bluuebunny/crossref_metadata_2025 huggingface dataset:
A Call for Caution in the Immunocompromised: Coronavirus Disease 2019 Associated With Mortality in a Vaccinated Lung Transplant Recipient
Authors: Hogan John I , Kotton Camille N
Published: November 2021

We describe a vaccinated lung transplant recipient who experienced a fatal outcome associated with coronavirus disease 2019 (COVID-19). Tocilizumab was administered. The patient exhibited clinical and radiographic evidence of colitis during the course of multiple secondary infections. This report emphasizes the need for more conservative precautions to prevent COVID-19 infection in transplant recipients.
Comparing the Diagnostic Accuracy of Clinician Judgment to a Novel Host Response Diagnostic for Acute Respiratory Illness
Authors: Jaffe Ian S , Jaehne Anja K , Quackenbush Eugenia , Ko Emily R , Rivers Emanuel P , McClain Micah T , Ginsburg Geoffrey S , Woods Christopher W , Tsalik Ephraim L
Published: November 2021

Background

Difficulty discriminating bacterial from viral infections drives antibacterial misuse. Host gene expression tests discriminate bacterial and viral etiologies, but their clinical utility has not been evaluated.

Methods

Host gene expression and procalcitonin levels were measured in 582 emergency department participants with suspected infection. We also recorded clinician diagnosis and clinician-recommended treatment. These 4 diagnostic strategies were compared with clinical adjudication as the reference. To estimate the clinical impact of host gene expression, we calculated the change in overall Net Benefit (∆NB; the difference in Net Benefit comparing 1 diagnostic strategy with a reference) across a range of prevalence estimates while factoring in the clinical significance of false-positive and -negative errors.

Results

Gene expression correctly classified bacterial, viral, or noninfectious illness in 74.1% of subjects, similar to the other strategies. Clinical diagnosis and clinician-recommended treatment revealed a bias toward overdiagnosis of bacterial infection resulting in high sensitivity (92.6% and 94.5%, respectively) but poor specificity (67.2% and 58.8%, respectively), resulting in a 33.3% rate of inappropriate antibacterial use. Gene expression offered a more balanced sensitivity (79.0%) and specificity (80.7%), which corresponded to a statistically significant improvement in average weighted accuracy (79.9% vs 71.5% for procalcitonin and 76.3% for clinician-recommended treatment; P<.0001 for both). Consequently, host gene expression had greater Net Benefit in diagnosing bacterial infection than clinician-recommended treatment (∆NB=6.4%) and procalcitonin (∆NB=17.4%).

Conclusions

Host gene expression–based tests to distinguish bacterial and viral infection can facilitate appropriate treatment, improving patient outcomes and mitigating the antibacterial resistance crisis.
The further economic consequences of Brexit: energy
Authors: Pollitt Michael G
Published: November 2021

The UK left the European single market in energy on 31 December 2020, having been a leading light in its promotion. It entered into a new energy relationship with the EU-27 as outlined in the EU–UK Trade and Cooperation Agreement (TCA) on 1 January 2021. This paper discusses what has happened to the UK energy sector since the Brexit referendum of June 2016. Since our previous paper on this topic in 2017, there has been a significant clarification in the impact of Brexit on the energy sector in the UK. We outline what the TCA says about energy. We then discuss the current and potential future effects of Brexit on the UK electricity and gas systems in turn. We observe that the likely economic welfare impacts on electricity are larger than the impacts on gas, but the overall microeconomic impact appears likely to be modest (but negative). We offer a number of concluding observations.
Elevated Kinesiophobia Is Associated With Reduced Recovery From Lower Extremity Musculoskeletal Injuries in Military and Civilian Cohorts
Authors: Chimenti Ruth L , Pacha Molly S , Glass Natalie A , Frazier Mathew , Bowles Amy O , Valantine Andrew D , Archer Kristin R , Wilken Jason M
Published: November 2021

Objective

The purpose of this study was to examine associations between level of kinesiophobia and improvement in physical function during recovery from lower extremity injury.

Methods

A total 430 adults (mean [SD]: age = 27.3 [6.4] years; sex = 70.5% men; body mass index = 27.6 [5.2] kg/m2) were included in the analyses. Using the Patient-Reported Outcomes Measurement Information System, physical function was evaluated in parallel with treatment from a physical therapist at the initial visit and every 3 weeks until final visit or up to 6 months. A Tampa Scale of Kinesiophobia (TSK-17) score of >41 indicated elevated TSK. Four TSK groups were identified: (1) TSK score improved from >41 at initial visit to <41 by final visit (TSK_I), (2) TSK score was <41 at initial and final visits (TSK−), (3) TSK score was >41 at initial and final visits (TSK+), and (4) TSK score worsened from <41 at initial visit to ≥41 by final visit (TSK_W). Linear mixed effects models were used to examine differences between groups in improved physical function over time, with adjustment for depression and self-efficacy.

Results

Groups with elevated kinesiophobia at the final visit had smaller positive improvements in physical function (mean change [95% CI]: TSK+ = 7.1 [4.8–9.4]; TSK_W: 6.0 [2.6–9.4]) compared with groups without elevated kinesiophobia at the final visit (TSK_I = 9.8 [6.4–13.3]; TSK− = 9.7 [8.1–11.3]) by 12 weeks.

