bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic heterogeneity drives phage-bacteria coevolution in the intestinal tract
Authors: Wenner Nicolas , Bertola Anouk , Larsson Louise , Rocker Andrea , Bekele Nahimi Amare , Sauerbeck Chris , Rocha Leonardo F. Lemos , Druelle Valentin , Harms Alexander , Diard Médéric
Published: November 2023

Phenotypic heterogeneity in bacteria can generate reversible resistance against various stressors, including predation by phages. This allows mixed populations of phenotypically resistant and sensitive bacteria to coexist with virulent phages. However, it remains unclear if these dynamics prevent the evolution of genetic resistance in bacteria and how they affect the evolution of phages. In this work, we focus on bistable alterations of the O-antigen (known as phase variation) inSalmonellaTyphimurium (S.Tm) to study how heterogeneous phenotypic resistance affects phage-bacteria coevolution. Our findings reveal that phase variation allows a stable coexistence ofS.Tm with a virulent T5-like phagein vitro. This coexistence is nevertheless short-lived whenS.Tm and the phage interact within the intestinal tract of mice. In this context, the phage evolves to also infect phenotypically resistantS.Tm cells, incidentally altering infectivity on otherSalmonellaserovars. In return, the broader host range of the evolved phages drives the evolution of genetic resistance inS.Tm, which results in phage extinction. This work demonstrates that phenotypic heterogeneity profoundly influences the antagonistic coevolution of phages and bacteria, with outcomes intricately tied to the ecological context.
Design of a symmetry-broken tetrahedral protein cage by a method of internal steric occlusion
Authors: Gladkov Nika , Scott Elena A. , Meador Kyle , Lee Eric J. , Laganowsky Arthur D. , Yeates Todd O. , Castells-Graells Roger
Published: November 2023

Methods in protein design have made it possible to create large and complex, self-assembling protein cages with diverse applications. These have largely been based on highly symmetric forms exemplified by the Platonic solids. Prospective applications of protein cages would be expanded by strategies for breaking the designed symmetry,e.g., so that only one or a few (instead of many) copies of an exterior domain or motif might be displayed on their surfaces. Here we demonstrate a straightforward design approach for creating symmetry-broken protein cages able to display singular copies of outward-facing domains. We modify the subunit of an otherwise symmetric protein cage through fusion to a small inward-facing domain, only one copy of which can be accommodated in the cage interior. Using biochemical methods and native mass spectrometry, we show that co-expression of the original subunit and the modified subunit, which is further fused to an outward-facing anti-GFP DARPin domain, leads to self-assembly of a protein cage presenting just one copy of the DARPin protein on its exterior. This strategy of designed occlusion provides a facile route for creating new types of protein cages with unique properties.
Diagnostic accuracy of a remote eye exam in measuring refractive errors and detecting cataract, glaucoma, and diabetic retinopathy
Authors: Moreira Taís de Campos , Pagano Cassia Garcia Moraes , Chagas Maria Eulália Vinadé , Falavigna Maicon , Rados Dimitris Rucks Varvaki , Silva Rodolfo Souza da , Harzheim Erno , Gonçalves Marcelo Rodrigues , Umpierre Roberto Nunes , de Azevedo Pietro Baptista , Waquil Alice Paul , Fabris Caroline , Lang Martha Pereira Lima , Szortika Adriana , Szortyka Anelise , de Araujo Aline Lutz , Cabral Felipe Cezar
Published: November 2023

Porpuse

Approximately 2.2 billion people worldwide have some type of visual impairment and among these, many could have been avoided or solved if adequate care had been provided in a timely manner. In these cases, telemedicine can assist in solving the problems of many ophthalmological conditions by providing support, performing screening, telediagnosis or supervision of distant appointments. The use of telemedicine for eye health is well established for some eye diseases, such as diabetic retinopathy, macular diseases and strabismus, however, there is a lack of information on diagnostic accuracy for other ophthalmological pathologies prevalent in the world population, such as refractive errors. To evaluate the reliability of the diagnosis made through teleophthalmology, using the ophthalmologist’s face-to-face diagnosis as the gold standard.

Methods

A diagnostic accuracy study was carried out, with 216 patients assessed by the TeleOftalmo project who underwent eye examinations both on-site and through telemedicine. The patients underwent refraction tests, intraocular pressure measurement, photodocumentation in the slit-lamp and subjective refraction using the visual acuity screen and the digital refractor.

Results

The conditions evaluated were refractive errors, cataracts, diabetic retinopathy and suspected glaucoma. Kappa values, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Approximately, 61.6% of the sample were women, with mean age of 47 years old. Kappa values show strong reliability regarding the diagnosis of cataracts (k = 0.86) and diabetic retinopathy (k = 0.79). Regarding refractive errors and suspected glaucoma, the kappa values were considered moderate (k = 0.598 and 0.478, respectively).

