bluuebunny/crossref_metadata_2025 huggingface dataset:
MultiNicheNet: a flexible framework for differential cell-cell communication analysis from multi-sample multi-condition single-cell transcriptomics data
Authors: Browaeys Robin , Gilis Jeroen , Sang-Aram Chananchida , De Bleser Pieter , Hoste Levi , Tavernier Simon , Lambrechts Diether , Seurinck Ruth , Saeys Yvan
Published: June 2023

Dysregulated cell-cell communication is a hallmark of many disease phenotypes. Due to recent advances in single-cell transcriptomics and computational approaches, it is now possible to study intercellular communication on a genome- and tissue-wide scale. However, most current cell-cell communication inference tools have limitations when analyzing data from multiple samples and conditions. Their main limitation is that they do not address inter-sample heterogeneity adequately, which could lead to false inference. This issue is crucial for analyzing human cohort scRNA-seq datasets, complicating the comparison between healthy and diseased subjects.

Therefore, we developed MultiNicheNet (https://github.com/saeyslab/multinichenetr), a novel framework to better analyze cell-cell communication from multi-sample multi-condition single-cell transcriptomics data. The main goals of MultiNicheNet are inferring the differentially expressed and active ligand-receptor pairs between conditions of interest and predicting the putative downstream target genes of these pairs. To achieve this goal, MultiNicheNet applies the principles of state-of-the-art differential expression algorithms for multi-sample scRNA-seq data. As a result, users can analyze differential cell-cell communication while adequately addressing inter-sample heterogeneity, handling complex multifactorial experimental designs, and correcting for batch effects and covariates. Moreover, MultiNicheNet uses NicheNet-v2, our new and substantially improved version of NicheNet’s ligand-receptor network and ligand-target prior knowledge model.

We applied MultiNicheNet to patient cohort data of several diseases (breast cancer, squamous cell carcinoma, multisystem inflammatory syndrome in children, and lung fibrosis). For these diseases, MultiNicheNet uncovered known and novel aberrant cell-cell signaling processes. We also demonstrated MultiNicheNet’s potential to perform non-trivial analysis tasks, such as studying between- and within-group differences in cell-cell communication dynamics in response to therapy. As a final example, we used MulitNicheNet to elucidate dysregulated intercellular signaling in idiopathic pulmonary fibrosis while correcting batch effects in integrated atlas data.

Given the anticipated increase in multi-sample scRNA-seq datasets due to technological advancements and extensive atlas-building integration efforts, we expect that MultiNicheNet will be a valuable tool to uncover differences in cell-cell communication between healthy and diseased states.
Faulty Metabolism: A Potential Instigator of an Aggressive Phenotype in Cdk5-dependent Medullary Thyroid Carcinoma
Authors: Gupta Priyanka , Herring Brendon , Kumar Nilesh , Telange Rahul , Garcia-Buntley Sandra S. , Caceres Tessa W. , Colantonio Simona , Williams Ford , Kurup Pradeep , Carter Angela M. , Lin Diana , Chen Herbert , Rose Bart , Jaskula-Sztul Renata , Mukhtar Shahid , Reddy Sushanth , Bibb James A.
Published: June 2023

Mechanistic modeling of cancers such as Medullary Thyroid Carcinoma (MTC) to emulate patient-specific phenotypes is challenging. The discovery of potential diagnostic markers and druggable targets in MTC urgently requires clinically relevant animal models. Here we established orthotopic mouse models of MTC driven by aberrantly active Cdk5 using cell-specific promoters. Each of the two models elicits distinct growth differences that recapitulate the less or more aggressive forms of human tumors. The comparative mutational and transcriptomic landscape of tumors revealed significant alterations in mitotic cell cycle processes coupled with the slow-growing tumor phenotype. Conversely, perturbation in metabolic pathways emerged as critical for aggressive tumor growth. Moreover, an overlapping mutational profile was identified between mouse and human tumors. Gene prioritization revealed putative downstream effectors of Cdk5 which may contribute to the slow and aggressive growth in the mouse MTC models. In addition, Cdk5/p25 phosphorylation sites identified as biomarkers for Cdk5-driven neuroendocrine tumors (NETs) were detected in both slow and rapid onset models and were also histologically present in human MTC. Thus, this study directly relates mouse and human MTC models and uncovers vulnerable pathways potentially responsible for differential tumor growth rates. Functional validation of our findings may lead to better prediction of patient-specific personalized combinational therapies.

Graphical abstract

Highlights

CGRP driven aberrant Cdk5 activation develops early onset aggressive MTC

Genetic alterations in mouse and human tumors disrupt common pathways

Aggressive tumor model characterized by alterations in metabolic pathways

Slow growing tumor model elicits disruption of mitotic spindle assembly
The Single-Cell Transcriptome Program of Nodule Development Cellular Lineages inMedicago truncatula
Authors: Pereira Wendell J. , Boyd Jade , Conde Daniel , Triozzi Paolo M. , Balmant Kelly M. , Dervinis Christopher , Schmidt Henry W. , Boaventura-Novaes Carolina , Chakraborty Sanhita , Knaack Sara A. , Gao Yueyao , Feltus Frank Alexander , Roy Sushmita , Ané Jean-Michel , Frugoli Julia , Kirst Matias
Published: June 2023

