bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction
Authors: Krogsaeter Einar K. , McKetney Justin , Marquez Angelica , Cakir Zeynep , Stevenson Erica , Jang Gwendolyn M. , Rao Antara , Zhou Anton , Huang Yadong , Krogan Nevan J. , Swaney Danielle L. 
Published: October 2023

SummaryApoE4 is the primary risk factor for Alzheimer’s Disease. While apoE is primarily expressed by astrocytes, AD pathology including endosomal abnormalities and mitochondrial dysfunction first occurs in neurons. Lysosomes are poised at the convergence point between these features. We find that apoE4-expressing cells exhibit lysosomal alkalinization, reduced lysosomal proteolysis, and impaired mitophagy. To identify driving factors for this lysosomal dysfunction, we performed quantitative lysosomal proteome profiling. This revealed that apoE4 expression results in lysosomal depletion of Lgals3bp and accumulation of Tmed5 in both Neuro-2a cells and postmitotic human neurons. Modulating the expression of both proteins affected lysosomal function, with Tmed5 knockdown rescuing lysosomal alkalinization in apoE4 cells, and Lgals3bp knockdown causing lysosomal alkalinization and reduced lysosomal density in apoE3 cells. Taken together, our work reveals that apoE4 exerts gain-of-toxicity by alkalinizing the lysosomal lumen, pinpointing lysosomal Tmed5 accumulation and Lgals3bp depletion as apoE4-associated drivers for this phenotype.
Loss of STIM2 in colorectal cancer drives growth and metastasis through metabolic reprogramming and PERK-ATF4 endoplasmic reticulum stress pathway
Authors: Pathak Trayambak , Benson J. Cory , Johnson Martin T. , Xin Ping , Abdelnaby Ahmed Emam , Walter Vonn , Koltun Walter A. , Yochum Gregory S. , Hempel Nadine , Trebak Mohamed 
Published: October 2023

AbstractThe endoplasmic reticulum (ER) stores large amounts of calcium (Ca2+), and the controlled release of ER Ca2+regulates a myriad of cellular functions. Although altered ER Ca2+homeostasis is known to induce ER stress, the mechanisms by which ER Ca2+imbalance activate ER stress pathways are poorly understood. Stromal-interacting molecules STIM1 and STIM2 are two structurally homologous ER-resident Ca2+sensors that synergistically regulate Ca2+influx into the cytosol through Orai Ca2+channels for subsequent signaling to transcription and ER Ca2+refilling. Here, we demonstrate that reduced STIM2, but not STIM1, in colorectal cancer (CRC) is associated with poor patient prognosis. Loss of STIM2 causes SERCA2-dependent increase in ER Ca2+, increased protein translation and transcriptional and metabolic rewiring supporting increased tumor size, invasion, and metastasis. Mechanistically, STIM2 loss activates cMyc and the PERK/ATF4 branch of ER stress in an Orai-independent manner. Therefore, STIM2 and PERK/ATF4 could be exploited for prognosis or in targeted therapies to inhibit CRC tumor growth and metastasis.HighlightsSTIM2 regulates ER Ca2+homeostasis independently of Orai and SOCE.STIM2 downregulation in colorectal cancer cells causes enhanced ER Ca2+and is associated with poor patient prognosis.STIM2 downregulation induces PERK/ATF4 dependent ER stress in colorectal cancer.Increased ER stress drives colorectal cancer metabolic reprogramming, growth, and metastasis.
A novel iPSC model reveals selective vulnerability of neurons in Multiple Sulfatase Deficiency
Authors: Pham Vi , Finoti Livia Sertori , Cassidy Margaret M. , Maguire Jean Ann , Gagne Alyssa L. , Waxman Elisa A. , French Deborah L. , King Kaitlyn , Wongkittichotee Parith , Hong Xinying , Schlotawa Lars , Davidson Beverly L. , Ahrens-Nicklas Rebecca C. 
Published: October 2023

