bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full-scale simulations to improve disaster preparedness in hospital pharmacies
Authors: Schumacher Laurence , Senhaji Salim , Gartner Birgit Andrea , Carrez Laurent , Dupuis Arnaud , Bonnabry Pascal , Widmer Nicolas 
Published: July 2022

Abstract
Purpose
Assess whether full-scale simulation exercises improved hospital pharmacies’ disaster preparedness.

Methods
Swiss hospital pharmacies performed successive full-scale simulation exercises at least four months apart. An interprofessional team created two scenarios, each representing credible regional-scale disasters involving approximately fifty casualties (a major road accident and a terrorist attack). Four exercise assessors used appraisal forms to evaluate participants’ actions and responses during the simulation (rating them using five-point Likert scales).

Results
Four hospital pharmacies performed two full-scale simulation exercises each. Differences between exercises one and two were observed. On average, the four hospitals accomplished 69% ± 6% of the actions expected of them during exercise one. The mean rate of expected actions accomplished increased to 84% ± 7% (p < 0.005) during exercise two. Moreover, the average quality of actions improved from 3.0/5 to 3.6/5 (p = 0.01), and the time required to gather a crisis management team drastically decreased between simulations (from 23 to 5 min). The main challenges were communication (reformulation) and crisis management. Simulation exercise number one resulted in three hospital pharmacies creating disaster action plans and the fourth improving its already existing plan.

Conclusion
This study highlighted the value of carrying out full-scale disaster simulations for hospital pharmacies as they improved overall institutional preparedness and increased staff awareness. The number of expected actions accomplished increased significantly. In the future, large-scale studies and concept dissemination are warranted.
Emergency departments in the United States treating high proportions of patients with ambulatory care sensitive conditions: a retrospective cross-sectional analysis
Authors: Hsuan Charleen , Zebrowski Alexis , Lin Michelle P. , Buckler David G. , Carr Brendan G. 
Published: July 2022

Abstract
Background
One in nine emergency department (ED) visits by Medicare beneficiaries are for ambulatory care sensitive conditions (ACSCs). This study aimed to examine the association between ACSC ED visits to hospitals with the highest proportion of ACSC visits (“high ACSC hospitals) and safety-net status.

Methods
This was a cross-sectional study of ED visits by Medicare fee-for-service beneficiaries ≥ 65 years using 2013–14 claims data, Area Health Resources File data, and County Health Rankings. Logistic regression estimated the association between an ACSC ED visit to high ACSC hospitals, accounting for individual, hospital, and community factors, including whether the visit was to a safety-net hospital. Safety net status was measured by Disproportionate Share Hospital (DSH) index patient percentage; public hospital status; and proportion of dual-eligible beneficiaries. Hospital-level correlation was calculated between ACSC visits, DSH index, and dual-eligible patients. We stratified by type of ACSC visit: acute or chronic.

Results
Among 5,192,729 ACSC ED visits, the odds of visiting a high ACSC hospital were higher for patients who were Black (1.37), dual-eligible (1.18), and with the highest comorbidity burden (1.26, p < 0.001 for all). ACSC visits had increased odds of being to high ACSC hospitals if the hospitals were high DSH (1.43), served the highest proportion of dual-eligible beneficiaries (2.23), and were for-profit (relative to non-profit) (1.38), and lower odds were associated with public hospitals (0.64) (p < 0.001 for all). This relationship was similar for visits to high chronic ACSC hospitals (high DSH: 1.59, high dual-eligibility: 2.60, for-profit: 1.41, public: 0.63, all p < 0.001) and to a lesser extent, high acute ACSC hospitals (high DSH: 1.02; high dual-eligibility: 1.48, for-profit: 1.17, public: 0.94, p < 0.001). The proportion of ACSC visits at all hospitals was weakly correlated with DSH proportion (0.2) and the proportion of dual-eligible patients (0.29), and this relationship was also seen for both chronic and acute ACSC visits, though stronger for the chronic ACSC visits.

