bluuebunny/crossref_metadata_2025 huggingface dataset:
The B56γ3-containing protein phosphatase 2A attenuates p70S6K-mediated negative feedback loop to enhance AKT-facilitated epithelial-mesenchymal transition in colorectal cancer
Authors: Hsiao Kai-Ching , Ruan Siou-Ying , Chen Shih-Min , Lai Tai-Yu , Chan Ren-Hao , Zhang Yan-Ming , Chu Chien-An , Cheng Hung-Chi , Tsai Hung-Wen , Tu Yi-Fang , Law Brian K. , Chang Ting-Tsung , Chow Nan-Haw , Chiang Chi-Wu
Published: July 2023

Background

Protein phosphatase 2A (PP2A) is one of the major protein phosphatases in eukaryotic cells and is essential for cellular homeostasis. PP2A is a heterotrimer comprising the dimeric AC core enzyme and a highly variable regulatory B subunit. Distinct B subunits help the core enzyme gain full activity toward specific substrates and contribute to diverse cellular roles of PP2A. PP2A has been thought to play a tumor suppressor and the B56γ3 regulatory subunit was shown to play a key tumor suppressor regulatory subunit of PP2A. Nevertheless, we uncovered a molecular mechanism of how B56γ3 may act as an oncogene in colorectal cancer (CRC).

Methods

Polyclonal pools of CRC cells with stable B56γ3 overexpression or knockdown were generated by retroviral or lentiviral infection and subsequent drug selection. Co-immunoprecipitation(co-IP) and in vitro pull-down analysis were applied to analyze the protein–protein interaction. Transwell migration and invasion assays were applied to investigate the role of B56γ3 in affecting motility and invasive capability of CRC cells. The sensitivity of CRC cells to 5-fluorouracil (5-FU) was analyzed using the PrestoBlue reagent assay for cell viability. Immunohistochemistry (IHC) was applied to investigate the expression levels of phospho-AKT and B56γ3 in paired tumor and normal tissue specimens of CRC. DataSets of TCGA and GEO were analyzed to investigate the correlation of B56γ3 expression with overall survival rates of CRC patients.

Results

We showed that B56γ3 promoted epithelial-mesenchymal transition (EMT) and reduced the sensitivity of CRC cells to 5-FU through upregulating AKT activity. Mechanistically, B56γ3 upregulates AKT activity by targeting PP2A to attenuate the p70S6K-mediated negative feedback loop regulation on PI3K/AKT activation. B56γ3 was highly expressed and positively correlated with the level of phospho-AKT in tumor tissues of CRC. Moreover, high B56γ3 expression is associated with poor prognosis of a subset of patients with CRC.

Conclusions

Our finding reveals that the B56γ3 regulatory subunit-containing PP2A plays an oncogenic role in CRC cells by sustaining AKT activation through suppressing p70S6K activity and suggests that the interaction between B56γ3 and p70S6K may serve as a therapeutic target for CRC.
Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression
Authors: Irmer Barnabas , Efing Janes , Reitnauer Lea Elisabeth , Angenendt Allegra , Heinrichs Saskia , Schubert Antonia , Schulz Matthias , Binder Claudia , Tio Joke , Hansen Uwe , Geyer Christiane , Gerwing Mirjam , Bleckmann Annalen , Menck Kerstin
Published: July 2023

Background

Extracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the creation of a favorable tumor microenvironment. So far, EV uptake and cargo delivery into target cells have been regarded as the main mechanisms for the pro-tumoral function of EVs. To test this hypothesis, we investigated the fate of the oncogenic transmembrane Wnt tyrosine kinase-like orphan receptor 1 and 2 (ROR1, ROR2) delivered via distinct EV subpopulations to breast cancer cells and aimed to unravel their impact on tumor progression.

Methods

EVs were isolated by differential ultracentrifugation from cell culture supernatant as well as plasma samples from healthy individuals (n = 27) and breast cancer patients (n = 41). EVs were thoroughly characterized by electron microscopy, nanoparticle tracking analysis, immunoblot, and flow cytometry. ROR transfer to target cells was observed using microscopy-based assays and biodistribution experiments were conducted in syngeneic mice. EV impact on cancer cell migration and invasion was tested in functional assays.

Results

We observed that the supernatant of ROR-overexpressing cells was sufficient for transferring the receptors to ROR-negative cells. Analyzing the secretome of the ROR-overexpressing cells, we detected a high enrichment of ROR1/2 on large and small EVs, but not on large oncosomes. Interestingly, the majority of ROR-positive EVs remained attached to the target cell surface after 24 h of stimulation and was quickly removed by treatment with trypsin. Nonetheless, ROR-positive EVs increased migration and invasion of breast cancer cells, even after chemically inhibiting EV uptake, in dependence of RhoA downstream signaling. In vivo, ROR-depleted EVs tended to distribute less into organs prone for the formation of breast cancer metastases. ROR-positive EVs were also significantly elevated in the plasma of breast cancer patients and allowed to separate them from healthy controls.

