bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small molecule STAT3/5 inhibitors exhibit therapeutic potential in acute myeloid leukemia and extra-nodal natural killer/T cell lymphoma
Authors: Pölöske Daniel , Sorger Helena , Schönbichler Anna , de Araujo Elvin D. , Neubauer Heidi A. , Orlova Anna , Timonen Sanna H. , Abdallah Diaaeldin I. , Ianevski Aleksandr , Kuusanmäki Heikki , Surbek Marta , Wagner Christina , Suske Tobias , Metzelder Martin L. , Bergmann Michael , Dahlhoff Maik , Grebien Florian , Fleck Roman , Pirker Christine , Berger Walter , Hadzijusufovic Emir , Sperr Wolfgang R. , Kenner Lukas , Valent Peter , Aittokallio Tero , Herling Marco , Mustjoki Satu , Gunning Patrick T. , Moriggl Richard 
Published: October 2023

AbstractThe oncogenic transcription factors STAT3, STAT5A and STAT5B are essential to steer hematopoiesis and immunity, but their enhanced expression and activation drives the development or progression of blood cancers. Current therapeutic strategies focus on blocking upstream tyrosine kinases, but frequently occurring resistance often leads to disease relapse, emphasizing the need for more targeted therapies. Here we evaluate JPX-0700 and JPX-0750, which are STAT3/5-specific covalent cysteine binders that lead to growth arrest of acute myeloid leukemia (AML) and natural killer/T cell lymphoma (NKCL) cell linesin vitroandin vivo, as well as reduce cell viability of primary AML blastsex vivo. Our non-PROTAC small molecular weight degraders selectively reduce STAT3/5 activation and total protein levels, as well as downstream target oncogene expression, exhibiting nanomolar to low micromolar efficacy. We found that both AML and NKCL cells hijack STAT3/5 signaling through either upstream activating mutations in tyrosine kinases, activating gain-of-function mutations in STAT3, mutational loss of negative STAT regulators, or genetic gains in anti-apoptotic, pro-proliferative or epigenetic-modifying STAT3/5 targets. Moreover, we have shown synergistic inhibitory action of JPX-0700 and JPX-0750 upon combinatorial use with approved chemotherapeutics (doxorubicin, daunorubicin, cytarabine), epigenetic enzyme blocker vorinostat, tyrosine kinase inhibitor cabozantinib or BCL-2 inhibitor venetoclax. Importantly, JPX-0700 or JPX-0750 treatment reduced leukemic cell growth in human AML/NKCL xenograft mouse models without adverse side effects. These potent small molecule degraders of STAT3/5 could propel further clinical development for use in AML and NKCL patients.
Longitudinal Observations of the Effects of Ischemic Stroke on Binaural Perception
Authors: Dietze Anna , Sörös Peter , Pöntynen Henri , Witt Karsten , Dietz Mathias 
Published: October 2023

AbstractAcute ischemic stroke, characterized by a localized reduction in blood flow to specific areas of the brain, has been shown to affect binaural auditory perception. In a previous study conducted during the acute phase of ischemic stroke, two tasks of binaural hearing were performed: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences (Dietze et al., 2022, Front. Neurosci. 16:1022354). Various lesion-specific, as well as individual, differences in binaural performance between patients in the acute phase of stroke and a control group were demonstrated. For the current study, we re-invited the same group of patients, whereupon a subgroup repeated the experiments during the subacute and chronic phases of stroke. Similar to the initial study, this subgroup consisted of patients with lesions in different locations, including cortical and subcortical areas. At the group level, the results from the tone-in-noise detection experiment remained consistent across the three measurement phases, as did the number of deviations from normal performance in the lateralization task. However, the performance in the lateralization task exhibited variations over time among individual patients. Some patients demonstrated improvements in their lateralization abilities, indicating recovery, whereas others’ lateralization performance deteriorated during the later stages of stroke. Notably, our analyses did not reveal consistent patterns for patients with similar lesion locations. These findings suggest that recovery processes are more individual than the acute effects of stroke on binaural perception. Individual impairments in binaural hearing abilities after the acute phase of ischemic stroke have been demonstrated and should therefore also be targeted in rehabilitation programs.
Sophocarpine inhibits TRP channels to produce anti-pruritic and analgesic effects in a mouse model of inflammatory itch and pain
Authors: Zeng Hekun , Li Peiyang , Zhou Dan , Zhang Zhe , Verkhratsky Alexei , Nie Hong 
Published: October 2023