Conclusion

The use of telemedicine has shown favorable results regarding the diagnosis of refractive errors, cataracts and diabetic retinopathy, as well as moderate reliability for suspected glaucoma.
Elevated Pre-Treatment Systemic Immuno-Inflammatory Indices, Triple-Negative Breast Cancer, and p53 Mutation are Associated with Early-Onset Breast Cancer in Southern Nigeria
Authors: Okoye Jude Ogechukwu , Samuel Dorcas Onyeka , Ezidiegwu Kosisochukwu Stephanie , Chiemeka Michael Emeka
Published: November 2023

Background

In West Africa, breast cancer (BC) patients have a mortality rate that is three times higher than those in North America and Northwestern Europe. This study aimed to identify high-risk patients by evaluating the pre-treatment systemic inflammatory indices, p53, and BRCA2 expressions in molecular sub-types of BC in West Africa.

Methods

This retrospective cohort study included 152 BC tissues, diagnosed between January 2017 and December 2022. The tissue sections were immunohistochemically stained for p53, BRCA2, hormone receptors, and human epidermal growth factor receptor 2 (HER2), scored, and analyzed accordingly. Statistical significance was set at p≤ 0.05.

Results

The frequency of early-onset BC (≤ 49 years) was 58.6% while the frequency of early-onset BC among patients with a family history of cancer was 76.5%. The frequency of late-stage BC was 84.9%. The frequency of luminal A and triple-negative BC (TNBC) was 1.7 times higher in early-onset BC. In comparison, the frequency of Luminal B/B-like and HER2-enriched BC was 1.9 times higher in late-onset BC (p= 0.022). The frequency of p53 and BRCA2 mutation was 1.6 times and 1.2 times higher in early-onset BC than in late-onset BC (p= 0.003 and p= 0.843, respectively). Significant differences in pre-treatment systemic inflammatory index were observed between patients with early-onset and late-onset BC, and ≤ 6 months survival and > 12 months survival (p< 0.05).

Conclusion

This study found a high incidence of early-onset BC, p53 mutation, and TNBC. Additionally, it suggests that pre-treatment systemic inflammatory indices can identify high-mortality-risk patients and early-onset BC.
Associations between D3Cr muscle mass and MR thigh muscle volume with strength, power, physical performance, fitness, and limitations in older adults in the SOMMA study
Authors: Cawthon Peggy M. , Blackwell Terri L. , Kritchevsky Stephen B. , Newman Anne B. , Hepple Russell T. , Coen Paul M. , Goodpaster Bret H. , Duchowny Kate , Hetherington-Rauth Megan , Mau Theresa , Shankaran Mahalakshmi , Hellerstein Marc , Evans William J. , Cummings Steven R.
Published: November 2023

Background

Different measures to assess muscle size - magnetic resonance (MR) derived thigh muscle volume and d3-creatine dilution derived muscle mass (D3Cr muscle mass) – may have similar associations with strength, power, physical performance, fitness, and functional limitations in older adults.

Methods

Men (N=345) and women (N=482) aged ≥70 years from the Study of Muscle, Mobility and Aging completed exams including leg extension strength (1-repetition max) and cardiopulmonary exercise testing to assess fitness (VO2peak). Correlations and adjusted regression models stratified by sex were used to assess the association between muscle size measures and study outcomes; we tested for sex interactions.

Results

D3Cr muscle mass and MR thigh muscle volume were correlated (men: r=0.62, women: r=0.51, p<.001). Lower D3Cr muscle mass and lower MR thigh muscle volume were associated with lower strength and lower VO2peak in both men and women; D3Cr muscle mass was more strongly associated with strength in men than in women (p-int<0.05). There were correlations, though less consistent, between muscle size or mass with physical performance and function. Associations between the muscle size measures and the study outcomes occasionally varied by sex, and associations of MR thigh muscle volume were, at times, slightly more strongly associated with the study outcomes than was D3Cr muscle mass.

Conclusions

Less muscle –measured by either D3Cr muscle mass or MR thigh muscle volume - was associated with lower strength and worse performance. Varied associations by sex and assessment method suggest consideration be given to which measurement to use in future studies.
Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension
Authors: Ahmad Sarfaraz , Deep Gagan , Punzi Henry A , Su Yixin , Singh Sangeeta , Kumar Ashish , Mishra Shalini , Saha Amit K , Wright Kendra N , VonCannon Jessica L , Dell’Italia Louis J , Meredith Wayne J , Ferrario Carlos M
Published: November 2023

BACKGROUND

Extracellular vesicles (EVs) have emerged as a promising liquid biopsy for various diseases. For the first time, using plasma and urinary EVs, we assessed the activity of renin-angiotensin system (RAS), a central regulator of renal, cardiac, and vascular physiology, in patients with control (Group I) or uncontrolled (Group II) primary hypertension.

METHODS

EVs were isolated from 34 patients with history of hypertension, and characterized for size and concentration by nanoparticle tracking analyses, exosomal biomarkers by immunogold labeling coupled with transmission electron microscopy, flow cytometry and immunoblotting. EVs were analyzed for the hydrolytic activity of chymase, angiotensin converting enzyme (ACE), ACE2, and neprilysin (NEP) by HPLC.

