bluuebunny/crossref_metadata_2025 huggingface dataset:
Microfluidics-free single-cell genomics with templated emulsification
Authors: Clark Iain C. , Fontanez Kristina M. , Meltzer Robert H. , Xue Yi , Hayford Corey , May-Zhang Aaron , D’Amato Chris , Osman Ahmad , Zhang Jesse Q. , Hettige Pabodha , Ishibashi Jacob S.A. , Delley Cyrille L. , Weisgerber Daniel W. , Replogle Joseph M. , Jost Marco , Phong Kiet T. , Kennedy Vanessa E. , Peretz Cheryl A. C. , Kim Esther A. , Song Siyou , Karlon William , Weissman Jonathan S. , Smith Catherine C. , Gartner Zev J. , Abate Adam R.
Published: June 2022

Single-cell RNA sequencing is now a standard method used to reveal the molecular details of cellular heterogeneity, but current approaches have limitations on speed, scale, and ease of use that stem from the complex microfluidic devices or fluid handling steps required for sample processing. We, therefore, developed a method that does not require specialized microfluidic devices, expertise, or hardware. Our approach is based on particle-templated emulsification, which allows single-cell encapsulation and barcoding of cDNA in uniform droplet emulsions with only a vortexer. PIP-seq accommodates a wide range of emulsification formats, including microwell plates and large-volume conical tubes, enabling thousands of samples or millions of cells to be processed in minutes. We demonstrate that PIP-seq produces high-purity transcriptomes in mouse-human mixing studies, is compatible with multi-omics measurements, and can accurately characterize cell types in human breast tissue when compared to a commercial microfluidic platform. Single-cell transcriptional profiling of mixed phenotype acute leukemia using PIP-seq revealed the emergence of heterogeneity within chemotherapy-resistant cell subsets that were hidden by standard immunophenotyping. PIP-seq is a simple, flexible, and scalable next-generation workflow that extends single-cell sequencing to new applications, including screening, diagnostics, and disease monitoring.
Aberrant MNX1 Expression Associated with t(7;12)(q36;p13) Pediatric Acute Myeloid Leukemia Induces the Disease Through Altering Histone Methylation
Authors: Waraky Ahmed , Östlund Anders , Nilsson Tina , Weichenhan Dieter , Lutsik Pavlo , Bähr Marion , Hey Joschka , Adamsson Jenni , Abdelrazak Morsy Mohammad Hamdy , Li Susann , Fogelstrand Linda , Plass Christoph , Palmqvist Lars
Published: June 2022

Certain subtypes of acute myeloid leukemia (AML) in children have inferior outcome. One of these has a translocation t(7;12)(q36;p13) leading to aMNX1::ETV6fusion along with high expression of MNX1. Here we identified the transforming event in this AML and possible ways of treatment. Only MNX1 was able to induce AML in mice, with similar gene expression and pathway enrichment to t(7;12) AML patient data. Importantly, this leukemia was only induced in immune incompetent mice using fetal but not adult hematopoietic stem and progenitor cells. The restriction in transforming capacity to cells from fetal liver is in alignment with t(7;12)(q36;p13) AML being mostly seen in infants. Expression of MNX1 led to increased histone 3 lysine 4 mono-, di- and trimethylation, reduction in H3K27me3, accompanied with changes in genome-wide chromatin accessibility and genome expression, likely mediated through MNX1 interaction with the methionine cycle and methyltransferases. MNX1 expression increased DNA damage, depletion of the Lin-/Sca1+/c-Kit+ population and skewing toward the myeloid lineage. These effects, together with leukemia development, was prevented by pretreatment with the S-adenosylmethionine analog Sinefungin. In conclusion, we have shown the importance of MNX1 in development of AML with t(7;12), supporting a rationale for targeting MNX1 and downstream pathways.
Assessing COVID-19 vaccination strategies in varied demographics using an individual-based model
Authors: Ben-Zuk Noam , Daon Yair , Sasson Amit , Ben-Adi Dror , Huppert Amit , Nevo Daniel , Obolski Uri
Published: June 2022

Background

New variants of SARS-CoV-2 are constantly discovered. Administration of COVID-19 vaccines and booster doses, combined with applications of non-pharmaceutical interventions (NPIs), is often used to prevent outbreaks of emerging variants. Such outbreak dynamics are further complicated by the population’s behavior and demographic composition. Hence, realistic simulations are needed to estimate the efficiency of proposed vaccination strategies in conjunction with NPIs.

Methods

We developed an individual-based model of COVID-19 dynamics that considers age-dependent parameters such as contact matrices, probabilities of symptomatic and severe disease, and households’ age distribution. As a case study, we simulate outbreak dynamics under the demographic compositions of two Israeli cities with different household sizes and age distributions. We compare two vaccination strategies: vaccinate individuals in a currently prioritized age group, or dynamically prioritize neighborhoods with a high estimated reproductive number. Total infections and hospitalizations are used to compare the efficiency of the vaccination strategies under the two demographic structures, in conjunction with different NPIs.

