office Buildings
Authors: Li Qing Yun , Han Jie , Lu Lin
Published: December 2020

The personal thermal sensation model is used as the main component for personalized conditioning system, which is an effective method to fulfill thermal comfort requirements of the occupants, considering the energy consumption. The Random Forest classification algorithm based thermal sensation model is developed in this study, which combines indoor air quality parameters, personal information, physiological factors and occupancy preferences on selection of 7-level of sensation: cold, cool, slightly cool, neutral, slightly warm, warm and hot. Our model shows better functionality, as well as performance and factor selection. As a result, our method has achieved 70.2% accuracy, comparing with the 57.4% accuracy of support vector machine, and 67.7% accuracy of neutral network in an ASHRAE RP-884 database. Therefore, our newly developed model can be used in personalized thermal adjustment systems with intelligent control functions.
An Attention Enhanced Cross-Modal Image–Sound Mutual Generation Model for Birds
Authors: Hao Wangli , Han Meng , Li Shancang , Li Fuzhong
Published: December 2020

Cross-modal bird image–audio mutual generation has appealing potential benefits for bird classification. To achieve promising cross-modal bird visual–audio mutual generation, we propose an attention enhanced cross-modal cycle adversarial generation network. Specifically, the attention module endows our model with long-term intra-modality dependency and inter-modality dependency capabilities, which can provide more information during the generation process and further improve the generation performance. Moreover, because there was no dataset concerning bird visual–audio mutual generation, the authors established a novel bird cross-modal generation dataset, called Bird_Crossmodal_Generation (BCG). Based on BCG, our model obtains promising performance and achieves significant improvement under both inception score and Frechet inception distance criteria. The experimental results validate the feasibility of the proposed task and the superiority of our model. Additionally, this investigation provides a basis for more researchers to develop cross-modality methods for bird visual–audio generation.
Cardiac arrest and COVID-19: inflammation, angiotensin-converting enzyme 2, and the destabilization of non-significant coronary artery disease—a case report
Authors: Colombier Sébastien , Mahendiran Thabodhan , Niclauss Lars , Kirsch Matthias
Published: December 2020

Background

The new β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to exhibit cardiovascular pathogenicity through use of angiotensin-converting enzyme 2 (ACE2) for cell entry and the development of a major systemic inflammation. Furthermore, cardiovascular comorbidities increase susceptibility to SARS-CoV-2 infection and the development of a severe form of COronaVIrus Disease 2019 (COVID-19).

Case summary

We describe the case of a COVID-19 patient whose inaugural presentation was a refractory cardiac arrest secondary to the destabilization of known, non-significant coronary artery disease. Patient was supported by venoarterial extracorporeal life support. After 12 h of support, cardiac function remained stable on low vasopressor support but the patient remained in a coma and brainstem death was diagnosed.

Discussion

Myocardial injury is frequently seen among critically unwell COVID-19 patients and increases the risk of mortality. This case illustrates several potential mechanisms that are thought to drive the cardiac complications seen in COVID-19. We present the potential role of inflammation and ACE2 in the pathophysiology of COVID-19.
Hemopericardium with subsequent cardiac tamponade secondary to rivaroxaban treatment: a case report
Authors: Shastri Pinang , Bhuta Sapan , Oostra Carson , Monroe Todd
Published: December 2020

Background

The use and utility of novel oral anticoagulants has been increasing in clinical practice due to their relatively lower incidence of side effects such as intracranial haemorrhage, particularly in the elderly, when compared with vitamin K antagonists. Rivaroxaban is a factor Xa and prothrombinase inhibitor indicated for stroke and venous thromboembolism prophylaxis in non-valvular atrial fibrillation as well as treatment of venous thromboembolism.

Case summary

A patient with history of paroxysmal atrial fibrillation on Rivaroxaban presented with generalized malaise, lightheadedness, and dizziness. The patient was found to be in profound cardiogenic shock despite unremarkable cardiac enzymes. Electrocardiogram revealed rate controlled atrial fibrillation and T-wave inversions in the inferolateral leads without associated electrical alternans. Bedside echocardiogram revealed a large pericardial effusion consistent with cardiac tamponade physiology. Following anticoagulation reversal, the patient underwent urgent pericardiocentesis yielding haemorrhagic fluid, with subsequent improvement in haemodynamic status. Despite the presence of retroperitoneal lymphadenopathy on previous computed tomography of the abdomen and concern for underlying malignant effusion secondary to lymphoma, cytology of the fluid revealed no evidence of malignant cells and follow-up flow cytometry and bone marrow biopsy were unremarkable.