Conclusions

Elevated kinesiophobia that persists or develops over the course of care is associated with less improvement in physical function within military and civilian cohorts.

Impact

The findings of this prospective longitudinal study support the need to assess for elevated kinesiophobia throughout the course of care because of its association with decreased improvement in physical function.

Lay Summary

To help improve your physical function, your physical therapist can monitor the interaction between fear of movement and your clinical outcomes over the course of treatment.
Trait Anhedonia in Schizophrenia: A Systematic Review and Comparative Meta-analysis
Authors: Krzyzanowski Daniel J , Wu Sally , Carnovale Michael , Agarwal Sri Mahavir , Remington Gary , Goghari Vina
Published: November 2021

Anhedonia, the reduced capacity to experience pleasure, has long been considered a prominent feature of schizophrenia spectrum disorders. Many domain-specific conceptualizations of anhedonia and pleasure capacity have been developed, and there currently exist a variety of self-report assessment tools that purport to assess these various domains. The current systematic review and meta-analysis (PROSPERO: CRD42020156169) aimed to quantify overall and domain-specific self-reported anhedonia in people with schizophrenia compared to nonpsychiatric controls. We performed a literature search of PsycINFO, MEDLINE, and Embase databases for dissertations and peer-reviewed articles published in English prior to June 2021. Studies employing a psychometrically validated self-report measure of anhedonia, pleasure experience or affect in people with schizophrenia, schizoaffective, or schizophreniform disorders; studies utilizing at least one clearly defined healthy or community control group for comparison; and studies providing sufficient data to calculate effect sizes were included in this review. Random and mixed effects meta-analyses, meta-regressions, and subgroup comparisons were run across domains of anhedonia to explore weighted mean effect sizes and their associated moderators. In total, 146 studies met inclusion criteria, yielding 390 Hedges’ g effect sizes from the included comparisons. People with schizophrenia reported moderate-to-large elevations in overall and domain-specific anhedonia. A sensitivity analysis accounting for high risk of bias studies did not significantly impact results. Lastly, patient sex, education, negative symptom severity, antipsychotic class, and trait negative affect differentially moderated effect sizes across domains of anhedonia. Despite the heterogeneity inherent in schizophrenia spectrum disorders, self-reported anhedonia is ubiquitously reported across self-report measures in this population.
Walking the talk? Innovation policy approaches to unleash the transformative potentials of the Nordic bioeconomy
Authors: Scordato Lisa , Bugge Markus M , Hansen Teis , Tanner Anne , Wicken Olav
Published: November 2021

This article explores whether and how innovation policies promote transitions to more sustainable configurations in socio-technical systems. Empirically it departs from an analysis of the bioeconomy policy strategies and instruments in four Nordic countries. The analysis highlights that while a transformative approach is present at the policy strategy level in the Nordic countries, the bioeconomy policy instruments implemented are significantly less transformative. The article argues that a bioeconomy transition that contributes to sustainable development will require a redirection of policies towards transformative failures (directionality, policy coordination, demand articulation, and reflexivity). In this regard, it is important that policymakers experiment with and explore ways of balancing between traditional market and innovation system approaches and new policy approaches for transformative change.
Electroencephalographic sleep macrostructure and sleep spindles in early infancy
Authors: Ventura Soraia , Mathieson Sean R , O’Toole John M , Livingstone Vicki , Ryan Mary-Anne , Boylan Geraldine B
Published: November 2021

Study Objectives

Sleep features in infancy are potential biomarkers for brain maturation but poorly characterized. We describe normative values for sleep macrostructure and sleep spindles at 4–5 months of age.

Methods

Healthy term infants were recruited at birth and had daytime sleep electroencephalograms (EEGs) at 4–5 months. Sleep staging was performed and five features were analyzed. Sleep spindles were annotated and seven quantitative features were extracted. Features were analyzed across sex, recording time (am/pm), infant age, and from first to second sleep cycles.

Results

We analyzed sleep recordings from 91 infants, 41% females. Median (interquartile range [IQR]) macrostructure results: sleep duration 49.0 (37.8–72.0) min (n = 77); first sleep cycle duration 42.8 (37.0–51.4) min; rapid eye movement (REM) percentage 17.4 (9.5–27.7)% (n = 68); latency to REM 36.0 (30.5–41.1) min (n = 66). First cycle median (IQR) values for spindle features: number 241.0 (193.0–286.5), density 6.6 (5.7–8.0) spindles/min (n = 77); mean frequency 13.0 (12.8–13.3) Hz, mean duration 2.9 (2.6–3.6) s, spectral power 7.8 (4.7–11.4) µV2, brain symmetry index 0.20 (0.16–0.29), synchrony 59.5 (53.2–63.8)% (n = 91). In males, spindle spectral power (µV2) was 24.5% lower (p = .032) and brain symmetry index 24.2% higher than females (p = .011) when controlling for gestational and postnatal age and timing of the nap. We found no other significant associations between studied sleep features and sex, recording time (am/pm), or age. Spectral power decreased (p < .001) on the second cycle.

Conclusion

This normative data may be useful for comparison with future studies of sleep dysfunction and atypical neurodevelopment in infancy.

Clinical Trial Registration: BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT) (BabySMART)

URL: https://clinicaltrials.gov/ct2/show/results/NCT03381027?view=results.

