bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical properties, accuracy, and multi-day performance of gelatine phantoms for electrophysiology
Authors: Owda Amani Yousef , Casson Alexander J.
Published: May 2020

Gelatine based phantoms for electrophysiology are becoming widely used as they allow the controlled validation of new electrode and new instrumentation designs. The phantoms mimic the electrical properties of the human body and allow a pre-recorded electrophysiology signal to beplayed-out, giving a known signal for the novel electrode or instrumentation to collect. Such controlled testing is not possible with on-person experiments where the signal to be recorded is intrinsically unknown. However, despite the rising interest in gelatine based phantoms there is relatively little public information about their electrical properties and accuracy, how these vary with phantom formulation, and across both time and frequency. This paper investigates ten different phantom configurations, characterising the impedance path through the phantom and comparing this impedance path to both previously reported electrical models of Ag/AgCl electrodes placed on skin and to a model made from ex vivo porcine skin. This article shows how the electrical properties of the phantoms can be tuned using different concentrations of gelatine and of sodium chloride (NaCl) added to the mixture, and how these properties vary over the course of seven days for a.c. frequencies in the range 20–1000 Hz. The results demonstrate that gelatine phantoms can accurately mimic the frequency response properties of the body–electrode system to allow for the controlled testing of new electrode and instrumentation designs.
Protein enhanced NIR-IIb emission of indocyanine green for functional bioimaging
Authors: He Mubin , Wu Di , Zhang Yuhuang , Fan Xiaoxiao , Lin Hui , Qian Jun
Published: May 2020

Fluorescence imaging performed in the 1500-1700 nm spectral range (labeled as near-infrared IIb, NIR-IIb) promises high imaging contrast and spatial resolution for its little photon scattering effect and minimum auto-fluorescence. Though inorganic and organic probes have been developed for NIR-IIb bioimaging, most are in preclinical stage, hampering further clinical application. Herein, we showed that indocyanine green (ICG), an US Food and Drug Administration (FDA)-approved agent, exhibited remarkable amount of NIR-IIb emission when dissolved into different protein solutions, including human serum albumin, rat bile, and fetal bovine serum. We performed fluorescence imaging in NIR-IIb window to visualize structures of lymph system, extrahepatic biliary tract and cerebrovascular. Results demonstrated that proteins promoted NIR-IIb emission of ICGin vivoand that NIR-IIb imaging with ICG preserved higher signal-to-background ratio (SBR) and spatial resolution compared with the conventional near-infrared II (NIR-II) fluorescence imaging. Our findings confirm that NIR-IIb fluorescence imaging can be successfully performed using the clinically approved agent ICG. Further clinical application in NIR-IIb region would hopefully be carried out with appropriate ICG-protein solutions.
SHP2 Inhibition Abrogates Adaptive Resistance to KRASG12C-Inhibition and Remodels the Tumor Microenvironment ofKRAS-Mutant Tumors
Authors: Fedele Carmine , Li Shuai , Teng Kai Wen , Foster Connor , Peng David , Ran Hao , Mita Paolo , Geer Mitchell , Hattori Takamitsu , Koide Akiko , Wang Yubao , Tang Kwan H. , Leinwand Joshua , Wang Wei , Diskin Brian , Deng Jiehui , Chen Ting , Dolgalev Igor , Ozerdem Ugur , Miller George , Koide Shohei , Wong Kwok-Kin , Neel Benjamin G.
Published: May 2020

KRASis the most frequently mutated oncogene in human cancer, and KRAS inhibition has been a longtime therapeutic goal. Recently, inhibitors (G12C-Is) that bind KRASG12C-GDP and react with Cys-12 were developed. Using new affinity reagents to monitor KRASG12Cactivation and inhibitor engagement, we found that, reflecting its action upstream of SOS1/2, SHP2 inhibitors (SHP2-Is) increased KRAS-GDP occupancy, enhancing G12C-I efficacy. SHP2-Is abrogated feedback signaling by multiple RTKs and blocked adaptive resistance to G12C-Isin vitro, in xenografts, and in syngeneicKRASG12C-mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) models. Biochemical analysis revealed enhanced suppression of ERK-, MYC-, anti-apoptotic-, and cell-cycle genes, and increased pro-apoptotic gene expression in tumors from combination-treated mice. SHP2-I/G12C-I also evoked favorable changes in the immune microenvironment, decreasing myeloid suppressor cells, increasing CD8+ T cells, and sensitizing tumors to PD-1 blockade. Experiments using cells expressing inhibitor-resistant SHP2 showed that SHP2 inhibition in PDAC cells is required for tumor regression and remodeling of the immune microenvironment, but also revealed direct inhibitory effects on angiogenesis resulting in decreased tumor vascularity. Our results demonstrate that SHP2-I/G12C-I combinations confer a substantial survival benefit in PDAC and NSCLC and identify additional combination strategies for enhancing the efficacy of G12C-Is.
Single cell atlas of beige remodeling of white adipose tissue reveals a myeloid to lymphoid shift during cold exposure compared to beta 3 adrenergic stimulation
Authors: Rabhi Nabil , Belkina Anna C. , Desevin Kathleen , Cortez Briana Noel , Farmer Stephen R.
Published: May 2020

White adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its related metabolic complications. Within the cell mixture that constitutes the stromal vascular fraction (SVF), WAT beiging is initiated through expansion and differentiation of adipocytes progenitor cells, however, the extent of the SVF cellular changes is still poorly understood. Additionally, direct beta 3 adrenergic receptor (Adrb3) stimulation has been extensively used to mimic physiological cold- induced beiging, yet it is still unknown whether Adrb3 activation induces the same WAT remodeling as cold exposure. Here, by using single cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling within white adipose tissue. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold exposure induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis, showed that Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cells recruitment. These findings provide new insight into the cellular dynamics during WAT beige remodeling and could ultimately lead to novel strategies to identify translationally-relevant drug targets to counteract obesity and T2D.
Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines
Authors: Boyoglu-Barnum Seyhan , Ellis Daniel , Gillespie Rebecca A. , Hutchinson Geoffrey B. , Park Young-Jun , Moin Syed M. , Acton Oliver , Ravichandran Rashmi , Murphy Mike , Pettie Deleah , Matheson Nick , Carter Lauren , Creanga Adrian , Watson Michael J. , Kephart Sally , Vaile John R. , Ueda George , Crank Michelle C. , Stewart Lance , Lee Kelly K. , Guttman Miklos , Baker David , Mascola John R. , Veesler David , Graham Barney S. , King Neil P. , Kanekiyo Masaru
Published: May 2020

Influenza vaccines that confer broad and durable protection against diverse virus strains would have a major impact on global health. However, next-generation vaccine design efforts have been complicated by challenges including the genetic plasticity of the virus and the immunodominance of certain epitopes in its glycoprotein antigens. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens display 20 hemagglutinin (HA) trimers in a highly immunogenic array, and their assemblyin vitroenables precisely controlled co-display of multiple distinct HAs in defined ratios. Nanoparticle immunogens displaying the four HAs of licensed quadrivalent influenza vaccines (QIV) elicited hemagglutination inhibition and neutralizing antibody responses to vaccine-matched strains that were equivalent or superior to commercial QIV in mice, ferrets, and nonhuman primates. The nanoparticle immunogens—but not QIV—simultaneously induced broadly protective antibody responses to heterologous viruses, including H5N1 and H7N9, by targeting the subdominant yet conserved HA stem. Unlike previously reported influenza vaccine candidates, our nanoparticle immunogens can alter the intrinsic immunodominance hierarchy of HA to induce both potent receptor-blocking and broadly cross-reactive stem-directed antibody responses and are attractive candidates for a next-generation influenza vaccine that could replace current seasonal vaccines.

One Sentence Summary

Nanoparticle immunogens displaying four seasonal influenza hemagglutinins elicit neutralizing antibodies directed at both the immunodominant head and the conserved stem and confer broad protective immunity.
Stop the crop: insights into the insecticidal mode of action of cinnamodial against mosquitoes
Authors: Kalsi Megha , Walter Anton , Lee Beenhwa , DeLaat Andrew , Trigueros Renata Rusconi , Happel Katharina , Sepesy Rose , Nguyen Bao , Manwill Preston K. , Rakotondraibe H. Liva , Piermarini Peter M.
Published: May 2020

Cinnamodial (CDIAL) is a drimane sesquiterpene dialdehyde found in the bark of Malagasy medicinal plants (Cinnamosmaspecies; family Canellaceae). We previously demonstrated that CDIAL was insecticidal, antifeedant, and repellent againstAedes aegyptimosquitoes. The goal of the present study was to generate insights into the insecticidal mode of action for CDIAL, which is presently unknown. We evaluated the effects of CDIALin vitroon the contractility of the ventral diverticulum (crop) in adult femaleAe. aegypti. The crop is a food storage organ surrounded by visceral muscle that spontaneously contractsin vitro. We found that CDIAL completely inhibited spontaneous contractions of the crop as well as those stimulated by the agonist 5-hydroxytryptamine. Several derivatives of CDIAL with known insecticidal activity also inhibited crop contractions. Morphometric analyses of crops suggested that CDIAL induced a tetanic paralysis that was dependent on extracellular Ca2+and inhibited by Gd3+, a non-specific blocker of plasma membrane Ca2+channels. Screening of numerous pharmacological agents revealed that a Ca2+ionophore (A23187) was the only compound other than CDIAL to completely inhibit crop contractions via a tetanic paralysis. Taken together, our results suggest that CDIAL inhibits crop contractility by elevating intracellular Ca2+through the activation of plasma membrane Ca2+channels thereby leading to a tetanic paralysis, which may explain the insecticidal effects of CDIAL against mosquitoes. Our pharmacological screening efforts also revealed the presence of two regulatory pathways in mosquito crop contractility not previously described: an inhibitory glutamatergic pathway and a stimulatory octopaminergic pathway. The latter was also completely inhibited by CDIAL.
Large-Scale Sparse Regression for Multiple Responses with Applications to UK Biobank
Authors: Qian Junyang , Tanigawa Yosuke , Li Ruilin , Tibshirani Robert , Rivas Manuel A. , Hastie Trevor
Published: May 2020

In high-dimensional regression problems, often a relatively small subset of the features are relevant for predicting the outcome, and methods that impose sparsity on the solution are popular. When multiple correlated outcomes are available (multitask), reduced rank regression is an effective way to borrow strength and capture latent structures that underlie the data. Our proposal is motivated by the UK Biobank population-based cohort study, where we are faced with large-scale, ultrahigh-dimensional features, and have access to a large number of outcomes (phenotypes): lifestyle measures, biomarkers, and disease outcomes. We are hence led to fit sparse reduced-rank regression models, using computational strategies that allow us to scale to problems of this size. We use an iterative algorithm that alternates between solving the sparse regression problem and solving the reduced rank decomposition. For the sparse regression component, we propose a scalable iterative algorithm based on adaptive screening that leverages the sparsity assumption and enables us to focus on solving much smaller sub-problems. The full solution is reconstructed and tested via an optimality condition to make sure it is a valid solution for the original problem. We further extend the method to cope with practical issues such as the inclusion of confounding variables and imputation of missing values among the phenotypes. Experiments on both synthetic data and the UK Biobank data demonstrate the effectiveness of the method and the algorithm. We presentmultiSnpnetpackage, available athttp://github.com/junyangq/multiSnpnetthat works on top of PLINK2 files, which we anticipate to be a valuable tool for generating polygenic risk scores from human genetic studies.
The dynamic modular fingerprints of the human brain at rest
Authors: Kabbara Aya , Paban Veronique , Hassan Mahmoud
Published: May 2020

The human brain is a dynamic modular network that can be decomposed into a set of modules and its activity changes permanently over time. At rest, several brain networks, known as Resting-State Networks (RSNs), emerge and cross-communicate even at sub-second temporal scale. Here, we seek to decipher the fast reshaping in spontaneous brain modularity and its relationship to RSNs. We use Electro/Magneto-Encephalography (EEG/MEG) to track dynamics of modular brain networks, in three independent datasets (N= 568) of healthy subjects at rest. We show the presence of striking spatiotemporal network pattern consistent over participants. We also show that some RSNs, such as default mode network and temporal network, are not necessary ‘unified units’ but rather can be divided into multiple sub-networks over time. Using the resting state questionnaire, our results revealed also that brain network dynamics are strongly correlated to mental imagery at rest. These findings add new perspectives to brain dynamic analysis and highlight the importance of tracking fast reconfiguration of electrophysiological networks at rest.
Abuse liability, antinociceptive, and discriminative stimulus properties of IBNtxA
Authors: Islam Ariful , Rahman Mohammad Atiqur , Brenner Megan B. , Moore Allamar , Kellmyer Alyssa , Buechler Harley , DiGiorgio Frank , Verchio Vincent , McCracken Laura , Sumi Mousumi , Hartley Robert , Lizza Joseph R. , Moura-Letts Gustavo , Fischer Bradford D. , Keck Thomas M.
Published: May 2020

Rationale

IBNtxA (3-iodobenzoyl naltrexamine) is a novel μ opioid receptor (MOR) agonist structurally related to the classical MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, producing a unique pharmacological profile resulting in antinociception with reduced side effects, including no conditioned place preference (CPP) when tested at a single dose. IBNtxA represents an intriguing lead compound for preclinical drug development targeting truncated MOR splice variants but further evaluation of its in vivo pharmacological profile is necessary to evaluate its potential.

Objective

The purpose of this study was to independently verify the antinociceptive properties of IBNtxA and to more completely examine the rewarding properties and discriminative stimulus effects of IBNtxA. These results will allow broader assessment of IBNtxA as a translational candidate or lead compound for further development.

Results

IBNtxA was synthesized and compared to morphine in a variety of mouse behavioral assays. 3 mg/kg IBNtxA was equipotent to 10 mg/kg morphine in a hot plate analgesia assay. In drug discrimination testing using mice trained to discriminate between 3 mg/kg IBNtxA and DMSO/saline vehicle, the κ agonist U-50488 fully substituted for IBNtxA. Classical μ agonist morphine, δ agonist SNC162, NOP agonist SCH 221510, and μ/NOP partial agonist buprenorphine each partially substituted for IBNtxA. IBNtxA up to 3 mg/kg did not produce a place preference in CPP. Pretreatment with 3 mg/kg IBNtxA but not 1 mg/kg IBNtxA attenuated acquisition of place preference for 10 mg/kg morphine. 3 mg/kg IBNtxA attenuated morphine-induced hyperlocomotion but did not alter naloxone-precipitated morphine withdrawal.

Conclusions

Overall IBNtxA has a complicated opioid receptor pharmacologyin vivo. These results indicate that IBNtxA produces potent antinociception and has low abuse liability, likely driven by substantial κ agonist signaling effects.
Mps2 links Csm4 and Mps3 to form a telomere-associated LINC complex in budding yeast
Authors: Fan Jinbo , Jin Hui , Koch Bailey A. , Yu Hong-Guo
Published: May 2020

The linker of the nucleoskeleton and cytoskeleton (LINC) protein complex is composed of a pair of transmembrane proteins: the KASH-domain protein localized to the outer nuclear membrane and the SUN-domain protein to the inner nuclear membrane. In budding yeast, the sole SUN-domain protein, Mps3, is thought to pair with either Csm4 or Mps2, two KASH-like proteins, to form two separate LINC complexes. Here we show that Mps2 mediates the interaction between Csm4 and Mps3 to form a heterotrimeric telomere-associated LINC (t-LINC) in budding yeast meiosis. Mps2 binds to Csm4 and Mps3, and all three are localized to the telomere. Telomeric localization of Csm4 depends on both Mps2 and Mps3; in contrast, Mps2’s localization depends on Mps3 but not Csm4. Mps2-mediated t-LINC regulates telomere movement and meiotic recombination. By ectopically expressingCSM4in vegetative yeast cells, we reconstitute the heterotrimeric t-LINC and demonstrate its ability to tether telomeres. Our findings therefore reveal the heterotrimeric composition of t-LINC in budding yeast and have implications for understanding LINC variant formation.
Diagrammatic Theory of RNA Structures and Ensembles with Trinucleotide Repeats
Authors: Mak Chi H. , Phan Ethan N. H.
Published: May 2020

Trinucleotide repeat expansion disorders (TRED) are associated with the overexpansion of (CNG) repeats on the genome. mRNA transcripts of sequences with greater than 60 to 100 (CNG) tandem units have been implicated in TRED pathogenesis. In this paper, we develop a diagrammatic theory to study the structural diversity of these (CNG)nRNA sequences. Representing structural elements on the chain’s conformation by a set of graphs and employing elementary diagrammatic methods, we have formulated a renormalization procedure to resum these graphs and arrive at a closed-form expression for the ensemble partition function. With a simple approximation for the renormalization and applied to extended (CNG)nsequences, this theory can comprehensively capture an infinite set of conformations with any number and any combination of duplexes, hairpins and 2-way junctions. To quantify the diversity of different (CNG)nensembles, the analytical equations derived from the diagrammatic theory were solved numerically to derive equilibrium estimates for the secondary structural contents of the chains. The results suggest that the structural ensembles of (CNG)nrepeat sequence with n ~ 60 are surprisingly diverse, and they are dominated largely by open segments, with only a small fraction of the nucleotides forming base pairs. At the same time, the variance in the secondary-structural contents on the chains is also quite large, indicating that their structures can undergo strong equilibrium fluctuations and are expected to be rather suspectable to perturbations.

STATEMENT OF SIGNIFICANCE

Trinucleotide repeat expansion disorders (TRED) are associated with the overexpansion of (CNG) repeats on the genome. mRNA transcripts of sequences with critical length greater than 60 to 100 (CNG) tandem units have been implicated in TRED pathogenesis, though their structures remain poorly characterized. Conventional view has tacitly assumed that conformations with maximal C:G base pairing dominate at equilibrium, but here we demonstrate that (CNG) repeat sequences are characterized by diverse ensembles of structurally heterogeneous folds and with a large variance of secondary structural contents. These ensembles of structures also undergo strong equilibrium fluctuations, rendering them rather susceptible to perturbations. These results were based on a novel diagrammatic approach to the ensemble partition function.
A hydraulic instability drives the cell death decision in the nematode germline
Authors: Chartier N. T. , Mukherjee A. , Pfanzelter J. , Fürthauer S. , Larson B. T. , Fritsch A.W. , Kreysing M. , Jülicher F. , Grill S. W.
Published: May 2020

Oocytes are large and resourceful. During oogenesis some germ cells grow, typically at the expense of others that undergo apoptosis. How germ cells are selected to live or die out of a homogeneous population remains unclear. Here we show that this cell fate decision inC. elegansis mechanical and related to tissue hydraulics. Germ cells become inflated when the pressure inside them is lower than in the common cytoplasmic pool. This condition triggers a hydraulic instability which amplifies volume differences and causes some germ cells to grow and others to shrink. Shrinking germ cells are extruded and die, as we demonstrate by reducing germ cell volumes via thermoviscous pumping. Together, this reveals a robust mechanism of mechanochemical cell fate decision making in the germline.
Impact assessment of accreditation in primary and secondary public Healthcare Institutions in the State of Kerala, India
Authors: Joseph Sindhu
Published: June 2020

Objectives

This study examines the impact of accreditation on the quality of public healthcare delivery in primary and secondary healthcare facilities in Kerala, India.

Study Design

A cross-sectional study.

Setting

Kerala State, India

Participants

Participants are the in-patients (621) who are admitted in medical wards at accredited (312) and non-accredited (309) public healthcare facilities.

Main Outcome Measures

Ten constructs used in the study, overarching the quality healthcare delivery, adapting previous studies, SERVQUAL, and Donabedian’s SPO models, are Physical Facility, Admission Services, Patient centeredness, Accessibility of Medical Care, Financial Factors, Professionalism, Staff Services, Medical Quality, Diagnostic Services, and Patient Satisfaction.

Methods

The study employed a positivist approach using a survey questionnaire. The study was conducted from July 2017 to July 2018, using stratified random sampling consists of the four strata; GHs, W&C hospitals, THQHs/THs and CHCs.

Results

Accreditation has a positive impact on patient satisfaction and other quality dimensions, overarching structural and procedural quality in primary healthcare facilities under the public sector in Kerala. Conversely, accreditation has not improved the quality dimensions in secondary healthcare facilities and thereby, the satisfaction of patients.

Conclusions

It cannot be assumed that accreditation is always associated with quality care in primary healthcare facilities. The implementation process must be systematic and must be regularly monitored to make it useful. Mere structural transformation through accreditation alone cannot guarantee patient satisfaction. Secondary healthcare facilities must be transformed into quality care centres through rhetoric action of the authorities concerned through organized efforts.
Emotional distress and associated sociodemographic risk factors during the COVID-19 outbreak in Spain
Authors: Muñoz-Navarro Roger , Cano Vindel Antonio , Schmitz Florian , Cabello Rosario , Fernández-Berrocal Pablo
Published: May 2020

Background

Spain is one of the countries that has been most affected by COVID-19 disease. However, the emotional distress on the Spanish population remains poorly understood. The aim of this study was to determine the presence of emotional disorders and related symptoms and to assess the influence of sociodemographic characteristics on this population.

Methods

We conducted a cross-sectional survey using an online platform. Participation was completely voluntary. Sociodemographic variables were collected and symptoms of anxiety, depression, and panic were assessed through three questionnaires: Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and the Patient Health Questionnaire-Panic Disorder (PHQ-PD). Chi-squared statistics were applied to determine the influence of sociodemographic variables on symptom severity and diagnosis.

Results

Most respondents (n = 1753) were female (76.8%), with a mean (SD) age of 40.4 (12.9) years; 39.1% were married and 39.5% held a high school degree. Severe and moderate symptoms of anxiety and depression were high (6.5% and 14.3%; 9.9% and 12.9%, respectively) and more than one in four participants (25.7%) experienced a panic attack. A high proportion of participants met diagnostic criteria for emotional disorders: 15.3% for GAD; 12.2% for MDD; and 17.2% for PD. Significant risk factors were as follows: female, young adult, single, unemployed, and low income.

Conclusion

Due to limitations related to the study design (convenience sample), the findings of these study may not be applicable to the general population. Nonetheless, the high prevalence of emotional symptoms and disorders in this sample suggests that mental health interventions are urgently needed in Spain.
Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL): findings from a UK population-based cohort
Authors: Lamb Maxine , Smith Alexandra G , Painter Daniel , Kane Eleanor , Bagguley Tim , Newton Robert , Howell Debra , Cook Gordon , de Tute Ruth , Rawstron Andrew , Patmore Russell , Roman Eve
Published: May 2020

Objective

To examine co-morbidity patterns in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL), both before and after premalignancy diagnosis; and compare their activity to that of the general population.

Design

Population-based patient cohort, within which each patient is matched at diagnosis to 10 age and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations, and Hospital Episode Statistics (HES).

Setting

The UK’s Haematological Malignancy Research Network; which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory.

Participants

All patients newly diagnosed 2009–15 with MGUS (n = 2203) or MBL (n = 561), and their age and sex-matched comparators (n = 27,638).

Main Outcome measures

Survival, and hospital inpatient and outpatient activity in the five years before, and three years after, diagnosis.

Results

Individuals with MGUS experienced excess morbidity in the 5-years before diagnosis, and excess mortality and morbidity in the 3-years after. Increased rate-ratios (RR) were evident for nearly all clinical specialties; the largest, both before and after diagnosis, being for nephrology (before RR = 4.38, 95% Confidence Interval 3.99–4.81; after RR = 14.7, 95% CI 13.5–15.9) and rheumatology (before RR = 3.38, 95% CI 3.16–3.61; after RR = 5.45, 95% CI 5.09–5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL.

Conclusions

From a haematological malignancy perspective, MGUS and MBL are generally considered to be relatively benign. Nonetheless, monoclonal gammopathy has the potential to cause systemic disease and wide-ranging damage to most organs and tissues. Hence, even though most people with monoclonal immunoglobulins never develop a B-cell malignancy or suffer from any other form of M-protein related organ/tissue related disorder, the consequences for those that do can be extremely serious.
Prevalence, clinical characteristics and treatment outcomes of HIV and SARS-CoV-2 co-infection: a systematic review and meta-analysis
Authors: Baluku Joseph Baruch , Olum Ronald , Agolor Curthbert , Nakakande Josephine , Russell Laura , Bongomin Felix , Nakawesi Jane
Published: June 2020

Objectives

To determine the prevalence, clinical characteristics and outcomes of HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection.

Methods

We searched Medline, Embase, Cochrane and Web of Science databases and grey literature for studies reporting epidemiological and clinical data of patients with HIV and SARS-CoV-2 co-infection. Eligible studies were all observational or interventional studies and commentaries in English language that reported patient data on HIV/SARS-CoV-2 co-infection. We used random effect meta-analysis to determine the pooled prevalence and mortality.

Results

Of the 17 eligible studies, there were 3 retrospective cohorts, 1 survey, 5 case series, 7 case reports and 1 commentary that reported on a total of 146 HIV infected individuals. The pooled prevalence of HIV among individuals with SARS-CoV-2 infection was 1.0% (95% CI: 0.0 – 3.0, I2= 79.3%, p = 0.01), whereas the prevalence of SARS-CoV-2 among HIV patients was 0.68% (95% CI: 0.34 – 1.34).There were 110 (83.8%) HIV/ SARS-CoV-2 co-infected males, and the age (range) of the co-infected was 30 – 60 years. A total of 129 (97.0%) were anti-retroviral therapy experienced, and 113 (85.6%) had a suppressed HIV viral load. The CD4 count (range) was 298 – 670 cells/mm3(n = 107). The commonest symptoms were fever (73.5%, n = 75) and cough (57.8%, n = 59). Sixty-two (65.3%) patients had at least one other comorbid condition, of which hypertension (26.4%, n = 38) was the commonest. Chest radiological imaging abnormalities were found in 46 (54.1%) cases. Twenty-eight cases (56.0%) were reported as mild. Recovery occurred in 120 (88.9%) cases, and the pooled mortality was 9% (95% CI: 3.0 – 15.0, I2= 25.6%, p = 0.24).

Conclusion

The prevalence of HIV/SARS-CoV-2 co-infection was low. The clinical characteristics and outcomes of HIV/SARS-CoV-2 co-infection are comparable to those reported among HIV negative SARS-CoV-2 cases.
Secreted inhibitors drive the loss of regeneration competence inXenopuslimbs
Authors: Aztekin C. , Hiscock T. W. , Gurdon J. B. , Jullien J. , Marioni J. C. , Simons B. D.
Published: June 2020

Absence of a specialised wound epidermis is hypothesised to block limb regeneration in higher vertebrates. To elucidate the cellular and molecular determinants of this tissue, we performed single-cell transcriptomics in regeneration-competent, -restricted, and -incompetentXenopustadpoles. We identified apical-ectodermal-ridge (AER) cells as the specialised wound epidermis, and found that their abundance on the amputation plane correlates with regeneration potential and injury-induced mesenchymal plasticity. By usingex vivoregenerating limb cultures, we demonstrate that extrinsic cues produced during limb development block AER cell formation. We identifyNoggin, a morphogen expressed in cartilage/bone progenitor cells, as one of the key inhibitors of AER cell formation in regeneration-incompetent tadpoles. Extrinsic inhibitory cues can be overridden byFgf10, which operates upstream ofNogginand blocks chondrogenesis. Together, these results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates.

One Sentence Summary

Extrinsic cues associated with chondrogenic progression inhibit AER cell formation and restrict limb regeneration potential.
Validation of Remote Testing using BrainCheck, a Computerized Neurocognitive Test
Authors: Ye Siao , Huang Bin , Sun Kevin , Phi Huy , Ghomi Reza Hosseini
Published: June 2020

Remote computerized neurocognitive testing (CNT) is a promising solution to have these assessments more accessible to a population facing a global pandemic and increased aging. BrainCheck (BC) is a CNT software available on iPhone, iPad, and computer browser, designed to fit the need for remote testing. Consistent measures across these varying platforms are necessary to ensure users have consistent cognitive assessments and results. We aimed to assess BC across all administration platforms and interactions to observe any differences in assessment performance. 75 participants were enrolled in the study and were divided into two groups: participants who took BC across multiple platforms and participants who took BC in both an administered and self-administered fashion. Here we found Stroop, Digit Symbol, and Trail A/B had significantly different performance across the platforms, while Flanker, Coordination, Matrix, Immediate and Delayed Recognitions did not. Also, we found that the test metrics did not show significant differences in performance between being administered and self-administering the test. We did observe quicker completion times during the second instance of the test when taken in quick succession (within a day apart, which would not be a typical clinical pattern) and despite this, composite scores did not change reflecting the resilience of BC to practice effects. In conclusion, our results demonstrate BC may be a robust, self-administered CNT solution with an appropriate adjustment for the platform used.
Structure of the human heterotetramericcis-prenyltransferase complex
Authors: Bar-El Michal Lisnyansky , Vankova Pavla , Man Petr , Haitin Yoni , Giladi Moshe
Published: June 2020

The humancis-prenyltransferase (hcis-PT) is an enzymatic complex essential for protein N-glycosylation. Synthesizing the precursor of the glycosyl carrier dolichol-phosphate, we reveal here that hcis-PT exhibits a novel heterotetrameric assembly in solution, composed of two catalytic dehydrodolichyl diphosphate synthase (DHDDS) and two inactive Nogo-B receptor (NgBR) subunits. The 2.3 Å crystal structure of the complex exposes a dimer-of-heterodimers arrangement, with DHDDS C-termini serving as homotypic assembly domains. Furthermore, the structure elucidates the molecular details associated with substrate binding, catalysis, and product length determination. Importantly, the distal C-terminus of NgBR transverses across the heterodimeric interface, directly participating in substrate binding and underlying the allosteric communication between the subunits. Finally, mapping disease-associated hcis-PT mutations involved in blindness, neurological and glycosylation disorders onto the structure reveals their clustering around the active site. Together, our structure of the hcis-PT complex unveils the dolichol synthesis mechanism and its perturbation in disease.
Loss of coiled-coil protein Cep55 impairs abscission processes and results in p53-dependent apoptosis in developing cortex
Authors: Little Jessica N. , McNeely Katrina C. , Michel Nadine , Bott Christopher J. , Lettieri Kaela S. , Hecht Madison R. , Martin Sara A. , Dwyer Noelle D.
Published: June 2020

To produce a brain of normal size and structure, embryonic neural stem cell (NSCs) must tightly regulate their cell divisions. Cerebral cortex NSCs undergo a polarized form of cytokinesis whose regulation is poorly understood. Cytokinetic abscission severs the daughter cells and is mediated by the midbody at the apical membrane. Here we elucidate the role of the coiled-coil midbody protein Cep55 in NSC abscission and brain development. A knockout of Cep55 in mice causes microcephaly with reduced NSCs and neurons, but relatively normal body size. Fixed and live analyses show NSCs lacking Cep55 have decreased but not eliminated ESCRT recruitment, and have abnormal abscission and higher rates of failure. P53-mediated apoptosis is greatly increased in the brain, but not other tissues, and p53 knockout partly rescues brain size. Thus, loss of Cep55 causes abscission defects and failures in multiple cell types, but the secondary p53 response and apoptosis is brain-specific.
Narrated Soviet tourist landscapes during late socialism
Authors: Rattus Kristel , Järs Anu
Published: June 2020

Purpose

The study aims to provide an insight into the inherent diversities and ambiguities of Soviet touristic landscapes during the period of late socialism by a means of Estonian biographical sources. Based on written narratives, the study focuses on the embodied ways in which Estonian travellers engaged with and experienced foreign landscapes and people during trips within the Soviet Union.

Design/methodology/approach

The study treats tourists’ travel landscapes as meaningful, lived experiences that highlight features and everyday life strategies that were characteristic of the Soviet period. Approaching via the lens of Estonian culture and nationality, the study analyses the meaningful experiences through which the narrators drew boundaries between the self and the other.

Findings

The Soviet tourism landscape of the 1960s–1980s was marked by sharp cultural contrasts. The landscapes that unfold in the narratives were full of contradictions, arousing feelings of both admiration and alienation. Whilst the ideological purpose of Soviet tourism was to build a “socialist nation”, the themed narratives, on the other hand, demonstrate the wide spectrum of everyday life practices, which show both the distancing of oneself from the Soviet system as well as conformation with it. Although tourism helped travellers accept the Union, this was achieved not by consenting to socialist ideology, but by becoming familiar with its heterogeneity.

Originality/value

Research on Soviet tourism has largely relied on archival sources and the press, which shed light mainly on the organisation and ideological basis of tourism. Drawing on oral sources, this study contributes to a more comprehensive understanding of the complex nature of Soviet tourist landscapes.
Self-selection and purchase value of research shoppers
Authors: Pallant Jason Ian , Sands Sean James , Ferraro Carla Renee , Pallant Jessica Leigh
Published: June 2020

Purpose

This paper investigates the degree to which self-selection explains the apparent higher purchase value of research shoppers.

Design/methodology/approach

An online survey was administered to 594 retail shoppers. The purchase value of research shoppers and single-channel shoppers was compared before and after propensity score matching to account for self-selection effects.

Findings

Prior to matching, research shoppers spend significantly more than single-channel shoppers. This difference persists after accounting for self-selection but is reduced by 25%. The impact of self-selection differs across product categories and channels, with the online channel most likely to lead to higher purchase value.

Practical Implications

The findings build on existing literature on the value of omni-channel retail strategies and provide insights for retailers to determine the likely impact of encouraging research shopping among their customers.

Originality/value

The research provides important insights into the role that self-selection plays in the value of multi-channel shoppers, and the likely value to retailers of omni-channel strategies.
Self-employment and wage difference an analysis for Brazil
Authors: França Marco Túlio Aniceto , Frio Gustavo Saraiva , Korzeniewicz Mariza Bethanya Dalla Vecchia
Published: June 2020

Purpose

The aim of this study is to evaluate the wage gap between men and women who seek self-employment in Brazil, whether because they want to become entrepreneurs out of necessity or because of the flexible hours.

Design/methodology/approach

The data used are from the 2015 National Household Sample Survey (PNAD) and the methods are the ordinary least squares (OLS) for the Mean and the unconditional quantile regression (RIF-regression) for the distribution of gains of both genders, both associated with the Oaxaca–Ransom decomposition in order to separate the differential between the part explained by attributes and the unexplained part.

Findings

The main results show that women earn less than men in the mean and throughout the distribution. The average difference is 27.79%, varying between 19.24 and 48.26% in the distribution. The inclusion of occupational variables shows that the glass door phenomenon exists even in self-employment, that is, women choose occupations with lower incomes.

Originality/value

Stimulating self-employment has been an alternative policy for the insertion of women in the labor market. This is the first study on the wage gap in self-employment in the Brazilian labor market. The presence of wage differentials among self-employed men and women throughout the distribution may point to the need for specific policies that not only target the mean. These policies would be related to sticky floor and to the glass ceiling. Another potential problem concerns the so-called glass door–women access the labor market via professions that pay less, otherwise, the problem points to occupational segregation against women.

Peer Review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-05-2019-0312
Determinants of infant mortality in Sierra Leone: applying Cox proportional hazards model
Authors: Naz Lubna , Patel Kamalesh Kumar
Published: June 2020

Purpose

The aim of this paper is to examine biological, maternal and socioeconomic determinants of infant mortality in Sierra Leone.

Design/methodology/approach

It uses an analytical framework and Cox proportional hazards regression to break down the effects of factors determining infant mortality. Factors utilized in the empirical investigation include sex of the child, birth size, birth spacing, mother's working status, age of mother, antenatal care, postnatal care, mother's anemia level, religion, mother's education and wealth status.

Findings

Results suggest that birth spacing of three years and above associated with a reduced risk of infant mortality contrasted with short birth intervals. Children born to nonanemic mothers have a lower hazard (22%) of infant mortality compared to those born to anemic mothers (HR = 0.78; 95% CI: 0.64–0.96). At least one antenatal care visit by mothers lowers infant mortality rate by 41% compared to no antenatal visits at all ( HR = 0.59; 95% CI: 0.36–0.96). Similarly, infants whose mothers have received postnatal care are at lower risk (31%) of dying than those whose mothers have not received (HR = 0.69; 95% CI: 0.52, 0.93). Infant mortality is likely to decrease with the increase in the birth order.

Practical implications

The family health and planning programs should aim at educating men and women about the usefulness of birth spacing methods.

Originality/value

This paper might be the first attempt to analyze the determinants of infant mortality by utilizing a methodological framework and Cox regression.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-08-2019-0478.
Rapport-building in luxury fashion retail: a collectivist culture case
Authors: Sresnewsky Katherine Braun Galvão Bueno , Yojo Angela Satiko , Veloso Andres Rodriguez , Torresi Laura
Published: June 2020

Purpose

Luxury companies have expanded globally, but little attention is given to the difficulties associated with expansion to culturally different countries, especially when focusing on training salespeople in rapport-building behaviors. To address this discussion, we answer these research questions: (1) Does the luxury fashion brand country of origin affect the rapport-building strategies of salespeople?; (2) How do luxury fashion employees classify customers from collectivistic cultures with emerging economies, such as that in Brazil?; and (3) What are the rapport-building strategies used by these salespeople for each of these luxury fashion customer segments?

Design/methodology/approach

The authors conducted in-depth interviews with salespeople, managers and team supervisors from four global luxury retailers from Britain, France and Italy that operate in Brazil. In total, the authors interviewed 20 employees with an average of greater than 7 years of experience in luxury sales. The authors based their analysis on a theoretically generated coding guide and content analysis theories.

Findings

When expanding to culturally different countries, retail companies should adopt glocal strategies, especially when luxury is involved and when customers demand exclusive attention from companies. Additionally, the authors suggest that the effectiveness of rapport building strategies is culturally dependent and should be adapted to the microlevel, especially for continental countries that are culturally diverse.

Research limitations/implications

This is employee-view research, with no inputs from customers or corporate managers. Luxury fashion brand stores did not grant permission for official research within their employees nor the observation of their customers during in-store interactions. Researchers interviewed employees as individual professionals, and their identities will remain anonymous.

Practical implications

When expanding to culturally different countries, luxury retailers should give special attention to the adaption of sales strategies, training and sales guidelines.

Originality/value

This study focuses on customer-employee rapport from the company's perspective.
An authentic flip subscription model for Africa: library as publisher service
Authors: Raju Reggie , Claassen Jill , Pietersen Jeremiah , Abrahamse Danielle
Published: June 2020

Purpose

This paper investigates the fit for purpose of the flip model proposed by Max Planck Society and Plan S for the African environment. This flipped model is examined against the backdrop of African imperatives, which is much broader than just flipping a journal pricing model from subscription to open access. This paper also seeks a viable alternative model that supports the growth of African scholarship and the dissemination thereof.

Design/methodology/approach

This paper adopts a descriptive research methodology, which allows for an in-depth analysis of a phenomenon. By using this method, this paper describes a flip model proposed by global north entities, which do not augur well for the growth of the OA movement in Africa.

Findings

The findings demonstrate that the global north centric flipped model exacerbates the inequality in the publishing landscape by further marginalizing the research voices from the global south. Africa is in dire need of an alternative that denorthernizes the publishing landscape, promote equity and equality, and is more inclusive of the research voices from Africa. South African academic libraries have demonstrated their willingness to experiment with and roll-out library publishing services. This proof of concept has been extended into a continental platform for the publication and dissemination of African scholarship.

Originality/value

This paper will be of interest to those who are grappling with viable alternatives to the current flip models, which include, inter alia, university leadership. This paper will also be of interest to global north libraries who are embarking on library publishing without the social justice obligation but are committed to the OA movement.