bluuebunny/crossref_metadata_2025 huggingface dataset:
Standing with the WHO
Authors: Cipriano Pamela F.
Published: August 2020

Hope for the future of global health.
New Indication for Solifenacin
Authors: Aschenbrenner Diane S.
Published: August 2020

Solifenacin succinate oral suspension (Vesicare LS) has been approved to treat neurogenic detrusor overactivity in children ages two years and older.
An Intimate Glimpse of Emergency Nurses at Work
Authors: Molyneux Jacob
Published: August 2020

A new film about ED nurses—made before COVID-19 raised the stakes—conveys hope even as it reveals a fraying safety net.
Nurses' Perceptions of Technology Used in Language Interpretation for Patients with Limited English Proficiency
Authors: Marcus Jessica , MacMillan Deborah , Ketchie Monica , Clark Patricia C.
Published: August 2020

Purpose:

This project examined nurses' positive and negative perceptions of the technology used in language interpretation for patients who have limited English proficiency (LEP). The intervention was guided by the technology acceptance model, a framework that addresses users' acceptance or rejection of computer-based technology.

Methods:

A sample of 47 nurses participated. Nurses' perceptions of an existing telephone-based remote interpretation technology were compared with their perceptions of a video remote interpretation (VRI) system. Instruments included a structured questionnaire to collect nurses' demographic and other characteristics and to measure their perceptions of the technology used in language interpretation; open-ended questions were added on how technology affected nursing care and nurses' rapport and communication with patients. Questionnaires on the telephone-based interpretation technology were administered, and after an eight-week trial of the VRI technology, questionnaires on the VRI system were administered.

Results:

Overall, positive perceptions of VRI were significantly higher and negative perceptions significantly lower compared with perceptions of telephone-based interpretation technology (P < 0.001 for both). Qualitative findings indicated that VRI technology improved communication and was less time consuming for nurses.

Conclusions:

Nurses preferred VRI technology because of its positive effects on time expenditure and communication. VRI technology is likely to be adopted successfully and ensures increased use of professional language interpretation for patients with LEP.
Antibiotics May Not Be Necessary for Some Patients with Diverticulitis
Authors: Rosenberg Karen
Published: August 2020

According to this study:

There is strong evidence that the use of antibiotics can be safely omitted in select patients who have uncomplicated acute diverticulitis.
A Case Report of Isopropanol Ingestion During the SARS-CoV-2 Pandemic
Authors: Meehan Caroline P. , Wightman Rachel S.
Published: August 2020

Introduction:

Patients with substance use disorder may be particularly vulnerable to withdrawal-related complications during the SARS-CoV-2 (COVID-19) pandemic. Limited availability of alcohol and other substances coupled with decreased accessibility to substance use treatment poses a substantial risk to this population. Isopropanol, the active ingredient in rubbing alcohol, is widely available; thus, it may be used in times of scarcity.

Case Report:

We present a case of intentional isopropanol ingestion used as an ethanol surrogate within the setting of the COVID-19 pandemic.

Conclusions:

Toxic alcohol ingestions are imperative considerations on the differential for the intoxicated patient particularly during resource-limited times.
Tibial Lengthening Technique
Authors: Rozbruch S. Robert
Published: August 2020

Lengthening of the tibia with a motorized internal nail is effective and has advantages over the traditional use of external fixation. Since nail entry is through the proximal end of the bone, it is indicated for skeletally mature patients. Principles of leg-lengthening must be followed but the techniques have been modified from those of external fixation. Fibula relationship to the tibia is protected with fibula length stabilization screws. If there is a deformity, then fixator assisted nailing and the use of blocking screws are used to acutely correct the alignment, and then gradual lengthening follows. Judicious use of soft-tissue procedures, such as fasciotomy, gastrocsoleus release, and peroneal nerve decompression are often needed.
Extramedullary Internal Limb Lengthening
Authors: Shannon Claire , Paley Dror
Published: August 2020

Extramedullary implantable limb lengthening (EMILL) uses an implantable nail attached to the bone like and internal-external fixator. Cantilever forces can be neutralized by inserting a small diameter solid rod as a guide inside the medullary canal. EMILL expands the indications for internal limb lengthening to younger children with smaller diameter and length bones and to bones with impassable medullary canals. One must follow the same principles as with external fixation lengthening including prevention of joint subluxation and contracture by preparatory surgery (eg, pelvic osteotomy), soft tissue releases, temporary arthrodesis, and bracing. Lengthening should be restricted to amounts no >5 cm to avoid complications. A retrospective review of EMILL cases performed at the authors’ institution since 2015 was performed. Thirteen patients underwent 14 EMILL procedures; 10 femurs and 4 tibias. Twelve of 13 patients lengthened to within 5 mm of their preoperative goal. There were no mechanical nail failures. No patient had a significant axial deviation of the bone during distraction. Three patients required unplanned operations. EMILL is safe and effective in patients who would otherwise require external fixation.
Endocrine therapy combined with targeted therapy in hormone receptor-positive metastatic breast cancer
Authors: Bian Li , Xu Feng-Rui , Jiang Ze-Fei
Published: August 2020

Increasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the “AI (aromatase inhibitor) era” represented by aromatase inhibitors, we have gradually entered the “post-AI era” represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the “combination of endocrine therapy and targeted therapy” era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.
C-arm-based flat-panel detector cone-beam computed tomography venography in the diagnosis of iliac vein compression syndrome
Authors: Wang Chang-Ming , Zhang Wei-Liang , Li Xuan
Published: August 2020

Background:

C-arm-based flat-panel detector cone-beam computed tomography (CBCT) venography has never been used in the management of iliac vein compression syndrome (IVCS). This study aimed to determine the technical feasibility and safety of CBCT venography in the diagnosis of IVCS compared with conventional venography (CV).

Methods:

Twenty patients with clinical manifestations of lower extremity venous insufficiency were prospectively enrolled between May 2018 and December 2018. Each patient underwent both CV and CBCT venography. The feasibility and safety of CBCT venography were assessed by technical success rate and complication rate. The relationships between the clinical indexes and the results of CBCT venography and CV were analyzed with correlation analysis. The consistency of the diagnosis of IVCS using each modality was analyzed by the kappa test.

Results:

The technical success rate was 100% for CBCT venography and for CV, without any complications. Compared with CV, CBCT venography was able to show more details of adjacent tissues which might be helpful for making etiological diagnosis. The stenosis rate under CBCT venography had excellent consistency with that under CV (kappa = 0.78, Chi-square test). The stenosis rate under CBCT venography was positively correlated with the presence of collateral veins (odds ratio 1.12, 95% confidence interval: [1.00, 1.26], P = 0.049), while the stenosis rate under CV was not. Unexpectedly, only one patient had a venous pressure gradient of more than 2 mmHg (1 mmHg = 0.133 kPa).

Conclusions:

For the diagnosis of IVCS, C-arm-based CBCT venography was technically feasible, with good safety. The presence of collateral veins on CBCT was clinically significant. A C-arm fluoroscopy-based technique that combines CV and CBCT might be a promising protocol for the management of IVCS during a single session.
What is the Nature of the Reach-and-Grasp Deficit in Glaucoma?
Authors: Corveleyn Xavier , Lenoble Quentin , Rouland Jean-François , Boucart Muriel
Published: August 2020

Précis:

In a reach-and-grasp task, patients with glaucoma exhibited a motor disorder, even when they had time to explore their environment. The motor performance of glaucoma patients should be taken into account in rehabilitation.

Purpose:

Vision plays an important role in planning and executing manual prehension (reaching and grasping). We assess the impact of glaucoma on motor production, as a function of the visual exploration time available to the patients.

Methods:

We compared performance in 2 reach-and-grasp tasks determined by whether or not the participants (16 glaucoma patients, 14 age-matched and 18 young controls) had time to explore the objects before reaching and grasping a target object defined by its color.

Results:

Differences were observed between glaucoma patients and age-matched controls on movement duration and peak velocity (reaching phase) only when participants were not provided time to look at the objects before the movement (immediate condition).

Conclusions:

Glaucoma patients exhibited a motor disorder (grasping phase) only when they had no time to explore their environment before performing the reach-and-grasp task. The motor abnormalities in reaching phase observed in glaucoma patients in previous studies seem to result from difficulties in target identification rather than from visuomotor deficits. From a clinical point of view, motor performances of glaucoma patients could be modulated by task, especially by temporal constraints of task.
Objectives to Assess Student Readiness for First, Full-Time Clinical Education Experiences in Physical Therapist Education
Authors: Dupre Anne-Marie , McAuley J. Adrienne , Wetherbee Ellen
Published: August 2020

Introduction.

To date, there is a lack of standardization across physical therapist education programs (PTEPs) in the United States as to what qualifies students to be ready for first, full-time clinical education experiences (CEEs). This study aimed to develop readiness objectives for first, full-time CEEs that will be applicable to all clinical settings, based on input from regional clinical faculty.

Methods.

Clinical faculty (n = 50) accepted an email invitation from the New England Consortium of Clinical Educators to participate in the study. Academic faculty (n = 20) served as facilitators and scribes during the in-person data collection and also completed the survey. Data saturation and consensus building were used in a 2-round modified-Delphi process. Readiness objectives were developed in-person, during the initial round, using the categories of the American Physical Therapy Association'sClinical Performance Instrument(CPI) and Bloom's Taxonomy to inform the process. The second round of data collection asked participants to rate the previously developed readiness objectives for degree of importance and appropriateness of performance level for first, full-time CEEs. This phase was completed via electronic survey.

Results.

Participants agreed that 22 readiness objectives were “very important.” Eleven of these readiness objectives were within the affective domain, specifically in theCPIcategories of Accountability, Professional Behaviors, Communication, and Cultural Competence. Of the remaining readiness objectives, 5 were directly related to patient safety.

Discussion and Conclusion.

The results of this study are consistent with other health care professional literatures that indicate clinical faculty prioritize students' behaviors in the affective domain and their ability to maintain patient safety. It is incumbent on the PTEPs to provide students opportunities for development and practice in these areas and assess performance related to these readiness objectives before the first, full-time CEEs. Utilization of these 22 readiness objectives is one method by which PTEPs may meet this expectation.
A novel splicing mutation in F8 causes various aberrant transcripts in a hemophilia A patient and identifies a new transcript from healthy individuals
Authors: Yi Sheng , Zuo Yangjin , Yu Qiuxia , Yang Qi , Li Mengting , Lan Yueyun , Huang Limei , Zhang Qinle , Qin Zailong , Luo Jingsi
Published: August 2020

Hemophilia A is an X-linked hemorrhagic disorder caused by deficiency or dysfunction of the coagulation factor VIII (FVIII), and a great variety of mutations in the factor VIII gene (F8) are identified. We aimed to identify the genetic defects of the F8 gene in a Chinese patient with moderate hemophilia A. We have identified a novel intronic variant in the hemophilia A patient by DNA sequence analysis, cDNA sequencing, and TA clone sequencing. An intronic variant, c.5816-1G>A, was identified and the cDNA sequencing confirmed the pathogenicity of the transition. TA clone sequencing showed that the splicing mutation produced two aberrant premRNA skipping exons (18 and exon 18 + 19, respectively). These aberrant mRNA forms maintain the reading frame and are predicted to code for deleted FVIII isoforms and the shorter abnormal transcript accounted for one-eighth of the total mRNA. There was a new unreported transcript with E22 spliced out in healthy individuals and our patient, whose specific functions need to be determined in further studies. Our study widens the mutation spectrum of the F8 gene. In addition, the study findings could provide the opportunity to reveal alternative splicing patterns.
Concurrent Subcutaneous Panniculitis-like T-Cell Lymphoma and B-Cell Acute Lymphoblastic Leukemia in 2 Pediatric Patients
Authors: Smith Geoffrey A. , Levinson Anya L. , Galvin Robert T. , Lalor Leah E. , McCalmont Timothy , Wang Linlin , Geis Michael C. , Odegaard Karah , Hupp Meghan , Maguiness Sheilagh , Turcotte Lucie M. , Cordoro Kelly M. , Hermiston Michelle L.
Published: August 2020

Subcutaneous panniculitis-like T-cell lymphoma is a cutaneous lymphoma characterized by CD8+ T-cell infiltrate in the subcutis that is rare in children. Acute lymphoblastic lymphoma is the most common pediatric malignancy and often presents with fevers and pancytopenia. Herein, we report 2 pediatric patients presenting with subcutaneous panniculitis-like T-cell lymphoma and B-cell acute lymphoblastic lymphoma, distinct hematologic malignancies arising from different lymphoid lineages, with no identifiable germline cancer predisposition.
Food Refusal Secondary to Psychosis
Authors: Pacilio Rachel M. , Coverdale John H. , Siddiqui Sameera , David Elizabeth H. , Gordon Mollie R.
Published: August 2020

The aim of this article is to emphasize that starvation is an important potential consequence of psychosis and to provide recommendations for management of this condition. A review of the literature on food refusal and starvation in patients with psychotic illnesses was performed. Our search strategy returned 54 articles with one article meeting inclusion criteria. Additional independent research returned an additional four cases of patients with psychosis engaging in self-starvation. The cases of several patients from our institution who engaged in self-starvation behaviors as a result of psychosis are also presented. The management and outcomes of each of these 10 patients are discussed. Starvation secondary to psychosis is an important but underappreciated consequence of psychosis that can lead to serious adverse outcomes in these patients. Few cases have been reported in the literature. More study is warranted to develop evidence-based management guidelines.
Voices
Authors: Ross Colin A.
Published: August 2020

Auditory hallucinations are widely regarded as symptoms of brain disease treated with medications. In an alternative paradigm, voices are understood as trauma-driven dissociated, disowned, or disavowed aspects of self; the goal is not to suppress them but to integrate them during psychotherapy. Auditory hallucinations are common in dissociative identity disorder, borderline personality disorder, and complex posttraumatic stress disorder and are not specific to psychosis. The features that differentiate psychotic from dissociative voices include the qualities of the voices themselves, as well as other symptoms: for example, compared with dissociative voices, psychotic voices are accompanied by less sociability, more formal thought disorder, more negative symptoms including blunted affect, and more delusions. The author proposes that the psychotherapy of dissociative voices can be indicated trans-diagnostically, including in a subgroup of individuals with diagnoses of schizophrenia. Psychotherapeutic strategies are illustrated with a case example.
A Brief Review of Scanning Electron Microscopy With Energy-Dispersive X-ray Use in Forensic Medicine
Authors: Gentile Guendalina , Andreola Salvatore , Bailo Paolo , Battistini Alessio , Boracchi Michele , Tambuzzi Stefano , Zoja Riccardo
Published: August 2020

Scanning electron microscopy with energy-dispersive x-ray (SEM/EDX) analysis is an investigation whose potential has become increasingly important in the field of forensic research and diagnosis. We present the procedure to perform a well–carried-out SEM/EDX analysis on corpses affected by different types of injuries, such as blunt force trauma, ligature strangulation, electrocution, sharp force trauma, gunshot wounds, and intoxication. After the areas of forensic interest have been macroscopically identified, the sampling can be performed in 2 different ways: apposition of the double-sided graphite tape on the damaged area or performing the excision of a biological sample. In both cases, a proper negative control sample is required. In all cases, SEM/EDX analysis can detect exogenous microtraces consistent with the types of injuries involved. In blunt force trauma, microparticles of different nature deriving from the contact of the blunt instrument with the victim may be observed; in sharp force trauma, metal microtraces (Fe, Cr, Al, Ti) can be identified. In ligature strangulation, exogenous microtraces may be found in the cutaneous furrow. In electrocution, it allows to identify the pathognomonic metal pattern (Cu, Zn, Fe) of the “electric mark.” In gunshot wounds, the main applications regards the detection of metal particles (Pb, Ba, Sb) of gunshot residues. Finally, in the analysis of intoxicants, it may identify traces of toxic substances. Thus, the authors conclude that SEM/EDX analysis can provide essential information to assist in the medicolegal investigation of death.
Serum lipid profile changes and their clinical diagnostic significance in COVID-19 Mexican Patients
Authors: Osuna-Ramos Juan Fidel , Rendón-Aguilar Horacio , Jesús-González Luis Adrián De , Reyes-Ruiz José Manuel , Espinoza-Ortega Arely Montserrat , Ochoa-Ramírez Luis Antonio , Romero-Utrilla Alejandra , Ríos-Burgueño Efrén , Soto-Almaral Alejandro , Ríos-Tostado Juan José , Romero-Quintana José Geovanni , Ponce-Ramos Héctor , Farfan-Morales Carlos Noe , Ángel Rosa María del , Barajas-Martínez Héctor , Rodríguez-Millán José , Velarde-Félix Jesús Salvador
Published: August 2020

Background

COVID-19 has been recognized as an emerging and rapidly evolving health condition. For this reason, efforts to determine changes in laboratory parameters of COVID-19 patients as biomarkers are urgent. Lipids are essential components of the human body, and their modulation has been observed implicated in some viral infections.

Methods

To evaluate the clinical diagnosis utility of the lipid profile changes in Mexican COVID-19 patients, the lipid profile of one hundred two COVID-19 positive patients from three hospitals in Culiacan, Sinaloa in northwest Mexico, was analyzed. ROC curves and binary logistic regression analysis were used as a predictive model to determine their clinical diagnostic utility.

Results

Significant changes in the serum lipid profile of patients with COVID-19, such as low levels of cholesterol, LDL, and HDL, while high triglycerides and VLDL were observed. The same abnormalities in the lipid profile among non-critical and critical COVID-19 patients were detected. The predictive model analysis suggests that cholesterol and LDL have AUC values of 0.710 and 0.769, respectively, for COVID-19 (p= 0.0002 and p= <0.0001), and LDL low levels might be a risk factor for critical COVID-19 (OR= 2.07, 95% IC: 1.18 to 3.63; p= 0.01).

Conclusion

Our findings suggest that low cholesterol and LDL levels could be considered an acceptable predictor for COVID-19, and low levels of LDL might be a risk factor for critical COVID-19 patients.
Early onset non-syndromic retinal degeneration due to variants in INPP5E: phenotypic expansion of the ciliary gene previously associated with Joubert syndrome
Authors: Sangermano Riccardo , Deitch Iris , Peter Virginie G. , Ba-Abbad Rola , Place Emily M. , Wagner Naomi E. , Fulton Anne B. , Coutinho-Santos Luisa , Rosin Boris , Dunet Vincent , AlTalbishi Ala’a , Banin Eyal , Sousa Ana Berta , Neves Mariana , Larson Anna , Quinodoz Mathieu , Michaelides Michel , Ben-Yosef Tamar , Pierce Eric A. , Rivolta Carlo , Webster Andrew R. , Arno Gavin , Sharon Dror , Huckfeldt Rachel M. , Bujakowska Kinga M.
Published: August 2020

Purpose

Pathogenic variants in INPP5E cause Joubert syndrome, a systemic disorder that can manifest with retinal degeneration among other clinical features. We aimed to evaluate the role of INPP5E variants in non-syndromic inherited retinal degenerations (IRDs) of varying severity.

Methods

Targeted or genome sequencing were performed in 12 unrelated non-syndromic IRD families from multiple research hospitals. Detailed clinical examination was conducted in all probands. The impact of new likely pathogenic variants was modeled on a tertiary INPP5E protein structure and all the new and published variants were analyzed for their deleteriousness and phenotypic correlation.

Results

Fourteen INPP5E rare alleles were detected, 12 of which were novel. Retinal degeneration in all 12 probands was clinically distinguishable on the basis of onset and severity into Leber congenital amaurosis (n=4) and a milder, later-onset rod-cone dystrophy (n=8). Two probands showed mild ciliopathy features that resolved in childhood. Analysis of the combined impact of both alleles in syndromic and non-syndromic INPP5E patients did not reveal clear genotype-phenotype correlation, suggesting involvement of genetic modifiers.

Conclusions

The study expands the phenotypic spectrum of disorders due to pathogenic variants in INPP5E and describes a new disease association with previously underdiagnosed forms of early-onset non-syndromic IRD.
Evidence for contribution of compound heterozygous variants in Wiskott-Aldrich syndrome like (WASL) gene for early onset Parkinson’s disease
Authors: Kumar Sumeet , Abbas Masoom M , Govindappa Shyla T. , Muthane Uday B. , Pandey Sanjay , Thelma B.K.
Published: August 2020

Background

Knowledge of genetic determinants in Parkinson’s disease is still limited. Familial forms of the disease continue to provide a rich resource to capture the genetic spectrum in disease pathogenesis, and this approach has been exploited in this study.

Methods

Informative members from a three-generation family of Indian ethnicity manifesting a likely autosomal recessive mode of inheritance of PD were used for whole exome sequencing. Variant data analysis and in vitro functional characterisation of putative disease causal variant(s) identified thereof were carried out in HEK-293 and SH-SY5Y cells using gene constructs of interest.

Results

In a rather uncommon observation, two compound heterozygous variants, a rare missense (c.1139C>T:p.P380L) and a novel splice variant (c.1456+5TAGAG>G) in Wiskott-Aldrich syndrome like gene (WASL, 7q31), both predicted to be deleterious were shared among the proband and her two affected siblings. WASL, a gene hitherto unreported for PD is known to regulate actin polymerisation via Arp2/3 complex. Based on exon trapping assay using pSPL3 vector in HEK-293 cells, the splice variant showed skipping of exon10. Functional characterisation of the missense variant in SH-SY5Y cells demonstrated: i) significant alterations in neurite length and number; ii) decreased ROS tolerance in mutation carrying cells on TBPH induction, and iii) increase in alpha-synuclein protein. Screening for WASL variants in two independent PD cohorts identified four individuals with heterozygous but none with biallelic variants.

Conclusion

WASL, with demonstrated functional relevance in neurons may be yet another putative disease causal gene for autosomal recessive PD encouraging assessment of its contribution across populations.
Assessing the role of inversions in maintaining genomic differentiation after secondary contact: local adaptation, genetic incompatibilities, and drift
Authors: Rafajlović Marina , Rambla Jordi , Feder Jeffrey L. , Navarro Arcadi , Faria Rui
Published: August 2020

Due to their effects on reducing recombination, chromosomal inversions may play an important role in speciation by establishing and/or maintaining linked blocks of genes causing reproductive isolation (RI) between populations. These views fit empirical data indicating that inversions typically harbour loci involved in RI. However, previous computer simulations of infinite populations with 2-4 loci involved in RI implied that, even with gene flux as low as 10−8between alternative arrangements, inversions may not have large, qualitative advantages over collinear regions in maintaining population differentiation after secondary contact. Here, we report that finite population sizes can help counteract the homogenizing consequences of gene flux, especially when several fitness-related loci reside within the inversion. In these cases, the persistence time of differentiation after secondary contact can be similar to when gene flux is absent, and notably longer than the persistence time without inversions. Thus, despite gene flux, population differentiation may be maintained for up to 100,000 generations, during which time new incompatibilities and/or local adaptations might accumulate and facilitate progress towards speciation. How often these conditions are met in nature remains to be determined.
Plant stem cell organization and differentiation at single-cell resolution
Authors: Satterlee James W. , Strable Josh , Scanlon Michael J.
Published: August 2020

Plants maintain populations of pluripotent stem cells in shoot apical meristems (SAMs), which continuously produce new aboveground organs. We used single-cell RNA sequencing to achieve an unbiased characterization of the transcriptional landscape of the maize shoot stem-cell niche and its differentiating cellular descendants. Stem cells housed in the SAM tip are engaged in genome integrity maintenance and exhibit a low rate of cell division, consistent with their contributions to germline and somatic cell fates. Surprisingly, we find no evidence for a canonical stem cell organizing center subtending these cells. In addition, we use trajectory inference to trace the gene expression changes that accompany cell differentiation. These data provide a valuable scaffold on which to better dissect the genetic control of plant shoot morphogenesis.
Single particle-resolution fluorescence microscopy of nanoplastics
Authors: Nguyen Brian , Tufenkji Nathalie
Published: August 2020

Understanding of nanoplastic prevalence and toxicology is limited by imaging challenges resulting from their small size. Fluorescence microscopy is widely applied to track and identify microplastics in laboratory studies and environmental samples. However, conventional fluorescence microscopy, due to diffraction, lacks the resolution to precisely localize nanoplastics in tissues, distinguish them from free dye, or quantify them in environmental samples. To address these limitations, we developed techniques to label nanoplastics for imaging with Stimulated Emission Depletion (STED) microscopy to achieve resolution at an order of magnitude superior to conventional fluorescence microscopy. These techniques include (1) passive sorption; (2) swell incorporation; and (3) covalent coupling of STED-compatible fluorescence dyes to nanoplastics. We demonstrate that our labeling techniques, combined with STED microscopy, can be used to resolve nanoplastics of different shapes and compositions as small as 50 nm. The longevity of the dye labeling is demonstrated in different media and conditions of biological and environmental relevance. We also test STED imaging of nanoplastics in exposure experiments with the model wormC. elegans. These techniques will allow more precise localization and quantification of nanoplastics in complex matrices.