Discussion

While hemopericardium is not listed as a known side effect of Rivaroxaban, previous cases of hemopericardium secondary to Rivaroxaban have been described in the literature secondary to pre-disposing risk factors including CYP450 drug interactions or cardiac device implantations. In this case, the patient experienced a spontaneous hemopericardium on Rivaroxaban without any previously elucidated risk factors or evidence of malignancy.
Incidence, prevalence, and trajectories of repetitive conduction patterns in human atrial fibrillation
Authors: van Rosmalen Frank , Maesen Bart , van Hunnik Arne , Hermans Ben J M , Bonizzi Pietro , Bidar Elham , Nijs Jan , Maessen Jos G , Verheule Sander , Delhaas Tammo , Schotten Ulrich , Zeemering Stef
Published: December 2020

Aims

Repetitive conduction patterns in atrial fibrillation (AF) may reflect anatomical structures harbouring preferential conduction paths and indicate the presence of stationary sources for AF. Recently, we demonstrated a novel technique to detect repetitive patterns in high-density contact mapping of AF. As a first step towards repetitive pattern mapping to guide AF ablation, we determined the incidence, prevalence, and trajectories of repetitive conduction patterns in epicardial contact mapping of paroxysmal and persistent AF patients.

Methods and results

A 256-channel mapping array was used to record epicardial left and right AF electrograms in persistent AF (persAF, n = 9) and paroxysmal AF (pAF, n = 11) patients. Intervals containing repetitive conduction patterns were detected using recurrence plots. Activation movies, preferential conduction direction, and average activation sequence were used to characterize and classify conduction patterns. Repetitive patterns were identified in 33/40 recordings. Repetitive patterns were more prevalent in pAF compared with persAF [pAF: median 59%, inter-quartile range (41–72) vs. persAF: 39% (0–51), P < 0.01], larger [pAF: = 1.54 (1.15–1.96) vs. persAF: 1.16 (0.74–1.56) cm2, P < 0.001), and more stable [normalized preferentiality (0–1) pAF: 0.38 (0.25–0.50) vs. persAF: 0.23 (0–0.33), P < 0.01]. Most repetitive patterns were peripheral waves (87%), often with conduction block (69%), while breakthroughs (9%) and re-entries (2%) occurred less frequently.

Conclusion

High-density epicardial contact mapping in AF patients reveals frequent repetitive conduction patterns. In persistent AF patients, repetitive patterns were less frequent, smaller, and more variable than in paroxysmal AF patients. Future research should elucidate whether these patterns can help in finding AF ablation targets.
Depressive Symptoms and Loneliness Among Black and White Older Adults: The Moderating Effects of Race
Authors: Taylor Harry O , Nguyen Ann W
Published: December 2020

Background and Objectives

Loneliness is consistently linked to worse depression/depressive symptoms; however, there are few studies that have examined whether the relationship between loneliness and depressive symptoms varies by race. The purpose of this study was to determine whether race moderated the relationship between loneliness and depressive symptoms.

Research Design and Methods

Data come from the 2014 wave of the Health and Retirement Study (HRS) Core survey and Psychosocial Leave-Behind Questionnaire; only black and white older adults were included in the analysis (N = 6,469). Depressive symptoms were operationalized by the eight-item Center for Epidemiological Studies—Depression scale; however, the “felt lonely” item was removed given concerns with collinearity. Loneliness was operationalized using the Hughes 3-Item Loneliness Scale. Sociodemographic variables included gender, age, education, household income, employment status, marital status, and living alone or with others. Furthermore, social support and negative interactions from family members and friends, and religious service attendance were included in the analysis. Lastly, we created an interaction term between race and loneliness. All analyses used survey weights to account for the complex multistage sampling design of the HRS. Missing data were multiply imputed.

Results

In multivariable analysis, we found race significantly moderated the relationship between loneliness and depressive symptoms while controlling for sociodemographic covariates, social support and negative interaction variables, and religious service attendance.