Results

We demonstrate the effectiveness of vaccination strategies targeting highly infected localities and of NPIs actively detecting asymptomatic infections. We further show that there are different optimal vaccination strategies for each demographic composition of sub-populations, and that their application is superior to a uniformly applied strategy.

Conclusion

Our study emphasizes the importance of tailoring vaccination strategies to subpopulations’ infection rates and to the unique characteristics of their demographics (e.g., household size and age distributions). The presented simulation framework and our findings can help better design future responses against the following emerging variants.
Association between perinatal mental health and reproductive and neonatal complications: a retrospective birth cohort study
Authors: Runkle Jennifer D. , Risley Kendra , Roy Manan , Sugg Maggie M.
Published: June 2022

Background

Maternal mental health as an important precursor to reproductive and neonatal complications remains understudied in the US, particularly in the Southeastern region, despite high medical costs and maternal morbidity, and infant burden.

Objective

This study sought to estimate the incidence of perinatal mental health disorders and the associated increased risk of leading pregnancy and infant complications.

Methods

A population-based retrospective birth cohort of delivery hospitalizations and readmissions was constructed for birthing populations in South Carolina, 1999 to 2017. Prevalence rates were calculated for perinatal mood and anxiety disorders (PMAD), severe mental illness (SMI), and maternal mental disorders of pregnancy (MDP). Poisson regression models using generalized estimating equations were used to estimate adjusted relative risks for the association between mental health conditions and severe maternal morbidity (SMM), hypertensive disorders of pregnancy (HDP), gestational diabetes (GD), cesarean delivery (CD), preterm birth (PTB), and low-birth weight (LBW).

Results

The most prevalent maternal mental condition was MDP (3.9%), followed by PMAD (2.7%) and SMI (0.13%). PMAD was associated with a higher risk of SMM, HDP, and CD, as well as a higher risk of PTB and LBW infants. SMI was associated with LBW, HDP, and CD. Pregnant populations with MDP were more at risk for SMM, PTB, HDP, LBW, and CD. Each maternal mental health outcome was associated with an elevated risk for hospital readmissions up to 45 days after delivery.

Discussion

Results demonstrated the escalating burden of PMAD and MDP for pregnant populations over time with important consequences related to maternal and infant morbidity.
Experimental and In Silico interaction studies of Alpha Amylase-Silver nanoparticle: a nano-bio-conjugate
Authors: Verma Awadhesh Kumar , Mishra Abhijeet , Dhiman Tarun Kumar , Sardar Meryam , Solanki Pratima R.
Published: June 2022

In the current work, biosynthesis of silver nanoparticle (Ag NPs) and interaction study between alpha amylase and Ag NPs/nanocluster has been performed via wet-lab as well as in silico approach. We have synthesized Ag NPs using alpha amylase enzyme which reduces the silver nitrate precursor forming the stable Ag NPs. UV-Visible spectroscopy and fluorescence spectroscopies were performed for optical characterization of Ag NPs. UV-Vis spectra showed the wide absorption band centered around 475 nm due to surface plasmon resonance. We have also observed gradual decrease in fluorescence intensity with the increase in incubation time. Also, shift in λmax of the emission spectra was recorded which clearly suggested the formation of nano-bio-conjugate. Circular dichroism spectra show the initial decrease in the ellipticity, when we added the silver nitrate, but after incubating for different time, there are no major changes in secondary structure of protein. In computational study we have modelled ground state configuration of (Ag)24 nanocluster using in silico approach. Further docking of the modelled optimized nanocluster with alpha amylase was performed and found that Ag-nanocluster showing non-covalent interaction with alpha amylase and forming stable docking complex.
A Conservative Approach for Describing Cancer Progression
Authors: Rossi Nicolò , Gigante Nicola , Vitacolonna Nicola , Piazza Carla
Published: June 2022

The field of tumor phylogenetics focuses on studying the differences within cancer cell populations and many efforts are done within the scientific community to build cancer progression models trying to understand the heterogeneity of such diseases. These models are highly dependent on the kind of data used for their construction and, as the experimental technologies evolve, it is of major importance to exploit their peculiarities. In this work we describe a cancer progression model based on Single Cell DNA Sequencing data. When constructing the model, we focus on tailoring the formalism on the specificity of the data, by defining a minimal set of assumptions to reconstruct a flexible DAG structured model, capable of identifying progression beyond the limitation of the infinite site assumption. We provide simulations and analytical results to show the features of our model, test it on real data, show how it can be integrated with other approaches to cope with input noise. Moreover, our framework can be exploited to produce simulated data that follows our theoretical assumptions. Finally, we provide an open source R implementation of our approach that is publicly available on BioConductor.
Two ligand-binding sites on SARS-CoV-2 non-structural protein 1 revealed by fragment-based x-ray screening
Authors: Ma Shumeng , Damfo Shymaa , Lou Jiaqi , Pinotsis Nikos , Bowler Matthew W. , Haider Shozeb , Kozielski Frank
Published: June 2022

