bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-series analysis of recent antihyperglycemic medication prescribing trends for a diverse sample of Medicare enrollees with type 2 diabetes mellitus in an integrated health system
Authors: Miller Michael J , DiNucci Anna J , Jalalzai Rabia , Rabinovich Nonna , Roblin Douglas W 
Published: February 2022

Abstract

Purpose
Despite high type 2 diabetes mellitus (T2DM) prevalence in Medicare enrollees, newer therapeutic options, and revised treatment guidelines, little is known about US antihyperglycemic prescribing trends after 2015. This research describes recent monthly antihyperglycemic prescribing trends in a large, diverse population of Medicare enrollees from the US Mid-Atlantic region.

Methods
Encounter data (July 2018-July 2020) for Medicare enrollees 65 years of age or older with T2DM were extracted from electronic health records of a large integrated health system. Descriptive time-series regression models were estimated to describe monthly prescribing rates (ie, prescription orders per 100 eligible plan members with T2DM) overall and by medication subgroups for all-eligible and continuously-eligible samples. Trends in monthly prescription orders per 100 eligible plan members with T2DM were reported.

Results
The monthly all-eligible member sample (n &gt; 22,000) exhibited an overall positive baseline monthly prescribing rate of 23.88 T2DM medication orders per 100 members with T2DM and a significant positive monthly prescribing rate trend (ie, change) of 0.12 T2DM medication orders per 100 members with T2DM (P &lt; 0.05). Subgroup T2DM medication order rates per 100 members with T2DM at baseline were 16.28 for first-generation medications, 3.87 for human insulins, 3.04 for insulin analogs, 0.58 for second-generation medications, and 0.11 for combination medications. Human insulins, insulin analogs, and second-generation medications had positive monthly trends (P &lt; 0.05). Among second-generation medications, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists had positive monthly trends (P &lt; 0.05). Continuously eligible members with T2DM (n = 19,185) had no significant overall monthly prescribing trend; however, human insulins, insulin analogs, and second-generation medications and the SGLT-2 inhibitor class had positive monthly prescribing trends (P &lt; 0.05).

Conclusion
In a diverse Medicare sample, this study observed increasing monthly trends for second-generation medications, human insulins, and insulin analogs consistent with emerging evidence. Among second-generation medications, SGLT-2 inhibitors became the most commonly prescribed over time.
Evaluating hematology/oncology clinical pharmacist activities via self-reported work sampling
Authors: Lee Julia S , Nickman Nancy A , Pace Makala 
Published: February 2022

Abstract

Purpose
Hematology/oncology clinical pharmacists’ work activities have been described in previous literature, but time spent on pharmacist tasks has not been well characterized. Random work sampling (WS) is a form of activity assessment to determine the proportion of time spent in various types of work. Based on results from previous WS evaluations at University of Utah and its Huntsman Cancer Hospital, activities were changed to maximize time dedicated to clinical activities and pharmacists’ benefit to providers and patients in both inpatient and ambulatory care settings. Therefore, updated random WS evaluations were completed during spring 2019 and fall 2020.

Methods
Personal digital assistant (PDA) devices were used to record hematology/oncology clinical pharmacists’ onsite or remote location and work activity data. Data were collected 8 times per hour on weekdays, with a goal of 275 observations per pharmacist. Results were then classified as clinical, professional, or technical activities.

Results
In 2019, 9,079 observations were recorded by 31 onsite pharmacists. In 2020, 28 pharmacists recorded 8,803 observations (5,524 during onsite work and 3,279 during remote work). The overall distribution of pharmacists’ work activities remained stable between 2019 and 2020, with 89% of activities classified as clinical or professional. Pharmacists spent a smaller proportion of time on in-person communication in 2020, balanced by increases in chart review and text-based communication. Onsite pharmacists reported a larger proportion of clinical activities, while remote pharmacists reported a larger proportion of professional activities.

