bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stakeholder perceptions of the use of a rapidly deployed modified ECHO to train and prepare healthcare providers for COVID-19
Authors: Casanova Madeline P , Blades Kayla C , Palmer Kathleen , Smith Lachelle H , Fuerst Peter , Seegmiller Jeffrey G , Baker Russell T 
Published: September 2022

Background: Innovative approaches to deliver timely information to rural healthcare providers are necessary with the COVID-19 pandemic. Project Extension for Community Healthcare Outcomes (ECHO) is a telementoring program designed to provide practitioners in rural communities with opportunities to engage in specialty training. We examined participant perceptions of a rapidly deployed, single continuing education session to improve healthcare provider preparedness for COVID-19 in Idaho. Methods: A modified Project ECHO session was developed to inform providers about emergency preparedness, treatment, testing, and resources for COVID-19. A post-session survey examined session impact and barriers on clinical practice. Results: Respondents believed the modified ECHO session increased COVID-19 knowledge and would improve their clinical practice and preparedness. Respondents were satisfied with the session and identified content, interdisciplinary collaboration, and format as beneficial; perceived barriers for utilizing session information included a lack of relevance of content and clinical applicability, and time constraints. Conclusions: A rapidly deployed modified Project ECHO session was perceived as an effective mechanism to foster collaboration and relay information to promote best practices at the start of the COVID-19 pandemic. An established Project ECHO network may be useful to rapidly exchange knowledge and information during a health emergency.
Increasing tissue requirements in lymphoma trials may exclude patients with high-risk disease or worse prognosis
Authors: Desai Sanjal H. , Mwangi Raphael , Ng Wern Lynn , King Rebecca L. , Maurer Matthew J. , Cerhan James R. , Feldman Andrew L. , Farooq Umar , Mou Eric , Habermann Thomas M. , Thompson Carrie A. , Wang Yucai , Witzig Thomas E. , Nowakowski Grzegorz S. 
Published: September 2022

Abstract
An enhanced understanding of the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has opened the door to clinical trials evaluating novel agents with subtype-specific activity. It is an emerging question whether core needle biopsies (CNB) can adequately meet the increasing tissue requirements of these clinical trials. This can potentially lead to selective enrollment of patients who can undergo excisional biopsy (EB). It is also important to know whether patients who can undergo extensive diagnostic work up differ in their disease characteristics and outcomes from those who cannot. In this observational study, we describe the characteristics, outcomes, and adequacy of diagnostic tissue in patients with newly diagnosed DLBCL and primary mediastinal large B-cell lymphoma who underwent EB vs CNB. Of the 1061 patients, 532 (49.8%) underwent EB and 529 (50.1%) underwent CNB. A significantly higher proportion of patients with CNB had advanced stage disease, an international prognostic index of ≥3, and inadequate tissue for molecular analyses. Patients with CNB had significantly worse 5-year event-free survival (67.6% vs 56.9%; hazard ratio [HR], 0.76; confidence interval [CI]95, 0.6-0.9, P &lt; .001) and 5-year overall survival (76.4% vs 69.2%; HR, 0.8; CI95, 0.6-0.9, P &lt; .001). Thus, patients who underwent CNB have poor-risk features and inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses, and might not meet the tissue requirements of biomarker-driven clinical trials. Thus, the increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of patients with high-risk DLBCL who need novel agents.
Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms
Authors: Chovanec Jack , Tunc Ilker , Hughes Jason , Halstead Joseph , Mateja Allyson , Liu Yihui , O’Connell Michael P. , Kim Jiwon , Park Young Hwan , Wang Qinlu , Le Quang , Pirooznia Mehdi , Trivedi Neil N. , Bai Yun , Yin Yuzhi , Hsu Amy P. , McElwee Joshua , Lassiter Sheryce , Nelson Celeste , Bandoh Judy , DiMaggio Thomas , Šelb Julij , Rijavec Matija , Carter Melody C. , Komarow Hirsh D. , Sabato Vito , Steinberg Joshua , Hafer Kurt M. , Feuille Elizabeth , Hourigan Christopher S. , Lack Justin , Khoury Paneez , Maric Irina , Zanotti Roberta , Bonadonna Patrizia , Schwartz Lawrence B. , Milner Joshua D. , Glover Sarah C. , Ebo Didier G. , Korošec Peter , Caughey George H. , Brittain Erica H. , Busby Ben , Metcalfe Dean D. , Lyons Jonathan J. 
Published: September 2022

Abstract
Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where basal serum tryptase (BST) levels &gt;20 ng/mL are a minor criterion for diagnosis. Although clonal myeloid neoplasms are rare, the common cause for elevated BST levels is the genetic trait hereditary α-tryptasemia (HαT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HαT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HαT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from overexpression of replicated TPSAB1 loci encoding canonical α-tryptase protein owing to coinheritance of a linked overactive promoter element. Modeling BST levels based on TPSAB1 replication number, we generate new individualized clinical reference values for the upper limit of normal. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels &gt;11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (eg, &gt;100 ng/mL), which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within normal limits for certain individuals with HαT.
Introducing oxygen transfer rate measurements as a novel method for time-resolved cytotoxicity assessment in shake flasks
Authors: Ihling Nina , Munkler Lara Pauline , Paul Richard , Lang Dietmar , Büchs Jochen 
Published: September 2022