ClinicalTrials.gov Identifier: NCT03381027
Zoletil promotes apoptosis in BV-2 microglial cells via induction of oxidative stress and neural inflammation
Authors: Kim Gyun Moo , Lee Chan , Jang Tae Chang
Published: November 2021

Zoletil® (ZOL) is a combination drug of tiletamine, a dissociative anesthetic and zolazepam, a minor tranquilize, which has been used to induce short-term anesthesia in various animals. Depending on the administered dose, the effects of ZOL can range from sedation to anesthesia. Here, we aimed to determine the neurotoxicity of ZOL and elucidate its mechanism of action using BV-2 microglial cells. The results of MTT reduction assay and TUNEL staining revealed that ZOL induced neuronal toxicity and apoptosis in BV-2 cells. ZOL caused apoptosis via phosphorylation of c-Jun N-terminal kinase, increased ratio of Bax to Bcl-2, disruption of mitochondrial membrane potential, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase. Furthermore, reactive oxygen species were involved in ZOL-induced neuronal cell death as assessed by 2′,7′-dichlorofluorescein diacetate staining. Moreover, BV-2 cells treated with ZOL exhibited increased expression of inflammatory enzymes, such as inducible nitric oxide synthase and cyclooxygenase-2, along with subsequent production of nitric oxide and prostaglandin E2. ZOL upregulated the expression of interleukin-1β, a proinflammatory cytokine. With respect to its molecular mechanism, ZOL increased the nuclear translocation and DNA binding of redox-sensitive transcription factor NF-κB, which seemed to be mediated by activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. These findings suggest that ZOL leads to apoptosis in BV-2 cells by inducing oxidative stress and inflammatory responses.
Cost-Effectiveness of Screening Preschool Children for Hearing Loss in Australia
Authors: Gumbie Mutsa , Parkinson Bonny , Dillon Harvey , Bowman Ross , Song Rachel , Cutler Henry
Published: November 2021

Objectives:

While all newborns in Australia are tested for congenital hearing loss through universal newborn hearing screening programs, some children will acquire hearing loss in their first five years of life. Delayed diagnosed or undiagnosed hearing loss in children can have substantial immediate- and long-term consequences. It can significantly reduce school readiness, language and communication development, social and emotional development, and mental health. It can also compromise lifetime educational achievements and employment opportunities and future economic contribution to society through lost productivity. The need for a universal hearing screening program for children entering their first year of primary school has been noted in two separate Australian Government hearing inquiries in the last decade. Sound Scouts is a hearing screening application (app) that tests for hearing loss in children using a tablet or mobile device, supervised by parents at home. It tests for sensorineural or permanent conductive hearing loss and central auditory processing disorder in children. In 2018 the Australian Government funded the roll-out of Sound Scouts to allow up to 600,000 children to test their hearing using Sound Scouts. This study estimated the cost-effectiveness of screening 5-year-old children for hearing loss using Sound Scouts at home, compared with no screening.

Design:

A decision-analytic model was developed to estimate the incremental costs and quality-adjusted life years (QALYs) of administering Sound Scouts over a 20-year time horizon. Testing accuracy was based on comparing Sound Scouts test results to clinical test results while other parameters were based on published data. Costs were estimated from the perspective of the Australian health care system. Univariate and probabilistic sensitivity analyses were undertaken.

Results:

Sound Scouts is estimated to result in an average incremental cost of A$61.02 and an average incremental increase in QALYs of 0.01. This resulted in an incremental cost-effectiveness ratio of A$5392 per QALY gained, which is likely to be considered cost-effective by Australian decision makers. Screening with Sound Scouts was found to have a 96.2 per cent probability of being cost-effective using a threshold of A$60,000 per QALY gained.

Conclusions:

Using Sound Scouts to screen five-year-old children for hearing loss (at home) is likely to be cost-effective. Screening children using Sound Scouts will result in early identification and intervention in childhood hearing loss, thereby reducing early childhood disadvantage through cumulative gains in quality of life, education, and economic outcomes over their lifetime.
Epigenetic therapy to enhance therapeutic effects of PD-1 inhibition in therapy-resistant melanoma
Authors: Sah Vasu R. , Karlsson Joakim , Jespersen Henrik , Lindberg Mattias F. , Nilsson Lisa M. , Ny Lars , Nilsson Jonas A.
Published: November 2021

Targeted therapy and immunotherapy have revolutionized the treatment of metastatic skin melanoma but around half of all patients develop resistance early or late during treatment. The situation is even worse for patients with metastatic uveal melanoma (UM). Here we hypothesized that the immunotherapy of therapy-resistant skin melanoma or UM can be enhanced by epigenetic inhibitors. Cultured B16F10 cells and human UM cells were treated with the histone deacetylase inhibitor (HDACi) entinostat or BETi JQ1. Entinostat-induced HLA expression and PD-L1, but JQ1 did not. A syngeneic mouse model carrying B16-F10 melanoma cells was treated with PD-1 and CTLA4 inhibitors, which was curative. Co-treatment with the bioavailable BETi iBET726 impaired the immunotherapy effect. Monotherapy of a B16-F10 mouse model with anti-PD-1 resulted in a moderate therapeutic effect that could be enhanced by entinostat. Mice carrying PD-L1 knockout B16-F10 cells were also sensitive to entinostat. This suggests HDAC inhibition and immunotherapy could work in concert. Indeed, co-cultures of UM with HLA-matched melanoma-specific tumor-infiltrating lymphocytes (TILs) resulted in higher TIL-mediated melanoma killing when entinostat was added. Further exploration of combined immunotherapy and epigenetic therapy in metastatic melanoma resistant to PD-1 inhibition is warranted.
Motivational Strategies and Concepts to Increase Participation and Adherence in Cardiac Rehabilitation
Authors: Bohplian Suweena , Bronas Ulf G.
Published: November 2021

Introduction:

Low participation and adherence to cardiac rehabilitation (CR) leads to ineffective care and increased risk of cardiac complications. There is a need to identify effective motivational strategies and concepts to increase participation and adherence to CR.