RESULTS

Plasma and urinary EVs were enriched for small EVs and expressed exosomal markers (CD63, CD9, and CD81). The size of urinary EVs (but not plasma EVs) was significantly larger in Group II compared to Group I. Differential activity of RAS enzymes was observed, with significantly higher chymase activity compared to ACE, ACE2, and NEP in plasma EVs. Similarly, urinary EVs exhibited higher chymase and NEP activity compared to ACE and ACE2 activity. Importantly, compared to Group I, significantly higher chymase activity was observed in urinary EVs (p = 0.03) from Group II, while no significant difference in activity was observed for other RAS enzymes.

CONCLUSIONS

Bioactive RAS enzymes are present in plasma and urinary EVs. Detecting chymase in plasma and urinary EVs uncovers a novel mechanism of angiotensin II-forming enzyme and could also mediate cell-cell communication and modulate signaling pathways in recipient cells.

GRAPHICAL ABSTRACT
Boston criteria v2.0 for cerebral amyloid angiopathy without hemorrhage: An MRI-neuropathological validation study
Authors: Switzer Aaron , Charidimou Antreas , McCarter Stuart J. , Vemuri Prashanthi , Nguyen Aivi , Przybelski Scott A. , Lesnick Timothy G. , Rabinstein Alejandro A. , Brown Robert D. , Knopman David S. , Petersen Ronald C. , Jack Clifford R. , Reichard R. Ross , Graff-Radford Jonathan
Published: November 2023

BACKGROUND

Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without intracerebral hemorrhage (ICH) or transient focal neurological episodes (TFNE) is unknown. We assessed the diagnostic performance of the Boston criteria version 2.0 for CAA diagnosis in a cohort of individuals presenting without symptomatic ICH.

METHODS

Fifty-four participants from the Mayo Clinic Study of Aging or Alzheimer’s Disease Research Center were included if they had an antemortem MRI with gradient-recall echo sequences and a brain autopsy with CAA evaluation. Performance of the Boston criteria v2.0 was compared to v1.5 using histopathologically verified CAA as the reference standard.

RESULTS

Median age at MRI was 75 years (IQR 65-80) with 28/54 participants having histopathologically verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95%CI: 13.2-48.7%) and 65.3% (95%CI: 44.3-82.8%) for probable CAA diagnosis (AUC 0.47) and 75.0% (55.1-89.3) and 38.5% (20.2-59.4) for any CAA diagnosis (possible + probable; AUC: 0.57), respectively. The v2.0 Boston criteria was not superior in performance compared to the prior v1.5 criteria for either CAA diagnostic category.

CONCLUSIONS

The Boston criteria v2.0 have low accuracy in patients who are asymptomatic or only have cognitive symptoms.. Additional biomarkers need to be explored to optimize CAA diagnosis in this population.
Ecological interactions between host, commensal and pathogenic bacteria in models for the intestinal epithelium
Authors: Nanlohy Nening M. , Johannesson Nina , Wijnands Lucas , Arroyo Laura , de Wit Jelle , den Hartog Gerco , Wolthers Katja C. , Sridhar Adithya , Fuentes Susana
Published: November 2023

Gut host physiology and the microbiome intricately interact in the complex ecosystem of the human digestive tract, playing a crucial role in maintaining overall health. In recent decades, the role of the gut microbiota in the defence against pathogens and modulating local and distal immunity has been well-established. The interactions between commensal and potential pathogenic bacteria with the intestinal epithelium can initiate immune responses in the epithelial cells, which, in turn, activate downstream immune responses in other immune cells. These intricate processes involved, especially when multiple microorganisms are present as seen in the intestinal microbiome, remain only partially understood. Previously, it was observed that in adults aged 60 years or older, the commensalRuminococcus torques(Rt) andEscherichia coliwere associated with influenza-like illness and a heightened pro-inflammatory immune profile. In this study, we used a CaCo-2 cell-based model and a human intestinal enteroid (HIE) model to explore epithelial responses to Rt and an adherent invasiveE. coli(AIEC) both individually and in co-cultures under anaerobic conditions. Additionally, CaCo-2 cells were co-cultured with peripheral blood mononuclear cells, revealing downstream activation of immune cells. While both systems showed comparable cytokine profiles, they differed in their responses to the different bacteria, with the organoid system being more representative for intestinal epithelial cells in humans. We provide mechanistic evidence of the pro-inflammatory responses associated with these bacteria in the intestinal ecosystem. These models, particularly in the context of combined infections, represent a valuable and promising avenue for future research. They contribute to a deeper understanding of the complex interactions between the gut microbiota, epithelial intestinal cells and immune cells in the gut ecosystem, thereby promoting advances in the field of gut health and host response.
Global distribution and diversity of marine Parmales
Authors: Ban Hiroki , Endo Hisashi ,   The EukBank Team, Kuwata Akira , Ogata Hiroyuki
Published: November 2023