Legumes can establish a symbiotic relationship with nitrogen-fixing rhizobia by developing nodules after root exposure to lipo-chito-oligosaccharides secreted by the bacteria. Nodule development initiates with anticlinal mitotic divisions in the pericycle and endodermal and inner cortical cells, establishing cell lineages that ultimately form each nodule compartment. We characterized these lineages by isolating and sequencing the transcriptome ofMedicago truncatulasingle nuclei derived from uninoculated roots and roots undergoing early nodule development at 24, 48, and 96 hours after inoculation. To enrich samples for cells responding to the rhizobia, we complemented the analysis of theMedicagowild-type genotype A17 with a mutant for the autoregulation of nodulation,sunn-4. Analysis of cell lineage trajectories derived from the cortex indicates that their transcriptome is initially enriched for cytokinin perception and signaling while repressing auxin accumulation. As these cells differentiate to form nodules, expression of genes related to auxin biosynthesis, transport, and signaling was enhanced, while genes involved in cytokinin degradation were activated as lineages bifurcated to form the nodule meristem and infection zones. While the contribution of auxin and cytokinin in nodule development has been recognized, this single-cell resource quantifies the expression of each of their regulators, receptors and targets as cells divide and differentiate to form each nodule compartment.
Predicting glycan structure from tandem mass spectrometry via deep learning
Authors: Urban James , Jin Chunsheng , Thomsson Kristina A. , Karlsson Niclas G. , Ives Callum M. , Fadda Elisa , Bojar Daniel
Published: June 2023

Glycans constitute the most complicated post-translational modification, modulating protein activity in health and disease. However, structural annotation from tandem mass spectrometry data is a bottleneck in glycomics, preventing high-throughput endeavors and relegating glycomics to a few experts. Trained on a newly curated set of 300,000 annotated MS/MS spectra, we present CandyCrunch, a dilated residual neural network predicting glycan structure from raw LC-MS/MS data in seconds (Top1 Accuracy: 87.7%). We developed an open-access Python-based workflow of raw data conversion and prediction, followed by automated curation and fragment annotation, with predictions recapitulating and extending expert annotation. We demonstrate that this can be used forde novoannotation, diagnostic fragment identification, and high-throughput glycomics. For maximum impact, this entire pipeline is tightly interlaced with our glycowork platform and can be easily tested athttps://colab.research.google.com/github/BojarLab/CandyCrunch/blob/main/CandyCru nch.ipynb. We envision CandyCrunch to democratize structural glycomics and the elucidation of biological roles of glycans.
The protein phosphatase PPKL is a key regulator of daughter parasite development inToxoplasma gondii
Authors: Yang Chunlin , Doud Emma H. , Sampson Emily , Arrizabalaga Gustavo
Published: June 2023

Apicomplexan parasites, includingToxoplasma gondii, encode many plant-like proteins, which play significant roles and present attractive targets for drug development. In this study, we have characterized the plant-like protein phosphatase PPKL, which is unique to the parasite and absent in its mammalian host. We have shown that its localization changes as the parasite divides. In non-dividing parasites, it is present in the cytoplasm, nucleus, and preconoidal region. As the parasite begins division, PPKL is enriched in the preconoidal region and the cortical cytoskeleton of the nascent parasites. Later in the division, PPKL is present in the basal complex ring. Conditional knockdown of PPKL showed that it is essential for parasite propagation. Moreover, parasites lacking PPKL exhibit uncoupling of division, with normal DNA duplication but severe defects in forming daughter parasites. While PPKL depletion does not impair the duplication of centrosomes, it affects the rigidity and arrangement of the cortical microtubules. Both Co-Immunoprecipitation and proximity labeling identified the kinase DYRK1 as a potential functional partner of PPKL. Complete knockout ofDYRK1phenocopies lack of PPKL, strongly suggesting a functional relationship between these two signaling proteins. Global phosphoproteomics analysis revealed a significant increase in phosphorylation of the microtubule-associated proteins SPM1 in PPKL-depleted parasites, suggesting PPKL regulates the cortical microtubules by mediating the phosphorylation state of SPM1. More importantly, the phosphorylation of cell cycle-associated kinase Crk1, a known regulator of daughter cell assembly, is altered in PPKL-depleted parasites. Thus, we propose that PPKL regulates daughter parasite development by influencing the Crk1-dependent signaling pathway.

Importance

Toxoplasma gondiican cause severe disease in immunocompromised or immunosuppressed patients and during congenital infections. Treating toxoplasmosis presents enormous challenges since the parasite shares many biological processes with its mammalian hosts, which results in significant side effects with current therapies. Consequently, proteins that are essential and unique to the parasite represent favorable targets for drug development. Interestingly,Toxoplasma, like other members of the phylum Apicomplexa, has numerous plant-like proteins, many of which play crucial roles and do not have equivalents in the mammalian host. In this study, we found that the plant-like protein phosphatase, PPKL, appears to be a key regulator of daughter parasite development. With the depletion of PPKL, the parasite shows severe defects in forming daughter parasites. This study provides novel insights into the understanding of parasite division and offers a new potential target for the development of antiparasitic drugs.
Single-cell transcriptional landscapes of bovine peri-implantation development
Authors: Scatolin Giovanna Nascimento , Ming Hao , Wang Yinjuan , Zhu Linkai , Castillo Emilio Gutierrez , Bondioli Kenneth , Jiang Zongliang
Published: June 2023

