bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential selection and maintenance of manure-originated multi-drug resistant plasmids at sub-clinical antibiotic concentrations
Authors: Tran Tam T. , Cole Marlena , Tomas Emily , Scott Andrew , Topp Edward
Published: March 2023

The goal of this study was to determine minimum selection concentrations of various antibiotics using four manure-originated multi-drug resistant plasmids in a surrogateEscherichia colihost. These plasmids carried genes conferring resistance phenotypes to several antibiotic classes including β-lactams, lincosamides, phenicols, macrolides, sulfonamides and tetracyclines. The minimum selection concentrations of antibiotics tested in nutrient-rich medium were determined: 14.1-28.2 mg/L for penicillin G, 0.1 mg/L for oxytetracycline, 0.45 mg/L for chlortetracycline, 2 mg/L for lincomycin, 1 mg/L for florfenicol, 1.3-4 mg/L for azithromycin, 0.13-0.25 mg/L for tetracycline, 0.004-0.01 mg/L for cefotaxime. Penicillin G, oxytetracycline, chlortetracycline, lincomycin and florfenicol had minimum selection concentrations in nutrient-defined medium slightly changed within 3.5-fold range compared to those in nutrient-rich medium. The minimum selection concentrations of antibiotics interfering folic acid synthesis in bacteria were also determined: 63 mg/L for sulfamethoxazole, 11.2 mg/L for sulfisoxazole and 0.06 mg/L for trimethoprim. Mixing two antibiotics changed minimum selection concentrations within 3.7-fold range compared to those in single antibiotic tests. Relatively high plasmid loss rates (> 90%) were observed when culturing plasmid-bearing strains in antibiotic-free nutrient-rich and nutrient-defined media. Overall results suggested that these plasmids can be maintained at concentrations environmentally relevant in waste water treatment plants, sewage, manure and manured soil although they are not stable in antibiotic-free environments.

IMPORTANCE

Antibiotic resistance crisis is a grave concern in healthcare systems around the world. To combat this crisis, we sought to find out how likely manure-originated multi-drug resistant plasmids are to be selected and maintained in different environment matrices. Our study showed that these plasmids conferring resistance to β-lactams, lincosamides, phenicols, macrolides, sulfonamides and tetracyclines can be selected at minimum selection concentrations which are lower than minimum inhibition concentrations of theE. colihost strain. Lincomycin, oxytetracycline, chlortetracycline, tetracycline, chloramphenicol, trimethoprim had minimum selection concentrations lower than the antibiotic concentrations in several environment matrices reported previously. Our findings suggest that despite the burden and the high rate of plasmid loss, these plasmids can still be selected, maintained and circulated well in some polluted environments.
Genetic characterization of extended-β-lactamase (ESBL) plasmids captured from dairy manures
Authors: Tran Tam , Thorne Joe , Scott Andrew , Robertson James , Nash John HE , Carrillo Catherine , Topp Edward
Published: March 2023

This study was to assess the gene diversity and characterize a large set of plasmids harboring extended β-lactamase (ESBL) genes from raw and digested dairy manure. A total of eighty-four plasmids that were captured in thisE. colirecipient were sequenced using Illumina MiSeq sequencing technology. Twenty-four plasmids of interest were subsequently sequenced using MinION technology in order that a hybrid assembly could be performed on short-and long-read sequences to circularize and complete these plasmids. The size of sequenced plasmids ranged between 40 and 260 kb with various incompatibility groups: IncC, IncI1, IncN, IncY, IncB/O/K/Z, IncX1, IncHI2, IncHI2A, IncFIB(K), IncFII. A variety of extended β-lactamase genes were identified:blaCTXM -1,blaCTXM -14,blaCTXM -15, blaCTXM-27, blaCTXM-55,blaCTXM-61,blaPER-1,blaIMP-27. Interestingly, theblaIMP-27gene, a novel metallo-β-lactamase discovered in the last decade, was found located on an integrated region in the host chromosome. And one plasmid carrying theblaCMY-2gene, an AmpC gene, also expressed ESBL phenotype. Four virulence factors, includingcia, cib, traTandterC,were detected on some of these plasmids. In addition, six type-2 toxin-antitoxin systems were detected: MazF/E, PemK/I, HipA/B, YdcE/D, RelB/E and HigB/A. Twenty-two out of twenty-four complete plasmids carried putative prophage regions; and most of prophage hits were marked as incomplete, except that the largest plasmid pT525A and the IncY plasmid pT415A had prophage hits with higher scores.

IMPORTANCE

The widespread of antibiotic resistant bacteria is largely due to the exchange of mobile genetic elements such as plasmids. Plasmids harboring extended β-lactamase (ESBL) genes originated from dairy manure potentially become entrained in manured soil, which subsequently enter the human food chain. Currently there is a lack of detailed information on these plasmids in the environment, specifically in dairy manure. This study unveils the abundance and diversity of ESBL-carrying plasmids from both raw and digested manures which were captured ingfp-labelledE. coliCV601. In addition, the study provides insightful information of plasmid characteristics including incompatibility groups, ESBL genes combined with other resistance genes, mobile genetic elements (transposons, insertion sequence), toxin-antitoxin systems, virulence factors and prophage sequences.
Meiotic prophase length modulates Tel1-dependent DNA double-strand break interference
Authors: Ruiz Luz María López , Johnson Dominic , Gittens William H. , Brown George , Allison Rachal M. , Neale Matthew J.
Published: March 2023