Discussion and Implications

Our findings demonstrate a differential racial effect for loneliness and depressive symptoms. For both blacks and whites, greater loneliness affected depressive symptoms; however, the effect was stronger among whites than it was for blacks. Given this is one of the first studies to examine the differential effects of race on loneliness and depressive symptoms, more research is necessary to determine the consistency of these results.
Pre-Exposure Prophylaxis (PrEP) Implementation for Gay, Bisexual, and Other Men Who Have Sex with Men: Implications for Social Work Practice
Authors: Lacombe-Duncan Ashley , Guta Adrian , Newman Peter A
Published: December 2020

Social workers have been critical in the response to HIV from its inception, in HIV prevention, support, and advocacy for stigmatized populations including gay, bisexual, and other men who have sex with men (GBM). Recently, social workers have been tasked with working in an era of increasingly biomedicalized HIV prevention, including pre-exposure prophylaxis (PrEP), a safe and highly effective new prevention technology. However, disparities in PrEP access due to structural barriers, including lack of health insurance coverage, and complex decision-making pathways and processes of engagement present substantial challenges for PrEP implementation. Ensuring equitable access to resources and supporting informed decision making are paramount to social work values, yet scant published literature has considered PrEP social work intervention. This article draws on qualitative data from 29 GBM respondents to highlight gaps in PrEP decision-making support and access that may be amenable to social work intervention. Authors describe opportunities for individual, interpersonal, organizational, and structural social work interventions to address multilevel gaps in PrEP implementation. Findings illuminate the complexity of individual experiences and social discourses regarding PrEP and their impact on GBM and raise important issues for social workers to consider in working with GBM clients, service providers, and administrators.
Age at maturation predicted from scale measurements in Pacific herring (Clupea pallasii)
Authors: Miller Sara E , Dressel Sherri C , Hinds Christine M , Buettner Detlef
Published: December 2020

Age at maturation is linked to population productivity and directly impacts forecasts of population biomass and resultant harvest limits set by management agencies. Based on the original concept that scale growth can be used as an index of body growth (length) from Johan Hjort and his collaborators, the current study examined a new way of estimating maturity empirically using scales for Pacific herring. We hypothesized that Pacific herring that will spawn in a particular year (spring) will have reached a sufficient size and have reduced growth (length) the summer prior, compared to immature herring, as energy will be allocated to reproduction rather than somatic length. Model results suggested that there was no difference in the measurement of all scale growth prior to the last increment (growth up until the summer prior) nor in the outer ring measurement (growth the summer prior to spawning) of immature and mature female herring; using scales to estimate maturity empirically was not successful in this study. It is possible that the sample size in this study may have been too low to detect differences in growth or differences in growth may be better represented by changes in length-specific mass.
Ex situandin situtarget strength measurements of European anchovy in the Bay of Biscay
Authors: Sobradillo B , Boyra G , Pérez-Arjona I , Martinez U , Espinosa V
Published: December 2020

This study measures the dorsal aspect target strength (TS; dB re 1 m2) and TS–length (standard length, SL; cm) relationships for European anchovy, attained both ex situ and in situ in two different seasons across 7 years in the Bay of Biscay. The measurements were made at three frequently used acoustic frequencies (38, 120, and 200 kHz). A backscattering model for physostome fish was utilized to help interpret the results. The obtained experimental mean TS for anchovies with an SL of 3.5–19.5 cm was −44.6 (±2.3), −46.9 (±3), and −48.4 (±2.7) dB at 38, 120, and 200 kHz, respectively, yielding b20 values of −66.4, −68.7, and −70.4 dB, respectively. The results were consistent across seasons and between in situ and ex situ conditions, presenting TS–length relationships with statistically significant slopes (p-values <0.05) for all frequencies. This research represents part of a series of efforts planned to obtain a comprehensive TS vs. length and depth relationship to update the acoustic assessment methodology of European anchovy in the Bay of Biscay.
Research on variable parameter power differential charge–discharge strategy of energy storage system in isolated island operating microgrid
Authors: Wu Tiezhou , Wang Jin , Qi Yibo , Rong Fumei
Published: December 2020

This paper proposed an improved particle swarm optimization (PSO) algorithm for the variable parameter power difference charging and discharging strategy of battery energy storage system (BESS). The charge and discharge power of the BESS under different load intervals and state of charge (SOC) intervals are distributed, and the objective functions of peak shaving and valley filling standard deviation and minimum SOC off-line rate are established. The simulation model of peak shaving and valley filling is built, and the results show that the standard deviation of peak shaving and valley filling reduced by 22.58% compared with PSO. The effectiveness and feasibility of the improved PSO are verified.
Clinical handover and handoff in healthcare: a systematic review of systematic reviews
Authors: Desmedt Melissa , Ulenaers Dorien , Grosemans Joep , Hellings Johan , Bergs Jochen
Published: December 2020

Purpose

The purpose of this systematic review is to appraise and summarize existing literature on clinical handover.

Data sources

We searched EMBASE, MEDLINE, Database of Abstracts of Reviews of Effects and Cochrane Database of Systematic Reviews.

Study selection

Included articles were reviewed independently by the review team.

Data extraction

The review team extracted data under the following headers: author(s), year of publication, journal, scope, search strategy, number of studies included, type of studies included, study quality assessment, used definition of handover, healthcare setting, outcomes measured, findings and finally some comments or remarks.

