bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges and solutions for transforming health ecosystems in low- and middle-income countries through artificial intelligence
Authors: López Diego M. , Rico-Olarte Carolina , Blobel Bernd , Hullin Carol 
Published: December 2022

BackgroundRecent studies demonstrate the potential of Artificial Intelligence to support diagnosis, mortality assessment, and clinical decisions in low-and-middle-income countries (LMICs). However, explicit evidence of strategies to overcome the particular challenges for transformed health systems in these countries does not exist.ObjectiveThe present study undertakes a review of research on the current status of artificial intelligence (AI) to identify requirements, gaps, challenges, and possible strategies to strengthen the large, complex, and heterogeneous health systems in LMICs.DesignAfter introducing the general challenges developing countries face, the methodology of systematic reviews and the meta-analyses extension for scoping reviews (PRISMA-ScR) is introduced according to the preferred reporting items. Scopus and Web of Science databases were used to identify papers published between 2011–2022, from which we selected 151 eligible publications. Moreover, a narrative review was conducted to analyze the evidence in the literature about explicit evidence of strategies to overcome particular AI challenges in LMICs.ResultsThe analysis of results was divided into two groups: primary studies, which include experimental studies or case studies using or deploying a specific AI solution (n= 129), and secondary studies, including opinion papers, systematic reviews, and papers with strategies or guidelines (n= 22). For both study groups, a descriptive statistical analysis was performed describing their technological contribution, data used, health context, and type of health interventions. For the secondary studies group, an in-deep narrative review was performed, identifying a set of 40 challenges gathered in eight different categories: data quality, context awareness; regulation and legal frameworks; education and change resistance; financial resources; methodology; infrastructure and connectivity; and scalability. A total of 89 recommendations (at least one per challenge) were identified.ConclusionResearch on applying AI and ML to healthcare interventions in LMICs is growing; however, apart from very well-described ML methods and algorithms, there are several challenges to be addressed to scale and mainstream experimental and pilot studies. The main challenges include improving the quality of existing data sources, training and modeling AI solutions based on contextual data; and implementing privacy, security, informed consent, ethical, liability, confidentiality, trust, equity, and accountability policies. Also, robust eHealth environments with trained stakeholders, methodological standards for data creation, research reporting, product certification, sustained investment in data sharing, infrastructures, and connectivity are necessary.Systematic review registration[https://rb.gy/frn2rz].
Correlations among peripheral blood markers, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events
Authors: Li Binghan , Du Bingying , Gu Zhengsheng , Wu Chenghao , Tan Yuhao , Song Chenrui , Xu Yawen , Yin Ge , Gao Xin , Wang Weisen , Sun Xu , Bi Xiaoying 
Published: December 2022

BackgroundBoth inflammation and cerebral white matter injury are closely associated with vascular cognitive impairment (VCI). The aim of this study was to analyze the correlation between peripheral serological markers, white matter injury, and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE); to identify potential biological markers for the diagnosis and prediction of VCI; and to provide a basis for the early diagnosis and intervention of VCI.MethodsWe collected clinical data, along with demographic and medical history data, from 151 NICE patients. Fasting venous blood samples were collected. Based on the Montreal Cognitive Assessment (MoCA) after admission, we divided the patients into normal cognitive function (NCF) and VCI groups, and then classified them into mild white matter hyperintensity (mWMH) and severe white matter hyperintensity (sWMH) based on Fazekas scores. The differences in serological marker levels were compared between the cognitive function groups and the white matter hyperintensity groups. Binary logistic regression models and receiver operating characteristic curves were used to analyze the diagnostic predictive value of serological markers for VCI in patients with NICE and in the white matter hyperintensity subgroups.ResultsAmong 151 patients with NICE, 95 were male and 56 were female. Lymphocyte count (OR = 0.405, p = 0.010, 95% CI [0.201, 0.806]), red blood cell count (OR = 0.433, p = 0.010, 95% CI [0.228, 0.821]), and hemoglobin level (OR = 0.979, p = 0.046, 95% CI [0.958, 0.999]) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age, granulocyte/lymphoid ratio (NLR), and neutrophil percentage but a lower MoCA score, hemoglobin level, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.713, p = 0.003, 95% CI [0.593, 0.833]) had an acceptable predictive value for the diagnosis of VCI, whereas white blood cell count (AUC = 0.672, p = 0.011, 95% CI [0.545, 0.799]), red blood cell count (AUC = 0.665, p = 0.014, 95% CI [0.545, 0.784]), and hemoglobin level (AUC = 0.634, p = 0.047, 95% CI [0.502, 0.765]) had marginal predictive value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups.ConclusionLymphocyte count, red blood cell count, and hemoglobin level were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.
Functional comorbidities and brain tissue changes before and after lung transplant in adults
Authors: Vandiver Matthew Scott , Roy Bhaswati , Mahmud Fahim , Lavretsky Helen , Kumar Rajesh 
Published: December 2022

BackgroundAdults undergoing lung transplant, as a lifesaving treatment for end stage lung disease, exhibit high levels of peri-operative neurocognitive dysfunction in multiple domains, including delirium, cognition, and autonomic deficits. These complications impact healthcare costs, quality of life, and patient outcomes. Post-operative symptoms likely result from loss of brain tissue integrity in sites mediating such regulatory functions. Our aim in this study was to examine peri-operative neurocognitive dysfunction and brain tissue changes after lung transplant in adults.MethodsWe retrospectively examined the UCLA lung transplant database to identify 114 lung transplant patients with pre-operative clinical and neurocognitive data. Of 114 patients, 9 lung transplant patients had pre- and post-transplant brain magnetic resonance imaging. Clinical and neurocognitive data were summarized for all subjects, and brain tissue volume changes, using T1-weighted images, before and after transplant were examined. T1-weighted images were partitioned into gray matter (GM)-tissue type, normalized to a common space, smoothed, and the smoothed GM-volume maps were compared between pre- and post-transplant (paired t-tests; covariate, age; SPM12, p &lt; 0.005).ResultsIncreased comorbidities, including the diabetes mellitus (DM), hypertension, kidney disease, and sleep disordered breathing, as well as higher rates of neurocognitive dysfunction were observed in the lung transplant patients, with 41% experiencing post-operative delirium, 49% diagnosed with a mood disorder, and 25% of patients diagnosed with cognitive deficits, despite incomplete documentation. Similarly, high levels of delirium, cognitive dysfunction, and mood disorder were noted in a subset of patients used for brain MRI evaluation. Significantly decreased GM volumes emerged in multiple brain regions, including the frontal and prefrontal, parietal, temporal, bilateral anterior cingulate and insula, putamen, and cerebellar cortices.ConclusionAdults undergoing lung transplant often show significant pre-operative comorbidities, including diabetes mellitus, hypertension, and chronic kidney disease, as well as neurocognitive dysfunction. In addition, patients with lung transplant show significant brain tissue changes in regions that mediate cognition, autonomic, and mood functions. The findings indicate a brain structural basis for many enhanced post-operative symptoms and suggest a need for brain tissue protection in adults undergoing lung transplant to improve health outcomes.
Continuous glucose monitoring reveals similar glycemic variability in individuals with obesity despite increased HOMA-IR
Authors: Cooper Dylan J. , Zarabi Sharon , Farrand Brianna , Becker Amanda , Roslin Mitchell 
Published: December 2022

Background/aimsContinuous glucose monitoring is a well-tolerated and versatile tool for management of diabetes and metabolic disease. While its use appears to be feasible to monitor glycemic profiles in diabetics, there is a paucity of data in individuals with obesity and normal glucose tolerance. The aim of this study is to investigate glucose fluctuations and insulin resistance patterns in normoglycemic participants with obesity vs. without obesity and contextualize these results against leading models for obesity.Materials and methodsWe designed a prospective, observational pilot study of two cohorts including 14 normoglycemic participants with obesity and 14 normoglycemic participants without obesity. Participants were monitored with continuous glucose monitoring (CGM) for five consecutive days. Insulin resistance levels were measured and glucometric data were extracted from CGM for all participants.ResultsFasting serum insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the group with obesity (P &lt; 0.05). While the group with obesity had a higher mean blood glucose (MBG), mean amplitude of glycemic excursions (MAGE), and continuous overall glycemic action-1 h (CONGA-1), these differences were not significant. On univariate linear regression, insulin resistance (HOMA-IR) was associated with body mass index (BMI), waist circumference (WC), cohort with obesity, cohort consuming a high glycemic diet, hemoglobin A1c (HbA1c), and fasting insulin levels. WC and fasting insulin levels remained predictors of HOMA-IR in our multivariable model.ConclusionWhile there is much excitement surrounding the use of commercial CGM products in obesity management, our results suggest that fasting insulin and HOMA-IR values may be more clinically useful than CGM data alone.
Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma
Authors: Wang Yadong , Wang Guanghui , Zheng Haotian , Liu Jichang , Ma Guoyuan , Huang Gemu , Song Qingtao , Du Jiajun 
Published: December 2022

With the development of technologies, multiple primary lung cancer (MPLC) has been detected more frequently. Although large-scale genomics studies have made significant progress, the aberrant gene mutation in MPLC is largely unclear. In this study, 141 and 44 lesions from single and multiple primary lung adenocarcinoma (SP- and MP-LUAD) were analyzed. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced by using the next-generation sequencing-based YuanSu450TM gene panel. We systematically analyzed the clinical features and gene mutations of these lesions, and found that there were six genes differently mutated in MP-LUAD and SP-LUAD lesions, including RBM10, CDK4, ATRX, NTRK1, PREX2, SS18. Data from the cBioPortal database indicated that mutation of these genes was related to some clinical characteristics, such as TMB, tumor type, et al. Besides, heterogeneity analysis suggested that different lesions could be tracked back to monophyletic relationships. We compared the mutation landscape of MP-LUAD and SP-LUAD and identified six differentially mutated genes (RBM10, CDK4, ATRX, NTRK1, PREX2, SS18), and certain SNV loci in TP53 and EGFR which might play key roles in lineage decomposition in multifocal samples. These findings may provide insight into personalized prognosis prediction and new therapies for MP-LUAD patients.
SPATA2 and CYLD inhibit T cell infiltration into colorectal cancer via regulation of IFN-γ/STAT1 axis
Authors: Tan Tze Guan , Zybina Yulia , McKenna Cooper , Olow Aleksandra , Rukmini Subhadra Jayaraman , Wong Michael Thomas , Sadekova Svetlana , Chackerian Alissa , Bauché David 
Published: December 2022

IntroductionColorectal cancer (CRC) is largely refractory to currently available immunotherapies such as blockade of programmed cell death protein-1 (PD-1).ResultsIn this study, we identified SPATA2 and its protein partner CYLD as novel regulators of CXC-ligand 10 (CXCL10), a T-cell-attractant chemokine, in CRC. By specifically deleting SPATA2 and CYLD in human and mouse CRC cell lines, we showed that these two proteins inhibit STAT1 accumulation and activation and subsequently CXCL10 expression in tumor cells. At steady-state, STAT1 is highly ubiquitinated in a SPATA2/CYLD-dependent manner. Finally, we demonstrated that tumor-specific deletion of SPATA2 and CYLD enhances anti-PD-1 response in vivo.DiscussionOur data suggest that SPATA2 and CYLD represent two potential novel targets for treatment of immune-excluded, PD-1-resistant tumors.
Photodynamic therapy in glioblastoma: Detection of intraoperative inadvertent 5-ALA mediated photodynamic therapeutical effect after gross total resection
Authors: Ferrés Abel , Di Somma Alberto , Mosteiro Alejandra , Topczewski Thomaz Eduardo , Roldán Pedro , Pedrosa Leire , Diao Diouldé , Pineda Estela , Sierra Àngels , Enseñat Joaquim , González-Sánchez José Juan 
Published: December 2022

IntroductionGlioblastoma (GBM) remains the most frequent and lethal primary brain tumor in adults, despite advancements in surgical resection techniques and adjuvant chemo- and radiotherapy. The most frequent recurrence pattern (75-90%) occurs in the form of continuous growth from the border of the surgical cavity, thus emphasizing the need for locoregional tumor control. Fluorescence-guided surgical resection using 5-ALA has been widely implemented in surgical protocols for such tumors. Recent literature also highlights the applicability of 5-ALA-mediated photodynamic therapy to obtain locoregional tumor control further. This study aims to identify if 5-ALA mediated photodynamic therapeutic effect after gross total glioblastoma resection has inadvertently occurred due to the exposition of protoporphyrin IX charged peripheral tumoral cells to operative room light sources.MethodsOf 146 patients who were intervened from glioblastoma between 2015 and 2020, 33 were included in the present study. Strict gross total resection (without supralocal resection) had been accomplished, and adjuvant chemoradiotherapy protocol was administered. Two comparison groups were created regarding the location of the recurrence (group A: up to 1 centimeter from the surgical cavity, and group B: beyond 1 centimeter from the surgical cavity). The cutoff point was determined to be 1 centimeter because of the visible light penetrance to the normal brain tissue.ResultsIn univariate analysis, both groups only differed regarding 5-ALA administration, which was significantly related to a minor relative risk of presenting the recurrence within the first centimeter from the surgical cavity (Relative Risk = 0,655 (95% CI 0,442-0,970), p-value=0,046). Results obtained in univariate analysis were corroborated posteriorly in multivariate analysis (RR=0,730 (95% CI 0,340-0,980), p=0,017).DiscussionIn the present study, a probable inadvertent 5-ALA photodynamic therapeutical effect has been detected in vivo. This finding widely opens the door for further research on this promising theragnostic tool.
Network pharmacological analysis of Xuefu Zhuyu decoction in the treatment of atherosclerosis
Authors: Yuan Jinxia , Yan Fei , Li Wei , Yuan Guoliang 
Published: December 2022

Objective: Using a network pharmacological approach, this study will evaluate the effect of Xuefu Zhuyu Decoction in the treatment of atherosclerosis.Methods: The data were imported into the STRING database to construct a protein-protein interaction network, and the network topology was analysed with the Bisogenet plug-in by Cytoscape 3.7.2. Using the R language Bioconductor platform, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for potential targets of Xuefu Zhuyu Decoction in the treatment of atherosclerosis were performed, and import the results were imported into Cytoscape 3.7.2. To map the results and create a KEGG network diagram, we used Cytoscape 3.7.2 for analysis.Results: A total of 91 chemical components and 1320 disease targets were obtained, including 138 cross-targets. TNF, AKT1 and ALB were identified as important targets, and Gene Ontology functional analysis indicated that biological process was the primary cause of oxidative stress. The primary action of molecular function is binding. KEGG has explored and enriched 149 signalling pathways, including the AGE-RAGE signalling system and the TNF signalling network. According to a study involving molecular docking, quercetin and β-carotene have a strong binding affinity for AKT1 and ALB.Conclusion: The potential of Xuefu Zhuyu Decoction to treat atherosclerosis through multiple components and targets provides a way to further study its mechanism.
Comprehensive transcriptome analysis reveals heat-responsive genes in flowering Chinese cabbage (Brassica campestris L. ssp. chinensis) using RNA sequencing
Authors: Ikram Muhammad , Chen Jingfang , Xia Yanshi , Li Ronghua , Siddique Kadambot H. M. , Guo Peiguo 
Published: December 2022

Flowering Chinese cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee, 2n=20, AA) is a vegetable species in southern parts of China that faces high temperatures in the summer and winter seasons. While heat stress adversely impacts plant productivity and survival, the underlying molecular and biochemical causes are poorly understood. This study investigated the gene expression profiles of heat-sensitive (HS) ‘3T-6’ and heat-tolerant (HT) ‘Youlu-501’ varieties of flowering Chinese cabbage in response to heat stress using RNA sequencing. Among the 37,958 genes expressed in leaves, 20,680 were differentially expressed genes (DEGs) at 1, 6, and 12 h, with 1,078 simultaneously expressed at all time points in both varieties. Hierarchical clustering analysis identified three clusters comprising 1,958, 556, and 591 down-regulated, up-regulated, and up- and/or down-regulated DEGs (3205 DEGs; 8.44%), which were significantly enriched in MAPK signaling, plant–pathogen interactions, plant hormone signal transduction, and brassinosteroid biosynthesis pathways and involved in stimulus, stress, growth, reproductive, and defense responses. Transcription factors, including MYB (12), NAC (13), WRKY (11), ERF (31), HSF (17), bHLH (16), and regulatory proteins such as PAL, CYP450, and photosystem II, played an essential role as effectors of homeostasis, kinases/phosphatases, and photosynthesis. Among 3205 DEGs, many previously reported genes underlying heat stress were also identified, e.g., BraWRKY25, BraHSP70, BraHSPB27, BraCYP71A23, BraPYL9, and BraA05g032350.3C. The genome-wide comparison of HS and HT provides a solid foundation for understanding the molecular mechanisms of heat tolerance in flowering Chinese cabbage.
The impact of computer–assisted technology on literacy acquisition during COVID-19-related school closures: Group–level effects and predictors of individual–level outcomes
Authors: Richter Caroline G. , Siegelman Noam , Mahaffy Kelly , Van Den Bunt Mark , Kearns Devin M. , Landi Nicole , Sabatini John , Pugh Kenneth , Hoeft Fumiko 
Published: December 2022

IntroductionThe COVID-19 pandemic led to school closure and loss of in-person instruction during the 2019–2020 academic year across the United States, which had a profound impact on the reading development of beginning readers. In this study we tested if a research-informed educational technology (EdTech) program–GraphoLearn–could help alleviate the COVID-19 slide. We also sought to understand the profiles of children who benefitted most from this EdTech program.MethodsWe tested participants’ (N = 172 K-2 children) early literacy skills using a standardized measure (STAR) before and after playing GraphoLearn, and used the pre to post difference as the dependent variable. We first compared children’s STAR actual and expected growth. Then we conducted a multiple regression analysis with data about engagement with GraphoLearn included as predictors. Additional predictors were extracted from GraphoLearn performance at study onset to assess children’s letter-sound knowledge, rime awareness, and word recognition.ResultsThe difference between actual average reading growth and expected growth in a regular school year was not statistically significant. This suggests that children in our sample seem to be gaining reading skills as expected in a regular school year. Our multiple linear regression model (which accounted for R2 = 48% of reading growth) showed that older children, with higher baseline GraphoLearn word recognition, who played more units in a fixed number of days, made significantly more early literacy progress.DiscussionWhile lacking a control group, our preliminary results suggest that an EdTech program such as GraphoLearn may be a useful reading instructional tool during school shutdowns. In addition, our results suggest that practice with GraphoLearn was more effective and efficient when foundational instruction was already in place.
Influence of emotion on precision grip force control: A comparison of pleasant and neutral emotion
Authors: Bunno Yoshibumi , Onigata Chieko 
Published: December 2022

ObjectiveThe present study aimed to investigate the impact of emotion on force steadiness of isometric precision pinch grip that is not direction-specific.MethodsThirty-two healthy volunteer subjects participated in the present study. Subjects were divided into two experimental groups: pleasant image group and neutral image group. The isometric precision pinch grip task was performed for three times. Specifically, the first task was performed before pleasant or neutral picture viewing, the second task was performed immediately after picture viewing, further the third task was performed 30 seconds after the second task. During the isometric precision pinch grip task, participants were asked to exert pinch grip force at 10% of maximal voluntary contraction with visual feedback. The coefficient of variation of force production and normalized root mean square value of electromyography activity were calculated.ResultsAfter pleasant picture viewing, coefficient of variation of pinch force production and normalized root mean square value of electromyography was decreased. While, in the neutral image condition, theses variables were not altered. More important, compared to the neutral image condition, pleasant emotion led to lower coefficient of variation of pinch grip force production.ConclusionThese findings indicate that pleasant emotion improves force control of isometric precision pinch grip. Therefore, in clinical settings, the emotional state of patients may affect the effectiveness of rehabilitation and should be taken into consideration.