bluuebunny/crossref_metadata_2025 huggingface dataset:
High-accuracy mapping of human and viral direct physical protein-protein interactions using the novel computational system AlphaFold-pairs
Authors: Poitras Christian , Lamontagne Felix , Grandvaux Nathalie , Song Hao , Pinard Maxime , Coulombe Benoit
Published: August 2023

Protein-protein interactions are central, highly flexible components of regulatory mechanisms in all living cells. Over the years, diverse methods have been developed to map protein-protein interactions. These methods have revealed the organization of protein complexes and networks in numerous cells and conditions. However, these methods are also time consuming, costly and sensitive to various experimental artifacts. To avoid these caveats, we have taken advantage of the AlphaFold-Multimer software, which succeeded in predicting the structure of many protein complexes. We designed a relatively simple algorithm based on assessing the physical proximity of a test protein with other AlphaFold structures. Using this method, named AlphaFold-pairs, we have successfully defined the probability of a protein-protein interaction forming. AlphaFold-pairs was validated using well-defined protein-protein interactions found in the literature and specialized databases. All pairwise interactions forming within the 12-subunit transcription machinery RNA Polymerase II, according to available structures, have been identified. Out of 66 possible interactions (excluding homodimers), 19 specific interactions have been found, and an additional previously unknown interaction has been unveiled. The SARS-CoV-2 surface glycoprotein Spike (or S) was confirmed to interact with high preference with the human ACE2 receptor when compared to other human receptors. Notably, two additional receptors, INSR and FLT4, were found to interact with S. For the first time, we have successfully identified protein-protein interactions that are likely to form within the reassortant Eurasian avian-like (EA) H1N1 swine G4 genotype Influenza A virus, which poses a potential zoonotic threat. Testing G4 proteins against human transcription factors and molecular chaperones (a total of 100 proteins) revealed strong specific interactions between the G4 HA and HSP90B1, the G4 NS and the PAQosome subunit RPAP3, as well as the G4 PA and the POLR2A subunit. We predict that AlphaFold-pairs will revolutionize the study of protein-protein interactions in a large number of healthy and diseased systems in the years to come.
Microevolutionary Hypothesis of the Obesity Epidemic
Authors: Fraiman Joseph , Baver Scott , Henneberg Maciej
Published: August 2023

The obesity epidemic represents potentially the largest phenotypic change inHomo sapienssince the origin of the species. Despite obesity’s high heritability, a change in the gene pool has not generally been presumed as a potential cause of the obesity epidemic. Here we advance the hypothesis that a rapid change in the obesogenic gene pool has occurred second to the introduction of modern obstetrics dramatically altering evolutionary pressures on obesity - the microevolutionary hypothesis of the obesity epidemic. Obesity is known to increase childbirth related mortality several fold. Prior to modern obstetrics, childbirth related mortality occurred in over 10% of women. After modern obstetrics, this mortality reduced to a fraction of a percent, thereby lifting a strong negative selection pressure. Regression analysis of data for ∼ 190 countries was carried out to examine associations between 1990 maternal death rates (MDR) and current obesity rates. Multivariate regression showed MDR correlated more strongly with national obesity rates than GDP, calorie intake and physical inactivity. Analyses controlling for confounders via partial correlation show that MDR explains approximately 11% of the variability of obesity rate between nations. For nations with MDR above the median (>0.45%), MDR explains over 20% of obesity variance, while calorie intake, and physical inactivity show no association with obesity in these nations. The microevolutionary hypothesis offers a parsimonious explanation of the global nature of the obesity epidemic.

Significance Statement

Humans underwent a rapid increase in obesity in the 20thcentury, and existing explanations for this trend are unsatisfactory. Here we present evidence that increases in obesity may be in large part attributable to microevolutionary changes brought about by dramatic reduction of childbirth mortality with the introduction of modern obstetrics. Given the higher relative risk of childbirth in women with obesity, obstetrics removed a strong negative selection pressure against obesity. This alteration would result in a rapid population-wide rise in obesity-promoting alleles. A cross-country analysis of earlier maternal death rates and obesity rate today found strong evidence supporting this hypothesis. These findings suggest recent medical intervention influenced the course of human evolution more profoundly than previously realized.
ReDis: efficient metagenomic profiling via assigning ambiguous reads
Authors: Song Chun , Guo Zule , Gu Ju , Ren Yong , Guo Hao , Liu Junfeng
Published: August 2023

Metagenomic profiling is one of the primary means of microbiome analysis, which includes classification of sequencing reads and quantification of their relative abundances. Although mang methods have been developed for metagenomic profiling, metagenomic profiling remains challenges on striking a delicate balance between accuracy and runtime as well as assigning the ambiguous reads. Here, we present a novel method, named ReDis, to overcome the above issues. ReDis combines Kraken2 with Minimap2 for aligning sequencing reads against a reference database with hundreds of gigabytes (GB) in size accurately within feasible time, and then uses a novel statistical model to assign the ambiguous reads for producing accurate abundance estimates. In contrast to the popular Kraken2+Bracken, ReDis improved the accuracy of abundance estimation on simulated reads from two highly similar genomes:Escherichia coliandShigella flexneri.