Results of data synthesis

First, research indicates that poor handover is associated with multiple potential hazards such as lack of availability of required equipment for patients, information omissions, diagnosis errors, treatment errors, disposition errors and treatment delays. Second, our systematic review indicates that no single tool arises as best for any particular specialty or use to evaluate the handover process. Third, there is little evidence delineating what constitutes best handoff practices. Most efforts facilitated the coordination of care and communication between healthcare professionals using electronic tools or a standardized form. Fourth, our review indicates that the principal teaching methods are role-playing and simulation, which may result in better knowledge transfer to the work environment, better health and patients’ well-being.

Conclusions

This review emphasizes the importance of staff education (including simulation-based and team training), non-technical skills and the implementation process of clinical handover in healthcare settings.
Umbilical Cord Mesenchymal Stem Cells for Inflammatory Regulation After Excision and Grafting of Severe Burn Wounds in Rats
Authors: Jian-Xing Duan , Wen-Jun Liu , Yue-Qin Zeng , Wang Di , Gao-Fei Zhang , Jia-Mei Li , Han-Xiao Lou
Published: December 2020

Severe burns predispose to shock and necessitate escharectomy and skin grafting. Previous studies show that mesenchymal stem cells are effective for burn wound healing and immune regulation. In this study, we combined escharectomy and skin grafting after burn injury with stem cell application, so as to examine the immune regulation of stem cells and the effect on the transplanted skin graft. SD rats were randomly divided into normal group, sham group, normal + hUCMSCs group, and normal + SB203580 group. Normal saline, hUCMSCs, and SB203580 were injected into the tail vein of each group, and serum inflammatory factors were detected by ELISA. The expression of p38 MAPK/NF-κB pathway proteins in rat liver was detected by western blot. Skin activity was detected by Trypan blue staining and western blot. Skin graft inflammatory infiltration was detected by histological analysis. We found that hUCMSCs could regulate the phosphorylation levels of P38MAPK and NF-B P65 proteins in the liver to reduce the inflammatory response. These effects could continue to reduce the production of inflammatory factors HMGB-1, IL-6, and TNF-α, and increase the anti-inflammatory factor IL-10. The infiltration of inflammatory cells in skin graft was significantly reduced in the normal + hUCMSCs group, and the macrophages in the hUCMSCs group polarized to the anti-inflammatory M2 direction in 3 days. However, the changes of skin graft activity and necroptosis markers protein RIP3 were not observed. The present study demonstrates the immunomodulatory effects of hUCMSCs on the systemic and skin graft microenvironment after excision.
A comprehensive three-phase opiate sparing multimodal pain protocol for hip arthroscopy: a retrospective review
Authors: Kolaczko Jensen G , Knapik Derrick M , Kroneberger Elisabeth , Chadha Amrita , Salata Michael J
Published: December 2020

The aim of this study is to assess the efficacy of a three-phase, multimodal, perioperative pain protocol for primary hip arthroscopy based on pain scores, narcotic use, time to discharge, hospital admission and complications. A retrospective study of patients undergoing primary hip arthroscopy over a 48-month time period was conducted. Patients were separated into a multimodal group consisting of non-narcotic medication, local analgesia and a peripheral nerve block (PNB) versus patients receiving only a PNB. Differences in post-anesthesia care unit (PACU) visual analog scores, PACU time to discharge, PACU opioid consumption, hospital admission and complications between protocols were recorded and analyzed. There were 422 patients who underwent 484 surgeries, with 15 patients crossing over pain protocol groups for surgery on the contralateral hip. One hundred and ninety-six patients underwent 213 procedures in the multimodal group and 241 patients underwent 271 procedures in the PNB group. No differences in baseline characteristics were appreciated between groups. Mean time to discharge was significantly shorter in the multimodal group (137.4 ± 49.3 min versus 176.3 ± 6.5 min; P < 0.001) which also had less post-operative admissions (0 versus 9; P = 0.006) than the PNB group. In patients who crossed over protocol groups, a statistically shorter time to discharge was appreciated with the multimodal protocol compared with the PNB protocol (119.9 ± 32.1 min versus 187.9 ± 9.2; P = 0.012). The three-phase, multimodal pain protocol led to significantly faster discharge times and fewer hospital admissions when compared with isolated PNB in patients undergoing primary hip arthroscopy.
Laryngotracheal stenosis following intubation and tracheostomy for COVID-19 pneumonia: a case report
Authors: Vasanthan Rishi , Sorooshian Parviz , Sri Shanmuganathan Vishnu , Al-Hashim Muhannad
Published: December 2020

