bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal-regulated unmasking of the nuclear localization motif in the PAS domain regulates the nuclear translocation of PASK
Authors: Xiao Michael , Dhungel Sajina , Azad Roksana , Favaro Denize C. , Rajesh Rajaian Pushpabai , Gardner Kevin H. , Kikani Chintan K. 
Published: September 2023

AbstractThe ligand-regulated PAS domains are one of the most diverse signal-integrating domains found in proteins from prokaryotes to humans. By biochemically connecting cellular processes with their environment, PAS domains facilitate an appropriate cellular response. PAS domain-containing Kinase (PASK) is an evolutionarily conserved protein kinase that plays important signaling roles in mammalian stem cells to establish stem cell fate. We have shown that the nuclear translocation of PASK is stimulated by differentiation signaling cues in muscle stem cells. However, the mechanistic basis of the regulation of PASK nucleo-cytoplasmic translocation remains unknown. Here, we show that the PAS-A domain of PASK contains a putative monopartite nuclear localization sequence (NLS) motif. This NLS is inhibited in cells via intramolecular association with a short linear motif, termed the PAS Interacting Motif (PIM), found upstream of the kinase domain. The interaction between the PAS-A domain and PIM is evolutionarily conserved and serves to retain PASK in the cytosol in the absence of signaling cues. Consistent with that, we show that metabolic inputs induce PASK nuclear import, likely by disrupting the PAS-A: PIM association. We suggest that a route for such linkage may occur through the PAS-A ligand binding cavity. We show that PIM recruitment and artificial ligand binding to the PAS-A domain occur at neighboring locations that could facilitate metabolic control of the PAS-PIM interaction. Thus, the PAS-A domain of PASK integrates metabolic signaling cues for nuclear translocation and could be targeted to control the balance between self-renewal and differentiation in stem cells.
Postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents: a simulation study
Authors: Schmid Laura , Klotz Thomas , Röhrle Oliver , Powers Randall K. , Negro Francesco , Yavuz Utku Ş. 
Published: September 2023

AbstractPostinhibitory excitation is a transient overshoot of a neuron’s baseline firing rate following an inhibitory stimulus and can be observedin vivoin human motoneurons. However, the biophysical origin of this phenomenon is still unknown and both reflex pathways and intrinsic motoneuron properties have been proposed. We hypothesized that postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents (h-currents). Using an electrical circuit model we investigated how h-currents can modulate the postinhibitory response of motoneurons. Further, we analyzed the spike trains of human motor units from the tibialis anterior muscle during reciprocal inhibition. The simulations revealed that the activation of h-currents by an inhibitory postsynaptic potential can cause a short-term increase in a motoneuron’s firing probability. This result suggests that the neuron can be excited by an inhibitory stimulus. In detail, the modulation of the firing probability depends on the time delay between the inhibitory stimulus and the previous action potential. Further, the strength of the postinhibitory excitation correlates with the amplitude of the inhibitory stimulus and is negatively correlated with the baseline firing rate as well as the level of input noise. Hallmarks of h-current activity, as identified from the modeling study, were found in 50 % of the human motor units that showed postinhibitory excitation. This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition.Author SummaryHuman movement is determined by the activity of specialized nerve cells, the motoneurons. Each motoneuron activates a specific set of muscle fibers. The functional unit consisting of a neuron and muscle fibers is called a motor unit. The activity of motoneurons can be observed noninvasively in living humans by recording the electrical activity of the motor units using the electromyogram. We studied the behavior of human motor units in an inhibitory reflex pathway and found an unexpected response pattern: a rebound-like excitation following the inhibition. This has occasionally been reported for human motor units, but its origin has never been systematically studied. In non-human cells of the neural system, earlier studies reported that a specific membrane protein, the so-called h-channel, can cause postinhibitory excitation. In our study, we use a computational motoneuron model to investigate whether h-channels can cause postinhibitory excitation as observed in the experimental recordings. Using the model, we developed a method to detect features of h-channel activity in human recordings. Because we found these features in a half of the recorded motor units, we conclude that h-channels can facilitate postinhibitory excitation in human motoneurons.
Anatomical Modeling and Optimization of Speckle Contrast Optical Tomography
Authors: Lin Chen-Hao P. , Orukari Inema , Frisk Lisa Kobayashi , Verma Manish , Chetia Sumana , Beslija Faruk , Eggebrecht Adam T. , Durduran Turgut , Culver Joseph P. , Trobaugh Jason W. 
Published: September 2023