AbstractMultiple sulfatase deficiency (MSD) is an ultra-rare, inherited lysosomal storage disease caused by mutations in the gene sulfatase modifying factor 1 (SUMF1). MSD is characterized by the functional deficiency of all sulfatase enzymes, leading to the storage of sulfated substrates including glycosaminoglycans (GAGs), sulfolipids, and steroid sulfates. Patients with MSD experience severe neurological impairment, hearing loss, organomegaly, corneal clouding, cardiac valve disease, dysostosis multiplex, contractures, and ichthyosis. Here, we generated a novel human model of MSD by reprogramming patient peripheral blood mononuclear cells to establish an MSD iPSC line (SUMF1p.A279V). We also generated an isogenic control iPSC line by correcting the pathogenic variant with CRISPR/Cas9 gene editing. We successfully differentiated these iPSC lines into neural progenitor cells (NPCs) and NGN2-induced neurons (NGN2-iN) to model the neuropathology of MSD. Mature neuronal cells exhibited decreasedSUMF1gene expression, increased lysosomal stress, impaired neurite outgrowth and maturation, reduced sulfatase activities, and GAG accumulation. Interestingly, MSD iPSCs and NPCs did not exhibit as severe of phenotypes, suggesting that as neurons differentiate and mature, they become more vulnerable to loss ofSUMF1. In summary, we demonstrate that this human iPSC-derived neuronal model recapitulates the cellular and biochemical features of MSD. These cell models can be used as tools to further elucidate the mechanisms of MSD pathology and for the development of therapeutics.
Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer’s Disease
Authors: Kallweit Lena , Hamlett Eric D. , Saternos Hannah , Gilmore Anah , Granholm Ann-Charlotte , Horowitz Scott 
Published: October 2023

ABSTRACTINTRODUCTIONAs the world population ages, new molecular targets in aging and Alzheimer’s Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored.METHODSIn this study, we examined human hippocampalpostmortemtissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.RESULTSWe found that rG4 immunostaining strongly increased in the hippocampus with both age and with AD severity. We further found that neurons with accumulation of phospho-tau immunostaining contained rG4s, that rG4 structure can drive tau aggregation, and that rG4 staining density depended on APOE genotype in the human tissue examined.DISCUSSIONCombined with previous studies showing the dependence of rG4 structure on stress and the extreme power of rG4s at oligomerizing proteins, we propose a model of neurodegeneration in which chronic rG4 formation is linked to proteostasis collapse. These morphological findings suggest that further investigation of RNA structure in neurodegeneration is a critical avenue for future treatments and diagnoses.
Investigating the recovery of community events in Scotland, post-COVID-19
Authors: Davies Nick , Robbins Lindsay , Baxter Daniel , Viol Maren , Graham Alannah , Halas Aleksandra 
Published: October 2023

PurposeCommunity events are significant for building community identity and cohesion. During 2020–2021, events largely halted due to coronavirus disease 2019 (COVID-19) and many communities lacked the capacity to recover their events quickly, in comparison to larger more well-resourced events. The study aims to understand and learn from the experiences of Scottish community event practitioners' during the disruption and recovery period for their events.Design/methodology/approachA targeted qualitative questionnaire elicited open-ended responses from people involved in the management and operation of community events in Scotland. Focus groups were also conducted with relevant practitioners to further elicit data.FindingsFour key themes emerged as follows: (1) COVID-19 fractured stakeholder networks and impacted the ability of community events to operate. Practices adapted to incorporate virtual events. (2) Events were considered as important for place-building and wider collective community benefits. This was brought more into focus for practitioners as a result of the pandemic. (3) Local authorities were variable in the level and support they gave community events. (4) Some positive changes were enforced through COVID-19, such as collaboration between small event collectives that can build resilience for community events in the future.Originality/valueThe research provides an analysis of community events, which are often small-scale, diverse, local, unique to destinations and under-researched compared to large events. It particularly builds understanding of their resilience to sectoral disruption, through the lens of recovery from the COVID-19 pandemic, an extraordinary disruptive event. This paper provides practical strategies for community actors and local authorities to improve event delivery and leverage community events as place-builders.
Lean Six Sigma and quality performance in Italian public and private hospitals: a gender perspective
Authors: Ciasullo Maria Vincenza , Douglas Alexander , Romeo Emilia , Capolupo Nicola 
Published: October 2023