The regular reappearance of coronavirus (CoV) outbreaks over the past 20 years has caused significant health consequences and financial burdens worldwide. The most recent and still ongoing novel CoV pandemic, caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has brought a range of devastating consequences. Due to the exceptionally fast development of vaccines, the mortality rate of the virus has been curbed to a significant extent. However, the limitations of vaccination efficiency and applicability, coupled with the still high infection rate, emphasise the urgent need for discovering safe and effective antivirals against SARS-CoV-2 through suppressing its replication and or attenuating its virulence. Non-structural protein 1 (nsp1), a unique viral and conserved leader protein, is a crucial virulence factor for causing host mRNA degradation, suppressing interferon (IFN) expression and host antiviral signalling pathways. In view of the essential role of nsp1 in the CoV life cycle, it is regarded as an exploitable target for antiviral drug discovery. Here, we report a variety of fragment hits against SARS-CoV-2 nspl identified by fragment-based screening via X-ray crystallography. We also determined the structure of nsp1 at atomic resolution (0.95 Å). Binding affinities of hits against nsp1 were determined by orthogonal biophysical assays such as microscale thermophoresis and thermal sift assays. We identified two ligand-binding sites on nsp1, one deep and one shallow pocket, which are not conserved between the three medially relevant SARS, SARS-CoV-2 and MERS coronaviruses. Our study provides an excellent starting point for the development of more potent nsp1-targeting inhibitors and functional studies on SARS-CoV-2 nsp1.
SARS2Mutant: SARS-CoV-2 Amino-Acid Mutation Atlas Database
Authors: Rahimian Karim , Mahmanzar Mohammadamin , Mahdavi Bahar , Arefian Ehsan , Kuehu Donna Lee , Deng Youping
Published: June 2022

The coronavirus disease 19 (COVID-19) is a highly pathogenic viral infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the global pandemic of 2020.A lack of therapeutic and preventive approaches including drugs and vaccines, has quickly posed significant threats to world health. A comprehensive understanding of the evolution and natural selection of SARS-CoV-2 against the host interaction and symptoms at the phenotype level could impact the candidate’s strategies for the fight against this virus.

SARS-CoV-2 Mutation (SARS2Mutant, http://sars2mutant.com/) is a database thatprovides comprehensive analysis results based on tens of thousands of high-coverage and high-quality SARS-CoV-2 complete protein sequences. The structure of this database is designed to allow the users to search for the three different strategies among amino acid substitution mutations based on gene name, geographical zone or comparative analysis. Based on each strategy, five data types are available to the user: mutated sample frequencies, heat map of the mutated amino acid positions, timeline trend for mutation survivals and natural selections, and charts of changed amino acids and their frequencies. Due to the increase of virus protein sequence samples published daily showing the latest trends of current results, all sequences in the database are reanalyzed and updated monthly. The SARS-2Mutant database providescurrent analysis and updated data of mutation patterns and conserved regions, helpful in developing and designing targeted vaccines, primers and drug discoveries.
Alterations in the Nasopharyngeal Microbiome Associated with SARS-CoV-2 Infection Status and Disease Severity
Authors: Gauthier Nick P.G. , Locher Kerstin , MacDonald Clayton , Chorlton Samuel D. , Charles Marthe , Manges Amee R.
Published: June 2022

Objectives

The COVID-19 pandemic and ensuing public health emergency has emphasized the need to study SARS-CoV-2 pathogenesis. The human microbiome has been shown to regulate the host immune system and may influence host susceptibility to viral infection, as well as disease severity. Several studies have assessed whether compositional alterations in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection. However, the results of these studies were varied, and many did not account for disease severity. This study aims to examine whether compositional differences in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection status and disease severity.

Methods

We performed Nanopore full-length 16S rRNA sequencing on 194 nasopharyngeal swab specimens from hospitalized and community-dwelling SARS-CoV-2-infected and uninfected individuals. Sequence data analysis was performed using the BugSeq 16S analysis pipeline.

Results

We found significant beta (PERMANOVA p < 0.05), but not alpha (Kruskal-Wallis p > 0.05) diversity differences in the nasopharyngeal microbiota among our study groups. We identified several differentially abundant taxa associated with SARS-CoV-2 infection status and disease severity using ALDEx2. Finally, we observed a trend towards higher abundance of Enterobacteriaceae in specimens from hospitalized SARS-CoV-2-infected patients.

Conclusions

This study identified several alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity. Understanding the role of the microbiome in infection susceptibility and severity may open new avenues of research for disease prevention and treatment.
The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder: a systematic review and meta-analysis
Authors: Almulla Abbas F. , Thipakorn Yanin , Vasupanrajit Asara , Abo Algon Ali Abbas , Tunvirachaisakul Chavit , Hashim Aljanabi Ashwan Abdulzahra , Oxenkrug Gregory , Al-Hakeim Hussein K. , Maes Michael
Published: June 2022

Background

There is now evidence that affective disorders including major depressive disorder (MDD) and bipolar disorder (BD) are mediated by immune-inflammatory and nitro-oxidative pathways. Activation of these pathways may be associated with activation of the tryptophan catabolite (TRYCAT) pathway leading to depletion of tryptophan (TRP) and increases in tryptophan catabolites (TRYCATs).