AbstractTraditional methods for mapping cerebral blood flow (CBF), such as positron emission tomography and magnetic resonance imaging, offer only isolated snapshots of CBF due to scanner logistics. Speckle contrast optical tomography (SCOT) is a promising optical technique for mapping CBF. However, while SCOT has been established in mice, the method has not yet been demonstrated in humans - partly due to a lack of anatomical reconstruction methods and uncertainty over the optimal design parameters. Herein we develop SCOT reconstruction methods that leverage MRI-based anatomical head models and finite-element modeling of the SCOT forward problem (NIRFASTer). We then simulate SCOT for CBF perturbations to evaluate sensitivity of imaging performance to exposure time and SD-distances. We find image resolution comparable to intensity-based diffuse optical tomography at superficial cortical tissue depth (∼1.5 cm). Localization errors can be reduced by including longer SD-measurements. With longer exposure times speckle contrast decreases, however, noise decreases faster, resulting in a net increase in SNR. Specifically, extending exposure time from 10μs to 10ms increased SCOT SNR by 1000X. Overall, our modeling methods provide anatomically-based image reconstructions that can be used to evaluate a broad range of tissue conditions, measurement parameters, and noise sources and inform SCOT system design.
Activin A targets extrasynaptic NMDA receptors to improve neuronal and behavioral deficits in a mouse model of Huntington disease
Authors: Nassrallah Wissam B. , Ramandi Daniel , Cheng Judy , Oh Jean , Mackay James , Sepers Marja D. , Lau David , Bading Hilmar , Raymond Lynn A. 
Published: September 2023

AbstractCortical-striatal synaptic dysfunction, including enhanced toxic signaling by extrasynaptic N-methyl-D-aspartate receptors (eNMDARs), precedes neurodegeneration in Huntington disease (HD). A previous study showed Activin A, whose transcription is upregulated by calcium influx via synaptic NMDARs, suppresses eNMDAR signaling. Therefore, we examined the role of Activin A in the YAC128 HD mouse model, comparing it to wild-type controls. We found decreased Activin A secretion in YAC128 cortical-striatal co-cultures, while Activin A overexpression in this model rescued altered eNMDAR expression. Striatal overexpression of Activin Ain vivoimproved motor learning on the rotarod task, and normalized striatal neuronal eNMDAR-mediated currents, membrane capacitance and spontaneous excitatory postsynaptic current frequency in the YAC128 mice. These results support the therapeutic potential of Activin A signaling and targeting eNMDARs to restore striatal neuronal health and ameliorate behavioral deficits in HD.
Project rescue: ventilators and data made for a pandemic world
Authors: Cherneski Jennifer 
Published: September 2023

Social implications
This case presents some of the entrepreneurial challenges faced by a female leader in the technology sector who conceived a new product based on her passion to help others especially those most disadvantaged.

Learning outcomes
Upon completion of this case study, students should be able to prepare supply chain and distribution analysis that considers ethics and sustainability, integrate philanthropic efforts as part of an organizational strategy and recognize strategies to promote equity within and beyond an organization.

Case overview/synopsis
Connie Stacey (she/her) is an entrepreneur and president of Growing Greener Innovations, an award-winning battery energy storage company based in Alberta, Canada, with a mission to end energy poverty globally. With the emergence of COVID-19 as a global pandemic in 2020, Stacey turned her attention to an innovation called Project Rescue, a ventilator that uses non-identifying patient vitals to track data. It serves as a pandemic early warning system, addressing two key challenges: pandemic data are prone to error, and real-time information is non-existent after the pandemic has spread. This new product was conceived based on her passion to help others, especially those most disadvantaged. This multi-faceted case focuses on the many challenges that Stacey and her team needed to address. The dilemma in this case centres on establishing supply chains amid a pandemic, as well as prioritizing the corporate social responsibility elements of philanthropy and equity within her organization (and beyond).

Complexity academic level
This case is appropriate for third- or fourth-year undergraduate or graduate-level students.

Supplementary materials
In addition to “call out boxes” throughout the case and teaching note, additional readings/links/videos are outlined below. (These supplementary materials, “Teaching Tips”, are included in the teaching notes as well.)

Subject code
CCS 11: Strategy.
Electric field and SAR distribution in the vicinity of dental implants exposed to the cell phone electromagnetic radiation
Authors: Jovanovic Dejan B. , Krasic Dragan , Cvetkovic Nenad N. , Vuckovic Dragan , Stanković Vladimir B. 
Published: September 2023

Purpose
The purpose of this paper is to determine the electric field and specific absorption rate (SAR) distribution within biological tissues in the vicinity of dental implants, exposed to the mobile phone radiation.

Design/methodology/approach
This research was performed for the frequency of 2.6 GHz, which corresponds to 4G mobile network. The adequate 3D realistic numerical models of the mobile phone user’s head, dental implants and actual smartphone model are created using packages based on the finite integral technique numerical method.