Conclusions

The oncogenic Wnt receptors ROR1/2 are transferred via EVs to the surface of ROR-negative cancer cells, in which they induce an aggressive phenotype supporting tumor progression.
Cost analysis and cost effectiveness of a subsidized community supported agriculture intervention for low-income families
Authors: Garner Jennifer A. , Hanson Karla L. , Jilcott Pitts Stephanie B. , Kolodinsky Jane , Sitaker Marilyn H. , Ammerman Alice S. , Kenkel Donald , Seguin-Fowler Rebecca A.
Published: July 2023

Background

The food system has a dynamic influence on disparities in food security and diet-related chronic disease. Community supported agriculture (CSA) programs, in which households receive weekly shares of produce from a local farmer during the growing season, have been examined as a possible food systems-based approach for improving diet and health outcomes. The purpose of this study was to estimate the cost of implementing and participating in a multi-component subsidized community supported agriculture intervention and calculate cost-effectiveness based on diet and food security impacts.

Methods

Using data from the Farm Fresh Foods for Healthy Kids (F3HK) randomized controlled trial in New York, North Carolina, Vermont, and Washington (n = 305; 2016–2018), we estimated programmatic and participant costs and calculated incremental cost-effectiveness ratios (ICERs) for caregivers’ daily fruit and vegetable (FV) intake, skin carotenoids, and household food security from program and societal perspectives.

Results

F3HK cost $2,439 per household annually ($1,884 in implementation-related expenses and $555 in participant-incurred costs). ICERs ranged from $1,507 to $2,439 per cup increase in caregiver’s FV intake (depending on perspective, setting, and inclusion of juice); from $502 to $739 per one thousand unit increase in skin carotenoid score; and from $2,271 to $3,137 per household shifted out of food insecurity.

Conclusions

Given the known public health, healthcare, and economic consequences of insufficient FV intake and living in a food insecure household, the costs incurred to support these positive shifts in individual- and household-level outcomes via a F3HK-like intervention may be deemed by stakeholders as a reasonable investment. This work helps to advance a critical body of literature on the cost-effectiveness of subsidized CSAs and other economic and food system interventions for the sake of evidence-based allocation of public health resources.

Trial registration

: ClinicalTrials.gov. NCT02770196. Registered 5 April 2016. Retrospectively registered. https://www.clinicaltrials.gov/ct2/show/NCT02770196.
Eulertigs: minimum plain text representation of k-mer sets without repetitions in linear time
Authors: Schmidt Sebastian , Alanko Jarno N.
Published: July 2023

A fundamental operation in computational genomics is to reduce the input sequences to their constituentk-mers. For maximum performance of downstream applications it is important to store thek-mers in small space, while keeping the representation easy and efficient to use (i.e. withoutk-mer repetitions and in plain text). Recently, heuristics were presented to compute a near-minimum such representation. We present an algorithm to compute a minimum representation in optimal (linear) time and use it to evaluate the existing heuristics. Our algorithm first constructs the de Bruijn graph in linear time and then uses a Eulerian-cycle-based algorithm to compute the minimum representation, in time linear in the size of the output.
COVID-19 and spontaneous pneumothorax: a survival analysis
Authors: Ershadi Reza , Rafieian Shahab , Salehi Mohammadreza , Kazemizadeh Hossein , Amini Hesam , Sohrabi Marjan , Samimiat Alireza , Sharafi Yaser , Dashtkoohi Mohadese , Vahedi Matin
Published: July 2023

Introduction

COVID-19 Patients may be at risk for involving with spontaneous pneumothorax. However, clinical data are lacking in this regard. In this study, we aimed to investigate the demographic, clinical, and radiological characteristics and survival predictors in COVID-19 patients with pneumothorax.

Methods

This is a retrospectivestudy conducted on COVID-19 patients with pneumothorax that had been hospitalized at hospital. l from December 2021 to March 2022. The chest computed tomography (CT) scan of all patients was reviewed by an experienced pulmonologist in search of pulmonary pneumothorax. Survival analysis was conducted to identify the predictors of survival in patients with COVID-19 and pneumothorax.

Results

A total of 67 patients with COVID-19 and pneumothorax were identified. Of these, 40.7% were located in the left lung, 40.7% were in the right lung, and 18.6% were found bilaterally. The most common symptoms in the patient with pneumothorax were dyspnea (65.7%), increased cough severity (53.7%), chest pain (25.4%), and hemoptysis (16.4%). The frequency of pulmonary left and right bullae, pleural effusion, andfungus ball were 22.4%, 22.4%, 22.4%, and 7.5%, respectively. Pneumothorax was managed with chest drain (80.6%), chest drain and surgery (6%), and conservatively (13.4%). The 50-day mortality rate was 52.2% (35 patients). The average survival time for deceased patients was 10.06 (2.17) days.