Aims

To systematically review and meta-analyze TRP, its competing amino-acids (CAAs) and TRYCAT data in MDD and BD.

Methods

This review searched PubMed, Google Scholar and SciFinder and included 121 full-text articles and 15470 individuals, including 8024 MDD/BD patients and 7446 healthy controls.

Results

TRP levels (either free and total) and the TRP/CAAs ratio were significantly decreased (p<0.0001) in MDD/BD as compared with controls with a moderate effect size (standardized mean difference for TRP: SMD=-0.513, 95% confidence interval, CI: -0.611; -0.414; and TRP/CAAs: SMD=-0.558, CI: -0.758; -0.358). Kynurenine (KYN) levels were significantly decreased in patients as compared with controls with a small effect size (p<0.0001, SMD= -0.213, 95%CI: -0.295; -0.131). These differences were significant in plasma (p<0.0001, SMD=-0.304, 95%CI: -0.415, -0.194) but not in serum (p=0.054) or the central nervous system (CNS, p=0.771). The KYN/TRP ratio, frequently used as an index of indoleamine-dioxygenase (IDO) activity, and neurotoxicity indices based on downstream TRYCATs were unaltered or even lowered in MDD/BD.

Conclusions

Our findings revealed that MDD/BD are accompanied by TRP depletion without IDO and TRYCAT pathway activation. Lowered TRP availability is probably the consequence of lowered serum albumin during the inflammatory response in affective disorders.
Computational Prediction of Synthetic Circuit Function Across Growth Conditions
Authors: Cummins Breschine , Moseley Robert C. , Deckard Anastasia , Weston Mark , Zheng George , Bryce Daniel , Nowak Joshua , Gameiro Marcio , Gedeon Tomas , Mischaikow Konstantin , Beal Jacob , Johnson Tessa , Vaughn Matthew , Gaffney Niall I. , Gopaulakrishnan Shweta , Urrutia Joshua , Goldman Robert P. , Bartley Bryan , Nguyen Tramy T. , Roehner Nicholas , Mitchell Tom , Vrana Justin D. , Clowers Katie J. , Maheshri Narendra , Becker Diveena , Mikhalev Ekaterina , Biggers Vanessa , Higa Trissha R. , Mosqueda Lorraine A. , Haase Steven B.
Published: June 2022

A challenge in the design and construction of synthetic genetic circuits is that they will operate within biological systems that have noisy and changing parameter regimes that are largely unmeasurable. The outcome is that these circuits do not operate within design specifications or have a narrow operational envelope in which they can function. This behavior is often observed as a lack of reproducibility in function from day to day or lab to lab. Moreover, this narrow range of operating conditions does not promote reproducible circuit function in deployments where environmental conditions for the chassis are changing, as environmental changes can affect the parameter space in which the circuit is operating. Here we describe a computational method for assessing the robustness of circuit function across broad parameter regions. Previously designed circuits are assessed by this computational method and then circuit performance is measured across multiple growth conditions in budding yeast. The computational predictions are correlated with experimental findings, suggesting that the approach has predictive value for assessing the robustness of a circuit design.
Large-scale structural rearrangements unleash indiscriminate nuclease activity of CRISPR-Cas12a2
Authors: Bravo Jack P. K. , Hallmark Thom , Naegle Bronson , Beisel Chase L. , Jackson Ryan N. , Taylor David W.
Published: June 2022

Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided degradation of non-specific single-stranded (ss)RNA, ssDNA and double-stranded (ds)DNA upon recognition of a complementary RNA target, culminating in abortive infection (Dmytrenko 2022). Here, we report structures of Cas12a2 in binary, ternary, and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of ‘aromatic clamp’ residues that are crucial for dsDNA degradation and invivoimmune system function. Our work provides a structural basis for this unprecedented mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates.
Glucocorticoid-sensitive period of corticotroph development – implications in early life stress
Authors: Peles Guy , Swaminathan Amrutha , Levkowitz Gil
Published: June 2022

Corticotrophs are intermediaries in the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in vertebrates’ stress response. The HPA axis displays an intricate mode of negative feedback regulation, whereby the peripheral effector, cortisol inhibits the secretion of its upstream regulator, adrenocorticotropic hormone (ACTH) from proopiomelanocortin (POMC)-expressing cells in the pituitary. While the feedback regulation of the HPA axis is well characterized in the adult organism, the effect of feedback regulation on the development of corticotrophs is poorly understood. Here, we study the effect of glucocorticoids on the development of POMC-expressing cells in the zebrafish pituitary. The development of POMC cells displayed striking robustness in terms of their steady increase in numbers between 2-6 days post fertilization. Inhibition of endogenous glucocorticoid synthesis resulted in an increase in POMC cell number due to reduced developmental feedback inhibition of cortisol on POMC cells. Conversely, addition of exogenous dexamethasone at a critical developmental window led to a decrease in POMC cell number, mimicking greater feedback control. Finally, developmental dysregulation of ACTH levels resulted in impaired anxiety-like and stress-coping behaviours. Hence, we identified a sensitive developmental window for the effect of glucocorticoids on corticotrophs and demonstrate the downstream effect on stress-responsive behaviour.
Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix
Authors: Norcross Rebecca G. , Abdelmoti Lina , Rouchka Eric C. , Andreeva Kalina , Tussey Olivia , Landestoy Daileen , Galperin Emilia
Published: June 2022