Conclusion
Continued WS assessment of work activity patterns will allow identification of opportunities to streamline workflows, maximize pharmacist engagement in clinical activities, and development of remote work policy.
Single-cell RNA sequencing data analysis based on non-uniformε−neighborhood network
Authors: Jia Junbo , Chen Luonan 
Published: February 2022

AbstractMotivationSingle-cell RNA sequencing (scRNA-seq) technology provides the possibility to study cell heterogeneity and cell development on the resolution of individual cells. Arguably, three of the most important computational targets on scRNA-seq data analysis are data visualization, cell clustering and trajectory inference. Although a substantial number of algorithms have been developed, most of them do not treat the three targets in a systematic or consistent manner.ResultsIn this article, we propose an efficient scRNA-seq analysis framework, which accomplishes the three targets consistently by non-uniform ε−neighborhood (NEN) network. First, a network is generated by our NEN method, which combines the advantages of both k-nearest neighbors (KNN) and ε−neighborhood (EN) to represent the manifold that data points reside in gene space. Then from such a network, we use its layout, its community and further its shortest path to achieve the purpose of scRNA-seq data visualization, clustering and trajectory inference. The results on both synthetic and real datasets indicate that our NEN method not only can visually provide the global topological structure of a dataset accurately compared with t-SNE (t-Distributed Stochastic Neighbor Embedding) and UMAP (Uniform Manifold Approximation and Projection), but also has superior performances on clustering and pseudotime ordering of cells over the existing approaches.Availability and implementationThis analysis method has been made into a python package called ccnet and is freely available at https://github.com/Just-Jia/ccNet.Supplementary informationSupplementary data are available at Bioinformatics online.
The largest digital database of fern and lycopod records from Honduras: spatial, temporal and collector biases
Authors: Batke Sven P , Dallimore Thom , Reyes-Chávez Johan , Maradiaga Rina Fabiola Diaz , Somers Edward , Jones Indiana , Atkinson Wendy , Acosta Lilian Ferrufino , Reid Geraldine 
Published: February 2022

Abstract
Honduras is one of the least botanically studied countries in Central America. Most of the scientific botanical information for Honduras is housed in globally distributed herbaria, an often-under-used resource. A recently published checklist of ferns and lycopods from Honduras indicated that for the 713 taxa, often few distribution data are available and that we still do not know where fern and lycopod collections have taken place in the past. Therefore, the aims of this work were to (1) bring together for the first time a comprehensive inventory of fern and lycopod records from international herbaria and to (2) identify spatial, temporal and collector biases of these collections. Published and unpublished herbarium inventories of ferns and lycopod records were accessed from 2212 global herbaria. Of these, 39 hosted Honduran fern and lycopod collections. The final database included 22 194 herbarium records. Spatial and idiosyncratic collection biases are shown, with collections hotspots in areas such the Department of Francisco Morazán near the TEFH and Escuela Agrícola Panamericana (EAP) herbaria, in Celaque National Park near the city of San Pedro Sula and Tela and Lancetilla Botanical Garden. This unique database deposited at EAP, TEFH, LIV and Edge Hill University will enable Hondurans to share information to support the protection, restoration and sustainable use of their ecosystems.
A map of neurofilament light chain species in brain and cerebrospinal fluid and alterations in Alzheimer’s disease
Authors: Budelier Melissa M. , He Yingxin , Barthelemy Nicolas R. , Jiang Hong , Li Yan , Park Ethan , Henson Rachel L. , Schindler Suzanne E. , Holtzman David M. , Bateman Randall J. 
Published: February 2022