Contact

h.guo@foxmail.comorjlsljf0101@126.com
WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury
Authors: Liu Yu , Zhao Zongren , Zheng Jinyu
Published: August 2023

Background

Traumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. However, there are no sensitive diagnostic or prognostic biomarkers to identify TBI, which leads to long-term consequences. In this study, we aim to identify genes that contribute to brain injury and to identify potential mechanisms for its progression in the early stages.

Method

From the Gene Expression Omnibus (GEO) database, we downloaded GSE2871’s gene expression profiles. Weighted gene coexpression network analyses (WGCNA) were conducted on differentially expressed genes (DEGs), and the DEGs were analyzed by Gene Set Enrichment Analysis(GSEA). An enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed for understanding the biological functions of genes. The potential biomarkers were identified using 3 kinds of machine learning algorithms. Nomogram was constructed using the “rms” package. And the receiver operating characteristic curve (ROC) was plotted to detect and validate our prediction model sensitivity and specifificity.

Results

Between samples with and without brain injury, 107 DEGs were identified, including 47 upregulated genes and 60 downregulated genes. On the basis of WGCNA and DEGs, 97 target genes were identified. In addition, biological function analysis indicated that target genes were primarily involved in the interaction of neuroactive ligands with receptors, taste transduction, cortisol synthesis and secretion, potassium ion transport. Based on machine learning algorithms, LOC103691092, Npw could be potentially useful biomarkers for TBI and showed good diagnostic values. Finally, a nomogram was constructed of the expression levels of these seven target genes to predict level of TBI, and the ROC showed that these genes can be used as hub genes after TBI.

Conclusion

LOC103691092, NPW, STK39, KCND3, APOC3, FOXE3, and CHRNB1 were identified as hub genes of TBI. These findings can provide a new direction for the diagnosis and treatment of TBI.
Integration of Mass Cytometry and Mass Spectrometry Imaging for Spatially Resolved Single Cell Metabolic Profiling
Authors: Nunes Joana B , Ijsselsteijn Marieke E , Abdelaal Tamim , Ursem Rick , van der Ploeg Manon , Everts Bart , Mahfouz Ahmed , Heijs Bram , de Miranda Noel FCC
Published: August 2023

Integration of spatial omics technologies can provide important insights into the biology of tissues. We combined mass spectrometry imaging-based metabolomics and imaging mass cytometry-based immunophenotyping on the same single tissue section to reveal metabolic heterogeneity within tissues and its association with specific cell populations like cancer cells or immune cells. This approach has the potential to greatly increase our understanding of tissue-level interplay between metabolic processes and their cellular components.
Altered reactivity to threatening stimuli inDrosophilamodels of Parkinson’s disease, revealed by a trial-based assay
Authors: Kajtor Márton , Billes Viktor A. , Király Bálint , Karkusova Patricia , Kovács Tibor , Stabb Hannah , Sviatkó Katalin , Vizi Andor , Ujvári Eszter , Balázsfi Diána , Seidenbecher Sophie E. , Kvitsiani Duda , Vellai Tibor , Hangya Balázs
Published: August 2023

The fruit flyDrosophila melanogasteremerges as an affordable, genetically tractable model of behavior and brain diseases. However, despite the surprising level of evolutionary conservation from flies to humans, significant genetic, circuit-level and behavioral differences hinder the interpretability of fruit fly models for human disease. Therefore, to allow a more direct fly-versus-human comparison, we surveyed the rarely exploited, rich behavioral repertoire of fruit flies with genetic alterations relevant to Parkinson’s disease (PD), including overexpression of human mutant Parkin or α-synuclein proteins and mutations in dopamine receptors. Flies with different genetic backgrounds displayed variable behaviors, including freezing, slowing and running, in response to predator-mimicking passing shadows used as threatening stimuli in a single-animal trial-based assay. We found that the expression of human mutant Parkin in flies resulted in reduced walking speed and decreased reactivity to passing shadows. Flies with dopamine receptor mutations showed similar alterations, consistent with the motor and cognitive deficits typical in humans with PD. We also found age-dependent trends in behavioral choice during the fly lifespan, while dopamine receptor mutant flies maintained their decreased general reactivity throughout all age groups. Our data demonstrate that single-trial behavioral analysis can reveal subtle behavioral changes in mutant flies that can be used to further our understanding of disease pathomechanisms and help gauge the validity of geneticDrosophilamodels of neurodegeneration, taking us one step closer to bridging the gap in fly-to-human translation.
Extinction risk predictions for the world’s flowering plants to support their conservation
Authors: Bachman Steven P. , Brown Matilda J.M. , Leão Tarciso C.C. , Lughadha Eimear Nic , Walker Barnaby E.
Published: August 2023

More than 70% of all vascular plants lack conservation status assessments. We aimed to address this shortfall in knowledge of species extinction risk by using the World Checklist of Vascular Plants to generate the first comprehensive set of predictions for a large clade: angiosperms (flowering plants, ∼330,000 species).