Purpose:

The aim of this review was to synthesize and integrate the current knowledge about motivational strategies and concepts to increase participation and adherence to CR.

Methods:

A literature search was performed using five electronic databases: CINAHL, Medline via PubMed, Scopus, Embase, and Rehabilitation & Sports Medicine Source. The search was limited to peer-reviewed studies, written in English, and publications from 2010 to 2019. A matrix and narrative synthesis were employed to organize and synthesize the findings, respectively.

Results:

Eight of 522 articles met the inclusion criteria. Four articles used motivational interviewing (MotI) and counseling strategy, three articles investigated the autonomy, competence, and relatedness of self-determination theory (SDT) concepts, and one article used a reinforced motivational strategy. Use of MotI led to improving the CR completion rate from 14% to 39%. The number of sessions attended/patient improved from 12 to 20 when the staff was provided attendance feedback and a reward. Autonomy, competence, and relatedness motivated patients to participate in and adhere to CR.

Conclusions:

Motivational interviewing and counseling, motivational and reinforcement strategies, and the autonomy, competence, and relatedness of SDT concepts should be utilized to promote participation and motivation for CR. The effects of these techniques on long-term CR require further research, including combining the identified methods to investigate the efficacy of these techniques on CR adherence.
First Human Cosavirus Detection From Cerebrospinal Fluid in Hospitalized Children With Aseptic Meningitis and Encephalitis in Iran
Authors: Moghaddam Farnoosh Sarkhani , Ghaderi Mostafa , Parsania Masoud , Mozhgani Sayed-Hamidreza , Arjmand Reza
Published: November 2021

Objective:

Human cosavirus (HCosV) is a newly recognized virus that seems to be partly related to nonpolio flaccid paralysis and acute gastroenteritis in pediatric patients. However, the relationship between HCosV and diseases in humans is unclear. To assess an investigation for the occurrence of HCosV among pediatric patients involved in meningitis and encephalitis, we implemented a real-time quantitative polymerase chain reaction assay for detection and quantification of HCosV in stool specimens.

Materials and Methods:

In this study, a total of 160 cerebrospinal fluid samples from September 2019 to October 2020 were collected from presenting pediatric patients with meningitis and encephalitis in a Karaj hospital, Iran. After viral RNA extraction, the real-time quantitative polymerase chain reaction was performed to amplify the 5′Un-Translated Region region of the HCosV genome and viral load was analyzed.

Results:

Of the 160 samples tested, the HCosV genomic RNA was detected in 2/160 (1.25%) of samples. The minimum viral load of HCosV was 3.5 × 103 copies/mL from 4 years male patient. The maximum viral load was determined to be 2.4 × 105 copies/mL in one sample obtained from 3.5 years female patient.

Conclusions:

This is the first documentation of HCosV detection in cerebrospinal fluid samples that better demonstrates relation of HCosV with neurologic diseases including meningitis and encephalitis. Also, these results indicate that HCosV has been circulating among Iranian pediatric patients.
DigiPrEP: A Pilot Trial to Evaluate the Feasibility, Acceptability, and Accuracy of a Digital Pill System to Measure PrEP Adherence in Men Who Have Sex With Men Who Use Substances
Authors: Chai Peter R. , Mohamed Yassir , Bustamante Maria J. , Goodman Georgia R. , Najarro Jesse , Castillo-Mancilla Jose , Baez Alejandro , Bronzi Olivia , Sullivan Matthew C. , Pereira Luis M. , Baumgartner Susan L. , Carnes Tony C. , Mayer Kenneth H. , Rosen Rochelle K. , Boyer Edward W. , O'Cleirigh Conall
Published: November 2021

Background:

Adherence to once daily oral preexposure prophylaxis (PrEP) for HIV prevention can be challenging for men who have sex with men (MSM) with substance use. Digital pill systems (DPS) comprise a radiofrequency emitter integrated into a gelatin capsule containing PrEP, which transmits data to a wearable Reader following ingestion, thereby enabling direct, real-time adherence measurement. This study evaluated the feasibility, acceptability, and accuracy of a DPS to measure PrEP adherence.

Methods:

A 90-day, single-arm, open-label, pilot demonstration trial was conducted with adult, cisgender, HIV-negative MSM on PrEP with nonalcohol substance use. Feasibility was measured via DPS engagement and timeline followback. Acceptability was assessed via qualitative user experience interviews. Accuracy was evaluated via DPS performance metrics, pill counts, and DBS to quantify tenofovir diphosphate.