Abstract
Neurofilament light is a well-established marker of both acute and chronic neuronal damage and is increased in multiple neurodegenerative diseases. However, the protein is not well characterized in brain tissue or body fluids, and it is unknown what neurofilament light species are detected by commercial assays and whether additional species exist. We developed an immunoprecipitation-mass spectrometry assay using custom antibodies targeting various neurofilament light domains, including antibodies targeting Coil 1A/1B of the rod domain (HJ30.13), Coil 2B of the rod domain (HJ30.4) and the tail region (HJ30.11). We utilized our assay to characterize neurofilament light in brain tissue and CSF of individuals with Alzheimer’s disease dementia and healthy controls. We then validated a quantitative version of our assay and measured neurofilament light concentrations using both our quantitative immunoprecipitation-mass spectrometry assay and the commercially available immunoassay from Uman diagnostics in individuals with and without Alzheimer’s disease dementia. Our validation cohort included CSF samples from 30 symptomatic amyloid-positive participants, 16 asymptomatic amyloid-positive participants, 10 symptomatic amyloid-negative participants and 25 amyloid-negative controls. We identified at least three major neurofilament light species in CSF, including N-terminal and C-terminal truncations, and a C-terminal fragment containing the tail domain. No full-length neurofilament light was identified in CSF. This contrasts with brain tissue, which contained mostly full-length neurofilament and a C-terminal tail domain fragment. We observed an increase in neurofilament light concentrations in individuals with Alzheimer’s disease compared with healthy controls, with larger differences for some neurofilament light species than for others. The largest differences were observed for neurofilament light fragments including NfL165 (in Coil 1B), NfL324 (in Coil 2B) and NfL530 (in the C-terminal tail domain). The Uman immunoassay correlated most with NfL324. This study provides a comprehensive evaluation of neurofilament light in brain and CSF and enables future investigations of neurofilament light biology and utility as a biomarker.
Historical mitochondrial genome introgression confounds species delimitation: evidence from phylogenetic inference in theOdorrana grahamispecies complex
Authors: Yuan Zhiyong , Wu Dongyi , Wen Yang , Xu Wei , Gao Wei , Dahn Hollis A , Liu Xiaolong , Jin Jieqiong , Yu Chuanxin , Xiao Heng , Che Jing 
Published: February 2022

AbstractSpecies delimitation is essential to informing conservation policy and understanding ecological and evolutionary processes. Most of our recent gains in knowledge on animal diversity rely on morphological characteristics and mitochondrial (mt) DNA variation. Concordant results based on both have led to an unprecedented acceleration in the identification of new species and enriched the field of taxonomy. However, discordances are also found commonly between morphological and mtDNA evidence. This confounds species delimitation, especially when gene flow or mt genome introgression has occurred. Here, we illustrate how mt genome introgression among species of the Odorrana grahami complex confounds species delimitation using the combined evidence of morphological characters, mt variation, and thousands of nuclear single-nucleotide polymorphisms (SNPs) from genotyping-by-sequencing (GBS). Fifty-eight samples across the distribution of the O. grahami complex were included. The mtDNA matrilineal genealogy indicated 2 clades, with O. grahami and Odorrana junlianensis clustered together. In contrast, all nuclear evidence including gene trees, species trees, and genetic structure analyses based on GBS data support 3 species with distinct genetic clusters. These 3 distinct genetic clusters also correspond to distinct morphological characters. They affirm the distinct taxonomic entities of both O. grahami and O. junlianensis, as well as a third clade distinct from either. Which species the third clade belongs to remains unclear and will require further testing. The nuclear genomic loci contradict the COI evidence, with indications of rampant historical mt genome introgression among the species of the O. grahami complex. These discordant signals previously confused species delimitation efforts in this group. Based on these findings, we recommend the integration of independent data, especially nuclear genomic evidence, in species delimitation so as to be robust against the pitfalls of mt introgression.
Coronavirus disease 2019-associated coronary endotheliitis and thrombotic microangiopathy causing cardiogenic shock: a case report
Authors: Valiton Valérian , Bendjelid Karim , Pache Jean-Claude , Roffi Marco , Meyer Philippe 
Published: February 2022

Abstract

Background
Coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract but serious cardiovascular complications have been reported. Up to one-third of patients admitted to the intensive care unit may develop an acute myocardial injury, characterized by cardiac troponin elevation. However, the pathology underlying COVID-19-associated myocardial injury has rarely been reported.