We used Bayesian Additive Regression Trees (BART) to predict the extinction risk of all angiosperms using predictors relating to range size, human footprint, climate, and evolutionary history and applied a novel approach to estimate uncertainty of individual species level predictions.

From our model predictions we estimate 45.1% of angiosperm species are potentially threatened with a lower bound of 44.5% and upper bound of 45.7%.

Our species-level predictions, with associated uncertainty estimates, do not replace full Red List assessments, but can be used to prioritise predicted threatened species for full Red List assessment and fast-track predicted non-threatened species for Least Concern assessments. Our predictions and uncertainty estimates can also guide fieldwork, inform systematic conservation planning and support global plant conservation efforts and targets.
Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR
Authors: Deng Jiahua , Yuan Yuchen , Cui Qiang
Published: August 2023

Modulating allosteric coupling offers unique opportunities for biomedical applications. Such efforts can benefit from efficient prediction and evaluation of allostery hotspot residues that dictate the degree of co-operativity between distant sites. We demonstrate that effects of allostery hotspot mutations can be evaluated qualitatively and semi-quantitatively by molecular dynamics simulations in a bacterial tetracycline repressor (TetR). The simulations recapitulate the effects of these mutations on abolishing the induction function of TetR and provide a rationale for the different degrees of rescuability observed to restore allosteric coupling of the hotspot mutations. We demonstrate that the same non-inducible phenotype could be the result of perturbations in distinct structural and energetic properties of TetR. Our work underscore the value of explicitly computing the functional free energy landscapes to effectively evaluate and rank hotspot mutations despite the prevalence of compensatory interactions, and therefore provide quantitative guidance to allostery modulation for therapeutic and engineering applications.

Abstract Figure

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Earliest observation of the tetracycline destructasetet(X3)
Authors: Grenier Frédéric , Lévesque Simon , Rodrigue Sébastien , Haraoui Louis-Patrick
Published: August 2023

Tigecycline is an antibiotic of last resort for infections with carbapenem-resistantAcinetobacter baumannii. Plasmids harboring variants of the tetracycline destructasetet(X)promote rising tigecycline resistance rates. We report the earliest observation oftet(X3)in a clinical strain predating tigecycline’s commercialization, suggesting selective pressures other than tigecycline contributed to its emergence.
Acute hyperoxia improves spinal cord oxygenation and circulatory function following cervical spinal cord injury in the rat
Authors: Lin Yen-Ting , Lee Kun-Ze
Published: August 2023

Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague–Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1–2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats via the optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) breathing. The results showed that contused animals had a significantly lower spinal cord oxygenation level than uninjured animals during normoxia. Cervical spinal cord contusion also significantly reduced peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure. Notably, the spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia could elevate blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function during acute cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.
Novel YAP1/TAZ pathway inhibitors identified through phenotypic screening with potent anti-tumor activity via blockade of GGTase-I / Rho-GTPase signaling
Authors: Graham Keith , Lienau Philip , Bader Benjamin , Prechtl Stefan , Naujoks Jan , Lesche Ralf , Weiske Joerg , Kuehnlenz Julia , Brzezinka Krzysztof , Potze Lisette , Zanconato Francesca , Nicke Barbara , Montebaur Anna , Bone Wilhelm , Golfier Sven , Kaulfuss Stefan , Kopitz Charlotte , Pilari Sabine , Steuber Holger , Hayat Sikander , Kamburov Atanas , Steffen Andreas , Schlicker Andreas , Buchgraber Philipp , Braeuer Nico , Font Nuria Aiguabella , Heinrich Tobias , Kuhnke Lara , Nowak-Reppel Katrin , Stresemann Carlo , Steigemann Patrick , Walter Annette O. , Blotta Simona , Ocker Matthias , Lakner Ashley , Mumberg Dominik , Eis Knut , Piccolo Stefano , Lange Martin
Published: August 2023

This study describes the identification and target deconvolution of novel small molecule inhibitors of oncogenic YAP1/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay. Target deconvolution studies identified the geranylgeranyltransferase-I (GGTase-I) complex, as the direct target of YAP1/TAZ pathway inhibitors. The novel small molecule inhibitors block the activation of Rho-GTPases, leading to subsequent inactivation of YAP1/TAZ and inhibition of cancer cell proliferation in vitro. Multi-parameter optimization resulted in BAY-593, an in vivo probe with favorable PK properties, which demonstrated anti-tumor activity and blockade of YAP1/TAZ signalingin vivo.

