bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid surveillance platforms for key SARS-CoV-2 mutations in Denmark
Authors: Spiess Katja , Gunalan Vithiagaran , Marving Ellinor , Nielsen Sofie Holdflod , Jørgensen Michelle G. P. , Fomsgaard Anna S. , Nielsen Line , Alfaro-Núñez Alonzo , M. Karst Søren ,   The Danish COVID-19 Genome Consortium (DCGC), Mortensen Shila , Rasmussen Morten , Lassaunière Ria , Worsøe Rosenstierne Maiken , Polacek Charlotta , Fonager Jannik , Cohen Arieh S. , Nielsen Claus , Fomsgaard Anders
Published: October 2021

Multiple mutations in SARS-CoV-2 variants of concern (VOCs) may increase, transmission, disease severity, immune evasion and facilitate zoonotic or anthoprozoonotic infections. Four such mutations, ΔH69/V70, L452R, E484K and N501Y, occur in the SARS-CoV-2 spike glycoprotein in combinations that allow detection of the most important VOCs. Here we present two flexible RT-qPCR platforms for small-and large-scale screening to detect these mutations, and schemes for adapting the platforms for future mutations. The large-scale RT-qPCR platform, was validated by pair-wise matching of RT-qPCR results with WGS consensus genomes, showing high specificity and sensitivity. Detection of mutations using this platform served as an important interventive measure for the Danish public health system to delay the emergence of VOCs and to gain time for vaccine administration. Both platforms are valuable tools for WGS-lean laboratories, as well for complementing WGS to support rapid control of local transmission chains worldwide.
Third vaccine doses could have indirectly averted >100,000 deaths in the USA by reducing transmission of the SARS-CoV-2 Delta variant
Authors: Gardner Billy J. , Kilpatrick A. Marm
Published: October 2021

Vaccination programs often focus on direct protection of individuals against disease and discount reductions in transmission, which can result in preventable disease and death. Initial clinical trials for most COVID-19 vaccines only measured direct protection, and dosing and vaccine selection decisions have, so far, ignored effects on transmission. Here we provide an empirical framework for incorporating indirect effects of COVID-19 vaccination on transmission in a continuous dynamic immune landscape. For the first time, we quantified relationships between neutralizing antibody titers and vaccine effectiveness for both susceptibility (VES) and infectiousness (VEI) and quantified changes in VE with waning and boosting of immunity. We used these relationships to quantify the impact that additional doses of mRNA vaccines (BNT162b2 and mRNA-1273) could have had in reducing transmission and deaths caused by the deadliest SARS-CoV-2 variant, Delta, in Autumn 2021. Neutralizing antibodies waned 8-fold in 2021 over the six months following initial vaccination with mRNA vaccines, which reduced VES33-38% (from 75-81% to 47-54%) and VEI62-65% (from 47-57% to 16-22%) against the Delta variant. Third doses increased neutralizing antibody titers 13-26-fold, which more than restored VE and reduced the relative risk of transmission 7-10-fold. Administering third doses by September 1, 2021 could have reduced the effective reproductive number Rtby 19%, stopped surges in transmission in many populations, and averted an estimated 111,491 deaths in the United States. Vaccination programs that incorporate effects on transmission in trial design, vaccination frequency, and vaccine choice are needed to address current and future public health challenges.

Significance

Vaccination programs for many diseases often focus primarily on people at risk of severe disease and sometimes discount indirect reductions in transmission. We developed a framework for estimating the effects of vaccination on transmission and used it to estimate the number of COVID-19 deaths that could have been averted by deploying third doses during the Delta variant surge to reduce transmission. We show that immunity against transmission had waned significantly in late 2021. However, widespread deployment of third doses could have restored protection, stopped surges of the Delta variant, and prevented more than 100,000 deaths in the United States. Vaccination programs should incorporate effects on transmission in initial trial design, vaccination frequency, and vaccine selection to address public health challenges.
Adaptive data-driven selection of sequences of biological and cognitive markers in pre-clinical diagnosis of dementia
Authors: Wyss Patric , Ginsbourger David , Shou Haochang , Davatzikos Christos , Klöppel Stefan , Abdulkadir Ahmed ,   the ISTAGING Study,   the Alzheimer’s Disease Neuroimaging Initiative,   the Australian Imaging Biomarkers and Lifestyle flagship study of ageing
Published: October 2021

Effective clinical decision procedures must balance multiple competing objectives such as time-to-decision, acquisition costs, and accuracy. We describe and evaluate POSEIDON, a data-driven method for PrOspective SEquentIal DiagnOsis with Neutral zones to individualize clinical classifications. We evaluated the framework with an application in which the algorithm sequentially proposes to include cognitive, imaging, or molecular markers if a sufficiently more accurate prognosis of clinical decline to manifest Alzheimer’s disease is expected. The algorithm chose to include optional invasive markers in 37 percent of cases at the cost of 1 percent lower accuracy. Applied to longitudinal data, POSEIDON selected 14 percent of all available measurements and concluded after an average follow-up time of 0.74 years at the expense of five percent lower accuracy. While effective in obtaining timely and economical decisions, our multi-objective evaluation implies that the implementation into consequential clinical applications remains controversial because of the intrinsic dependence on inherently subjective prescribed cost parameters.
Interaction Between Transcribing RNA Polymerase and Topoisomerase I Prevents R-loop Formation in E. coli
Authors: Sutormin Dmitry , Galivondzhyan Alina , Musharova Olga , Travin Dmitrii , Rusanova Anastasiya , Obraztsova Kseniya , Borukhov Sergei , Severinov Konstantin
Published: October 2021