Parmales (Bolidophyceae) is a minor eukaryotic phytoplankton group, sister to diatoms, that exists as two distinct forms of unicellular organisms: silicified cells and naked flagellates. Since their discovery, many field studies of Parmales have been performed, but their global distribution remains under-investigated. Here, we compile over 3,000 marine DNA metabarcoding datasets targeting the V4 region of the 18S rRNA gene from the EukBank database. By linking this large dataset with the latest morphological and genetic information, we provide updated estimates on the diversity and distribution of Parmales in the global ocean at a fine taxonomic resolution. Parmalean amplicon sequence variants (ASVs) were detected in nearly 90% of the analyzed samples. However, the relative abundance of parmaleans in the eukaryotic community is less than 0.2% on average, and the estimated true richness of parmalean ASVs is about 316 ASVs, confirming their low abundance and low diversity. Phylogenetic analysis clearly divides these algae into four clades, and three known morphotypes of silicified cells were classified into three different clades. The abundance of Parmales is generally high in the pole and decreases toward the tropics, and individual clades/subclades show further distinctions in distributions. Overall, our results suggest their clade/subclade-specific adaptation to different ecological niches.
Identification of A Potential Inhibitor for Anticancer Target MTHFD2 by Consensus Docking and Molecular Dynamics
Authors: Zhou Huiyuan , Hong Yebin , Beckford Floyd A.
Published: November 2023

The bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) has been recognized as a promising anticancer drug target because it is overexpressed in various types of cancer and is associated with poor prognosis. In the present study, we aimed to discover potential inhibitors from the Enamine HTS library which consists of over one million compounds. A consensus docking-based virtual screening workflow was adopted and two hits, E96 and E41, were identified for being ranked in the top 5 in all docking programs used. To validate the virtual screening result, the binding modes of the two hits were visually inspected with reference to previously published inhibitors B01 and D56, and a similar pattern of binding was observed between the hits and established ligands, indicating the reliability of the docking protocol. The subsequent molecular dynamics simulation and a series of analyses including root mean square deviation, root mean square fluctuation, and radius of gyration reveal that E96 achieved a more stable binding to the receptor than E41. The binding free energy predicted by MM/GBSA calculation confirms E96’s potential to be a potent inhibitor for the target MTHFD2 as it outperforms E41 and the established ligands. In conclusion, this computational study contributes to the drug discovery efforts for the anticancer drug target MTHFD2 by suggesting ligand E96 for further structure-based optimization andin vitro/vivoexperimental validation.
Dynamics ofTrypanosoma cruziinfection in hamsters and novel association with progressive motor dysfunction
Authors: Langston Harry , Francisco Amanda Fortes , Doidge Ciaran , Roberts Chrissy H. , Khan Archie A. , Jayawardhana Shiromani , Taylor Martin C. , Kelly John M. , Lewis Michael D.
Published: November 2023

Chagas disease is a zoonosis caused by the protozoan parasiteTrypanosoma cruzi.Clinical outcomes range from long-term asymptomatic carriage to cardiac, digestive, neurological and composite presentations that can be fatal in both acute and chronic stages of the disease. Studies ofT. cruziin animal models, principally mice, have informed our understanding of the biological basis of this variability and its relationship to infection and host response dynamics. Hamsters have higher translational value for many human infectious diseases, but they have not been well developed as models of Chagas disease. We transposed a real-time bioluminescence imaging system forT. cruziinfection from mice into female Syrian hamsters (Mesocricetus auratus). This enabled us to study chronic tissue pathology in the context of spatiotemporal infection dynamics. Acute infections were widely disseminated, whereas chronic infections were almost entirely restricted to the skin and subcutaneous adipose tissue. Neither cardiac nor digestive tract disease were reproducible features of the model. Skeletal muscle had only sporadic parasitism in the chronic phase, but nevertheless displayed significant inflammation and fibrosis, features also seen in mouse models. Whereas mice had normal locomotion, all chronically infected hamsters developed hindlimb muscle hypertonia and a gait dysfunction resembling spastic diplegia. With further development, this model may therefore prove valuable in studies of peripheral nervous system involvement in Chagas disease.
ASox2Enhancer Cluster Regulates Region-Specific Neural Fates from Mouse Embryonic Stem Cells
Authors: Tobias Ian C , Moorthy Sakthi D , Shchuka Virlana M , Langroudi Lida , Cherednychenko Mariia , Gillespie Zoe E , Duncan Andrew G , Tian Ruxiao , Gajewska Natalia A , Di Roberto Raphaël B , Mitchell Jennifer A
Published: November 2023

Embryonic development depends on spatially and temporally orchestrated gene regulatory networks. Expressed in neural stem and progenitor cells (NSPCs), the transcription factor sex-determining region Y box 2 (Sox2) is critical for embryogenesis and stem cell maintenance in neural development. WhereasSox2is regulated by a distal cluster of enhancers in embryonic stem cells (ESCs), enhancers closer to the gene have been implicated inSox2transcriptional regulation in the neural lineage. Using functional genomics data, and deletion analysis we show that a downstream enhancer cluster regulatesSox2transcription in NSPCs derived from mouse ESCs. By generating allelic mutants using CRISPR-Cas9 mediated deletions, we show that this proximal enhancer cluster, termedSox2regulatory regions 2-18 (SRR2-18), is acisregulator ofSox2transcription during neural differentiation. Transcriptome analyses demonstrate that loss of even one copy of SRR2-18 disrupts the region-specific identity of NSPCs. Biallelic deletion of thisSox2neural enhancer cluster causes reduced SOX2 protein, less frequent interaction with transcriptional machinery, and leads to perturbed chromatin accessibility genome-wide further affecting the expression of neurodevelopmental and anterior-posterior regionalization genes. Furthermore, homozygous NSPC deletants exhibit self-renewal defects and impaired differentiation into cell types found in the brain. Altogether, our data define acis-regulatory enhancer cluster controllingSox2transcription in NSPCs and highlight the sensitivity of neural differentiation processes to decreasedSox2transcription, which influences their differentiation into posterior neural fates, specifically the caudal neural tube.
Intrinsically disordered regions and RNA binding domains contribute to protein enrichment in biomolecular condensates inXenopusoocytes
Authors: O’Connell Liam C. , Johnson Victoria , Hutton Anika K. , Otis Jessica P. , Murthy Anastasia C. , Liang Mark C. , Wang Szu-Huan , Fawzi Nicolas L. , Mowry Kimberly L.
Published: November 2023

Proteins containing both intrinsically disordered regions (IDRs) and RNA binding domains (RBDs) can phase separatein vitro, forming bodies similar to cellular biomolecular condensates. However, how IDR and RBD domains contribute toin vivorecruitment of proteins to biomolecular condensates remains poorly understood. Here, we analyzed the roles of IDRs and RBDs in L-bodies, biomolecular condensates present inXenopusoocytes. We show that a cytoplasmic isoform of hnRNPAB, which contains two RBDs and an IDR, is highly enriched in L-bodies. While both of these domains contribute to hnRNPAB self-association and phase separationin vitroand mediate enrichment into L-bodies in oocytes, neither the RBDs nor the IDR replicate the localization of full-length hnRNPAB. Our results suggest a model where the additive effects of the IDR and RBDs regulate hnRNPAB partitioning into L-bodies. This model likely has widespread applications as proteins containing RBD and IDR domains are common biomolecular condensate residents.
DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2
Authors: Rezi Csenge K. , Aslanyan Mariam G. , Diwan Gaurav D. , Cheng Tao , Chamlali Mohamed , Junger Katrin , Anvarian Zeinab , Lorentzen Esben , Pauly Kleo B. , Afshar-Bahadori Yasmin , Fernandes Eduardo F. A. , Qian Feng , Tosi Sébastien , Christensen Søren T. , Pedersen Stine F. , Strømgaard Kristian , Russell Robert B. , Miner Jeffrey H. , Mahjoub Moe R. , Boldt Karsten , Roepman Ronald , Pedersen Lotte B.
Published: November 2023

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout ofDlg1in mouse kidney caused ciliary elongation and cystogenesis, and cell-based proximity labelling proteomics and fluorescence microscopy showed alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20 and polycystin-2 (PC2) were reduced in cilia of DLG1 deficient cells compared to control cells. This phenotype was recapitulatedin vivoand rescuable by re-expression of wildtype DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggested that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.
Cracking the conundrum of e-cargo logistics: curious case of LoadExx
Authors: Varghese Ann Mary , Jayanth R. Sai Shiva , Jacob Remya Tressa , Srivastava Abhishek , Pradhan Rudra Prakash
Published: November 2023

Learning outcomes

The learning outcomes of this case study are to understand the business model canvas and value propositions and apply advanced business innovation tools in electric vehicle business models; evaluate the current cargo vehicle scenarios at national and global levels and draw out the possibilities and costs for a new player; extrapolate the future scenario of the cargo economy, its electrification and positioning in a business-to-business (B2B) and business-to-customer (B2C) segment, especially for a developing economy; and improve the student’s ability to get organisational buy-in and execute new business models.

Case overview/synopsis

LoadExx is a fully electrified electric cargo service focusing on logistics in Kolkata, a metropolitan city in the eastern part of the country. The service of LoadExx commenced in January 2021 in the B2B segment after overcoming its then issues of driver hesitancy and customer anxiety and financial issues to adopt electrified cargo systems. The conundrum faced by LoadExx in its commencement thus had been solved under the able guidance of its owner Amit Arora. The case study was positioned four months after the commencement of LoadExx. To gain market power and traction, Arora and his team came up with the idea of market expansion. However, the current conundrum was whether LoadExx would enter the B2C segment in its current location or expand with the same business model to other parts of the country. The expansion was to be implemented in the immediate future to retain its rarity and reduce the imitability of the business model of LoadExx. This case study details the logistics and market operations of the cargo sector, especially electric cargo, in a developing economy, especially India. A teaching note supplementing the “Cracking the conundrum of e-cargo logistics: curious case of LoadExx” case study has been provided.

Complexity academic level

This case study is designed for undergraduate and postgraduate students and senior management professionals in executive education programmes undertaking courses in logistics management and supply chain operations and related cargo logistics courses. This case study denotes integrating key processes from end-users and gaining the trust of drivers, thereby showing the perspective of the plight and conundrums of a cargo aggregator working in the B2C segment. This case study could be used to discuss concepts related to not-for-profit firms, aggregators, policymakers and think tanks.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 9: Operations and logistics.
Quality-oriented human resource practices (QHRP), ambidextrous culture and organizational ambidexterity: a study of green agro-food companies
Authors: Moreno-Luzon Maria , Gil-Marques Maria , Lloria M. Begoña , Salas-Vallina Andres
Published: November 2023

Purpose

The purpose of this paper is to examine the effect of quality-oriented human resource practices (QHRP) on organizational ambidexterity. Furthermore, the mediating role of ambidextrous culture in the relationship between QHRP and organizational ambidexterity was assessed.

Design/methodology/approach

Drawing on data from 350 green agro-food companies with two respondents in each company, structural equation models were used.

Findings

This paper has been drawn up to provide some responses to the needs of the companies to be ambidextrous while applying QHRP. The findings show that there is a positive effect of QHRP on organizational ambidexterity. In addition, ambidextrous culture mediated the relationship between QHRP and organizational ambidexterity.

Practical implications

This research reveals key managerial aspects for QHRP implementation that facilitate firms to be more ambidextrous, and thus more efficient and innovative.

Originality/value

The authors illustrate the connection between quality-oriented human resource practices (QHRPs) and organizational ambidexterity under the dynamic capabilities theory. The findings contribute to the empirical evidence on the antecedents of organizational ambidexterity, and suggest that these specific QHRPs influence an organization's baseline beliefs and values and support the development of ambidextrous capabilities by means of an ambidextrous culture.
Toward a moral approach to stakeholder management: insights from the inclusion of marginalized stakeholders in the operations of social enterprises
Authors: Taylor Kelsey M. , Rosca Eugenia
Published: November 2023

Purpose

Previous literature on sustainable supply chain management has largely adopted an instrumental view of stakeholder management and has focused on understanding the effect of powerful stakeholders who have a more decisive influence on an organization's supply chain decisions. Social enterprises have emerged as organizations that often aim to create impact by integrating marginalized stakeholders into their operations and supply chains. This study examines the trade-offs that social enterprises experience due to their moral stance toward stakeholder engagement, evidenced in their commitment to serving marginalized stakeholders, as well as the responses adopted to these trade-offs.

Design/methodology/approach

The study follows a theory elaboration approach through a multiple case study design. The authors draw on insights from stakeholder theory and use the empirical insights to expand current constructs and relationships in a novel empirical context. Based on an in-depth analysis of primary and secondary qualitative data on ten social enterprises, the authors examine how these organizations integrate marginalized stakeholders into various roles in their operations.

Findings

When integrating marginalized customers, suppliers and employees, social enterprises face affordability, reliability and efficiency trade-offs. Each trade-off represents conflicts between the organization's needs and the needs of marginalized stakeholders. In response to these trade-offs, social enterprises choose to internalize the costs through slack creation or vertical integration or externalize the costs to stakeholders. The ability to externalize is contingent on the growth orientation of the organization and the presence of like-minded B2B (Business-to-Business) customers. These responses reflect whether organizations accept the trade-offs at the expense of one or more stakeholders or if they avoid the trade-offs and find mutually beneficial solutions.

Originality/value

Building on the empirical insights, the authors elaborate on stakeholder theory with a focus on the integration of marginalized stakeholders by emphasizing a moral justification for stakeholder engagement, identifying the nature of the underlying trade-offs which can arise when various stakeholder needs are in conflict and examining the contingencies affecting organizational responses to these trade-offs.
From fair supervisor to satisfied employee: a comparative study of six organizational justice mechanisms
Authors: Adamovic Mladen
Published: November 2023

Purpose

This research paper aims to elucidate why and how a fair supervisor influences an employee's job satisfaction. While various theoretical approaches have been explored and numerous explanatory mechanisms investigated in prior organizational justice research, it is still unclear which explanatory mechanism is the dominant one to explain fairness effects. To address this gap, the author compares six distinct explanatory mechanisms of fairness effects on job satisfaction.

Design/methodology/approach

The author conducted a three-phase survey study with 309 employees from diverse organizations. The author measured all variables twice to control for stability effects and ensure stable findings. The author combined a path analysis with bootstrapping procedures using Mplus 8.3 software.

Findings

The influence of supervisor fairness on job satisfaction is primarily transmitted through an employee's negative emotions, a mechanism often examined in previous organizational justice research adopting the moral perspective of fairness.

Practical implications

Supervisors can increase employees' satisfaction with their jobs by treating them fairly and promoting a fair work environment. To increase the benefits of workplace fairness, supervisors can focus on the intervening mechanisms, such as emotions.