Conclusions

Our results demonstrated that those with pleural effusion or pulmonary bullae have a lower survival rate. Further studies are required to investigate the incidence and causality relation between COVID-19 and pneumothorax.
Variability of toe pressures during haemodialysis: comparison of people with and without diabetes; a pilot study
Authors: Carle Rachel , Tehan Peta , Stewart Sarah , Semple David , Pilmore Andrew , Carroll Matthew R.
Published: July 2023

Background

Diabetes, end stage renal disease (ESRD), and peripheral arterial disease (PAD) are associated with a higher risk of diabetes‐related lower limb amputation. Timely identification of PAD with toe systolic blood pressure (TSBP) and toe‐brachial pressure index (TBPI) is critical in order to implement foot protection strategies to prevent foot complications in people with ESRD. There is limited evidence describing the effect of haemodialysis on TSBP and TBPI. This study aimed to determine the variability of TSBP and TBPI during haemodialysis in people with ESRD, and to determine whether any observed variability differed between people with and without diabetes.

Methods

TSBP and TBPI were taken before dialysis (T1), one hour into dialysis (T2) and in the last 15 min of dialysis (T3) during a single dialysis session. Linear mixed effects models were undertaken to determine the variability in TSBP and TBPI across the three time points and to determine whether this variability differed between people with and without diabetes.

Results

Thirty participants were recruited, including 17 (57%) with diabetes and 13 (43%) with no diabetes. A significant overall reduction in TSBP was observed across all participants (P < 0.001). There was a significant reduction in TSBP between T1 and T2 (P < 0.001) and between T1 and T3 (P < 0.001). There was no significant overall change in TBPI over time (P = 0.62). There was no significant overall difference in TSBP between people with diabetes and people with no diabetes (mean difference [95% CI]: ‐9.28 [‐40.20, 21.64], P = 0.54). There was no significant overall difference in TBPI between people with diabetes and people with no diabetes (mean difference [95% CI]: ‐0.01 [‐0.17, 03.16], P = 0.91).

Conclusion

TSBP and TBPI are an essential part of vascular assessment of the lower limb. TBPI remained stable and TSBP significantly reduced during dialysis. Given the frequency and duration of dialysis, clinicians taking toe pressures to screen for PAD should be aware of this reduction and consider how this may have an impact on wound healing capacity and the development of foot related complications.
Efficacy of mHealth and education-led peer counseling for patients with hypertension and coronary artery disease in Pakistan: study protocol for a double-blinded pragmatic randomized-controlled trial with factorial design
Authors: Arshed Muhammad , Zakar Rubeena , Umer Muhammad Farooq , Kiran Mehwish , Ullah Najeeb , Iftikhar Ghazala , Fischer Florian
Published: July 2023

Background

Hypertension is a highly relevant public health challenge. Digital interventions may support improving adherence to anti-hypertensive medications and alter health behavior. Therefore, this protocol describes a study that aims to assess the effectiveness of mHealth and educational support through peer counseling (Ed-counselling) to control blood pressure in hypertensive patients when compared to standard care.

Methods

We chose a double-blinded pragmatic randomized-controlled with factorial design for this investigation. The trial is going to recruit 1648 hypertensive patients with coronary artery disease at the age of 21 to 70 years. All participants will already be on anti-hypertensive medication and own a smartphone. They will be randomized into four groups with each having 412 participants. The first group will only receive standard care; while the second group, in addition to standard care, will receive monthly Ed-counselling (educational booklets with animated infographics and peer counseling); the third group will receive daily written and voice reminders and an education-led video once weekly together with standard care; while the fourth one gets both interventions given to second and third groups respectively. All groups will be followed-up for 1 year (0, 6, and 12 months). The primary outcome will be the change in systolic blood pressure while secondary outcomes include health-related quality of life and changes in medication adherence. For measuring changes in systolic blood pressure (SBP) and adherence scores difference at 0, 6, and 12 months between and within the group, parametric (ANOVA/repeated measure ANOVA) and non-parametric tests (Kruskal-Wallis test/Friedman test) will be used. By using the general estimating equation (GEE) with negative binomial regression, at 12 months, the covariates affecting primary and secondary outcomes will be determined and controlled. The analysis will be intention-to-treat. All the outcomes will be analyzed at 0, 6, and 12 months; however, the final analysis will be at 12 months from baseline.

Discussion

Besides adding up to existing evidence in the literature on the subject, our designed modules using mHealth technology can help in reducing hypertension-related morbidity and mortality in developing countries.
Worldwide productivity and research trend of publications concerning tumor immune microenvironment (TIME): a bibliometric study
Authors: Liu Yao-Ge , Jiang Shi-Tao , Zhang Lei , Zheng Han , Zhang Ting , Zhang Jun-Wei , Zhao Hai-Tao , Sang Xin-Ting , Xu Yi-Yao , Lu Xin
Published: July 2023

Background

As the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective.

