bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using big data and Population Health Management to assess care and costs for patients with severe mental disorders and move toward a value-based payment system
Authors: Tozzi Valeria D. , Banks Helen , Ferrara Lucia , Barbato Angelo , Corrao Giovanni , D’avanzo Barbara , Di Fiandra Teresa , Gaddini Andrea , Compagnoni Matteo Monzio , Sanza Michele , Saponaro Alessio , Scondotto Salvatore , Lora Antonio 
Published: September 2023

Abstract
Background
Mental health (MH) care often exhibits uneven quality and poor coordination of physical and MH needs, especially for patients with severe mental disorders. This study tests a Population Health Management (PHM) approach to identify patients with severe mental disorders using administrative health databases in Italy and evaluate, manage and monitor care pathways and costs. A second objective explores the feasibility of changing the payment system from fee-for-service to a value-based system (e.g., increased care integration, bundled payments) to introduce performance measures and guide improvement in outcomes.

Methods
Since diagnosis alone may poorly predict condition severity and needs, we conducted a retrospective observational study on a 9,019-patient cohort assessed in 2018 (30.5% of 29,570 patients with SMDs from three Italian regions) using the Mental Health Clustering Tool (MHCT), developed in the United Kingdom, to stratify patients according to severity and needs, providing a basis for payment for episode of care. Patients were linked (blinded) with retrospective (2014–2017) physical and MH databases to map resource use, care pathways, and assess costs globally and by cluster. Two regions (3,525 patients) provided data for generalized linear model regression to explore determinants of cost variation among clusters and regions.

Results
Substantial heterogeneity was observed in care organization, resource use and costs across and within 3 Italian regions and 20 clusters. Annual mean costs per patient across regions was €3,925, ranging from €3,101 to €6,501 in the three regions. Some 70% of total costs were for MH services and medications, 37% incurred in dedicated mental health facilities, 33% for MH services and medications noted in physical healthcare databases, and 30% for other conditions. Regression analysis showed comorbidities, resident psychiatric services, and consumption noted in physical health databases have considerable impact on total costs.

Conclusions
The current MH care system in Italy lacks evidence of coordination of physical and mental health and matching services to patient needs, with high variation between regions. Using available assessment tools and administrative data, implementation of an episodic approach to funding MH could account for differences in disease phase and physical health for patients with SMDs and introduce performance measurement to improve outcomes and provide oversight.
Patient satisfaction survey of the “Healthy Heart” pharmaceutical care service – evaluation of pharmacy labelling with pharmaceutical pictograms
Authors: Merks Piotr , Religioni Urszula , Jaguszewski Miłosz , Barańska Agnieszka , Neumann-Podczaska Agnieszka , Kaźmierczak Justyna , Blicharska Eliza , Šola Katarina Fehir , Vaillancourt Regis 
Published: September 2023

Abstract
Introduction
Low adherence is a major challenge in healthcare worldwide, being particularly dangerous for patients with chronic diseases, such as cardiovascular diseases and heart failure, where strict adherence is essential. Non-adherence is observed in almost half of patients, and the consequences encompass a lack of therapeutic effects, health deterioration, decreased quality of life, and even death. For cardiovascular patients, the great importance of health education and pharmaceutical education can be provided within pharmaceutical care in community pharmacies. Therefore, our study aimed at evaluating the level of satisfaction with the “Healthy Heart” pharmaceutical service, in which patients received pictograms with dosage information affixed to their medication.

Material and methods
The study was designed for patients who had been prescribed an antiplatelet medication for the first time. The patients were recruited by 577 pharmacies that took part in the study after completing a special course. Ultimately, 1590 patients were enrolled in the study. The project ran from November 2019 to January 2022.

Results
Most of patients had a positive attitude to the “Healthy Heart” pharmaceutical service. More than 85% of the respondents were of the opinion that the pictograms facilitated the use of the medication, and 81.7% of the respondents stated that the system of labels helped in adherence. Over 66% of the respondents thought that such labels should be included in pharmacy services, and 77.92% of the participants reported that this system of labelling medications should be offered through all pharmacies.

Conclusions
Pharmaceutical labels in the pharmacists’ everyday practice can largely improve patient adherence. These efforts, provided as part of their pharmaceutical services, can have a huge influence on optimisation of patient health outcomes.
Genetic predisposition to nonalcoholic fatty liver disease: insights from ANGPTL8 gene variants in Iranian adults
Authors: Saghafi Samira , Chamani Elham , Salmani Fatemeh , Fadaei Reza , Shafiei Efat , Moradi Nariman , Tavakoli Tahmine 
Published: September 2023

AbstractNonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease with a global prevalence, and modulation of ANGPTL8 expression has emerged as a promising predictor of NAFLD susceptibility. This research was conducted to scrutinize ANGPTL8 protein expression in NAFLD patients and elucidate the interplay between ANGPTL8 gene polymorphisms and their lipid profiles, thus shedding new light on the pathophysiology of this complex disease. The study comprised 423 unrelated participants, including 222 healthy controls and 201 individuals with NAFLD, screened using FibroScan/ultrasonography and laboratory tests. The main goal focused on the genotype and allele frequency distribution in the ANGPTL8 gene, specifically analyzing two genetic variations: rs737337 (T/C) and rs2278426 (C/T). The participants diagnosed with NAFLD were slightly younger (P ≥ 0.05) and had a higher body mass index (BMI) than the individuals in the control group. Notably, there was a significant difference in the occurrence of the rs737337 polymorphism between the NAFLD and control groups, with a lower frequency observed in the NAFLD group. Our results indicated that individuals with the TC + CC genotype and C allele of rs737337 (T/C) had a decreased risk of higher levels of ALT and AST. Conversely, those with the CT, CT + TT genotype, and T allele of rs2278426 (C/T) exhibited an increased risk of higher levels of ALT and AST. The results imply that the rs2278426 (C/T) variant of the ANGPTL8 gene is more strongly linked to an increased risk of NAFLD compared to the rs737337 polymorphism. However, additional research is needed to understand the specific molecular mechanisms responsible for the upregulation of ANGPTL8 in individuals with NAFLD.
Descriptive ethnobotanical studies are needed for the rescue operation of documenting traditional knowledge
Authors: Łuczaj Łukasz 
Published: September 2023

AbstractIn this essay, I claim that the primary aim of ethnobiological research is now to document disappearing traditional knowledge. This is an absolute priority due to the rate at which biocultural biodiversity in the world is disappearing. Rather than diverting our efforts into inflating the theoretical part of ethnobotany, we should concentrate on knowledge documentation to facilitate its circulation in the communties that hold it or at least to preserve it for future generations, even in the static form of databases or video recordings.
ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization
Authors: Schlüter Agatha , Vélez-Santamaría Valentina , Verdura Edgard , Rodríguez-Palmero Agustí , Ruiz Montserrat , Fourcade Stéphane , Planas-Serra Laura , Launay Nathalie , Guilera Cristina , Martínez Juan José , Homedes-Pedret Christian , Albertí-Aguiló M. Antonia , Zulaika Miren , Martí Itxaso , Troncoso Mónica , Tomás-Vila Miguel , Bullich Gemma , García-Pérez M. Asunción , Sobrido-Gómez María-Jesús , López-Laso Eduardo , Fons Carme , Del Toro Mireia , Macaya Alfons ,   HSP/ataxia workgroup, García-Cazorla Àngels , Ortiz-Martínez Antonio José , Ignacio-Ortez Carlos , Cáceres-Marzal Cristina , Martínez-Salcedo Eduardo , Mondragón Elisabet , Barredo Estíbaliz , Airaldi Ileana Antón , Martínez Javier Ruiz , Ramos Joaquin A. Fernández , Vázquez Juan Francisco , Díez-Porras Laura , Vázquez-Cancela María , O’Callaghan Mar , Sánchez Tamara Pablo , Nedkova Velina , Pérez Ana Isabel Maraña , Beltran Sergi , Gutiérrez-Solana Luis G. , Pérez-Jurado Luis A. , Aguilera-Albesa Sergio , de Munain Adolfo López , Casasnovas Carlos , Pujol Aurora 
Published: September 2023

AbstractBackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient’s standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.
Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy
Authors: Liu Zheng-Zhao , Huang Yan , Hong Chun-Gu , Wang Xin , Duan Ran , Liu Jian-Yang , He Jia-Lin , Duan Da , Xie Hui , Lu Ming 
Published: September 2023

Abstract
Background and aims
Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study aims to investigate whether OM-MSCs are a promising alternative source for treating refractory epilepsy clinically and uncover the mechanism by OM-MSCs administration on an epileptic mouse model.

Methods
OM-MSCs were isolated from turbinal and characterized by flow cytometry. Autologous human OM-MSCs treatment on a patient was carried out using intrathecal administration. Epileptic mouse model was established by 1 mg/kg scopolamine and 300 mg/kg pilocarpine treatment (intraperitoneal). Stereotaxic microinjection was employed to deliver the mouse OM-MSCs. Mouse electroencephalograph recording was used to investigate the seizures. Brain structure was evaluated by magnetic resonance imaging (MRI). Immunohistochemical and immunofluorescent staining of GFAP, IBA1, MAP2, TUBB3, OLIG2, CD4, CD25, and FOXP3 was carried out to investigate the neural cells and Treg cells. QRT-PCR and ELISA were performed to determine the cytokines (Il1b, Il6, Tnf, Il10) on mRNA and protein level. Y-maze, the object location test, and novel object recognition test were performed to measure the cognitive function. Footprint test, rotarod test, balance beam test, and grip strength test were conducted to evaluate the locomotive function. Von Frey testing was carried out to assess the mechanical allodynia.

Results
Many beneficial effects of the OM-MSC treatment on disease status, including seizure type, frequency, severity, duration, and cognitive function, and no apparent adverse effects were observed at the 8-year follow-up case. Brain MRI indicated that autologous OM-MSC treatment alleviated brain atrophy in epilepsy patients. A study in an epileptic mouse model revealed that OM-MSC treatment recruited Treg cells to the brain, inhibited inflammation, rebuilt the neural network, and improved the cognitive, locomotive, and perceptive functions of epileptic mice.

Conclusions
Autologous OM-MSC treatment is efficacious for improving chronic refractory epilepsy, suggesting a future therapeutic candidate for epilepsy.
Trial registration: The study was registered with Chinese Clinical Trial Registry (ChiCTR2200055357).
Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice
Authors: Yang Jing , Yang Na , Zhao Huifang , Qiao Yan , Li Yanqiu , Wang Chunfang , Lim Kah-Leong , Zhang Chengwu , Yang Wulin , Lu Li 
Published: September 2023

Abstract
Background
Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored.

Methods
In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior.

Results
It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect.

Conclusion
This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.
LOGICS: Learning optimal generative distribution for designing de novo chemical structures
Authors: Bae Bongsung , Bae Haelee , Nam Hojung 
Published: September 2023

AbstractIn recent years, the field of computational drug design has made significant strides in the development of artificial intelligence (AI) models for the generation of de novo chemical compounds with desired properties and biological activities, such as enhanced binding affinity to target proteins. These high-affinity compounds have the potential to be developed into more potent therapeutics for a broad spectrum of diseases. Due to the lack of data required for the training of deep generative models, however, some of these approaches have fine-tuned their molecular generators using data obtained from a separate predictor. While these studies show that generative models can produce structures with the desired target properties, it remains unclear whether the diversity of the generated structures and the span of their chemical space align with the distribution of the intended target molecules. In this study, we present a novel generative framework, LOGICS, a framework for Learning Optimal Generative distribution Iteratively for designing target-focused Chemical Structures. We address the exploration—exploitation dilemma, which weighs the choice between exploring new options and exploiting current knowledge. To tackle this issue, we incorporate experience memory and employ a layered tournament selection approach to refine the fine-tuning process. The proposed method was applied to the binding affinity optimization of two target proteins of different protein classes, κ-opioid receptors, and PIK3CA, and the quality and the distribution of the generative molecules were evaluated. The results showed that LOGICS outperforms competing state-of-the-art models and generates more diverse de novo chemical structures with optimized properties. The source code is available at the GitHub repository (https://github.com/GIST-CSBL/LOGICS).
The power of humorous audio: exploring emotion regulation in traffic congestion through EEG-based study
Authors: Zhang Lekai , Wang Yingfan , He Kailun , Zhang Hailong , Xing Baixi , Liu Xiaofeng , Hu Fo 
Published: September 2023

AbstractTraffic congestion can lead to negative driving emotions, significantly increasing the likelihood of traffic accidents. Reducing negative driving emotions as a means to mitigate speeding, reckless overtaking, and aggressive driving behaviors is a viable approach. Among the potential methods, affective speech has been considered one of the most promising. However, research on humor-based affective speech interventions in the context of driving negative emotions is scarce, and the utilization of electroencephalogram (EEG) signals for emotion detection in humorous audio studies remains largely unexplored. Therefore, our study first designed a highly realistic experiment scenario to induce negative emotions experienced by drivers in congested traffic conditions. Subsequently, we collected drivers’ EEG signals and subjective questionnaire ratings during the driving process. By employing one-way analysis of variance (ANOVA) and t tests, we analyzed the data to validate the success of our experiment in inducing negative emotions in drivers during congested road conditions and to assess the effectiveness of humorous audio in regulating drivers’ negative emotions. The results indicated that humorous audio effectively alleviated drivers’ negative emotions in congested road conditions, with a 145.84% increase in arousal and a 93.55% increase in valence ratings compared to control conditions. However, it should be noted that humorous audio only restored drivers’ emotions to the level experienced during normal driving. Our findings offer novel insights into regulating drivers’ negative emotions during congested road conditions.
Does repeated exposure to hydrogen peroxide induce Candida auris resistance?
Authors: Cobrado Luis , Ricardo Elisabete , Ramalho Patricia , Fernandes Angela Rita , Rodrigues Acacio Goncalves 
Published: September 2023

Abstract
Background
To minimize environmental colonization by microorganisms that may persist and thrive in healthcare settings, thus reducing healthcare-associated infections (HAIs), new insights over already known biocides are certainly of relevance. Although the efficacy of hydrogen peroxide (H2O2) against the emergent yeast Candida auris is moderately documented, concerns over the potential induction of resistance after repeated exposure do persist. The main objective of the present study was to evaluate the hypothetical induction of Candida auris resistance following 30 days of consecutive exposure to lethal and sublethal concentrations of H2O2. Furthermore, the authors aimed to elucidate about the rank of efficacy of H2O2 against C. auris comparing to other Candida species and whether different strains of C. auris may display different susceptibilities to H2O2.

Methods
During the induction of resistance assays, both type strains and clinical isolates of Candida auris, Candida albicans and Candida parapsilosis were exposed repeatedly to defined concentrations of H2O2, for 30 days.

Results
After that period, no significant differences were found when comparing the minimal inhibitory concentration values of H2O2 in case of the induced strains versus each respective positive control. Moreover, H2O2 displayed similar effectiveness against all the tested Candida species and no differences were demonstrated among the distinct strains of C. auris.

Conclusions
The adoption of H2O2 solutions in routine protocols in order to promote disinfection standards against Candida auris, improving patient safety and reducing healthcare costs, is certainly welcomed.
m1A Regulatory gene signatures are associated with certain immune cell compositions of the tumor microenvironment and predict survival in kidney renal clear cell carcinoma
Authors: Zhou Linjun , Zhou Weidong , Li Yuan , Hua Ruifang 
Published: September 2023

AbstractAdenosine N1 methylation (m1A) of RNA, a type of post-transcriptional modification, has been shown to play a significant role in the progression of cancer. The objective of the current research was to analyze the genetic alteration and prognostic significance of m1A regulators in kidney renal clear cell carcinoma (KIRC). Genomic and clinicopathological characteristics were obtained from 558 KIRC patients in the Cancer Genome Atlas (TCGA) and Gene Omnibus Expression (GEO) databases. Alterations in the gene expression of ten m1A-regulators were analyzed and survival analysis was performed using the Cox regression method. We also identified three clusters of patients based on their distinct m1A alteration patterns, using integrated analysis of the ten m1A-related regulators, which were significantly related to overall survival (OS), disease-free survival (DFS) and tumor microenvironment (TME) immune cell infiltration cells in KIRC. Our findings showed that m1A alteration patterns have critical roles in determining TME complexity and its immune cell composition. Furthermore, different m1A expression patterns were significantly associated with DFS and OS rates in KIRC patients. In conclusion, the identified m1A RNA modification patterns offer a potentially effective way to classify KIRC patients based on their TME immune cell infiltration, enabling the development of more personalized and successful treatment strategies for these patients.