Results:

Sixteen MSM enrolled (median age, 32 years), and 15 completed the study. Engagement remained stable over time. Emergent nonadherence patterns included intercurrent substance use. The DPS was largely acceptable based on interviews; the predominant barrier to use was the Reader. DPS-recorded ingestions totaled 1099, including 83.9% were detected by Reader and 16.1% were reported manually. The DPS recorded 92.2% of 1192 total expected ingestions per pill counts. Point-biserial correlation (R = 0.58; 95% CI: 0.21 to 0.80; P = 0.047) and Pearson correlation (month 1: R = 0.85; 95% CI: 0.57 to 0.95; P = 0.0002; month 3: R = 0.75; 95% CI: 0.17 to 0.94; P = 0.0197) showed strong correlations between DPS-recorded adherence and tenofovir diphosphate in dried blood spots.

Conclusion:

DPS are a feasible, acceptable, and accurate method of measuring PrEP adherence in MSM with substance use. Future investigations should incorporate DPS into behavioral interventions targeting nonadherence.
Characterization of Treatment Modalities for Patients With Syndromic Craniosynostosis in Relation to Degree of Midface Hypoplasia and Patient’s Age Using Longitudinal Follow-Up Data
Authors: Yang Il-Hyung , Chung Jee Hyeok , Lee Hyeok Joon , Park Juhwan , Oh Yoon-Kyo , Cho Il-Sik , Kim Sukwha , Baek Seung-Hak
Published: November 2021

The purpose of this study was to investigate the type and frequency of use of treatment modalities (Tx-Mods) in patients with syndromic craniosynostosis (SC) using longitudinal follow-up data. A total of 28 patients with SC (24 Crouzon, 2 Apert, and 2 Antley-Bixler syndromes), who were treated at the Department of Orthodontics, Seoul National University Dental Hospital, Seoul, South Korea between 1998 and 2020, was included. According to the degree of midface hypoplasia (MH) at the initial visit (T1), the patients were divided into the mild-MH (78°≤SNA < 80°, n = 8), moderate-MH (76≤SNA < 78°, n = 7), and severe-MH (SNA < 76°, n = 13) groups. T1-age and Tx-Mods, including cal-varial surgery (CALS), orthopedic treatment (OPT), fixed orthodontic treatment, and midface advancement surgery in childhood (MAS-child) and adulthood (MAS-adult), were investigated. Complexity of MAS-adult was graded as follows: 0, no surgery; 1, orthognathic surgery; 2, distraction osteogenesis (DOG); 3, combination of distraction osteogenesis and orthognathic surgery. Then, statistical analysis was performed. Percentage distribution of Tx-Mods was 71.4% in CALS, 21.4% in MAS-child, 42.9% in OPT, 100% in fixed orthodontic treatment, and 89.3% in MAS-adult. 92.9% of patients underwent MAS more than once. The number of MAS increased according to the severity of MH (P < 0.05). The complexity of MAS-adult increased as T1-age and severity of MH increased (all P < 0.05); whereas it decreased when CALS and OPT were performed (all P < 0.05). However, MAS in childhood did not guarantee the avoidance of additional MAS in adulthood (P > 0.05). These findings may be used as basic guidelines for successful treatment planning and prognosis prediction in patients with SC.
Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection
Authors: Chhajer Harsh , Rizvi Vaseef A. , Roy Rahul
Published: November 2021

Life cycle processes of positive-strand (+)RNA viruses are broadly conserved across families, yet they employ different strategies to grow in the cell. Using a generalized dynamical model for intracellular (+)RNA virus growth, we decipher these life cycle determinants and their dependencies for several viruses and parse the effects of viral mutations, drugs and host cell permissivity. We show that poliovirus employs rapid replication and virus assembly, whereas the Japanese encephalitis virus leverages its higher rate of translation and efficient cellular reorganization compared to the hepatitis C virus. Stochastic simulations demonstrate infection extinction if all seeding (inoculating) viral RNA degrade before establishing robust replication critical for infection. The probability of this productive cellular infection, ‘cellular infectivity’, is affected by virus–host processes and defined by early life cycle events and viral seeding. An increase in cytoplasmic RNA degradation and delay in vesicular compartment formation reduces infectivity, more so when combined. Synergy among these parameters in limiting (+)RNA virus infection as predicted by our model suggests new avenues for inhibiting infections by targeting the early life cycle bottlenecks.
Cryptochrome magnetoreception: four tryptophans could be better than three
Authors: Wong Siu Ying , Wei Yujing , Mouritsen Henrik , Solov'yov Ilia A. , Hore P. J.
Published: November 2021

The biophysical mechanism of the magnetic compass sensor in migratory songbirds is thought to involve photo-induced radical pairs formed in cryptochrome (Cry) flavoproteins located in photoreceptor cells in the eyes. In Cry4a—the most likely of the six known avian Crys to have a magnetic sensing function—four radical pair states are formed sequentially by the stepwise transfer of an electron along a chain of four tryptophan residues to the photo-excited flavin. In purified Cry4a from the migratory European robin, the third of these flavin–tryptophan radical pairs is more magnetically sensitive than the fourth, consistent with the smaller separation of the radicals in the former. Here, we explore the idea that these two radical pair states of Cry4a could exist in rapid dynamic equilibrium such that the key magnetic and kinetic properties are weighted averages. Spin dynamics simulations suggest that the third radical pair is largely responsible for magnetic sensing while the fourth may be better placed to initiate magnetic signalling particularly if the terminal tryptophan radical can be reduced by a nearby tyrosine. Such an arrangement could have allowed independent optimization of the essential sensing and signalling functions of the protein. It might also rationalize why avian Cry4a has four tryptophans while Crys from plants have only three.
Science popularization in nineteenth century France: Nérée Boubée (1806–1862) and the journal
L'Écho du Monde Savant
Authors: Figueirôa Silvia F. de M.
Published: November 2021