Supporting healthy pregnancy outcomes requires a comprehensive understanding of the cellular hierarchy and underlying molecular mechanisms during peri-implantation development. Here, we present a single-cell transcriptome-wide view of the bovine peri-implantation embryo development at day 12, 14, 16 and 18, when most of the pregnancy failure occurs in cattle. We defined the development and dynamic progression of cellular composition and gene expression of embryonic disc, hypoblast, and trophoblast lineages during bovine peri-implantation development. Notably, the comprehensive transcriptomic mapping of trophoblast development revealed a previously unrecognized primitive trophoblast cell lineage that is responsible for pregnancy maintenance in bovine prior to the time when binucleate cells emerge. We analyzed novel markers for the cell lineage development during bovine early development. We also identified cell-cell communication signaling underling embryonic and extraembryonic cell interaction to ensure proper early development. Collectively, our work provides foundational information to discover essential biological pathways underpinning bovine peri-implantation development and the molecular causes of the early pregnancy failure during this critical period.

Significance Statement

Peri-implantation development is essential for successful reproduction in mammalian species, and cattle have a unique process of elongation that proceeds for two weeks prior to implantation and represents a period when many pregnancies fail. Although the bovine embryo elongation has been studied histologically, the essential cellular and molecular factors governing lineage differentiation remain unexplored. This study profiled the transcriptome of single cells in the bovine peri-implantation development throughout day 12, 14, 16, and 18, and identified peri-implantation stage-related features of cell lineages. The candidate regulatory genes, factors, pathways and embryonic and extraembryonic cell interactions were also prioritized to ensure proper embryo elongation in cattle.
Structure and dynamics of endogenous protein complexes in human heart tissue captured by native nanoproteomics
Authors: Chapman Emily A. , Roberts David S. , Tiambeng Timothy N. , Andrews Jãán , Wang Man-Di , Reasoner Emily A. , Melby Jake A. , Li Brad H. , Kim Donguk , Alpert Andrew J. , Jin Song , Ge Ying
Published: June 2023

Protein complexes are highly dynamic entities that display substantial diversity in their assembly, post-translational modifications, and non-covalent interactions, allowing them to play critical roles in various biological processes. The heterogeneity, dynamic nature, and low abundance of protein complexes in their native states present tremendous challenges to study using conventional structural biology techniques. Here we develop a “native nanoproteomics” strategy for the native enrichment and subsequent native top-down mass spectrometry (nTDMS) of of low-abundance protein complexes. Specifically, we demonstrate the first comprehensive characterization of the structure and dynamics of cardiac troponin (cTn) complexes directly from human heart tissue. The endogenous cTn complex is effectively enriched and purified using peptide-functionalized superparamagnetic nanoparticles under non-denaturing conditions to enable the isotopic resolution of cTn complexes, revealing their complex structure and assembly. Moreover, nTDMS elucidates the stoichiometry and composition of the heterotrimeric cTn complex, localizes Ca2+binding domains (II-IV), defines cTn-Ca2+binding dynamics, and provides high-resolution mapping of the proteoform landscape. This native nanoproteomics strategy opens a new paradigm for structural characterization of low-abundance native protein complexes.
Intrinsic Homeostatic Plasticity in Mouse and Human Sensory Neurons
Authors: McIlvried Lisa A. , Del Rosario John Smith , Pullen Melanie Y. , Wangzhou Andi , Sheahan Tayler D. , Shepherd Andrew J. , Slivicki Richard A. , Lemen John A. , Price Theodore J. , Copits Bryan A. , Gereau Robert W.
Published: June 2023

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons under normal conditions or altered after chronic pain is unknown. Here, we showed that sustained depolarization induced by 30mM KCl induces a compensatory decrease in the excitability in mouse and human sensory neurons. Moreover, voltage-gated sodium currents are robustly reduced in mouse sensory neurons contributing to the overall decrease in neuronal excitability. Decreased efficacy of these homeostatic mechanisms could potentially contribute to the development of the pathophysiology of chronic pain.
SpatialView: An interactive web application for visualization of multiple samples in spatial transcriptomics experiments
Authors: Mohanty Chitrasen , Prasad Aman , Cheng Lingxin , Arkin Lisa M. , Shields Bridget E. , Drolet Beth , Kendziorski Christina
Published: June 2023

Spatial transcriptomics (ST) experiments provide spatially localized measurements of genome-wide gene expression allowing for an unprecedented opportunity to investigate cellular heterogeneity and organization within a tissue. Statistical and computational frameworks exist that implement robust methods for pre-processing and analyzing data in ST experiments. However, the lack of an interactive suite of tools for visualizing ST data and results currently limits the full potential of ST experiments. To fill this gap, we developed SpatialView, an open-source web browser-based interactive application for visualizing data and results from multiple 10x Genomics ST experiments. We anticipate SpatialView will be useful to a broad array of clinical and basic science investigators utilizing ST to study disease.

