bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hybrid Strategy Improved Whale Optimization Algorithm for Web Service Composition
Authors: Ju Chuanxiang , Ding Hangqi , Hu Benjia
Published: November 2021

With the rapid growth of the number of web services on the Internet, various service providers provide many similar services with the same function but different quality of service (QoS) attributes. It is a key problem to be solved urgently to select the service composition quickly, meeting the users’ QoS requirements from many candidate services. Optimization of web service composition is an NP-hard issue and intelligent optimization algorithms have become the mainstream method to solve this complex problem. This paper proposed a hybrid strategy improved whale optimization algorithm, which is based on the concepts of chaos initialization, nonlinear convergence factor and mutation. By maintaining a balance between exploration and exploitation, the problem of slow or early convergence is overcome to a certain extent. To evaluate its performance more accurately, the proposed algorithm was first tested on a set of standard benchmarks. After, simulations were performed using the real quality of web service dataset. Experimental results show that the proposed algorithm is better than the original version and other meta-heuristic algorithms on average, as well as verifies the feasibility and stability of web service composition optimization.
Provable Data Possession Schemes from Standard Lattices for Cloud Computing
Authors: Luo Fucai , Al-Kuwari Saif , Lin Changlu , Wang Fuqun , Chen Kefei
Published: November 2021

Provable Data Possession (PDP) is of crucial importance in public cloud storage since it allows users to check the integrity of their outsourced data without downloading it. However, the existing PDP schemes, which are based on classical number-theoretic assumptions, are insecure under quantum attacks. In this paper, we propose the first PDP scheme from standard lattices, using a specific leveled fully homomorphic signature (FHS) scheme. To remove the complex key management of PDP cryptosystem on the public key infrastructure (PKI) setting, we employ a specific leveled identity-based (ID-based) FHS scheme to construct the first ID-based PDP scheme from standard lattices. Our two PDP schemes are secure under the standard small integer solution (SIS) assumption, which is conjectured to withstand quantum attacks. Furthermore, we conduct experimental evaluations to validate the feasibility of the proposed PDP schemes in practice.
A Systematic Review of Simulation Models to Track and Address the Opioid Crisis
Authors: Cerdá Magdalena , Jalali Mohammad S , Hamilton Ava D , DiGennaro Catherine , Hyder Ayaz , Santaella-Tenorio Julian , Kaur Navdep , Wang Christina , Keyes Katherine M
Published: November 2021

The opioid overdose crisis is driven by an intersecting set of social, structural, and economic forces. Simulation models are a tool to help us understand and address thiscomplex, dynamic, and nonlinear social phenomenon. We conducted a systematic review of the literature on simulation models of opioid use and overdose up to September 2019. We extracted modeling types, target populations, interventions, and findings; created a database of model parameters used for model calibration; and evaluated study transparency and reproducibility. Of the 1,398 articles screened, we identified 88 eligible articles. The most frequent types of models were compartmental (36%), Markov (20%), system dynamics (16%), and agent-based models (16%). Intervention cost-effectiveness was evaluated in 40% of the studies, and 39% focused on services for people with opioid use disorder (OUD). In 61% of the eligible articles, authors discussed calibrating their models to empirical data, and in 31%, validation approaches used in the modeling process were discussed. From the 63 studies that provided model parameters, we extracted the data sources on opioid use, OUD, OUD treatment, cessation or relapse, emergency medical services, and death parameters. From this database, potential model inputs can be identified and models can be compared with prior work. Simulation models should be used to tackle key methodological challenges, including the potential for bias in the choice of parameter inputs, investment in model calibration and validation, and transparency in the assumptions and mechanics of simulation models to facilitate reproducibility.
A conserved loop structure of GH19 chitinases assists the enzyme function from behind the core-functional region
Authors: Kawamoto Daiki , Takashima Tomoya , Fukamizo Tamo , Numata Tomoyuki , Ohnuma Takayuki
Published: November 2021

Plant GH19 chitinases have several loop structures, which may define their enzymatic properties. Among these loops, the longest loop, Loop-III, is most frequently conserved in GH19 enzymes. A GH19 chitinase from the moss Bryum coronatum (BcChi-A) has only one loop structure, Loop-III, which is connected to the catalytically important β-sheet region. Here, we produced and characterized a Loop-III-deleted mutant of BcChi-A (BcChi-A-ΔIII) and found that its stability and chitinase activity were strongly reduced. The deletion of Loop-III also moderately affected the chitooligosaccharide binding ability as well as the binding mode to the substrate-binding groove. The crystal structure of an inactive mutant of BcChi-A-ΔIII was successfully solved, revealing that the remaining polypeptide chain has an almost identical fold to that of the original protein. Loop-III is not necessarily essential for the folding of the enzyme protein. However, closer examination of the crystal structure revealed that the deletion of Loop-III altered the arrangement of the catalytic triad, Glu61, Glu70 and Ser102, and the orientation of the Trp103 side chain, which is important for sugar residue binding. We concluded that Loop-III is not directly involved in the enzymatic activity but assists the enzyme function by stabilizing the conformation of the β-sheet region and the adjacent substrate-binding platform from behind the core-functional regions.
International Law
Authors: Hernández Gleider
Published: November 2021