Simon-Suzanne-Nérée Boubée was born in Toulouse (France) in May 1806 and died in August 1862 in Luchon (France). This paper discusses Boubée's activities as a science popularizer exemplified through the journal
L'Écho du Monde Savant
, published in Paris from 1834 to 1846.
L'Écho
intended to ‘present a summary of the most important news taking place within the savant world’ to the public. In this journal Boubée published a broad range of topics, for example, advocating the crucial role and extent of geology, and the utmost value of industry and agriculture. The working hypothesis is that Boubée's convictions and profile, intertwined with some relevant trends within the French intellectual context—as manifested in science and technology matters—constituted the propelling force for his project to popularize science. Boubée's commitments to popular education, together with other aspects such as valuing the knowledge of workers, and praise for women's education and their scientific activity, were aligned with contemporary political and social movements. Like many practitioners of science hitherto unknown to historians, his work deserves deeper appreciation.
Regulation of transforming growth factor-β signalling by SUMOylation and its role in fibrosis
Authors: Wang Xinyi , Liu Ting , Huang Yifei , Dai Yifeng , Lin Hui
Published: November 2021

Fibrosis is an abnormal healing process that only repairs the structure of an organ after injury and does not address damaged functions. The pathogenesis of fibrosis is multifactorial and highly complex; numerous signalling pathways are involved in this process, with the transforming growth factor-β (TGF-β) signalling pathway playing a central role. TGF-β regulates the generation of myofibroblasts and the epithelial–mesenchymal transition by regulating transcription and translation of downstream genes and precisely regulating fibrogenesis. The TGF-β signalling pathway can be modulated by various post-translational modifications, of which SUMOylation has been shown to play a key role. In this review, we focus on the function of SUMOylation in canonical and non-canonical TGF-β signalling and its role in fibrosis, providing promising therapeutic strategies for fibrosis.
tRNA copy number and codon usage in the sea cucumber genome provide insights into adaptive translation for saponin biosynthesis
Authors: Liu Chengzhang , Yuan Jianbo , Zhang Xiaojun , Jin Songjun , Li Fuhua , Xiang Jianhai
Published: November 2021

Genomic tRNA copy numbers determine cytoplasmic tRNA abundances, which in turn influence translation efficiency, but the underlying mechanism is not well understood. Using the sea cucumber
Apostichopus japonicus
as a model, we combined genomic sequence, transcriptome expression and ecological food resource data to study its codon usage adaptation. The results showed that, unlike intragenic non-coding RNAs, transfer RNAs (tRNAs) tended to be transcribed independently. This may be attributed to their specific Pol III promoters that lack transcriptional regulation, which may underlie the correlation between genomic copy number and cytoplasmic abundance of tRNAs. Moreover, codon usage optimization was mostly restrained by a gene's amino acid sequence, which might be a compromise between functionality and translation efficiency. Genes for stress responses were highly optimized for most echinoderms, while enzymes for saponin biosynthesis (LAS, CYPs and UGTs) were especially optimized in sea cucumbers, which might promote saponin synthesis as a defence strategy. The genomic tRNA content of
A. japonicus
was positively correlated with amino acid content in its natural food particles, which should promote its efficiency in protein synthesis. We propose that coevolution between genomic tRNA content and codon usage of sea cucumbers facilitates their saponin synthesis and survival using food resources with low nutrient content.
Maintenance and loss of endocytic organelle integrity: mechanisms and implications for antigen cross-presentation
Authors: Childs Eleanor , Henry Conor M. , Canton Johnathan , Reis e Sousa Caetano
Published: November 2021

The membranes of endosomes, phagosomes and macropinosomes can become damaged by the physical properties of internalized cargo, by active pathogenic invasion or by cellular processes, including endocytic maturation. Loss of membrane integrity is often deleterious and is, therefore, prevented by mitigation and repair mechanisms. However, it can occasionally be beneficial and actively induced by cells. Here, we summarize the mechanisms by which cells, in particular phagocytes, try to prevent membrane damage and how, when this fails, they repair or destroy damaged endocytic organelles. We also detail how one type of phagocyte, the dendritic cell, can deliberately trigger localized damage to endocytic organelles to allow for major histocompatibility complex class I presentation of exogenous antigens and initiation of CD8
+
T-cell responses to viruses and tumours. Our review highlights mechanisms for the regulation of endocytic organelle membrane integrity at the intersection of cell biology and immunology that could be co-opted for improving vaccination and intracellular drug delivery.
Molecular and morphological approach to study the innexin gap junctions in
Rhynchosciara americana
Authors: Neves Jorge Henrique , Rezende-Teixeira Paula , Palomino Natalia Bazan , Machado-Santelli Glaucia Maria
Published: November 2021

