bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescription patterns and compliance with World Health Organization recommendations for the management of uncomplicated and severe malaria: A prospective, real-world study in sub-Saharan Africa
Authors: Baraka Vito , Nhama Abel , Aide Pedro , Bassat Quique , David Agatha , Gesase Samwel , Gwasupika Jonathan , Hachizovu Sebastian , Makenga Geofrey , Ntizimira Christian Ruchaho , Obunge Orikomaba , Tshefu Kitoto Antoinette , Cousin Marc , Otsyula Nekoye , Pathan Rashidkhan , Risterucci Céline , Su Guoqin , Manyando Christine 
Published: July 2023

Abstract
Background
This study aimed to evaluate the gap between guidelines and local clinical practice for diagnosis and treatment of uncomplicated and severe malaria, the patient characteristics, diagnostic approach, treatment, and compliance to standard guideline recommendations.

Methods
This was a multicentre, observational study conducted between October 2020 and March 2021 in which patients of all ages with symptoms suggestive of malaria and who visited a healthcare facility were prospectively enrolled in six countries in sub-Saharan Africa (The Democratic Republic of the Congo, Mozambique, Nigeria, Rwanda, The United Republic of Tanzania, and Zambia).

Results
Of 1001 enrolled patients, 735 (73.4%) patients had confirmed malaria (based on overall judgment by investigator) at baseline (uncomplicated malaria: 598 [81.4%] and severe malaria: 137 [18.6%]). Of the confirmed malaria patients, 533 (72.5%) were administered a malaria rapid diagnostic test. The median age of patients was 11 years (range: 2 weeks–91 years) with more patients coming from rural (44.9%) than urban (30.6%) or suburban areas (24.5%). At the community level, 57.8% of patients sought advice or received treatment for malaria and 56.9% of patients took one or more drugs for their illness before coming to the study site. In terms of early access to care, 44.1% of patients came to the study site for initial visit ≥ 48 h after symptom onset. In patients with uncomplicated malaria, the most prescribed treatments were artemisinin-based combination therapy (ACT; n = 564 [94.3%]), primarily using artemether-lumefantrine (82.3%), in line with the World Health Organization (WHO) treatment guidelines. In addition, these patients received antipyretics (85.6%) and antibiotics (42.0%). However, in those with severe malaria, only 66 (48.2%) patients received parenteral treatment followed by oral ACT as per WHO guidelines, whereas 62 (45.3%) received parenteral treatment only. After receiving ambulatory care, 88.6% of patients with uncomplicated malaria were discharged and 83.2% of patients with severe malaria were discharged after hospitalization. One patient with uncomplicated malaria having multiple co-morbidities and three patients with severe malaria died.

Conclusions
The findings of this study suggest that the prescribed treatment in most patients with uncomplicated malaria, but not of those with severe malaria, was in alignment with the WHO recommended guidelines.
The confidante method to measure abortion: implementing a standardized comparative analysis approach across seven contexts
Authors: Owolabi Onikepe O. , Giorgio Margaret , Leong Ellie , Sully Elizabeth 
Published: July 2023

Abstract
Background
Obtaining representative abortion incidence estimates is challenging in restrictive contexts. While the confidante method has been increasingly used to collect this data in such settings, there are several biases commonly associated with this method. Further, there are significant variations in how researchers have implemented the method and assessed/adjusted for potential biases, limiting the comparability and interpretation of existing estimates. This study presents a standardized approach to analyzing confidante method data, generates comparable abortion incidence estimates from previously published studies and recommends standards for reporting bias assessments and adjustments for future confidante method studies.

Methods
We used data from previous applications of the confidante method in Côte d’Ivoire, Ethiopia, Ghana, Java (Indonesia), Nigeria, Uganda, and Rajasthan (India). We estimated one-year induced abortion incidence rates for confidantes in each context, attempting to adjust for selection, reporting and transmission bias in a standardized manner.

Findings
In each setting, majority of the foundational confidante method assumptions were violated. Adjusting for transmission bias using self-reported abortions consistently yielded the highest incidence estimates compared with other published approaches. Differences in analytic decisions and bias assessments resulted in the incidence estimates from our standardized analysis varying widely from originally published rates.