Conclusion
Visits to hospitals with a high proportion of acute ACSC ED visits may be less likely to be to hospitals classified as safety net hospitals than those with a high proportion of chronic ACSC visits.
Initial presentation for acute low back pain: is early physical therapy associated with healthcare utilization and spending? A retrospective review of a National Database
Authors: Marrache Majd , Prasad Niyathi , Margalit Adam , Nayar Suresh K. , Best Matthew J. , Fritz Julie M. , Skolasky Richard L. 
Published: July 2022

Abstract
Background
Early initiation of physical therapy (PT) has been associated with lower healthcare costs and utilization; however, these studies have been limited to single institutions or healthcare systems. Our goal was to assess healthcare utilization and spending among patients who present for the first time with low back pain (LBP), according to whether they received early physical therapy (PT), using a large, nationwide sample; and geographic variation in rates of early PT and 30-day LBP-related spending.

Methods
Using the Truven MarketScan database, we identified nearly 980,000 US adults ages 18–64 years who initially presented with acute LBP from 2010 through 2014 and did not have nonmusculoskeletal causes of LBP. Approximately 110,000 patients (11%) received early PT (≤2 weeks after presentation). We compared healthcare utilization and spending at 30 days and 1 year after presentation between patients who received early PT and those who did not. Alpha = 0.05.

Results
At 30 days, early PT was associated with lower odds of chiropractor visits (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.40–0.42), pain specialist visits (OR = 0.49, 95% CI = 0.47–0.51), emergency department visits (OR = 0.51, 95% CI = 0.49–0.54), advanced imaging (OR = 0.57, 95% CI = 0.56–0.58), orthopaedist visits (OR = 0.67, 95% CI = 0.66–0.69), and epidural steroid injections (OR = 0.68, 95% CI = 0.65–0.70). At 1 year, early PT was associated with less healthcare utilization. At 30 days, patients with early PT had lower mean LBP-related spending ($1180 ± $1500) compared with those without early PT ($1250 ± $2560) (P < 0.001). At 1 year, LBP-related spending was significantly less among patients who did not receive early PT ($2510 ± $3826) versus those who did ($2588 ± $3704). Early PT rates (range, 4–25%; P < 0.001) and 30-day LBP-related spending differed by state (range, $421 to −$410; P < 0.001).

Conclusion
Early PT for acute LBP was associated with less 30-day and 1-year healthcare utilization and less 30-day LBP-related spending. Early PT rates and 30-day spending differed by US state.

Level of evidence
IV
Evaluation of new and old biomarkers in dogs with degenerative mitral valve disease
Authors: Klein Stephanie , Nolte Ingo , Granados-Soler José Luis , Lietz Philipp , Sehn Maximiliane , Raue Jonathan Friedemann , Rohn Karl , Packeiser Eva-Maria , Bach Jan-Peter 
Published: July 2022

AbstractBackgroundDogs with degenerative mitral valve disease are commonly presented to small animal clinicians. Diagnosis, clinical staging, and therapeutic design are based on a combination of clinical examination, radiography, and echocardiography. To support diagnosis and clinical monitoring, a multi-marker-based approach would be conceivable. The aim of this study was to investigate the suitability of Galectin-3 and interleukin-1 receptor-like 1 protein (ST2) in dogs with degenerative mitral valve disease in accordance with N-terminal-prohormone-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). For this purpose, serum concentrations of Galectin-3 and ST2 of 64 dogs with different stages of mitral valve disease and 21 dogs without cardiac disease were analyzed at the first examination and six months later. Echocardiography, blood cell count and clinical chemistry were performed and established biomarkers NT-proBNP and cTnI were measured additionally. Differences in the biomarker concentrations between all groups at both timepoints and the change in biomarker concentrations from first to second evaluation was investigated. Furthermore, correlations of each biomarker, between biomarkers and echocardiographic measurements, were calculated. Finally, the receiver-operating characteristic curve and the area under the curve analysis were performed to differentiate between disease stages and controls.ResultsSerum concentrations of Galectin-3 and ST2 were not statistically different between canine patients in the respective stages of mitral valve disease or in comparison to dogs in the control group at any timepoint. A significant increase in ST2 concentrations from the baseline to the follow-up examination was observed in dogs classified as stage B1 and the control group. The concentrations of NT-proBNP and cTnI in stage C dogs were significantly increased in comparison to the other groups.ConclusionsIn this study, no relation between Galectin-3 and ST2 levels to the presence or stage of mitral valve disease could be detected. Nevertheless, considering the increase in ST2 concentrations from the first to second measurement, its value on monitoring disease progress could be feasible. In agreement with previous studies, NT-proBNP and cTnI have once more proven their utility in assessing disease severity. The approach of examining new cardiac biomarkers in dogs is still worth pursuing.
APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer
Authors: Peng Li , Liu Yuwei , Chen Jing , Cheng Mengxin , Wu Ying , Chen Min , Zhong Ya , Shen Dan , Chen Ling , Ye Xujun 
Published: July 2022