AbstractBackground and objectiveItch, an unpleasant sensation prompting the urge to scratch, and pain, aimed at detecting potential harm through acute withdrawal or protective behaviors, are increasingly recognized as interconnected phenomena. The co-occurrence of itch and pain symptoms in various diseases impairs therapeutic efficacy and the quality of life. In this study, we investigated the potential antipruritic and analgesic effects of sophocarpine (SC), an active compound ofSophorae Flavesentis Radix, in a murine model of inflammatory itch and pain, and sought to elucidate the underlying mechanisms.MethodThe anti-pruritic and analgesic effects of three doses of SC (60 mg/kg, 30 mg/kg, 10 mg/kg) were tested by analyzing the scratching and wiping behaviors in squaric acid dibutylester (SABDE)-induced allergic contact dermatitis (ACD) mouse model accompany by itch and pain, respectively. Psoriasis area and severity index (PASI) score was used to test the anti-inflammatory effect of SC. The underlying mechanisms were studied by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Additionally, the anti-pruritic and analgesic effects of SC were further tested in mice with intradermal injection of allyl-isothiocyanate (AITC), a TRPA1 agonist, or capsaicin (CAP), a TRPV1 agonist, respectively. The relationships between SC, AITC, CAP and TRPV1, TRPA1 were simulated by molecular docking.ResultsSC treatment significantly decreased scratching bouts and wipes, as well as the PASI score. Administration of SC reduced the mRNA and protein expression of both TRPA1 and TRPV1. Moreover, pretreatment of SC decreased scratching bouts and wipes induced by AITC as well as by CAP. Molecular docking revealed potential competitive binding between SC and AITC on TRPA1, and SC and CAP on TRPV1.ConclusionWe demonstrated that SC has strong anti-pruritic and analgesic effects by targeting the TRPA1 and TRPV1 ion channels, and is a potential competitive inhibitor of TRPA1 and TRPV1. These findings suggest that SC has significant therapeutic potential in the therapy of diseases with inflammatory itch and pain.
Tracking neurons across days with high-density probes
Authors: van Beest Enny H. , Bimbard Célian , Fabre Julie M. J. , Takács Flóra , Coen Philip , Lebedeva Anna , Harris Kenneth , Carandini Matteo 
Published: October 2023

SummaryNeural activity spans multiple scales from milliseconds to months. Its evolution can be recorded with chronic electrodes, and especially with high-density arrays such as Neuropixels probes, which measure each spike at tens of sites and record hundreds of neurons. These arrays often record units with consistent spike waveforms over time, but produce vast amounts of data that require new approaches for tracking neurons across recordings. To meet this need, we developed UnitMatch, an open-access pipeline that operates after spike sorting, based only on each unit’s average spike waveform. We tested UnitMatch in Neuropixels recordings from the mouse brain, where it tracked neurons across weeks. In visual cortex, a neuron’s selectivity for visual stimuli and correlation with other neurons remained stable over days. In striatum, neuronal responses changed across days during learning of a task. UnitMatch is thus a promising tool to reveal invariance or plasticity in neural activity across days.
Surveillance and Stability of SARS-CoV-2 Wastewater Samples in Minnesota
Authors: Osborn Mark J. , Champeau Shannon , Meyer Carolyn , Hayden Mason , Landini Laura , Stark Stacey , Preeket Stephanie , Vetter Sara , Lynfield Ruth , Huff Daniel , Schacker Timothy W. , Doss Charles R. 
Published: October 2023

AbstractWastewater-based epidemiology provides an approach for assessing the prevalence of pathogens such as COVID-19 in a sewer service area. In this study, SARS-CoV-2 RNA was measured serially in 44 wastewater treatment plants of varying service capacities comprising approximately 67% of the population of Minnesota, from September 2020 through December 2022. We employed linear regression models to establish a predictive relationship between the weekly SARS-CoV-2 RNA concentrations in wastewater and clinical case counts. Metrics were assessed under specified transformation and normalization methods which we confirmed by cross-validation averaged across the enrolled treatment plants. We report that the relationship between COVID-19 incidence and SARS-CoV-2 RNA in wastewater may be treatment plant-specific. Toward establishing guidelines for pathogen surveillance, we further studied storage and time-to-analysis for RNA wastewater data and observed large effects of storage temperature, indicating that collection methods may have an important effect on the utility and validity of wastewater data for infectious disease monitoring. Our findings are additive for any large-scale wastewater surveillance program.
Generation of a porcine cell line stably expressing pig TMPRSS2 for efficient isolation of viruses from pigs with respiratory diseases
Authors: Tanaka Yuri L , Shofa Maya , Butlertanaka Erika P , Niazi Ahmad Massoud , Hirai Takuya , Mekata Hirohisa , Saito Akatsuki 
Published: October 2023

AbstractPigs are important animals for meat production but can carry several zoonotic diseases, including Japanese encephalitis virus, Nipah virus, and influenza viruses. SeveralOrthomyxoviridaeandCoronavirinaerespiratory viruses require cleavage of envelope proteins to acquire viral infectivity and consequently need a host protease or the addition of exogenous trypsin for efficient propagation. Host TMPRSS2 is a key protease responsible for viral cleavage. Stable expression of human TMPRSS2 in African green monkey-derived Vero cells can enhance the porcine epidemic diarrhea virus. However, considering the narrow host tropism of viruses, a porcine cell line expressing pig TMPRSS2 could be optimal for replicating pig-derived viruses. Herein, we generated and evaluated a pig-derived PK-15 cell line stably expressing pig TMPRSS2. This cell line markedly and specifically enhanced the growth of influenza viruses. Therefore, PK-15 cells expressing pig TMPRSS2 could be a valuable and promising tool for virus isolation, vaccine production, and virological studies.
A familiar face and person processing area in the human temporal pole
Authors: Deen Ben , Husain Gazi , Freiwald Winrich A. 
Published: October 2023

AbstractHow does the brain process the faces of familiar people? Neuropsychological studies have argued for an area of the temporal pole (TP) linking faces with person identities, but magnetic susceptibility artifacts in this region have hampered its study with fMRI. Using data acquisition and analysis methods optimized to overcome this artifact, we identify a familiar face response in TP, reliably observed in individual brains. This area responds strongly to visual images of familiar faces over images of unfamiliar faces, objects, and scenes. However, TP did not just respond to images of faces, but also to a variety of high-level cognitive tasks that involve thinking about people, including semantic, episodic, and theory of mind tasks. The response profile of TP contrasted from a nearby region of perirhinal cortex that responded specifically to faces, but not to social cognition tasks. TP was functionally connected with a distributed network in association cortex associated with social cognition, while PR was functionally connected with face-preferring areas of ventral visual cortex. This work identifies a missing link in the human familiar face processing system that specifically processes familiar faces, and is well placed to integrate visual information about faces with higher-order conceptual information about other people. The results suggest that separate streams for person and face processing reach anterior temporal areas positioned at the top of the cortical hierarchy.
Principals in Indian inclusive schools: bridge over troubled waters
Authors: Srinivasavarathan Sarikha , Rajendran Poornima 
Published: October 2023

PurposeThe international academic literature agrees that principals act as change agents and are vital in creating and promoting an inclusive school culture. In this article, the authors proclaim that Indian schools lack school leadership to accomplish inclusive education (IE) characterized by local needs. The article emphasizes the importance of school principals and discusses how principal vacancies, insufficient training and lack of autonomy jeopardize inclusive and equitable quality education in Indian schools. Contextualized policies, professional standards for principals, research that highlights principals' perspectives and autonomy for principals are required to strengthen principals, who are the primary advocates for IE, to create a more democratic, equitable and just society.Design/methodology/approachThe authors base their arguments and opinions on the latest National Education Policy (NEP, 2020), data/statistics from various educational organizations in India, and research findings of global scholars.FindingsThe data and statistics show that principals in Indian schools do not receive the essential assistance to implement IE successfully. A lack of adequate data regarding the subject of debate is another point made by the authors.Social implicationsUnderstanding the hardships faced by Indian school principals would help readers recognize the leadership challenges for IE in India. Addressing these challenges is one of the best ways to fulfill the equity and inclusion goals emphasized in UN Sustainable Development Goal #4.Originality/valueThis article is the first to emphasize the importance of prioritizing principals in Indian schools, among other agents when trying to achieve inclusion.
The user cost of capital and corporate investment in the Latin American economies: a novel approach
Authors: Doruk Ömer Tuğsal 
Published: October 2023

PurposeIn the current study, corporate investment is examined by using a user cost of capital model for two important Latin American economies: Brazil and Mexico. In this paper, a dynamic user cost of capital model is employed. The extended model also accounts the investment model with the convex adjustment cost. Moreover, the link between structural change, financial liberalization and investment is also investigated. The present study, therefore, sheds new lights on the investment behavior of the Latin American emerging markets.Design/methodology/approachThe differenced generalized method of moments approach is employed to control the endogeneity, heteroscedasticity and autocorrelation for modeling the corporate investment over 20 years for both countries.Findings The findings indicate that the dynamic user cost of capital-based investment model explains the corporate investment in Brazil and Mexico. Especially, the interest rate and depreciation explain the investment behavior of nonfinancial firms in both countries. At the same time, structural change and financial liberalization do not have a significant impact on interest rates, an important user cost of capital.Originality/value This is the first study examines the corporate investment using dynamic user costs of capital approach for an emerging market. The user cost of capital-based investment models is clearly understudied models for emerging markets. This study is particularly important for emerging markets as investment models need to have a theoretical background.
Analyzing the efficiency of intellectual capital: a new approach based on DEA-MPI technology
Authors: Habib Ahmed Mohamed , Mourad Nahia 
Published: October 2023

PurposeThis study develops a robust model to measure intellectual capital efficiency (ICE). It also analyzes ICE across Gulf companies, sectors and countries.Design/methodology/approachThis study uses data envelopment analysis (DEA), the Malmquist productivity index (MPI), difference tests and additional analyses on a dataset consisting of 276 firm-year observations.FindingsThe findings indicate that the study model is robust to additional analysis. The results show significant differences in ICE between firms during the study period and noteworthy differences between countries, where the Qatari and Bahraini firms achieved the best ICE compared to other countries.Practical implicationsThe results of this study have significant ramifications for increasing knowledge of ICE analysis models among relevant parties. In addition, the findings may affect trading strategies because investors and financiers are motivated by the potential for lucrative financial returns on their investments in companies that prioritize ICE strategies.Originality/valueThis research contributes to the literature by proposing a robust model for estimating the ICE. It also compares ICE across Gulf companies, industries and countries to shed light on their ICE challenges.
Microfinance institutions managers' motivation towards environment protection through green microfinance: the case of the developing country of Cabo Verde
Authors: Leite Zenaida Neves , Sá Elisabete Sampaio 
Published: October 2023

