bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractEmbryonic 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

AbstractProteins 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

SummaryPolarized 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

PurposeThe 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/approachDrawing on data from 350 green agro-food companies with two respondents in each company, structural equation models were used.FindingsThis 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 implicationsThis research reveals key managerial aspects for QHRP implementation that facilitate firms to be more ambidextrous, and thus more efficient and innovative.Originality/valueThe 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

PurposePrevious 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/approachThe 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.FindingsWhen 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/valueBuilding 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

PurposeThis 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/approachThe 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.FindingsThe 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 implicationsSupervisors 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/valueFirst, 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

PurposeThis 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/approachThe 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.FindingsMachiavellianism 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 implicationsFindings provide practical implications for the management of task performance and human resources.Originality/valueThis 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

AbstractImmediate 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

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

AbstractIntroductionDurvalumab 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.MethodsThis 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.DiscussionWe 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

ZusammenfassungDie 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

ZusammenfassungHintergrundDermatopathologische 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 MethodikIn 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.ErgebnisseIm 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.SchlussfolgerungenKI‐basierte Verfahren können mit einer hohen Genauigkeit im Routinebetrieb Basalzellkarzinome erkennen und signifikant die dermatopathologische Arbeit unterstützen.