Abstract
Background
Aberrant alternative splicing (AS) contributes to tumor progression. Previous studies have shown that apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression. It is unknown whether APEX1 functions in tumor progression by regulation of AS. It is also unknown whether APEX1 can regulate non-small-cell lung cancer (NSCLC) proliferation and apoptosis. We analyzed APEX1 expression levels in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database. The impact of APEX1 over expression on A549 cell proliferation and apoptosis was detected by the methyl thiazolyl tetrazolium assay and by flow cytometry. The transcriptome of A549 cells with and without APEX1 over expression was determined by Illumina sequencing, followed by analysis of AS. RT-qPCR validated expression of APEX1-related genes in A549 cells. We have successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS.

Results
APEX1 expression was shown to be upregulated in NSCLC samples and to reduce cell proliferation and induce apoptosis of A549 cells. In addition, APEX1 regulated AS of key tumorigenesis genes involved in cancer proliferation and apoptosis within MAPK and Wnt signaling pathways. Each of these pathways are involved in lung cancer progression. Furthermore, validated AS events regulated by APEX1 were in key tumorigenesis genes; AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), and SMAD3 (SMAD Family Member 3). These genes encode signaling pathway transcription regulatory factors.

Conclusions
We found that increased expression of APEX1 was an independent prognostic factor related to NSCLC progression. Therefore, APEX1 regulation of AS may serve as a molecular marker or therapeutic target for NSCLC treatment.
Association between lipid profiles and viral respiratory infections in human sputum samples
Authors: Humes Sara T. , Iovine Nicole , Prins Cindy , Garrett Timothy J. , Lednicky John A. , Coker Eric S. , Sabo-Attwood Tara 
Published: July 2022

Abstract
Background
Respiratory infections such as influenza account for significant global mortality each year. Generating lipid profiles is a novel and emerging research approach that may provide new insights regarding the development and progression of priority respiratory infections. We hypothesized that select clusters of lipids in human sputum would be associated with specific viral infections (Influenza (H1N1, H3N2) or Rhinovirus).

Methods
Lipid identification and semi-quantitation was determined with liquid chromatography and high-resolution mass spectrometry in induced sputum from individuals with confirmed respiratory infections (influenza (H1N1, H3N2) or rhinovirus). Clusters of lipid species and associations between lipid profiles and the type of respiratory viral agent was determined using Bayesian profile regression and multinomial logistic regression.

Results
More than 600 lipid compounds were identified across the sputum samples with the most abundant lipid classes identified as triglycerides (TG), phosphatidylethanolamines (PE), phosphatidylcholines (PC), Sphingomyelins (SM), ether-PC, and ether-PE. A total of 12 lipid species were significantly different when stratified by infection type and included acylcarnitine (AcCar) (10:1, 16:1, 18:2), diacylglycerols (DG) (16:0_18:0, 18:0_18:0), Lysophosphatidylcholine (LPC) (12:0, 20:5), PE (18:0_18:0), and TG (14:1_16:0_18:2, 15:0_17:0_19:0, 16:0_17:0_18:0, 19:0_19:0_19:0). Cluster analysis yielded three clusters of lipid profiles that were driven by just 10 lipid species (TGs and DGs). Cluster 1 had the highest levels of each lipid species and the highest prevalence of influenza A H3 infection (56%, n = 5) whereas cluster 3 had lower levels of each lipid species and the highest prevalence of rhinovirus (60%; n = 6). Using cluster 3 as the reference group, the crude odds of influenza A H3 infection compared to rhinovirus in cluster 1 was significantly (p = 0.047) higher (OR = 15.00 [95% CI: 1.03, 218.29]). After adjustment for confounders (smoking status and pulmonary comorbidities), the odds ratio (OR) became only marginally significant (p = 0.099), but the magnitude of the effect estimate was similar (OR = 16.00 [0.59, 433.03]).