Availability

SpatialView is available athttps://github.com/kendziorski-lab/SpatialView; a demo application is available athttps://www.biostat.wisc.edu/~kendzior/spatialviewdemo/

Contact

cmohanty2@wisc.edu,ckendziorski@wisc.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Impact of inoculation practices on microbiota assembly and community stability in a fabricated ecosystem
Authors: Lin Hsiao-Han , Torres Marta , Adams Catharine A. , Andeer Peter F. , Owens Trenton K. , Zhalnina Kateryna , Jabusch Lauren K. , Carlson Hans K. , Kuehl Jennifer V. , Deutschbauer Adam M. , Northen Trent R. , Glass N. Louise , Mortimer Jenny C.
Published: June 2023

Studying plant-microbe-soil interactions is challenging due to their high complexity and variability in natural ecosystems. While fabricated ecosystems provide opportunities to recapitulate aspects of these systems in reduced complexity and controlled environments, inoculation can be a significant source of variation. To tackle this, we evaluated how different bacteria inoculation practices and plant harvesting time points affect the reproducibility of a microbial synthetic community (SynCom) in association with the model grassBrachypodium distachyon. We tested three microbial inoculation practices: seed inoculation, transplant inoculation, and seedling inoculation; and two harvesting points: early (14-day-old plants) and late (21 days post-inoculation). We grew our plants and bacterial strains in sterile devices (EcoFABs) and characterized the microbial community from root, rhizosphere, and sand using 16S ribosomal RNA gene sequencing. The results showed that inoculation practices significantly affected the rhizosphere microbial community only when harvesting at an early time point but not at the late stage. As the SynCom showed a persistent association withB. distachyonat 21 days post-inoculation regardless of inoculation practices, we assessed the reproducibility of each inoculation method and found that transplant inoculation showed the highest reproducibility. Moreover, plant biomass was not adversely affected by transplant inoculation treatment. We concluded that bacteria inoculation while transplanting coupled with a later harvesting time point gives the most reproducible microbial community in the EcoFAB-B. distachyon-SynCom fabricated ecosystem and recommend this method as a standardized protocol for use with fabricated ecosystem experimental systems.
Super-resolution histology of paraffin-embedded samples via photonic chip-based microscopy
Authors: Villegas-Hernández Luis E. , Dubey Vishesh K. , Mao Hong , Pradhan Manohar , Tinguely Jean-Claude , Hansen Daniel H. , Acuña Sebastián , Zapotoczny Bartłomiej , Agarwal Krishna , Nystad Mona , Acharya Ganesh , Fenton Kristin A. , Danielsen Håvard E. , Ahluwalia Balpreet Singh
Published: June 2023

Fluorescence-based super-resolution optical microscopy (SRM) techniques allow the visualization of biological structures beyond the diffraction limit of conventional microscopes. Despite its successful adoption in cell biology, the integration of SRM into the field of histology has been deferred due to several obstacles. These include limited imaging throughput, high cost, and the need for complex sample preparation. Additionally, the refractive index heterogeneity and high labeling density of commonly available formalin-fixed paraffin-embedded (FFPE) tissue samples pose major challenges to applying existing super-resolution microscopy methods. Here, we demonstrate that photonic chip-based microscopy alleviates several of these challenges and opens avenues for super-resolution imaging of FFPE tissue sections. By illuminating samples through a high refractive-index waveguide material, the photonic chip-based platform enables ultra-thin optical sectioning via evanescent field excitation, which reduces signal scattering and enhances both the signal-to-noise ratio and the contrast. Furthermore, the photonic chip provides decoupled illumination and collection light paths, allowing for total internal reflection fluorescence (TIRF) imaging over large and scalable fields of view. By exploiting the spatiotemporal signal emission via MUSICAL, a fluorescence fluctuation-based super-resolution microscopy (FF-SRM) algorithm, we demonstrate the versatility of this novel microscopy method in achieving superior contrast super-resolution images of diverse FFPE tissue sections derived from human colon, prostate, and placenta. The photonic chip is compatible with routine histological workflows and allows multimodal analysis such as correlative light-electron microscopy (CLEM), offering a promising tool for the adoption of super-resolution imaging of FFPE sections in both research and clinical settings.
Structural assembly of the bacterial essential interactome
Authors: Gómez Borrego Jordi , Torrent Marc Burgas
Published: June 2023

The study of protein interactions in living organisms is fundamental to understanding biological processes and central metabolic pathways. However, our understanding of the bacterial interactome remains limited, hindering the identification of new drug targets and the development of new therapeutic strategies. Here, we predict the assembly of the essential proteins in bacteria using the deep learning protein folding algorithm Alphafold2. We modeled 1089 interactions between essential proteins in bacteria and generated 115 high-accuracy models. Our analysis reveals previously unknown details about the assembly mechanisms of these complexes, highlighting the importance of specific structural features in their stability and function. Furthermore, we identify several novel protein-protein interactions that provide new targets for drug development. Our work provides a framework for predicting the interactome of other bacteria and highlights the potential of deep learning algorithms in advancing our understanding of the complex biology of living organisms.
Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modelling
Authors: Mäaki-Marttunen Tuomo , Blackwell Kim T. , Akkouh Ibrahim , Shadrin Alexey , Valstad Mathias , Elvsåashagen Tobjørn , Linne Marja-Leena , Djurovic Srdjan , Einevoll Gaute T. , Andreassen Ole A.
Published: June 2023

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modelling of post-synaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD). We combined our model with data from post-mortem mRNA expression studies (CommonMind gene-expression datasets) to assess the consequences of altered expression of plasticity-regulating genes for the amplitude of LTP and LTD. Our results show that the expression alterations observedpost mortem, especially those in anterior cingulate cortex, lead to impaired PKA-pathway-mediated LTP in synapses containing GluR1 receptors. We validated these findings using a genotyped EEG dataset where polygenic risk scores for synaptic and ion channel-encoding genes as well as modulation of visual evoked potentials (VEP) were determined for 286 healthy controls. Our results provide a possible genetic mechanism for plasticity impairments in schizophrenia, which can lead to improved understanding and, ultimately, treatment of the disorder.
Empowering leadership questionnaire: Brazilian adaptation and validation
Authors: Ferraro Tânia , Lott Ana Cristina de Oliveira
Published: June 2023

Purpose

The present study aims to present the adaptation and validation of the empowering leadership questionnaire (ELQ) for a sample of Brazilian workers (N = 827).

Design/methodology/approach

The procedures of items translation, adaptation and back-translation of the original instrument were carried out. Data collection was performed using the snowball method. Data were evaluated with confirmatory factor analysis.

Findings

The results showed that the factor structure was maintained as in the portuguese (from Portugal) and English versions (original). Convergent validity was tested using the ethical leadership at work questionnaire (ELW). The analyses showed that the measure has good psychometric qualities, reliability indices and convergent validity results with the ELW.

Research limitations/implications

The ELQ can still be used to identify the presence of empowering leadership (diagnostic phase) and contribute to proposing organizational interventions that lead to healthier and more productive work environments. Its convergent validity with ethical leadership suggests that managers can apply both (empowering and ethical leadership complementarily) to create quality interactions between leaders and team members that increase workers’ autonomy and allow them to respond promptly to organizational challenges.

Originality/value

Using the ELQ can represent an important tool for the theoretical and practical development of studies of empowering leadership with Brazilian samples.
The nexus between cultural values and perceptions of corporate sustainable development
Authors: Deirmentzoglou Georgios A. , Agoraki Konstantina K. , Patsoulis Patroklos
Published: June 2023

Purpose

This study aims to investigate the influence of cultural values on perceptions of corporate sustainable development (CSD). In recent years, the intensity of the connection between cultural values and SD has been a heavily debated topic. Subsequently, this issue has gained considerable attention from management academics.

Design/methodology/approach

To shed light on this phenomenon, this study uses econometric techniques (linear regression) and conducts a survey of business executives in medium and large firms to search for evidence that cultural values significantly affect perceptions of CSD.

Findings

The findings indicate that forward-looking executives who envision themselves as individuals rather than members of a group exhibit more positive perceptions of CSD practices than the rest.

Originality/value

To the best of the authors’ knowledge, this is the first empirical assessment of cultural values on the perceptions of the three aspects (economic, social and environmental) of CSD.
Measuring employee empowering and ownership under accountability pressure: the case of J&J Industries
Authors: Garcia Fernando , Smith Stephen Ray , Helms Marilyn Michelle
Published: June 2023

Research Methodology

Data used to develop the case included primary data from employees and supervisors of a commercial floorcovering manufacturing plant in Northwest Georgia. The case company is not disguised.

The survey was developed using existing instruments from the Organizational Behavior and Human Resources Literature. Instruments were listed in Exhibits 2 through 7. The survey administration had the support of the Vice President for Resources and Facilities, and employees and their supervisors were given time to complete the surveys. The data gathered was analyzed by the researcher using SPSS statistical software.

Case overview/synopsis

Established in 1957, J&J started as a family-owned business but had grown and diversified its product offerings by focusing on commercial flooring. It survived several economic downturns and remained competitive in a market dominated by more prominent flooring manufacturers. J&J Industries strived to empower its 800 employees with various incentive programs. Employees remained loyal to J&J; many had worked for the company for over 15 years. However, management wanted to measure the impact of empowering and initiatives on employee performance and satisfaction to determine the real power of employee incentive programs. The Resources and Facilities Vice President employed Professor Lopez, a Management Professor, to develop a survey to measure these constructs and analyze the data to guide future incentive programs. Data from the employee and supervisor survey was provided along with the statistical analysis results for interpretation and recommendations for VP Fordham.