Findings
The obtained results yield to a conclusion that the presence of dental implants affects the increase in electric field intensity and SAR values within biological tissues in its vicinity.

Research limitations/implications
The presented procedure is limited to the 4G mobile network frequency of 2.6 MHz. The study should be extended to other mobile network frequencies to be more general.

Practical implications
The criteria for selection of the materials used for dental implants production should be extended with the recommended material characteristics related to their influence on the electric field and SAR distribution, to keep their values in the limits prescribed by standards.

Social implications
The obtained results provide the foundation for future research in mobile devices’ electromagnetic fields’ influence on human health.

Originality/value
The accurate determination of the electric field and SAR values within different biological tissues and organs in the vicinity of dental implants exposed to mobile phone electromagnetic radiation, demands highly realistic model of observed biological structures. For purposes of the current study, the procedure for modeling of highly nonhomogeneous structure with finite number of homogenous domains having known electromagnetic parameters is described in the paper. As a result, the 3D complex users’ head model formed of 16 homogeneous domains of different electromagnetic parameters is created.
Birth and evolution of “social studies” in Myanmar: dramatic changes in contents and approaches
Authors: Tanaka Yoshitaka 
Published: September 2023

PurposeThis research clarifies the birth and evolution of “Social Study” in Myanmar through analyzing the differences of contents and approaches between “Social Studies” under the military administration and that under the recent democratic administration.Design/methodology/approachThe author obtained “Social Studies” textbooks that were used both in the past as well as in present day and translated them into English. The textbooks’ contents were analyzed in detail while referring Japanese and American “Social Studies” textbooks. Specifically, the author focused on the content structure of the textbooks and the learning objectives and approaches used. Each textbook was analyzed in accordance with the era in which they were used considering the social and political conditions at those times. In addition, the author clarified the necessary competencies for the people of Myanmar during the new era through discussions with many Myanmar educators. Based on this research, the author advised the Ministry of Education on the content of new “Social Studies” textbooks and supported their development.FindingsThe idea of child-centered education introduced under the military administration was further strengthened in the recent new “Social Studies” textbooks allowing students to learn by tapping into their interests and also encouraging deep thinking and creativity. This approach changed their learning from memorization without deep thinking in the past to contemplating things and creating new ideas.Originality/valueThe findings can provide curriculum developers and educators in other countries with a broad direction on how to reform “Social Studies” and related subjects curricula and textbooks in their own countries in the future.
Tourists' satisfaction and sense of belonging in adopting responsible behaviors: the role of on-site and social media involvement in cultural tourism
Authors: Dini Mauro , Curina Ilaria , Francioni Barbara , Hegner Sabrina , Cioppi Marco 
Published: September 2023

PurposeThe study aims to analyze the relationship between tourists' satisfaction and their sense of belonging in a specific cultural destination by also investigating the moderating role of their on-site involvement, both offline (on-site activities at the destination) and online (social media activities). A further objective lies in exploring the relationship between tourists' sense of belonging and their adoption of environmentally responsible behavior while at the destination. Finally, the paper attempts to determine whether said behavior can predict tourists' pro-environmental behavior and recommendation intention.Design/methodology/approachTo reach these objectives, a survey and a structural equation model, based on a sample of 647 visitors of an important world Heritage site UNESCO (i.e. Urbino), have been adopted.FindingsFindings reveal a positive influence of sense of belonging on satisfaction and environmentally responsible behavior, which, in turn, influences pro-environmental behavior and Recommendation intention, thus triggering a virtuous process in the tourists' formation as responsible and loyal travelers. Moreover, results underline how the relationship between satisfaction and sense of belonging is significantly strengthened when tourists' on-site activity involvement increases. Conversely, the moderating role of social media involvement is not supported.Practical implicationsThe present study offers important implications for different actors in the tourism sector, such as policy makers, destination marketing organizations (DMOs) and tourism operators.Social implicationsThe present study explores the role of social media involvement, specifically during the tourist's holiday.Originality/valueThis study enriches the empirical evidence in the cultural tourism through an analysis focused on the tourists' perspective, especially by investigating the relationship between satisfaction and emotional constructs (i.e. sense of belonging) that are able to bring environmental and loyalty benefits to the destination. Moreover, although existing research has highlighted the positive influence of the tourists' involvement on their experience, there is a paucity of studies jointly analyzing the on-site and online activities in the sustainability field.
Resourced provision in mainstream schools for students with special educational needs and/or disabilities: Inclusive service or safe space?
Authors: Strogilos Vasilis , Ward Rebecca J. 
Published: September 2023

