bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Relationship Between Household Income and Healthcare Travel Patterns
Authors: Bemanian Amin , Mosser Jonathan F
Published: September 2023

Introduction

Transportation is a social determinant of health which affects how easily individuals attend clinic appointments, obtain medications, or seek emergency care. Despite the importance of transportation, there are few large-scale studies characterizing typical transportation behaviors related to seeking healthcare. This study investigates demographic differences in travel times and transportation mode for healthcare/medical related trips using the National Household Travel Survey (NHTS) dataset and identifies potential access inequities.

Methods

Medical trip data was obtained from the 2017 NHTS dataset. All analysis was adjusted by survey weights. Multiple linear regression models were developed to investigate the relationships between demographic variables, transportation mode, and travel time. Additionally, a logistic regression model was used to investigate the relationship between demographics and transportation mode.

Results

Medical trips using public transportation were found to be significantly longer relative to personal automobile trips. Higher household income was found to be associated with shorter travel times, but the effect size decreased with the inclusion of transportation mode. Higher household income respondents were also likely to use public transportation. Respondent race was not significantly associated with any differences in travel times, but there were significant differences across races in public transportation use.

Conclusions

This study demonstrates that individuals with lower household incomes tended to have longer medical trips. Additionally, it identifies public transit to be a potential mediating factor for this difference, as lower-income residents were significantly more likely to use public transit. This analysis highlights the importance of maintaining accessible and efficient public transportation for access to healthcare, especially for populations which have traditionally been at-risk for health disparities.
Single-cell atlas of ABCA7 loss-of-function reveals impaired neuronal respiration via choline-dependent lipid imbalances
Authors: von Maydell Djuna , Wright Shannon , Bonner Julia Maeve , Staab Colin , Spitaleri Andrea , Liu Liwang , Pao Ping-Chieh , Yu Chung Jong , Scannail Aine Ni , Li Mingpei , Boix Carles A. , Mathys Hansruedi , Leclerc Guillaume , Menchaca Gloria Suella , Welch Gwyneth , Graziosi Agnese , Leary Noelle , Samaan George , Kellis Manolis , Tsai Li-Huei
Published: September 2023

Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase the risk of Alzheimer’s disease (odds ratio ∼2), yet the pathogenic mechanisms and the neural cell types affected by these variants remain largely unknown. Here, we performed single-nuclear RNA sequencing of 36 humanpost-mortemsamples from the prefrontal cortex of 12 ABCA7 LoF carriers and 24 matched non-carrier control individuals. ABCA7 LoF was associated with gene expression changes in all major cell types. Excitatory neurons, which expressed the highest levels of ABCA7, showed transcriptional changes related to lipid metabolism, mitochondrial function, cell cycle-related pathways, and synaptic signaling. ABCA7 LoF-associated transcriptional changes in neurons were similarly perturbed in carriers of the common AD missense variant ABCA7 p.Ala1527Gly (n = 240 controls, 135 carriers), indicating that findings from our study may extend to large portions of the at-risk population. Consistent with ABCA7’s function as a lipid exporter, lipidomic analysis of isogenic iPSC-derived neurons (iNs) revealed profound intracellular triglyceride accumulation in ABCA7 LoF, which was accompanied by a relative decrease in phosphatidylcholine abundance. Metabolomic and biochemical analyses of iNs further indicated that ABCA7 LoF was associated with disrupted mitochondrial bioenergetics that suggested impaired lipid breakdown by uncoupled respiration. Treatment of ABCA7 LoF iNs with CDP-choline (a rate-limiting precursor of phosphatidylcholine synthesis) reduced triglyceride accumulation and restored mitochondrial function, indicating that ABCA7 LoF-induced phosphatidylcholine dyshomeostasis may directly disrupt mitochondrial metabolism of lipids. Treatment with CDP-choline also rescued intracellular amyloidβ-42 levels in ABCA7 LoF iNs, further suggesting a link between ABCA7 LoF metabolic disruptions in neurons and AD pathology. This study provides a detailed transcriptomic atlas of ABCA7 LoF in the human brain and mechanistically links ABCA7 LoF-induced lipid perturbations to neuronal energy dyshomeostasis. In line with a growing body of evidence, our study highlights the central role of lipid metabolism in the etiology of Alzheimer’s disease.
Automated detection and classification of polioviruses from nanopore sequencing reads using piranha
Authors: O’Toole Áine , Colquhoun Rachel , Ansley Corey , Troman Catherine , Maloney Daniel , Vance Zoe , Akello Joyce , Bujaki Erika , Majumdar Manasi , Khurshid Adnan , Arshad Yasir , Alam Muhammad Masroor , Martin Javier , Shaw Alexander G , Grassly Nicholas C , Rambaut Andrew
Published: September 2023

Widespread surveillance, rapid detection and appropriate intervention will be critical for successful eradication of poliovirus. With deployable next-generation sequencing (NGS) approaches, such as Oxford Nanopore Technologies’ MinION, the time from sample to result can be significantly reduced compared to cell culture and Sanger sequencing. We developed piranha (poliovirus investigation resource automating nanopore haplotype analysis) to aid routine poliovirus testing of both stool and environmental samples and alleviate the bioinformatic bottleneck that often exists for labs adopting novel NGS approaches. Piranha can be used for efficient intratypic differentiation of poliovirus serotypes, for classification of Sabin-like polioviruses and for detection of wild-type and vaccine derived polioviruses. It produces interactive, distributable html reports, as well as summary csv files and consensus poliovirus FASTA sequences. The reports describe each nanopore sequencing run with interpretable plots enabling researchers to easily detect the presence of poliovirus in samples and quickly disseminate their results.
Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control
Authors: Zhang Limei , Hernández Vito S. , Zetter Mario A. , Hernández-Pérez Oscar R. , Hernández-González Rafael , Camacho-Arroyo Ignacio , Eiden Lee E. , Millar Robert P.
Published: September 2023

Background

Kisspeptin (KP) signaling in the brain is defined by the anatomical distribution of KP-producing neurons, their fibers, receptors, and connectivity. Technological advances have prompted a re-evaluation of these chemoanatomical aspects, originally studied in the early years after the discovery of KP and its receptorKiss1r.We have previously characterized(1) seven KP neuronal populations in the mouse brain at the mRNA level, including two novel populations, and examined their short-term response to gonadectomy.

Methods

In this study, we mapped KP fiber distribution in rats and mice using immunohistochemistry under intact and short- and long-term post-gonadectomy conditions.Kiss1rmRNA expression was examined via RNAscope, in relation to vesicular GABA transporter (Slc32a1) in whole mouse brain and to KP and vesicular glutamate transporter 2 (Kiss1andSlc17a6) in hypothalamic RP3V and arcuate regions.

Results

We identified KP fibers in 118 brain regions, primarily in extra-hypothalamic areas associated with sensorial processing and behavioral state control. KP-immunoreactive fiber density and distribution were largely unchanged by gonadectomy.Kiss1rwas expressed prominently in sensorial and state control regions such as septal nuclei, the suprachiasmatic nucleus, locus coeruleus, hippocampal layers, thalamic nuclei, and cerebellar structures. Co-expression ofKiss1randKiss1was observed in hypothalamic neurons, suggesting both autocrine and paracrine KP signaling mechanisms.

Conclusion

These findings enhance our understanding of KP signaling beyond reproductive functions, particularly in sensorial and behavioral state regulation. This study opens new avenues for investigating KP’s role in controlling complex physiological processes, including those not related to reproduction.
Differing effects of alcohol use on epigenetic and brain age in adult children of alcoholic parents
Authors: Scholl Jamie L. , Pearson Kami , Fercho Kelene A. , Van Asselt Austin J. , Kallsen Noah A. , Ehli Erik. A. , Potter Kari N. , Brown-Rice Kathleen A. , Forster Gina L. , Baugh Lee A.
Published: September 2023

It is known that being the adult child of an alcoholic (ACoA) can confer a wide variety of increased health and psychological risks, including higher rates of anxiety, depression, and posttraumatic stress disorder symptoms. Additionally, ACoAs are at greater risk of developing substance use disorders than individuals from non-alcoholic families. To better understand the psychobiological factors underlying these risks, ACoA individuals with risky hazardous alcohol use (n=14) and those not engaged in hazardous use (n=14) were compared to a group of healthy controls. We examined structural brain differences and applied machine learning algorithms to predict biological brain and DNA methylation ages to investigate differences between these groups. Contrary to our hypothesis, we found that hazardous and non-hazardous ACoA groups had lower predicted brain ages than the healthy control group (n=100), which may result from neuro-developmental differences between ACoA groups and controls. When examining specific brain regions, we observed decreased cortical volume within bilateral pars orbitalis and frontal poles, as well as the left middle temporal gyrus and entorhinal cortex within the hazardous alcohol ACoA group, all areas consistent with previous research examining how alcohol use affects brain structure. When looking at the epigenetic aging data, the hazardous ACoA participants had increased predicted epigenetic age difference scores compared to the control group (n=34) and the non-hazardous ACoA participant groups. In summary, the results demonstrate a decreased brain age in the ACoAs compared to control, concurrent with increased epigenetic age specifically in the hazardous ACoA group, laying the foundation for future research to identify individuals that may have an increased susceptibility to developing hazardous alcohol use. Together, these results provide a better understanding of the associations between epigenetic factors, brain structure, and alcohol use disorders.
Photoemission electron microscopy for connectomics
Authors: Boergens Kevin M. , Wildenberg Gregg , Li Ruiyu , Lambert Lola , Moradi Amin , Stam Guido , Tromp Rudolf , van der Molen Sense Jan , King Sarah B. , Kasthuri Narayanan
Published: September 2023

