bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia
Authors: Malyukova Alena , Lahnalampi Mari , Falqués-Costa Ton , Pölönen Petri , Sipola Mikko , Mehtonen Juha , Teppo Susanna , Viiliainen Johanna , Lohi Olli , Hagström-Andersson Anna K , Heinäniemi Merja , Sangfelt Olle 
Published: March 2023

ABSTRACTTargeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of precision therapies is limited in part because of the cellular heterogeneity of tumors. A better mechanistic understanding of how drug effect is linked to cancer cell state diversity is crucial for identifying effective combination therapies that can overcome the heterogeneity to prevent disease recurrence. Here, we characterized at the level of gene regulatory networks and at single-cell resolution the effect of G2/M cell cycle checkpoint inhibition in acute lymphoblastic leukemia (ALL) and demonstrate that WEE1 targeted therapy impinges on cell fate decision regulatory circuits. We found highest inhibition of recovery of proliferation in ALL cells with KMT2A-rearrangment (KMT2A-r), compared to cells of other leukemia subgroups. Single-cell transcriptome and chromatin accessibility profiling of (KMT2A::AFF1) RS4;11 cells treated with the WEE1 inhibitor AZD1775 revealed diversification of cell states at the fate decision points, with a fraction of cells exhibiting strong activation of p53-driven processes linked to induction of apoptosis and senescence, and disruption of a core KMT2A-RUNX1-MYC regulatory network through CDK1-mediated RUNX1 degradation. In RS4;11 cells and in patient-derived xenograft (PDX) model, we uncovered that in this cell state diversification induced by WEE1 inhibition, a subpopulation transitioned to a cell state characterized by activation of transcription factors regulating pre-B cell fate, lipid metabolism and pre-BCR signaling which supported a drug tolerance. Sequential treatment targeting the drug tolerant subpopulation with BCR-signaling inhibitors dasatinib, ibrutinib, or perturbing metabolism by fatostatin or AZD2014 after AZD1775 administration, effectively counteracted drug tolerance that drove recovery of leukemic cells. Collectively, our findings provide new insights into the tight connectivity of gene regulatory programs associated with cell cycle and cell fate regulation, and a rationale for sequential administration of WEE1 inhibitors with low toxicity inhibitors of pre-BCR signaling or metabolism.
Climbing fiber multi-innervation of mouse Purkinje dendrites with arborization common to human
Authors: Busch Silas E. , Hansel Christian 
Published: March 2023

AbstractCanonically, each Purkinje cell in the adult cerebellum receives only one climbing fiber from the inferior olive. Underlying current theories of cerebellar function is the notion that this highly conserved one-to-one relationship renders Purkinje dendrites into a single computational compartment. However, we show that multiple primary dendrites are a near-universal morphological feature in human. Using tract-tracing, immunolabeling, andin vitroelectrophysiology, we demonstrate in mice that ∼25% of mature polydendritic cells receive more than one climbing fiber input. Two-photon calcium imagingin vivoreveals that separate dendrites can exhibit distinct response properties to sensory stimulation, indicating some polydendritic cells integrate functionally independent climbing fiber receptive fields. These findings reveal that Purkinje cells are morphologically and functionally more diverse than previously thought.
Farmer's financial literacy and its determinants: evidence from South Asia
Authors: Das Soumyadwip , Maji Sumit Kumar 
Published: March 2023