Methods

We acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package “Bibliometrix” was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers.

Results

A total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately.

Conclusions

This research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in “TIME and cancer prognosis”, “cancer immunotherapy”, and “immune checkpoint”. Our researchers identified the following areas: “immune checkpoint-based immunotherapy”, “precise immunotherapy” and “immunocyte pattern”, which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.
Bioaccumulation of potentially toxic elements by indigenous and exotic trees growing around a copper leaching plant in Mufulira, Zambia
Authors: Mulenga Charles , Phiri Darius , Ortega-Rodriguez Daigard Ricardo , Meincken Martina
Published: July 2023

Potentially toxic elements (PTEs) from mining industries pollute the surrounding environment and threaten the health of communities. Worldwide, exotic and indigenous trees are being recommended for green belts to trap dust and thereby limit the dispersion of PTEs. This study compares the potential of exotic (Eucalyptus grandis and E. camaldulensis) and native (Brachystegia longifolia) tree species in Zambia to accumulate PTEs and evaluate their ability to biomonitor heavy metal pollution. Tree bark and leaf samples were collected from 10 trees per study species growing at the same site downwind from a copper-leaching plant. Thirty topsoil samples were collected one metre from each sampled tree trunk. Portable X-ray fluorescence was used to analyse the elemental composition and concentration of trace elements in plant and soil samples. Pollution indices were used to establish the status and degree of soil contamination, while the bioaccumulation factor determined the ability of the studied species to accumulate PTEs. Heavy metals, including Mn, Ni, Pb, Cd, Cu, Fe and Zn were detected across soil and biomass samples, with a significant variation between species and plant parts. The pollution indices established that the soil at the study site is highly contaminated with Cu. The concentration of the studied trace elements varied across species following the order E. grandis > B. longifolia > E. camaldulensis in both tree bark and leaves. Determined bioaccumulation factors indicated Cd, Mn and Zn accumulation abilities of all the studied species suggesting their biomonitoring and phytoremediation potential. This implies that the study species have the potential to biomonitor Cd, Mn and Zn. Furthermore, a higher concentration of Cu was detected in B. longifolia bark, suggesting that this tree species can be used to biomonitor Cu pollution attributed to emissions from industrial activities. This study presents new insights into improving the management of polluted environments through biomonitoring and bioaccumulation of PTEs which can guide the selection of appropriate species for greenbelts in industrial areas.
Assessing seed and breeding interventions for organic farming using a multiagent value chain approach
Authors: Winter Eva , Grovermann Christian , Messmer Monika M. , Aurbacher Joachim
Published: July 2023

According to the EU’s organic regulation, the use of organic seed is generally binding in organic farming. Because of an organic seed shortage, derogations to use nonorganic seed can be obtained. By 2036, the EU plans to phase out these derogations and achieve 100% organic seed use. Previous attempts at achieving this, though, have failed. Ensuring organic seed supply is of particular EU-wide importance to meet EU policy goals, such as the farm-to-fork strategy. To assess the impact of measures to smooth this transition, we developed the VAL-MAS model (VALue chain Multi-Agent System). VAL-MAS is a multiagent model based on a heterogeneous agent population and mathematical programming that can provide insights into the performance of different seed system interventions. We selected organic fresh market carrots in Germany for their importance in the national and European organic sector as an example case. Our model suggests that the end of the derogation system poses a challenge to the seed value chain in terms of seed supply and farm incomes. The most effective mitigation solution is an investment in improved pest control during seed multiplication, accompanied by a stepwise phasing out of derogations for the use of nonorganic seed.
Media screen time use and mental health in school aged children during the pandemic
Authors: Hmidan Amira , Seguin Diane , Duerden Emma G.
Published: July 2023

Background

Children’s screen time activity has increased significantly during the pandemic. Extended school closures and heightened parent stress are associated with children’s behavioural difficulties and time spent watching screens. The primary aim of this study was to determine which school and household factors were associated with challenging behaviours in Canadian schoolchildren during the COVID-19 pandemic.

Methods

This longitudinal survey study examined the association amongst screen time, internalizing and externalizing behaviours in school-aged children at two time points over the 2020–2021 academic school year. Parents completed survey measures on their parental involvement, stress levels, and their child’s screen time use as well as their emotional and behavioural difficulties.

Results

Children’s average daily screen time was 4.40 h (SE = 18.45) at baseline and 3.89 h (SE = 16.70) at 1-year follow up, with no significant change across the school year (p = .316). Increased screen time use was associated with a greater incidence of internalizing behaviours in children (p = .03). Children who spent more time on screens and who were in households with parents reporting higher stress levels had increased internalizing behaviours (p < .001). No association between screen time use and externalizing behaviours was evident; however, parent stress was positively associated with children’s externalizing behaviours (p < .001).