Conclusions
In this study, human sputum lipid profiles were shown to be associated with distinct types of viral infection. Better understanding the relationship between respiratory infections of global importance and lipids contributes to advancing knowledge of pathogenesis of infections including identifying populations with increased susceptibility and developing effective therapeutics and biomarkers of health status.
Sequence, structure, and function of the Dps DNA-binding protein from Deinococcus wulumuqiensis R12
Authors: Chen Yao , Yang Zhihan , Zhou Xue , Jin Mengmeng , Dai Zijie , Ming Dengming , Zhang Zhidong , Zhu Liying , Jiang Ling 
Published: July 2022

AbstractDeinococcus wulumuqiensisR12, which was isolated from arid irradiated soil in Xinjiang province of China, belongs to a genus that is well-known for its extreme resistance to ionizing radiation and oxidative stress. The DNA-binding protein Dps has been studied for its great contribution to oxidative resistance. To explore the role of Dps inD. wulumuqiensisR12, the Dps sequence and homology-modeled structure were analyzed. In addition, thedpsgene was knocked out and proteomics was used to verify the functions of Dps inD. wulumuqiensisR12. Docking data and DNA binding experiments in vitro showed that the R12 Dps protein has a better DNA binding ability than the Dps1 protein fromD. radioduransR1. When thedpsgene was deleted inD. wulumuqiensisR12, its resistance to H2O2and UV rays was greatly reduced, and the cell envelope was destroyed by H2O2treatment. Additionally, the qRT-PCR and proteomics data suggested that when thedpsgene was deleted, the catalase gene was significantly down-regulated. The proteomics data indicated that the metabolism, transport and oxidation–reduction processes ofD. wulumuqiensisR12 were down-regulated after the deletion of thedpsgene. Overall, the data conformed that Dps protein plays an important role inD. wulumuqiensisR12.
Flagella disruption in Bacillus subtilis increases amylase production yield
Authors: Fehler Annaleigh Ohrt , Kallehauge Thomas Beuchert , Geissler Adrian Sven , González-Tortuero Enrique , Seemann Stefan Ernst , Gorodkin Jan , Vinther Jeppe 
Published: July 2022

Abstract
Background
Bacillus subtilis is a Gram-positive bacterium used as a cell factory for protein production. Over the last decades, the continued optimization of production strains has increased yields of enzymes, such as amylases, and made commercial applications feasible. However, current yields are still significantly lower than the theoretically possible yield based on the available carbon sources. In its natural environment, B. subtilis can respond to unfavorable growth conditions by differentiating into motile cells that use flagella to swim towards available nutrients.

Results
In this study, we analyze existing transcriptome data from a B. subtilis α-amylase production strain at different time points during a 5-day fermentation. We observe that genes of the fla/che operon, essential for flagella assembly and motility, are differentially expressed over time. To investigate whether expression of the flagella operon affects yield, we performed CRISPR-dCas9 based knockdown of the fla/che operon with sgRNA target against the genes flgE, fliR, and flhG, respectively. The knockdown resulted in inhibition of mobility and a striking 2–threefold increase in α-amylase production yield. Moreover, replacing flgE (required for flagella hook assembly) with an erythromycin resistance gene followed by a transcription terminator increased α-amylase yield by about 30%. Transcript levels of the α-amylase were unaltered in the CRISPR-dCas9 knockdowns as well as the flgE deletion strain, but all manipulations disrupted the ability of cells to swim on agar.

Conclusions
We demonstrate that the disruption of flagella in a B. subtilis α-amylase production strain, either by CRISPR-dCas9-based knockdown of the operon or by replacing flgE with an erythromycin resistance gene followed by a transcription terminator, increases the production of α-amylase in small-scale fermentation.
Impact of COVID-19 among people who use drugs: A qualitative study with harm reduction workers and people who use drugs
Authors: Conway Fiona N. , Samora Jake , Brinkley Katlyn , Jeong Haelim , Clinton Nina , Claborn Kasey R. 
Published: July 2022

Abstract
Background
Fatal drug overdoses in the USA hit historical records during the COVID-19 pandemic. Throughout the pandemic, people who used drugs had greater odds of contracting COVID-19, increased drug use due to COVID-related stress, and heightened levels of anxiety and depression. This qualitative study examined the specific ways the pandemic negatively impacted people who use drugs.

Methods
Qualitative interviews with 24 people who use drugs and 20 substance use harm reduction workers were conducted. Data from the qualitative interviews were analyzed using applied thematic analysis to identify emergent themes based on the a priori research goals.