PurposeThe objective of this study is to ascertain the financial literacy (FL) of the farmers in three South Asian economies (India, Bangladesh and Pakistan). Further, an effort was made to explore various demographic and socioeconomic antecedents of FL of the farmers.Design/methodology/approachThe study used secondary data of 11,025, 782 and 657 farmers from India, Bangladesh and Pakistan respectively from Financial Inclusion Insights (2017) database. “Big five” FL questions were used to measure the FL of the farmers. Appropriate statistical techniques and censored Tobit regression were used to identify the determinants of such FL.FindingsBangladeshi farmers (48.75%: Moderate) were found to exhibit greater FL as compared to Pakistani (38.96%: Poor) and Indian (32.61%: Poor) farmers. The outcome of the study revealed that the farm ownership and educational attainment of the farmers significantly determined FL of the farmers in all three Asian countries. Financial confidence and gender were observed to exacerbate a positive influence on the level of FL of farmers belonging to India and Pakistan. Age, marital status, financial inclusion and economic status were found to be the major determinants of FL of Indian farmers.Originality/valueThere is a dearth of studies in the scholarship examining the FL of farmers in both developed and developing economies. The present study makes an original contribution to the literature by unearthing FL amongst farmers and its determinants in three South Asian economies using a large sample of 12,464 farmers for the first time.Peer reviewThe peer-review history for this article is available at: https://publons.com/publon/10.1108/IJSE-12-2022-0776
The role of waste-to-energy in waste management in Egypt: a techno-economic analysis
Authors: Nassar Heba , Biltagy Marwa , Safwat Aya Mohamed 
Published: March 2023

PurposeEgypt has set plans to transform into a green economy which requires major reforms in the waste sector as one of the most vital sectors crucial for this transformation. This study aims at inspecting the current status of the Egyptian waste sector to highlight the major policy reforms needed. Furthermore, it assesses the economic viability of establishing waste-to-energy (WtE) projects under the current regulations that govern the sector.Design/methodology/approachThe study employed an inductive analytical approach to scrutinize the institutional and regulatory framework of the waste and WtE sectors. Furthermore, a novel techno-economic analysis was conducted to assess the profitability of a WtE plant that employs moving grate incineration technology.FindingsThe analysis of the waste sector revealed its deteriorating state and the dire need for immediate restructuring through more stringent regulations to establish an integrated waste management system (IWMS) that incorporates WtE technologies as well as a number of corrective actions that would help enhance the sector. Additionally, the techno-economic analysis revealed the need to amend the current WtE regulation to comprise a gate fee as an indispensable revenue stream for WtE projects.Originality/valueThis study is one of a few studies that uses a new technique of analysis to explore the potential role that WtE projects can play in Egypt as a part of an IWMS that aims at transforming the waste sector into a resource sector while providing a renewable and sustainable source of energy.
Achieving organizational performance by integrating industrial Internet of things in the SMEs: a developing country perspective
Authors: Mukherjee Subhodeep , Baral Manish Mohan , Chittipaka Venkataiah , Nagariya Ramji , Patel Bharat Singh 
Published: March 2023

PurposeThis research investigates the adoption of the industrial Internet of things (IIoT) in SMEs to achieve and increase organizational performance. With the latest technology, small and medium-sized enterprises (SMEs) can create a competitive edge in the market and better serve customers.Design/methodology/approachTwelve hypotheses are proposed for this study. This study constructed a questionnaire based on technological, organizational, environmental and human perspectives. A survey is conducted on the SMEs of India using the questionnaire.FindingsEight hypotheses were accepted, and four hypotheses were not supported. The hypotheses rejected are infrastructure, organizational readiness, internal excellence and prior experience. The findings suggested that adopting IIoT in SMEs will increase organizational performance.Research limitations/implicationsThis study will be helpful for the manager, top management and policymakers. This study identified the areas SMEs need to work on to adopt the technologies.Originality/valueIn the literature, no article considered IIoT adoption in SME firms as a human factor. Therefore, this study is unique, including human, technological, organizational and environmental factors.
Factors influencing small and medium-sized enterprise (SME) resilience during the COVID-19 outbreak
Authors: Thekkoote Ramadas 
Published: March 2023

PurposeThis research paper highlights the economic impact on small and medium-sized enterprises (SMEs) due to Coronavirus outbreaks. It proposes factors that influence the strengthening and survival of SMEs.Design/methodology/approachIn this research, resilience is reflected in the following aspects hope, problem resolution and persistence. This quantitative study analyses a purposive sample of 120 small and medium-sized firms in India. The study's primary data are the responses to questionnaires issued to respondents, analyzed and hypotheses formed and tested using the structural equation modeling (SEM) technique.FindingsThe study results show that all the variables significantly reduce the impact of COVID-19 on SMEs. The presented model is expected to help researchers, business modelers, analysts and real professionals with further studies in the SME context.Originality/valueThis new approach adds to the business resilience knowledge of SMEs and has practical implications for manufacturing organizations seeking to become robust during and after COVID-19.
Warmer and more seasonal climates reduce the effect of top‐down population control: An example with aphids and ladybirds
Authors: Ge Xuezhen , Griswold Cortland K. , Newman Jonathan A. 
Published: March 2023

Abstract

Thermal performance within predator–prey systems may have profound effects on species interactions under climate change. However, how the thermal response of predators and prey to climate change affects their interactions is still understudied.

To examine the responses of a predator–prey system to climate change, we constructed a biologically detailed stage‐structured population dynamic model using aphids (prey) and ladybirds (predator) as a model system. We explore the system's dynamics across the entire feasible parameter space of annual mean temperature and seasonality. Within this space, we explore all qualitatively possible scenarios of thermal performance mismatches to gain insight into how these affect the interacting species' responses to climatic change.

We find that, generally, warmer and less seasonal climates are the most favourable climate conditions for both species. Our results also indicate that predation always has a stronger effect on aphid abundance than the climate in tropical and subtropical regions for all the thermal performance mismatch scenarios. Furthermore, predation's (biotic) effect on prey abundance will generally decrease relative to the effect of climate (abiotic) when future climates become warmer and more seasonal.

Our research highlights that the effects of increasing seasonality are consistent with climate having a proportionally larger impact on species pairs with different thermal performances than predation.

Read the free Plain Language Summary for this article on the Journal blog.
Backloading to extinction: Coping with values conflict in the administration of Australia's federal biodiversity offset policy
Authors: Evans Megan C. 
Published: March 2023

AbstractPolicy‐makers are frequently required to consider and manage conflicting public values. An example of this in the environmental domain is biodiversity offset policy, which governments worldwide have adopted as a mechanism to balance environmental protection with socio‐economic development. However, little work has examined administrative practices underpinning biodiversity offset policy implementation, and how the adoption of coping strategies to manage value conflicts may influence resulting policy outcomes. This study fills this research gap using a case study of Australia's federal biodiversity offset policy under the Environment Protection and Biodiversity Conservation (EPBC) Act 1999. Using data from 13 interviews of federal policy administrators, I show that the introduction of a new policy in 2012 enabled a shift from the use of precedent to a technical approach for setting offset requirements under the EPBC Act. Yet, multiple sources of policy ambiguity remain, and administrators have adopted post‐approval condition‐setting, or ‘backloading’—a form of cycling, facilitated by structural separation—to defer detailed assessments of offset requirements until after biodiversity losses are approved. Backloading thus undermines the effectiveness of environmental policy and will persist as coping strategy unless policy ambiguity is reduced via legislative amendments and adequate resourcing of biodiversity conservation.Points for practitioners
Biodiversity offset policy requires administrators to manage conflicting environmental and socioeconomic values.
Technical decision tools reduce reliance on case‐by‐case decision‐making, but multiple ambiguities persist.
Backloading (post‐approval condition‐setting) defers values conflict, but reduces transparency, accountability, and policy effectiveness.
Policy ambiguity must be reduced at the political level to facilitate effective biodiversity conservation.
MOVEMENT 2. FORMALIZING ARRANGEMENTS: Re‐signification and the Making of Governable Spaces
Authors:   The Re‐Arrangements Collective, Cante Fabien , Hussain Ajmal , Makori Timo , Mohamed Surer Qassim , Osbourne Alana , Pilo’ Francesca , Ramakrishnan Kavita , Simone AbdouMaliq , Sitas Rike , Suhail Adeem 
Published: March 2023

AbstractThe second movement considers (re)arrangements as projects of formalization that seek to impose and even fix a form to spaces historically constructed as marginal. This impositional arrangement operates as a governmental desire to fix a form by re‐signifying both subjects and spaces.
IFIH1 was predicted as a key biomarker in primary Sjögren's syndrome based on transcriptome analysis and experimental verification in patients and mice
Authors: Wu Dan , Chen Liang , Wang Dandan , Wang Yuchun , Yao Genhong , Sun Lingyun 
Published: March 2023

AbstractObjectivesTo investigate the novel key genes and biological processes that may lead to primary Sjögren’ s syndrome (pSS).MethodsWe downloaded datasets about peripheral blood samples of pSS patients and healthy controls (GSE51092, GSE84844, and GSE66795) from Gene Expression Omnibus database. The weighted co‐expression network analysis and differential expression analysis first were implemented. After that, protein–protein network interaction and Support Vector Machines were applied in the meantime to take intersection for key genes. Moreover, we conducted immune cell infiltration analysis to explore the relationship between the gene expression and concentration of immune cells in peripheral blood. Lastly, the expression of key genes was verified in pSS patients and murine models by reverse‐transcription polymerase chain reaction. Meanwhile, correlation analysis of gene expression and disease activity was also performed.ResultsOnly 1 key gene, interferon induced with helicase c domain 1 (IFIH1), was identified to be both significantly up‐regulated and important for the diagnosis of pSS. The increased expression of IFIH1 in peripheral blood was confirmed in data sets, patients and non‐obese diabetic (NOD) mice. Its expression was correlated with disease activity in patients as well. In addition, the IFIH1 expression was also increased in spleen and salivary glands infiltrated with lymphocytes in NOD mice. Furthermore, immune cell infiltration analysis showed that the expression of IFIH1 was positively correlated with the proportion of memory B cells and activated dendritic cells, and negatively correlated with the proportion of macrophage M0.ConclusionsHere, bioinformatics analyses and experimental assays were performed to provide a new insight for understanding of pSS. IFIH1 may be a new diagnostic marker or therapeutic target for pSS.
Immunomodulatory properties of mesenchymal stem cells: A potential therapeutic strategy for allergic rhinitis
Authors: Wang Ming , Zhao Ning , Wang Chengshuo , Jin Zi‐Bing , Zhang Luo 
Published: March 2023

AbstractAllergic rhinitis is a highly prevalent chronic inflammatory disorder of the nasal mucosa that poses a significant burden on patients' health and quality of life. Current therapies for allergic rhinitis are unable to reinstate immune homeostasis or are restricted by specific allergens. Potential therapeutic strategies for allergic rhinitis are urgently needed. Mesenchymal stem cells (MSCs) are immune‐privileged, have strong immunomodulatory effects, and can be easily isolated from various sources. Thus, MSC‐based therapies demonstrate potential for treating inflammatory diseases. Recently, numerous studies have investigated the therapeutic effects of MSCs in animal models of allergic rhinitis. Here, we review the immunomodulatory effects and mechanisms of MSCs on allergic airway inflammation, especially allergic rhinitis, highlight the recent research regarding MSCs in the modulation of immune cells, and discuss the clinical potential of MSC‐based therapy for allergic rhinitis.
Managerial leadership behaviors: A longitudinal investigation of the role of job demands and resources, and implications for managers' own well‐being
Authors: Tóth‐Király István , Katz‐Zeitlin Ethan , Houle Simon A. , Fernet Claude , Morin Alexandre J. S. 
Published: March 2023

AbstractAlthough ample research has documented the implications, and organizational drivers, of leadership behaviors, very little research has considered these associations, and their consequences, from the perspective of managers. The present four‐wave longitudinal study addresses this limitation by focusing, using the Job Demands‐Resources model, on the work‐related drivers (job control, recognition, and workload) of transformational, transactional and laissez‐faire leadership behaviors, and the associations between these behaviors and manifestations of managers' psychological well‐being at work (job satisfaction, burnout, and turnover intentions). Analyzing data from 691 high‐level managers (i.e. school principals) using novel random intercept cross‐lagged panel model analyses, our results revealed that higher levels of job control and recognition, and lower levels of workload, predicted higher levels of transformational and transactional leadership behaviors. In contrast, laissez‐faire leadership behaviors were only negatively predicted by recognition. Transformational leadership was associated with the most desirable outcome levels (higher levels of job satisfaction, lower levels of turnover intentions and burnout), followed by transactional and laissez‐faire leadership. Most of these associations were limited to the between‐person‐level, reflecting stable mechanisms of influence, rather than at the within‐person level, suggesting the presence of homeostatic mechanism helping high levels managers to maintain a stable level of functioning over time.
Seasonality in the equatorial tropics: Flower, fruit, and leaf phenology of montane trees in the highlands of Southwest Uganda
Authors: Ssali Fredrick , Sheil Douglas 
Published: March 2023