Case summary
Three days after being diagnosed for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a 52-year-old woman without a notable past medical history developed cardiogenic shock with severely reduced left ventricular ejection fraction (LVEF) at 25%. Coronary angiography was normal. Endomyocardial biopsy demonstrated coronary endotheliitis with multiple microvascular thromboses but no lymphocytic infiltrate and a negative polymerase chain reaction for SARS-CoV-2. The patient was implanted with a short-term LV assist device (Impella CP®, Abiomed, Aachen, Germany) and treated with therapeutic anticoagulation. She suffered from concomitant respiratory failure that required 14 days of orotracheal intubation, 10 days of dexamethasone, and broad-spectrum antibiotics. Clinical outcome was favourable with weaning of the Impella device after 6 days and full recovery of LVEF (65%) at 30 days. Cardiac magnetic resonance performed at Day 30 showed no evidence of myocarditis or scars and confirmed the normalization of LVEF.

Discussion
This case highlights how COVID-19-associated coronary endotheliitis and thrombotic microangiopathy, in the absence of myocarditis, may induce transient severe LV dysfunction and cardiogenic shock.
Endothelial superoxide dismutase 2 is decreased in sickle cell disease and regulates fibronectin processing
Authors: Dosunmu-Ogunbi Atinuke , Yuan Shuai , Shiwarski Daniel J , Tashman Joshua W , Reynolds Michael , Feinberg Adam , Novelli Enrico M , Shiva Sruti , Straub Adam C 
Published: February 2022

Abstract
Sickle cell disease (SCD) is a genetic red blood cell disorder characterized by increased reactive oxygen species (ROS) and a concordant reduction in antioxidant capacity in the endothelium. Superoxide dismutase 2 (SOD2) is a mitochondrial-localized enzyme that catalyzes the dismutation of superoxide to hydrogen peroxide. Decreased peripheral blood expression of SOD2 is correlated with increased hemolysis and cardiomyopathy in SCD. Here, we report for the first time that endothelial cells exhibit reduced SOD2 protein expression in the pulmonary endothelium of SCD patients. To investigate the impact of decreased SOD2 expression in the endothelium, SOD2 was knocked down in human pulmonary microvascular endothelial cells (hPMVECs). We found that SOD2 deficiency in hPMVECs results in endothelial cell dysfunction, including reduced cellular adhesion, diminished migration, integrin protein dysregulation, and disruption of permeability. Furthermore, we uncover that SOD2 mediates changes in endothelial cell function via processing of fibronectin through its inability to facilitate dimerization. These results demonstrate that endothelial cells are deficient in SOD2 expression in SCD patients and suggest a novel pathway for SOD2 in regulating fibronectin processing.
“Who Wants to Know all this Stuff?!”
Authors: Alkhatib Sami , Kelly Ryan , Waycott Jenny , Buchanan George , Grobler Marthie , Wang Shuo 
Published: February 2022

Abstract
The paper, ‘“Who Wants to Know all this Stuff?!”: Understanding Older Adults’ Privacy Concerns in Aged Care Monitoring Devices’, by Sami Alkhatib, Ryan Kelly, Jenny Waycott, George Buchanan, Marthie Grobler and Shuo Wang, published in Interacting with Computers (November 2021), explores the use of care technology and the privacy concerns of older people.
Compassionate use of meropenem/vaborbactam for infections caused by KPC-producing Klebsiella pneumoniae: a multicentre study
Authors: Tumbarello Mario , Raffaelli Francesca , Cascio Antonio , Falcone Marco , Signorini Liana , Mussini Cristina , De Rosa Francesco Giuseppe , Losito Angela Raffaella , De Pascale Gennaro , Pascale Renato , Giacobbe Daniele Roberto , Oliva Alessandra , Farese Alberto , Morelli Paola , Tiseo Giusy , Meschiari Marianna , Del Giacomo Paola , Montagnani Francesca , Fabbiani Massimiliano , Vargas Joel , Spanu Teresa , Bassetti Matteo , Venditti Mario , Viale Pierluigi 
Published: February 2022

Abstract

Objectives
To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam.