Complexity academic level

The target audience for this case is primarily students in a research methodology course and students studying quantitative regression analysis and interpretation. The focus is predominantly on graduate-level students in Master of Business Administration or Master of Accounting programs in business. Graduate students should have completed courses in management or organizational behavior, business statistics or quantitative methods or data visualization and cleaning as background knowledge for this case. Specifically, students should understand regression analysis and know when and how the tool is used for managerial decision-making.
Increasing the Powers of the Secretary of State for the Home Department to Strip Individuals of their British Citizenship: R (on the application of Begum) v SSHD
Authors: Riaz Ayesha
Published: June 2023

In R (on the application of Begum) v Secretary of State for the Home Department, Ms Shamima Begum was deprived of her British citizenship by the Secretary of State for the Home Department, as she had chosen to flee to Syria, and aligned herself with Islamic State of Iraq and Levant. To safeguard the UK's national security, the Supreme Court held that Ms Begum could not return to the UK to challenge the legality of the decision to deprive her of her citizenship. Accordingly, this matter was recently heard in the Special Immigration Appeals Commission whilst Ms Begum remained outside the UK. This piece argues that, as a result of this decision, the equilibrium of power has further shifted in favour of the executive/Secretary of State for the Home Department. This has the effect of attenuating the powers of the appellate bodies to hear cases regarding deprivation of citizenship matters.
Does the number of cycles of neoadjuvant therapy affect the efficacy of neoadjuvant chemoimmunotherapy for non‐small cell lung cancer in locally advanced stage? Retrospective experience based on a single center
Authors: Zhu Di , Huang Zhida , Xiao Kai , Bian Dongliang , Zhang Jing , Zhang Zhonghong , Zhu Shuncang , Yin Laibo , Zhu Jialong , Zhang Peng
Published: June 2023

Background

The number of cycles of neoadjuvant therapy programmed cell death 1 (PD‐1) inhibitor for locally advanced non‐small cell lung cancer (NSCLC) remains controversial.

Methods

From October 2019 to March 2022, neoadjuvant chemoimmunotherapy followed by radical surgery for NSCLC patients with stage II–III were retrospectively reviewed in Shanghai Pulmonary Hospital. The radiologic response was assessed according to the Response Evaluation Criteria for Solid Tumors version 1.1. The major pathological response was defined as no more than 10% residual tumor. Student's t‐test, chi‐square test, and Mann‐Whitney test were used for univariate analysis, logistic regression analysis was used for multivariate analysis. All statistical analyses were calculated by SPSS software (version 26).

Results

Among 108 patients, the number of patients who received 2‐cycle (2‐cycle group) and more than 2‐cycle (>2‐cycle group) neoadjuvant chemoimmunotherapy were 75 (69.4%) and 33 (30.6%), respectively. Compared with patients in the >2‐cycle group, patients in the 2‐cycle group had significantly smaller diagnostic radiological tumor size (37.0 mm vs. 49.6 mm, p = 0.022) and radiological tumor regression rate (36% vs. 49%, p = 0.007). However, no significant difference in pathological tumor regression rate was observed between patients in the 2‐cycle group and >2‐cycle group. Further logistic regression analysis demonstrated that the neoadjuvant chemoimmunotherapy cycle could independently affect the radiographic response (odds ratio [OR]: 0.173, 95% confidence interval [CI]: 0.051–0.584, p = 0.005) but not for pathological response (OR: 0.450, 95% CI: 0.161–1.257, p = 0.127).

Conclusions

For patients diagnosed with stage II–III NSCLC, the number of neoadjuvant cycles administered can significantly influence the radiographic efficacy of chemoimmunotherapy.
Discovery of a potent inhibitor of chaperone‐mediated autophagy that targets the HSC70–LAMP2A interaction in non‐small cell lung cancer cells
Authors: Dong Rui‐Fang , Qin Cheng‐Jiao , Yin Yong , Han Liang‐Liang , Xiao Cheng‐Mei , Wang Kai‐Di , Wei Rong‐Yuan , Xia Yuan‐Zheng , Kong Ling‐Yi
Published: June 2023

Background and Purpose

Chaperone‐mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered.

Experimental Approach

Levels of CMA in non‐small cell lung cancer (NSCLC) tissue samples were confirmed by tyramide signal amplification dual immunofluorescence assay. High‐content screening was performed based on CMA activity, to identify potential inhibitors of CMA. Inhibitor targets were determined by drug affinity responsive target stability‐mass spectrum and confirmed by protein mass spectrometry. CMA was inhibited and activated to elucidate the molecular mechanism of the CMA inhibitor.

Key Results

Suppression of interactions between HSC70 and LAMP2A blocked CMA in NSCLC, restraining tumour growth. Polyphyllin D (PPD) was identified as a targeted CMA small‐molecule inhibitor through disrupting HSC70–LAMP2A interactions. The binding sites for PPD were E129 and T278 at the nucleotide‐binding domain of HSC70 and C‐terminal of LAMP2A, respectively. PPD accelerated unfolded protein generation to induce reactive oxygen species (ROS) accumulation by inhibiting HSC70–LAMP2A–eIF2α signalling axis. Also, PPD prevented regulatory compensation of macroautophagy induced by CMA inhibition via blocking the STX17–SNAP29–VAMP8 signalling axis.