Gap junctions mediate communication between adjacent cells and are fundamental to the development and homeostasis in multicellular organisms. In invertebrates, gap junctions are formed by transmembrane proteins called innexins. Gap junctions allow the passage of small molecules through an intercellular channel, between a cell and another adjacent cell. The dipteran
Rhynchosciara americana
has contributed to studying the biology of invertebrates and the study of the interaction and regulation of genes during biological development. Therefore, this paper aimed to study the
R. americana
innexin-2 by molecular characterization, analysis of the expression profile and cellular localization. The molecular characterization results confirm that the message is from a gap junction protein and analysis of the expression and cellular localization profile shows that innexin-2 can participate in many physiological processes during the development of
R. americana
.
Green quantitative spectrofluorometric analysis of rupatadine and montelukast at nanogram scale using direct and synchronous techniques
Authors: Ghonim Rana , El-Awady Mohamed I. , Tolba Manar M. , Ibrahim Fawzia
Published: November 2021

Two green-sensitive spectrofluorometric methods were investigated for assay of rupatadine (RUP) [method I] and its binary mixture with montelukast (MKT) [method II]. Method I depends on measuring native fluorescence of RUP in the presence of 0.10 M H2SO4and 0.10%w/v sodium dodecyl sulfate at 455 nm after excitation at 277 nm. The range of the first method was 0.20–2.00 µg ml−1with detection and quantitation limits of 59.00 and 179.00 ng ml−1, respectively. Method II depends on the first derivative synchronous spectrofluorometry. The derivative intensities were measured for the two drugs in an aqueous solution containing Mcllvaine's buffer pH 2.60 at fixed Δλof 140 nm. Each drug was estimated at zero-contribution of the other. The intensity was measured at 261 and 371 nm for RUP and MKT, respectively. The method was linear over 0.10–4.00 and 0.20–1.60 µg ml−1with limits of detection 31.00 and 66.00 ng ml−1and limits of quantitation 94.00 and 200.00 ng ml−1for RUP and MKT, respectively. The method was extended to determine this mixture in laboratory-prepared mixtures and combined tablets. Method validation was performed according to ICH guidelines. Statistical interpretation of data revealed good agreement with the comparison method. Method greenness was confirmed by applying three different assessment tools.
Biomembranes undergo complex, non-axisymmetric deformations governed by Kirchhoff–Love kinematicsand revealed by a three-dimensional computational framework
Authors: Auddya Debabrata , Zhang Xiaoxuan , Gulati Rahul , Vasan Ritvik , Garikipati Krishna , Rangamani Padmini , Rudraraju Shiva
Published: November 2021

Biomembranes play a central role in various phenomena like locomotion of cells, cell-cell interactions, packaging and transport of nutrients, transmission of nerve impulses, and in maintaining organelle morphology and functionality. During these processes, the membranes undergo significant morphological changes through deformation, scission, and fusion. Modelling the underlying mechanics of such morphological changes has traditionally relied on reduced order axisymmetric representations of membrane geometry and deformation. Axisymmetric representations, while robust and extensively deployed, suffer from their inability to model-symmetry breaking deformations and structural bifurcations. To address this limitation, a three-dimensional computational mechanics framework for high fidelity modelling of biomembrane deformation is presented. The proposed framework brings together Kirchhoff–Love thin-shell kinematics, Helfrich-energy-based mechanics, and state-of-the-art numerical techniques for modelling deformation of surface geometries. Lipid bilayers are represented as spline-based surface discretizations immersed in a three-dimensional space; this enables modelling of a wide spectrum of membrane geometries, boundary conditions, and deformations that are physically admissible in a three-dimensional space. The mathematical basis of the framework and its numerical machinery are presented, and their utility is demonstrated by modelling three classical, yet non-trivial, membrane deformation problems: formation of tubular shapes and their lateral constriction, Piezo1-induced membrane footprint generation and gating response, and the budding of membranes by protein coats during endocytosis. For each problem, the full three-dimensional membrane deformation is captured, potential symmetry-breaking deformation paths identified, and various case studies of boundary and load conditions are presented. Using the endocytic vesicle budding as a case study, we also present a ‘phase diagram’ for its symmetric and broken-symmetry states.
Muography as a new complementary tool in monitoring volcanic hazard: implications for early warning systems
Authors: Leone Giovanni , Tanaka Hiroyuki K. M. , Holma Marko , Kuusiniemi Pasi , Varga Dezső , Oláh László , Presti Domenico Lo , Gallo Giuseppe , Monaco Carmelo , Ferlito Carmelo , Bonanno Giovanni , Romeo Giuseppe , Thompson Lee , Sumiya Kenji , Steigerwald Sara , Joutsenvaara Jari
Published: November 2021

Muography uses muons naturally produced in the interactions between cosmic rays and atmosphere for imaging and characterization of density differences and time-sequential changes in solid (e.g. rocks) and liquid (e.g. melts ± dissolved gases) materials in scales from tens of metres to up to a few kilometres. In addition to being useful in discovering the secrets of the pyramids, ore prospecting and surveillance of nuclear sites, muography successfully images the internal structure of volcanoes. Several field campaigns have demonstrated that muography can image density changes relating to magma ascent and descent, magma flow rate, magma degassing, the shape of the magma body, an empty conduit diameter, hydrothermal activity and major fault lines. In addition, muography is applied for long-term volcano monitoring in a few selected volcanoes around the world. We propose using muography in volcano monitoring in conjunction with other existing techniques for predicting volcanic hazards. This approach can provide an early indication of a possible future eruption and potentially the first estimate of its scale by producing direct evidence of magma ascent through its conduit in real time. Knowing these issues as early as possible buy critically important time for those responsible for the local alarm and evacuation protocols.
PccGEO: prior constraints conditioned genetic elements optimization
Authors: Xu Hanwen , Zhang Pengcheng , Wang Haochen , Wei Lei , Hu Zhirui , Wang Xiaowo
Published: November 2021