Laryngotracheal stenosis (LTS) is a rare but serious condition characterized by narrowing of the airway. Iatrogenic injury from endotracheal intubation or tracheostomy insertion is the most common cause of LTS. We present the first reported experience of managing a patient diagnosed with subglottic stenosis (a subtype of LTS) following previous intubation and tracheostomy for coronavirus disease 2019 (COVID-19). This patient required an urgent surgical tracheostomy and subsequent referral to a tertiary airway surgery unit for definitive treatment, which included microlaryngoscopy, laser excision and balloon dilatation. This case highlights that LTS should be included in the differential diagnosis for patients re-presenting with breathing difficulties after prolonged intubation or tracheostomy for COVID-19. Furthermore, it raises the concern of a rise in the incidence of this condition and an increased burden on the few units specializing in airway surgery.
Health Behavior Differences Between Male and Female U.S. Military Personnel by Sexual Orientation: The Importance of Disaggregating Lesbian, Gay, and Bisexual Groups
Authors: Jeffery Diana D , Beymer Matthew R , Mattiko Mark J , Shell Donald
Published: December 2020

Introduction

The aims of the study are to identify health-related behaviors associated with sexual orientation among active duty military personnel and to compare those behaviors when lesbian, gay, and bisexual (LGB) groups are aggregated and disaggregated.

Materials and Methods

We used public data from the 2015 Health-Related Behavior Survey of Active Duty Military Personnel. Binomial logistic regression analyses were used to examine differences between and within heterosexual, same-sex, and bisexual groups as predicted by the following correlates: demographic characteristics, physical activity, substance use, probable mood disorders, unwanted sexual contact, physical abuse, suicidal behaviors, and sexually transmitted infection (STI).

Results

In univariate analyses, rates of lifetime unwanted sexual contact and lifetime suicidal ideation were significantly higher for bisexual females compared to other groups. The results of regression analyses differed depending on whether LGB groups were aggregated or disaggregated. Aggregated LGB versus heterosexual model found significant differences with respect to unwanted sexual contact, lifetime suicide attempt, STI, smoking, and marijuana use. Disaggregated models found different patterns of significant correlates, e.g., correlates comparing gays to heterosexual males were STI, sexual contact, lifetime suicide attempt, and age; correlates comparing lesbians to heterosexual females were heavy drinking, probable post-traumatic stress disorder, ever used marijuana, lifetime suicide attempt, lifetime physical abuse, and smoking.

Conclusion

The findings are consistent with those of previous research showing highest risk for suicidal behaviors and substance abuse among bisexual individuals. We recommend that future studies and clinical care consider LGB sexual identities as heterogeneous groups; otherwise, risks for adverse health behaviors may be overlooked.
X-ray Dips in AGN and Microquasars – Collapse Timescales of Inner Accretion Disc
Authors: Shende Mayur B , Chauhan Prashali , Subramanian Prasad
Published: December 2020

The temporal behaviour of X-rays from some AGN and microquasars is thought to arise from the rapid collapse of the hot, inner parts of their accretion discs. The collapse can occur over the radial infall timescale of the inner accretion disc. However, estimates of this timescale are hindered by a lack of knowledge of the operative viscosity in the collisionless plasma comprising the inner disc. We use published simulation results for cosmic ray diffusion through turbulent magnetic fields to arrive at a viscosity prescription appropriate to hot accretion discs. We construct simplified disc models using this viscosity prescription and estimate disc collapse timescales for 3C 120, 3C 111, and GRS 1915+105. The Shakura-Sunyaev α parameter resulting from our model ranges from 0.02 to 0.08. Our inner disc collapse timescale estimates agree well with those of the observed X-ray dips. We find that the collapse timescale is most sensitive to the outer radius of the hot accretion disc.
The distribution and properties of DLAs at z ≤ 2 in the EAGLE simulations
Authors: Garratt-Smithson Lilian , Power Chris , Lagos Claudia del P , Stevens Adam R H , Allison James R , Sadler Elaine M
Published: December 2020