The extracellular signal-regulated kinase (ERK1/2) pathway is essential in embryonic development. The scaffold protein Shoc2 is a critical modulator of ERK1/2 signals, and mutations in the shoc2 gene lead to the human developmental disease known as Noonan-like syndrome with loose anagen hair (NSLH). The loss of Shoc2 and the shoc2 NSLH-causing mutations affect the tissues of neural crest (NC) origin. In this study, we utilized the zebrafish model to dissect the role of Shoc2-ERK1/2 signals in the development of NC. These studies established that the loss of Shoc2 significantly altered the expression of transcription factors regulating the specification and differentiation of NC cells. Using comparative transcriptome analysis of NC-derived cells from shoc2 CRISPR/Cas9 mutant larvae, we found that Shoc2-mediated signals regulate gene programs at several levels, including expression of genes coding for the proteins of extracellular matrix (ECM) and ECM regulators. Together, our results demonstrate that Shoc2 is an essential regulator of NC development. This study also indicates that disbalance in the turnover of the ECM may lead to the abnormalities found in NSLH patients.
Structure-based Discovery of Conformationally Selective Inhibitors of the Serotonin Transporter
Authors: Singh Isha , Seth Anubha , Billesbølle Christian B. , Braz Joao , Rodriguiz Ramona M. , Roy Kasturi , Bekele Bethlehem , Craik Veronica , Huang Xi-Ping , Boytsov Danila , Lak Parnian , O’Donnell Henry , Sandtner Walter , Roth Bryan L. , Basbaum Allan I. , Wetsel William C. , Manglik Aashish , Shoichet Brian K. , Rudnick Gary
Published: June 2022

The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has an unusual anti-depressant profile and stabilizes the inward-open conformation. Unfortunately, ibogaine is promiscuous and cardiotoxic, limiting understanding of inward-open state ligands. We computationally docked over 200 million small molecules against the ibogaine stabilized inward-open state of SERT. Thirty-six top-ranking compounds were synthesized and thirteen inhibited with potencies ranging from 29 to 5000 nM. Structure-based optimization led to two novel inhibitors with Ki values down to 3 nM. The new molecules stabilized an outward-closed state of the transporter and had little activity against off-targets. A cryo-EM structure of one of these bound to SERT confirmed the predicted geometry. In mouse behavioral assays, both had anxiolytic and anti-depressant activity, with potencies up to 200 better than fluoxetine.
Regulation of nuclear actin levels and MRTF/SRF target gene expression during PC6.3 cell differentiation
Authors: Kyheröinen Salla , Hyrskyluoto Alise , Sokolova Maria , Vartiainen Maria K.
Published: June 2022

Actin has important functions in both cytoplasm and nucleus of the cell, with active nuclear transport mechanisms maintaining the cellular actin balance. Nuclear actin levels are subject to regulation during many cellular processes from cell differentiation to cancer. Here we show that nuclear actin levels increase upon differentiation of PC6.3 cells towards neuron-like cells. Photobleaching experiments demonstrate that this increase is due to decreased nuclear export of actin during cell differentiation. Increased nuclear actin levels lead to decreased nuclear localization of MRTF-A, a well-established transcription cofactor of SRF. In line with MRTF-A localization, transcriptomics analysis reveals that MRTF/SRF target gene expression is first transiently activated, but then substantially downregulated during PC6.3 cell differentiation. This study therefore describes a novel cellular context, where regulation of nuclear actin is utilized to tune MRTF/SRF target gene expression during cell differentiation.
Knowledge recombination, environmental turbulence and firms' innovation quality: the evidence from Chinese pharmaceutical industry
Authors: Luo Zhen , Callaert Julie , Zeng Deming , Looy Bart Van
Published: June 2022

Purpose

Shifting focus from innovation quantity to innovation quality becomes a priority in innovation study, business and policy. This paper aims to figure out whether and how knowledge recombination (recombinant exploration/recombinant exploitation) affects firms' innovation quality (technological value/economic value) and how these relationships are moderated by environmental turbulence (technological turbulence/market turbulence) in the context of open innovation.

Design/methodology/approach

A panel data set is built on 373 Chinese pharmaceutical firms' patents and new product data from 1997 to 2020. And a negative binomial regression model is applied to test the hypotheses.

Findings

The analyses indicate that (1) recombinant exploration favors technological value but hinders economic value, while (2) recombinant exploitation benefits both. Regarding environmental turbulence's moderating effects, (3) technological turbulence has opposite moderating effects on the impacts of recombinant exploration versus exploitation on technological value, whereas (4) market turbulence benefits the impacts of both on economic value.

