bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets
Authors: Agamah Francis E. , Damena Delesa , Skelton Michelle , Ghansah Anita , Mazandu Gaston K. , Chimusa Emile R. 
Published: October 2021

Abstract
Background
The emergence and spread of malaria drug resistance have resulted in the need to understand disease mechanisms and importantly identify essential targets and potential drug candidates. Malaria infection involves the complex interaction between the host and pathogen, thus, functional interactions between human and Plasmodium falciparum is essential to obtain a holistic view of the genetic architecture of malaria. Several functional interaction studies have extended the understanding of malaria disease and integrating such datasets would provide further insights towards understanding drug resistance and/or genetic resistance/susceptibility, disease pathogenesis, and drug discovery.

Methods
This study curated and analysed data including pathogen and host selective genes, host and pathogen protein sequence data, protein–protein interaction datasets, and drug data from literature and databases to perform human-host and P. falciparum network-based analysis. An integrative computational framework is presented that was developed and found to be reasonably accurate based on various evaluations, applications, and experimental evidence of outputs produced, from data-driven analysis.

Results
This approach revealed 8 hub protein targets essential for parasite and human host-directed malaria drug therapy. In a semantic similarity approach, 26 potential repurposable drugs involved in regulating host immune response to inflammatory-driven disorders and/or inhibiting residual malaria infection that can be appropriated for malaria treatment. Further analysis of host–pathogen network shortest paths enabled the prediction of immune-related biological processes and pathways subverted by P. falciparum to increase its within-host survival.

Conclusions
Host–pathogen network analysis reveals potential drug targets and biological processes and pathways subverted by P. falciparum to enhance its within malaria host survival. The results presented have implications for drug discovery and will inform experimental studies.
Study protocol for an evaluability assessment of an anti-human trafficking program
Authors: Wretman Christopher J. , Macy Rebecca J. , Stylianou Amanda M. , Teekah Anita S. , Ebright Elizabeth N. , Kim Jeongsuk , Luo Jia , Rizo Cynthia Fraga 
Published: October 2021

Abstract
Background
Human trafficking is a serious global challenge associated with a complex array of health inequities for individuals, families, and communities. Consequently, in addition to a conventional criminal justice approach, anti-trafficking scholars have increasingly called for a public health approach to address this global challenge. Such calls have emphasized that a comprehensive, robust, and social justice-informed public health strategy for anti-trafficking must include services to facilitate survivors’ HT exit and recovery, and to prevent their re-victimization. Fortunately, many community-based organizations and non-governmental organizations worldwide have heeded these calls and developed anti-trafficking programs for survivors. Unfortunately, despite the growing numbers of organizations providing anti-trafficking services, research concerning these programs’ effectiveness remains nascent overall, and even more scant when filtered through an equity focus.

Methods
To advance the field by developing guidance concerning how best to evaluate anti-human trafficking programs, an ongoing research project aims to conduct a mixed methods evaluability assessment of a prominent anti-trafficking program using a social justice framework. Guided by well-established evaluability assessment frameworks, the study activities include four sequential steps: (a) focusing the assessment, (b) developing the program theory and logic, (c) gathering feedback, and (d) applying the assessment findings. Activities will include qualitative interviews and focus groups, observations, and quantitative analysis of program data among others. Human subjects and ethical review for the evaluability assessment has been granted by the Office of Human Subjects Research at The University of North Carolina at Chapel Hill.

Discussion
Once completed, evaluability assessment results will provide evidence and products that have the potential to guide both evaluation research and service provision not only for the specific organization under study, but also for other anti-human trafficking programs worldwide. Findings will be developed into a variety of dissemination products tailored for both practice professionals and researchers. In the interim, this protocol manuscript offers research strategies and recommendations that can help inform the development of other studies in the developing field of anti-trafficking program evaluation research.
Community-based health financing: empirical evaluation of the socio-demographic factors determining its uptake in Awka, Anambra state, Nigeria
Authors: Iyalomhe Felix O. , Adekola Paul O. , Cirella Giuseppe T. 
Published: October 2021