Conclusions and Implications

PPD is a targeted CMA inhibitor that blocked both HSC70–LAMP2A interactions and LAMP2A homo‐multimerization. CMA suppression without increasing the regulatory compensation from macroautophagy is a good strategy for NSCLC therapy.
Caregiver openness in emotionally focused family therapy: A critical shift
Authors: Quinn Brittany , Davis Sean , Greaves Bryson , Furrow James , Palmer‐Olsen Lisa , Woolley Scott
Published: June 2023

Through the application of a discovery‐oriented task analysis, this research delineated specific therapist behaviors that resulted in a successful caregiver openness event in emotionally focused family therapy (EFFT). EFFT experts were recruited via email and asked to submit family therapy recordings where they believed a caregiver openness event occurred. Ten family therapy recordings were submitted by three experts. Within these recordings, 12 caregiver openness events were discovered and critically analyzed. Nine themes were identified and interventions therapists applied to accomplish these themes were delineated using the emotionally focused therapy‐coding scheme (EFT‐CS). These themes included: (1) validating and reframing the child's protected stance, (2) processing the impact of the child's unmet attachment longings, (3) validating the caregiver's blocked relational stance, (4) expanding caregiving intentions, (5) enacting the caregiver's intentions to meet the child's attachment longings, (6) processing the enactment, (7) processing and promoting caregiver accessibility to the child's response, (8) heightening the caregiver's accessible stance, and (9) enhancing shifting family dynamics. Additional findings, implications for clinical practice, training, and future research are discussed.
Bacterial species distribution on the genital skin of hospitalized patients with stroke manifesting incontinence‐associated dermatitis: A cross‐sectional study
Authors: Kohta Masushi , Koyanagi Hiroe , Inagaki Yoshinobu , Nishikawa Keiji , Kobayashi Nanako , Tamura Shigeru , Ishikawa Miyuki , Banno Yumi , Takekoshi Kanako , Mano Keiko , Sugama Junko
Published: June 2023

Aim

To compare the isolated and identified bacterial species colonizing on the genital skin between patients with and without incontinence‐associated dermatitis.

Methods

This cross‐sectional study included 102 patients with stroke admitted to an acute hospital in Japan. Swabs were collected, and bacterial species found in swabs were isolated and identified using a selective agar medium and simple identification kits. In addition to demographic information, severity of incontinence‐associated dermatitis and the total bacterial counts were measured.

Results

Incontinence‐associated dermatitis was present in 53.9% of the participants. Staphylococcus aureus was found in 50% of the participants with incontinence‐associated dermatitis and only 17.9% of those without incontinence‐associated dermatitis (P = 0.0029). Bacterial species distribution by erythema and skin erosion, which denote severity of incontinence‐associated dermatitis, was different, but not significant; additionally, the total number of bacterial colonies was equivalent.

Conclusions

Bacterial species distribution differed between patients with and without incontinence‐associated dermatitis, whereas the total number of bacterial colonies was equivalent. A high detection rate of S. aureus on genital skin sites potentially affects the presence of incontinence‐associated dermatitis and its severity. Geriatr Gerontol Int 2023; 23: 537–542.
Traceability strategy choice in competing supply chains based on blockchain technology
Authors: Chen Ting , Li Yongjian , Xu Fangchao
Published: June 2023

Blockchain can help reduce fraud and improve visibility and traceability in supply chains. It has attracted significant investments in commercial practices, especially in the luxury industry. With the recent upgradation of consumption worldwide, consumers care more about the source of information and the value of products. Will tracing products using blockchain technology help competing luxury brands gain consumer trust and cultivate new competitive advantages? This paper proposes a supply chain model comprising two competing manufacturers selling online through retail or direct channels. It also explores whether and how manufacturers implement traceability strategies, including building traceability systems or joining third‐party blockchain platforms, considering blockchain's traceability. The results show that, when only one party adopts the traceability strategy, being the first mover to join a third‐party blockchain platform with high traceability is always beneficial for improving the profits of all parties. In this scenario, the blockchain platform should adopt as high traceability as possible. When both parties choose to trace the product source, a win–win strategy for them is to join third‐party blockchain platforms with low traceability. In this scenario, the untraced party is motivated to implement a traceability strategy. Furthermore, if consumer perceptions of traceability are high, an untraced manufacturer can obtain higher profits using the traceability strategy. Otherwise, low consumer perception of traceability leads to low‐price competition, which is harmful to luxury brands.
RETRACTED: Risk predictions of hospital‐acquired pressure injury in the intensive care unit based on a machine learning algorithm
Authors: Tehrany Pooya M. , Zabihi Mohammad Reza , Ghorbani Vajargah Pooyan , Tamimi Pegah , Ghaderi Aliasghar , Norouzkhani Narges , Zaboli Mahdiabadi Morteza , Karkhah Samad , Akhoondian Mohammad , Farzan Ramyar
Published: June 2023