PurposeThe paper explores the beliefs and perceptions of microfinance institution (MFI) managers about environmental threats and the role that green microfinance can play in mitigating them, to assess their influence on these institutions' engagement in green activities.Design/methodology/approachDrawing on protection motivation theory, the study follows a qualitative case study approach, focusing on the MFIs of the developing country of Cabo Verde.FindingsFindings indicate that MFI managers understand and are aware of the environmental threats and identify their customers as the most vulnerable to them. They seem motivated to increase their green activity in the future as it is generally seen as effective in mitigating the problems. However, their response capacity is hindered by limitations such as a lack of financial conditions and technical environmental knowledge.Social implicationsMFIs play an important role in promoting self-employment and breaking the poverty cycle, but their funds are also often used to develop environmentally damaging practices. Green microfinance can contribute to targeting a triple bottom line; considering together people, profit and the planet, provided implementation challenges are addressed.Originality/valueAlthough the environmental behaviour of MFIs has been previously studied, the understanding of the core beliefs of MFI managers that can support their environmental actions is still limited. Thus, the study contributes to advancing the knowledge of green microfinance by considering individual-level factors in understanding organisational greening.
Nudging digital entrepreneurs: the influence of the Google Play Store top developer award on technological innovation
Authors: Kuk George 
Published: October 2023

PurposeThis study explores how app store awards shape the behavior of leading digital entrepreneurs, focusing on their engagement in technological innovation through feedback and re-signaling mechanisms. It aims to reveal the nudging effect of award signals on entrepreneurial behavior.Design/methodology/approachIn this study, data from 349 leading mobile app entrepreneurs in the UK Google Play Store were collected over an extended period from various sources. Functionality novelty and explorative behavior were assessed by analyzing app release date and permission technologies in comparison to both their own prior apps and those of their closest competitors. Hypothesized relationships were tested using accelerated failure time parametric models.FindingsThis study extends the literature on signaling by showing that (1) the top developer award signal served to nudge entrepreneurs to improve the functionality novelty of their apps and those who succeeded were less likely to switch to another product category, (2) the award signal created a window of opportunity for non-award entrepreneurs to respond and those who released new apps around the midpoint of a normal app development cycle significantly improved the likelihood of winning the award in a subsequent round of award-giving, and (3) the effect of functionality novelty on winning the award was more pronounced when non-award entrepreneurs pursued more explorative than exploitative behavior in app development.Originality/valueThe results offer novel insights into an understudied area, specifically the influence of online award signals on nudging entrepreneurs to pursue technological innovation. The research also highlights the crucial role played by the app store as an intermediary signaler.
Are we only all by ourselves? A double-level perspective to cope with the insecurity of the nonstandard gig work model
Authors: Chen Jianyu 
Published: October 2023

PurposeThe emerging nonstandard employment (i.e. gig work) makes gig workers face a series of forms of labor insecurity. Prior studies focus on the linkage between gig work insecurity and precariousness. However, how gig workers and platforms jointly handle gig work insecurity has been so far overlooked. To this end, this study aims to explore how gig platforms and workers jointly cope with the insecurity of the gig work model.Design/methodology/approachBuilding upon the JD-R model, this study used a double-level perspective to hypothesize how gig platforms and workers jointly cope with gig work insecurity. Second, 248 questionnaire data were collected from workers who worked for several gig platforms (e.g. Meituan, Eleme, DidiTax, Zhihu and Credamo) in China. Third, the analysis method based on the partial least squares structural equation model (PLS-SEM) was employed to test the study theoretical model.FindingsEmpirical findings show that gig workers can cope with gig work insecurity by crafting their work; gig platforms' formalization governance not only reduces gig work insecurity but also helps gig workers address it by more easily crafting their work.Practical implicationsGig workers do always have not enough job resources and motivation to work hard. Gig workers merely rely on job crafting to cope with the insecurity of the gig work model, which is insufficient. Gig platforms should also formalize their current governance mechanisms, which can supplement gig workers' job resources and reduce their job demands so as to help them cope with such gig work insecurity.Originality/valueThese results advance the understanding of the joint roles of gig platforms and workers in addressing gig work insecurity and improve governance effectiveness and value of gig platforms.