AbstractBackgroundThere is an increasing global concern of financing poor people who live in low- and middle-income countries. The burden of non-communicable diseases of these people is, by in large, connected to a lack of access to effective and affordable medical care, weak financing, and delivery of health services. Policymakers have assumed, until recently, that poor people in developing countries would not pay health insurance premiums for the cost of future hospitalization. The emergence of community-based health financing (CBHF) has brought forth a renewed and empowered alternative. CBHF schemes are designed to be sustainable, varying in size, and well organized. Developing countries, such as Nigeria, have been testing and finetuning such schemes in the hope that they may 1 day reciprocate high-income countries.MethodsA sample size of 372 respondents was used to assess the slums of Awka, the capital city of Anambra State, Nigeria, and empirically evaluate the socio-demographic characteristics of those who uptake CBHF using the provider Jamii Bora Trust (JBT). Cross-sectional research used a quantitative research approach with the instrumentality of structured questionnaires. Descriptive analysis was adopted to determine the socio-demographic characteristics of those who have CBHF uptake in Awka and evaluate the presence and benefits of CBHF in the city’s slums.ResultsThe results show that more youth and middle-aged persons from 18 to 50 years are more insured (i.e., 73.8% combined) than those who are over 50 years of age. Gender distribution confirm more females (i.e., 61.9%) to be health-insured than their male counterpart (i.e., 38.1%). This perhaps reflected the reproductive roles by women and the fact that women have better health-seeking behavioral attitude. Moreover, the results correlate with previous studies that confirm women are more involved in local sustainable associations in low-income settings, of this nature, in sub-Saharan Africa. Corroborating this further, married people are more insured (i.e., 73.8%) than those who are not married (i.e., 26.2%) and insured members report higher use of hospitalization care than the non-insured.ConclusionCBHF uptake favored members in the lower income quintiles who are more likely to use healthcare services covered by the JBT scheme. This confirmed that prepayment schemes and the pooling of risk could reduce financial barriers to healthcare among the urban poor. Recommendations are suggested to improve enrollment levels in the CBHF programs.
Prevalence of β-lactamase-encoding genes and molecular typing of Acinetobacter baumannii isolates carrying carbapenemase OXA-24 in children
Authors: Yousefi Nojookambari Neda , Sadredinamin Mehrzad , Dehbanipour Razieh , Ghalavand Zohreh , Eslami Gita , Vaezjalali Maryam , Nikmanesh Bahram , Yazdansetad Sajjad 
Published: October 2021

Abstract
Background
β-Lactam antibiotics have been broadly used for the treatment of Acinetobacter baumannii infections, resulting in development of β-lactam inactivating β-lactamases. Here, we described antibiotic resistance rate, prevalence of β-lactamase-encoding genes, and clonal relationships of A. baumannii strains isolated from children referred to Children’s Medical Center in Tehran, Iran, during 2019–2020.

Methods
A total of 60 non-replicate A. baumannii isolates were recovered from clinical specimens of pediatric patients. Antibiotic susceptibility testing was done by the disc diffusion method. Colistin susceptibility of isolates was performed by the broth microdilution method. β-lactamase-encoding genes were characterized by PCR. The presence of ISAba1 element upstream of the several oxacillinase genes was also checked. Genetic relatedness of isolates was determined by using random amplification of polymorphic DNA (RAPD) typing.

Results
The antimicrobial susceptibility tests showed that 83.3% of A. baumannii isolates were MDR, and 40% XDR. Both MDR and XDR A. baumannii isolates were susceptible to colistin. The frequency of blaOXA-51-like, blaOXA-23-like, blaTEM, blaOXA-24-like, blaPER, blaSHV, blaCTX-M, blaOXA-58-like, and blaIMP was 100, 93.33, 60, 36.67, 28.33, 8.33, 5, 3.33, and 1.67%, respectively. Coexistence of ISAba1/blaOXA-23-like and ISAba1/blaOXA-51-like was observed in 65% and 85% of isolates, respectively. RAPD analysis revealed 4 common types and 2 single types of A. baumannii isolates.

Conclusions
The multiple clones harboring blaOXA-23-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23-like were responsible for the spread of A. baumannii isolates in our clinical wards. Dissemination of the well-established clones is worrisome and would become therapeutic challenges due to the possible transferring genetic elements associated with resistance.
Understanding of catalytic ROS generation from defect-rich graphene quantum-dots for therapeutic effects in tumor microenvironment
Authors: Wang Xichu , Hu Chuangang , Gu Zi , Dai Liming 
Published: October 2021

AbstractOwing to their low cost, high catalytic efficiency and biocompatibility, carbon-based metal-free catalysts (C-MFCs) have attracted intense interest for various applications, ranging from energy through environmental to biomedical technologies. While considerable effort and progress have been made in mechanistic understanding of C-MFCs for non-biomedical applications, their catalytic mechanism for therapeutic effects has rarely been investigated. In this study, defect-rich graphene quantum dots (GQDs) were developed as C-MFCs for efficient ROS generation, specifically in the H2O2-rich tumor microenvironment to cause multi-level damages of subcellular components (even in nuclei). While a desirable anti-cancer performance was achieved, the catalytic performance was found to strongly depend on the defect density. It is for the first time that the defect-induced catalytic generation of ROS by C-MFCs in the tumor microenvironment was demonstrated and the associated catalytic mechanism was elucidated. This work opens a new avenue for the development of safe and efficient catalytic nanomedicine.
Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis
Authors: Li Shenglong , Liu Jie , Liu Siyu , Jiao Weijie , Wang Xiaohong 
Published: October 2021

AbstractObjectivesThis study aimed to investigate the roles of adipose mesenchymal stem cell (AMSC)-derived extracellular vesicles (EVs) binding with chitosan oligosaccharides (COS) in cartilage injury, as well as the related mechanisms.ResultsIL-1β treatment significantly inhibited the viability and migration of chondrocytes and enhanced cell apoptosis (P < 0.05), while chitosan oligosaccharides and extracellular vesicles-chitosan oligosaccharide conjugates (EVs-COS/EVs-COS conjugates) reversed the changes induced by IL-1β (P < 0.05), and the effects of extracellular vesicles-chitosan oligosaccharide conjugates were better than those of chitosan oligosaccharides (P < 0.05). After cartilage damage, IL-1β, OPN, and p53 were significantly upregulated, COL1A1, COL2A1, OCN, RUNX2, p-Akt/Akt, PI3K, c-Myc, and Bcl2 were markedly downregulated, and extracellular vesicles-chitosan oligosaccharide conjugates reversed the expression induced by cartilage injury. Through sequencing, 760 differentially expressed genes (DEGs) clustered into four expression patterns were associated with negative regulation of the canonical Wnt, PI3K-Akt, AMPK, and MAPK signaling pathways.ConclusionExtracellular vesicles-chitosan oligosaccharide conjugates may serve as a new cell-free biomaterial to facilitate cartilage injury repair and improve osteoarthritis.Graphical Abstract
Texture feature extraction from microscope images enables a robust estimation of ER body phenotype in Arabidopsis
Authors: Basak Arpan Kumar , Mirzaei Mohamadreza , Strzałka Kazimierz , Yamada Kenji 
Published: October 2021

Abstract
Background
Cellular components are controlled by genetic and physiological factors that define their shape and size. However, quantitively capturing the morphological characteristics and movement of cellular organelles from micrograph images is challenging, because the analysis deals with complexities of images that frequently lead to inaccuracy in the estimation of the features. Here we show a unique quantitative method to overcome biases and inaccuracy of biological samples from confocal micrographs.

Results
We generated 2D images of cell walls and spindle-shaped cellular organelles, namely ER bodies, with a maximum contrast projection of 3D confocal fluorescent microscope images. The projected images were further processed and segmented by adaptive thresholding of the fluorescent levels in the cell walls. Micrographs are composed of pixels, which have information on position and intensity. From the pixel information we calculated three types of features (spatial, intensity and Haralick) in ER bodies corresponding to segmented cells. The spatial features include basic information on shape, e.g., surface area and perimeter. The intensity features include information on mean, standard deviation and quantile of fluorescence intensities within an ER body. Haralick features describe the texture features, which can be calculated mathematically from the interrelationship between the pixel information. Together these parameters were subjected to multivariate analysis to estimate the morphological diversity. Additionally, we calculated the displacement of the ER bodies using the positional information in time-lapse images. We captured similar morphological diversity and movement within ER body phenotypes in several microscopy experiments performed in different settings and scanned under different objectives. We then described differences in morphology and movement of ER bodies between A. thaliana wild type and mutants deficient in ER body-related genes.

Conclusions
The findings unexpectedly revealed multiple genetic factors that are involved in the shape and size of ER bodies in A. thaliana. This is the first report showing morphological characteristics in addition to the movement of cellular components and it quantitatively summarises plant phenotypic differences even in plants that show similar cellular components. The estimation of morphological diversity was independent of the cell staining method and the objective lens used in the microscopy. Hence, our study enables a robust estimation of plant phenotypes by recognizing small differences in complex cell organelle shapes and their movement, which is beneficial in a comprehensive analysis of the molecular mechanism for cell organelle formation that is independent of technical variations.
Mapping out epistemic justice in the clinical space: using narrative techniques to affirm patients as knowers
Authors: Rosen Leah Teresa 
Published: October 2021

AbstractEpistemic injustice sits at the intersection of ethics, epistemology, and social justice. Generally, this philosophical term describes when a person is wrongfully discredited as a knower; and within the clinical space, epistemic injustice is the underlying reason that some patient testimonies are valued above others. The following essay seeks to connect patterns of social prejudice to the clinical realm in the United States: illustrating how factors such as race, gender identity, and socioeconomic status influence epistemic credence and associatively, the quality of healthcare a person receives.After describing how epistemic injustice disproportionately harms already vulnerable patients, I propose a narrative therapy intervention. This intervention can help providers re-frame their relationships with patients, in such that they come to view patients as valuable sources of unique knowledge. Though I identify this intervention as a valuable step in addressing clinical epistemic injustice, I call upon medical educators and practitioners to further uplift the voices, perspectives, and stories of marginalized patients.
Perceived healthcare stigma among patients in opioid substitution treatment: a qualitative study
Authors: Garpenhag Lars , Dahlman Disa 
Published: October 2021

Abstract
Background
People with substance use disorders (SUD) including patients in opioid substitution treatment (OST) are subject to stigma, and have generally poor health and barriers towards seeking healthcare. Experience of stigma might negatively affect healthcare seeking, but this topic is sparsely investigated. The aim of this study was to explore OST patients’ past and present experiences of substance use stigma in healthcare settings, in order to provide insight into the challenges that people with opioid use disorder may face when using health services, and the strategies they use to cope with them.

Methods
Six focus groups with 23 OST patients were moderated by OST staff, and conducted with a questioning route focusing on health literacy. Experiences associated with stigma and its consequences that were spontaneously brought up by participants were assessed in a secondary analysis using a thematic approach.

Results
Experiences of stigma from a wide range of healthcare settings were reported. Medical records and patients’ oral information regarding substance use, OST medication or hepatitis C infection were identified as circumstances bringing unwanted attention to the SUD. Participants reported various forms of poor treatment, believed to reflect views of people with SUD as morally culpable, intimidating, curious, untrustworthy and less valuable than other patients, sometimes with tangible effects on the quality of healthcare. Stigma in healthcare settings affected healthcare seeking behaviors, and could result in patients concealing their OST status or substance use history.

Conclusion
This study highlights several aspects of perceived healthcare stigma that can shed light on difficulties that OST patients might experience when navigating the healthcare system. The results implicate a need to investigate attitudes towards OST patients, and the aptitude to deal with patients with SUD, among healthcare professionals, as well as a need for interventions addressing knowledge deficits and issues tied to values and patient reception among healthcare staff.
Cone beam CT-based dose accumulation and analysis of delivered dose to the dominant intraprostatic lesion in primary radiotherapy of prostate cancer
Authors: Tamihardja Jörg , Cirsi Sinan , Kessler Patrick , Razinskas Gary , Exner Florian , Richter Anne , Polat Bülent , Flentje Michael 
Published: October 2021

Abstract
Background
Evaluation of delivered dose to the dominant intraprostatic lesion (DIL) for moderately hypofractionated radiotherapy of prostate cancer by cone beam computed tomography (CBCT)-based dose accumulation and target coverage analysis.

Methods
Twenty-three patients with localized prostate cancer treated with moderately hypofractionated prostate radiotherapy with simultaneous integrated boost (SIB) between December 2016 and February 2020 were retrospectively analyzed. Included patients were required to have an identifiable DIL on bi-parametric planning magnetic resonance imaging (MRI). After import into the RayStation treatment planning system and application of a step-wise density override, the fractional doses were computed on each CBCT and were consecutively mapped onto the planning CT via a deformation vector field derived from deformable image registration. Fractional doses were accumulated for all CBCTs and interpolated for missing CBCTs, resulting in the delivered dose for PTVDIL, PTVBoost, PTV, and the organs at risk. The location of the index lesions was recorded according to the sector map of the Prostate Imaging Reporting and Data System (PIRADS) Version 2.1. Target coverage of the index lesions was evaluated and stratified for location.

Results
In total, 338 CBCTs were available for analysis. Dose accumulation target coverage of PTVDIL, PTVBoost, and PTV was excellent and no cases of underdosage in DMean, D95%, D02%, and D98% could be detected. Delivered rectum DMean did not significantly differ from the planned dose. Bladder mean DMean was higher than planned with 19.4 ± 7.4 Gy versus 18.8 ± 7.5 Gy, p < 0.001. The penile bulb showed a decreased delivered mean DMean with 29.1 ± 14.0 Gy versus 29.8 ± 14.4 Gy, p < 0.001. Dorsal DILs, defined as DILs in the posterior medial peripheral zone of the prostate, showed a significantly lower delivered dose with a mean DMean difference of 2.2 Gy (95% CI 1.3–3.1 Gy, p < 0.001) compared to ventral lesions.

Conclusions
CBCT-based dose accumulation showed an adequate delivered dose to the dominant intraprostatic lesion and organs at risk within planning limits. Cautious evaluation of the target coverage for index lesions adjacent to the rectum is warranted to avoid underdosage.