Practical implications

This research provides the answer to practitioners' question that “How to improve innovation quality?” That is “Think from a recombination logic, clarify your internal value preference and the external turbulence.”

Originality/value

From an emerging perspective of innovation, this research expands the innovation quality research to a recombination logic. A multi-dimensional research framework is developed to clarify the complex relationships between knowledge recombination and innovation quality. Finally, two moderators, technological versus market turbulence, formulate more targeted implications for firms' innovation management in open innovation.
Impact of lean principles on operational performance in high uncertainty
Authors: Thoumy Mira , Jobin Marie-Helene , Baroud Juliette , El Nakhel Khalil Claude
Published: June 2022

Purpose

The purpose of this research is to study the impact of perceived adoption of Lean principles on operational performance in Lebanese pharmaceutical industries.

Design/methodology/approach

A quantitative method was implemented using a questionnaire that targeted 253 respondents working in eight good manufacturing practices (GMP) certified Lebanese pharmaceutical companies. Reliability analysis was performed using SPSS, and the research hypotheses were tested using regression analysis.

Findings

The results demonstrated that Lean principles positively and directly affected operational performance. It also positively affected operational performance factors of quality, cost and time. However, the analysis of each of Lean principles impact on operational performance cost was analyzed perfection, value, and value stream mapping (VSM) significantly increased operational performance. In addition, pull only positively augmented the cost reduction, whereas flow did not show any effects on any of operational performance’s factors.

Practical implications

In addition to enhancing operational performance, the positive effect of the perceived adoption of Lean principles on performance is also explained by managers’ efforts in studying the flow of actions in their processes to reduce wastes. To face uncertainty, training and building a workforce that is able to implement Lean principles, equipping this workforce with needed artifacts, and promoting a high-performance culture are crucial for the successful implementation of Lean principles.

Originality/value

Lean approach has become a major pathway of improvement especially in pharmaceutical companies. Few studies analyzed the impact of each of the Lean principles on the operational performance in companies that operate in era of uncertainty. Furthermore, the perceived adoption of Lean principles is under investigated in the Middle East in general and in Lebanon in particular.
Investigating the effect of service feedback and physician popularity on physician demand in the virtual healthcare environment
Authors: Shah Adnan Muhammad , Muhammad Wazir , Lee KangYoon
Published: June 2022

Purpose

This study examines how service feedback and physician popularity affect physician demand in the context of virtual healthcare environment. Based on the signaling theory, the critical factor of environment uncertainty (i.e. disease risk) and its impact on physician demand is also investigated. Further, the research on the endogeneity of online reviews in healthcare is also examined in the current study.

Design/methodology/approach

A secondary data econometric analysis using 3-wave data sets of 823 physicians obtained from two PRWs (Healthgrades and Vitals) was conducted. The analysis was run using the difference-in-difference method to consider physician and website-specific effects.

Findings

The study's findings indicate that physician popularity has a stronger positive effect on physician demand compared with service feedback. Improving popularity leads to a relative increase in the number of appointments, which in turn enhance physician demand. Further, the impact of physician popularity on physician demand is positively mitigated by the disease risk.

Originality/value

The authors' research contributes to a better understanding of the signaling transmission mechanism in the online healthcare environment. Further, the findings provide practical implications for key stakeholders into how an efficient feedback and popularity mechanism can be built to enhance physician service outcomes in order to maximize the financial efficiency of physicians.
Marginalized engineering students' narrative construction through photo elicitation
Authors: Maitra Debalina , Coley Brooke
Published: June 2022

Purpose

The goal of this study is to explore an immediate step in understanding the lived experiences of under-represented students through metaphor construction and possibly collect more in-depth data through photograph-based interviews.

Design/Methodology/Approach

This article introduced photo-elicitation based narrative interviews as a qualitative methodology while interviewing fourteen undergraduate community college students mostly from underrepresented groups (URGs). At the beginning of each interview, the authors probed the participants with 8 photographs chosen by the research team to represent a diverse set of experiences in engineering. The authors conducted a thematic analysis of the interview data.

Findings

The findings suggested that the inclusion of photo-elicitation often catalyzed consumption of representations, images, metaphors, and voice to stories passed unnoticed; and finally produces more detailed descriptions and complements semi-structured narrative interviews.

Research Limitations/Implications

This study advances the scholarship that extends photograph driven interviews/photo elicitation methodology while interviewing marginalized population and offers a roadmap for what a multi-modal, arts-based analysis process might look like for in-depth interviews.

Practical Implications

The use of photo-elicitation in our research enabled a deeper, more poignant exploration of the URG students' experience of navigating engineering. The participants were able to relate to the photographs and shared their life narratives through them; hence, use of photographs can be adapted in future research.

Social Implications

Our research revealed that PEI has excellent potential to capture marginalized narratives of URGs, which is not well explored in educational research, specially, in higher education. In our research, PEI promoted more culturally inclusive approaches positioning the participants as experts of their own narratives.

Originality/Value

The study presented in this paper serves as an example of qualitative research that expands methodological boundaries and centers the role of power, marginalization, and creativity in research. This work serves as a unique and important contribution to the photo-elicitation literature, offering a critical roadmap for researchers who are drawn to photo elicitation/photograph driven interviews as a method to explore their inquiry.
A full-section asphalt concrete waterproof sealing structure for the high-speed railway subgrade
Authors: Fu Qinghong
Published: June 2022

Purpose

This study aims to investigate the service performances of a new full-section asphalt concrete waterproof sealing structure (FSACWSS) for the high-speed railway subgrade through on-site tracking, monitoring and post-construction investigation.

Design/methodology/approach

Based on the working state of the waterproof sealing structure, the main functional characteristics were analyzed, and a kind of roller-compacted high elastic modulus asphalt concrete (HEMAC) was designed and evaluated by several groups of laboratory tests. It is applied to an engineering test section, and the long-term performance monitoring and subgrade dynamic performance testing system were installed to track and monitor working performances of the test section and the adjacent contrast section with fiber-reinforced concrete.

Findings

Results show that both the dynamic performance of the track structure and the subgrade in the test section meet the requirements of the specification limits. The water content in the subgrade of the test section is maintained at 8–18%, which is less affected by the weather. However, the water content in the subgrade bed of the contrast section is 10–35%, which fluctuates significantly with the weather. The heat absorption effect of asphalt concrete in the test section makes the temperature of the subgrade at the shoulder larger than that in the contrastive section. The monitoring value of the subgrade vertical deformation in the test section is slightly larger than that in the contrastive section, but all of them meet the limit requirements. The asphalt concrete in the test section is in good contact with the base, and there are no diseases such as looseness or spalling. Only a number of cracks are found at the joints of the base plates. However, there are more longitudinal and lateral cracks in the contrastive section, which seriously affects the waterproof and sealing effects. Besides, the asphalt concrete is easier to repair, featuring good maintainability.

Originality/value

This research can provide a basis for popularization and application of the asphalt concrete waterproof sealing structure in high-speed railways.
How can green innovation from manufacturers benefit from supplier networks?
Authors: Cheng Colin C.J. , Hsu Shu-Han , Sheu Chwen
Published: June 2022

Purpose

Prior research on supply chain management has advanced substantially our understanding of how suppliers’ knowledge affects manufacturers’ green innovation. However, overlooking the suppliers’ diverse green knowledge in supplier networks, namely, green knowledge diversity, has limited our understanding of both supply chain management and green innovation development. To address this important issue, this study aims to rely on social network theory as the overarching framework and knowledge-based view as the underlying theoretical foundation to examine how green knowledge diversity contributes to manufacturers’ green innovation performance, while considering three types of supplier network properties (network strength, network heterogeneity and network density).

Design/methodology/approach

This study collects both survey and secondary proxy data from 209 manufacturing firms over three time periods (mid-2018, mid-2019 and mid-2020). PROCESS macro is applied to test the research hypotheses.

Findings

The results provide compelling evidence that green knowledge management processes partially mediate the effect of green knowledge diversity on manufacturers’ green innovation performance. The effect of green knowledge diversity is strengthened by supplier network strength and supplier network heterogeneity, but hindered by supplier network density.

Practical implications

This study provides a practical guide to help manufacturers enhance green innovation performance by properly managing and leveraging their suppliers’ diverse green knowledge domains in supplier networks.

Originality/value

This study contributes to the supply chain management and green innovation literature by offering novel theoretical and empirical insights into how manufacturers can use their supplier networks to strengthen green innovation.
Smart working in the travel agencies and employees’ quality of life
Authors: Girish V.G. , Lee Jin-Young , Lee Choong-Ki , Olya Hossein
Published: June 2022

Purpose

This paper aims to understand the impact of smart working on employees’ quality of life. The service-dominant logic indicates that key actors, including employees, are resource integrators. This empirical study contributes to the current knowledge of transformative service by expounding on smart working practices and their relationship with self-efficacy and, ultimately, quality of life of employees.

Design/methodology/approach

This study contends that smart working enhances employees’ self-efficacy. The current research uses conservation of resources (COR) theory as a basis in hypothesizing that self-efficacy serves as a key resource, which can stimulate workplace creativity, job satisfaction and quality of life. An onsite survey is conducted among employees who have been involved in smart working in the travel agency context.

Findings

Smart working has a positive effect on self-efficacy, which positively influences workplace creativity, job satisfaction and quality of life. Workplace creativity enhances job satisfaction but does not influence quality of life. Job satisfaction boosts quality of life, which is important to tourism services and their employees amid various crises.

Research limitations/implications

Consistent with COR theory, the immediate recommendation to managers is to invest in smart working, which can lead to employees’ creativity, job satisfaction and quality of life.