Determining the spatial distribution and intrinsic physical properties of neutral hydrogen on cosmological scales is one of the key goals of next-generation radio surveys. We use the EAGLE galaxy formation simulations to assess the properties of damped Lyman α absorbers (DLAs) that are associated with galaxies and their underlying dark matter haloes between 0 ≤ z ≤ 2. We find that the covering fraction of DLAs increases at higher redshift; a significant fraction of neutral atomic hydrogen (H i) resides in the outskirts of galaxies with stellar mass ≥1010 M⊙; and the covering fraction of DLAs in the circumgalactic medium (CGM) is enhanced relative to that of the interstellar medium (ISM) with increasing halo mass. Moreover, we find that the mean density of the H i in galaxies increases with increasing stellar mass, while the DLAs in high- and low-halo mass systems have higher column densities than those in galaxies with intermediate halo masses (∼1012 M⊙ at z = 0). These high-impact CGM DLAs in high-stellar mass systems tend to be metal poor, likely tracing smooth accretion. Overall, our results point to the CGM playing an important role in DLA studies at high redshift (z ≥ 1). However, their properties are impacted both by numerical resolution and the detailed feedback prescriptions employed in cosmological simulations, particularly that of active galactic nuclei.
Silver in biology and medicine: opportunities for metallomics researchers
Authors: Betts Harley D , Whitehead Carole , Harris Hugh H
Published: December 2020

The antibacterial properties of silver have been known for centuries and the threat of antibiotic-resistant bacteria has led to renewed focus on the noble metal. Silver is now commonly included in a range of household and medical items to imbue them with bactericidal properties. Despite this, the chemical fate of the metal in biological systems is poorly understood. Silver(I) is a soft metal with high affinity for soft donor atoms and displays much similarity to the chemistry of Cu(I). In bacteria, interaction of silver with the cell wall/membrane, DNA, and proteins and enzymes can lead to cell death. Additionally, the intracellular generation of reactive oxygen species by silver is posited to be a significant antimicrobial action. While the antibacterial action of silver is well known, bacteria found in silver mines display resistance against it through use of a protein ensemble thought to have been specifically developed for the metal, highlighting the need for judicious use. In mammals, ∼10–20% of ingested silver is retained by the body and thought to predominantly localize in the liver or kidneys. Chronic exposure can result in argyria, a condition characterized by blue staining of the skin, resulting from subdermal deposition of silver [as Ag(0)/sulfides], but more insidious side effects, such as inclusions in the brain, seizures, liver/kidney damage, and immunosuppression, have also been reported. Here, we hope to highlight the current understanding of the biological chemistry of silver and the necessity for continued study of these systems to fill existing gaps in knowledge.
The importance of infants’ lipid intake in human milk research
Authors: George Alexandra D , Gay Melvin C L , Wlodek Mary E , Geddes Donna T
Published: December 2020

Human milk lipids are among the many nutrients delivered to the infant, providing >50% of the infant’s calorie intake. These lipids are highly complex and variable, and bioactive, contributing to infant growth, development, and health. The lipid concentration of milk samples is often measured in human cohorts; however, few studies measure infant intake of milk. Intake is important because it considers the variability of both lipid concentration and infants’ consumed volume of milk. Measurement of infants’ lipid intake in exclusively breastfeeding infants requires 3 main considerations: human milk sampling protocol (ie, the collection of representative samples); measurement of the infant milk intake, because volume varies widely between infants; and appropriate analytical laboratory methods. The purpose of this review was to provide an overview of existing methodology and demonstrate the importance of measuring infants’ lipid intake to understand the impact that human milk lipids have on infant outcomes.
Robotic Resection of a Nerve Sheath Tumor Via a Retroperitoneal Approach
Authors: Rapoport Benjamin I , Sze Christina , Chen Xi , Hussain Ibrahim , Bilsky Mark H , Laufer Ilya , Goh Alvin C , Barzilai Ori
Published: December 2020

BACKGROUND

Resection of large nerve sheath tumors in the lumbar spine using minimally invasive approaches is challenging, as approaches to tumors in this region may require facetectomy or partial resection of adjacent ribs for access to the involved neuroforamen and instrumentation across the involved joint to prevent subsequent kyphotic deformity.

OBJECTIVE

To describe a robot-assisted retroperitoneal approach for resection of a lumbar nerve sheath tumor, obviating the need for facetectomy and instrumentation. The operation is described, together with intraoperative images and an annotated video, in the context of a schwannoma arising from the right L1 root.

METHODS

The operation was performed by a urologic surgeon and a neurosurgeon. The patient was placed in lateral position, and the da Vinci Xi robot was used for retroperitoneal access via 5 ports along the right flank. Ultrasound was used to localize the tumor within the psoas. The tumor capsule was defined and released. Encountered nerves were stimulated, allowing small sensory nerves to be identified and safely divided. The tumor was traced into the right L1-L2 neuroforamen and removed.

RESULTS

Complete en bloc resection of the tumor was achieved, including the paraspinal and foraminal components, without any removal of bone and without violation of the dura.