International Law presents a comprehensive approach to the subject, providing a contemporary account of international law. The text offers critical and stimulating coverage of the central issues in public international law, introducing the key areas of debate. It encourages readers to engage with areas of legal debate and controversy and consider how they affect the world today. Topics covered include: the structure of international law; the subjects within the field of international law; international law in operation; international disputes and responses to breaches in international law; and specialized regimes, which includes the law of armed conflict, refugee law, international criminal law, the law of the sea, the environment and protection, and international economic law.
The effect of allergy and asthma as a comorbidity on the susceptibility and outcomes of COVID-19
Authors: Gao Ya-dong , Agache Ioana , Akdis Mübeccel , Nadeau Kari , Klimek Ludger , Jutel Marek , Akdis Cezmi A
Published: November 2021

The coronavirus disease 2019 (COVID-19) pandemic causes an overwhelming number of hospitalization and deaths with a significant socioeconomic impact. The vast majority of studies indicate that asthma and allergic diseases do not represent a risk factor for COVID-19 susceptibility nor cause a more severe course of disease. This raises the opportunity to investigate the underlying mechanisms of the interaction between an allergic background and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The majority of patients with asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies and drug allergies exhibit an over-expression of type 2 immune and inflammatory pathways with the contribution of epithelial cells, innate lymphoid cells, dendritic cells, T cells, eosinophils, mast cells, basophils, and the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31. The potential impact of type 2 inflammation-related allergic diseases on susceptibility to COVID-19 and severity of its course have been reported. In this review, the prevalence of asthma and other common allergic diseases in COVID-19 patients is addressed. Moreover, the impact of allergic and non-allergic asthma with different severity and control status, currently available asthma treatments such as inhaled and oral corticosteroids, short- and long-acting β2 agonists, leukotriene receptor antagonists and biologicals on the outcome of COVID-19 patients is reviewed. In addition, possible protective mechanisms of asthma and type 2 inflammation on COVID-19 infection, such as the expression of SARS-CoV-2 entry receptors, antiviral activity of eosinophils and cross-reactive T-cell epitopes, are discussed. Potential interactions of other allergic diseases with COVID-19 are postulated, including recommendations for their management.
In vitro study of factors influencing the duration of antimicrobial protection of antimicrobial-impregnated external ventricular drains
Authors: Lang Elodie , Hulin Anne , Egbeola-Martial Julia , Woerther Paul-Louis , Drouard Leonard , Roujansky Ariane , Tomberli Françoise , Bardon Jean , Schimpf Caroline , Senova Suhan , Cook Fabrice , Lebeaux David , Mounier Roman
Published: November 2021

Background

In vitro and clinical studies assessing the duration of the protective activity of antimicrobial-impregnated external ventricular drains (AI-EVDs) gave conflicting results.

Objectives

To identify factors associated with decreased antimicrobial activity of AI-EVDs that were not taken into account in previous in vitro models.

Methods

We performed in vitro experiments with Bactiseal™ AI-EVDs, under different conditions. Tested parameters were chosen to mimic conditions in which AI-EVDs are used: perfusion by saline (at different flow rates) or not perfused, dwelling medium (air, saline, saline+protein, lipid) and temperature. Antimicrobial activity was assessed by measurement of inhibitory diameters of a 0.5 cm portion of an AI-EVD (cut every 2 days) placed onto agar plates covered by a standardized Staphylococcus spp. inoculum (three different isolates). MS was used to measure concentrations of rifampicin and clindamycin after 48 h of dwelling.

Results

In univariate analysis, most of the tested factors were associated with reduced antimicrobial activity: liquid media (as compared with ambient air), perfusion whatever the rate flow (as compared with no perfusion) and presence of protein in the media. In multivariate analysis, dwelling in media (lipid or saline) was the most constantly associated with a reduction of inhibition diameters (P < 0.01), as compared with ambient air. After 48 h of dwelling, the clindamycin concentration was higher than 100 and 450 mg/L in saline and saline+BSA, respectively.

Conclusions

The medium in which an AI-EVD is dwelling plays a significant role in the duration of AI-EVD activity. These results may explain conflicting results between clinical and in vitro studies.
A procedure for removal of cyanuric acid in swimming pools using a cell-free thermostable cyanuric acid hydrolase
Authors: Guo Feng , McAuliffe Joseph C , Bongiorni Cristina , Latone Jacob A , Pepsin Mike J , Chow Marina S , Dhaliwal Raj S , Hoffmann Katherine M , Brazil Bill T , Heng Meng H , Robinson Serina L , Wackett Lawrence P , Whited Gregory M
Published: November 2021

Cyanuric acid (CYA) is used commercially for maintaining active chlorine to inactivate microbial and viral pathogens in swimming pools and hot tubs. Repeated CYA addition can cause a lack of available chlorine and adequate disinfection. Acceptable CYA levels can potentially be restored via cyanuric acid hydrolases (CAH), enzymes that hydrolyze CYA to biuret under mild conditions. Here we describe a previously unknown CAH enzyme from Pseudolabrys sp. Root1462 (CAH-PR), mined from public databases by bioinformatic analysis of potential CAH genes, which we show to be suitable in a cell-free form for industrial applications based upon favorable enzymatic and physical properties, combined with high-yield expression in aerobic cell culture. The kinetic parameters and modeled structure were similar to known CAH enzymes, but the new enzyme displayed a surprising thermal and storage stability. The new CAH enzyme was applied, following addition of inexpensive sodium sulfite, to hydrolyze CYA to biuret. At the desired endpoint, hypochlorite addition inactivated remaining enzyme and oxidized biuret to primarily dinitrogen and carbon dioxide gases. The mechanism of biuret oxidation with hypochlorite under conditions relevant to recreational pools is described.
Isolation and analysis of a sake yeast mutant with phenylalanine accumulation
Authors: Nishimura Akira , Isogai Shota , Murakami Naoyuki , Hotta Natsuki , Kotaka Atsushi , Matsumura Kengo , Hata Yoji , Ishida Hiroki , Takagi Hiroshi
Published: November 2021

Sake is a traditional Japanese alcoholic beverage brewed by the yeast Saccharomyces cerevisiae. Since the consumption and connoisseurship of sake has spread around the world, the development of new sake yeast strains to meet the demand for unique sakes has been promoted. Phenylalanine is an essential amino acid that is used to produce proteins and important signaling molecules involved in feelings of pleasure. In addition, phenylalanine is a precursor of 2-phenylethanol, a high-value aromatic alcohol with a rose-like flavor. As such, adjusting the quantitative balance between phenylalanine and 2-phenylethanol may introduce value-added qualities to sake. Here, we isolated a sake yeast mutant (strain K9-F39) with phenylalanine accumulation and found a missense mutation on the ARO80 gene encoding the His309Gln variant of the transcriptional activator Aro80p involved in the biosynthesis of 2-phenylethanol from phenylalanine. We speculated that mutation of ARO80 would decrease transcriptional activity and suppress the phenylalanine catabolism, resulting in an increase of intracellular phenylalanine. Indeed, sake brewed with strain K9-F39 contained 60% increase in phenylalanine, but only 10% less 2-phenylethanol than sake brewed with the parent strain. Use of the ARO80 mutant in sake brewing may be promising for the production of distinctive new sake varieties.

One-Sentence Summary

The ARO80 mutant is appropriate for controlling the content of phenylalanine and 2-phenylethanol.
Experience and Outcomes of Breastfed Infants of Women Living With HIV in the United States: Findings From a Single-Center Breastfeeding Support Initiative
Authors: Yusuf Hasiya E , Knott-Grasso Mary Ann , Anderson Jean , Livingston Alison , Rosenblum Nadine , Sturdivant Heather , Byrnes Kristen C , Powell Anna , Sheffield Jeanne S , Enns Justine , Persaud Deborah , Golden William Christopher , Agwu Allison L
Published: November 2021

We assessed breastfeeding outcomes for a cohort of infants born to women living with HIV (WLHIV) at an urban health care center in the United States. Ten infants were exclusively breastfed for a mean duration of 4.4 (1.0-8.6) months. All had negative HIV RNA PCRs at a median age of 16 months.
Hydrogen peroxide modulates silica deposits in sorghum roots
Authors: Zexer Nerya , Elbaum Rivka
Published: November 2021

Hydrated silica (SiO2·nH2O) aggregates in the root endodermis of grasses. Application of soluble silicates (Si) to roots is associated with variations in the balance of reactive oxygen species (ROS), increased tolerance to a broad range of stresses affecting ROS concentrations, and early lignin deposition. In sorghum (Sorghum bicolor L.), silica aggregation is patterned in an active silicification zone (ASZ) by a special type of aromatic material forming a spotted pattern. The deposition has a signature typical of lignin. Since lignin polymerization is mediated by ROS, we studied the formation of root lignin and silica controlled by ROS via modulating hydrogen peroxide (H2O2) concentrations in the growth medium. Sorghum seedlings were grown hydroponically and supplemented with Si, H2O2, and KI, an ionic compound that catalyses H2O2 decomposition. Lignin and silica deposits in the endodermis were studied by histology, scanning electron and Raman microscopies. Cell wall composition was quantified by thermal gravimetric analysis. Endodermal H2O2 concentration correlated to the extent of lignin-like deposition along the root, but did not affect its patterning in spots. Our results show that the ASZ spots were necessary for root silica aggregation, and suggest that silicification is intensified under oxidative stress as a result of increased ASZ lignin-like deposition.
Inflow of low-metallicity cool gas in the halo of the Andromeda galaxy
Authors: Afruni Andrea , Pezzulli Gabriele , Fraternali Filippo
Published: November 2021

As the closest L* galaxy to our own Milky Way, the Andromeda galaxy (M31) is an ideal laboratory for studies of galaxy evolution. The AMIGA project has recently provided observations of the cool (T ∼ 104 K) phase of the circumgalactic medium (CGM) of M31, using HST/COS absorption spectra along ∼40 background QSO sightlines, located up to and beyond the galaxy virial radius. Based on these data, and by the means of semi-analytic models and Bayesian inference, we provide here a physical description of the origin and dynamics of the cool CGM of M31. We investigate two competing scenarios, in which (i) the cool gas is mostly produced by supernova(SN)-driven galactic outflows or (ii) it mostly originates from infall of gas from the intergalactic medium. In both cases, we take into account the effect of gravity and hydrodynamical interactions with a hot corona, which has a cosmologically motivated angular momentum. We compare the outputs of our models to the observed covering factor, silicon column density and velocity distribution of the AMIGA absorbers. We find that, to explain the observations, the outflow scenario requires an unphysically large (> 100%) efficiency for SN feedback. Our infall models, on the other hand, can consistently account for the AMIGA observations and the predicted accretion rate, angular momentum and metallicity are consistent with a cosmological infall from the intergalactic medium.
Proton cyclotron and mirror instabilities in marginally stable solar wind plasma
Authors: Yoon P H , Sarfraz M , Ali Z , Salem C S , Seough J
Published: November 2021

This paper formulates a velocity moment-based quasi-linear theory that combines the impacts of weakly unstable proton–cyclotron- (or, equivalently, electromagnetic ion cyclotron) and proton-mirror instabilities on the solar wind plasma initially characterized by an excessive perpendicular proton temperature anisotropy. The present formalism is an alternative to the existing model in that the weakly unstable modes are characterized by analytical formalism that involves the assumption of weak growth rate and/or fluid-theoretical dispersion relation, in place of numerical root-finding method based on the transcendental plasma dispersion function. This results in an efficient numerical platform for analyzing the quasi-linear development of the said instabilities. Such a formalism may be useful in the larger context of global solar wind modelling effort where an efficient calculation of self-consistent wave–particle interaction process is called for. A direct comparison with spacecraft observations of solar wind proton data distribution shows that the present weak growth rate formalism of quasi-linear calculation produces results that are consistent with the observation.
BrdU immuno-tagged G-quadruplex ligands: a new ligand-guided immunofluorescence approach for tracking G-quadruplexes in cells
Authors: Masson Thibaut , Landras Guetta Corinne , Laigre Eugénie , Cucchiarini Anne , Duchambon Patricia , Teulade-Fichou Marie-Paule , Verga Daniela
Published: November 2021

G-quadruplexes (G4s) are secondary structures forming in G-rich nucleic acids. G4s are assumed to play critical roles in biology, nonetheless their detection in cells is still challenging. For tracking G4s, synthetic molecules (G4 ligands) can be used as reporters and have found wide application for this purpose through chemical functionalization with a fluorescent tag. However, this approach is limited by a low-labeling degree impeding precise visualization in specific subcellular regions. Herein, we present a new visualization strategy based on the immuno-recognition of 5-bromo-2′-deoxyuridine (5-BrdU) modified G4 ligands, functionalized prior- or post-G4-target binding by CuAAC. Remarkably, recognition of the tag by antibodies leads to the detection of the modified ligands exclusively when bound to a G4 target both in vitro, as shown by ELISA, and in cells, thereby providing a highly efficient G4-ligand Guided Immunofluorescence Staining (G4-GIS) approach. The obtained signal amplification revealed well-defined fluorescent foci located in the perinuclear space and RNase treatment revealed the preferential binding to G4-RNA. Furthermore, ligand treatment affected significantly BG4 foci formation in cells. Our work headed to the development of a new imaging approach combining the advantages of immunostaining and G4-recognition by G4 ligands leading to visualization of G4/ligands species in cells with unrivaled precision and sensitivity.
WHIRLY1 of Barley and Maize Share a PRAPP Motif Conferring Nucleoid Compaction
Authors: Oetke Svenja , Scheidig Axel J , Krupinska Karin
Published: November 2021

WHIRLY1 in barley was shown to be a major architect of plastid nucleoids. Its accumulation in cells of Escherichia coli coincided with an induction of nucleoid compaction and growth retardation. While WHIRLY1 of maize had similar effects on E. coli cells, WHIRLY1 proteins of Arabidopsis and potato as well as WHIRLY2 proteins had no impact on nucleoid compaction in E. coli. By mutagenesis of HvWHIRLY1 the PRAPP motif at the N-terminus preceding the highly conserved WHIRLY domain was identified to be responsible for the nucleoid compacting activity of HvWHIRLY1 in bacteria. This motif is found in WHIRLY1 proteins of most members of the Poaceae family, but neither in the WHIRLY2 proteins of the family nor in any WHIRLY protein of eudicot species such as Arabidopsis thaliana. This finding indicates that a subset of the monocot WHIRLY1 proteins has acquired a specific function as nucleoid compacters by sequence variation in the N-terminal part preceding the conserved WHIRLY domain and that in different groups of higher plants the compaction of nucleoids is mediated by other proteins.
Allosteric Modulation of the Sigma-1 Receptor Elicits Antipsychotic-like Effects
Authors: Chen Jiali , Li Guangying , Qin Pingping , Chen Jiaojiao , Ye Na , Waddington John L , Zhen Xuechu
Published: November 2021

Allosteric modulation represents an important approach in drug discovery because of its advantages in safety and selectivity. SOMCL-668 is the first selective and potent sigma-1 receptor allosteric modulator, discovered in our laboratory. The present work investigates the potential therapeutic effects of SOMCL-668 on phencyclidine (PCP)-induced schizophrenia-related behavior in mice and further elucidates underlying mechanisms for its antipsychotic-like effects. SOMCL-668 not only attenuated acute PCP-induced hyperactivity and PPI disruption, but also ameliorated social deficits and cognitive impairment induced by chronic PCP treatment. Pretreatment with the selective sigma-1 receptor antagonist BD1047 blocked the effects of SOMCL-668, indicating sigma-1 receptor-mediated responses. This was confirmed using sigma-1 receptor knockout mice, in which SOMCL-668 failed to ameliorate PPI disruption and hyperactivity induced by acute PCP and social deficits and cognitive impairment induced by chronic PCP treatment. Additionally, in vitro SOMCL-668 exerted positive modulation of sigma-1 receptor agonist-induced intrinsic plasticity in brain slices recorded by patch-clamp. Furthermore, in vivo lower dose of SOMCL-668 exerted positive modulation of improvement in social deficits and cognitive impairment induced by the selective sigma-1 agonist PRE084. Also, SOMCL-668 reversed chronic PCP-induced down-regulation in expression of frontal cortical p-AKT/AKT, p-CREB/CREB and BDNF in wide-type but not sigma-1 knockout mice. Moreover, administration of the PI3K/AKT inhibitor LY294002 abolished amelioration by SOMCL-668 of chronic PCP-induced schizophrenia-related behaviors by inhibition of BDNF expression. The present data provide initial, proof-of-concept evidence that allosteric modulation of the sigma-1 receptor may be a novel approach for the treatment of psychotic illness.
Protected through Part-time Employment? Labor Market Status, Domestic Responsibilities, and the Life Satisfaction of German Women during the COVID-19 Pandemic
Authors: Bertogg Ariane , Kulic Nevena , Strauss Susanne
Published: November 2021

The COVID-19 lockdown measures have challenged individuals to reconcile employment, childcare, and housework. This article addresses whether these challenges have reduced life satisfaction among German women by focusing on their labor market status and drawing upon a topical online survey (Kantar) collected in Germany at two points in time: May 2020 and November 2020. We find that part-time employed women were better protected against a decline in life satisfaction, but only during the first lockdown. Economically inactive women were most likely to experience a decline in life satisfaction during the first lockdown, but least likely during the second lockdown. Life satisfaction has further decreased between the first and the second lockdown, and the likelihood of a decrease has converged for full-time, part-time, and economically inactive women.
The dark septate endophyte Phialocephala sphaeroides confers growth fitness benefits and mitigates pathogenic effects of Heterobasidion on Norway spruce
Authors: Wen Zilan , Terhonen Eeva , Asiegbu Fred O
Published: November 2021

Forest trees frequently interact with a diverse range of microorganisms including dark septate endophytes (DSEs) and fungal pathogens. Plant defense responses to either individual pathogens or endophytes have been widely studied, but very little is known on the effect of coinfection on host defenses. To study the impact of coinfection or tripartite interaction on plant growth and host defenses, Norway spruce (Picea abies (L.) Karst) seedlings were inoculated with a DSE Phialocephala sphaeroides or with a root pathogen Heterobasidion parviporum Niemela & Korhonen or coinfected with both fungi. The results showed that the DSE promoted the root growth of spruce seedlings. Control seedlings without any inoculum were subjected to sequencing and used as a baseline for identification of differentially expressed genes (DEGs). RNA-seq analysis of seedlings inoculated with P. sphaeroides, infected with H. parviporum or coinfected with both fungi resulted in a total of 5269 DEGs. The majority of DEGs were found in P. sphaeroides-inoculated seedlings. Lignin biosynthesis pathways were generally activated during fungal infections. The pattern was distinct with endophyte inoculation. The majority of the genes in the flavonoid biosynthesis pathway were generally suppressed during fungal infections. A specific transcriptional response to P. sphaeroides inoculation was the increased transcripts of genes involved in jasmonic acid biosynthesis, mitogen-activated protein kinases signaling pathway, plant hormone signal transduction and calcium-mediated signaling. This may have potentially contributed to promoting the root growth of seedlings. Although the coinfection suppressed the induction of numerous genes, no negative effect on the growth of the spruce seedlings occurred. We conclude that the subsequent H. parviporum infection triggered reprogramming of host metabolism. Conversely, the endophyte (P. sphaeroides), on the other hand, counteracted the negative effects of H. parviporum on the growth of the spruce seedlings.
Exploring Residents’ Well-Being and Burnout via Qualitative Ecological Momentary Assessment
Authors: Shea Judy A. , Bellini Lisa M. , Desai Sanjay V. , Barg Frances K. , Eriksen Whitney , Wietlisbach Larissa E. , Yakubu Abdul-Rakeem , Asch David A.
Published: November 2021

Purpose

Most of what is known about resident burnout and wellness comes from cross-sectional snapshot surveys. The purpose of this study was to elicit qualitative perspectives on wellness from a cohort of internal residents over time using ecological momentary assessment.

Method

Drawing on principles of ecological momentary assessment, 13 different open-ended survey prompts were delivered between October and March during the 2019–2020 academic year. Participants were 88 randomly selected internal medicine residents from 4 internal medicine training programs in the Northeast.

Results

The response rate was 95%. Three main themes regarding wellness were self, program/education environment, and medical/structural system. A fourth theme, the desire to provide quality patient care, cut across all other themes. The patient care theme repeatedly stressed residents’ desire to spend more time with patients. The self theme primarily reflected messages about personal emotions and the need for work–life balance and wellness. The program/education environment theme reflected the value of learning, teamwork and community, and program culture. The medical/structural system theme showed that residents’ experiences were shaped by the efficiency of their days and largely a product of their schedules and administrative support. Closing advice to future trainees was optimistic and reassuring.

Conclusions

While findings support much of what has been learned via single-occasion survey snapshots, an ecological momentary assessment design allowed a deeper dive into contextual associations. The results affirm the primacy of patient care and also highlight the value of teamwork and culture. Peers and program leaders are heavily influential in setting the tone for the learning experience, whether for the day or with a more enduring message of respect and support. There is opportunity to maximize high- or higher-value learning experiences for residents and find solutions to reduce and reframe the perceived “low-value administrative work” that is part of care coordination.
Persistent opioid use in cataract surgery pain management and the role of nonopioid alternatives
Authors: Davidson Richard S. , Donaldson Kendall , Jeffries Maggie , Khandelwal Sumitra , Raizman Michael , Rodriguez Torres Yasaira , Kim Terry
Published: November 2021

Cataracts are a leading cause of preventable blindness globally. Although care varies between developing and industrialized countries, surgery is the single effective approach to treating cataracts. From the earliest documented primitive cataract removals to today's advanced techniques, cataract surgery has evolved dramatically. As surgical techniques have developed, so have approaches to surgical pain management. With current cataract surgical procedures and advanced technology, anesthesia and intraoperative pain management have shifted to topical/intracameral anesthetics, with or without low-dose systemic analgesia and anxiolysis. Despite this, pain and discomfort persist in some patients and are underappreciated in modern cataract surgery. Although pain management has progressed, opioids remain a mainstay intraoperatively and, to a lesser extent, postoperatively. This article discusses the evolution of pain management in cataract surgery, particularly the use of opioids and the associated risks as well as how ophthalmology can have a positive impact on the opioid crisis.
Selective Microvascular Tissue Transfection Using Minicircle DNA for Systemic Delivery of Human Coagulation Factor IX in a Rat Model Using a Therapeutic Flap
Authors: Than Peter A. , Davis Christopher R. , Rennert Robert C. , Morrison Shane D. , Findlay Michael W. , Kay Mark A. , Gurtner Geoffrey C.
Published: November 2021

Background:

Gene therapy is a promising treatment for protein deficiency disorders such as hemophilia B. However, low tissue selectivity and efficacy are limitations of systemic vector delivery. The authors hypothesized that selective transfection of rat superficial inferior epigastric artery flaps could provide systemic delivery of coagulation factor IX, preventing the need for systemic vector administration.

Methods:

Minicircle DNA containing green fluorescent protein, firefly luciferase, and human coagulation factor IX was created. Vector constructs were validated by transfecting adipose-derived stromal cells isolated from Wistar rat superficial inferior epigastric artery flaps and evaluating transgene expression by fluorescence microscopy, bioluminescence, and enzyme-linked immunosorbent assay. Minicircle DNA luciferase (10 and 30 μg) was injected into murine (wild-type, C57/BL/6) inguinal fat pads (n = 3) and followed by in vivo bioluminescence imaging for 60 days. Wistar rat superficial inferior epigastric artery flaps were transfected with minicircle DNA human coagulation factor IX (n = 9) with plasma and tissue transgene expression measured by enzyme-linked immunosorbent assay at 2 and 4 weeks.

Results:

Transfected adipose-derived stromal cells expressed green fluorescent protein for 30 days, luciferase for 43 days, and human coagulation factor IX (21.9 ± 1.2 ng/ml) for 28 days in vitro. In vivo murine studies demonstrated dose-dependence between minicircle DNA delivery and protein expression. Ex vivo rat superficial inferior epigastric artery flap transfection with minicircle DNA human coagulation factor IX showed systemic transgene expression at 2 (266.6 ± 23.4 ng/ml) and 4 weeks (290.1 ± 17.1 ng/ml) compared to control tissue (p < 0.0001).

Conclusions:

Rat superficial inferior epigastric artery flap transfection using minicircle DNA human coagulation factor IX resulted in systemic transgene detection, suggesting that selective flap or angiosome-based tissue transfection may be explored as a treatment for systemic protein deficiency disorders such as hemophilia B.
Uptake, Retention, and Adherence to Pre-exposure Prophylaxis (PrEP) in TRIUMPH: A Peer-Led PrEP Demonstration Project for Transgender Communities in Oakland and Sacramento, California
Authors: Sevelius Jae M. , Glidden David V. , Deutsch Madeline , Welborn Layla , Contreras Alejandro , Salinas Arianna , Venegas Luz , Grant Robert M.
Published: November 2021

Background:

TRIUMPH (Trans Research–Informed communities United in Mobilization for the Prevention of HIV) was a community-led, transgender-specific pre-exposure prophylaxis (PrEP) demonstration project at 2 community-based clinical sites in California. TRIUMPH used peer health education, community mobilization, and clinical integration of PrEP with hormone therapy to promote PrEP knowledge and acceptability. The goal of this study was to evaluate PrEP uptake, retention, and adherence among TRIUMPH participants and examine site-based differences.

Methods:

Eligible participants were adult transgender and gender diverse people interested in PrEP. Participants were seen at baseline and at 1, 3, 6, 9, and 12 months for PrEP provision, clinical visits, and HIV testing. PrEP uptake was defined as dispensation of PrEP, PrEP retention was defined as proportion of expected visits completed among those who initiated PrEP, and PrEP adherence was assessed by measuring tenofovir diphosphate concentrations in dried blood spots. Logistic regression models quantified the association of variables with PrEP outcomes.

Results:

TRIUMPH enrolled 185 participants; the median age was 28 years (interquartile range: 23–35), 7% was Black, and 58% was Latinx. PrEP uptake was as follows: 78% in Oakland and 98% in Sacramento; 91% among trans women, 96% among trans men, and 70% among nonbinary participants. Almost half (47%) rarely/never believed about HIV, and 42% reported condomless sex act in the past 3 months. Participants who reported higher numbers of sex partners were more likely to be retained and adherent; other predictors of adherence included not having a primary partner and not experiencing violence in the past 3 months.

Conclusions:

This community-led, trans-specific PrEP demonstration project documents high levels of PrEP initiation in a young transgender and gender diverse cohort at risk of HIV acquisition.
Pro-Resolving Mediator Resolvin E1 Restores Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome
Authors: Luo Jun , Zhang Wen-Yan , Li Hui , Zhang Pu-Hong , Tian Chao , Wu Cheng-Hua , Zhao An-Ning , Chen Man-Ling , Guo Yi-Fan , Cho Young-Chang , Jin Sheng-Wei , Hao Yu
Published: November 2021

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 μg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8–9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 μg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na+/K+-ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P 
< 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P 
< 0.001), mitigated lung injury scores (13.38 vs. 7.0, P 
< 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro. In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3’-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.
Narwhals react to ship noise and airgun pulses embedded in background noise
Authors: Tervo Outi M. , Blackwell Susanna B. , Ditlevsen Susanne , Conrad Alexander S. , Samson Adeline L. , Garde Eva , Hansen Rikke G. , Mads Peter Heide-Jørgensen
Published: November 2021

Anthropogenic activities are increasing in the Arctic, posing a threat to niche-conservative species with high seasonal site fidelity, such as the narwhalMonodon monoceros. In this controlled sound exposure study, six narwhals were live-captured and instrumented with animal-borne tags providing movement and behavioural data, and exposed to concurrent ship noise and airgun pulses. All narwhals reacted to sound exposure with reduced buzzing rates, where the response was dependent on the magnitude of exposure defined as 1/distance to ship. Buzzing rate was halved at 12 km from the ship, and whales ceased foraging at 7–8 km. Effects of exposure could be detected at distances > 40 km from the ship.At only a few kilometres from the ship, the received high-frequency cetacean weighted sound exposure levels were below background noise indicating extreme sensitivity of narwhals towards sound disturbance and demonstrating their ability to detect signals embedded in background noise. The narwhal's reactions to sustained disturbance may have a plethora of consequences both at individual and population levels. The observed reactions of the whales demonstrate their auditory sensitivity but also emphasize, that anthropogenic activities in pristine narwhal habitats needs to be managed carefully if healthy narwhal populations are to be maintained.
The interplay between Fano and Fabry–Pérot resonances in dual-period metagratings
Authors: Zhou Hagström Joar , Maurel Agnès , Pham Kim
Published: November 2021

We study theoretically and numerically the occurrence of Fano resonances in a metagrating made of slits with some symmetry breaking resulting in a dual period. At low frequency, a grating composed of long enough slits supports Fabry–Pérot resonances on which Fano resonances superimpose when the grating acquires dual period. The resulting spectrum exhibits flat-banded peaks interrupted by sharp dips with successions of perfect and zero transmissions. To model these scattering properties, homogenization theory is used resulting in an effective problem governing the solutions in the two, non-identical, slits, which are coupled through jump conditions at the grating interfaces. These jumps efficiently encode the effect of the evanescent field able to resonate in the radiative region due to the folding of the spoof plasmon polaritons branches. The model is validated with direct numerics and a local analysis allows us to characterize the resonant mechanisms.
Decoupling cooperation and punishment in humans shows that punishment is not an altruistic trait
Authors: Burton-Chellew Maxwell N. , Guérin Claire
Published: November 2021

Economic experiments have suggested that cooperative humans will altruistically match local levels of cooperation (conditional cooperation) and pay to punish non-cooperators (altruistic punishment). Evolutionary models have suggested that if altruists punish non-altruists this could favour the evolution of costly helping behaviours (cooperation) among strangers. An often-key requirement is that helping behaviours and punishing behaviours form one single conjoined trait (strong reciprocity). Previous economics experiments have provided support for the hypothesis that punishment and cooperation form one conjoined, altruistically motivated, trait. However, such a conjoined trait may be evolutionarily unstable, and previous experiments have confounded a fear of being punished with being surrounded by cooperators, two factors that could favour cooperation. Here, we experimentally decouple the fear of punishment from a cooperative environment and allow cooperation and punishment behaviour to freely separate (420 participants). We show, that if a minority of individuals is made immune to punishment, they (i) learn to stop cooperating on average despite being surrounded by high levels of cooperation, contradicting the idea of conditional cooperation and (ii) often continue to punish, ‘hypocritically’, showing that cooperation and punishment do not form one, altruistically motivated, linked trait.
A Flexible Data-Driven Framework for COVID-19 Case Forecasting Deployed in a Developing-world Public Health Setting
Authors: Jain Sansiddh , Tiwari Avtansh , Bannur Nayana , Deva Ayush , Shingi Siddhant , Shah Vishwa , Kulkarni Mihir , Deka Namrata , Ramaswami Keshav , Khare Vasudha , Maheshwari Harsh , Dhavala Soma , Sreedharan Jithin , White Jerome , Merugu Srujana , Raval Alpan
Published: November 2021

Forecasting infection case counts and estimating accurate epidemiological parameters are critical components of managing the response to a pandemic. This paper describes a modular, extensible framework for a COVID-19 forecasting system, primarily deployed during the first Covid wave in Mumbai and Jharkhand, India. We employ a variant of the SEIR compartmental model motivated by the nature of the available data and operational constraints. We estimate best fit parameters using Sequential Model-Based Optimization (SMBO), and describe the use of a novel, fast and approximate Bayesian model averaging method (ABMA) for parameter uncertainty estimation that compares well with a more rigorous Markov Chain Monte Carlo (MCMC) approach in practice. We address on-the-ground deployment challenges such as spikes in the reported input data using a novel weighted smoothing method. We describe extensive empirical analyses to evaluate the accuracy of our method on ground truth as well as against other state-of-the-art approaches. Finally, we outline deployment lessons and describe how inferred model parameters were used by government partners to interpret the state of the epidemic and how model forecasts were used to estimate staffing and planning needs essential for addressing COVID-19 hospital burden.

CCS CONCEPTS

Applied computing → Health care information systems; Forecasting;

Computing methodologies → Modeling methodologies.
Effect of electroMagnetic Interference from smartPHone On cardiac implaNtable Electronic device (EMI-PHONE study)
Authors: Apakuppakul Sanatcha , Methachittiphan Nilubon , Apiyasawat Sirin
Published: November 2021

Background

Smartphone can emit two types of electromagnetic waves, static field from magnet and dynamic field from calling. Previous evidence showed the interference effects from old generation of mobile phones to cardiac implantable electronic device (CIEDs). The current generation of smartphones and CIEDS are reportedly better designed to reduce electromagnetic interference (EMI). We seek to find the presence and the magnitude of EMI from the current generation of smartphones.

Methods

A total of 80 consecutive subjects with CIEDs (Included pacemaker, ICD, CRT-D, CRT-P) were recruited from our CIEDs clinic and were tested for EMI. Each subject was tested with three different smartphones (Nokia 3310, Iphone 7, and Samsung 9S). Each phone was attached to chest wall at 0 cm at pulse generator site, at atrial lead, and at ventricular lead site. During the tests, real-time interrogations were performed to detect any EMI from smartphone in stand-by mode, and during calling-in and out for 30 seconds. After the tests, post-test interrogation was performed to detect any parameters changes. Adverse events including pacemaker inhibition, false ICD shock, CIEDs device malfunction, and urgent electrophysiologist consultations were recorded.

Results

Of all 80 subjects (Mean age 70.5±12.9 year-old, 50% male) recruited in the study, all completed the tests according to our protocol. The most common type of CIEDs tested was pacemaker (N=56, 70%), followed by ICD (N=16, 20%), and CRT (N=8, 10%). Most patients (N=62, 77.5%) had more than one lead implanted. The mean year of implantation was 5.2±2.8 (Devices were implanted since 2008-2019). Of all the tests performed, there was no EMI or adverse events observed.

Conclusion

Current generation of smartphones have no EMI effect to CIEDs and can be used safely without any adverse events including pacemaker inhibition, false ICD shock and CIEDs device malfunction.
Likelihood of being Physically Inactive from a Nationally Representative sample of Autistic Children
Authors: Vasudevan Vijay
Published: November 2021

Despite the many health risks of physical inactivity, studies have demonstrated individual, family, and environmental determinants of inactivity for autistic children. However, these studies never examined these correlates at the same time. Therefore, the purpose of this study was to explore these ecological domains concurrently when examining physical inactivity correlates for autistic children. This study used data from the 2016-2020 National Survey of Children’s Health. The authors predicted physical inactivity while controlling for child, parental/household, and neighborhood correlates with autism status as the comparison group. When controlling for covariates, children with co-occurring autism and intellectual and developmental disability (IDD) (adjusted odds ratio (aOR)= 1.91, 95% confidence interval (CI): 1.36-2.68) or ASD only (aOR = 1.91, CI: 1.48-2.48) were significantly more likely to be inactive when compared to children without autism or IDD. However, autism medicine and autism severity were not predictors for obese autistic children. These findings indicate that it is important to take a holistic, ecological approach when exploring the correlates of inactivity for autistic children.