Originality/value

To the best of the authors’ knowledge, this empirical study is the first to assess the viability of smart working in the travel agency context. Smart working offers positive outcomes, such as convenience for employees to work independently, improving workplace creativity, job satisfaction and quality of life. Travel agencies are mainly categorized as small and medium enterprises (SMEs). In the future, SMEs may also introduce smart working that can eventually become their competitive advantage to retain talented employees.
After‐hours radiology reporting in an Australian tertiary hospital: Factors influencing the rate of discrepancy for computed tomography reporting
Authors: Howie Allister R. , Gajera Jay , Ong David , Roberts Marian
Published: June 2022

Introduction

Demand for after‐hours radiology services across Australia has been rapidly increasing for many years. Public hospital radiology departments are generally staffed by trainees after hours, often 1–2 doctors. This study reviewed 1 year of after‐hours data at a tertiary hospital in Sydney, to determine overall discrepancy rates and factors which influenced the rate of discrepancy after hours. Overall radiology and after‐hours case volumes are increasing, and the goal was to ensure that our department practices are within safe limits at current staffing levels.

Methods

After‐hours computed tomography scan reports issued by registrars were reviewed over 1 year between 01 January 2019 and 01 January 2020. Data recorded included overall case numbers on each shift, discrepancy rates and rates of clinically significant discrepancy. Caseload was measured by equivalent ascribed reporting time as described by Pitman et al. (2018).

Results

There were 10,886 cases reported after hours during the study period and 1,412 discrepancies (13% cases). Of these, 300 (3.7%) were clinically significant. Factors that increased the rate of significant discrepancy included shifts with caseloads greater than 3 h of equivalent consultant reporting time per 8‐h shift and the radiology trainee's level of training. The frequency of discrepancy for trauma cases was similar to non‐trauma after adjusting for study type; however, the frequency of significant discrepancy was higher.

Conclusion

In all instances, the rates of discrepancy and clinically significant discrepancy remained well within ranges previously described.
The complete and closed genome of the facultative generalist Candidatus Endoriftia persephone from deep‐sea hydrothermal vents
Authors: De Oliveira André Luiz , Srivastava Abhishek , Espada‐Hinojosa Salvador , Bright Monika
Published: June 2022

The mutualistic interactions between Riftia pachyptila and its endosymbiont Candidatus Endoriftia persephone (short Endoriftia) have been extensively researched. However, the closed Endoriftia genome is still lacking. Here, by employing single‐molecule real‐time sequencing we present the closed chromosomal sequence of Endoriftia. In contrast to theoretical predictions of enlarged and mobile genetic element‐rich genomes related to facultative endosymbionts, the closed Endoriftia genome is streamlined with fewer than expected coding sequence regions, insertion‐, prophage‐sequences and transposase‐coding sequences. Automated and manually curated functional analyses indicated that Endoriftia is more versatile regarding sulphur metabolism than previously reported. We identified the presence of two identical rRNA operons and two long CRISPR regions in the closed genome. Additionally, pangenome analyses revealed the presence of three types of secretion systems (II, IV and VI) in the different Endoriftia populations indicating lineage‐specific adaptations. The in depth mobilome characterization identified the presence of shared genomic islands in the different Endoriftia drafts and in the closed genome, suggesting that the acquisition of foreign DNA predates the geographical dispersal of the different endosymbiont populations. Finally, we found no evidence of epigenetic regulation in Endoriftia, as revealed by gene screenings and absence of methylated modified base motifs in the genome. As a matter of fact, the restriction‐modification system seems to be dysfunctional in Endoriftia, pointing to a higher importance of molecular memory‐based immunity against phages via spacer incorporation into CRISPR system. The Endoriftia genome is the first closed tubeworm endosymbiont to date and will be valuable for future gene oriented and evolutionary comparative studies.
High‐dimensional immune profiles correlate with phenotypes of peanut allergy during food‐allergic reactions
Authors: Klueber Julia , Czolk Rebecca , Codreanu‐Morel Françoise , Montamat Guillem , Revets Dominique , Konstantinou Maria , Cosma Antonio , Hunewald Oliver , Skov Per Stahl , Ammerlaan Wim , Hilger Christiane , Bindslev‐Jensen Carsten , Ollert Markus , Kuehn Annette
Published: June 2022

Background

Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo.

Aims

To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA).

Methods

Children with a positive (OFC+, n = 16) or a negative (OFC−, n = 10) OFC‐outcome were included (controls, n = 7). Single‐cell mass cytometry/unsupervised analysis allowed unbiased immunophenotyping during OFC.

Results

Peripheral immune profiles correlated with OFC outcome. OFC+‐profiles revealed mainly decreased Th2 cells, memory Treg and activated NK cells, which had an increased homing marker expression signifying immune cell migration into effector tissues along with symptom onset. OFC−‐profiles had also signs of ongoing inflammation, but with a signature of a controlled response, lacking homing marker expression and featuring a concomitant increase of Th2‐shifted CD4+ T cells and Treg cells. Low versus high threshold reactivity‐groups had differential frequencies of intermediate monocytes and myeloid dendritic cells at baseline. Low threshold was associated with increased CD8+ T cells and reduced memory cells (central memory [CM] CD4+ [Th2] T cells, CM CD8+ T cells, Treg). Immune signatures also discriminated patients with preferential skin versus gastrointestinal symptoms, whereby skin signs correlated with increased expression of CCR4, a molecule enabling skin trafficking, on various immune cell types.

Conclusion

We showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA.