bluuebunny/crossref_metadata_2025 huggingface dataset:
B-330 Homogeneous Enzyme Immunoassay for Hydrocodone
Authors: Chung K , Pham M , Houts T , O’Malley R
Published: September 2023

Background

Hydrocodone is a semi-synthetic derivative of codeine and produces opioid-like effects similar to morphine. Hydrocodone (Trade names: Vicodin, Lortab, Hycodan, Vicoprofen) is one of the most frequently prescribed opioids in the U.S. as an antitussive (cough suppressant) and narcotic analgesic agent for the treatment of moderate to severe pain. Its ease of prescription and opioid-like effects has led to widespread drug diversion and abuse. The two commercially available homogeneous immunoassays for the detection of hydrocodone in urine at a cutoff of 300 ng/mL suffer undesirable cross-reactivity to oxycodone and morphine at concentrations below 25 000 ng/mL. ARK Diagnostics has developed the ARK Hydrocodone Assay to detect hydrocodone at a cutoff of 300 ng/mL with no cross-reactivity to oxycodone, morphine, and codeine at concentrations below 100 000 ng/mL.

Methods

The ARK™ Hydrocodone Assay is a liquid stable homogeneous enzyme immunoassay, consisting of two reagents, with a cutoff of 300 ng/mL and semi-quantitative range up to 800 ng/mL. The performance of this assay was evaluated on the Beckman Coulter AU680 Automated Clinical Chemistry Analyzer. Precision, spiked recovery, specificity, Histogram Overlap Analysis of ±25% controls and the cutoff, and method comparison with LC-MS/MS were evaluated.

Results

In semi-quantitative mode, total precision ranged from 3.9% to 9.9%CV. Spiked recovery of hydrocodone ranged from 86.2% (720 ng/mL) to 102.9% (240 ng/mL). The active metabolite, hydromorphone, showed an approximate equivalence to the 300 ng/mL hydrocodone cutoff at 299 ng/mL (100.3% cross-reactivity). Histogram overlap analysis showed no overlap between cutoff and control levels. Method correlation with LC-MS/MS using authentic urine samples showed an excellent agreement with a specificity of 100% and sensitivity of 96.9% (98 positives and 128 negatives).

Conclusion

The ARKTM Hydrocodone Assay measures hydrocodone and its metabolite hydromorphone in human urine with acceptable performance. The assay is sensitive, rapid, and applicable to a wide range of clinical chemistry analyzers.
B-332 Evaluation of the Analytical Performance of Seven Therapeutic Drug Monitoring Assays on the Atellica® CI 1900 Analyzer
Authors: Bogard A , Coward T , Kolewe K , Paudel P , Tyler C , Arrode-Bruses G , Rhea-McManus J , Snyder J
Published: September 2023

Background

The Atellica® CI 1900 Analyzer is an automated, mid-throughput integrated chemistry and immunoassay analyzer employing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica CH Vancomycin (Vanc), Carbamazepine (Carb), Gentamicin (Gent), Phenytoin (Phny), Tobramycin (Tob), Valproic Acid (VPA), and Theophylline (Theo) assays* on the Atellica CI 1900 Analyzer.

Methods

The Atellica CI 1900 Vanc, Carb, Gent, Phny, Tob, VPA, and Theo assays use the same reagents and calibrators as the Atellica chemistry assays. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples. One aliquot of each sample pool was tested in duplicate in two runs per day ≥2 h apart on each analyzer for ≥20 days. MC studies were performed according to CLSI EP09-A3. Individual native and contrived human serum samples were analyzed using the Atellica chemistry assays on both the Atellica CH and Atellica CI 1900 Analyzers. Precision and MC were evaluated with three reagent lots on one system.

Results

Representative precision and MC results observed from one reagent lot across indicated sample ranges are listed in the table below for each assay. Over the seven assays tested, repeatability and within-lab % CVs were <6.5% and <11.0%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion

Evaluation of the Atellica CH Vanc, Carb, Gent, Phny, Tob, VPA, and Theo assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica CH 930 Analyzer.*The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.
B-361 Novel Blood-based Assay for Early Cancer Detection Demonstrates High Precision and Reproducibility on Low Tumor Content
Authors: Charlton J , Gilley C , Brown E , Gowen K , Williams M , DuRoss C , Sun J , Gregg J
Published: September 2023

Background

Early detection of cancer has significant potential to impact human health and society by decreasing cancer-related morbidity and mortality. While previous approaches to identify cancer-informative biomarkers are predominantly statistical, Harbinger Health has utilized foundational discoveries from developmental biology to design a targeted methylation assay for early cancer detection from cell-free DNA (cfDNA) extracted from plasma. Utilizing this biologically informed approach, we developed a fixed multi-layered logistic regression-based machine learning algorithm, trained with an in-house generated dataset of 1046 samples (621 cancer, 425 non-cancer) that predicts a binary classification (yes/no) for cfDNA samples processed through our assay. We have previously reported high sensitivity for multi-cancer detection, including for early-stage disease.

Methods

Here, we perform a comprehensive independent analytical validation of our assay and algorithm, encompassing 69 subjects: 19 with newly diagnosed treatment-naïve cancer (8 different cancer types) and 50 individuals with no history, diagnosis, or cancer symptoms. In total, we utilized 122 replicate samples to assess reproducibility and precision, 8 non-template controls (water) to determine limit of blank (LOB), and cohorts of matched biopsy and cfDNA to determine tumor content limit of detection (LOD).

Results

Precision was assessed within five different sub-studies, by comparing concordance of predicted binary cancer classification between replicate samples, giving results of 0.90 (0.95 CI: 0.764–0.959) for inter-run precision, 1.00 (0.95 CI: 0.796–1.000) for intra-run precision, 1.00 (0.95 CI: 0.871–1.000) for inter-operator precision, 0.96 (0.95 CI: 0.930–0.998) for inter-instrument precision and 0.83 (0.95 CI: 0.641–0.933) for inter-day precision. To determine LOB, we carried 8 non-template controls (water) through the entire assay and detected on average ∼0.02% unique aligned reads of a true sample on the same sequencing run. Finally, to assess tumor content LOD, we developed methodology that uses methylation signal to estimate the amount of tumor-derived DNA in each cfDNA sample and validated our estimates using whole exome sequencing, an orthogonal gold-standard approach. We then assessed the relationship between tumor content and classifier sensitivity using our training data of 625 cancer cfDNA samples and determined that our tumor content LOD whereby 95% true cancer samples were correctly predicted to be 0.037%.

Conclusion

Our assay shows high performance and high technical reproducibility. Our previously reported high sensitivity for stage 1 and stage 2 cancers, as well as extremely low tumor content LOD reported here supports our ability to perform early-stage multi-cancer detection, where the levels of circulating tumor DNA are low.
B-373 The Development of a Logic-Gate Probe to Investigate Hypoxia in Cancer Stem Cells
Authors: Swartchick C B , Chan J
Published: September 2023

Background

Cancer stem cells (CSCs) represent only a small fraction of the tumor population, yet they present a profound challenge to cancer treatment. CSCs contribute to tumor complexity via their unique ability to self-renew, develop into multiple lineages, and maintain an unchecked proliferation potential. To identify CSCs, the cytoprotective enzyme aldehyde dehydrogenase 1A1 (ALDH1A1) is a well-annotated biomarker of cancer stemness which is associated with a poor prognosis in patients with gastric and lung cancers when overexpressed. Within CSCs, ALDH1A1 functions to regulate oxidative stress by transforming biological aldehydes into their corresponding non-toxic carboxylic acid counterparts and further is linked to the retinaldehyde signaling pathway. Beyond this enzyme, oxygen availability within the tumor microenvironment (TME) can also influence stemness properties. Specifically, hypoxia, is required to maintain the CSC phenotype by prolonging the undifferentiated state.

Methods

To study the mechanistic underpinnings of complex relationship in vivo new technologies are needed as current approaches are insufficient. Indeed, probes have been developed to study ALDH1A1 and hypoxia in parallel, however, imaging approaches lack the requisite resolution to ensure they are reporting on the same CSC population. To this end, we have designed a powerful logic-gate probe that links the reporters of ALDH1A1 activity and oxygenation in a unique manner such that different readouts will result (color of light) depending on the TME environment.

Results

Our lab has previously developed a near-infrared hypoxia-sensing fluorescent probe that is fundamental to our current logic-gate design. This component has been validated in 4T1 murine breast cancer cells, to yield a 1.6-fold increase in ratiometric fluorescence response when incubated under hypoxic conditions as compared to its normoxic controls. Additionally, the ALDH1A1 sensing component has been validated via purified enzyme to yield an increase in bioluminescent signal enabling its use for future in vivo studies.

Conclusion

This technology has important clinical implications to understand the mechanistic underpinnings between oxygenation and cancer stemness. Further research is being conducted to further test the hypothesis that metformin (anticancer drug) kills cancer by altering oxygen metabolism which in turn depletes the CSC population. Furthermore, this probe has far-reaching implications in monitoring novel therapeutic cancer treatment.
Multi-omics analysis reveals the potential pathogenesis and therapeutic targets of diabetic kidney disease
Authors: Wei Lan , Gao Jingjing , Wang Liangzhi , Tao Qianru , Tu Chao
Published: September 2023

Clinicians have long been interested in understanding the molecular basis of diabetic kidney disease (DKD)and its potential treatment targets. Its pathophysiology involves protein phosphorylation, one of the most recognizable post-transcriptional modifications, that can take part in many cellular functions and control different metabolic processes. In order to recognize the molecular and protein changes of DKD kidney, this study applied Tandem liquid chromatography-mass spectrometry (LC-MS/MS) and Next-Generation Sequencing, along with Tandem Mass Tags (TMT) labeling techniques to evaluate the mRNA, protein and modified phosphorylation sites between DKD mice and model ones. Based on Gene Ontology (GO) and KEGG pathway analyses of transcriptome and proteome, The molecular changes of DKD include accumulation of extracellular matrix, abnormally activated inflammatory microenvironment, oxidative stress and lipid metabolism disorders, leading to glomerulosclerosis and tubulointerstitial fibrosis. Oxidative stress has been emphasized as an important factor in DKD and progression to ESKD, which is directly related to podocyte injury, albuminuria and renal tubulointerstitial fibrosis. A histological study of phosphorylation further revealed that kinases were crucial. Three groups of studies have found that RAS signaling pathway, RAP1 signaling pathway, AMPK signaling pathway, PPAR signaling pathway and HIF-1 signaling pathway were crucial for the pathogenesis of DKD. Through this approach, it was discovered that targeting specific molecules, proteins, kinases and critical pathways could be a promising approach for treating DKD.
Innovation and competitiveness in the copper-mining GVC: developing local suppliers in Peru
Authors: Bamber Penny , Fernandez-Stark Karina , Molina Oswaldo
Published: September 2023

Although Peru is one of the main producers of copper worldwide, the domestic industry has not yet fully taken advantage of the potential that the exploitation of this commodity offers. This paper explores the opportunities and challenges that Peruvian suppliers face in their insertion into the mining global value chain. Our analysis is based on a mixed-methods approach, combining both quantitative and qualitative primary and secondary sources, including semi-structured interviews with key actors in the Peruvian mining sector. Our findings suggest that the weak presence of Peruvian suppliers in a sector dominated by few foreign firms is due to global industry dynamics as well as the underdeveloped capabilities of local firms operating in a fragile local institutional setting. However, their opportunities for their insertion are primarily in areas where new solutions are required, which places a demand on the supplier’s innovative capacity.
Burden of ischemic stroke in mainland China and Taiwan province from 1990 to 2019: with forecast for the next 11 years
Authors: Yu Jia , Liu Fude , Cheng Yawen , Wang Jianyi , Ma Wenlong , Chen Chen , Sun Peng , Shang Suhang
Published: September 2023

Ischemic stroke is featured with high incidence, mortality, and disability. The aim of this study is to use Global Burden of Disease database to describe and compare the burden of ischemic stroke in mainland China and Taiwan province and to further predict the expected changes in the next 11 years using statistical modeling methods. Information on ischemic stroke incidence and mortality in China (mainland and Taiwan province) during 1990–2019 was obtained from the Global Burden of Disease database to analyze the effects of region, gender, and age on the incidence and mortality of ischemic stroke in China. The autoregressive integrated moving average model was used to predict the age-standardized incidence rate and age-standardized mortality rate of ischemic stroke in males and females in mainland China and Taiwan province in the next 11 years. The period from 1990 to 2019 witnessed an overall upward trend in the number of incidence and deaths in mainland China and Taiwan province. In 2019, there were nearly 2.87 million ischemic incidence cases with stroke in mainland China, with more female patients than male in the age group of over 60 years. Among the nearly 1.03 million deaths, the death toll of men under the age of 85 years was higher than that of women, while in Taiwan province, the number of incidence was 28 771, with more female patients of all ages than male. Among the 6788 deaths, the death toll of men under the age of 80 years was higher than that of women. In 2019, the age group with the highest number of patients in the two regions was 65–69 years, while the highest number of deaths was found in people aged 85 years and above. As our autoregressive integrated moving average model predicted, the age-standardized incidence rate value of ischemic stroke is expected to be 163.23/100 000 persons in mainland China by 2030, which would continue to increase, while the age-standardized mortality rate value of ischemic stroke is expected to be 16.41/100 000 persons in Taiwan province by 2030, which showed a decreasing trend. Disease burden of ischemic stroke is still increasing in mainland China and Taiwan province, and health resources should be deployed to implement effective prevention and control strategies, taking into account region, gender, and age.
‘Low-value’ clinical care in general practice: a cross-sectional analysis of low-value care in early-career GPs’ practice
Authors: Ralston Anna , Fielding Alison , Holliday Elizabeth , Ball Jean , Tapley Amanda , van Driel Mieke , Davey Andrew , Turner Rachel , Moad Dominica , FitzGerald Kristen , Spike Neil , Mitchell Ben , Tran Michael , Fisher Katie , Magin Parker
Published: September 2023

Nonevidence-based and ‘low-value’ clinical care and medical services are ‘questionable’ clinical activities that are more likely to cause harm than good or whose benefit is disproportionately low compared with their cost. This study sought to establish general practitioner (GP), patient, practice, and in-consultation associations of an index of key nonevidence-based or low-value ‘questionable’ clinical practices.

The study was nested in the Registrar Clinical Encounters in Training study—an ongoing (from 2010) cohort study in which Australian GP registrars (specialist GP trainees) record details of their in-consultation clinical and educational practice 6-monthly. The outcome factor in analyses, performed on Registrar Clinical Encounters in Training data from 2010 to 2020, was the score on the QUestionable In-Training Clinical Activities Index (QUIT-CAI), which incorporates recommendations of the Australian Choosing Wisely campaign. A cross-sectional analysis used negative binomial regression (with the model including an offset for the number of times the registrar was at risk of performing a questionable activity) to establish associations of QUIT-CAI scores.

A total of 3206 individual registrars (response rate 89.9%) recorded 406 812 problems/diagnoses where they were at risk of performing a questionable activity. Of these problems/diagnoses, 15 560 (3.8%) involved questionable activities being performed.

In multivariable analyses, higher QUIT-CAI scores (more questionable activities) were significantly associated with earlier registrar training terms: incidence rate ratios (IRRs) of 0.91 [95% confidence interval (CI) 0.87, 0.95] and 0.85 (95% CI 0.80, 0.90) for Term 2 and Term 3, respectively, compared to Term 1. Other significant associations of higher scores included the patient being new to the registrar (IRR 1.27; 95% CI 1.12, 1.45), the patient being of non-English-speaking background (IRR 1.24; 95% CI 1.04, 1.47), the practice being in a higher socioeconomic area decile (IRR 1.01; 95% CI 1.00, 1.02), small practice size (IRR 1.05; 95% CI 1.00, 1.10), shorter consultation duration (IRR 0.99 per minute; 95% CI 0.99, 1.00), and fewer problems addressed in the consultation (IRR 0.84; 95% CI 0.79, 0.89) for each additional problem].

Senior registrars’ clinical practice entailed less ‘questionable’ clinical actions than junior registrars’ practice. The association of lower QUIT-CAI scores with a measure of greater continuity of care (the patient not being new to the registrar) suggests that continuity should be supported and facilitated during GP training (and in established GPs’ practice).
Analysis of the stepwise acquisition of blaCTX-M-2 and subsequent acquisition of either blaIMP-1 or blaIMP-6 in highly conserved IncN-pST5 plasmids
Authors: Ikegaya Kazuko , Aoki Kotaro , Komori Kohji , Ishii Yoshikazu , Tateda Kazuhiro
Published: September 2023

Objectives

ESBL and carbapenemase genes in Enterobacterales spread via plasmids. Nosocomial outbreaks caused by Enterobacterales producing both CTX-M-2 and either IMP-1 or IMP-6-type carbapenemases have been reported. These organisms carry the incompatibility type N plasmid belonging to plasmid ST 5 (IncN-pST5). We investigated the construction process of the ESBL and carbapenemase genes co-carrying IncN-pST5.

Methods

We retrospectively performed draft WGS analysis for blaIMP- or blaCTX-M-positive Enterobacterales in our strain collection (n = 281).

Results

We selected four types of Escherichia coli plasmids for our study: type A, which carries both blaCTX-M-2 and blaIMP-1 (n = 6); type B, which carries both blaCTX-M-2 and blaIMP-6 (n = 2); type C, which carries blaCTX-M-2 (n = 10); and type D, which carries no β-lactamase genes (n = 1). It should be noted that type D plasmid was only detected in E. coli TUM2805, which carries the blaCTX-M-14 on the IncB/O/B/Z plasmid. Long-read sequencing using MinION revealed that all types of IncN-pST5 were highly conserved and carried a class 1 integron. Integron numbers were type A for In798, type B for In1690, type C for In127 and type D for In207. Because the gene cassettes downstream of blaIMP were different between In798 and In1690, the change from blaIMP-1 to blaIMP-6 by point mutation was unlikely. Representative plasmids from types A, B and C were conjugatively transferred with quite a high frequency between 1.3 × 10−1 and 2.5 × 10−2.

Conclusions

This study suggested that IncN-pST5 acquired blaCTX-M-2 by ISEcp1 in a stepwise manner, followed by either blaIMP-1 or blaIMP-6 into a class 1 integron.
Current Evidence for Combined Targeted Therapy for the Treatment of Inflammatory Bowel Disease
Authors: Wetwittayakhlang Panu , Lakatos Peter L
Published: September 2023

Biologicals and small molecules have revolutionized the medical management of inflammatory bowel diseases (IBD), yet they are only effective in a proportion of patients, and their impact on changing the natural history of the disease is still debatable. Recently, the concept of combining targeted biologics and small-molecule therapies has been introduced to the treatment of IBD. Dual-targeted therapy (sequential and combined), which is the combination of two targeted therapies, might be a reasonable choice for patients to break through the therapeutic ceiling. A recent randomized clinical trial (VEGA) provided the first controlled evidence that the short-term combination of two biological agents may lead to superior disease control than either of the agents alone in patients with ulcerative colitis (UC) without jeopardizing safety. Multiple studies are underway in both Crohn’s disease and UC. Additionally, real-world evidence is accumulating in IBD patients receiving combination therapies with concomitant IBD and extraintestinal manifestations or in patients with medically refractory IBD. Of note, the majority of these patients were exposed to multiple biological agents earlier and lost response to at least one of the agents in the combination. This review summarizes current knowledge regarding this attractive novel therapeutic option in IBD. Clearly, more controlled data are needed to evaluate optimal timing, efficacy, and mitigation of safety concerns.
Axonal regrowth under release of myelin-associated glycoprotein: chemotaxis by pioneer Schwann cells and Cajal’s gigantic clubs
Authors: Torigoe Kojun
Published: September 2023

Myelin-associated glycoprotein (MAG), released from pre-degenerated distal nerves following axotomy, blocks the regrowth of sprouts and naked axons. Ensheathed axons, however, continue to elongate and reach MAG-releasing distal nerves. To determine the regenerative mechanism of ensheathed axons without navigators of axonal growth cones by the film model method, we inserted a MAG-releasing distal nerve segment treated with liquid nitrogen (N2DS) between the two films, facing the proximal end of the common peroneal nerves in mice transected 4 days earlier for axons to become ensheathed. On the third postoperative day (Day 3), axon fascicles, subjected to silver staining, extended toward N2DS but with few branches, forming terminal swellings called Cajal’s gigantic clubs (CGCs) that are filled with axonal growth cones. Filter paper wetted with either 250 pg/ml MAG or N2DS showed the same configurations when inserted between the two films. This effect was lost following anti-MAG treatment; fascicles strayed near the parent nerve with numerous branches, formed a net of axons and tapered toward thin tips at their ends, just like controls without N2DS. Schwann cell bundles on Day 3 detected with anti-S100, formed sheaths of CGCs at their ends and connected to pioneer Schwann cells (pSCs). To analyze the physiology of Schwann cells, independent of axons, the parent nerve transected 4 days prior was crushed. On Day 2, with pSCs ahead, Schwann cell bundles extended toward N2DS. On Day 4, main bundles regressed, leaving pSCs motionless. Thus, MAG is a candidate chemoattractant for both pSCs and CGCs.
Double-modified oncolytic adenovirus armed with a recombinant interferon-like gene enhanced abscopal effects against malignant glioma
Authors: Jiang Shan , Chai Hui-Hui , Fang Xian-Long , Xu Hou-Shi , Li Tian-Wen , Tang Qi-Sheng , Gu Jin-Fa , Zhang Kang-Jian , Liu Xin-Yuan , Shi Zhi-Feng , Cao Xue-Ping , Wu Zan-Yi , Zhou Liang-Fu
Published: September 2023

Background

The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments.

Methods

To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide.

Results

By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model.

Conclusions

Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.
P03 Long term denosumab treatment in osteoporosis - a case series
Authors: Premathilake Nimanthi , Nandagudi Anupama
Published: September 2023

Introduction

Studies have shown that denosumab reduces fracture risk and increases bone mineral density and is associated with low adverse events over 10 years. We have reviewed 3 patients in our hospital who have been successfully treated with denosumab 20 injections.

Case description

Clinical details of these patients are outlined in the table.

Discussion

All three patients have responded well to denosumab therapy with definite improvement of T scores and positive bone mineral density change compared to baseline, in both spine and hip regions. They have not experienced significant side effects related to treatment. The second patient was treated as possible fracture as the x-rays were not convincing of definitive fracture. Patient 3, despite having very low T scores and multiple fragility fractures in 2012, has not incurred further fractures following the commencement of denosumab.

Key learning points

Denosumab has shown satisfactory improvement in these patients without significant adverse effects, following completion of 10 years of therapy. This is in par with previous studies that demonstrated efficacy and safety profile of Denosumab.
Unpacking reappraisal: a systematic review of fMRI studies of distancing and reinterpretation
Authors: Denny Bryan T , Jungles Mallory L , Goodson Pauline N , Dicker Eva E , Chavez Julia , Jones Jenna S , Lopez Richard B
Published: September 2023

In recent decades, a substantial volume of work has examined the neural mechanisms of cognitive reappraisal. Distancing and reinterpretation are two frequently used tactics through which reappraisal can be implemented. Theoretical frameworks and prior evidence have suggested that the specific tactic through which one employs reappraisal entails differential neural and psychological mechanisms. Thus, we were motivated to assess the neural mechanisms of this distinction by examining the overlap and differentiation exhibited by the neural correlates of distancing (specifically via objective appraisal) and reinterpretation. We analyzed 32 published functional magnetic resonance imaging (fMRI) studies in healthy adults using multilevel kernel density analysis. Results showed that distancing relative to reinterpretation uniquely recruited right bilateral dorsolateral PFC (DLPFC) and left posterior parietal cortex, previously associated with mentalizing, selective attention and working memory. Reinterpretation relative to distancing uniquely recruited left bilateral ventrolateral PFC (VLPFC), previously associated with response selection and inhibition. Further, distancing relative to reinterpretation was associated with greater prevalence of bilateral amygdala attenuation during reappraisal. Finally, a behavioral meta-analysis showed efficacy for both reappraisal tactics. These results are consistent with prior theoretical models for the functional neural architecture of reappraisal via distancing and reinterpretation and suggest potential future applications in region-of-interest specification and neural network analysis in studies focusing on specific reappraisal tactics.
Understanding career transitions of applied researchers to universities: evidence from Germany
Authors: Garcia Chavez Cecilia , Howoldt David , Hoyer Patrick , Karaulova Maria , Kroll Henning , Schubert Torben
Published: September 2023

This paper analyses the conditions and factors influencing non-university researchers’ career transitions back into academia. Using affiliation data in publications of German researchers, their cross-sector career transitions from the public research organisation Fraunhofer-Gesellschaft and industry to universities are analysed. Although the rate of transitions is small, there are distinctive windows of opportunity at a junior career stage, especially for Fraunhofer researchers. Researchers who publish more and in more acclaimed journals, Fraunhofer researchers who co-publish with universities, and women are more likely to gain a university affiliation over the course of their career. These results indicate the influence of institutional proximity for cross-domain career transitions. The quality and impact of academic knowledge could be improved if the higher education sector was more open to recruitment of researchers from other sectors. Policy needs to target the barriers that preclude applied researchers from pursuing university careers.
Photosynthetic and biochemical responses of four subtropical tree seedlings to reduced dry season and increased wet season precipitation and variable N deposition
Authors: Wu Ting , Song Yuting , Tissue David , Su Wei , Luo Hanyu , Li Xu , Yang Shimin , Liu Xujun , Yan Junhua , Huang Juan , Liu Juxiu
Published: September 2023

Interspecific variations in phenotypic plasticity of trees that are affected by climate change may alter the ecosystem function of forests. Seedlings of four common tree species (Castanopsis fissa, Michelia macclurei, Dalbergia odorifera and Ormosia pinnata) in subtropical plantations of southern China were grown in the field under rainout shelters and subjected to changing precipitation (48 L of water every 4 days in the dry season, 83 L of water every 1 day in the wet season; 4 g m−2 year−1 of nitrogen (N)), low N deposition (48 L of water every 2 days in the dry season, 71 L of water every 1 day in the wet season; 8 g m−2 year−1 N), high N deposition (48 L of water every 2 days in the dry season, 71 L of water every 1 day in the wet season; 10 g m−2 year−1 N) and their interactive effects. We found that the changes in seasonal precipitation reduced the light-saturated photosynthetic rate (Asat) for C. fissa due to declining area-based foliar N concentrations (Na). However, we also found that the interactive effects of changing precipitation and N deposition enhanced Asat for C. fissa by increasing foliar Na concentrations, suggesting that N deposition could alleviate N limitations associated with changing precipitation. Altered precipitation and high N deposition reduced Asat for D. odorifera by decreasing the maximum electron transport rate for RuBP regeneration (Jmax) and maximum rate of carboxylation of Rubisco (Vcmax). Ormosia pinnata under high N deposition exhibited increasing Asat due to higher stomatal conductance and Vcmax. The growth of D. odorifera might be inhibited by changes in seasonal precipitation and N deposition, while O. pinnata may benefit from increasing N deposition in future climates. Our study provides an important insight into the selection of tree species with high capacity to tolerate changing precipitation and N deposition in subtropical plantations.
An In-Depth Evaluation of Powdery Mildew Hosts Reveals One of the World’s Most Common and Widespread Groups of Fungal Plant Pathogens
Authors: Bradshaw Michael J. , Boufford David , Braun Uwe , Moparthi Swarnalatha , Jellings Keila , Maust Autumn , Pandey Binod , Slack Suzanne , Pfister Donald H.
Published: September 2023

Powdery mildews are highly destructive fungal plant pathogens that have a significant economic impact on both agricultural and ecological systems worldwide. The intricate relationship between powdery mildews and their host plants has led to cospeciation. In this study, we conducted an extensive evaluation of powdery mildew hosts to provide an updated understanding of the host ranges and distributions of these fungi. The “United States National Fungus Collections Fungus-Host Dataset” is the primary source of information for our analyses. The analysis of the dataset demonstrated the worldwide prevalence of powdery mildews; the data contained over 72,000 reports of powdery mildews, representing ∼8.7% of all host-fungal records. We have updated the taxonomy and nomenclature of powdery mildews. In total, powdery mildews infect ∼10,125 host taxa belonging to 205 families of flowering plants, which accounts for 1,970 genera in 200 countries across six continents. Furthermore, we estimate that powdery mildews infect approximately 2.9% of described angiosperm species. Our study underscores the need for regular updates on powdery mildew host information due to the continuously evolving taxonomy and the discovery of new host taxa. Since 1986, we estimate an additional 1,866 host taxa, 353 genera, and 36 families have been reported. Additionally, the identification of powdery mildew hosts provides valuable insights into the coevolutionary dynamics between the fungi and their plant hosts. Overall, this updated list provides valuable insights into the taxonomy and geographic distribution of powdery mildew species, which builds upon the previous work of Amano in 1986. Discerning the geographic spread and host range of economically significant plant pathogens is vital for biosecurity measures and identifying the origins and expansion of potentially harmful pathogens.
Recovery Plan for Ralstonia solanacearum Race 3 Biovar 2 (Phylotype IIB, Sequevars 1 and 2) Causing Brown Rot of Potato, Bacterial Wilt of Tomato, and Southern Wilt of Geranium
Authors: Dickstein Ellen R. , Bocsanczy Ana Maria , Champoiseau Patrice G. , Jones Jeffrey B. , Norman David J. , Paret Mathews , Sharma Anuj , Momol Timur M. , Allen Caitilyn , Huang Qi , Miller Sally A. , Shadman-Adolpho Sylvia , Evans-Goldner Lynn , Liu Zhaowei , Bulluck Russ , Cardwell Kitty , Fajardo Julius E.
Published: September 2023

Ralstonia solanacearum is a species complex of bacterial plant pathogens that cause bacterial wilt on a wide range of crops in tropical and subtropical regions. Among the different subgroups of this complex, race 3 biovar 2 (R3bv2) is of particular concern because it can infect potato, tomato, and geranium in temperate climates and is regulated as a select agent in the United States. This document presents a recovery plan for R3bv2 as part of the National Plant Disease Recovery System (NPDRS) in the United States. The plan provides a brief overview of the disease; its taxonomy, distribution, detection, and management; and the current infrastructure, needs, and experts for effective response and recovery. It also identifies research, education, and extension priorities for mitigating R3bv2, such as developing disease management tactics, detection tools, an impact network analysis, and stakeholder education. The plan is intended to help the USDA guide further efforts directed toward plant disease recovery and to ensure a reasonable level of crop production in the event of a high-consequence plant disease outbreak.
Sacral Stress Fracture in Athletes With Overuse
Authors: Nakamae Toshio , Kamei Naosuke , Kanda Tsukasa , Imada Takeo , Adachi Nobuo
Published: September 2023

Study Design:

This was a narrative review.

Objectives:

The purpose of this study was to report the physical and radiologic characteristics of sacral stress fractures in 11 athletes and to review the current literature on sacral stress fractures.

Summary of Background Data:

Sacral stress fractures are rarely reported as a cause of low back pain in athletes.

Patients and Methods:

We retrospectively analyzed 11 athlete patients with sacral stress fractures and low back pain. All patients received conservative treatments, such as rest from sporting activities and physical therapy. Clinical data, such as age, sex, athletic activity, region of tenderness, and duration of low back pain, and radiologic data, such as information from plain radiographs and fracture lines on magnetic resonance imaging (MRI), were evaluated.

Results:

The study included 11 athlete patients (5 males and 6 females) with sacral stress fractures, and their mean age was 18.7 years (range, 15–38 y). The sports that caused the stress fractures were baseball, badminton, and basketball in 2 patients each and football, judo, marathon, volleyball, and dance in 1 patient each. All patients had tenderness on the sacrum. The mean duration of low back pain was 1.8 weeks (range, 1–4 wk). Fracture lines on MRI were observed only in the caudal-ventral part of the sacrum in 7 patients and extended from the inferolateral angle of the sacrum to the superior lateral sacral alar in 4 patients.

Conclusions:

The study findings demonstrated that MRI and tenderness were useful for detecting the presence of sacral stress fractures in athletes. Moreover, fracture lines in the sacrum may progress from the caudal-ventral part of the sacrum to the cranio-dorsal direction.
Omega-3 Fatty Acids as Antiarrhythmic Drugs: Upstream Target Modulators Affecting Acute and Long-Term Pathological Alterations in Cardiac Structure and Function
Authors: Driscoll David F. , Welty Francine K. , Bistrian Bruce R.
Published: September 2023

OBJECTIVES:

Postoperative atrial fibrillation (POAF) is a common complication in the acute care period following coronary artery bypass grafting (CABG) surgery that is associated with significant morbidity and mortality in both short-term and long-term settings. Recently, the Vaughn Williams Classification of antiarrhythmic agents, first proposed in 1975 and widely viewed as the authoritative description of their electrophysiologic actions, was updated and notably omega-3 fatty acids (Ω-3 fatty acids) have been included in class VII, described as “upstream target modulators,” to mitigate pathological structural and electrophysiological remodeling changes in the aged and/or injured myocardium.

DATA SOURCES:

A PubMed literature search was performed.

STUDY SELECTION:

Studies examining the significance of complications in patients undergoing isolated CABG surgery were selected for inclusion.

DATA EXTRACTION:

Relevant data were qualitatively assessed and narratively summarized.

DATA SYNTHESIS:

POAF occurs in approximately 30% of patients, and inflammation from chronic coronary artery disease preoperatively, as well as acute atrial inflammation from surgery postoperatively are the leading causes. Inflammation underlies its pathophysiology; therefore Ω-3 fatty acids not only exhibit antiarrhythmic properties but are an effective anti-inflammatory treatment that may reduce the clinical risks of POAF.

CONCLUSIONS:

At present no effective prophylaxis is available to address POAF following CABG surgery. Clinical approaches that focus on the inflammatory response in this setting may optimize the response to treatment. The current literature supports the hypothesis that Ω-3 fatty acids may acutely reduce the inflammatory response via favorable alterations in the metabolism of prostaglandins and leukotrienes (eicosanoids) and specialized pro-resolving mediators.
Relationship Between Intensive Care Nurses' Attitudes and Behaviors Toward End-of-Life Care and Ethical Attitudes
Authors: Efil Sevda , Turen Sevda , Demir Gül
Published: September 2023

Background

Nurses are in a central position to improve care for dying patients and their families by challenging current end-of-life practices in their settings. Nurses who care for such patients experience the associated ethical dilemmas. However, the relation between their attitude and behavior regarding end-of-life care and their ethical attitudes is not known.

Objectives

The aim of this study was to examine the relation between the attitudes and behaviors of intensive care unit nurses to end-of-life care and their ethical attitudes in the care process.

Methods

The research was conducted in Antalya, one of the most populous provinces in Turkey, with 287 intensive care nurses working in 4 different hospitals. The research data were collected between June 30 and August 30, 2021. Self-report data were collected using a Nurses' Description Form, the Attitudes and Behaviors of ICU Nurses to End-of-Life Care Scale, and the Ethical Attitude Scale for Nursing Care.

Results

The mean score of the intensive care nurses for attitude and behaviors to end-of-life care was 62.36 ± 13.22, and their mean score for ethical attitude for nursing care was 149.76 ± 24.98.

Conclusion

It was found that intensive care nurses' attitudes and behaviors to end-of-life care had a positive correlation on their ethical attitudes in the care process (P < .001).

Discussion

It would be of interest to understand how these attitudes impact clinical decision-making for the ultimate understanding of whether nurses' attitudes can be a barrier to the delivery of quality end-of-life care.
Negative-Control Exposures: Adjusting for Unmeasured and Measured Confounders With Bounds for Remaining Bias
Authors: Flanders W. Dana
Published: September 2023

Negative-control exposures can be used to detect and even adjust for confounding that remains after control of measured confounders. A newly described method allows the analyst to reduce residual confounding by unmeasured confounders U by using negative-control exposures to define and select a subcohort wherein the U-distribution among the exposed is similar to that among the unexposed. Here, we show that conventional methods can be used to control for measured confounders in conjunction with the new method to control for unmeasured ones. We also derive an expression for bias that remains after applying this approach. We express remaining bias in terms of a “balancing” parameter and show that this parameter is bounded by a summary variational distance between the U-distribution in the exposed and the unexposed. These measures describe and bound the extent of remaining confounding after using negative controls to adjust for unmeasured confounders with conventional control of measured confounders.
Massachusetts Prevalence of Opioid Use Disorder Estimation Revisited: Comparing a Bayesian Approach to Standard Capture–Recapture Methods
Authors: Wang Jianing , Doogan Nathan , Thompson Katherine , Bernson Dana , Feaster Daniel , Villani Jennifer , Chandler Redonna , White Laura F. , Kline David , Barocas Joshua A.
Published: September 2023

Background:

The National Survey on Drug Use and Health (NSDUH) estimated the prevalence of opioid use disorder (OUD) among the civilian, noninstitutionalized people aged 12 years or older in Massachusetts as 1.2% between 2015 and 2017. Accurate estimation of the prevalence of OUD is critical to the success of treatment and resource planning. Various indirect estimation approaches have been used but are subject to data availability and infrastructure-related issues.

Methods:

We used 2015 data from the Massachusetts Public Health Data Warehouse (PHD) to compare the results of two approaches to estimating OUD prevalence in the Massachusetts population. First, we used a seven-dataset capture–recapture analysis under log–linear model parameterization, controlling for the source dependence and effects of age, sex, and county through stratification. Second, we applied a benchmark-multiplier method in a Bayesian framework by linking health care claims data to death certificate data assuming an extrapolation of death rates from observed untreated OUD to unobserved OUD.

Results:

Our estimates for OUD prevalence among Massachusetts residents (aged 18–64 years) were 4.62% (95% CI = 4.59%, 4.64%) in the capture–recapture approach and 4.29% (95% CrI = 3.49%, 5.32%) in the Bayesian model. Both estimates were approximately four times higher than NSDUH estimates.

Conclusion:

The synthesis of our findings suggests that the disease surveillance system misses a large portion of the population with OUD. Our study also suggests that concurrent use of multiple methods improves the justification and facilitates the triangulation and interpretation of the resulting estimates.

Trial registration:

ClinicalTrials.gov Identifier: NCT04111939.
Explaining Health Disparities in the Sexual Minority Population
Authors: Ruther Matthew H. , Hsieh Ning
Published: September 2023

Individual health is affected not only by characteristics and behaviors of the individual, but also by the environment in which the individual lives. Although neighborhood effects are well-established in the health literature, whether these effects are different for sexual minority populations is unknown. There is evidence that the neighborhoods in which sexual minorities reside are distinct from those in which heterosexuals reside, which could give rise to differential neighborhood effects. This research uses restricted data from the National Center for Health Statistics Research Data Center—which include neighborhood identifiers—to investigate health-relevant differences between the neighborhoods in which heterosexuals and sexual minorities reside. We also provide preliminary evidence on whether neighborhood effects explain any or all the disparities in health behaviors or health outcomes between sexual minority and heterosexual populations or mediate or moderate the effects of other covariates in explaining these disparities.