1

Detailing the physical basis of neural circuits with large-volume serial electron microscopy (EM), ‘connectomics’, has emerged as an invaluable tool in the neuroscience armamentarium. However, imaging synaptic resolution connectomes is currently limited to either transmission electron microscopy (TEM) or scanning electron microscopy (SEM). Here, we describe a third way, using photoemission electron microscopy (PEEM) which illuminates ultra-thin brain slices collected on solid substrates with UV light and images the photoelectron emission pattern with a wide-field electron microscope. PEEM works with existing sample preparations for EM and routinely provides sufficient resolution and contrast to reveal myelinated axons, somata, dendrites, and sub-cellular organelles. Under optimized conditions, PEEM provides synaptic resolution; and simulation and experiments show that PEEM can be transformatively fast, at Gigahertz pixel rates. We conclude that PEEM imaging leverages attractive aspects of SEM and TEM, namely reliable sample collection on robust substrates combined with fast wide-field imaging, and could enable faster data acquisition for next-generation circuit mapping.
Utilizing ChatGPT to select literature for meta-analysis shows workload reduction while maintaining a similar recall level as manual curation
Authors: Cai Xiangming , Geng Yuanming , Du Yiming , Westerman Bart , Wang Duolao , Ma Chiyuan , Garcia Vallejo Juan J.
Published: September 2023

Background

Large language models (LLMs) like ChatGPT showed great potential in aiding medical research. A heavy workload in filtering records is needed during the research process of evidence-based medicine, especially meta-analysis. However, no study tried to use LLMs to help screen records in meta-analysis.

Objective

In this research, we aimed to explore the possibility of incorporating ChatGPT to facilitate the screening step based on the title and abstract of records during meta-analysis.

Methods

To assess our strategy, we selected three meta-analyses from the literature, together with a glioma meta-analysis embedded in the study, as additional validation. For the automatic selection of records from curated meta-analyses, a four-step strategy called LARS-GPT was developed, consisting of (1) criteria selection and single-prompt (prompt with one criterion) creation, (2) best combination identification, (3) combined-prompt (prompt with one or more criteria) creation, and (4) request sending and answer summary. Recall, workload reduction, precision, and F1 score were calculated to assess the performance of LARS-GPT.

Results

A variable performance was found between different single-prompts with a mean recall of 0.841. Based on these single-prompts, we were able to find combinations with performance better than the pre-set threshold. Finally, with a best combination of criteria identified, LARS-GPT showed a 39.5% workload reduction on average with a recall greater than 0.9.

Conclusions

We show here the groundbreaking finding that automatic selection of literature for meta-analysis is possible with ChatGPT. We provide it here as a pipeline, LARS-GPT, which showed a great workload reduction while maintaining a pre-set recall.
Developmental pathways of physical aggression from infancy to early school age
Authors: Nærde Ane , Janson Harald Tage , Stoolmiller Mike
Published: September 2023

This study identified latent trajectories of physical aggression from infancy to preschool age and tested for (a) early parent, parenting and child predictor effects on trajectory membership and (b) trajectory-effects net of parent, parenting, and child predictor effects on Grade 2 social, behavioral and academic functioning. We used data from the Behavior Outlook Norwegian Developmental Study (BONDS), comprising 1,159 children (559 girls). Parents reported on risk and protective factors, and on physical aggression from 1 to 5 years; teachers reported on Grade 2 outcomes. We employed latent class growth curve analyses to identify nine aggression trajectories. In fully adjusted models testing simultaneously all associations among predictors, trajectories, and outcomes, maternal and paternal harsh parenting, child gender, and sibling presence predicted trajectory membership, which significantly predicted Grade 2 externalizing. Child gender had a pervasive influence on all outcomes as well as on trajectory membership. This is the first trajectory study that attempts to sort out which predictors are most proximal, more distal, or just confounded, with their relative direct effect sizes, and to link early paternal as well as maternal harsh parenting with children’s development of physical aggression from infancy to preschool age. Our findings underscore the need to include fathers in developmental research and early prevention and intervention efforts.
Multi-Generation Ecosystem Selection Of Rhizosphere Microbial Communities Associated With Plant Genotype and Biomass InArabidopsis thaliana
Authors: Shankar Nachiket , Shetty Prateek , Melo Tatiana C , Kesseli Rick
Published: September 2023