Conclusions

Children’s screen time use has remained high during the pandemic and is associated with anxious and depressive symptoms. Children who spent more time on screens and who were in households with parents reporting higher stress levels had increased internalizing behaviours. Parent stress was positively associated with children’s externalizing behaviours. Targeted family intervention plans focused on reducing parent stress and screen time use may aid in improving children’s mental health during the ongoing pandemic.
Influence of mental health on information seeking, risk perception and mask wearing self-efficacy during the early months of the COVID-19 pandemic: a longitudinal panel study across 6 U.S. States
Authors: Welton-Mitchell Courtney , Dally Miranda , Dickinson Katherine L. , Morris-Neuberger Lindsay , Roberts Jennifer D. , Blanch-Hartigan Danielle
Published: July 2023

Background

Understanding factors that influence information seeking, assessment of risk and mitigation behaviors is critical during a public health crises. This longitudinal study examined the influence of self-reported mental health during the early months of the COVID-19 pandemic on information seeking, risk perception and perceived mask wearing ability. Mental health screener items included fear, anger, and hopelessness in addition to avoidance, diminished functional ability and global distress. Theoretical models inform hypotheses linking mental health items and outcomes.

Methods

The research employed a longitudinal 6-state 3-wave online panel survey, with an initial sample of 3,059 participants (2,232 included in longitudinal analyses). Participants roughly represented the states’ age, race, ethnicity, and income demographics.

Results

Women, those who identified as Hispanic/Latinx, Black Americans and lower income participants reported higher overall rates of distress than others. Information seeking was more common among older persons, Democrats, retirees, those with higher education, and those who knew people who had died of COVID-19. Controlling for such demographic variables, in multivariable longitudinal models that included baseline mental health measures, distress and fear were associated with increased information seeking. Distress and fear were also associated with increased risk perception, and feelings of hopelessness were associated with lower reported mask-wearing ability.

Conclusions

Results advance understanding of the role mental health can play in information seeking, risk perception and mask wearing with implications for clinicians, public health practitioners and policy makers.
Reconstructing long-term settlement histories on complex alluvial floodplains by integrating historical map analysis and remote-sensing: an archaeological analysis of the landscape of the Indus River Basin
Authors: Garcia-Molsosa Arnau , Orengo Hector A. , Petrie Cameron A.
Published: July 2023

Alluvial floodplains were one of the major venues of the development and long-term transformation of urban agrarian-based societies. The historical relationship between human societies and riverine environments created a rich archaeological record, but it is one that is not always easy to access due to the dynamism of alluvial floodplains and the geomorphological processes driven their hydrological regimes. Alluvial floodplains are also targeted for urban and agricultural expansion, which both have the potential to pose threats to cultural heritage and the environment if not carefully managed. Analysis that combines Historical Cartography and Remote Sensing sources to identify potential archaeological sites and river palaeochannels is an important first step towards the reconstruction of settlement patterns in different historical periods and their relationship to the history of hydrological networks. We are able to use different computational methods to great effect, including algorithms to enhance the visualization of different features of the landscape; and for processing large quantity of data using Machine-Learning based methods. Here we integrate those methods for the first time in a single study case: a section of the Indus River basin. Using a combined approach, it has been possible to map the historical hydrological network in a detail never achieved before and identify hundreds of potential archaeological sites previously unknown. Discussing these datasets together, we address the interpretation of the archaeological record, and highlight how Remote Sensing approaches can inform future research, heritage documentation, management, and preservation. The paper concludes with a targeted analysis of our datasets in the light of previous field-based research in order to provide preliminary insights on how long-term processes might have re-worked historical landscapes and their potential implications for the study of settlement patterns in different Historical periods in this region, thereby highlighting the potential for such integrated approaches.
The evolution of Big Data in neuroscience and neurology
Authors: Dipietro Laura , Gonzalez-Mego Paola , Ramos-Estebanez Ciro , Zukowski Lauren Hana , Mikkilineni Rahul , Rushmore Richard Jarrett , Wagner Timothy
Published: July 2023

Neurological diseases are on the rise worldwide, leading to increased healthcare costs and diminished quality of life in patients. In recent years, Big Data has started to transform the fields of Neuroscience and Neurology. Scientists and clinicians are collaborating in global alliances, combining diverse datasets on a massive scale, and solving complex computational problems that demand the utilization of increasingly powerful computational resources. This Big Data revolution is opening new avenues for developing innovative treatments for neurological diseases. Our paper surveys Big Data’s impact on neurological patient care, as exemplified through work done in a comprehensive selection of areas, including Connectomics, Alzheimer’s Disease, Stroke, Depression, Parkinson’s Disease, Pain, and Addiction (e.g., Opioid Use Disorder). We present an overview of research and the methodologies utilizing Big Data in each area, as well as their current limitations and technical challenges. Despite the potential benefits, the full potential of Big Data in these fields currently remains unrealized. We close with recommendations for future research aimed at optimizing the use of Big Data in Neuroscience and Neurology for improved patient outcomes.
Understanding the antecedents of intention for using mobile learning
Authors: Kashive Neerja , Phanshikar Dharini
Published: July 2023