Originality/value

First, the author provides a fine-grained understanding of why supervisor fairness increases job satisfaction. Second, the author clarifies how the effects of supervisor fairness are transmitted. Third, the author identifies the most critical mediator to explain how supervisor fairness affects job satisfaction.
Leaders' Machiavellianism and subordinates' task performance: a multilevel investigation
Authors: Saleem Sharjeel , Tourigny Louise , Kundi Yasir Mansoor , Raziq Muhammad Mustafa , Gohar Aqsa
Published: November 2023

Purpose

This study aims at analyzing the detrimental cross-level serial effects of leaders' Machiavellianism and abusive supervision on subordinates' burnout and task performance. The general aggression model and conservation of resources theory guide our research model.

Design/methodology/approach

The authors developed a multilevel design and used multisource data. The authors collected data from 50 bank branches located in Pakistan. A total of 50 branch supervisors participated, which yielded 200 supervisor-subordinate dyads. Machiavellianism was self-assessed by the supervisors who further rated the specific task performance of each of their respective subordinates. Burnout and abusive supervision ratings were provided by the subordinates. Abusive supervision scores were aggregated at the group level.

Findings

Machiavellianism has an indirect negative effect on individual-level task performance through the serial cross-level mediating effects of abusive supervision at the group level and attendant individual-level burnout.

Practical implications

Findings provide practical implications for the management of task performance and human resources.

Originality/value

This study offers a comprehensive cross-level model to analyze the effect of Machiavellianism on group-level and individual-level outcomes known to affect the effectiveness of leaders.
Biomarkers of immediate drug hypersensitivity
Authors: Mayorga Cristobalina , Ariza Adriana , Muñoz‐Cano Rosa , Sabato Vito , Doña Inmaculada , Torres Maria J.
Published: November 2023

Immediate drug hypersensitivity reactions (IDHRs) are a burden for patients and the health systems. This problem increases when taking into account that only a small proportion of patients initially labelled as allergic are finally confirmed after an allergological workup. The diverse nature of drugs involved will imply different interactions with the immunological system. Therefore, IDHRs can be produced by a wide array of mechanisms mediated by the drug interaction with specific antibodies or directly on effector target cells. These heterogeneous mechanisms imply an enhanced complexity for an accurate diagnosis and the identification of the phenotype and endotype at early stages of the reaction is of vital importance. Currently, several endophenotypic categories (type I IgE/non‐IgE, cytokine release, Mast‐related G‐protein coupled receptor X2 (MRGPRX2) or Cyclooxygenase‐1 (COX‐1) inhibition and their associated biomarkers have been proposed. A precise knowledge of endotypes will permit to discriminate patients within the same phenotype, which is crucial in order to personalise diagnosis, future treatment and prevention to improve the patient's quality of life.
Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study
Authors: Maddaloni Chiara , De Rose Domenico Umberto , Perulli Marco , Martini Ludovica , Bersani Iliana , Campi Francesca , Savarese Immacolata , Dotta Andrea , Ronchetti Maria Paola , Auriti Cinzia
Published: November 2023

Aim

To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls.

Methods

In this prospective study, we enrolled 25 uninfected full‐term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points.

Results

In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut‐off but not those of presepsin.

Conclusion

In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.
Rationale and design of a multicenter, randomized phase II trial of durvalumab with or without multitarget tyrosine kinase inhibitor as maintenance treatment in extensive‐stage small‐cell lung cancer patients (DURABLE study)
Authors: Zhang Bo , Zhong Hua , Shi Chunlei , Gao Zhiqiang , Zhong Runbo , Gu Aiqin , Wang Weimin , Chu Tianqing , Xiong Liwen , Zhang Wei , Wang Huimin , Zhang Xueyan , Han Baohui
Published: November 2023

Introduction

Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients.

Methods

This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Discussion

We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients.
Wirkweise, Indikationen und Therapieempfehlungen der extrakorporalen Photopherese (ECP)
Authors: Cho Ara , Paulitschke Verena , Knobler Robert
Published: November 2023

Die extrakorporale Photopherese (ECP) hat in jüngster Zeit bei der Behandlung verschiedener Krankheiten an Bedeutung gewonnen. Ursprünglich als neue Therapie zur Behandlung von Patienten mit kutanem T‐Zell‐Lymphom vorgestellt, hat sich der Indikationsbereich für die ECP auf Hämatologie und Transplantationsimmunologie erweitert. Die ECP hat ihren festen Platz im Therapieplan bei kutanen T‐Zell‐Lymphomen, systemischer Sklerose, Graft‐versus‐Host‐Erkrankung, Organtransplantationen wie Herz und Lunge, teilweise als Erstlinientherapie und sehr häufig in Kombination mit verschiedenen systemischen immunsuppressiven Therapien. Das Verfahren besteht im Wesentlichen aus drei Schritten: Leukapherese, Photoaktivierung und Reinfusion. Im folgenden Artikel werden die noch nicht vollständig verstandenen Wirkmechanismen dargestellt, die fünf häufigsten Indikationen für die Behandlung mit ECP diskutiert und Therapieempfehlungen für die jeweilige Indikation gegeben.
Einsatz künstlicher Intelligenz mittels Deep Learning in der dermatopathologischen Routinediagnostik des Basalzellkarzinoms
Authors: Duschner Nicole , Baguer Daniel Otero , Schmidt Maximilian , Griewank Klaus Georg , Hadaschik Eva , Hetzer Sonja , Wiepjes Bettina , Le'Clerc Arrastia Jean , Jansen Philipp , Maass Peter , Schaller Jörg
Published: November 2023

Hintergrund

Dermatopathologische Institute stehen aufgrund immer höherer Anforderungen bei andererseits schwindenden Ressourcen vor zunehmenden Herausforderungen. Basalzellkarzinome stellen einen Großteil des Einsendeguts mit entsprechendem Arbeitsaufwand dar. Gleichzeitig ermöglicht die Digitalisierung von Glasobjektträgern den Einsatz künstlicher Intelligenz (KI)‐basierter Verfahren in der Dermatopathologie. Bislang haben diese Verfahren keinen Einzug in die Routinediagnostik gefunden. Ziel dieser Studie war daher, den Einsatz eines KI‐basierten Modells zur automatisierten Basalzellkarzinom‐Erkennung zu etablieren.

Patienten und Methodik

In drei dermatopathologischen Zentren wurden während des täglichen Routinebetriebs Basalzellkarzinom‐Fälle digitalisiert und sowohl klassisch am Mikroskop als auch mittels KI‐basierter Methodik basierend auf neuronalen Netzen mit U‐Net‐Architektur befundet.

Ergebnisse

Im Routinebetrieb erzielte das Modell eine Sensitivität von 98,23 % und eine Spezifität von 98,51 % (Zentrum 1). Das Modell konnte übergangslos in den anderen Zentren Einsatz finden und erreichte ähnlich hohe Genauigkeiten in der Basalzellkarzinom‐Erkennung (Sensitivität von 97,67 % beziehungsweise 98,57 %, Spezifität von 96,77 % beziehungsweise 98,73 %). Zusätzlich wurden eine automatisierte, KI‐basierte Basalzellkarzinom‐Subtypisierung und Tumordickenmessung etabliert.

Schlussfolgerungen

KI‐basierte Verfahren können mit einer hohen Genauigkeit im Routinebetrieb Basalzellkarzinome erkennen und signifikant die dermatopathologische Arbeit unterstützen.
Management der Psoriasisarthritis durch Dermatologen – eine deutschlandweite Umfrage
Authors: König Anke , Hofmann Matthias , Kaufmann Roland , Müller‐Stahl Jutta , Pinter Andreas
Published: November 2023

Hintergrund und Zielsetzung

Die Psoriasisarthritis (PsA) erfordert für bestmögliche therapeutische Ergebnisse eine frühzeitige Diagnose und den Einsatz adäquater antirheumatischer Therapien sowie der regelmäßigen Überprüfung des Therapieerfolges. Ziel dieser Studie war es, die routinemäßigen Überwachungsmaßnahmen für Patienten mit gesicherter PsA und Psoriasis vulgaris (PsO) durch Dermatologen zu untersuchen und Daten zu generieren, wie die Bedingungen für ein optimales Therapiemanagement bei Dermatologen sichergestellt werden können.

Patienten und Methodik

Diese nichtinterventionelle, prospektive, epidemiologische Querschnittsstudie (2016–2019) umfasste Patienten mit bestätigter PsA, die sich bei einem Dermatologen in Behandlung befanden. Für Zentrums‐ und Patientencharakteristika sowie die Daten zur PsA‐Überwachung und ‐Behandlung, stratifiziert nach verschiedenen Zentrumsarten, wurden deskriptive statistische Analysen durchgeführt.

Ergebnisse

212 Patienten von 34 niedergelassenen Ärzten, 5 nichtuniversitären Krankenhäusern und 9 Universitätskliniken wurden eingeschlossen. Die Mehrheit der PsA‐Patienten wurde von Rheumatologen (> 55% in jedem Zentrumstyp) in einem frühen oder mittleren Stadium (> 59%) diagnostiziert. Die Behandlung der PsA wurde hingegen am häufigsten von Dermatologen eingeleitet (niedergelassene Ärzte: 69,6%, Krankenhäuser: 60,9%, Universitätskliniken: 82.9%). In Universitätskliniken wurden die Patienten häufiger mit Biologika behandelt (alleinige Therapie: 43,9%, in Kombination mit weiteren systemischen Therapien: 26,8%) als bei niedergelassenen Ärzten (alleinige Therapie: 44,6%, Kombinationstherapie: 13,5%) und in nichtuniversitären Krankenhäusern (alleinige Therapie: 34,8%, Kombination: 8,7%).

Schlussfolgerungen

Da die PsA‐Diagnose am häufigsten von Rheumatologen gestellt wurde, während hingegen die Behandlung von mild bis moderater PsA hauptsächlich von Dermatologen eingeleitet wird, ist eine optimale Zusammenarbeit zwischen diesen Fachärzten von entscheidender Bedeutung.