Synopsis

We show that Stimulated Emission Depletion (STED) microscopy can be used to image single nanoplastics of different compositions and shapes. This will allow researchers to study environmentally-relevant nanoplastics and their interactions with organisms in relevant exposure scenarios.

TOC Graphic
Inhibiting coronavirus replication in cultured cells by chemical ER stress
Authors: Shaban Mohammed Samer , Müller Christin , Mayr-Buro Christin , Weiser Hendrik , Albert Benadict Vincent , Weber Axel , Linne Uwe , Hain Torsten , Babayev Ilya , Karl Nadja , Hofmann Nina , Becker Stephan , Herold Susanne , Schmitz M. Lienhard , Ziebuhr John , Kracht Michael
Published: August 2020

Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. Proteome-wide data sets revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including HERPUD1, an essential factor of ER quality control, and ER-associated protein degradation complexes. The data show that thapsigargin hits a central mechanism required for CoV replication, suggesting that thapsigargin (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs.

One Sentence Summary / Running title

Suppression of coronavirus replication through thapsigargin-regulated ER stress, ERQC / ERAD and metabolic pathways
Induction of selective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir
Authors: Rao Shringar , Lungu Cynthia , Crespo Raquel , Steijaert Thijs H. , Gorska Alicja , Palstra Robert-Jan , Prins Henrieke A. B. , van Ijcken Wilfred , Mueller Yvonne M. , van Kampen Jeroen J. A. , Verbon Annelies , Katsikis Peter D. , Boucher Charles A. B. , Rokx Casper , Gruters Rob A. , Mahmoudi Tokameh
Published: August 2020

An innovative approach to eliminate HIV-1-infected cells emerging out of latency, the major hurdle to HIV-1 cure, is to pharmacologically reactivate viral expression and concomitantly trigger intracellular pro-apoptotic pathways in order to selectively induce cell death (ICD) of infected cells, without reliance on the extracellular immune system. In this work we demonstrate the effect of DEAD-box polypeptide 3, X-Linked (DDX3) inhibitors on selectively inducing cell death in latent HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1 (PLWHIV). RNA sequencing analysis revealed that while overall gene expression was minimally dysregulated, DDX3 inhibition in independent donor CD4+ T cells led to significant downregulation of BIRC5 and HSPB1A, genes critical to cell survival during HIV-1 infection. We used single-cell FISH-Flow technology to characterise latency reversal and the contribution of viral RNA to inducing cell death; pharmacological targeting of DDX3 induced HIV-1 RNA expression, resulting in phosphorylation of IRF3, upregulation of IFNβ and selective induction of apoptosis in viral RNA-expressing CD4+ T cells from PLWHIV but not bystander cells. DDX3 inhibitor treatment of CD4+ T cells from PLWHIV in anin vitroculture model over five days resulted in an approximately 50% reduction of the inducible latent HIV-1 reservoir as determined by quantitation of CA HIV-1 RNA, by TILDA, as well as by FISH-Flow technology. Our data support the translation of DDX3 inhibitor class compounds into HIV-1 curative strategies and provide proof of concept for pharmacological reversal of latency coupled to induction of apoptosis towards elimination of the inducible reservoir.
Deep learning enables the design of functionalde novoantimicrobial proteins
Authors: Caceres-Delpiano Javier , Ibañez Roberto , Alegre Patricio , Sanhueza Cynthia , Paz-Fiblas Romualdo , Correa Simon , Retamal Pedro , Cristóbal Jiménez Juan , Álvarez Leonardo
Published: August 2020

Protein sequences are highly dimensional and present one of the main problems for the optimization and study of sequence-structure relations. The intrinsic degeneration of protein sequences is hard to follow, but the continued discovery of new protein structures has shown that there is convergence in terms of the possible folds that proteins can adopt, such that proteins with sequence identities lower than 30% may still fold into similar structures. Given that proteins share a set of conserved structural motifs, machine-learning algorithms can play an essential role in the study of sequence-structure relations. Deep-learning neural networks are becoming an important tool in the development of new techniques, such as protein modeling and design, and they continue to gain power as new algorithms are developed and as increasing amounts of data are released every day. Here, we trained a deep-learning model based on previous recurrent neural networks to design analog protein structures using representations learning based on the evolutionary and structural information of proteins. We test the capabilities of this model by creatingde novovariants of an antifungal peptide, with sequence identities of 50% or lower relative to the wild-type (WT) peptide. We show byin silicoapproximations, such as molecular dynamics, that the new variants and the WT peptide can successfully bind to a chitin surface with comparable relative binding energies. These results are supported byin vitroassays, where thede novodesigned peptides showed antifungal activity that equaled or exceeded the WT peptide.
The circadian oscillator analysed at the single-transcript level
Authors: Phillips Nicholas E. , Hugues Alice , Yeung Jake , Durandau Eric , Nicolas Damien , Naef Felix
Published: August 2020