Interpretation
We recommend that future studies clearly state which biases were assessed, if associated assumptions were violated, and how violations were adjusted for. This will improve the utility of confidante method estimates for national-level decision making and as inputs for global or regional model-based estimates of abortion.
Integration of single-cell regulon atlas and multi-omics data for prognostic stratification and personalized treatment prediction in human lung adenocarcinoma
Authors: Xiong Yi , Zhang Yihao , Liu Na , Li Yueshuo , Liu Hongwei , Yang Qi , Chen Yu , Xia Zhizhi , Chen Xin , Wanggou Siyi , Li Xuejun 
Published: July 2023

AbstractTranscriptional programs are often dysregulated in cancers. A comprehensive investigation of potential regulons is critical to the understanding of tumorigeneses. We first constructed the regulatory networks from single-cell RNA sequencing data in human lung adenocarcinoma (LUAD). We next introduce LPRI (Lung Cancer Prognostic Regulon Index), a precision oncology framework to identify new biomarkers associated with prognosis by leveraging the single cell regulon atlas and bulk RNA sequencing or microarray datasets. We confirmed that LPRI could be a robust biomarker to guide prognosis stratification across lung adenocarcinoma cohorts. Finally, a multi-omics data analysis to characterize molecular alterations associated with LPRI was performed from The Cancer Genome Atlas (TCGA) dataset. Our study provides a comprehensive chart of regulons in LUAD. Additionally, LPRI will be used to help prognostic prediction and developing personalized treatment for future studies.
Relation between interleukin-6 concentrations and oxidative status of HIV infected patients with /or at risk of Kaposi disease in Yaounde
Authors: Voufo Roger Ahouga , Kouotou Armand Emmanuel , Tatah Nchinda Jones , TeTo Georges , Gueguim Cédric , Ngondé Chantal Marie Essome , Njiguet Tepa Armand Gabin , Gabin Arnaud , Amazia Falmata , Yembeau Natacha Lena , Kouanfack Charles , Anatole Pieme Constant 
Published: July 2023

Abstract
Objective
To investigate the relation between interleukin-6 concentration and oxidative status of HIV infected patients with or at risk of Kaposi’s disease in Yaoundé.

Methods
We conducted a two-months cross-sectional study on 87 consenting HIV infected patients followed at the Day Hospital of the Yaoundé Central Hospital. Serum/plasma obtained after centrifugation of blood collected in dry/EDTA tubes was used for the determination of Human Herpes Virus-8 antigen (HHV-8) and Interleukin-6 (IL-6) by the ELISA technique, and that of oxidative stress markers: Malondialdehyde (MDA) reduced Glutathione (GSH) and total antioxidant capacity by spectrophotometry.

Results
Subjects belonging to the [40–50[year-old age group were mainly represented in our study population with 43.7%. The average age was 44.6 ± 10.4 years with extremes ranging from 26 to 72 years. The sex ratio was 0.24. Our population was mainly represented by people infected with HIV type I (90.8%) and 3.4% had developed clinical signs of Kaposi’s disease. The prevalence of the HHV-8 antigen was 57.5%. Immune and oxidative parameters did not vary with age, sex and therapeutic line. We noted a significant increase in IL-6 concentrations in patients positive to the HHV-8 antigen for IL-6 concentrations < 37 (P = 0.005; CI= [0.40; 0.59]. MDA and GSH concentrations increased significantly with the HHV-8 infection (P < 0.0001; CI= [0.40; 0.59] and P < 0.0001; CI= [13.30;21.45], respectively). Total antioxidant capacity (FRAP) decreased significantly with HHV-8 infection (P = 0.004; CI= [-69.18; -13.78]). We noted a significant increase in MDA concentrations in patients taking their ARVs irregularly, (P < 0.0001).

Conclusion
Our study showed a weak positive correlation between IL-6 and MDA, a strong negative correlation between FRAP and MDA and a strong positive correlation between MDA and GSH highlighting the association of these few markers of oxidative stress and Il-6 to the risk of Kaposi’s disease.
Gaps in the evidence underpinning high-risk medical devices in Europe at market entry, and potential solutions
Authors: Hulstaert Frank , Pouppez Céline , Primus-de Jong Célia , Harkin Kathleen , Neyt Mattias 
Published: July 2023

Abstract
Aim
To determine the level of evidence for innovative high-risk medical devices at market entry.

Methods
We reviewed all Belgian healthcare payer (RIZIV-INAMI) assessor reports on novel implants or invasive medical devices (n = 18, Class IIb-III) available between 2018 to mid-2019 on applications submitted for inclusion on their reimbursement list. We also conducted a review of the literature on evidence gaps and an analysis of relevant legal and ethical frameworks within the European context.

Findings
Conformity assessment of medical devices is based on performance, safety, and an acceptable risk-benefit balance. Information submitted for obtaining CE marking is confidential and legally protected, limiting access to clinical evidence. Seven out of the 18 RIZIV-INAMI assessor reports (39%) included a randomized controlled trial (RCT) using the novel device, whilst 2 applications (11%) referred to an RCT that used a different device. The population included was inappropriate or unclear for 3 devices (17%). Only half of the applications presented evidence on quality of life or functioning and 2 (11%) presented overall survival data. Four applications (22%) included no data beyond twelve months. The findings from the literature demonstrated similar problems with the study design and the clinical evidence.

Discussion and conclusions
CE marking does not indicate that a device is effective, only that it complies with the law. The lack of transparency hampers evidence-based decision making. Despite greater emphasis on clinical benefit for the patient, the provisions of the European Medical Device Regulation (MDR) are not yet fully aligned with international ethical standards for clinical research. The MDR fails to address key issues, such as the lack of access to data submitted for CE marking and a failure to require evidence of clinical effectiveness. Indeed, a first report shows no improvement in the clinical evidence for implantable devices generated under the MDR. Thus, patients may continue to be exposed to ineffective or unsafe novel devices. The Health Technology Assessment Regulation plans for Joint Scientific Consultations for specific high-risk devices before companies begin their pivotal clinical investigations. The demanded comparative evidence should facilitate payer decisions. Nevertheless, there is also a need for legislation requiring comparative RCTs assessing patient-relevant outcomes for high-risk devices to ensure implementation, including development and implementation of common specifications for study designs.
Non-viral gene delivery to human mesenchymal stem cells: a practical guide towards cell engineering
Authors: Carballo-Pedrares Natalia , Ponti Federica , Lopez-Seijas Junquera , Miranda-Balbuena Diego , Bono Nina , Candiani Gabriele , Rey-Rico Ana 
Published: July 2023

AbstractIn recent decades, human mesenchymal stem cells (hMSCs) have gained momentum in the field of cell therapy for treating cartilage and bone injuries. Despite the tri-lineage multipotency, proliferative properties, and potent immunomodulatory effects of hMSCs, their clinical potential is hindered by donor variations, limiting their use in medical settings. To address this challenge, gene delivery technologies have emerged as a promising approach to modulate the phenotype and commitment of hMSCs towards specific cell lineages, thereby enhancing osteochondral repair strategies. This review provides a comprehensive overview of current non-viral gene delivery approaches used to engineer MSCs, highlighting key factors such as the choice of nucleic acid or delivery vector, transfection strategies, and experimental parameters. Additionally, it outlines various protocols and methods for qualitative and quantitative evaluation of their therapeutic potential as a delivery system in osteochondral regenerative applications. In summary, this technical review offers a practical guide for optimizing non-viral systems in osteochondral regenerative approaches.Graphical AbstracthMSCs constitute a key target population for gene therapy techniques. Nevertheless, there is a long way to go for their translation into clinical treatments. In this review, we remind the most relevant transfection conditions to be optimized, such as the type of nucleic acid or delivery vector, the transfection strategy, and the experimental parameters to accurately evaluate a delivery system. This survey provides a practical guide to optimizing non-viral systems for osteochondral regenerative approaches.
Parental support for physical activity and children’s physical activities: a cross-sectional study
Authors: Hosokawa Rikuya , Fujimoto Megumi , Katsura Toshiki 
Published: July 2023

Abstract
Background
Physical activity (PA) in school-aged children is imperative for physical and mental development. However, there has been reduced PA among children in recent years owing to environmental changes, resulting in declining physical strength and athletic ability. Although parents’ and children’s PA has been found to be correlated, the specific parental caregiving attitudes associated with children’s actual levels of PA during school-age years remain unknown. Therefore, this study aimed to examine the relationship between parental support for PA and children’s levels of PA.

Methods
In 2017, a self-reported questionnaire survey was administered to 1,515 third-grade students (8–9 years old) and their caregivers in Nagoya, Aichi, a major metropolitan area in Japan. The main items surveyed included the attitudes of children and parents towards PA and the children’s actual PA level. Multiple regression analysis was conducted with parental involvement related to PA as the explanatory variable and children’s PA as the objective variable.

Results
In total, 717 children with valid responses were included in the analysis. The mean age of the children was 9.08 ± 0.33 years; 366 (51.0%) were boys, and 351 (49.0%) were girls. For moderate-to-vigorous and vigorous PA, PA levels tended to be significantly higher in children whose parents provided logistic support such as enrolling their children in a sports club. However, for moderate PA and walking, PA levels tended to be significantly higher in children whose parents used community resources. Modeling and limiting sedentary activities were not associated with children’s PA.

Conclusions
The results of this study suggest that direct parental assistance for PA such as logistic support encourages children to engage in moderate-to-vigorous PA; in addition, parental use of community resources may encourage children to engage in moderate and light PA such as walking. Conversely, indirect and negative involvement such as modeling and limiting sedentary activities were not associated with children’s PA. Therefore, logistic support may need to be strengthened to encourage moderate-to-vigorous and vigorous PA, which is important for children’s health.
User authentication and access control to blockchain-based forensic log data
Authors: Islam Md. Ezazul , Islam Md. Rafiqul , Chetty Madhu , Lim Suryani , Chadhar Mehmood 
Published: July 2023

AbstractFor dispute resolution in daily life, tamper-proof data storage and retrieval of log data are important with the incorporation of trustworthy access control for the related users and devices, while giving access to confidential data to the relevant users and maintaining data persistency are two major challenges in information security. This research uses blockchain data structure to maintain data persistency. On the other hand, we propose protocols for the authentication of users (persons and devices) to edge server and edge server to main server. Our proposed framework also provides access to forensic users according to their relevant roles and privilege attributes. For the access control of forensic users, a hybrid attribute and role-based access control (ARBAC) module added with the framework. The proposed framework is composed of an immutable blockchain-based data storage with endpoint authentication and attribute role-based user access control system. We simulate authentication protocols of the framework in AVISPA. Our result analysis shows that several security issues can efficiently be dealt with by the proposed framework.
Exploring the impact of measurement error in police recorded crime rates through sensitivity analysis
Authors: Pina-Sánchez Jose , Brunton-Smith Ian , Buil-Gil David , Cernat Alexandru 
Published: July 2023

AbstractIt is well known that police recorded crime data is susceptible to substantial measurement error. However, despite its limitations, police data is widely used in regression models exploring the causes and effects of crime, which can lead to different types of bias. Here, we introduce a new R package (‘rcme’: Recounting Crime with Measurement Error) that can be used to facilitate sensitivity assessments of the impact of measurement error in analyses using police recorded crime rates across a wide range of settings. To demonstrate the potential of such sensitivity analysis, we explore the robustness of the effect of collective efficacy on criminal damage across Greater London’s neighbourhoods. We show how the crime reduction effect attributed to collective efficacy appears robust, even when most criminal damage incidents are not recorded by the police, and if we accept that under-recording rates are moderately affected by collective efficacy.
Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis
Authors: Matrishin Cole B. , Haase Elaine M. , Dewhirst Floyd E. , Mark Welch Jessica L. , Miranda-Sanchez Fabiola , Chen Tsute , MacFarland Donald C. , Kauffman Kathryn M. 
Published: July 2023

Abstract
Background
Porphyromonas gingivalis (hereafter “Pg”) is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. One of the key forces often shaping strain-level diversity in microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg.

Results
Here we systematically addressed the question of whether Pg are infected by phages—and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain-level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures.

Conclusion
This work definitively establishes that phages are a major unrecognized force shaping the ecology and intra-species strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly.
CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes
Authors: Zhu Chaonan , Baumgarten Nina , Wu Meiqian , Wang Yue , Das Arka Provo , Kaur Jaskiran , Ardakani Fatemeh Behjati , Duong Thanh Thuy , Pham Minh Duc , Duda Maria , Dimmeler Stefanie , Yuan Ting , Schulz Marcel H. , Krishnan Jaya 
Published: July 2023

Abstract
Background
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding.

Methods
The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed.

Results
By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs.

Conclusions
IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.