Results
Thematic analysis identified several common experiences during the pandemic among people who use drugs. These included mental distress due to financial strain and social isolation; increased drug use; increased risky drug-seeking and use behaviors due to changes in the drug markets; and reduced access to harm reduction, treatment, and recovery support services.

Conclusions
Our study highlighted critical systemic failures that contributed to the rise in overdose deaths during the COVID-19 pandemic. Addressing these challenges through policy reform and improved funding models will ensure the sustainability of harm reduction services and increase access to substance use treatment among highly vulnerable people who use drugs.
Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model
Authors: Freitag Kiara , Sterczyk Nele , Wendlinger Sarah , Obermayer Benedikt , Schulz Julia , Farztdinov Vadim , Mülleder Michael , Ralser Markus , Houtman Judith , Fleck Lara , Braeuning Caroline , Sansevrino Roberto , Hoffmann Christian , Milovanovic Dragomir , Sigrist Stephan J. , Conrad Thomas , Beule Dieter , Heppner Frank L. , Jendrach Marina 
Published: July 2022

AbstractBackgroundDeposition of amyloid beta (Aβ) and hyperphosphorylated tau along with glial cell-mediated neuroinflammation are prominent pathogenic hallmarks of Alzheimer’s disease (AD). In recent years, impairment of autophagy has been identified as another important feature contributing to AD progression. Therefore, the potential of the autophagy activator spermidine, a small body-endogenous polyamine often used as dietary supplement, was assessed on Aβ pathology and glial cell-mediated neuroinflammation.ResultsOral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation. Mechanistically, single nuclei sequencing revealed AD-associated microglia to be the main target of spermidine. This microglia population was characterized by increased AXL levels and expression of genes implicated in cell migration and phagocytosis. A subsequent proteome analysis of isolated microglia confirmed the anti-inflammatory and cytoskeletal effects of spermidine in APPPS1 mice. In primary microglia and astrocytes, spermidine-induced autophagy subsequently affected TLR3- and TLR4-mediated inflammatory processes, phagocytosis of Aβ and motility. Interestingly, spermidine regulated the neuroinflammatory response of microglia beyond transcriptional control by interfering with the assembly of the inflammasome.ConclusionsOur data highlight that the autophagy activator spermidine holds the potential to enhance Aβ degradation and to counteract glia-mediated neuroinflammation in AD pathology.
Protocol: rhPCR and SNaPshot assays to distinguish Plasmodiophora brassicae pathotype clusters
Authors: Tso Heather H. , Galindo-González Leonardo , Locke Troy , Strelkov Stephen E. 
Published: July 2022

Abstract
Background
Clubroot of canola (Brassica napus), caused by the soilborne pathogen Plasmodiophora brassicae, has become a serious threat to canola production in Canada. The deployment of clubroot-resistant (CR) cultivars is the most commonly used management strategy; however, the widespread cultivation of CR canola has resulted in the emergence of new pathotypes of P. brassicae capable of overcoming resistance. Several host differential sets have been reported for pathotype identification, but such testing is time-consuming, labor-intensive, and based on phenotypic classifications. The development of rapid and objective methods that allow for efficient, cost-effective and convenient pathotyping would enable testing of a much larger number of samples in shorter times. The aim of this study was to develop two pathotyping assays, an RNase H2-dependent PCR (rhPCR) assay and a SNaPshot assay, which could quickly differentiate P. brassicae pathotypes.

Results
Both assays clearly distinguished between pathotype clusters in a collection of 38 single-spore isolates of P. brassicae. Additional isolates pathotyped from clubbed roots and samples from blind testing also were correctly clustered. The rhPCR assay generated clearly differentiating electrophoretic bands without non-specific amplification. The SNaPshot assay was able to detect down to a 10% relative allelic proportion in a 10:90 template mixture with both single-spore isolates and field isolates when evaluated in a relative abundance test.

Conclusions
This study describes the development of two rapid and sensitive technologies for P. brassicae pathotyping. The high-throughput potential and accuracy of both assays makes them promising as SNP-based pathotype identification tools for clubroot diagnostics. rhPCR is a highly sensitive approach that can be optimized into a quantitative assay, while the main advantages of SNaPshot are its ability to multiplex samples and alleles in a single reaction and the detection of up to four allelic variants per target site.