bluuebunny/crossref_metadata_2025 huggingface dataset:
GestaltMatcher: Overcoming the limits of rare disease matching using facial phenotypic descriptors
Authors: Hsieh Tzung-Chien , Bar-Haim Aviram , Moosa Shahida , Ehmke Nadja , Gripp Karen W. , Pantel Jean Tori , Danyel Magdalena , Mensah Martin Atta , Horn Denise , Rosnev Stanislav , Fleischer Nicole , Bonini Guilherme , Hustinx Alexander , Schmid Alexander , Knaus Alexej , Javanmardi Behnam , Klinkhammer Hannah , Lesmann Hellen , Sivalingam Sugirthan , Kamphans Tom , Meiswinkel Wolfgang , Ebstein Frédéric , Krüger Elke , Küry Sébastien , Bézieau Stéphane , Schmidt Axel , Peters Sophia , Engels Hartmut , Mangold Elisabeth , Kreiß Martina , Cremer Kirsten , Perne Claudia , Betz Regina C. , Bender Tim , Grundmann-Hauser Kathrin , Haack Tobias B. , Wagner Matias , Brunet Theresa , Bentzen Heidi Beate , Averdunk Luisa , Coetzer Kimberly Christine , Lyon Gholson J. , Spielmann Malte , Schaaf Christian , Mundlos Stefan , Nöthen Markus M. , Krawitz Peter
Published: January 2021

A large fraction of monogenic disorders causes craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this “supervised” approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we created GestaltMatcher, which uses a deep convolutional neural network based on the DeepGestalt framework. We used photographs of 17,560 patients with 1,115 rare disorders to define a “Clinical Face Phenotype Space”. Distance between cases in the phenotype space defines syndromic similarity, allowing test patients to be matched to a molecular diagnosis even when the disorder was not included in the training set. Similarities among patients with previously unknown disease genes can also be detected. Therefore, in concert with mutation data, GestaltMatcher could accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism, as well as enable the delineation of novel phenotypes.
Autoimmunity to the Lung Protective Phospholipid-Binding Protein Annexin A2 Predicts Mortality Among Hospitalized COVID-19 Patients
Authors: Zuniga Marisol , Gomes Claudia , Carsons Steven E. , Bender Michael T. , Cotzia Paolo , Miao Qing Robert , Lee David C. , Rodriguez Ana
Published: January 2021

Background

Annexin A2 is a phospholipid-binding protein involved in fibrinolysis, cell membrane stabilization and repair, and ensuring the integrity of the pulmonary microvasculature. Given the autoantibodies observed in COVID-19 and that Annexin A2 is a known target of antiphospholipid antibodies, we studied autoimmunity directed against Annexin A2 among hospitalized COVID-19 patients.

Methods

We used ELISA to identify the levels of IgG autoantibodies recognizing Annexin A2 and A5 among 86 hospitalized cases of COVID-19. Using logistic regression, we analyzed the association between anti-Annexin A2 and A5 antibody levels with mortality after adjusting for age, sex, race and key comorbidities.

Results

We found higher average levels of anti-Annexin A2 antibodies among hospitalized COVID-19 patients that died when compared with non-critical hospitalized COVID-19 patients (p-value = 0.006) and critically ill COVID-19 patients (p-value = 0.04). No significant differences in anti-Annexin A5 antibody levels were identified. Regression analysis showed that anti-Annexin A2 antibody levels as measured in relative units strongly predicted mortality with an odds ratio of 9.3 (95% CI: 1.9 to 44.6, p=0.005). In contrast, anti-Annexin A5 antibody levels were not associated with higher mortality (95% CI: 0.5 to 15.2, p=0.22).

Conclusions

We determined that anti-Annexin A2 antibodies were elevated among hospitalized COVID-19 patients and these levels predicted mortality. It is known that inhibition of Annexin A2 induces systemic thrombosis, cell death, and non-cardiogenic pulmonary edema. Autoimmunity to Annexin A2 is a potential mechanism that may explain the key clinical findings of severe COVID-19.
An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosis post-mortem motor cortex and cerebrospinal fluid
Authors: Petrozziello Tiziana , Amaral Ana C. , Dujardin Simon , Farhan Sali M.K. , Chan James , Trombetta Bianca A. , Kivisäkk Pia , Mills Alexandra N. , Bordt Evan A. , Kim Spencer E. , Dooley Patrick M. , Ghosal Anubrata , Gomez-Isla Teresa , Hyman Bradley T. , Arnold Steven E. , Spires-Jones Tara , Cudkowicz Merit E. , Berry James D. , Sadri-Vakili Ghazaleh
Published: January 2021

Although the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimer’s disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS.
Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data
Authors: Volz Erik , Mishra Swapnil , Chand Meera , Barrett Jeffrey C. , Johnson Robert , Geidelberg Lily , Hinsley Wes R , Laydon Daniel J , Dabrera Gavin , O’Toole Áine , Amato Roberto , Ragonnet-Cronin Manon , Harrison Ian , Jackson Ben , Ariani Cristina V. , Boyd Olivia , Loman Nicholas J , McCrone John T , Gonçalves Sónia , Jorgensen David , Myers Richard , Hill Verity , Jackson David K. , Gaythorpe Katy , Groves Natalie , Sillitoe John , Kwiatkowski Dominic P. ,   The COVID-19 Genomics UK (COG-UK) consortium, Flaxman Seth , Ratmann Oliver , Bhatt Samir , Hopkins Susan , Gandy Axel , Rambaut Andrew , Ferguson Neil M
Published: January 2021

The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.
Development of Electrospun Nanofibrous Filters for Controlling Coronavirus Aerosols
Authors: Wang Haihuan , Shen Hongchen , Zhou Zhe , Zhang Mengyang , Han Minghao , Durkin David P. , Shuai Danmeng , Shen Yun
Published: January 2021

Airborne transmission of SARS-CoV-2 plays a critical role in spreading COVID-19. To protect public health, we designed and fabricated electrospun nanofibrous air filters that hold promise for applications in personal protective equipment and indoor environment. Due to ultrafine nanofibers (∼300 nm), the electrospun air filters had a much smaller pore size compared to the surgical mask and cloth masks (a couple of microns versus tens to hundreds of microns). A coronavirus strain was used to generate aerosols for filtration efficiency tests, which can better represent SARS-CoV-2 than other agents used for aerosol generation in previous studies. The electrospun air filters showed excellent performance by capturing up to 99.9% of coronavirus aerosols, which outperformed many commercial face masks. In addition, since NaCl aerosols have been widely used in filtration tests, we compared the filtration efficiency obtained from the coronavirus aerosols and the NaCl aerosols. The NaCl aerosols were demonstrated as an eligible surrogate for the coronavirus aerosols in the filtration tests, when air filters and face masks with diverse pore sizes, morphologies, and efficiencies were used. Our work paves a new avenue for advancing air filtration by developing electrospun nanofibrous air filters for controlling SARS-CoV-2 airborne transmission. Moreover, the removal efficiency of the NaCl aerosols can be reasonably translated into understanding how air filters capture the coronavirus aerosols.

Table of Contents
Integrative Bioinformatics Analysis Identifies Noninvasive miRNA Biomarkers for Lung Cancer
Authors: Gao Andrew
Published: January 2021

Non-small cell lung cancer (NSCLC), a subtype of lung cancer, affects millions of people. While chemotherapy and other treatments have improved, the 5 year survival rate of NSCLC patients is still only 21%. Early diagnosis is essential for increasing survival as treatments have higher effectiveness at earlier stages of NSCLC. Noninvasive blood-based liquid biopsy tests for NSCLC may be useful for diagnosis and prognosis. MicroRNA (miRNA) and messenger RNA present in blood can serve as biomarkers for such tests. The present study identified 13 miRNAs that are underexpressed in the tissue and blood of NSCLC patients using Gene Expression Omnibus data. Following Kaplan Meier analysis, miR-140-3p, miR-29c, and miR-199a were selected as candidate biomarkers and demonstrated statistically significant prognostic power. An ROC analysis of miR-140-3p expression between NSCLC patients and controls had an area under curve value of 0.85. Functional enrichment analysis of the miRNA target genes revealed several overrepresented pathways relevant to cancer. Eight target genes were hub genes of the protein protein interaction network and possessed significant prognostic power. A combination of IL6, SNAI1, and CDK6 achieved a hazard ratio of 1.4 with p < 0.001. These biomarkers are especially valuable because they can be identified in blood and reflect the tumor state. Since all miRNAs were underexpressed in both tissue and blood, detecting expression of a biomarker miRNA in blood provides information on its expression in tissue as well. These miRNAs may be useful biomarkers for NSCLC prognostic and diagnostic tests and should be further studied.
Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2
Authors: Trombetta Bianca A. , Kandigian Savannah E. , Kitchen Robert R. , Grauwet Korneel , Kivisäkk Webb Pia , Miller Glenn A. , Jennings Charles G. , Jain Sejal , Miller Samara , Kuo Yikai , Sweeney Thadryan , Gilboa Tal , Norman Maia , Simmons Daimon P. , Ramirez Christopher E. , Bedard Melissa , Fink Catherine , Ko Jina , De León Peralta Esmarline J. , Watts Gerald , Gomez-Rivas Emma , Davis Vannessa , Barilla Rocky , Wang Jianing , Cunin Pierre , Bates Samuel , Morrison-Smith Chevaun , Nicholson Benjamin , Wong Edmond , El-Mufti Leena , Kann Michael , Bolling Anna , Fortin Brooke , Ventresca Hayden , Zhou Wen , Pardo Santiago , Kwock Megan , Hazra Aditi , Cheng Leo , Ahmad Q. Rushdy , Toombs James A. , Larson Rebecca , Pleskow Haley , Luo Nell Meosky , Samaha Christina , Pandya Unnati M. , De Silva Pushpamali , Zhou Sally , Ganhadeiro Zakary , Yohannes Sara , Gay Rakiesha , Slavik Jacqueline , Mukerji Shibani S. , Jarolim Petr , Walt David R. , Carlyle Becky C. , Ritterhouse Lauren L. , Suliman Sara
Published: January 2021

Background

COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed.

Methods

We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays’ performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence.

Results

Combined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 μg/mL), followed by a similar LOD of 1.5 μg/mL for CareHealth, Cellex, KHB, and Vivachek.

Conclusion

We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.
Assessment of Polarized Piezoelectric SrBi4Ti4O15Nanoparticles as an alternative antibacterial agent
Authors: Swain Subhasmita , Rautray Tapash Ranjan
Published: January 2021

Strontium bismuth titanate nanoparticles (SrBi4Ti4O15/SBT NPs,) and their polarized counterparts were prepared to assess their antibacterial efficacy on biomaterials. The structural properties of the SBT NPs were performed by X-ray diffraction and the antibacterial efficacy was evaluated againstStaphyllococcus aureus (S. aureus)pathogenic bacteria. Significant antibacterial activity of polarized SBT specimen was observed againstS. aureusbacteria. Results presented in this work confirmed that polarized SBT can effectively combat bacterial growth and prevent biofilm formation activity of pathogenic bacteria and hence they can be used as alternative antimicrobial agents.
The Impact of the November 2020 English National Lockdown on COVID-19 case counts
Authors: Hunter Paul R , Brainard Julii , Grant Alastair
Published: January 2021

In the UK the epidemic of COVID-19 continues to pose a significant threat to public health. On the 14th October the English government introduced a tier system for control of the epidemic but just 3 weeks later a National lockdown across all areas of England was implemented. When English areas emerged from Lockdown many were placed in different tiers (most typically moved up at least one tier). However, the effectiveness of the tier system has been challenged by the emergence of a new variant of SARS-CoV-2 which appears to be much more infectious. In addition, from early November a trial mass testing service was being run in Liverpool. We used publicly available data of daily cases by local authority (local government areas) and estimated the reproductive rate (R value) of the epidemic based on 7-day case numbers compared with the previous 7-day period. There was a clear surge in infections from a few days before to several days after the lockdown was implemented. But this surge was almost exclusively associated with Tier 1 and Tier 2 authorities. In Tier 3 authorities where hospitality venues were only allowed to operate as restaurants there was no such surge. After this initial surge, cases declined in all three tiers with the R value dropping to a mean of about 0.7 independent of tier. London, The South East and East of England Regions saw rising infection rates in the last week or so of lockdown primarily in children of secondary school age. We could find no obvious benefit of the trial mass screening programme in Liverpool city. We conclude that in Tiers 1 and 2 much of the beneficial impact of the national lockdown was lost probably because of the leak of its likely implementation five days early leading to increased socialising in these areas before the start of lockdown. We further conclude that given that the new variant is estimated to have an R value of between 0.39 and 0.93 greater than previous variants, any lockdown as strict as the November one would be insufficient to reverse the increase in infections by itself. The value of city-wide mass testing to control the epidemic remains uncertain.
The ancient cardioprotective mechanisms of ACE2 bestow SARS-CoV-2 with a wide host range
Authors: Castiglione Gianni M. , Zhou Lingli , Xu Zhenhua , Neiman Zachary , Hung Chien-Fu , Duh Elia J.
Published: January 2021

SARS-CoV-2 infects a broader range of mammalian species than previously anticipated, suggesting there may be additional unknown hosts wherein the virus can evolve and potentially circumvent effective vaccines. We find that SARS-CoV-2 gains a wide host range by binding ACE2 sites essential for ACE2 carboxypeptidase activity. Six mutations found only in rodent species immune to SARS-CoV-2 are sufficient to abolish viral binding to human and dog ACE2. This is achieved through context-dependent mutational effects (intramolecular epistasis) conserved despite ACE2 sequence divergence between species. Across mammals, this epistasis generates sequence-function diversity, but through structures all bound by SARS-CoV-2. Mutational trajectories to the mouse conformation not bound by SARS-CoV-2 are blocked, by single mutations functionally deleterious in isolation, but compensatory in combination, explaining why human polymorphisms at these sites are virtually non-existent. Closed to humans, this path was opened to rodents via permissive cardiovascular phenotypes and ancient increases to ACE2 activity, serendipitously granting SARS-CoV-2 immunity. This reveals how ancient evolutionary trajectories are linked with unprecedented phenotypes such as COVID-19 and suggests extreme caution should be taken to monitor and prevent emerging animal reservoirs of SARS-CoV-2.

One sentence summary

A conserved mechanism essential for ACE2 catalytic activity is exploited by SARS-CoV-2 binding, allowing the virus to infect a wide range of species.
High rates of diabetes and pre-diabetes in postpartum period in Indian GDM women
Authors: Chittaranjan S Yajnik , Sonali S Wagle , Sharvari R Shukla , Shailaja D Kale , Rasika S Ladkat , Himangi G Lubree , Dattatray S Bhat , Nilam S Memane , Phatak Sanat , Meenakumari K
Published: January 2021

Aim

To investigate postpartum glucose intolerance in South Asian Indian GDM women within 1 year of delivery.

Methods

Between 2001-2005, 220 women were treated for GDM at the Diabetes Unit, King Edward Memorial Hospital, Pune. GDM was diagnosed by 75g OGTT [WHO 1999 pregnancy criteria]. OGTT was repeated 3 months to 1 year postpartum. One hundred and nineteen non-GDM women were also studied.

Results

Of 220 GDM women [30years, BMI 26.0kg/m2] 9 women continued to be diabetic after delivery and a further 111 attended OGTT within one year of delivery. Two had IFG, 16 IGT and 23 diabetes [WHO 1999], thus 50[42%] women were glucose intolerant. Of the non-GDM, 1 had IFG, 8 IGT and 3 diabetes (10% glucose intolerant). Those who were hyperglycemic at follow up had stronger family history of diabetes [64% vs. 58%], were shorter [154.6 vs. 156.5cm], had higher FPG concentrations during pregnancy [5.27 vs. 4.99 mmol/L], and higher BMI [26.3 vs.25.0kg/m2] and waist circumference [88.0 vs. 82.3cm] at follow up compared to normoglycemic women. Hyperglycemia was not associated with GAD antibody positivity (4 vs 3 in normoglycemic).

Conclusion

We describe one of the highest rates of postpartum hyperglycemia within a short time after delivery in young urban GDM women from India. Majority of risk factors for GDM were present from before pregnancy, and we propose that metabolic disturbances were also likely present. This has implications for peri-conceptional epigenetic programming of diabetes in the offspring. Pre-pregnancy screening and treatment of glucose intolerance and its risk factors in the high-risk populations could be an important measure for primordial prevention of diabetes.

Key messages

We describe one of the highest rates of postpartum hyperglycemia in young urban GDM women from India within a short time after delivery.

Our results invite further research and policy discussion for screening and treatment of glucose intolerance before pregnancy in high-risk populations.
Directed brain connectivity identifies widespread functional network changes in Parkinson’s disease
Authors: Mijalkov Mite , Volpe Giovanni , Pereira Joana B.
Published: January 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by topological changes in large-scale functional brain networks. These networks are commonly analysed using undirected correlations between the activation signals of brain regions. However, this approach suffers from an important drawback: it assumes that brain regions get activated at the same time, despite previous evidence showing that brain activation features causality, with signals being typically generated in one region and then propagated to other ones. Thus, in order to address this limitation, in this study we developed a new method to assess whole-brain directed functional connectivity in patients with PD and healthy controls using anti-symmetric delayed correlations, which capture better this underlying causality. To test the potential of this new method, we compared it to standard connectivity analyses based on undirected correlations. Our results show that whole-brain directed connectivity identifies widespread changes in the functional networks of PD patients compared to controls, in contrast to undirected methods. These changes are characterized by increased global efficiency, clustering and transitivity as well as lower modularity. In addition, changes in the directed connectivity patterns in the precuneus, thalamus and superior frontal gyrus were associated with motor, executive and memory deficits in PD patients. Altogether, these findings suggest that directional brain connectivity is more sensitive to functional network changes occurring in PD compared to standard methods. This opens new opportunities for the analysis of brain connectivity and the development of new brain connectivity markers to track PD progression.
Conserved Gsx2/Ind homeodomain monomer versus homodimer DNA binding defines regulatory outcomes in flies and mice
Authors: Salomone Joseph , Qin Shenyue , Fufa Temesgen D. , Cain Brittany , Farrow Edward , Guan Bin , Hufnagel Robert B. , Nakafuku Masato , Lim Hee-Woong , Campbell Kenneth , Gebelein Brian
Published: January 2021

How homeodomain proteins gain sufficient specificity to control different cell fates has been a long-standing problem in developmental biology. The conserved Gsx homeodomain proteins regulate specific aspects of neural development in animals from flies to mammals, and yet they belong to a large transcription factor family that bind nearly identical DNA sequences in vitro. Here, we show that the mouse and fly Gsx factors unexpectedly gain DNA binding specificity by forming cooperative homodimers on precisely spaced and oriented DNA sites. High-resolution genomic binding assays revealed that Gsx2 binds both monomer and homodimer sites in the developing mouse ventral telencephalon. Importantly, reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In Drosophila, the Gsx homolog, Ind, similarly represses or stimulates transcription in a site-dependent manner via an autoregulatory enhancer containing a combination of monomer and homodimer sites. Integrating these findings, we test a model showing how the homodimer to monomer site ratio and the Gsx protein levels defines gene up-regulation versus down-regulation. Altogether, these data serve as a new paradigm for how cooperative homeodomain transcription factor binding can increase target specificity and alter regulatory outcomes.
Expression of Cloned Genes in Pichia pastoris Using the Methanol-Inducible Promoter AOX1
Authors: Kielkopf Clara L. , Bauer William , Urbatsch Ina L.
Published: January 2021

Pichia pastoris is a methylotrophic yeast capable of metabolizing methanol as its sole carbon source. Growth in methanol-containing medium results in dramatic induction of genes in the alcohol oxidation pathway including alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD), and dihydroxyacetone synthase (DHAS). These proteins may comprise up to 30% of the biomass. Investigators have exploited these methanol-dependent genes to generate tightly regulated expression vectors. Most Pichia vectors use the strong and tightly regulated AOX1 promoter to drive heterologous protein expression. Obtaining integrated Pichia transformants requires more DNA than transformations into Saccharomyces cerevisiae, where the gene is expressed from episomal plasmids; however, transformants are extremely stable and can be stored for many years.
Study on the structural phase transitions in NaSICON-type compounds using Ag3Sc2(PO4)3 as a model system
Authors: Redhammer Günther J. , Tippelt Gerold , Stahl Quirin , Benisek Artur , Rettenwander Daniel
Published: January 2021

NaSICON (Na Super-Ionic CONducting) structured materials are among the most promising solid electrolytes for Li-ion batteries and `beyond Li-ion' batteries (e.g. Na and K) due to their superior ionic conductivities. Although this material has been well known for decades, its exact phase behaviour is still poorly understood. Herein, a starting material of Na3Sc2(PO4)3 single crystals is used, grown by flux methodology, where Na is subsequently chemically replaced by Ag, in order to take advantage of the higher scattering contrast of Ag. It is found that the NaSICON-type compound shows two phase transitions from a low-temperature monoclinic α-phase to a monoclinic β-phase at about 180 K and to a rhombohedral γ-phase at about 290 K. The framework of [Sc2(PO4)3]3− is rigid and does not change significantly with temperature and change of symmetry. The main driving force for the phase transitions is related to order–disorder phenomena of the conducting cations. The sensitivity of the phase behaviour on the ordering of these ions suggests that small compositional changes can have a great impact on the phase behaviour and, hence, on the ionic conductivity of NaSICON-structured materials.
Past, present and future of the Spanish labour market: when the pandemic meets the megatrends
Authors: Dolado Juan J. , Felgueroso Florentino , Jimeno Juan F.
Published: January 2021

Purpose

This paper aims to review the experience so far of the Spanish labour market during the Covid-19 crisis in the light of the existing institutions, its performance during past recessions and the policy measures adopted during the pandemic. Emphasis is placed on the role of worldwide trends in labour markets because of automation and artificial intelligence, in shaping a potential recovery of this (hopefully) transitory shock through a big reallocation process of employment and economic activity. It also highlights some innovations to employment and social policies needed to smooth the reallocation process and lessen the rise in inequality associated to technological trends.

Design/methodology/approach

Theory and empirics.

Findings

The Spanish labour market will subject to a great reallocation shock as a result of Covid-19 and secular technological changes. Reforms need to be undertaken.

Originality/value

An overview and some new results.
Next time, with empathy: revisiting the studio pedagogy for transitional housing for refugees
Authors: Swaranjali Pallavi , Patel Tina , Espersen-Peters Kurt
Published: January 2021

Purpose

Showing empathy can be, at best, a tricky prospect; teaching empathy is downright daunting. The authors taught an interior design studio project that designed hypothetical transitional housing for refugees coming to Canada. As the project evolved, it became imperative that students needed to address tangible issues experienced by the refugee client, namely trauma, rootlessness and marginalization and authentically empathize with their client. Hence, instructors needed to accurately structure and facilitate this engagement. The purpose of this paper is to present a summary of the evolution of this studio project as a case study, the revision of the project's pedagogical goals and establishing a new set of design parameters that engage the “self” and the “other” through alternate modes of thinking and reasoning.

Design/methodology/approach

The paper is centered on a reflective case study of the studio project and the student's work. The results of the reflection are contextualized within pedagogical framework that emphasize alternate forms of teaching and learning that promotes authentic empathetic engagement.

Findings

The summary of these reflections arises from organically questioning the nature of traditional design studio pedagogy. It proposes divergent approaches, such as “abductive reasoning”, posing the project as a “wicked problem” to encourages lateral explorations and connections.

Originality/value

This paper questions the value of prescriptive design process and guides student learning by providing an experimental toolkit that encourages alternative exploration, research and thinking.
Migration and comparative advantages: new evidence on the EU-MENA region
Authors: Ferragina Anna Maria , Iandolo Stefano , Taymaz Erol
Published: January 2021

Purpose

This study aims to consider how migrants may act as channel of diffusion of knowledge which contributes to the dynamics of trade and comparative advantages of EU and MENA countries for the period 1990–2015.

Design/methodology/approach

Adopting an IV approach and a gravity framework to instrument for migration, the authors document how variations in stocks of migrants coming from (in) countries that are already competitive exporters of a given product impact on the probability that the destination (home) country starts to export competitively new products or succeed in exporting more intensively.

Findings

Controlling for potential confounding factors which can be correlated to knowledge flows and productivity shifts, the authors find trade-promoting effects via migration flows (mostly immigration) between the two areas, testing our hypotheses by different technology classes of products and different specifications.

Originality/value

The contribution of this work to the literature is threefold. First, by providing evidence on international knowledge diffusion induced by migration flows between MENA and EU regions, like no other work before, the authors document the effects of migration on trade and comparative advantages. Second, unlike standard literature on migration-trade link, the authors focus more on long-term structural changes in comparative advantages than on trade volumes. Third, we exploit how the effect of migration on margins of trade varies according to different types of goods, classified by technological level.
An improved lean assessment based on employee perception
Authors: Huang Zhengyin , Harris Gregory , Loyd Nicholas
Published: January 2021

Purpose

The Toyota Production System has been studied for its business success for several decades. Many companies have tried to imitate but have not achieved Toyota-like results. Failure in the ability to replicate Toyota's supportive culture has been suggested as a cause for the lack of success. Studies on lean implementation have been conducted from external views focusing on visible indicators, but few seek the employee's perception of lean initiatives. The authors propose a Toyota Production System – Toyota Way (TPS-TW) model approach using employee perception and quantitative performance metrics.

Design/methodology/approach

This research represents an improvement of a lean assessment instrument using quantifiable performance metrics for validation and testing it in the Chinese automotive industry. A survey was developed and executed in the Chinese automotive industry with participants involved with lean implementation. Experts helped examine the content validity, and reliability analysis was used to study the structure of the assessment instrument and evaluate internal consistency. Confirmatory factor analysis and structured equation modeling were used to test the construct validity. Finally, survey results and actual performance were analyzed.

Findings

The results of this research validated the TPS-TW model and assessment instrument in the Chinese automotive industry.

Originality/value

This research validates an employee perception survey that can be utilized by organizations to understand the state of their lean implementation. The research supports the use of employee perception to reflect the reality of a lean initiative and proves the TPS-TW model is an effective theoretical framework for assessment.
Cash flow uncertainty and IPO underpricing: evidence from income guarantee in Thai REITs
Authors: Saengchote Kanis , Charoenpanich Chittisa
Published: January 2021

Purpose

The purpose of this article is to investigate the relationship between cash flow uncertainty and the underpricing of real estate investment trust (REIT) initial public offerings (IPOs) using hand-collected data on income guarantee in Thailand from January 2005 to December 2019.

Design/methodology/approach

This article uses linear regression to determine the relationship between underpricing (initial return) and proxy for cash flow uncertainty (income guarantee), controlling for other factors. Because issuers can use several actions to signal their quality under asymmetric information, the joint decisions are analyzed as simultaneous equations and estimated using three-stage least square (3SLS) to address potential endogeneity concern.

Findings

This article finds that underpricing, on average, is negatively related to income guarantee, which is a proxy for ex ante cash flow uncertainty. The relationship is economically and statistically significant and robust to simultaneous equations estimation. Further investigation shows that REITs with income guarantee tend to have lower systematic risk (measured by CAPM beta) and returns, making the nature of some REITs more debt-like than equity-like.

Practical implications

For issuers, the result suggests that offering income guarantee (which is more costly for assets with lower quality) can be a useful signal of asset quality to investors and reduce IPO discount. For institutional and retail investors, the results are informative about the risk-return tradeoffs in REIT IPO investment opportunities. Income guarantees makes REIT exposure more fix income-like, so there is a need to consider the credibility of the guarantor as well.

Originality/value

This article is the first to use income guarantee as an ex ante measure of cash flow uncertainty and explicitly investigates its linkage to IPO underpricing. This aspect of uncertainty and IPO underpricing remains little-studied in the academic literature. It also contributes to the growing literature of REIT IPOs in Asia.
Development of a work–family conflict scale for spouses or partners of police officers
Authors: Amendola Karen L. , Valdovinos Olson Maria , Grieco Julie , Robbins Teresina G.
Published: January 2021

Purpose

The purpose of this research is to initiate the development of a police-specific measure of work–family conflict (WFC) to assess spouse and/or partner perceptions of the impact of WFC on them, their family and/or their personal lives by tapping existing dimensions of WFC and proposing three dimensions that may be specific to the policing profession. This developmental and exploratory work will serve as the basis for sample data collection with spouses of police.

Design/methodology/approach

For over five decades, researchers have examined the construct of WFC, a phenomenon that refers to the impact of work-related issues on the family of the worker. Despite the fact that policing is a high-stress profession, now under considerable scrutiny and increasing public pressure, much less is known about WFC in police families and the perceptions of spouses and/or partners of police officers regarding WFC. The methodology for developing this scale follows that recommended by psychometricians in the construction of reliable and valid scales for use in both descriptive and predictive research.

Findings

The data reported were generated from an initial content validity study relying on 14 subject matter experts with backgrounds in policing, police research and/or psychometrics and approximately 20 spouses/partners (significant others of police officers). The findings provide preliminary evidence for six potential dimensions of WFC totaling 34 items.

Originality/value

While some researchers have assessed the extent to which certain work-related factors impact police officers' family members, none have tapped additional domain-specific items for police while also surveying spouses and/or partners of officers.
Doing good does you good? The financial impact of individual CSR dimensions: A Malaysian context
Authors: Tan Kim-Lim , Ho Jie Min , Pidani Rita , Goveravaram Archana Das
Published: January 2021

Purpose

Although corporate social responsibility–corporate financial performance (CSR-CFP) research topics have been widely investigated, previous research has yet to examine the relationship between the specific dimension of CSR and CFP among Malaysian public-listed companies. Through literature review, it has been found that the CSR-CFP studies conducted in Malaysia have omitted the role of workplace diversity dimension in contribution to CFP. Failure to consider this variable may risk misrepresenting the relationship between CSR and CFP, thereby preclude consensus on the direction of the relationship between the variables. The purpose of this study is to investigate the relationship between individual CSR dimensions and CFP.

Design Methodology Approach

By using the CSR dimension disclosure-scoring method and cross-sectional data analysis, this research has conducted a content analysis on annual reports of the sample companies to evaluate the influence of CSR practices on companies’ profitability during 2015.

Findings

The results show that companies displaying CSR behavior are associated with higher CFP. That is to say, there is a positive relationship between CSR and CFP. However, the result has further revealed that the five CSR dimensions in isolation would differently associate with the two proxies of CFP.

Originality Value

To the best of the authors’ knowledge, this is the first study in Malaysia that considers workplace diversity issues as one of the dimensions of CSR. The findings will thus bring new insights into CSR application in Malaysia and its association with the CFP.
L'accès des jeunes au marché du travail au Togo et au bénin: Une évidence paramétrique et semi‐paramétrique
Authors: Midagbodji Koami M. , Egbendewe Aklesso Y. G.
Published: January 2021

L'objectif de cet article est d'analyser les opportunités d'accès des jeunes au marché du travail au Togo et au Bénin. Pour ce faire, des modèles paramétriques (probit) et semi‐paramétriques (Klein & Spady a indice unique) ont été appliqués aux données d'Enquêtes de la Transition vers la Vie Active (ETVA) réalisées en 2012 sur les jeunes de 15 à 29 ans. Les résultats révèlent principalement que l'accès au marché du travail est difficile pour les jeunes éduqués. Cette difficulté est due à un chômage structurel qui s'établit pour ces jeunes. Aussi, le contexte professionnel des parents influence fortement les jeunes à se maintenir dans le même secteur d'activité que leurs parents.
Clinical profiles of placenta accreta spectrum: the PACCRETA population‐based study
Authors: Kayem G , Seco A , Beucher G , Dupont C , Branger B , Crenn Hebert C , Huissoud C , Fresson J , Winer N , Langer B , Rozenberg P , Morel O , Bonnet MP , Perrotin F , Azria E , Carbillon L , Chiesa C , Raynal P , Rudigoz RC , Dreyfus M , Vendittelli F , Patrier S , Deneux‐Tharaux C , Sentilhes L
Published: January 2021

Objective

To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section.

Design

Prospective population‐based study.

Setting

All 176 maternity hospitals of eight French regions.

Population

Two hundred and forty‐nine women with PAS, from a source population of 520 114 deliveries.

Methods

Women with PAS were classified into two risk‐profile groups, with or without the high‐risk combination of placenta praevia (or an anterior low‐lying placenta) and at least one prior caesarean. These two groups were described and compared.

Main outcome measures

Population‐based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes.

Results

The PAS population‐based incidence was 4.8/10 000 (95% CI 4.2–5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally.

Conclusion

More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean.

Tweetable abstract

Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.
The fentanyl phase of the opioid epidemic in Cuyahoga County, Ohio, United States
Authors: Deo Vaishali S. , Gilson Thomas P. , Kaspar Claire , Singer Mendel E.
Published: January 2021

Since late 2014, fentanyl has become the major driver of opioid mortality in the United States. However, a descriptive analysis of fentanyl victims is limited. We studied the 2016 fentanyl and heroin overdose deaths and compared them to previously studied heroin‐associated fatalities from 2012 over a wide range of demographic and investigative variables, including overdose scene findings, toxicology results, and prescription drug history. We observed a significant increase in fentanyl‐related deaths (n = 421, 2016) versus heroin deaths (n = 160, 2012) but the baseline demographics between both cohorts remained similar. Victims were predominantly of ages 35–64 years (60%–64%), White (83%–85%), and male (73%–76%). 2016 fentanyl decedents were more likely to have naloxone administered upon overdose, and the majority still had a positive prescription history for a controlled substance. Toxicology data showed a decrease in mean morphine and 6‐monoacetylmorphine concentrations when cointoxication with fentanyl occurred. Our study emphasizes the medical examiner's role as a public health data source and bridge between different stakeholders combating the opioid epidemic.
The online behaviors of Islamic state terrorists in the United States
Authors: Whittaker Joe
Published: January 2021

Research Summary

This study offers an empirical insight into terrorists’ use of the Internet. Although criminology has previously been quiet on this topic, behavior‐based studies can aid in understanding the interactions between terrorists and their environments. Using a database of 231 US‐based Islamic State terrorists, four important findings are offered: (1) This cohort utilized the Internet heavily for the purposes of both networking with co‐ideologues and learning about their intended activity. (2) There is little reason to believe that these online interactions are replacing offline ones, as has previously been suggested. Rather, terrorists tend to operate in both domains. (3) Online activity seems to be similar across the sample, regardless of the number of co‐offenders or the sophistication of attack. (4) There is reason to believe that using the Internet may be an impediment to terrorists’ success.

Policy Implications

The findings of this study have two important policy implications. First, it is vital to understand the multiplicity of environments in which terrorists inhabit. Policy makers have tended to emphasize the online domain as particularly dangerous and ripe for exploitation. While this is understandable from one perspective, simplistic and monocausal explanations for radicalization must be avoided. Terrorists operate in both the online and offline domain and there is little reason to believe that the former is replacing the latter. The two may offer different criminogenic inducements to would‐be terrorists, and at times they may be inseparably intertwined. Second, when policy responses do focus on online interventions, it is vital to understand the unintended consequences. This is particularly the case for content removal, which may inadvertently be aiding terrorists and hampering law enforcement investigations.