Methods
A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included.

Results
The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy &gt;48 h after infection onset. Outcomes were unrelated to the isolate’s ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia.

Conclusions
With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.
Development of Kudzu (Pueraria Montana var. lobata) Reference Materials for the Determination of Isoflavones and Toxic Elements
Authors: Lippert J Andreas , Rimmer Catherine A , Phillips Melissa M , Nelson Michael A , Barber Charles A , Wood Laura J , Long Stephen E , Bryan Colleen E , Sharpless Katherine E , Yen James , Kuszak Adam J , Wise Stephen A 
Published: February 2022

Abstract

Background
In collaboration with the Office of Dietary Supplements at the National Institutes of Health, the National Institute of Standards and Technology issued a suite of botanical matrix reference materials (RMs) and Standard Reference Material® (SRM) for determination of isoflavones and toxic elements in kudzu dietary supplement ingredients.

Objective
RM 8650 Pueraria montana var. lobata (Kudzu) Rhizome, SRM 3268 Pueraria montana var. lobata (Kudzu) Extract, and RM 8652 Kudzu-Containing Solid Oral Dosage Form were issued with values assigned for isoflavones (puerarin, daidzin, and daidzein), toxic elements (arsenic, cadmium, and lead), and selenium.

Methods
Isoflavone values were assigned using liquid chromatography with UV absorbance or mass spectrometry detection. Element values were assigned using inductively coupled plasma mass spectrometry and results from an interlaboratory comparison exercise.

Results
Mass fractions for puerarin were 32.2 ± 3.2 mg/g, 128 ± 13 mg/g, and 68.2 ± 6.9 mg/g in RM 8650, SRM 3268, and RM 8652, respectively. Arsenic increases from 156 ± 14 ng/g to 849 ± 83 ng/g and cadmium decreases from 348 ± 14 ng/g to 82.1 ± 4.9 ng/g from rhizome to extract.

Conclusion
The kudzu RM/SRM suite complements previously issued soy-related SRMs with values assigned for isoflavones, which have been studied for their potential health benefits, and expands the analytical resource by providing values for puerarin, an isoflavone not found in soy.

Highlights
The three new kudzurmaterials are for use in the determination of isoflavones, toxic elements, and selenium. For the isoflavones, these new kudzu materials provide higher levels of daidzin and daidzein than existing soy-related SRMs, and they provide a value for an isoflavone not in existing SRMs (puerarin). Toxic elements in RM 8650 and SRM 3268 provide new botanical matrixes for use by dietary supplement manufacturers for the verification of the safety of their raw materials.
Pediatric Burn Care in the Developing World: Where Are the Gaps in Research and What Can Be Done?
Authors: Bresler Richard Mark , Barksdale Elizabeth , Hansen Erik Nels 
Published: February 2022

Abstract
Burns are the fourth most common cause of injury worldwide. The burden of burn injury is largely carried by low- and middle-income countries (LMICs) with children in these regions being particularly vulnerable to burns. The purpose of this scoping review is to identify knowledge gaps in global pediatric burn care experience in an effort to help prioritize future research. Using the 6-stage Arksey and O’Malley framework for conducting a scoping review, pediatric burn care literature was reviewed over a 10-year period from 2010 to 2020. Studies from low-resource settings were included and categorized by geographic location, study patient population, study type, type of burn, and level of evidence. Of 107 included studies, 34% and 49% originated from LMICs in South Asia and Sub-Saharan Africa, respectively. Qualitative/observational (73%) and epidemiological single-center (20%) publications comprised the majority of included papers. The majority (95%) of all papers regardless of geographical location were lower levels of evidence (Level 3 or below). Our study identified four primary knowledge gaps: 1) a paucity of high-quality studies to guide burn care in LMICs; 2) an under-representation of articles from certain geographical locations; 3) few therapeutic and economic articles to guide resource allocation; and 4) a lack of articles with long-term patient follow-up. Efforts to address these disparities could help reduce the pediatric burn burden of disease in resource-poor settings.