Functional genetic elements are one of the most essential units for synthetic biology. However, both knowledge-driven and data-driven methodology can hardly accomplish the complicated task of genetic elements design efficiently due to the lack of explicit regulatory logics and training samples. Here, we proposed a knowledge-constraint deep learning model named PccGEO to automatically design functional genetic elements with high success rate and efficiency. PccGEO utilized a novel “fill-in-the-flank” strategy with a conditional generative adversarial network structure to optimize the flanking regions of known functional sequences derived from the biological prior knowledge, which can efficiently capture the implicit patterns with a reduced searching space. We applied PccGEO in the design ofEscherichia colipromoters, and found that the implicit patterns in flanking regions matter to the properties of promoters such as the expression level. The PccGEO-designed constitutive and inducible promoters showed more than 91.6% chance of success by in vivo validation. We further utilized PccGEO by setting a limited frequency of nucleotide modifications and surprisingly found that the expression level ofE. colisigma 70 promoters could show up to a 159.3-fold increase with only 10-bp nucleotide modifications. The results supported that the implicit patterns are important in the design of functional gene elements and validated the strong capacity of our method in the efficient design of functional genetic elements.

Availability

https://github.com/WangLabTHU/PccGEO
Does social capital provide marketing benefits for startup business? An emerging economy perspective
Authors: Mukul Kumar , Pandey Neeraj , Saini Gordhan K.
Published: November 2021

Purpose

This study explores the relevance of social capital resources generated through networks to address the marketing challenges of startups. It looks into the marketing issues faced by startup firms in emerging markets and examines how they leverage their social capital to reach out to their customers and other stakeholders for marketing their products and services.

Design/methodology/approach

The case study analysis using the abduction method, semi-structured interview and content analysis were used for answering the research questions.

Findings

This study finds the importance of developing social capital by startups for marketing activities. Social capital also acts as a strategic advantage that the competitors cannot easily emulate. Findings show that the development of social capital happens through the network of startup entrepreneurs and social connections involving customers, dealers and suppliers, among others.

Originality/value

This study is a novel attempt to emphasize the potential of social capital for marketing activities in a startup firm. This study expands the literature on social capital with a marketing perspective in an emerging economy context. The academic and managerial implications have also been highlighted in the study.
What colour are you? Smartphone addiction traffic lights and user profiles
Authors: San-Martín Sonia , Jiménez Nadia
Published: November 2021

Purpose

The key concern nowadays is smartphone addiction and user profiles. Following the risk and protective factors framework, the authors aim to characterize smartphone users according to two levels: (1) individual: referred to the use (i.e. boredom proneness, compulsive app downloading smartphone addiction) and (2) microsystem: referred to family and peers (i.e. family harmony and phubbing). Besides, the authors will derive useful managerial implications and strategies.

Design/methodology/approach

First, an extensive literature revision and in-depth interviews with experts were employed to identify the addiction-related variables at the individual and microsystem level. Second, information was collected from a sample of 275 Spanish smartphone users, and a K-means clustering algorithm was employed to classify smartphone users.

Findings

The proposed traffic lights schema identifies three users’ profiles (red, yellow and green) regarding their smartphone addiction and considering individual and microsystem critical variables.

Originality/value

This study proposes a practical and pioneer traffic lights schema to classify smartphone users and facilitate each cluster's strategies development.
Examining of the effect of HRM in mitigating negative effects of LM&SS on employee well-being in health care
Authors: De Koeijer Relinde , Paauwe Jaap , Huijsman Robbert , Strating Mathilde
Published: November 2021

Purpose

This study aims to examine the effect of human resource management (HRM) in mitigating negative effects of Lean management and Six Sigma (LM&SS) on employee well-being in health care. The authors subdivide well-being into three components: happiness, trust and health.

Design/methodology/approach

This is a cross-sectional, multisite survey study in internal service units of hospitals. Data analyzed using multivariate regression come from a sample of 1,886 survey respondents (42 units,N= 218 supervisors,N= 1,668 employees) in eight Dutch academic hospitals that have implemented LM&SS.

Findings

The present study findings show no or weak effects of LM&SS on the happiness and health component of employee well-being. In addition, the authors found a significant but weak direct positive effect (ß= 0.07) of the LM&SS bundle on the trusting relationships component of well-being. Therefore, moderating effects of HRM practices on the relationship between LM&SS and employee well-being seem less relevant because an existing relationship between LM&SS and employee well-being is a prerequisite for moderation (Hayes, 2009). There were unexpected side effects. Inspired by research that discusses direct effects of HRM on employee well-being, the authors tested this relationship and found that HRM has a direct positive effect on trust and happiness of employees in health care. For the health component of well-being, the present results show a weak negative effect of HRM.

Practical implications

This study results in a cautiously optimistic view about LM&SS in health care, provided that it is applied in a targeted manner (to improve the performance of their processes) and that HRM is strategically aligned with the goals of LM&SS to improve employees’ happiness and trusting relationships.

Originality/value

Unique features of the study are the focus on the consequences for employees’ well-being related to LM&SS in health care, the role of HRM in regard to this relationship and the participation of all eight Dutch academic hospitals in this research.