Pressure injury (PI), or local damage to soft tissues and skin caused by prolonged pressure, remains controversial in the medical world. Patients in intensive care units (ICUs) were frequently reported to suffer PIs, with a heavy burden on their life and expenditures. Machine learning (ML) is a Section of artificial intelligence (AI) that has emerged in nursing practice and is increasingly used for diagnosis, complications, prognosis, and recurrence prediction. This study aims to investigate hospital‐acquired PI (HAPI) risk predictions in ICU based on a ML algorithm by R programming language analysis. The former evidence was gathered through PRISMA guidelines. The logical analysis was applied via an R programming language. ML algorithms based on usage rate included logistic regression (LR), Random Forest (RF), Distributed tree (DT), Artificial neural networks (ANN), SVM (Support Vector Machine), Batch normalisation (BN), GB (Gradient Boosting), expectation–maximisation (EM), Adaptive Boosting (AdaBoost), and Extreme Gradient Boosting (XGBoost). Six cases were related to risk predictions of HAPI in the ICU based on an ML algorithm from seven obtained studies, and one study was associated with the Detection of PI risk. Also, the most estimated risksSerum Albumin, Lack of Activity, mechanical ventilation (MV), partial pressure of oxygen (PaO2), Surgery, Cardiovascular adequacy, ICU stay, Vasopressor, Consciousness, Skin integrity, Recovery Unit, insulin and oral antidiabetic (INS&OAD), Complete blood count (CBC), acute physiology and chronic health evaluation (APACHE) II score, Spontaneous bacterial peritonitis (SBP), Steroid, Demineralized Bone Matrix (DBM), Braden score, Faecal incontinence, Serum Creatinine (SCr) and age. In sum, HAPI prediction and PI risk detection are two significant areas for using ML in PI analysis. Also, the current data showed that the ML algorithm, including LR and RF, could be regarded as the practical platform for developing AI tools for diagnosing, prognosis, and treating PI in hospital units, especially ICU.
Psychometric validation of the Perceived Perioperative Competence Scale‐Revised Short Form
Authors: Gillespie Brigid M. , Harbeck Emma , Sutherland‐Fraser Sally , Nicholson Patricia , Boric Tina
Published: June 2023

Aim

To develop a parsimonious, shortened version of the Perceived Perioperative Competence Scale‐Revised for perioperative nurses to complete as part of their specialty training while retaining good psychometric properties.

Design

A longitudinal online survey was adopted.

Methods

A national sample of perioperative nurses from Australia completed an online survey at two different time points 6 months apart between February and October 2021. Confirmatory factor analysis was conducted for item reduction and construct validity, while criterion, convergent validity and internal consistency were examined.

Results

Usable data for psychometric assessment were obtained from 485 operating room nurses at time 1 and 164 nurses at time 2. The original 40‐item revised scale was reduced to an 18‐item measure, maintaining its six domains. Cronbach's alpha for the 18‐item scale was .92 at time 1 and .90 at time 2. Scale validation demonstrated moderate to weak positive relationships in perceived competence scores relative to general self‐efficacy, years of operating room experience, postgraduate education and recency of training.

Conclusions

Results suggest the 18‐item Perceived Perioperative Competence Scale‐Revised Short Form has initial robust psychometric properties and may be implemented in clinical settings as part of perioperative transition‐to‐practice, orientation programs and yearly professional development reviews.

Implications for the Profession

This short‐form scale can help prepare perioperative nurses to demonstrate clinical competence in a climate of increasing professional demands using a valid measure of competence required in clinical practice.

Impact

Short and validated scales of perioperative competence are needed in clinical practice. Assessment of practising operating room nurses' perceived competence is essential in quality care provision, workforce planning and human resource management. This study provides an 18‐item measure of the previously validated 40‐item Perceived Perioperative Competence Scale‐Revised. This scale can help provide an option for future testing of perioperative nurses' competence in clinical or research settings.

Patient or Public Contribution

Perioperative nurses were involved in the design of the study, particularly in the assessment of validation of the tools used in the study.
Identification and validation of SOCS1/2/3/4 as potential prognostic biomarkers and correlate with immune infiltration in glioblastoma
Authors: Dai Lirui , Han Yongjie , Yang Zhuo , Zeng Yuling , Liang Wulong , Shi Zimin , Tao Yiran , Liang Xianyin , Liu Wanqing , Zhou Shaolong , Xing Zhe , Hu Weihua , Wang Xinjun
Published: June 2023

Suppressor of cytokine signalling (SOCS) 1/2/3/4 are involved in the occurrence and progression of multiple malignancies; however, their prognostic and developmental value in patients with glioblastoma (GBM) remains unclear. The present study used TCGA, ONCOMINE, SangerBox3.0, UALCAN, TIMER2.0, GENEMANIA, TISDB, The Human Protein Atlas (HPA) and other databases to analyse the expression profile, clinical value and prognosis of SOCS1/2/3/4 in GBM, and to explore the potential development mechanism of action of SOCS1/2/3/4 in GBM. The majority of analyses showed that SOCS1/2/3/4 transcription and translation levels in GBM tissues were significantly higher than those in normal tissues. qRT‐PCR, western blotting (WB) and immunohistochemical staining were used to verify that SOCS3 was expressed at higher mRNA and protein levels in GBM than in normal tissues or cells. High SOCS1/2/3/4 mRNA expression was associated with poor prognosis in patients with GBM, especially SOCS3. SOCS1/2/3/4 were highly contraindicated, which had few mutations, and were not associated with clinical prognosis. Furthermore, SOCS1/2/3/4 were associated with the infiltration of specific immune cell types. In addition, SOCS3 may affect the prognosis of patients with GBM through JAK/STAT signalling pathway. Analysis of the GBM‐specific protein interaction (PPI) network showed that SOCS1/2/3/4 were involved in multiple potential carcinogenic mechanisms of GBM. In addition, colony formation, Transwell, wound healing and western blotting assays revealed that inhibition of SOCS3 decreased the proliferation, migration and invasion of GBM cells. In conclusion, the present study elucidated the expression profile and prognostic value of SOCS1/2/3/4 in GBM, which may provide potential prognostic biomarkers and therapeutic targets for GBM, especially SOCS3.