The role of the microbiome in shaping the host phenotype has emerged as a critical area of investigation, with implications in ecology, evolution, and host health. The complex and dynamic interactions involving plants and their diverse rhizosphere microbial communities are influenced by a multitude of factors, including but not limited to soil type, environment, and plant genotype. Understanding the impact of these factors on microbial community assembly is key to yielding host-specific and robust benefits for plants, yet remains challenging. Here we ran an artificial ecosystem selection experiment, over eight generations, inArabidopsis thalianaLerand Cvi to select soil microbiomes associated with higher or lower biomass of the host. This resulted in divergent microbial communities, shaped by a complex interplay between random environmental variations, plant genotypes, and biomass selection pressures. In the initial phases of the experiment, the genotype and the biomass selection treatment have modest but significant impacts. Over time, the plant genotype and biomass treatments gain more influence, explaining ∼40% of the variation in the microbial community composition. Furthermore, a genotype-specific association of a plant growth-promoting rhizobacterial taxa,Labraceaewith LerandRhizobiaceaewith Cvi, is observed under selection for high biomass.
Partial alopecia area retains bulge hair follicle progenitor cells in Indian androgenetic alopecia patients
Authors: Hegde Akshay , Saha Dyuti , Somaiah Savitha , Jamora Colin
Published: September 2023

Androgenic alopecia (AGA) is a pathological condition characterized by the progressive decrease of scalp hair follicle density. Completely bald areas of AGA scalp still retain hair follicle stem cells but the progenitor cells are drastically decreased in number. However, it is unknown when the progenitor cells begin to diminish in number during the progression of AGA. Despite the prevalence of AGA in 58% of the Indian male population, no study to date has characterized the hair follicle stem and progenitor cell populations in AGA patients in this ethnic group. We observed that the partially bald area retains progenitor cells expressing CD34 and Sox9 but they are not present in the hair follicles in the completely bald area. Our study sheds light on the timeframe for effective therapeutic interventions based on modulating regulatory mechanisms to reinitiate the existing inactive follicle stem cells.
Genome of the endangered eastern quoll (Dasyurus viverrinus) reveals signatures of historical decline and pelage color evolution
Authors: Hartley Gabrielle A. , Frankenberg Stephen R. , Robinson Natasha M. , MacDonald Anna J. , Hamede Rodrigo K. , Burridge Christopher P. , Jones Menna E. , Faulkner Tim , Shute Hayley , Rose Karrie , Brewster Robert , O’Neill Rachel , Renfree Marilyn B. , Pask Andrew J. , Feigin Charles Y.
Published: September 2023

The eastern quoll (Dasyurus viverrinus) is an endangered marsupial mesopredator native to Australia. Since the extirpation of the last mainland Australian populations in the late 20th century, wild populations of this species have been restricted to two islands at the far southern end of its historical range. Eastern quolls are the subject of captive breeding programs and attempts have recently been made to re-establish a population in mainland Australia through translocations. However, few resources currently exist to guide the genetic management of this species. Here, we generated a chromosome-scale reference genome for the eastern quoll, along with gene annotations supported by multi-tissue transcriptomes. Through comparisons with related species, we find that our reference genome is among the most complete marsupial assemblies currently available. Using this assembly, we infer the species’ demographic history and identify potential evidence of a long-term decline beginning in the late Pleistocene. Finally, we identify a deletion at theASIPlocus that likely drives differences in pelage color between the eastern quoll and the closely related Tasmanian devil (Sarcophilus harrisii). The genomic resources we present are valuable new tools for evolutionary and conservation genomic studies.
Phosphatidylserine clustering by membrane receptors triggers LC3-associated phagocytosis
Authors: Boada-Romero Emilio , Guy Clifford S. , Palacios Gustavo , Mari Luigi , Li Zhenrui , Green Douglas R.
Published: September 2023

LC3-associated phagocytosis (LAP) represents a non-canonical function of autophagy proteins in which ATG8 family proteins (LC3 and GABARAP proteins) are lipidated onto single-membrane phagosomes as particles are engulfed by phagocytic cells1–4. LAP plays roles in innate immunity5, inflammation and anti-cancer6responses and is initiated upon phagocytosis of particles that stimulate Toll-like receptors (TLR), Fc-receptors, and upon engulfment of dying cells6. However, how this molecular route is initiated remains elusive. Here we report that receptors that engage LAP enrich phosphatidylserine (PS) in the phagosome membrane via membrane-proximal domains that are necessary and sufficient for LAP to proceed. Subsequently, PS recruits the Rubicon-containing PI3-kinase complex to initiate the enzymatic cascade leading to LAP. Manipulation of plasma membrane PS content, PS-binding by Rubicon, or the PS-clustering domains of receptors prevents LAP and phagosome maturation. We found that pharmacologic inhibition of PS clustering promotes the ability of dendritic cells to induce anti-cancer responses to engulfed tumor cells. Therefore, the initiation of LAP represents a novel mechanism of PS-mediated signal transduction upon ligation of surface receptors.
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

The 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

Postinhibitory 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 Summary

Human 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.
Emergence ofProchlorococcusin the Tonian oceans and the initiation of Neoproterozoic oxygenation
Authors: Zhang Hao , Wang Sishuo , Liao Tianhua , Crowe Sean A. , Luo Haiwei
Published: September 2023

Prochlorococcusare the smallest and most abundant photosynthetic organisms on Earth, contributing up to 50% of the chlorophyll in the oligotrophic oceans. Despite being important in regulating the carbon cycle in today's ocean, the ecological significance ofProchlorococcusin Earth's history remains elusive. Our new robustly calibrated molecular clock analysis reveals thatProchlorococcusemerged in the deep photic zone of the Tonian (1,000-720 Mya) oceans. The classical light-harvesting antenna complex in Cyanobacteria, i.e., the phycobilisome, was replaced inProchlorococcusby the chlorophyll‐based antenna, enabling more efficient use of blue light that penetrates into deeper water. Importantly,Prochlorococcuscolonization of deep water enhanced access to phosphate, which was abundant in upwelled seawater, but likely scarce in the Tonian surface ocean, promoting expansion ofProchlorococcus, displacement of incumbent low-light adapted anoxygenic photoferrotrophs, and associated increases in photosynthetic oxygen production. Colonization of deeper waters would also have improved access to ammonium, leading to the neutral loss of nitrate utilization genes. Our research thus documents the conspicuous emergence of new photosynthetic bacterial lineages in the run-up to the Neoproterozoic oxygenation event, implying an additional layer of eco-evolutionary complexity during this pivotal interval in Earth's history.
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

Traditional 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

Cortical-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

Purpose

This 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/approach

The 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.

Findings

The 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/value

The 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

Purpose

The 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/approach

To 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.

Findings

Findings 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 implications

The present study offers important implications for different actors in the tourism sector, such as policy makers, destination marketing organizations (DMOs) and tourism operators.

Social implications

The present study explores the role of social media involvement, specifically during the tourist's holiday.

Originality/value

This 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

Although 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

Introduction

Combined 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.

Methods

Our 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.

Discussion

Since 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 details

This 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

Background

The 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.

Methods

This 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.

Results

A 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.

Conclusion

Encouraging 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.
Identification, location and characterisation of spawning grounds and nurseries in the littoral zone of Lake Kivu (eastern DR Congo)
Authors: Mazambi Jacques Lutete , Micha Jean‐Claude , Kaningini Boniface Mwenyemali , Bahati Emilie Kaningini , Alimasi Wilondja , Riziki Jacques Walumona , Ntakimazi Gaspard , Masilya Pascal Mulungula
Published: September 2023

Worldwide biodiversity is on the brink of extinction following the complete disappearance of many forest and freshwater vertebrates. This disappearance is closely linked to the reduction and disturbance of habitats, which should instead benefit from special conservation. In the case of lake ecosystems, fish spawning grounds remain the most vulnerable. This study aims to identify, characterise and locate fish spawning and nursery sites in Lake Kivu for better conservation. Sixteen sampling sites were selected along the shoreline of the Bukavu sub‐basin. Physico‐chemical parameters were measured in situ, and fish were captured using multi‐mesh nets, identified and dissected, gonads observed and sexual maturity stages determined. Twenty‐five fish species were identified, but 17 of these use the selected sampling sites as spawning and/or nursery. Eleven spawning and nine nursery sites were identified and located. Physico‐chemical analyses showed that temperature (F = 2.124, p = 0.011), dissolved oxygen (F = 2.792, p < 0.001), depth (F = 5.915, p < 0.001) and transparency (F = 3.421, p = 0.004) were significantly different, which characterise each site and may be key factors in species distribution between spawning sites. Fish size–weight relationships indicate allometric growths. The results of this research contribute to empirical knowledge of fish spawning grounds.