The circadian clock is an endogenous and self-sustained oscillator that anticipates daily environmental cycles and coordinates physiology accordingly. While rhythmic gene expression of circadian genes is well-described in populations of cells, the single-cell mRNA dynamics of multiple core-clock genes remain largely unknown. Here we use single molecule fluorescence in-situ hybridization (smFISH) at multiple time points to measure pairs of core-clock transcripts,Rev-erbα(Nr1d1),Cry1andBmal1, in mouse fibroblasts at single-molecule resolution. The mean mRNA level oscillates over 24 hours for all three genes, but mRNA numbers show considerable spread between cells. While transcript number scales with cell size for all genes, gene-to-gene correlations of mRNA number depends on the gene pair. To account for these features of the data, we develop a probabilistic model for multivariate smFISH mRNA counts that quantifies changes in transcriptional bursting across genes and over circadian time. We identify a mixture model of negative binomials as the preferred model of the mRNA count distributions, which accounts for cell-to-cell heterogeneity, notably in cell size. The paired count data and modelling allows the decomposition of mRNA variability into distinct noise sources, showing that circadian clock time contributes only a small fraction of the total variability in mRNA number between cells. Thus, our results highlight the intrinsic biological challenges in estimating circadian phase from single-cell mRNA counts and suggest that circadian phase in single cells is encoded post-transcriptionally.
Examining transformational and transactional leadership styles and safety citizenship behaviors in the power distribution sector: evidence from Ghana
Authors: Dartey-Baah Kwasi , Quartey Samuel Howard , Adotey Angeline
Published: August 2020

Purpose

This study aims to investigate the influence of transformational and transactional leadership styles and their related dimensions on safety citizenship behaviors (SCBs) in the power distribution sector (PDS) in Ghana.

Design/methodology/approach

As a cross-sectional survey approach, questionnaires were used to collect data from managers of power distribution centers. Valid questionnaires were retrieved from 197 managers across four power distribution centers. The hypotheses were tested using Pearson correlation analysis and standard multiple regression analysis.

Findings

The results revealed that both transformational and transactional leaders have a positive influence on SCBs. The results also showed that some of the dimensions of transformational and transactional leadership styles cannot strongly predict SCBs in the PDS.

Research limitations/implications

The study was limited by the use of cross-sectional data which did not allow the study to examine any changes in some of the constructs examined with time. The results are occupation-, industry- and country-specific.

Practical implications

Several management implications are discussed, such as managers recognizing that both leadership behaviors can be the basis for SCBs and for mitigating the socioeconomic consequences of unsafe employee behaviors.

Originality/value

The paper’s principal theoretical contribution is the application of social exchange theory toward an understanding of SCBs in a high-risk sector. Energy sector reforms in developing countries are inconceivable without safety consideration.
How to enhance supplier performance in China: interplay of contracts, relational governance and legal development
Authors: Zhang Qiyuan , Jin Jason Lu , Yang Defeng
Published: August 2020

Purpose

Given the pivotal influence of institutional forces, an important yet underexplored question in supply chain management literature is how contractual and relational governance jointly affect supplier performance under weak legislative environments. This study tends to solve the debate by distinguishing contractual definability from contractual enforceability and by considering the contingent role of legal development in China.

Design/methodology/approach

Using a combined dataset of secondary data and a survey of 224 buyer–supplier dyads in China, this study examines how contractual definability and contractual enforceability interact with relational governance differently in driving supplier performance, and assesses the contingent role of legal development.

Findings

This study finds that contractual definability complements yet contractual enforceability substitutes relational governance in affecting supplier performance. Moreover, legal development weakens the complementary effect but strengthens the substitutive effect.

Originality/value

The study firstly enriches supply chain management literature by classifying the roles of contracts into contractual definability and contractual enforceability and showing their differential interplay with relational governance. Second, the study contributes to the complements–substitutes debate by revealing the shifting role of legal development. Third, the research enriches the understanding of supply chain management in the Chinese market.
Passion-driven entrepreneurship in small and medium-sized towns: empirical evidence from Italy
Authors: Pagano Alessandro , Petrucci Francesco , Bocconcelli Roberta
Published: August 2020

Purpose

This paper aims to examine the emergence of passion-driven entrepreneurship within the context of small and medium-sized towns (SMSTs). SMSTs are seen as peripheral areas lacking the resources to support autonomous economic development and renewal. The paper explores the relationship between entrepreneurship and the context of SMSTs through the concepts of entrepreneurial passion (EP) and domain passion (DP). Industrial marketing and purchasing approach is adopted as a theoretical foundation to conduct the analysis through the actors–activities–resource framework.

Design/methodology/approach

This paper adopts a multiple case-study methodology. Two passion-driven entrepreneurial ventures (PDEVs) have been traced from the conception of the initial idea until the new ventures establishment.

Findings

EP and DP emerge as key resources in transforming the initial idea into a real entrepreneurial venture in resource-scarce settings as SMSTs. Shared passion fosters the involvement of local actors and the propensity to overcome relevant hurdles in the entrepreneurial process.

Originality/value

This paper contributes to the literature on entrepreneurship through the analysis of the role of PDEVs in SMSTs’ contexts. It highlights the role of “passion for place” as a new dimension of passion in entrepreneurial studies. From a managerial perspective, it emphasizes the role of passion as a key resource for networking and marketing. From a policy perspective, it calls for monitoring and support for training, funding and networking.
A framework for modeling the knowledge of workplace relocation
Authors: Hassanain Mohammad A. , Ibrahim Ahmed M.
Published: August 2020

Purpose

The purpose of this study is to propose a framework model for workplace relocation.

Design/methodology/approach

Published literature was reviewed to comprehend the broad aspects of workplace relocation. The current practices of workplace relocation were investigated by corporate real estate (CRE) professionals. A generic framework model was developed to guide organizations upon the process of workplace relocation, over its lifecycle. The framework is validated by semi-structured interviews, conducted to ascertain its importance and applicability.

Findings

A validated integration definition for function modeling framework for the process of workplace relocation was developed. It consisted of three systematic processes, aligned with its lifecycle, namely, initiate the pre-relocation activities; implement the relocation activities; and conduct the post-relocation activities.

Originality/value

The workplace is a linkage between people, business processes and information technology, that provides a physical medium for interactions and provision of services. Workplace relocation is an opportunity to introduce elements of change. Yet the process of workplace relocation has been under-valued by practitioners in the CRE industry. The developed framework can be adopted as a standardized process for the relocation of workplace facilities. In terms of clearly structuring the workplace relocation processes, the study contributes to making these processes more transparent and aids accountability for decision-making. It is a time-saver and guiding model for organizations endeavoring on relocation.
Transitioning towards circular systems: property rights in waste
Authors: Steenmans Katrien , Malcolm Rosalind
Published: August 2020

Purpose

The purpose of this paper is to explore the impact that property rights can have on the implementation of circular waste economies, in which waste is reused, recycled or recovered, within the European Union’s Waste Framework Directive.

Design/methodology/approach

A theoretical lens is applied to the legal definition as well as production and treatment cycle of waste to understand the property rights that can exist in waste.

Findings

This paper argues that even though different property rights regimes can apply to waste during its creation, disposal and recovery, the waste management regulatory and legal system is currently predominantly set up to support waste within classic forms of private property ownership. This tends towards commodification and linear systems, which are at odds with an approach that treats waste as a primary wanted resource rather than an unwanted by-product. It is recommended that adopting state or communal property approaches instead could affect systemic transformative change by facilitating the reconceptualisation of waste as a resource for everyone to use.

Research limitations/implications

The property rights issues are only one dimension of a bigger puzzle. The roles of social conceptualisation, norms, regulations and policies in pursuing circular strategies are only touched upon, but not fully explored in this paper. These provide other avenues that can be underpinned by certain property regimes to transition to circular economies.

Originality/value

The literature focused on property rights in waste has been very limited to date. To the best of the authors’ knowledge, this paper is the first to consider this question in detail from a legal perspective.
Roger Martin: The problematic economic efficiency mindset that threatens corporations and democratic society
Authors: Leavy Brian
Published: August 2020

Purpose

“On its current path, American democratic capitalism is, I believe, heading for an ugly fall.” So warns Roger L. Martin in his new book, When More is Not Better: Overcoming America’s Obsession with Economic Efficiency. Professor Martin has been concerned for some time now about the capability of the American capitalistic model in its current guise to deliver continued prosperity for the many and keep the American democratic dream alive.

Design/methodology/approach

Martin sees a serious problem in how the benefits of the American economy and its corporations are distributed; this has been shifting for some time now from a largely Gaussian (widely spread) to an increasingly Pareto (narrowly spread) pattern.

Findings

The shape of this distribution is getting ever more extreme, leading to a situation in which the richest families in the country are reaping a wildly disproportionate share of the benefits of economic growth. This kind of distribution tends to be self-reinforcing and that is not consistent with a well-functioning democratic capitalist system.

Practical implications

The actors within the system will keep adjusting to any change in the rules of engagement, and the tendency for them to keep “gaming” the system should be anticipated as both natural and inevitable and provided for accordingly. Breaking the company into subject-matter siloes has little chance of helping the company prosper. It tends to cause independent pursuits of efficiency that don’t add up to effectiveness.

Originality/value

The author of 11 books, Professor Martin has been ranked at the top of numerous lists of the world’s best strategic thinkers, and is a seminal contributor to the design thinking and integrative thinking movements. In his writings he seeks “to develop a new understanding of the broader public conversation around shared and sustainable prosperity, an essential piece of democratic capitalism.” A long-time consultant to major global firms, he offers insights for corporate executives.