AbstractPhenology influences many forest functions and can inform forest conservation and management, yet representative phenological data for most common tropical forest tree species remain sparse or absent. Between June 2011 and December 2013, we investigated flowering, fruiting, and leafing patterns in the Bwindi Impenetrable National Park, a montane forest located near the equator in Uganda, drawing on 16,410 observations of 530 trees of 54 species located between 2066 and 2527 m in elevation. The park's climate is equatorial with two wet and dry seasons each year. Flowering and fruiting were strongly seasonal while patterns in leafing were less pronounced. Flower occurrence peaked at the beginning of the short dry season followed by a pronounced trough during the beginning and the middle of the short wet season. Fruit occurrence had a pronounced peak during high rainfall months in March through April with most fruits ripening during drier months in May through July. Fruit scarcity was observed for a 4‐month period spanning September to December and most flushing of leaves noted at the end of the wet season in November and December. Our binomial generalized linear mixed models indicated that flowering and fruiting were negatively associated with temperature and that leafing activity was positively associated with rainfall and temperature. These findings are consistent with the insolation‐ and water‐limitation hypotheses suggesting that the seasonally varying availability of resources such as light, water, and nutrients determines these phenological patterns. Ideally, prolonged, multi‐year community‐level studies would be supported so as to better characterize the influence of climate and of climate variability.
Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID‐19
Authors: Batioglu‐Karaaltin Aysegul , Yigit Ozgur , Cakan Dogan , Akgul Ozer , Yigit Enes , Yilmaz Yetkin Zeki , Cakir Kays‐ı Burak , Ciftci Gamze , Boyoğlu Nihal Seden , Cagliyan Abdurrahman , Can Efe , Dikme Ozgur , Hacioglu Yalcin , Balkan Ilker Inanc , Enver Ozgur , Ozdogan Hasan Ahmet 
Published: March 2023

AbstractObjectiveThe present study aimed to investigate the in vivo activity of nasal irrigation (NI) with saline, NI with povidone–iodine (PVP–I) 1%, NI with a mix of hypertonic alkaline and PVP–I 1% against Severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2).DesignThis study was a prospective randomised clinical trial.SettingA multicenter study involving tertiary care centres.ParticipantsThe study included adult outpatients whose qualitative SARS‐CoV‐2 RT‐PCR tests in nasopharyngeal swabs were positive. One hundred twenty patients were divided into four equal groups. Standard COVID‐19 treatment was given to Group 1, NI containing saline was added to patients' treatment in Group 2, NI containing 1% PVP–I solution was added to patients' treatment in Group 3, and NI containing 1% PVP–I solution and the hypertonic alkaline solution was added to patients' treatment in Group 4.Main Outcome MeasuresOn the first day of diagnosis (Day 0), nasopharyngeal swab samples were taken, on the third and fifth days the nasopharyngeal viral load (NVL) reduction in quantitative RT‐PCR test was calculated.ResultsBetween the zeroth to third days and zeroth to fifth days, the NVL reduction was significant in all groups (p < .05). In paired comparisons of groups, the NVL decrease in Group 4 in the first 3 days was significantly lower than all groups (p < .05). The NVL decrease in Groups 3 and 4 in the first 5 days were significantly lower than Group 1 (p < .05).ConclusionThis study revealed that the use of NI of 1% PVP–I and the hypertonic alkaline solution mixture was more effective in reducing NVL.