Abstract
Background
Determining the cytotoxicity of test substances is essential for the safety assessment of chemicals. To quantify the cytotoxicity, dose–response curves are determined and the half-maximum inhibitory concentration (IC50) is subsequently calculated. Results often rely on a single endpoint evaluation which typically requires manual sampling and subsequent sample analysis to determine the IC50. Hence, no information on culture behavior are available during treatment. Here, measurement of the oxygen transfer rate (OTR) was applied as a method for time-resolved assessment of the cytotoxicity to (a) provide information on culture behavior during treatment and (b) quantitatively assess the cytotoxic effect of a test substance.

Results
To investigate the applicability of the method, different types and concentrations of test substances were added and the OTR was measured for two different CHO suspension cell lines in shake flasks: (a) For CHO cell line one, culture behavior was not affected when 0.1 mM ZnCl2 was added. However, for both cell lines, adding up to 0.2 mM CoCl2 led to a decrease in the OTR that was concentration dependent. For CHO cell line two, adding up to 5% DMSO led to a concentration-dependent decrease in the OTR and in the slope of the OTR; (b) From the measured OTR, dose–response curves were established and used to calculate the IC50. For cell line one, the IC50 for CoCl2 was 0.03 mM while the IC50 from a comparative measurement based on trypan blue exclusion was 0.06 mM. Cell line two was less susceptible to CoCl2 as the IC50 was not reached at the concentrations tested. For DMSO, single OTR values and determined slopes were used for evaluation. In both cases, the IC50 was calculated to 2.3%.

Conclusions
Our approach provides a method for analyzing the cytotoxicity of a test substance based on OTR measurements. This method provides (i) insights on culture behavior, (ii) information on the progression of cytotoxicity, (iii) dose–response curves, and (iv) a first indication of IC50 values. Quantitative assessment of cytotoxicity is possible non-invasively and in real-time during treatment. Compared to traditional endpoint evaluation, our method simplifies experimentations and enhances the comparison of assay results.
Identification of a hippocampal lncRNA-regulating network in a natural aging rat model
Authors: Qi Li , Li Xiao , Liu Shi-min , Jiao Dan-li , Hu Dan , Ju Xin-yao , Zhao Shu-yu , Si Shu-han , Hu Li , Li Guo-na , Ma Bing-zhe , Zhou Shuang , Zhao Chen 
Published: September 2022

Abstract
Background
Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed.

Results
A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM—receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA–miRNA–mRNA target pairs were confirmed in this lncRNA‒miRNA‒mRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs.

Conclusions
We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.
Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing
Authors: Mansbart Felix , Kienberger Gerda , Sönnichsen Andreas , Mann Eva 
Published: September 2022

Abstract
Background
Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.

Methods
A comprehensive literature search was performed (last update March 25th 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology.

Results
Eighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality.

Conclusions
It cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.
Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016–2020)
Authors: Geebelen Laurence , Lernout Tinne , Devleesschauwer Brecht , Kabamba-Mukadi Benoît , Saegeman Veroniek , Belkhir Leïla , De Munter Paul , Dubois Bénédicte , Westhovens Rene ,   Humtick Hospital Group, Giot Jean-Baptiste , Léonard Philippe , Vangheluwe Riet , Wieërs Grégoire , Marot Jean-Christophe , Evrard Frédéric , Delaere Bénédicte , Noirhomme Séverine , Binnemans Els , Vanhoof Johan , Van Oyen Herman , Speybroeck Niko , Tersago Katrien 
Published: September 2022

Abstract
Background
Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors.

Methods
A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present.

Results
Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7–12.9) in EM patients and 20.9% (95% CI 6.8–64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98–12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes.

Conclusions
In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.
Association of human myxovirus resistance protein A with severity of COVID-19
Authors: Lehtinen Otto , Broman Niklas , Waris Matti , Vuorinen Tytti , Peltola Ville , Löyttyniemi Eliisa , Oksi Jarmo , Feuth Thijs 
Published: September 2022