This study aimed to identify the factors, which affect the continuance of mobile learning. The study has looked at epistemological, social, and security risk factors based on Magsayo (Interact Technol Smart Educ 20(2):177–208) and how they affect the perceived functional benefits (PFB) and perceived learner value (PLV). Further locus of control and self-efficacy are two personal factors that are investigated in the study to understand mobile learning acceptance continuance. 260 respondents of the study were students and professionals from India who have used mobile for learning. Based on previous research, hypotheses were formulated and tested empirically by building a model using smart PLS structure equation modeling. It was observed that epistemological, security risk and social factors did affect the computer self-efficacy and locus of control of the learners. Epistemological and social factors do contribute to developing PFB and PLV leading to higher mobile learning acceptance continuance. PFB and PLV also showed mediating effects. Based on Magsayo's (2023) previous work, the study has a unique contribution in showing that epistemological and social factors along with security risk do help in developing PFB and PLV leading to higher mobile learning acceptance continuance. These findings can help us understand ways to the development of mobile learning content and context for higher impact.
Improving reflective evaluations of sport through repeated experiences of fun—rationale, design, feasibility, and acceptability of the PlayFit Youth Sport Program
Authors: Ladwig Matthew A. , Sciamanna Christopher N. , Luzier Gavin , Blaker Joshua M. , Agans Jennifer P. , Visek Amanda J.
Published: July 2023

Introduction

Adolescents who drop out of sport often report that it had become less ‘fun’ and ‘enjoyable’ over time. Although preadolescent sport typically emphasizes experiences of fun, emphases on competition and elite performance often dominate during adolescence. We theorized that adherence to adolescent sport might be improved if the overarching goal were to maximize repeated experiences of fun during sport and, subsequently, increase reflective evaluations of sport enjoyment. To that end, this manuscript reports on the rationale and design of the PlayFit Youth Sport Program (PYSP), as well as its preliminary feasibility and acceptability. The main objectives were to evaluate the feasibility of recruitment strategies and data collection procedures and the acceptability of the intervention.

Setting

An outdoor, multipurpose grass field at a south-central Pennsylvania middle school.

Methods

A mixed-methods, single-arm feasibility trial lasting for 8 weeks (August–October 2021) offered 3-times per week for 1-h per session. The equipment, ruleset, and psychosocial environment of the PYSP sport games were modified to reduce several of the constraints theorized to impair experiences of fun during sport and hamper reflective evaluations of enjoyment afterward.

Results

Eleven healthy, but sedentary adolescents in grades 5–7 completed the program. The median number of sessions attended (of 16 possible) was 12 (range = 6–13). Post-intervention, 9/10 respondents indicated that they ‘looked forward’ to the PYSP, 8/10 would recommend it to a friend, and 8/10 were interested in continuing the program. Ten of 11 participant guardians expressed interest in reenrolling their children if the PYSP were offered again. Some changes recommended were to improve recruitment via advertising the positive aspects of the program and “word of mouth” techniques, offering the program immediately following the school day, having contingencies for inclement weather, and minor changes to the sport equipment to improve the experience among the population the PYSP intends to attract.

Conclusions

The adjustments recommended in this preliminary work could be used to further refine the PYSP. A future efficacy trial could explore whether the PYSP may reduce attrition for adolescents who experience existing sport programs negatively by offering an alternative that better matches their unique needs and preferences.
Anti-diabetic properties of traditional herbal concoction containing Eleutherine palmifolia (L.) Merr., Momordica charantia L., and Syzygium polyanthum (Wight.): a bibliometric analysis
Authors: Hairani Muhammad Afnan Shakir , Abdul Majid Fadzilah Adibah , Zakaria Nor Hafizah , Hudiyanti Dwi , Fadhlina Anis , Sheikh Hassan Ibrahim
Published: July 2023

Eleutherine palmifolia, Momordica charantia, and Syzygium polyanthum are herbal plants, traditionally used as natural remedies for diabetes. There have been numerous articles published on the anti-diabetic efficacy of these plants; yet, no bibliometric study on the subject is available. In this study, the published papers on the utilization of E. palmifolia, M. charantia, and S. polyanthum as anti-diabetic agents were examined using bibliometric approach, focusing on countries, organizations, authors, and keywords. The phytochemicals, pharmacological properties, and mechanism of action of each herbal plant associated with diabetes were also discussed in detail. The data were searched through the SCOPUS database and bibliometric analysis was performed using VOSviewer software. The World Flora Online (WFO) was used to confirm the identity of the plant species. A total of 1008 articles were retrieved with M. charantia (977 articles) showing the highest number of publishing articles compared to E. palmifolia (9 articles), and S. polyanthum (22 articles). Upon further review of these plants, the findings showed that each plant has active ingredients that can prevent as well as control the complications of diabetes. Eleutherol, eleuthenone, eleutherinoside A, kuguacin, momordicin, vicine, squalene, myricitrin and epigallocatechin gallate (EGCG) were among the phytochemicals responsible for the effect. The possible underlying mechanisms of action were attributed to lowering blood glucose, increasing insulin production, inhibiting intestinal glucose absorption, and enhancing glucose uptake by the muscles. Based on the review, it is evidenced that the individual plants demonstrated a promising anti-diabetic activity, thus, it is recommended to conduct further studies using a polyherbal mixture, combining these three extracts and analyzing using in vitro and in vivo models.

Graphical Abstract
Outcome of ALL With ALL-BFM-95 Protocol in Nepal
Authors: Sharma Poudyal Bishesh , Paudel Bishal , Tuladhar Sampurna , Neupane Samir , Bhattarai Kushal , Joshi Utsav
Published: July 2023

PURPOSE

Data on survival outcomes in patients with acute lymphoblastic leukemia (ALL) originating from Nepal are limited. We aim to present the real-world data on treatment outcomes of patients with de novo ALL treated with pediatric ALL-Berlin-Frankfurt-Muenster (BFM)-95 protocol in Nepal.

PATIENTS AND METHODS

We used the medical records of 103 consecutive patients with ALL treated in our center from 2013 to 2016 to evaluate the overall survival (OS) and relapse-free survival (RFS) and analyzed the effects of clinicopathologic factors on survival outcomes in patients with ALL.

RESULTS

The 3-year OS and RFS in the entire cohort was 89.4% (95% CI, 82.1 to 96.7) and 87.3% (95% CI, 79.8 to 94.7), with a mean OS and RFS of 79.4 months (95% CI, 74.2 to 84.5) and 76.6 months (95% CI, 70.8 to 82.4), respectively. Patients with prednisone good response (PGR) showed better mean OS and RFS, whereas complete marrow response on day 33 was associated with better mean OS alone. Patients with Philadelphia (Ph)-positive ALL showed worse mean RFS compared to those with Ph-negative status. On multivariate analysis, PGR (hazard ratio [HR], 0.11; 95% CI, 0.03 to 0.49; P = .004) and sagittal vein thrombosis (SVT; HR, 5.95; 95% CI, 1.30 to 27.18; P = .02) were the only independent predictors of OS and RFS, respectively. Adverse events on BFM-95 protocol included SVT (4.9%), peripheral neuropathy (7.8%), myopathy (20.4%), hyperglycemia (24.3%), intestinal obstruction (7.8%), avascular necrosis of femur (6.8%), and mucositis (46%).

CONCLUSION

BFM-95 protocol appears to be a safe and effective strategy in adolescent and young adults and adult Nepalese population with ALL with a low toxicity profile.
An AI Approach to Generating MIDD Assets Across the Drug Development Continuum
Authors: Barrett Jeffrey S , Goyal Rahul K , Gobburu Jogarao , Baran Szczepan , Varshney Jyotika
Published: July 2023

Model-informed drug development involves developing and applying exposure-based, biological, and statistical models derived from preclinical and clinical data sources to inform drug development and decision-making. Discrete models are generated from individual experiments resulting in a single model expression that is utilized to inform a single stage-gate decision. Other model types provide a more holistic view of disease biology and potentially disease progression depending on the appropriateness of the underlying data sources for that purpose. Despite this awareness, most data integration and model development approaches are still reliant on internal (within company) data stores and traditional structural model types. An AI/ML-based MIDD approach relies on more diverse data and is informed by past successes and failures including data outside a host company (external data sources) that may enhance predictive value and enhance data generated by the sponsor to reflect more informed and timely experimentation. The AI/ML methodology also provides a complementary approach to more traditional modeling efforts that support MIDD and thus yields greater fidelity in decision-making. Early pilot studies support this assessment but will require broader adoption and regulatory support for more evidence and refinement of this paradigm. An AI/ML-based approach to MIDD has the potential to transform regulatory science and the current drug development paradigm, optimize information value, and increase candidate and eventually product confidence with respect to safety and efficacy. We highlight early experiences with this approach using the AI compute platforms as representative examples of how MIDD can be facilitated with an AI/ML approach.

Graphical abstract
Tissue Acceleration as a Novel Metric for Surgical Performance During Carotid Endarterectomy
Authors: Sugiyama Taku , Ito Masaki , Sugimori Hiroyuki , Tang Minghui , Nakamura Toshitaka , Ogasawara Katsuhiko , Matsuzawa Hitoshi , Nakayama Naoki , Lama Sanju , Sutherland Garnette R. , Fujimura Miki
Published: July 2023

BACKGROUND AND OBJECTIVES:

Gentle tissue handling to avoid excessive motion of affected fragile vessels during surgical dissection is essential for both surgeon proficiency and patient safety during carotid endarterectomy (CEA). However, a void remains in the quantification of these aspects during surgery. The video-based measurement of tissue acceleration is presented as a novel metric for the objective assessment of surgical performance. This study aimed to evaluate whether such metrics correlate with both surgeons' skill proficiency and adverse events during CEA.