SIGNIFICANCE

YAP1/TAZ have been shown to be aberrantly activated oncogenes in several human solid tumors, resulting in enhanced cell proliferation, metastasis and provision of a pro-tumorigenic microenvironment, making YAP1/TAZ targets for novel cancer therapies. Yet, the development of effective inhibitors of these potent oncogenes has been challenging. In this work, we break new ground in this direction through the identification of novel inhibitors of YAP1/TAZ activity.

Graphical abstract

HIGHLIGHTS

Novel YAP1/TAZ pathway inhibitors identified by phenotypic high-throughput screen

Target deconvolution identifies GGTase-I as the direct target of the novel YAP1/TAZ pathway inhibitors

GGTase-I inhibitors block Rho-GTPase signaling and downstream YAP1/TAZ

GGTase-I inhibitor BAY-593 demonstrates potent anti-tumor activityin vivo
Stumpy forms are the predominant transmissible forms ofTrypanosoma brucei
Authors: Ngoune Jean Marc Tsagmo , Sharma Parul , Crouzols Aline , Petiot Nathalie , Rotureau Brice
Published: August 2023

Schusteret al. demonstrated that bloodstream slender forms of African trypanosomes are readily transmissible to young tsetse flies where they can complete their complex life cycle (1). In their experimental conditions, a single slender parasite was sufficient for productive infection. Here, we compared the infectivity of slender and stumpy bloodstream forms in adult flies with a mature immune system, and without using any chemical compounds that would alter the insect immune response and/or promote the infection. After ingestion of slender forms, infected flies were observed only in one out of 24 batches of non-immunocompetent teneral flies and with a high number of parasites. In contrast, infected flies were detected in 75% (18/24) of the batches infected with stumpy parasites, and as few as 10 stumpy parasites produced mature infections in immune adult flies. We discuss that, although Schusteret al. have demonstrated the intrinsic capacity of slender form trypanosomes to infect young and naive tsetse flies, highlighting the remarkable plasticity and adaptability of these protists, this phenomenon is unlikely to significantly contribute to the epidemiology of African trypanosomiases. According to both experimental and field observations, stumpy forms appear to be the most adapted forms for African trypanosome transmission from the mammalian host to the tsetse fly vector in natural conditions.
A novel glideosome-associated protein S14 coordinates sporozoite gliding motility and infectivity in mosquito and mammalian hosts
Authors: Ghosh Ankit , Varshney Aastha , Narwal Sunil Kumar , Nirdosh  , Gaurav Sachin , Gupta Roshni , Ahmed Shakil , Mishra Satish
Published: August 2023

Plasmodiumsporozoites are the infective forms of the malaria parasite in the vertebrate host. Gliding motility allows sporozoites to migrate and invade the salivary gland and hepatocytes. Invasion is powered by an actin-myosin motor complex linked to glideosome. However, the gliding complex and the role of several glideosome-associated proteins (GAPs) are poorly understood. In silico analysis of a novel protein, S14, which is uniquely upregulated in salivary gland sporozoites, suggested its association with glideosome-associated proteins. We confirmedS14expression in sporozoites using real-time PCR. Further, theS14gene was endogenously tagged with 3XHA-mCherry to study expression and localization. We found its expression and localization on the inner membrane of sporozoites. By targeted gene deletion, we demonstrate that S14 is essential for sporozoite gliding motility, salivary gland, and hepatocyte invasion. The gliding and invasion-deficientS14KO sporozoites showed normal expression and organization of IMC and surface proteins. Using in silico and the yeast two-hybrid system, we showed the interaction of S14 with the glideosome-associated proteins GAP45 and MTIP. Together, our data show that S14 is a glideosome-associated protein and plays an essential role in sporozoite gliding motility, which is critical for the invasion of the salivary gland, hepatocyte, and malaria transmission.
A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease
Authors: Lim Kyungtae , Rutherford Eimear N. , Sun Dawei , Van den Boomen Dick J. H. , Edgar James R. , Bang Jae Hak , Matesic Lydia E. , Lee Joo-Hyeon , Lehner Paul J. , Marciniak Stefan J. , Rawlins Emma L. , Dickens Jennifer A.
Published: August 2023

Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant1–3. AT2 dysfunction underlies many lung diseases including interstitial lung disease (ILD), in which some inherited forms result from mislocalisation of surfactant protein C (SFTPC) variants4,5. Disease modelling and dissection of mechanisms remains challenging due to complexities in deriving and maintaining AT2 cellsex vivo.Here, we describe the development of expandable adult AT2-like organoids derived from human fetal lung which are phenotypically stable, can differentiate into AT1-like cells and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH, demonstrating that their depletion phenocopies the pathological SFTPC redistribution seen for the SFTPC-I73T variant. In summary, we demonstrate the development of a novel alveolar organoid model and use it to identify effectors of SFTPC maturation necessary for AT2 health.
Novel pathogenicPDX1gene variant in a Korean family with maturity-onset diabetes of the young
Authors: Kim Hyunji , Kim Hwa Young , Kim Jae Hyun , Seo Soo Hyun , Park Kyung Un
Published: August 2023

The diagnosis of maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus caused by a mutation in a single gene, is often uncertain until genetic testing is performed. We report a 13-yr-old Korean boy who was initially diagnosed with type 2 diabetes (T2DM). MODY was suspected because of his nonobese body habitus and family history of multiple affected members. Targeted panel sequencing of all MODY-related genes was performed using the NextSeq 550Dx platform (Illumina). Sanger sequencing was performed using blood samples from the parents, siblings, and other relatives. A frameshift variant in the 3′ region of the last exon ofPDX1was detected in the patient and his family members with diabetes. PP1_Moderate criterion was applied and this variant was confirmed to be the genetic cause of diabetes in the family and classified as likely pathogenic. The study highlights the importance of genetic testing for nonobese, early-onset diabetic patients with multiple affected family members. Increased awareness and aggressive genetic testing for MODY are needed.
Are shadow banks a threat to the financial stability of EMEs?
Authors: Arora Dhulika , Kashiramka Smita
Published: August 2023

Purpose

Shadow banks or non-bank financial intermediaries (NBFIs) are facilitators of credit, especially in emerging market economies (EMEs). However, there are certain risks associated with them, such as their unchecked leverage and interconnectedness with the rest of the financial system. In light of this, the present study analyses the impact of the growth of shadow banks on the stability of the banking sector and the overall stability of the financial system. The authors further examine the effect of the growth of finance companies (a type of NBFIs) on financial stability.

Design/methodology/approach

The study employs data of 11 EMEs (monitored by the Financial Stability Board (FSB)) for the period 2002–2020 to examine the above relationships. Panel-corrected standard errors method and Driscoll–Kray standard error estimation are deployed to conduct the analysis.

Findings

The results signify that the growth of the shadow banking sector and the growth of lending to the shadow banking sector are negatively associated with the stability of the banking sector and increases the vulnerability of the financial system (overall instability). This implies that the higher the growth of the shadow banks, the higher the financial fragility. Finance companies are also found to negatively affect financial stability. These findings are validated by different estimation methods and point out the risks posed by the NBFI sector.

Originality/value

The extant study builds a composite index (Financial Vulnerability Index (FVI)) to measure financial stability; thus, the findings contribute to the evolving literature on shadow banks.
Examine the impact of green methods and technologies on the environmental sustainability of supportive education buildings, perspectives of circular economy and net-zero carbon operation
Authors: Moghayedi Alireza , Michell Kathy , Hübner Dylan , Le Jeune Karen , Massyn Mark
Published: August 2023

Purpose

This study investigates the barriers and drivers of using green methods and technologies (GMTs) in supportive educational buildings (SEBs) in South Africa, and assesses their impact on the circular economy (CE) in achieving net-zero carbon goals. While there has been extensive literature on green building technologies, there is limited research on the barriers and drivers of using GMT in SEBs, as well as their impact on the circular economy (CE) in achieving net-zero carbon goals.

Design/methodology/approach

This study adopts an interpretivist approach with an ontological basis, using an overarching case study of a SEB at the University of Cape Town (UCT). Semistructured interviews were conducted with executive UCT management, and a field survey of a UCT supportive education building was performed.

Findings

At UCT, multiple GMTs have been installed across various buildings to enhance monitoring and management of water and energy consumption. Moreover, initiatives to positively influence student behavior, such as water and energy-saving campaigns around UCT premises, have been introduced. The findings further indicate that UCT has recently emphasized the implementation of GMTs, resulting in improved resource efficiency, CE practices and progress toward achieving net-zero carbon targets for supportive education buildings and the university as a whole.

Originality/value

This research highlights the positive impact of GMTs on a SEB’s CE and net-zero carbon operations. As a result, facility managers should consider incorporating GMTs when planning the development or refurbishment of SEBs.
Leveraging autonomous mobile robots for Industry 4.0 warehouses: a multiple case study analysis
Authors: Grover Abhay Kumar , Ashraf Muhammad Hasan
Published: August 2023

Purpose

Despite its potential, warehouse managers still struggle to successfully assimilate autonomous mobile robots (AMRs) in their operations. This paper means to identify the moderating factors of AMR assimilation for production warehouses that influence the digital transformation of their intralogistics via AMRs.

Design/methodology/approach

Drawing on innovation of assimilation theory (IAT), this study followed an explorative approach using the principles of the case study method in business research. The cases comprised of four AMR end users and six AMR service providers. Data were collected through semi-structured interviews.

Findings

Four clusters of moderators that affect each stage of AMR assimilation were identified. These clusters include organizational attributes of end users (i.e. production warehouses), service attributes of service providers, technology attributes of AMRs and relational attributes between the AMR service providers and the AMR end users.

Originality/value

The authors extend the IAT framework by identifying various moderating factors between different stages of the AMR assimilation process. To the authors' knowledge, this is the first study to introduce the perspective of AMR end users in conjunction with AMR service providers to the “Industry 4.0” technology assimilation literature. The study propositions regarding these factors guide future intralogistics and AMR research.
Lean monitoring: action research in manufacturing
Authors: Kassem Bassel , Rossini Matteo , Costa Federica , Portioli-Staudacher Alberto
Published: August 2023

Purpose

This study aims to study the implementation of lean thinking at the strategic level of an Italian manufacturing company. Companies implementing continuous improvement (CI) projects in their production processes often take the monitoring phase for granted. This research deploys an A3 lean thinking project in the monitoring phase of strategic KPIs upon completion of several ongoing improvement projects.

Design/methodology/approach

The research methodology is action research aiming at disseminating the problems that the company is facing. The study relies on the lean action plan developed by Womack and Jones (2003): Planning for lean and Lean action. Lean planning consists of the following steps: find a change agent; get the knowledge; find a lever. Lean action uses the A3 lean approach.

Findings

The company reached high-performance improvements due to the proposed lean action plan.

Research limitations/implications

This study contributes by presenting a lean action plan in the monitoring phase, highlighting the importance of the lean thinking-monitoring continuum in reducing time waste for faster diagnosis and using action research to analyze and instill reflective learning.

Originality/value

The research relies on the A3 methodology to showcase the benefits that a mature paradigm, often coined to production, still has unexplored potentials.
TNF‐like weak inducer of apoptosis inhibition is comparable to IL‐13 blockade in ameliorating atopic dermatitis inflammation
Authors: Gupta Rinkesh K. , Miller Jacqueline , Croft Michael
Published: August 2023

Background

Targeting IL‐13 is highly efficacious in patients with Th2‐biased atopic dermatitis (AD), but inhibition of other inflammatory molecules might also limit disease. We investigated the importance of the TNF family cytokine TNF‐like weak inducer of apoptosis (TWEAK; TNFSF12) to keratinocyte dysregulation and the pathogenesis of AD in mice and also tested if blocking TWEAK has a similar therapeutic effect as targeting IL‐13.

Methods

Conditional knockout mice lacking Fn14 (TNFRSF12A), the receptor for TWEAK, only in keratinocytes, were repetitively sensitized with house dust mite allergen and analyzed for AD‐like skin inflammation. To determine the translational potential, wild‐type mice with AD were therapeutically treated with anti‐TWEAK and/or anti‐IL‐13 antibodies, and skin inflammation was assessed.

Results

Mice deficient in Fn14 in keratinocytes were resistant to developing maximal clinical features of AD, exhibiting reduced epidermal hyperplasia and dermal thickening, less skin infiltration of immune cells, and downregulated inflammatory gene expression. Moreover, therapeutic neutralization of TWEAK in wild‐type mice with AD reduced all of the pathological features to a comparable extent as blocking IL‐13.

Conclusions

The activity of TWEAK in keratinocytes contributes to AD development, and neutralizing TWEAK represents a future potential therapeutic option in human AD similar to targeting IL‐13.
Optimizing efficiency and resilience of no‐take marine protected areas for fish conservation under climate change along the coastlines of China Seas
Authors: Lin Li , Liu Yang , Yan Yang , Kang Bin
Published: August 2023

Climate change is one of the major threats to coastal fish biodiversity, and optimization of no‐take marine protected areas (MPAs) is imminent. We predicted fish redistribution under climate change in coastal China Seas with joint species distribution modeling and prioritized areas for conservation with Zonation, for which we used core area zonation (CAZ) and additive benefit function (ABF). Based on our results, we devised an expansion plan of no‐take MPAs. Under climate change, fish were redistributed northward along the coast. These redistributions were segmented by the Yangtze River estuary and its adjacent waters, indicating a possible biogeographical barrier. Under CAZ and ABF, significantly more fish habitat was conserved than under random prioritization (p < 0.001, Cohen's d = –0.36 and –0.62, respectively). The ABF better represented areas with higher species richness, whereas CAZ better represented core habitats for species with narrow distributions. Without accounting for species redistribution, the expanded MPAs were mainly distributed in the northwest of the South China Sea, the East China Sea, the north of the Yellow Sea, and the west of the Bohai Sea. When accounting for species redistribution, the proposed MPAs were mainly distributed in the north of the Bohai Sea and southwest of the Yellow Sea, corresponding to the northern species redistributions. These MPAs conserved less habitat for fishes at present but protected more and better quality habitat for fishes in 2050 and 2100 than those MPAs that did not account for species redistribution, indicating improved fish conservation under climate change. Incorporating species redistribution and trade‐offs between areas with high species richness and areas that contain habitats for rare species are suggested to address coastal fish conservation under climate change. This work provides valuable information for fish conservation and is a precursor to systematic conservation planning along the coastlines of China Seas.
Islet graft function by mixed meal tolerance testing is sustained over 4 years in young children undergoing total pancreatectomy with islet autotransplantation
Authors: Gnikpingo Taylor , Benson Sydney , Hodges James S. , Downs Elissa , Cook Marie , Schwarzenberg Sarah J. , Chinnakotla Srinath , Bellin Melena D.
Published: August 2023

Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post‐ pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n = 52, age 3–11 years) versus adolescents (n = 82, age 12–18 years). For MMTT, children consumed Boost HP and we sampled C‐peptide and glucose repeatedly over 2 h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre‐TPIAT and 3, 6 months, 1, 2, 3, and 4 years post‐TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p = .003) but IEQ/kg was higher in young children (p < .001) because of their lower weight. AUC C‐peptide in young children increased somewhat over 4 years, but was stable in adolescents (p = .0013). AUC glucose increased more in adolescents over time post‐TPIAT (p = .0024). Islet function by AUC C‐peptide:AUC glucose ratio was better preserved in young children (p < .001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant.
Hepatitis C and heart transplantation: An update
Authors: Nunez Marina , Kelkar Anita A.
Published: August 2023

There are limited data regarding heart transplantation in the setting of hepatitis C virus (HCV) infection in either recipients or donors, as the practice was infrequent, given concerns of worse post‐transplant outcomes. This changed dramatically after the development of highly effective HCV therapies, namely direct‐acting antivirals (DAAs). Additionally, nucleic acid testing currently in use establishes more precisely the risk of HCV transmission from donors. As a result, chronic HCV infection in itself is no longer a barrier for heart transplant candidates, and the use of HCV‐positive organs for HCV‐infected and non‐infected transplant candidates has increased dramatically. A review of the literature revealed that in the pre‐DAA era, HCV seropositive heart transplant patients had a higher mortality than their seronegative counterparts. However, short‐term data suggest that the differences in survival have been erased in the DAA era. Heart transplantation from HCV‐viremic donors to HCV‐uninfected recipients has become increasingly common as the number of deceased donors with HCV viremia has increased over the past years. Preliminary outcome reports are very encouraging, although further data are needed with regard to long‐term safety. New information continues to be incorporated to optimize protocols that guide this practice.
The Substitution Effect of Preferential Tariffs on Nontariff Measures: Evidence from Vietnam
Authors: Nguyen Chuc Dinh , Hayakawa Kazunobu
Published: August 2023

This study empirically investigates the effects of ASEAN Trade in Goods Agreement (ATIGA) tariffs on nontariff measures (NTMs) in Vietnam from 2012 to 2018. Our findings reveal the following: First, our gravity estimation demonstrates that although the reduction of ATIGA tariffs increases Vietnam's imports, the introduction of certain NTM types, particularly price control and finance measures, decreases them. Second, the reduction of ATIGA tariffs tends to introduce price control measures in particular. Third, when ATIGA tariffs decrease, the pre‐shipment inspection, nonautomatic licensing, and finance measures are more likely to be eliminated for products in which Vietnam has high export competitiveness. Fourth, both ATIGA tariffs and ASEAN+1 free trade agreement tariffs have significant effects on the introduction of NTMs in Vietnam. Finally, we found that the reduction in ATIGA tariffs also results in decreasing most favored nation tariffs.
Cerebral palsy pain instruments: Recommended tools for clinical research studies by the National Institute of Neurological Disorders and Stroke Cerebral Palsy Common Data Elements project
Authors: Schiariti Verónica , Shierk Angela , Stashinko Elaine E. , Sukal‐Moulton Theresa , Feldman Robin S. , Aman Clara , Mendoza‐Puccini M. Carolina , Brandenburg Joline E. ,   the National Institute of Neurological Disorders and Stroke Cerebral Palsy Common Data Elements Oversight Committee
Published: August 2023

Aim

This study describes the process of updating the cerebral palsy (CP) common data elements (CDEs), specifically identifying tools that capture the impact of chronic pain on children's functioning.

Method

Through a partnership between the American Academy for Cerebral Palsy and Developmental Medicine and the National Institute of Neurological Disorders and Stroke (NINDS), the CP CDEs were developed as data standards for clinical research in neuroscience. Chronic pain was underrepresented in the NINDS CP CDEs version 1.0. A multi‐step methodology was applied by an interdisciplinary professional team. Following an adapted CP chronic pain tools' rating system, and a review of psychometric properties, clinical utility, and compliance with inclusion/exclusion criteria, a set of recommended pain tools was posted online for external public comment in May 2022.

Results

Fifteen chronic pain tools met inclusion criteria, representing constructs across all components of the International Classification of Functioning, Disability and Health.

Interpretation

This paper describes the first condition‐specific pain CDEs for a pediatric population. The proposed set of chronic pain tools complement and enhance the applicability of the existing pediatric CP CDEs. The novel CP CDE pain tools harmonize the assessment of chronic pain, addressing not only intensity of chronic pain, but also the functional impact of experiencing it in everyday activities.
“Bronchogenic cyst impersonating a pericardial lesion”: A case report
Authors: Javier Cruz‐Zarrabal , Santibañez‐Escobar Felipe , Aranda‐Fraustro Alberto , Arias‐Godinez Jose A , Fritche‐Salazar Juan F , Ortiz‐Leon Xochitl A , G Rodriguez‐Zanella Hugo , Ruiz Esparza‐Dueñas Maria E , Posada‐Martinez Edith L
Published: August 2023

A 32‐year‐old female presented with palpitations and chest discomfort. The patient had a history of pericardiotomy due to pericardial effusion. Multimodal imaging, including echocardiography, cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) showed a single mass in the pericardium as the cause of the symptoms. Furthermore, its location and potential complications were accurately defined. The patient underwent a successful surgical resection of the pericardial cyst, microscopic histopathological examination was compatible with a bronchogenic cyst, a very rare congenital malformation. The article discusses the rarity of bronchogenic cysts in the pericardium and the importance of accurate diagnosis and appropriate treatment.
Substantial fitness costs in terms of parasitization rates, offspring production and sex ratio of Wolbachia infection in Nasonia vitripennis without modified host preference
Authors: Kalyanaraman Dhevi , Riemsloh Katharina Meyer Zu , Kürschner Liv Kristin , Gadau Jürgen , Lammers Mark
Published: August 2023

Wolbachia is a genus of endosymbiotic bacteria that is widespread among arthropods. It is responsible for manipulating various host phenotypes and often affects their host's fitness. We used the generalist parasitoid wasp Nasonia vitripennis and its endosymbiont Wolbachia to test whether and how Wolbachia affects the fitness of N. vitripennis by comparing the host preference and parasitization rate of cured and uncured N. vitripennis lines.

We reared four genotypes of wasps, each with Wolbachia infection or cured of infection, using two different host species, namely Calliphora vomitoria and Lucilia sericata, for 3–4 generations before measuring their host preference because rearing history has previously been shown to influence host preference in N. vitripennis. We found that all experimental groups significantly preferred C. vomitoria pupae. Neither rearing history nor Wolbachia infection altered N. vitripennis female's innate host preference.

Furthermore, we investigated whether Wolbachia infection may affect Nasonia's parasitization rate, offspring production and sex ratio using parasitization assays of two wasp genotypes with and without Wolbachia infection. Our results show that uncured wasps have fitness costs of harbouring Wolbachia in terms of reduced parasitization rate and offspring production in one of the host genotypes and reduced proportion of female offspring in the second host genotype tested, highlighting the context‐dependency of host–endosymbiont relationships.
Cutaneous involvement in Ph‐negative myeloproliferative neoplasms: from extramedullary hematopoiesis to myeloid metastasis with histiocytic differentiation. A systematic review of the literature
Authors: Bonometti Arturo
Published: August 2023

Myeloid neoplasms may metastasize to the skin, presenting a wide range of clinical‐pathological features that often lead to a reduction in patients' survival. The presentation varies depending on the category of myeloid neoplasm and its prognostic significance. The literature has specifically focused on the features of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML). In this article, we aimed to uncover the peculiarities of clonal skin proliferations in the course of Ph‐negative myeloproliferative neoplasms (MPNs). We conducted a systematic review and statistical analysis of the literature data. MPN patients mainly exhibited cutaneous extramedullary hematopoiesis, while a minority displayed cutaneous histiocytic lesions. Furthermore, these patients showed lower survival rates compared to the median survival of MPN patients, especially when calculating survival from the appearance of cutaneous lesions. Our work highlights, for the first time, the prognostic relevance and histological heterogeneity of cutaneous lesions in MPN. Moreover, it emphasizes the importance of dermatological and histological examinations when cutaneous lesions are present.
Exploring the anti‐inflammatory activity of sulforaphane
Authors: Treasure Katie , Harris James , Williamson Gary
Published: August 2023

Dysregulation of innate immune responses can result in chronic inflammatory conditions. Glucocorticoids, the current frontline therapy, are effective immunosuppressive drugs but come with a trade‐off of cumulative and serious side effects. Therefore, alternative drug options with improved safety profiles are urgently needed. Sulforaphane, a phytochemical derived from plants of the brassica family, is a potent inducer of phase II detoxification enzymesvianuclear factor‐erythroid factor 2–related factor 2 (NRF2) signaling. Moreover, a growing body of evidence suggests additional diverse anti‐inflammatory properties of sulforaphane through interactions with mediators of key signaling pathways and inflammatory cytokines. Multiple studies support a role for sulforaphane as a negative regulator of nuclear factor kappa‐light chain enhancer of activated B cells (NF‐κB) activation and subsequent cytokine release, inflammasome activation and direct regulation of the activity of macrophage migration inhibitory factor. Significantly, studies have also highlighted potential steroid‐sparing activity for sulforaphane, suggesting that it may have potential as an adjunctive therapy for some inflammatory conditions. This review discusses published research on sulforaphane, including proposed mechanisms of action, and poses questions for future studies that might help progress our understanding of the potential clinical applications of this intriguing molecule.