Bacterial topoisomerase I (TopoI) removes excessive negative supercoiling and is thought to relax DNA molecules during transcription, replication and other processes. Using ChIP-Seq, we show that TopoI of Escherichia coli (EcTopoI) is co-localized, genome-wide, with RNA polymerase (RNAP) in transcription units. Treatment with transcription elongation inhibitor rifampicin leads to EcTopoI relocation to promoter regions, where RNAP also accumulates. When a 14 kDa RNAP-binding EcTopoI C-terminal domain (CTD) is overexpressed, co-localization of EcTopoI and RNAP along the transcription units is reduced. Pull-down experiments directly show that the two enzymes interact in vivo. Using ChIP-Seq and Topo-Seq, we demonstrate that EcTopoI is enriched and in and upstream (within up to 12-15 Kbs) of highly-active transcription units, indicating that EcTopoI relaxes negative supercoiling generated by transcription. Uncoupling of the RNAP-EcTopoI interaction by either overexpression of EcTopoI CTD or deletion of EcTopoI domains involved in the interaction is toxic for cells and leads to excessive negative plasmid supercoiling. Moreover, the CTD overexpression leads to R-loops accumulation genome-wide, indicating that the RNAP-EcTopoI interaction is required for prevention of R-loops formation.

Article Highlights

TopoI colocalizes genome-wide and interacts with RNAP in E. coli

Disruption of the interaction between TopoI and RNAP decreases cells viability, leads to hypernegative DNA supercoiling, and R-loops accumulation

TopoI and DNA gyrase are enriched, respectively, upstream and downstream of transcription units in accordance with twin-domain model of Liu and Wang

TopoI recognizes its cleavage sites through a specific motif and by sensing negative supercoiling
Architecture of the cytoplasmic face of the nuclear pore
Authors: Bley Christopher J. , Nie Si , Mobbs George W. , Petrovic Stefan , Gres Anna T. , Liu Xiaoyu , Mukherjee Somnath , Harvey Sho , Huber Ferdinand M. , Lin Daniel H. , Brown Bonnie , Tang Aaron W. , Rundlet Emily J. , Correia Ana R. , Chen Shane , Regmi Saroj G. , Dasso Mary , Patke Alina , Palazzo Alexander F. , Kossiakoff Anthony A. , Hoelz André
Published: October 2021

The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating the NPC symmetric core architecture, the asymmetrically decorated cytoplasmic face, essential for mRNA export and a hotspot for nucleoporin-associated diseases, has remained elusive. Here, we report a composite structure of the entire human cytoplasmic face obtained by combining biochemical reconstitution, crystal structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation, accounting for a third of the NPC’s mass. Whereas an evolutionarily conserved ∼540 kDa hetero-hexameric cytoplasmic filament nucleoporin complex is anchored by species-specific motifs above the central transport channel, attachment of the pentameric NUP358 bundles depends on the double-ring arrangement of the coat nucleoporin complex. Our results and the predictive power of our composite structure provide a rich foundation for elucidating the molecular basis of mRNA export and nucleoporin diseases.

One sentence summary

An interdisciplinary analysis established the near-atomic molecular architecture of the cytoplasmic face of the human nuclear pore complex.
Structural determinants in the Staphylococcus aureus derived phenol-soluble modulin α2 peptide required for neutrophil formyl peptide receptor activation
Authors: Viklund Moa , Fredriksson Johanna , Holdfeldt André , Lind Simon , Franzyk Henrik , Dahlgren Claes , Sundqvist Martina , Forsman Huamei
Published: October 2021

Highly pathogenic Staphylococcus aureus strains produce phenol-soluble modulins (PSMs), peptides which are formylated N-terminally. Nanomolar concentrations of PSMα2 are recognized by formyl peptide receptor 2 (FPR2), but unlike the prototypic FPR2 agonist WKYMVM, PSMα2 is a biased signaling agonist. A shortened N-terminal PSMα2 variant, consisting of the five N- terminal residues, is selectively recognized by the closely related FPR1, showing that the C- terminal part of PSMα2 confers FPR2 selectivity, while the N-terminal part may interact with the FPR1 binding site. In the present study, a combined pharmacological and genetic approach, involving primary neutrophils and engineered FPR “knock-in” and “knock-out” cells, was used to gain molecular insights into FPR1 and FPR2 recognition of formyl peptides and the receptor downstream signaling induced by these peptides. In comparison to the full-length PSMα2, we show that the peptide in which the N-terminal part of PSMα2 was replaced by fMIFL (an FPR1- selective peptide agonist) potently activates both FPRs for production of superoxide anions and β- arrestin recruitment. A shortened analogue of PSMα2 (PSMα21-12), lacking the nine C-terminal residues activated both FPR1 and FPR2 to produce ROS, whereas β-arrestin recruitment was only mediated through FPR1. However, a single amino acid replacement (Gly-2 to Ile-2) in PSMα21-12 was sufficient to alter FPR2 signaling to include β-arrestin recruitment, highlighting a key role of Gly-2 in conferring FPR2 biased signaling. In conclusion, we provide novel structural insights into FPR1 and FPR2 recognition as well as the signaling induced by interaction with formyl peptides derived from PSMα2, originating from Staphylococcus aureus bacteria.
Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads
Authors: Ramiro Iris Bea. L. , Bjørn-Yoshimoto Walden E. , Imperial Julita S. , Gajewiak Joanna , Watkins Maren , Taylor Dylan , Resager William , Ueberheide Beatrix , Bräuner-Osborne Hans , Whitby Frank G. , Hill Christopher P. , Martin Laurent F. , Patwardhan Amol , Concepcion Gisela P. , Olivera Baldomero M. , Safavi-Hemami Helena
Published: October 2021

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms, but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential.

One Sentence Summary

Somatostatin drug design by fish-hunting cone snails
Diversity, function and evolution of marine microbe genomes
Authors: Chen Jianwei , Guo Yang , Jia Yangyang , Liu Guilin , Li Denghui , Xu Dayou , Wang Bing , Zhou Li , Peng Ling , Zhao Fang , Zhu Yuanfang , Sun Jiahui , Ye Chen , Wang Jun , Zhang He , Liu Shanshan , Seim Inge , Liu Xin , Xu Xun , Yang Huanming ,   GOMP Consortium, Kristiansen Karsten , Fan Guangyi
Published: October 2021

Trillions of marine bacterial, archaeal and viral species contribute to the majority diversity of life on Earth. In the current study, we have done a comprehensive review of all the published studies of marine microbiome by re-analyzing most of the available high throughput sequencing data. We collected 17.59 Tb sequencing data from 8,165 metagenomic and prokaryotic samples, and systematically evaluated the genome characters, including genome size, GC content, phylogeny, and the functional and ecological roles of several typical phyla. A genome catalogue of 9,070 high quality genomes and a gene catalogue including 156,209,709 genes were constructed, representing the most integrate marine prokaryotic datasets till now. The genome size of Alphaproteobacteria and Actinobacteria was significant correlated to their GC content. A total of 44,322 biosynthetic gene clusters distributed in 53 types were detected from the reconstructed marine prokaryotic genome catalogue. Phylogenetic annotation of the 8,380 bacterial and 690 archaeal species revealed that most of the known bacterial phyla (99/111), including 62 classes and 181 orders, and four extra unclassified genomes from two candidate novel phyla were detected. In addition, taxonomically unclassified species represented a substantial fraction of 64.56% and 80.29% of the phylogenetic diversity of Bacteria and Archaea respectively. The genomic and ecological features of three groups of Cyanobacteria, luminous bacteria and methane-metabolizing archaea, including inhabitant preference, geolocation distribution and others were through discussed. Our database provides a comprehensive resource for marine microbiome, which would be a valuable reference for studies of marine life origination and evolution, ecology monitor and protection, bioactive compound development.
A system for CBAF reconstitution reveals roles for BAF47 domains and BCL7 in nucleosome ejection
Authors: Mulvihill Timothy S. , Nelson Mary L. , Verma Naveen , Jones Kevin B. , Cairns Bradley R.
Published: October 2021

Canonical BAF (CBAF) is an essential 12-protein chromatin-remodeling complex that slides and/or ejects nucleosomes using the alternative catalytic ATP-dependent DNA translocases BRG1 or BRM. Currently, the regulation of BRG1/BRM activity and nucleosome ejection remain incompletely understood. To address this, we developed a system for full CBAF reconstitution and purification, and created a novel nucleosome ejection assay. ARID1A and DPF2 were dispensable for assembly and chromatin remodeling activity, contrasting with prior work. The actin-related protein BAF53A and β-actin components interacted and enhanced DNA translocation, and were required for BCL7A incorporation, which potentiated ejection. BAF47 also regulated ejection, utilizing two stimulatory domains and an autoinhibitory domain. Finally, we provide evidence for ‘direct’ nucleosome ejection at low nucleosome density on closed circular arrays. Taken together, we provide powerful new tools for CBAF mechanistic investigation and reveal new roles for several CBAF components.
Application of sequence semantic and integrated cellular geography approach to study biogenesis of exonic circular RNA
Authors: Kumar Rajnish , Lahiri Tapobrata , Pal Manoj Kumar
Published: October 2021

Background

Concurrent existence of lncRNA and circular RNA at both nucleus and cytosol within a cell at different proportion is well reported. Secondly, information on genes transcribing both circular and lncRNAs along with total number of RBP binding sites for both of these RNA types is extractable from databases. This study showed how these apparently unconnected pieces of reports could be put together to build a model leading to biogenesis of circular RNA.

Results

As a result of this study, a model was built under the premises that, sequences with special semantics were molecular precursors in biogenesis of circular RNA which occurred through catalytic role of some specific RBPs. The model outcome was further strengthened by fulfillment of three logical lemmas which were extracted and assimilated in this work using a novel data analytic approach, Integrated Cellular Geography. Result of the study was found to be in well agreement with proposed model. Furthermore this study also indicated that biogenesis of circular RNA was a post-transcriptional event.

Conclusions

Overall, this study provides a novel systems biology based model under the paradigm of Integrated Cellular Geography which can assimilate independently performed experimental results and data published by global researchers on RNA biology to provide important information on biogenesis of exonic circular RNAs considering lncRNAs as precursor molecule.
Extracellular loop 2 of G protein-coupled olfactory receptors is critical for odorant recognition
Authors: Yu Yiqun , Pacalon Jody , Ma Zhenjie , Xu Lun , Belloir Christine , Topin Jeremie , Briand Loïc , Golebiowski Jérôme , Cong Xiaojing
Published: October 2021

G protein-coupled olfactory receptors (ORs) enable us to detect innumerous odorants. They are also ectopically expressed, emerging as attractive drug targets. ORs can be promiscuous or highly specific, which is part of Nature’s strategy for odor discrimination. This work demonstrates that the extracellular loop 2 (ECL2) plays critical roles in OR promiscuity and specificity. Using site-directed mutagenesis and molecular modeling, we constructed 3D OR models in which ECL2 forms a lid of the orthosteric pocket. ECL2 controls the shape and the volume of the odorant-binding pocket, maintains the pocket hydrophobicity and acts as a gatekeeper of odorant binding. The interplay between the specific orthosteric pocket and the variable, less specific ECL2 controls OR specificity and promiscuity. The 3D models enabled virtual screening of new OR agonists and antagonists, exhibiting 78% hit rate in cell assays. This approach can be generalized to structure-based ligand screening for other GPCRs that lack high-resolution 3D structures.
Geological processes mediate a subsurface microbial loop in the deep biosphere
Authors: Gittins Daniel A. , Desiage Pierre-Arnaud , Morrison Natasha , Rattray Jayne E. , Bhatnagar Srijak , Chakraborty Anirban , Zorz Jackie , Li Carmen , Horanszky Oliver , Cramm Margaret A. , Webb Jamie , MacDonald Adam , Fowler Martin , Campbell D. Calvin , Hubert Casey R. J.
Published: October 2021

Summary paragraph

The deep biosphere is the largest microbial habitat on Earth and features abundant bacterial endospores1,2. Whereas dormancy and survival at theoretical energy minima are hallmarks of subsurface microbial populations3, the roles of fundamental ecological processes like dispersal and selection in these environments are poorly understood4. Here we combine geophysics, geochemistry, microbiology and genomics to investigate biogeography in the subsurface, focusing on bacterial endospores in a deep-sea setting characterized by thermogenic hydrocarbon seepage. Thermophilic endospores in permanently cold seabed sediments above petroleum seep conduits were correlated with the presence of hydrocarbons, revealing geofluid-facilitated cell migration pathways originating in deep oil reservoirs. Genomes of thermophilic bacteria highlight adaptations to life in anoxic petroleum systems and reveal that these dormant populations are closely related to oil reservoir microbiomes from around the world. After transport out of the subsurface and into the deep-sea, thermophilic endospores re-enter the geosphere by sedimentation. Viable thermophilic endospores spanning the top several metres of the seabed correspond with total endospore counts that are similar to or exceed the global average. Burial of dormant cells enables their environmental selection in sedimentary formations where new petroleum systems establish, completing a geological microbial loop that circulates living biomass in and out of the deep biosphere.
Notch signaling determines cell-fate specification of the two main types of vomeronasal neurons of rodents
Authors: Katreddi Raghu Ram , Taroc Ed Zandro M. , Hicks Sawyer M , Lin Jennifer M , Liu Shuting , Xiang Mengqing , Forni Paolo E.
Published: October 2021

The ability of terrestrial vertebrates to find food, mating partners and to avoid predators heavily relies on the detection of chemosensory information from the environment. The olfactory system of most vertebrate species comprises two distinct chemosensory systems usually referred to as the main and the accessory olfactory system. Olfactory sensory neurons of the main olfactory epithelium detect and transmit odor information to main olfactory bulb (MOB), while the chemosensory neurons of the vomeronasal organ detect semiochemicals responsible for social and sexual behaviors and transmit information to the accessory olfactory bulb (AOB). The vomeronasal sensory epithelium (VNE) of most mammalian species contains uniform vomeronasal (VN) system with vomeronasal sensory neurons (VSNs) expressing vomeronasal receptors of the V1R family. However, rodents and some marsupials have developed a more complex binary VN system, where VNO containing a second main type of VSNs expressing vomeronasal receptors of the V2R family is identified. In mice, V1R and V2R VSNs form from a common pool of progenitors but have distinct differentiation programs. As they mature, they segregate in different regions of the VNE and connect with different parts of the AOB. How these two main types of VSNs are formed has never been addressed. In this study, using single cell RNA sequencing data, we identified differential expression of Notch1 receptor and Dll4 ligand among the neuronal precursors at the VSN dichotomy. We further demonstrated with loss of function (LOF) and gain of function (GOF) studies that Dll4-Notch1 signaling plays a crucial role in triggering the binary dichotomy between the two main types of VSNs in mice.

Graphical Abstract
Salts of purine alkaloids caffeine and theobromine with 2,6-dihydroxybenzoic acid as coformer: structural, theoretical, thermal and spectroscopic studies
Authors: Gołdyn Mateusz , Komasa Anna , Pawlaczyk Mateusz , Lewandowska Aneta , Bartoszak-Adamska Elżbieta
Published: October 2021

The study of various forms of pharmaceutical substances with specific physicochemical properties suitable for putting them on the market is one of the elements of research in the pharmaceutical industry. A large proportion of active pharmaceutical ingredients (APIs) occur in the salt form. The use of an acidic coformer with a given structure and a suitable pK
a value towards purine alkaloids containing a basic imidazole N atom can lead to salt formation. In this work, 2,6-dihydroxybenzoic acid (26DHBA) was used for cocrystallization of theobromine (TBR) and caffeine (CAF). Two novel salts, namely, theobrominium 2,6-dihydroxybenzoate, C7H9N4O2
+·C7H5O4
− (I), and caffeinium 2,6-dihydroxybenzoate, C8H11N4O2
+·C7H5O4
− (II), were synthesized. Both salts were obtained independently by slow evaporation from solution, by neat grinding and also by microwave-assisted slurry cocrystallization. Powder X-ray diffraction measurements proved the formation of the new substances. Single-crystal X-ray diffraction studies confirmed proton transfer between the given alkaloid and 26DHBA, and the formation of N—H...O hydrogen bonds in both I and II. Unlike the caffeine cations in II, the theobromine cations in I are paired by noncovalent N—H...O=C interactions and a cyclic array is observed. As expected, the two hydroxy groups in the 26DHBA anion in both salts are involved in two intramolecular O—H...O hydrogen bonds. C—H...O and π–π interactions further stabilize the crystal structures of both compounds. Steady-state UV–Vis spectroscopy showed changes in the water solubility of xanthines after ionizable complex formation. The obtained salts I and II were also characterized by theoretical calculations, Fourier-transform IR spectroscopy (FT–IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and elemental analysis.
An examination of board diversity and corporate social responsibility disclosure: evidence from banking sector in the Arabian Gulf countries
Authors: Issa Ayman , Zaid Mohammad A.A. , Hanaysha Jalal Rajeh , Gull Ammar Ali
Published: October 2021

Purpose

The purpose of this study is to examine the impact of board diversity (e.g. education, gender, nationality and royal family members) on voluntary corporate social responsibility (CSR) disclosure for a sample of banks listed in the Arabian Gulf Council countries.

Design/methodology/approach

The authors use the Global Reporting Initiative guidelines to construct the CSR disclosure index. The empirical analysis is based on the data of banks listed in the Gulf Cooperation Council countries over the period 2011–2019. To tackle the potential issue of endogeneity, the authors apply the system generalized method of moments (GMM) estimation approach to investigate the relationship between board diversity and CSR disclosure index.

Findings

The findings of the analysis show that there is a significant relationship between board diversity and the level of voluntary CSR disclosure. Specifically, the authors find that diversity captured by the education level, nationality and the presence of royal family members on board is positively associated with the level of voluntary CSR disclosure while diversity captured by the gender of board members is negatively associated with the level of voluntary CSR disclosure.

Practical implications

The regulators, policymakers, stakeholders and the board of directors become aware of the diversity mechanisms that must be used to promote CSR practices in the banking sector of Arabian Gulf countries.

Originality/value

The authors extend the existing literature by providing empirical evidence on the association between board diversity and voluntary CSR disclosure practices of banks operating in the Arabian Gulf countries. This study also highlights that board gender diversity may have a different impact on voluntary CSR disclosure between developed countries and developing countries. This paper also provides preliminary evidence on the importance of education level, the presence of foreign and royal directors on board to influence CSR practices of banks operating in the Arabian Gulf countries.
Designing innovative jobs: a fuzzy-set configurational analysis of job characteristics
Authors: Cangialosi Nicola , Battistelli Adalgisa , Odoardi Carlo
Published: October 2021

Purpose

How to design jobs to support innovation is an issue that has received plenty of consideration over the past years. Building on the job characteristics model, the present study is set up to identify configurations of perceived job characteristics for innovation.

Design/methodology/approach

By adopting a fuzzy-set configurational approach (fsQCA), the research question is addressed through a two-wave self-report survey of 199 employees of an Italian manufacturing company.

Findings

Results reveal four compatible configurations of job characteristics leading to high levels of innovative work behavior and two for low levels.

Practical implications

The results offer guidance for managers and organizations that aim to strengthen employee-driven innovation by offering different recipes of job design to maximize the chance of boosting innovative behaviors among their workers.

Originality/value

This research is one of the first to empirically test the relation of job characteristics for innovative behavior using a configurational approach. By doing so it contributes to the literature by advancing the notion that innovative endeavors are determined by the holistic effects of different interdependent configurations of job characteristics.
Hindsight is 2020: identifying missed leadership opportunities to reduce employee turnover intention amid the COVID-19 shutdown
Authors: Robertson Melva B.
Published: October 2021

Purpose

The purpose of this paper is to highlight how organizational leaders influenced the high 2021 turnover rates amid the COVID-19 shutdown.

Design/methodology/approach

This paper explores several factors that contributed to employee turnover intention before the pandemic and how unresolved leadership behaviors and toxic organizational cultures exacerbated circumstances that led to what is now known as The Great Resignation of 2021.

Findings

This paper suggests that while the pandemic shutdown temporarily paused employee turnover, organizational leaders missed an opportunity to retain their employees by not recognizing and changing factors that led to pre-existing employee turnover intention.

Originality/value

This paper explores solutions to help leaders support and retain current and future employees as the pandemic continues and in the event of futures crises. It offers recommendations for leadership development support to help strengthen leaders in their highly complex roles.
Broadband seismic source data acquisition and processing to delineate iron oxide deposits in the Blötberget mine‐central Sweden
Authors: Pertuz Tatiana , Malehmir Alireza , Bos Jordan , Brodic Bojan , Ding Yinshuai , de Kunder Richard , Marsden Paul
Published: October 2021

A prototype electromagnetic vibrator, referred to here as E‐Vib, was upgraded and developed for broadband hardrock and mineral exploration seismic surveys. We selected the iron oxide mine in Blötberget, central Sweden, for a test site in 2019 for the newly developed E‐Vib because of the availability of earlier seismic datasets (from 2015 to 2016) for verification of its performance for hardrock imaging purposes. The two‐dimensional data acquisition consisted of a fixed geometry with 550 receiver locations spaced at every 5 m, employing both cabled and wireless seismic recorders, along an approximately 2.7 km long profile. The E‐Vib operated at every second receiver station (i.e. 10 m spacing) with a linear sweep of 2–180 Hz and with a peak force of 7 kN. The processing workflow took advantage of the broadband signal generated by the E‐Vib in this challenging hardrock environment with varying ground conditions. The processed seismic section shows a set of reflections associated with the known iron oxide mineralization and a major crosscutting reflection interpreted to be from a fault system likely to be crosscutting the mineralization. The broadband source data acquisition and subsequent processing helped to improve signal quality and resolution in comparison with the earlier workflows and data where a drophammer seismic source was used as the seismic source. These results suggest new possibilities for the E‐Vib source for improved targeting in hardrock geological settings.
Long‐term captivity is associated with changes to sensory organ morphology in a critically endangered insect
Authors: Freelance Christopher B. , Magrath Michael J. L. , Elgar Mark A. , Wong Bob B. M.
Published: October 2021

Captive breeding programmes are key to many threatened species reintroduction strategies but could potentially be associated with adaptations to captivity that are maladaptive in their natural habitat. Despite the importance of sensory ecology to biological fitness, few studies explore sensory system adaptations to captivity. Captive environments are devoid of predators and provide ready access to food sources and potential mates, thus reducing the need for individuals to use signals and cues to identify and locate resources or detect potential threats. With reduced complexity of the signalling environment, relaxation of selective pressures may favour reduced investment in sensory organs in captivity.

We test this prediction in an iconic critically endangered invertebrate, the Lord Howe Island stick insect Dryococelus australis, which was extirpated from the island in the 1920s/30s and rediscovered on a nearby volcanic stack, Ball's Pyramid, in 2001.

Using historical specimens from these populations and specimens from the 8–10th and 14th generations of a long‐term conservation captive breeding programme, we examine differences in behaviourally relevant morphological traits of the compound eyes (visual organs) and antennae (olfactory organs).

We find that captivity is associated with smaller compound eye size, smaller eye ommatidia and reduced density of antennal odour receptors. These morphological changes are indicative of reduced sensitivity to visual and olfactory signals and cues, and therefore are likely to have fitness implications when reintroducing a captive population into the wild.

Synthesis and applications. We observe differences in sensory organ morphology between wild and captive‐bred populations of the critically endangered Lord Howe Island stick insect. Our results emphasise the importance of incorporating evolutionary biology and sensory ecology into conservation programme design: to minimise the potential for captive breeding environments to compromise sensory systems that support appropriate behaviours upon reintroduction of populations into a natural habitat.
Optimizing flower fields as an effective farmland eco‐scheme also during non‐breeding
Authors: Rieger Mirjam R. , Mailänder Sarah , Stier Lea , Santon Matteo , Staggenborg Julia , Anthes Nils
Published: October 2021

The Common Agricultural Policy (CAP) of the European Union implements several farmland eco‐schemes, but most are considered ineffective in halting the population declines of farmland birds. Sown flower fields are among the few eco‐scheme types that rate as clearly beneficial. Yet, current CAP regulations lack minimum criteria for flower fields to qualify as eco‐scheme, and thus only partially exploit their potential biodiversity benefits.

Earlier research on the attraction of farmland birds to different types of sown flower fields has focused on the breeding season. We know far less about relative use of these fields during the non‐breeding season, when food limitation can become severe. We therefore compared the attractiveness of four flower field types in SW Germany to 17 bird species during autumn and winter. Based on replicate surveys on 75–168 fields, we analysed bird incidences across these four types, and in relation to vegetation structure and landscape features.

Flower field types showed little variation in species richness, but striking differences in selection by particular species. Finches and tits were disproportionally abundant on fields in their first year since sowing, buntings and whinchat on fields in later successional stages. Most flower fields established under CAP greening regulations were ploughed between September and November in their sowing year. Therefore, such fields fail to support farmland birds and other wildlife during a critical phase in their annual cycle.

Birds were consistently more abundant on larger fields with a differentiated vegetation structure. Flower fields along hedgerows and groves primarily attracted inhabitants of woodland ecotones, while farmland birds had higher incidences on fields embedded in open landscapes.

Policy implications. EU member states currently revise their regulations for farmland eco‐schemes, including sown flower fields. We propose minimum quality standards to assure that such fields effectively support farmland birds also during the non‐breeding season. Standards include a minimum maintenance for two years, more diversified seed mixtures, field sizes exceeding 12 m width or 0.18 ha area, and local diversity in flower field placement relative to other landscape elements such as hedgerows.
Response and safety of whole‐brain radiotherapy plus temozolomide for patients with brain metastases of non‐small‐cell lung cancer: A meta‐analysis
Authors: Han Jianguo , Qiu Ming , Su Li , Wu Chong , Cheng Si , Zhao Zhijun , Li Danxia , Wang Menghui , Tao Wei , Du Shiwei
Published: October 2021

Objective

The aim of the present work was to investigate the response and safety of whole‐brain radiotherapy (WBRT) plus temozolomide (TMZ) for patients with brain metastases of non‐small‐cell lung cancer (NSCLC).

Methods

The electronic databases of Pubmed, EMbase, Cochrane, Wangfang, china national knowledge infrastructure (CNKI), and Google scholar were systematically searched to identify the prospective randomized trials relevant to WBRT plus TMZ for patients with brain metastases of NSCLC. The data associated with treatment response and toxicity were extracted from original included studies. The relative risk (RR) for treatment response and toxicity between WBRT+TMZ and WBRT alone was pooled by fixed or random effect model. Publication bias was investigated by Begg's funnel plot and Egger's line regression test.

Results

Twenty‐five clinical trials fulfilled the inclusion criteria and were included in the meta‐analysis. The pooled results showed WBRT+TMZ can significant improve the objective response rate (ORR) compared with WBRT alone (RR = 1.43, 95% confidence interval [CI] 1.32–1.55, p < 0.05) under a fixed effect model. WBRT+TMZ significantly increased the III–IV hematological toxicity compared to WBRT alone (RR = 1.66, 95% CI 1.12–2.54, p < 0.05) in the fixed effect model. Grade III–IV gastrointestinal toxicity was increased in WBRT+TMZ compared to WBRT alone (RR = 1.72, 95% CI 1.29–2.30, p < 0.05). Begg's funnel plot and Egger's line regression test indicated publication bias.

Conclusion

Based on the present work, WBRT+TMZ can improve the ORR for brain metastases of NSCLC, but the risk of treatment‐associated grade III/IV hematological toxicity and gastrointestinal toxicity were also increased compared to WBRT alone.
Spatio‐temporal variation in tick community composition and abundance in a wildlife–livestock interface within Nyanga National Park, Zimbabwe
Authors: Mutizhe Silas W. , Mhlanga Lindah , Sithole Rudo , Maya Banele T. , Sibanda Artwell , Mpofu Protect
Published: October 2021

Human settlement expansion around Nyanga National Park has led to increased wildlife–livestock interaction. Tick community dynamics was evaluated in high, medium and low wildlife–livestock interaction sectors designated by extent of livestock incursions. Out of a total of 4281 ticks recorded, 39.8% were Rhipicephalus zambeziensis and 28.2% Rhipicephalus appendiculatus. Hyalomma truncatum, Rhipicephalus simus, Rhipicephalus decoloratus and Amblyomma variegatum were each less than seven percent, whereas Hyalomma rufipes, Rhipicephalus compositus, Amblyomma hebraeum, Rhipicephalus evertsi evertsi and Haemaphysalis leachi were each less than three percent. Tick species richness (S = 11) was highest in high interaction sectors. Amblyomma variegatum, A. hebraeum, R. compositus and R. eversti evertsi did not occur in low interaction sectors, whereas Ha. leachi was not recorded within shrublands and at high altitude. Tick abundance (p = 0.046) and diversity (p = 0.044) were only significantly influenced by interaction intensity. This could be attributed to greater host availability and increased animal bidirectional movement across the interface. Tick abundance was highest during summer. Tick dense spatial distribution was projected in areas where interaction is high. Increased interaction will increase abundance and spread of ticks into new areas within the park unless strategies to prevent animal bidirectional movement are instituted.
A retrospective cohort study of tubal occlusion or salpingectomy for permanent contraception in Australia
Authors: Baltus Tanja , Brown James , Kapurubandara Supuni
Published: October 2021

Background:

Laparoscopic permanent contraception was previously accomplished most commonly using tubal occlusion procedures. Bilateral salpingectomy (BS) has recently been introduced as an alternative due to possibly superior contraception and greater protection against ovarian cancer.

Aims:

The aim of this study is to assess uptake, feasibility and perioperative outcomes of laparoscopic BS as an alternative to tubal occlusion in Australia.

Materials and Methods:

A retrospective review of permanent female contraception at two Australian hospitals from January 2014 through December 2020 was performed. The primary outcome was the uptake of BS. Secondary outcomes were feasibility, procedure length, number of ports, perioperative complications and admission length.

Results:

A total of 414 women were included; 92 (22.2%) underwent BS and 322 (77.8%) underwent tubal occlusion. There was a slow uptake of BS from 2014 to 2016 (0–3.2%), with a steep uptake from 2017 to 2020 (30–72%) (P = 0.001). Procedure feasibility was 96.8% (62/64) and 99.3% (282/284) for BS and tubal occlusion group, respectively (P = 0.64). BS procedure time was longer by 23 min (P < 0.001). Three or more surgical ports were used in all cases of BS compared to 4.5% of the tubal occlusion group (P < 0.001). There were no intraoperative complications. There were nine and six postoperative complications in the tubal occlusion versus BS group, respectively (P = 0.10). The median admission length was 7.1 (tubal occlusion) versus 7.3 (BS) h (P = 0.10), with five unintended overnight admissions.

Conclusion:

BS is an increasing choice for permanent contraception. It appears equally feasible as tubal occlusion but typically requires a longer procedure time and a minimum of three surgical ports.
Characteristics of COVID‐19 patients up to 6 months of age admitted to a paediatric emergency department
Authors: Bellini Tommaso , Rotulo Gioacchino Andrea , Caruggi Samuele , Carta Sabina , Bonato Irene , Piccotti Emanuela
Published: October 2021

Very young age could be a potential risk factor for community‐acquired severe acute respiratory syndrome coronavirus 2, due to immature immune systems. We retrospectively enrolled 39 infants up to 6 months of age who had presented to our tertiary Italian children's hospital emergency room between 9 March 2020 and 8 March 2021 and tested positive for the virus. Of those, 38 had a non‐specific mild or asymptomatic clinical course and only one patient was admitted to intensive care with severe symptoms. We concluded that very young infants with COVID‐19 had a generally favourable disease course.
Physostigmine should be used more readily for antimuscarinic toxicity: PRO
Authors: Dawson Andrew
Published: October 2021

Physostigmine is the preferred treatment for antimuscarinic toxicity. Its use has a clear biological rationale and is supported by extensive clinical use which demonstrated effectiveness and safety.
Impact of target‐mediated drug disposition on hetrombopag pharmacokinetics and pharmacodynamics in Chinese healthy subjects and patients with chronic idiopathic thrombocytopenic purpura
Authors: Wang Zhenlei , Zeng Zhijun , Ye Lijun , Zhu Xiaohong , Pei Yuwen , Wang Yongsheng , Zheng Li
Published: October 2021

Aims

The pharmacokinetics (PK) of hetrombopag were found to be nonlinear across evaluated dose ranges. The aim of this study was to develop a mechanism‐based population pharmacokinetic/pharmacodynamic (PopPK/PD) model and to provide a reasonable expected therapeutic dose for a future confirmatory clinical study of hetrombopag.

Methods

Nonlinear mixed‐effects modelling was performed using pooled 2168 hetrombopag concentrations and 1526 platelet counts from 72 healthy subjects and 32 chronic idiopathic thrombocytopenic purpura (ITP) patients from two phase I studies and one phase II study. The final model was evaluated via goodness‐of‐fit plots, visual predictive check and nonparametric bootstrap. Simulations from the validated PopPK/PD model were used to devise an expected therapeutic dose for later confirmatory clinical study.

Results

The pharmacokinetic data of hetrombopag were well described by a modified target‐mediated drug disposition (TMDD) model with dual sequential first‐order absorption. Mean parameter estimates (interindividual variability) were CL/F 7.66 L/h (63.5%), Vc/F 30.0 L (77.2%) and Kdeg 0.693/h (87.1%). The pharmacodynamic profile was well described by a five‐compartment lifespan model with four‐transit and one‐platelet compartments. Simulation results suggested that chronic ITP patients following 10 mg once‐daily hetrombopag would able to achieve an ideal platelet count level (50‐200 × 109/L).

Conclusion

TMDD was the primary reason leading to nonlinear PK profile of hetrombopag. Our PK/PD modelling and simulation results support 10 mg once‐daily as the recommended therapeutic dose for chronic ITP patients in subsequent confirmatory clinical study of hetrombopag.
Cytoreductive nephrectomy and exposure to sunitinib – a post hoc analysis of the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial
Authors: Abu‐Ghanem Yasmin , van Thienen Johannes V. , Blank Christian , Aarts Maureen J. B. , Jewett Michael , de Jong Igle Jan , Lattouf Jean‐Baptiste , van Melick Harm H. E. , Wood Lori , Mulders Peter , Rottey Sylvie , Wagstaff John , Zondervan Patricia , Powles Tom , Neven Anouk , Collette Laurence , Tombal Bertrand , Haanen John , Bex Axel
Published: October 2021

Objective

To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm.

Patients and Methods

A post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention‐to‐treat population of the immediate and deferred arm. Descriptive methods and 95% confidence‐intervals (CI) were used.

Results

In the deferred arm, 97.7% (95% CI 89.3–99.6%; n = 48) received sunitinib vs 80% (95% CI 66.9–88.7%, n = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm.

Conclusions

In comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit.