bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost savings of paper analytical devices (PADs) to detect substandard and falsified antibiotics: Kenya case study
Authors: Chen Hui-Han , Higgins Colleen , Laing Sarah K. , Bliese Sarah L. , Lieberman Marya , Ozawa Sachiko 
Published: March 2021

Background: Over 10% of antibiotics in low- and middle-income countries (LMICs) are substandard or falsified. Detection of poor-quality antibiotics via the gold standard method, high-performance liquid chromatography (HPLC), is slow and costly. Paper analytical devices (PADs) and antibiotic paper analytical devices (aPADs) have been developed as an inexpensive way to estimate antibiotic quality in LMICs. Aim: To model the impact of using a rapid screening tools, PADs/aPADs, to improve the quality of amoxicillin used for treatment of childhood pneumonia in Kenya. Methods: We developed an agent-based model, ESTEEM (Examining Screening Technologies with Economic Evaluations for Medicines), to estimate the effectiveness and cost savings of incorporating PADs and aPADs in amoxicillin quality surveillance in Kenya. We compared the current testing scenario (batches of entire samples tested by HPLC) with an expedited HPLC scenario (testing smaller batches at a time), as well as a screening scenario using PADs/aPADs to identify poor-quality amoxicillin followed by confirmatory analysis with HPLC. Results: Scenarios using PADs/aPADs or expedited HPLC yielded greater incremental benefits than the current testing scenario by annually averting 586 (90% uncertainty range (UR) 364–874) and 221 (90% UR 126–332) child pneumonia deaths, respectively. The PADs/aPADs screening scenario identified and removed poor-quality antibiotics faster than the expedited or regular HPLC scenarios, and reduced costs significantly. The PADs/aPADs scenario resulted in an incremental return of $14.9 million annually compared with the reference scenario of only using HPLC. Conclusion: This analysis shows the significant value of PADs/aPADs as a medicine quality screening and testing tool in LMICs with limited resources.
The relationship between breast density, age, and mammographic lesion type among Chinese breast cancer patients from a large clinical dataset
Authors: Ji Yu , Li Boxin , Zhao Rui , Zhang Ying , Liu Junjun , Lu Hong 
Published: March 2021

Abstract
Background
The purpose of this study was to investigate the relationship between breast density, age, and mammographic lesion type among Chinese breast cancer patients included in a large clinical dataset.

Methods
A review of mammographic images acquired between July 2014 and June 2017 from a total of 9716 retrospectively registered breast cancer patients was conducted. Mammographic breast density was defined according to the American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) 4-class density rating. Mammographic lesion types were defined according to the ACR BI-RADS, including mass, mass with calcifications, calcifications, architectural distortion/asymmetries, and architectural distortion/asymmetries with calcifications. Three experienced breast radiologists interpreted all mammograms. The chi-square (χ2) test and Pearson correlation analyses were performed to assess the relationship between breast density, age, and mammographic lesion type.

Results
A significant inverse relationship was observed between the BI-RADS breast density rating given by radiologists and patient age (r = − 0.521, p < 0.01). The breast density distribution in breast cancer patients from China reversed at the age of 55 years, and exhibited one age peak in the age 55–59 year group. The percentage of lesions with calcifications decreased with increasing age (p < 0.01), and increased with increasing breast density (p < 0.01).

Conclusions
In general, we identified a relationship between patient breast density, age, and mammographic lesion type. This finding may provide a basis for clinical diagnoses and support development of breast cancer screening programs in China.
Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development
Authors: Huang Xing , Tang Tianyu , Zhang Gang , Liang Tingbo 
Published: March 2021

Abstract
Background
The mRNA-based cancer vaccine has been considered a promising strategy and the next hotspot in cancer immunotherapy. However, its application on cholangiocarcinoma remains largely uncharacterized. This study aimed to identify potential antigens of cholangiocarcinoma for development of anti-cholangiocarcinoma mRNA vaccine, and determine immune subtypes of cholangiocarcinoma for selection of suitable patients from an extremely heterogeneous population.

Methods
Gene expression profiles and corresponding clinical information were collected from GEO and TCGA, respectively. cBioPortal was used to visualize and compare genetic alterations. GEPIA2 was used to calculate the prognostic index of the selected antigens. TIMER was used to visualize the correlation between the infiltration of antigen-presenting cells and the expression of the identified antigens. Consensus clustering analysis was performed to identify the immune subtypes. Graph learning-based dimensionality reduction analysis was conducted to visualize the immune landscape of cholangiocarcinoma.

Results
Three tumor antigens, such as CD247, FCGR1A, and TRRAP, correlated with superior prognoses and infiltration of antigen-presenting cells were identified in cholangiocarcinoma. Cholangiocarcinoma patients were stratified into two immune subtypes characterized by differential molecular, cellular and clinical features. Patients with the IS1 tumor had immune “hot” and immunosuppressive phenotype, whereas those with the IS2 tumor had immune “cold” phenotype. Interestingly, patients with the IS2 tumor had a superior survival than those with the IS1 tumor. Furthermore, distinct expression of immune checkpoints and immunogenic cell death modulators was observed between different immune subtype tumors. Finally, the immune landscape of cholangiocarcinoma revealed immune cell components in individual patient.

Conclusions
CD247, FCGR1A, and TRRAP are potential antigens for mRNA vaccine development against cholangiocarcinoma, specifically for patients with IS2 tumors. Therefore, this study provides a theoretical basis for the anti-cholangiocarcinoma mRNA vaccine and defines suitable patients for vaccination.
Pexidartinib treatment in Alexander disease model mice reduces macrophage numbers and increases glial fibrillary acidic protein levels, yet has minimal impact on other disease phenotypes
Authors: Boyd Michelle M. , Litscher Suzanne J. , Seitz Laura L. , Messing Albee , Hagemann Tracy L. , Collier Lara S. 
Published: March 2021

Abstract
Background
Alexander disease (AxD) is a rare neurodegenerative disorder that is caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament that is primarily expressed by astrocytes. In AxD, mutant GFAP in combination with increased GFAP expression result in astrocyte dysfunction and the accumulation of Rosenthal fibers. A neuroinflammatory environment consisting primarily of macrophage lineage cells has been observed in AxD patients and mouse models.

Methods
To examine if macrophage lineage cells could serve as a therapeutic target in AxD, GFAP knock-in mutant AxD model mice were treated with a colony-stimulating factor 1 receptor (CSF1R) inhibitor, pexidartinib. The effects of pexidartinib treatment on disease phenotypes were assessed.

Results
In AxD model mice, pexidartinib administration depleted macrophages in the CNS and caused elevation of GFAP transcript and protein levels with minimal impacts on other phenotypes including body weight, stress response activation, chemokine/cytokine expression, and T cell infiltration.

Conclusions
Together, these results highlight the complicated role that macrophages can play in neurological diseases and do not support the use of pexidartinib as a therapy for AxD.
Osteoid osteoma: the great mimicker
Authors: Carneiro Bruno C. , Da Cruz Isabela A. N. , Ormond Filho Alípio G. , Silva Igor P. , Guimarães Júlio B. , Silva Flávio D. , Nico Marcelo A. C. , Stump Xavier M. G. R. G. 
Published: March 2021

AbstractOsteoid osteoma is a painful, benign and common bone tumor that is prevalent in young adults. The typical clinical presentation consists of pain that becomes worse at night and is relieved by nonsteroidal anti-inflammatory drugs. The most common imaging finding is a lytic lesion, known as a nidus, with variable intralesional mineralization, accompanied by bone sclerosis, cortical thickening and surrounding bone marrow edema, as well as marked enhancement with intravenous contrast injection. When the lesion is located in typical locations (intracortical bone and the diaphyses of long bones), both characteristic clinical and radiological features are diagnostic. However, osteoid osteoma is a multifaceted pathology that can have unusual presentations, such as intraarticular osteoid osteoma, epiphyseal location, lesions at the extremities and multicentric nidi, and frequently present atypical clinical and radiological manifestations. In addition, many conditions may mimic osteoid osteoma and vice versa, leading to misdiagnosis. Therefore, it is essential to understand these musculoskeletal diseases and their imaging findings to increase diagnostic accuracy, enable early treatment and prevent poor prognosis.
Thyroid hormone: sex-dependent role in nervous system regulation and disease
Authors: Baksi Shounak , Pradhan Ajay 
Published: March 2021

AbstractThyroid hormone (TH) regulates many functions including metabolism, cell differentiation, and nervous system development. Alteration of thyroid hormone level in the body can lead to nervous system-related problems linked to cognition, visual attention, visual processing, motor skills, language, and memory skills. TH has also been associated with neuropsychiatric disorders including schizophrenia, bipolar disorder, anxiety, and depression. Males and females display sex-specific differences in neuronal signaling. Steroid hormones including testosterone and estrogen are considered to be the prime regulators for programing the neuronal signaling in a male- and female-specific manner. However, other than steroid hormones, TH could also be one of the key signaling molecules to regulate different brain signaling in a male- and female-specific manner. Thyroid-related diseases and neurological diseases show sex-specific incidence; however, the molecular mechanisms behind this are not clear. Hence, it will be very beneficial to understand how TH acts in male and female brains and what are the critical genes and signaling networks. In this review, we have highlighted the role of TH in nervous system regulation and disease outcome and given special emphasis on its sex-specific role in male and female brains. A network model is also presented that provides critical information on TH-regulated genes, signaling, and disease.
Empowering large chemical knowledge bases for exposomics: PubChemLite meets MetFrag
Authors: Schymanski Emma L. , Kondić Todor , Neumann Steffen , Thiessen Paul A. , Zhang Jian , Bolton Evan E. 
Published: March 2021

AbstractCompound (or chemical) databases are an invaluable resource for many scientific disciplines. Exposomics researchers need to find and identify relevant chemicals that cover the entirety of potential (chemical and other) exposures over entire lifetimes. This daunting task, with over 100 million chemicals in the largest chemical databases, coupled with broadly acknowledged knowledge gaps in these resources, leaves researchers faced with too much—yet not enough—information at the same time to perform comprehensive exposomics research. Furthermore, the improvements in analytical technologies and computational mass spectrometry workflows coupled with the rapid growth in databases and increasing demand for high throughput “big data” services from the research community present significant challenges for both data hosts and workflow developers. This article explores how to reduce candidate search spaces in non-target small molecule identification workflows, while increasing content usability in the context of environmental and exposomics analyses, so as to profit from the increasing size and information content of large compound databases, while increasing efficiency at the same time. In this article, these methods are explored using PubChem, the NORMAN Network Suspect List Exchange and the in silico fragmentation approach MetFrag. A subset of the PubChem database relevant for exposomics, PubChemLite, is presented as a database resource that can be (and has been) integrated into current workflows for high resolution mass spectrometry. Benchmarking datasets from earlier publications are used to show how experimental knowledge and existing datasets can be used to detect and fill gaps in compound databases to progressively improve large resources such as PubChem, and topic-specific subsets such as PubChemLite. PubChemLite is a living collection, updating as annotation content in PubChem is updated, and exported to allow direct integration into existing workflows such as MetFrag. The source code and files necessary to recreate or adjust this are jointly hosted between the research parties (see data availability statement). This effort shows that enhancing the FAIRness (Findability, Accessibility, Interoperability and Reusability) of open resources can mutually enhance several resources for whole community benefit. The authors explicitly welcome additional community input on ideas for future developments.
Energy-efficient time and energy resource allocation in non-selfish symbiotic cognitive relaying sensor network with privacy preserving for smart city
Authors: Li Ping , Liu Yu , Gao Xiang , Li Huibo , Gong Peng 
Published: March 2021

AbstractEnergy efficiency and privacy preserving have become essential for the wireless sensor networks. In this paper, a joint energy and time resource allocation problem for the cognitive users (CUs) in a non-selfish symbiotic cognitive relaying scheme (NSCRS) is considered. We aim to maximize the total energy efficiency (EE) of the primary user and CUs with the consideration of information privacy under the total energy constraints of CUs. With full channel state information (CSI), an optimal energy and time resource allocation algorithm is proposed based on the exhaustive searching. Besides, in order to reduce the overhead of CSI feedback, a suboptimal algorithm, in which only the partial instantaneous CSI is required, is additionally proposed. Simulation results demonstrate the EE of primary and CUs in the NSCRS with consideration of information privacy can be greatly improved by the proposed algorithms.
Legislation and current developments in adverse drug reaction reporting in Mongolia: how far are we?
Authors: Zulzaga Zuzaan , Myagmarsuren Erdenetuya , Woerdenbag Herman J. , van Puijenbroek Eugene P. 
Published: March 2021

AbstractMonitoring adverse drug reactions is a vital issue to ensure drug safety and to protect the general public from medication-related harmful effects. In order to properly monitor drug safety, a regulatory system needs to be in place as well as an infrastructure that allows for analyzing national and international safety data. In Mongolia, adverse drug reaction (ADR) reporting activities have been implemented in the past decade. During this period, the basic structure and legal basis of an adverse drug reaction monitoring system was established. Because of the fragmented but growing healthcare system and the complexity of pharmaceutical issues in Mongolia, a sustainable process for the development of the adverse drug reaction reporting system is a key issue. The aim of this article is to disclose the Mongolian situation for the rest of the world and to share experiences on how an ADR reporting system can be developed towards a higher and more advanced level to contribute to both national and international drug safety issues. In this article, we review the features of the Mongolian health care and pharmaceutical systems, as well as the current development of the adverse drug reaction reporting system.
Toxoplasma gondii seroprevalence among pregnant women in Rabat, Morocco
Authors: Laboudi Majda , Taghy Zoubida , Duieb Oussama , Peyron François , Sadak Abderrahim 
Published: March 2021

Abstract
Background
Toxoplasmosis is an infectious disease caused by a protozoan parasite named Toxoplasma gondii (T.gondii). Pregnant women are considered one of the risk groups. The objective of this retrospective study is to provide an updated estimate of the seroprevalence of anti-T. gondii antibodies among a group of Moroccan pregnant women monitored at the Parasitology Laboratory of the National Institute of Hygiene in Rabat in Morocco.

Methods
Serum samples were tested for the presence of specific anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using indirect enzyme-linked immunosorbent assay (ELISA). Anti-Toxoplasma IgM- and IgG-positive cases were also evaluated with the anti-Toxoplasma IgG avidity test. All cases were evaluated according to the age, parity, and historical of abortion.

Results
Among 677 pregnant women, 94.1% (637/677) were serologically screened for the first time and therefore had no knowledge of their serological status, and only 5.9% (40/677) were screened for the second or third time. The overall anti-T. gondii IgG and IgM seropositivity among the 637 pregnant women included in the study analysis was 43% (274/637) and 3.9% (25/637), respectively. The use of the IgG avidity test allowed excluding recent infection among 83% of cases with IgG and IgM positive sera. The mean age was 29.4 ± 6.3 years. The result of the bivariate analysis revealed that the age influenced significantly the seroprevalence rate, while the parity and the existence of previous spontaneous abortion did not have any significant statistical correlation with seropositivity to T. gondii.

Conclusion
This study shows that 43% of pregnant women were positive and 57% of them had no antibody against the T. gondii infection. However, the pregnancy follow-up and the counseling of pregnant women remain essential for the prevention of congenital toxoplasmosis.
Application of 3D printing and distributed manufacturing during the first-wave of COVID-19 pandemic. Our experience at a third-level university hospital
Authors: Perez-Mañanes Rubén , José Sonia García-de San , Desco-Menéndez Manuel , Sánchez-Arcilla Ignacio , González-Fernández Esmeralda , Vaquero-Martín Javier , González-Garzón Javier Pascau , Mediavilla-Santos Lydia , Trapero-Moreno Diego , Calvo-Haro José Antonio 
Published: March 2021

Abstract
Background
3D printing and distributed manufacturing represent a paradigm shift in the health system that is becoming critical during the COVID-19 pandemic. University hospitals are also taking on the role of manufacturers of custom-made solutions thanks to 3D printing technology.

Case Presentation
We present a monocentric observational case study regarding the distributed manufacturing of three groups of products during the period of the COVID-19 pandemic from 14 March to 10 May 2020: personal protective equipment, ventilatory support, and diagnostic and consumable products. Networking during this period has enabled the delivery of a total of 17,276 units of products manufactured using 3D printing technology. The most manufactured product was the face shields and ear savers, while the one that achieved the greatest clinical impact was the mechanical ventilation adapters and swabs. The products were manufactured by individuals in 57.3% of the cases, and our hospital acted as the main delivery node in a hub with 10 other hospitals. The main advantage of this production model is the fast response to stock needs, being able to adapt almost in real time.

Conclusions
The role of 3D printing in the hospital environment allows the reconciliation of in-house and distributed manufacturing with traditional production, providing custom-made adaptation of the specifications, as well as maximum efficiency in the working and availability of resources, which is of special importance at critical times for health systems such as the current COVID-19 pandemic.
Comparative study between medial canthus episcleral block versus peribulbar block in intracapsular cataract surgery
Authors: Abd el raof Elsayed Ahmed Fayez , Zaghlol Mohammed Ali Ahmed , Allah Sherif Samir Wahba Rizk , Mohamed Ahmed Moustafa Mohamed 
Published: March 2021

Abstract
Background
Ophthalmic regional anesthesia is now the most common anesthetic technique used for eye surgeries. There are various modes of needle-based ophthalmic anesthesia which are retrobulbar, peribulbar, and episcleral. The sub-Tenon episcleral anesthesia technique became a potential alternative to the retrobulbar and peribulbar anesthesia in most of the anterior and posterior segment eye surgeries; this is due to its better safety profile and tolerability than the other blocks. The aim of this study was to compare between medial episcleral block and peribulbar block in intracapsular cataract surgery as regards anesthesia and akinesia of the eye, the need of supplementation of local anesthetic, and finally the safety profile of each block. This was a prospective, comparative, randomized, double-blinded clinical study. It was carried out on 60 patients that were scheduled for intracapsular cataract surgery in ophthalmic surgery unit. The patients were randomly allocated into two equal groups; group A received medial canthus episcleral block technique and group B received peribulbar block technique.

Results
Results of this prospective, comparative, randomized, double-blinded study showed no statistical difference between the two groups as regards demographic and vital data. As regards Akinesia score, the ESA group had better akinesia score at 1, 5, and 10 min and at the end of surgery than PBA group (P value, 0.001). No patient in the ESA group received supplemental injection via inferotemporal peribulbar block technique, while 66.7% of PBA group was in need of supplementation. Regarding time to onset of acceptable akinesia score; ESA group had a faster onset with high statistical significance (P value, 0.001). Numeric pain scale was better in ESA group than PBA group with high statistical significance. There were chemosis after injection in two of the ESA group (6.6%). On the other hand, slight pricking pain at the end pf surgery developed in two cases in the PBA group.

Conclusion
Medial canthal episcleral technique proved to be superior in motor akinesia score, time to onset of acceptable akinesia score, and numeric pain scale in comparison to peribulbar anesthesia with high statistical significance between the two groups. Both techniques proved to be safe with no incidence of major complications.