CONCLUSION

In selected patients, a robot-assisted retroperitoneal approach represents a minimally invasive alternative to traditional approaches for resection of lumbar nerve sheath tumors. This approach obviates the need for bone removal and instrumented spinal fusion. Interdisciplinary collaboration, as well as use of adjunctive technologies, including intraoperative ultrasound and neurophysiologic monitoring, is advised.
Pain Experiences of Adults With Sickle Cell Disease and Hematopoietic Stem Cell Transplantation: A Qualitative Study
Authors: Abu Al Hamayel Nebras , Waldfogel Julie M , Hannum Susan M , Brodsky Robert A , Bolaños-Meade Javier , Gamper Christopher J , Jones Richard J , Dy Sydney M
Published: December 2020

Objective

Despite increasing use of hematopoietic stem cell transplantation (HSCT) for adults with sickle cell disease (SCD), little is known about pain management experiences throughout this process. The objective of this study was to explore patients’ experiences with pain and pain management during and after HSCT for SCD.

Methods

We conducted a qualitative interview study with 10 patients who underwent HSCT for SCD. We transcribed interviews verbatim and inductively identified codes. We used thematic analysis alongside a constant comparative method to develop and refine a codebook that aided in the identification of themes.

Results

Four key themes emerged. (1) The pain trajectory: patients described a fluctuating course of pain during HSCT, which often extended long afterwards and impacted all aspects of life, particularly affected by pre-HSCT experiences; (2) The role of opioids—a double-edged sword: patients described opioids as reducing pain but insufficiently to balance significant adverse effects and burden; (3) Patient-centered decision making in pain management: patients described insufficient agency in decisions about opioid use and weaning; and (4) Consequences of health-related stigma: patients described experiences with stigma, mainly related to opioid use and weaning, as similar to pre-HSCT.

Conclusions

From the perspective of patients who have undergone HSCT for SCD, clinicians should use a patient-centered approach, integrating non-opioid approaches into pain management, particularly psychosocial support. As transplant for SCD becomes increasingly available, incorporating patient perspectives may improve health care delivery and overall patient experiences.
The Price of Law: The Case of the Eurozone Collective Action Clauses
Authors: Carletti Elena , Colla Paolo , Gulati Mitu , Ongena Steven
Published: December 2020

We analyze the price effect of the introduction of collective action clauses (CACs) in newly issued sovereign bonds of eurozone countries as of January 1, 2013. By allowing a majority of creditors to modify payment obligations, such clauses reduce the likelihood of holdouts, while facilitating strategic default by the sovereign. We find that CAC bonds trade in the secondary market at lower yields than otherwise similar no-CAC bonds. The yield differential widens in countries with worse ratings and in those with stronger legal systems, especially if of midrange quality. Hence, CACs are seen as pro- rather than anticreditor provisions.
Animal models of narcolepsy and the hypocretin/orexin system: Past, present, and future
Authors: Tisdale Ryan K , Yamanaka Akihiro , Kilduff Thomas S
Published: December 2020

Animal models have advanced not only our understanding of the etiology and phenotype of the sleep disorder narcolepsy but have also informed sleep/wake regulation more generally. The identification of an inheritable narcolepsy phenotype in dogs in the 1970s allowed the establishment of a breeding colony at Stanford University, resulting in studies that provided the first insights into the genetics and neurotransmitter systems that underlie cataplexy and rapid-eye movement sleep atonia. Although the discovery of the hypocretin/orexin neuropeptides in 1998 initially seemed unrelated to sleep/wake control, the description of the phenotype of the prepro-orexin knockout (KO) mouse as strongly resembling cataplexy, the pathognomonic symptom of narcolepsy, along with identification of a mutation in hypocretin receptor-2 gene as the source of canine narcolepsy, unequivocally established the relationship between this system and narcolepsy. The subsequent discovery of hypocretin neuron degeneration in human narcolepsy demystified a disorder whose etiology had been unknown since its initial description 120 years earlier. These breakthroughs prompted the development of numerous other animal models that have allowed manipulation of the hypocretin/orexin system, thereby advancing our understanding of sleep/wake circuitry. While animal models have greatly informed understanding of this fascinating disorder and the role of the hypocretin/orexin system in sleep/wake control, the question of why these neurons degenerate in human narcolepsy is only beginning to be understood. The development of new immune-mediated narcolepsy models are likely to further inform the etiology of this sleep disorder and animal models will undoubtedly play a critical role in the development of novel narcolepsy therapeutics.
Building a biofoundry
Authors: Holowko Maciej B , Frow Emma K , Reid Janet C , Rourke Michelle , Vickers Claudia E
Published: December 2020

A biofoundry provides automation and analytics infrastructure to support the engineering of biological systems. It allows scientists to perform synthetic biology and aligned experimentation on a high-throughput scale, massively increasing the solution space that can be examined for any given problem or question. However, establishing a biofoundry is a challenging undertaking, with numerous technical and operational considerations that must be addressed. Using collated learnings, here we outline several considerations that should be addressed prior to and during establishment. These include drivers for establishment, institutional models, funding and revenue models, personnel, hardware and software, data management, interoperability, client engagement and biosecurity issues. The high cost of establishment and operation means that developing a long-term business model for biofoundry sustainability in the context of funding frameworks, actual and potential client base, and costing structure is critical. Moreover, since biofoundries are leading a conceptual shift in experimental design for bioengineering, sustained outreach and engagement with the research community are needed to grow the client base. Recognition of the significant, long-term financial investment required and an understanding of the complexities of operationalization is critical for a sustainable biofoundry venture. To ensure state-of-the-art technology is integrated into planning, extensive engagement with existing facilities and community groups, such as the Global Biofoundries Alliance, is recommended.
Medicine donation programmes supporting the global drive to end the burden of neglected tropical diseases
Authors: Bradley Mark , Taylor Rachel , Jacobson Julie , Guex Morgane , Hopkins Adrian , Jensen Julie , Leonard Lynn , Waltz Johannes , Kuykens Luc , Sow Papa Salif , Madeja Ulrich-Dietmar , Hida Takayuki , Ole-Moiyoi Kileken , King Jonathan , Argaw Daniel , Mohamed Jamsheed , Polo Maria Rebollo , Yajima Aya , Ottesen Eric
Published: December 2020

Neglected tropical diseases (NTDs) are targeted for global control or elimination. Recognising that the populations most in need of medicines to target NTDs are those least able to support and sustain them financially, the pharmaceutical industry created mechanisms for donating medicines and expertise to affected countries through partnerships with the WHO, development agencies, non-governmental organisations and philanthropic donors. In the last 30 y, companies have established programmes to donate 17 different medicines to overcome the burden of NTDs. Billions of tablets, capsules, intravenous and oral solutions have been donated, along with the manufacturing, supply chains and research necessary to support these efforts. Industry engagement has stimulated other donors to support NTDs with funds and oversight so that the ‘heath benefit’ return on investment in these programmes is truly a ‘best value in public health’. Many current donations are ‘open-ended’, promising support as long as necessary to achieve defined health targets. Extraordinary global health advances have been made in filariasis, onchocerciasis, trachoma, trypanosomiasis, leishmaniasis, schistosomiasis, intestinal parasites and others; and these advances are taking place in the context of strengthening health systems and meeting the global development goals espoused by the WHO. The pharmaceutical manufacturers, already strong collaborators in initiating or supporting these disease-targeted programmes, have committed to continuing their partnership roles in striving to meet the targets of the WHO's new NTD roadmap to 2030.
Quantitative differences between intra-host HCV populations from persons with recently established and persistent infections
Authors: Icer Baykal Pelin B , Lara James , Khudyakov Yury , Zelikovsky Alex , Skums Pavel
Published: December 2020

Detection of incident hepatitis C virus (HCV) infections is crucial for identification of outbreaks and development of public health interventions. However, there is no single diagnostic assay for distinguishing recent and persistent HCV infections. HCV exists in each infected host as a heterogeneous population of genomic variants, whose evolutionary dynamics remain incompletely understood. Genetic analysis of such viral populations can be applied to the detection of incident HCV infections and used to understand intra-host viral evolution. We studied intra-host HCV populations sampled using next-generation sequencing from 98 recently and 256 persistently infected individuals. Genetic structure of the populations was evaluated using 245,878 viral sequences from these individuals and a set of selected features measuring their diversity, topological structure, complexity, strength of selection, epistasis, evolutionary dynamics, and physico-chemical properties. Distributions of the viral population features differ significantly between recent and persistent infections. A general increase in viral genetic diversity from recent to persistent infections is frequently accompanied by decline in genomic complexity and increase in structuredness of the HCV population, likely reflecting a high level of intra-host adaptation at later stages of infection. Using these findings, we developed a machine learning classifier for the infection staging, which yielded a detection accuracy of 95.22 per cent, thus providing a higher accuracy than other genomic-based models. The detection of a strong association between several HCV genetic factors and stages of infection suggests that intra-host HCV population develops in a complex but regular and predictable manner in the course of infection. The proposed models may serve as a foundation of cyber-molecular assays for staging infection, which could potentially complement and/or substitute standard laboratory assays.