AbstractBackgroundIn this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients.MethodsAll 304 patients admitted for COVID-19 in our hospital until 30th of April 2021 were included in this study. MxA was measured from peripheral blood samples in 268 cases. Patients were divided into groups based on their level of MxA on admission. We studied baseline characteristics and severity of disease on admission based on clinical parameters and inflammatory biomarker levels in each group. Severity of disease during hospitalization was determined by the applied level of respiratory support, by the usage of corticosteroids and by the duration of hospitalization.ResultsHigher MxA levels on admission were associated with a shorter duration of symptoms before admission, and with more severe disease. Adjusted Odds Ratios for any respiratory support were 9.92 (95%CI 2.11–46.58; p = 0.004) in patients with MxA between 400 μg/L and 799 μg/L (p = 0.004) and 20.08 (95%CI 4.51–89.44; p < 0.001) in patients with MxA ≥ 800 μg/L in comparison with patients with initial MxA < 400 μg/L. The usage of corticosteroids was significantly higher in the high-MxA group (77%) in comparison with the intermediate-MxA group (62%, p = 0.013) and low-MxA group (47%, p < 0.001).ConclusionsHigher initial levels of MxA were associated with more severe COVID-19. MxA may be a helpful additional biomarker to predict the severity of the disease.
Association between plasma cadmium and renal stone prevalence in adults in rural areas of Guangxi, China: a case–control study
Authors: Li You , He Kailian , Cao Liang , Tang Xu , Gou Ruoyu , Luo Tingyu , Xiao Song , Chen Ziqi , Li Tingjun , Qin Jian , Zhang Zhiyong , Cai Jiansheng 
Published: September 2022

Abstract
Background
Kidney stones have become a worldwide public health problem. The purpose of this research is to study the relationship between plasma cadmium level and the prevalence of kidney stones in an adult population.

Methods
The data of this study were based on a current survey conducted from December 2018 to November 2019 in Gongcheng Yao Autonomous County, Guangxi, China. A total of 940 study subjects of the same sex and age (within 2 years of each other) according to 1:1 matching were selected for a case–control study. The diagnosis of kidney stones was based on the presence of strong light spots, patches, clusters, or bands within the renal sinus region, followed by an echo-free bundle of acoustic images. Plasma metal elements were determined by the metal plasma method. The relationship between plasma cadmium concentration and the prevalence of kidney stones was assessed using logistic regression and restricted cubic spline regression.

Results
The crude ratio for kidney stones in the highest quartile of plasma cadmium was 1.164 (95% CI, 1.121 to 2.324) compared with the lowest quartile. A positive correlation was found between the two (P for trend = 0.039). After adjusting for potential confounders, the ratio of plasma cadmium to kidney stones in the highest quartile was 1.606 (95% CI, 1.100 to 2.344) compared with the lowest quartile, and the findings remained unchanged.

Conclusion
The odds of kidney stones in adults increased with increasing plasma cadmium exposure, and high plasma cadmium may be a risk factor for kidney stones.
“SpezPat”- common advance directives versus disease-centred advance directives: a randomised controlled pilot study on the impact on physicians’ understanding of non-small cell lung cancer patients’ end-of-life decisions
Authors: Koenig Julia Felicitas Leni , Asendorf Thomas , Simon Alfred , Bleckmann Annalen , Truemper Lorenz , Wulf Gerald , Overbeck Tobias R. 
Published: September 2022

AbstractBackgroundThe advance directive represents patients’ health care choices and fosters patients’ autonomy. Nevertheless, understanding patients’ wishes based on the information provided in advance directives remains a challenge for health care providers. Based on the ethical premises of positive obligation to autonomy, an advanced directive that is disease-centred and details potential problems and complications of the disease should help health care providers correctly understand patients’ wishes. To test this hypothesis, a pilot-study was conducted to investigate whether physicians could make the correct end-of-life decision for their patients when patients used a disease-centred advance directive compared to a common advance directive. Material and methodsA randomised, controlled, prospective pilot study was designed that included patients with non-small cell lung cancer (NSCLC) stage VI from the Department of Haematology and Medical Oncology, University Medical Centre, Goettingen. Patients were randomised into intervention and control groups. The control group received a common advance directive, and the intervention group received a disease-centred advance directive. Both groups filled out their advance directives and returned them. Subsequently, patients were asked to complete nine medical scenarios with different treatment decisions. For each scenario the patients had to decide whether they wanted to receive treatment on a 5-point Likert scale. Four physicians were given the same scenarios and asked to decide on the treatment according to the patients’ wishes as stated in their advance directives. The answers by patients and physicians were then compared to establish whether physicians had made the correct assumptions.ResultsRecruitment was stopped prior to reaching anticipated sample target. 15 patients with stage IV NSCLC completed the study, 9 patients were randomised into the control group and 6 patients in the intervention group. A total of 135 decisions were evaluated. The concordance between physicians’ and patients’ answers, was 0.83 (95%-CI 0.71–0.91) in the intervention group, compared to 0.60 (95%-CI 0.48–0.70) in the control group, and the difference between the two groups was statistically significant (p = 0.005).ConclusionThis pilot study shows that disease-centred advance directives help physicians understand their NSCLC patients’ wishes more precisely and make treatment choices according to these wishes.Trial registrationThe study is registered at the German Clinical Trial Register (no. DRKS00017580, registration date 27/08/2019).