AbstractAlthough the number of resource provision (RP) classrooms for the education of students with special educational needs and/or disabilities (SEND) in English mainstream schools has increased, very little is known about their functioning and impact. Through collaborative research, based on critical communicative methodology, this study aims to (i) evaluate with the participants the effective practices and challenges in educating students with SEND in RP and mainstream classrooms, and (ii) discuss the position of RP within the inclusion and exclusion debate. Reflective conversations, communicative focus groups and communicative observations were conducted with teachers, teaching assistants, mothers and students in three schools. Two different models were identified in the conceptualisation and practice of RP; either as a service to promote the education and inclusion of students with SEND in mainstream classroom/school, or as a space for specialised provision with opportunities for inclusion. These models reflect two different approaches in the education of these students, the rights‐ and the needs‐based approach respectively. We argue that RP as inclusive service should be prioritised. However, flexibility in its conceptualisation and functioning, either as inclusive service or safe space, can positively contribute towards a realistic approach to inclusion combining human rights and individual diversity perspectives.
Phase II study of IRInotecan treatment after COmbined chemo‐immunotherapy for extensive‐stage small cell lung cancer: Protocol of IRICO study
Authors: Tomono Hiromi , Taniguchi Hirokazu , Fukuda Minoru , Ikeda Takaya , Nagashima Seiji , Akagi Kazumasa , Ono Sawana , Umeyama Yasuhiro , Shimada Midori , Gyotoku Hiroshi , Takemoto Shinnosuke , Hisamatsu Yasushi , Morinaga Ryotaro , Tagawa Ryuta , Ogata Ryosuke , Dotsu Yosuke , Senju Hiroaki , Soda Hiroshi , Nakatomi Katsumi , Hayashi Fumiko , Sugasaki Nanae , Kinoshita Akitoshi , Mukae Hiroshi 
Published: September 2023

AbstractIntroductionCombined treatment using anti‐programmed death‐ligand 1 antibody (anti‐PD‐L1) and platinum‐etoposide is the current standard first‐line treatment for patients with extensive‐stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES‐SCLC after the first‐line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES‐SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second‐ or later‐line setting for patients with ES‐SCLC who have been previously treated with combined treatment.MethodsOur study will enroll total 30 patients who are diagnosed with ES‐SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression‐free survival, and safety.DiscussionSince the present first‐line treatment has been changed to the combined treatment, the second‐ or later‐line treatment should be re‐evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re‐evaluates the clinical benefits of irinotecan after combined treatment with anti‐PD‐L1 and platinum‐etoposide for patients with ES‐SCLC.Registration detailsThis study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.
Effectiveness and safety of human type 5 recombinant adenovirus (H101) in malignant tumor with malignant pleural effusion and ascites: A multicenter, observational, real‐world study
Authors: Wang Baocheng , Zhong Chen , Liao Zijun , Wang Haitao , Cai Xiuyu , Zhang Yanbing , Wang Jun , Wang Tianxiao , Yao Hongtao 
Published: September 2023

AbstractBackgroundThe aim of this study was to analyze the effectiveness and safety of H101 in Chinese patients with malignant pleural effusion and ascites (MPE/MA) in the real world.MethodsThis multicenter, observational, real‐world study recruited patients with MPE/MA caused by malignant tumor receiving H101‐containing treatment between January 2020 and June 2022. Effectiveness was evaluated by overall remission rate (ORR), and safety was evaluated based on adverse events (AEs). Subgroup analysis was performed on patients grouped according to tumor type, the volume of MPE and MA, and dosage of H101.ResultsA total of 643 eligible patients were enrolled, and 467 received H101 monotherapy and 176 received H101 combined with chemotherapy. The ORR of total patients was60.3% with 388 case of PR. In the H101 monotherapy group, the decrease of MPE or MA was achieved in 282 (60.4%, PR) patients, 176 (37.7%, NC) patients showed no change in volume of MPE or MA, and nine (1.9%, PD) patients showed an increase, yielding an ORR of 60.4% (282/467). The ORR for the combination therapy group was 60.2% (106/176), with 106 cases of PR, 69 cases of NC and one case of PD. Subgroup analyses based on tumor type, volume of MPE and MA, and dosage of H101 all showed high ORR, approximately 60%. The main AEs associated with H101‐containing regimens were fever, nausea and vomiting. No serious AEs occurred in both groups.ConclusionEncouraging clinical benefits and manageable toxicity of H101 against MPE/MA were preliminarily observed in the real‐world clinical setting, indicating that the H101‐containing regimen is reliable, safe, and feasible, providing a novel and effective option for the treatment of this disease.