PurposeLean Six Sigma in public and private healthcare organisations has received considerable attention over the last decade. Nevertheless, such process improvement methodologies are not generalizable, and their effective implementation relies on contextual variables. The purpose of this study is to explore the readiness of Italian hospitals for Lean Six Sigma and Quality Performance Improvement (LSS&QPI), with a focus on gender differences.Design/methodology/approachA survey comprising 441 healthcare professionals from public and private hospitals was conducted. Multivariate analysis of variance was used to determine the mean scores on the LSS&QPI dimensions based on hospital type, gender and their interaction.FindingsThe results showed that public healthcare professional are more aware of quality performance improvement initiatives than private healthcare professionals. Moreover, gender differences emerged according to the type of hospital, with higher awareness for men than women in public hospitals, whereas for private hospitals the opposite was true.Research limitations/implicationsThis study contributes to the Lean Six Sigma literature by focusing on the holistic assessment of LSS&QPI implementation.Practical implicationsThis study informs healthcare managers about the revolution within healthcare organisations, especially public ones. Healthcare managers should spend time understanding Lean Six Sigma as a strategic orientation to promote the “lean hospital”, improving processes and fostering patient-centredness.Originality/valueThis is a preliminary study focussing on analysing inter-relationship between perceived importance of soft readiness factors such as gender dynamics as a missing jigsaw in the current literature. In addition, the research advances a holistic assessment of LSS&QPI, which sets it apart from the studies on single initiatives that have been documented to date.
Towards a design science research (DSR) methodology for operational excellence (OPEX) initiatives
Authors: Antony Jiju , Sony Michael , Lameijer Bart , Bhat Shreeranga , Jayaraman Raja , Gutierrez Leopoldo 
Published: October 2023

PurposeDesign science research (DSR) is a structured approach for solving complex ill-structured problems in organizations through the development of an artefact followed by its validation. This paper aims to evaluate existing DSR methodology and propose specific accents to promote DSR for environmental, social and governance (ESG)-oriented operational excellence (OPEX) initiatives within organizations.Design/methodology/approachThis commentary paper is based on an abductive reasoning approach to evaluate and understand DSR and assess its effectiveness for developing solutions to typical ESG-oriented OPEX-based problems within organizations.FindingsExisting literature on DSR is reviewed, after which it is evaluated on its ability to contribute to the implementation of sustainable solutions for ESG-oriented OPEX-based problems. Based on the review, specific DSR methodological accents are proposed for the development of ESG-oriented OPEX-based solutions in organizations.Research limitations/implicationsThis conceptual paper contributes to the conceptual understanding of the applicability, limitations and contextual preconditions for applying DSR. This paper proposes an explicit and, in some ways, alternative view on DSR research for OPEX researchers to apply and further the body of knowledge on matters of sustainability (ESG) in operations management.Practical implicationsCurrently, there is limited understanding and application of the DSR methodology for OPEX-based problem-solving initiatives, as appears in the scant literature on DSR applied for the implementation of OPEX based initiatives for ESG purposes. This paper aims to challenge and provide accents for DSR applied to OPEX-related problems by means of a DSR framework and thereby promotes intervention-based studies among researchers.Originality/valueThe proposed step-by-step methodology contains novel elements and is expected to be of help for OPEX-oriented academicians and practitioners in implementing DSR methodology for practical related problems which need research interventions from academics from Higher Education Institutions.
Negative density‐regulated contest performance promotes conflict resolution in a tree lizard
Authors: Hsu Jung‐Ya , Chou Chun‐Chia , Liao Chen‐Pan , Lin Jhan‐Wei , Cheng Ren‐Chung , Huang Wen‐San 
Published: October 2023

Abstract

Territoriality is a behavioural adaptation resulting from intraspecific competition and reflects the strategy of how individuals share limited resources in the environment. As a consequence, territorial contests and levels of aggressiveness are strongly influenced by population density.

The positive relationship between population density and the intensity of intraspecific competition may appear straightforward. However, empirical evidence regarding this association remains inconclusive. This ambiguity may be attributed to studies that have predominantly focussed on specific fight‐associated traits while overlooking potential interactions between multiple phenotypic characteristics and population dynamics.

To examine the effects of population density and other ecological factors on the variation in fight behaviour as well as fight‐associated morphology and performance. We conducted population surveys and behavioural experiments using the Swinhoe's tree lizard across eight populations.

Our findings revealed that males from higher density populations tended to engage in less intense fights and exhibited a weaker resident advantage in fights, which coincided with our findings on lower rates of injuries, weaker bite forces and smaller body sizes (and vice versa). Male‐specific variation in fight behaviour, morphology and performance along a density gradient suggests different evolutionary equilibria in territoriality influenced by local costs and benefits.

Our study supports the significant role of negative density dependence as a fundamental regulator of eco‐evolutionary dynamics. The observed phenotypic variation emphasizes the importance of ecological and social factors in shaping ontogenetic growth and life‐history strategies. Our findings provide a basis for future investigations into pace‐of‐life syndromes and shed light on how phenotypic adaptation may shape population structure.

Read the free Plain Language Summary for this article on the Journal blog.
Going the Extra Mile, Now or After a While: The Impact of Employee Proactivity in Retail Service Encounters on Customers’ Shopping Responses
Authors: Otterbring Tobias , Arsenovic Jasenko , Samuelsson Peter , Malodia Suresh , Dhir Amandeep 
Published: October 2023

AbstractEmployee proactivity has been discussed as a key predictor of firm success and organizational performance. However, previous proactivity research has rarely focused on customers, and the few available proactivity studies from retail settings are either cross‐sectional, solely based on subjective outcomes (e.g. customer satisfaction) or restricted to aggregated data of objective outcomes (e.g. profits per store). We investigate the causal effect of employee proactivity in retail service encounters on customers’ actual purchase behaviour and satisfaction ratings at the fine‐grained level of individual customers. By integrating theories on social perception with prior proactivity findings, we find that employee proactivity positively predicts customers’ shopping responses. This finding extends from correlational to experimental designs across sample types and paradigms, is replicated in actual retail settings, and is mediated by customers’ perceptions of employee warmth and competence. Furthermore, the effect generalizes across several focal outcomes, including behavioural variables (spending and purchase likelihood), and is moderated by the time to employee‐initiated contact in a way that goes against customers’ own beliefs. In sum, the present research quantifies the financial consequences of employee proactivity and indicates that in ordinary retail service encounters, high proactivity can compensate for delays, thus counteracting the aversive aspects of waiting.
Oil price movements and agricultural production from heterogeneous sub‐sectors: Analysing the Dutch disease in an African resource‐rich economy
Authors: Ike George N. , Usman Ojonugwa , Köksal Cihat 
Published: October 2023

AbstractThe economy of a developing country like Nigeria has evolved from a strong dependence on agricultural exports in the 1960s to an unhealthy reliance on crude oil exports. This has led to a large agricultural trade deficit that requires a better understanding of the dynamic relationship between oil price booms and agricultural production. To this end, the study not only isolates the effect of oil price movements on agricultural production from heterogeneous sub‐sectors in Nigeria but also tests for Dutch disease symptoms using annual data from 1970 to 2019. Employing the auto‐regressive distributed lag (ARDL) cointegration and dynamic simulations as well as dynamic Granger causality techniques, the study shows that in the long run, oil price booms affect the food sector and the livestock sector heterogeneously. An increase in the oil price undercuts the production performance of the food sector. Also, because of the strong linkage between domestic livestock production and the global livestock market, an increase in domestic production has a weak predictive content for oil price booms. The policy implications of these findings include the sterilization of oil revenues outside the country and collaboration with foreign investors to provide much‐needed investment in the agricultural sector through various incentive schemes.
Adherence to the Mediterranean diet is associated with a reduced DAS28 index among patients with rheumatoid arthritis: Case study from KRRD
Authors: Alawadhi Balqees , Alsaber Ahmad , Shatawan Israa , Al‐Herz Adeeba , Setiya Parul , Saleh Khulood , Al‐Awadhi Adel , Hasan Eman , Al‐Kandari Waleed , Mokaddem Khaled , Ghanem Aqeel , Attia Yousef , Hussain Mohammed , Alhadhood Naser , Ali Yaser , Tarakmeh Hoda , Aldabie Ghaydaa , AlKadi Amjad , Alhajeri Hebah , Aldei Ali 
Published: October 2023

AbstractBackgroundRheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity.ObjectiveThe present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA.MethodsAdult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross‐sectional study conducted on 754 RA patients visits aged (21–79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14‐item Questionnaire (paper or web‐based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity.ResultsThe finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28 < 3.2, DAS28 ≥ 3.2), several Mediterranean survey components showed statistically significant differences. Patients with a Mediterranean score ≤ 5 was more likely to have hazard effects for DAS28 than those with a Mediterranean score of ≥10 (HR = 0.17, CI [0.08–0.37], p < .001). The finding shows that, Mediterranean levels ≤5, on biologics treatment, CRP, and patient global assessment were significantly associated with overall survival. Additionally, the MedDiet was found to be a significant predictor of DAS28 in the random forest decision tree plot, along with tender, RF, and creatinine. MedDiet patients had a lower DAS28 score than others.ConclusionThe findings suggest that optimal drug treatment and a restrictive diet can help to improve DAS28 score for patients with RA. More patients in the cohort DAS28 <3.2 used olive oil, servings of vegetables, fruits, and legumes. In contrast, more patients in the cohort DAS28 ≥ 3.2 consumed red meat, butter, sweetened or soft drinks, cakes, cookies, or biscuits, and tomato sauce.
Rituximab induction and reinduction in granulomatosis with polyangiitis and microscopic polyangiitis: A retrospective multicenter study in Taiwan
Authors: Hsieh Tsu‐Yi , Chen Ming‐Han , Wu Chen‐Ching , Hong Wei‐Jhe , Lu Cheng‐Hsun , Lu Chun‐Chi , Lu Ling‐Ying , Hsieh Song‐Chou , Tsai Chang‐Youh , Wu Chien‐Sheng ,   for the Taiwan Vasculitis Study Group
Published: October 2023

AbstractObjectivesThis study aimed to investigate the clinical outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) under rituximab induction and reinduction therapy in Taiwan.MethodsWe performed a retrospective study in patients with GPA or MPA receiving rituximab therapy from August 2008 to July 2020 in seven medical centers in Taiwan. The clinical characteristics and outcomes of these patients were analyzed.ResultsIn total, 53 patients (18 with GPA and 35 with MPA) were included. Kidney involvement (82.9% vs. 22.2%, p < .001) and initial creatinine (3.25 ± 2.37 vs. 1.07 ± 0.82, p < .001) were significantly higher in MPA. Within 24 weeks after the first course of rituximab, there were seven deaths (five due to infection and two due to active disease) in patients with MPA (7/35, 20%) compared to 0 in patients with GPA. Of 33 patients receiving rituximab for kidney involvement, 23 survived and were free from renal replacement therapy at 24 weeks. Their chronic kidney disease (CKD) stages improved in 2 but progressed in 7, while 24 had stable CKD stages. Death or end‐stage renal disease (ESRD) was associated with infection and higher initial creatinine. Reinduction therapy for relapse was required in 18 (39.1%) of 46 survivors, which was associated with anti‐proteinase 3 (PR3) positive (odds ratio 3.667, p = .049) and younger age with a cutoff of 49.4 (AUC = 0.679, p = .030, sensitivity = 66.67%, specificity = 75%).ConclusionSignificant mortality occurred after rituximab induction, especially in patients with MPA. In survivors, age younger than 50 and anti‐PR3 positive were associated with the risk of relapse requiring reinduction.