METHODS:

In a retrospective study including 117 patients who underwent CEA, acceleration of the carotid artery was measured during exposure through a video-based analysis. Tissue acceleration values and threshold violation error frequencies were analyzed and compared among the surgeon groups with different surgical experience (3 groups: novice, intermediate, and expert). Multiple patient-related variables, surgeon groups, and video-based surgical performance parameters were compared between the patients with and without adverse events during CEA.

RESULTS:

Eleven patients (9.4%) experienced adverse events after CEA, and the rate of adverse events significantly correlated with the surgeon group. The mean maximum tissue acceleration and number of errors during surgical tasks significantly decreased from novice, to intermediate, to expert surgeons, and stepwise discriminant analysis showed that the combined use of surgical performance factors could accurately discriminate between surgeon groups. The multivariate logistic regression analysis revealed that the number of errors and vulnerable carotid plaques were associated with adverse events.

CONCLUSION:

Tissue acceleration profiles can be a novel metric for the objective assessment of surgical performance and the prediction of adverse events during surgery. Thus, this concept can be introduced into futuristic computer-aided surgeries for both surgical education and patient safety.
Simulation study of comparative dosimetric analysis of coplanar horizontal-port scanned carbon-ion beam therapy in the head and neck
Authors: Ebner Daniel , Koto Masashi , Furuichi Wataru , Mori Shinichiro
Published: July 2023

Objective:

Carbon-ion radiotherapy (CIRT) has demonstrated success in treating radioresistant disease within the head and neck, owing to its unique physical and radiobiological properties. Construction cost remains prohibitive; a center offering only a horizontal port may bridge this difficulty, but removal of the vertical port may prohibit treatment of disease near critical organs-at-risk. Building a center only containing a horizontal treatment port has been proposed as one method for cost savings.

Methods:

20 complex cases of head and neck cancer previously treated with conventional CIRT were retrospectively planned using horizontal-port-only treatment incorporating non-coplanar treatment angles to achieve greater degrees of freedom. These were dosimetrically compared with the previous plans.

Results:

Comparable D95 coverage of both planning target volume and gross tumor volume with ability to meet organ-at-risk constraints were feasible with horizontal-port-only treatment. Collectively differences were noted in PTV D95, brain stem Dmax, contralateral eye Dmax and V10 Gy (RBE); further qualitative differences were noted on a plan-by-plan basis dependent on disease location.

Conclusion:

Horizontal-port-only treatment employing non-coplanar angles was feasible for complicated head and neck disease typically treated with CIRT, though careful consideration is necessary on a plan-by-plan basis.

Advances in knowledge:

It is worth noting that non-coplanar approaches are not typically used with the current treatment gantry and may extend further the difference between horizontal port planning and a gantry-based gold-standard.
The rise of preprints in earth sciences
Authors: Pourret Olivier , Ibarra Daniel Enrique
Published: July 2023

The rate of science information's spread has accelerated in recent years. In this context, it appears that many scientific disciplines are beginning to recognize the value and possibility of sharing open access (OA) online manuscripts in their preprint form. Preprints are academic papers that are published but have not yet been evaluated by peers. They have existed in research at least since the 1960s and the creation of ArXiv in physics and mathematics. Since then, preprint platforms—which can be publisher- or community-driven, profit or not for profit, and based on proprietary or free and open source software—have gained popularity in many fields (for example, bioRxiv for the biological sciences). Today, there are many platforms that are either disciplinary-specific or cross-domain, with exponential development over the past ten years. Preprints as a whole still make up a very small portion of scholarly publishing, but a large group of early adopters are testing out these value-adding tools across a much wider range of disciplines than in the past. In this opinion article, we provide perspective on the three main options available for earth scientists, namely EarthArXiv, ESSOAr/ESS Open Archive and EGUsphere.
“Grabbing” Autonomy When the Learning Environment Doesn’t Support it: An Evidence-based Guide for Medical Learners
Authors: Neufeld Adam
Published: July 2023

According to self-determination theory (SDT), environments which support the basic psychological needs for autonomy, competence, and relatedness will facilitate autonomous motivation, learning, and wellness. On the other hand, environments which introduce external controls and power dynamics into the equation will do the opposite. Educational studies support these principles, yet most have focused on learners’ need satisfaction as a passive process (e.g., via support or hindrance by educators), rather than the agentic pursuit that SDT emphasizes. In this commentary, I draw on my experience as a practicing physician and SDT researcher, and focus on how medical learners can “grab” more autonomy when the learning environment does not support it. I present a hypothetical case of a preceptor whose teaching style is controlling and unfortunately well-known to medical learners. I then unpack the case and outline different strategies that medical learners can use to navigate this type of interpersonal conflict.