During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, inS. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we demonstrate that DSB clustering is abolished when meiotic prophase timing is extended via deletion of theNDT80transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, genome-wide maps of Spo11-DSB formation generated in the absence of Tel1 are skewed towards regions that load pro-DSB factors early—revealing regions of preferential priming—but this effect is abolished whenNDT80is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering—a phenomenon that is exacerbated intel1Δ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control.
Reduction of aggressive behaviour following hypothalamic deep brain stimulation: involvement of 5-HT1Aand testosterone
Authors: Gouveia Flavia Venetucci , Diwan Mustansir , Martinez Raquel CR , Giacobbe Peter , Lipsman Nir , Hamani Clement
Published: March 2023

Background

Aggressive behaviour (AB) may occur in patients with different neuropsychiatric disorders. Although most patients respond to conventional treatments, a small percentage continue to experience AB despite optimized pharmacological management and are considered to be treatment-refractory. For these patients, hypothalamic deep brain stimulation (pHyp-DBS) has been investigated. The hypothalamus is a key structure in the neurocircuitry of AB. An imbalance between serotonin (5-HT) and steroid hormones seems to exacerbate AB.

Objectives

To test whether pHyp-DBS reduces aggressive behavior in mice through mechanisms involving testosterone and 5-HT.

Methods

Male mice were housed with females for two weeks. These resident animals tend to become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5h/day for 8 consecutive days prior to daily encounters with the intruder. After testing, blood and brain were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT1Aantagonist) or saline injections prior to pHyp-DBS. After the first 4 encounters, the injection allocation was crossed, and animals received the alternative treatment during the next 4 days.

Results

DBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1Areceptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS.

Conclusions

This study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1Amechanisms.

HIGHLIGHTS

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Posterior hypothalamus DBS reduces aggressive behavior in mice

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Aggressive behavior was correlated with plasma testosterone levels

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DBS increased 5-HT1A receptor density in the orbitofrontal cortex and amygdala

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Pre-treatment with 5-HT1A antagonist (WAY) blocked the anti-aggressive effect of DBS
AN ARTIFICIAL INTELLIGENCE FOR RAPID IN-LINE LABEL-FREE HUMAN PLURIPOTENT STEM CELL COUNTING AND QUALITY ASSESSMENT
Authors: Ragunton Britney , Van Buskirk Steve , Wakefield Devin , Ranadive Ninad , Pipathsouk Andrew , Pei Baikang , Zhou Hong , Yamawaki Tracy , Berke Mike , Li Chi-Ming , Hale Christopher , Wang Songli , Chambers Stuart M.
Published: March 2023

The current state-of-the-art in hPSC culture is a bespoke and user-dependent process limiting the scale and complexity of the experiments performed and introducing operator-to-operator and day-to-day variation. Artificial intelligence (AI) offers the speed and flexibility to bridge the gap between a human-dependent process and industrial-scale automation.

We evaluated an AI approach for counting exact cell numbers of undifferentiated human induced pluripotent stem cells in brightfield images for automating hPSC culture. The neural network generates a topological density map for accurate cell counts. We found that the image-based AI algorithm can determine a precise number of hPSCs and is superior to fluorescence-labeled object detection; the algorithm can ignore well edges, meniscus effects, and dust, achieving an average error of 5.6%. We have built a prototype capable of making a go/no go decision for stem cell passaging to perform 26,400 individual well-level counts from 422,400 images in 12 hours at low cost.
Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses
Authors: Song Sang-Ho , Augustine George J.
Published: March 2023

Synapsins cluster synaptic vesicles (SVs) to provide a reserve pool (RP) of SVs that maintains synaptic transmission during sustained activity. However, it is unknown how synapsins cluster SVs. Here we show that either liquid-liquid phase separation (LLPS) or tetramerization-dependent cross-linking can cluster SVs, depending upon whether a synapse is excitatory or inhibitory. Cell-free reconstitution revealed that both mechanisms can cluster SVs, with tetramerization bring more effective. At inhibitory synapses, perturbing synapsin-dependent LLPS impairs SV clustering and synchronization of GABA release, while perturbing synapsin tetramerization does not. At glutamatergic synapses, the opposite is true: synapsin tetramerization enhances clustering of glutamatergic SVs and mobilization of these SVs from the RP, while synapsin LLPS does not. Comparison of inhibitory and excitatory transmission during prolonged synaptic activity revealed that synapsin LLPS serves as a brake to limit GABA release, while synapsin tetramerization enables rapid mobilization of SVs from the RP to sustain glutamate release.
An integrated RNA-proteomic landscape of drug induced senescence in a cancer cell line
Authors: Stevenson Thomas , Al-Roshdi Maha , Görtler Franziska , Grellscheid Sushma Nagaraja
Published: March 2023

Senescent cells are characterized by an arrest in proliferation. In addition to replicative senescence resulting from telomere exhaustion, sub-lethal genotoxic stress resulting from DNA damage, oncogene activation, mitochondrial dysfunction or reactive metabolites also elicits a senescence phenotype. Senescence is a controlled programme affecting a wide variety of biological processes with some core hallmarks of senescence as well as tissue specific changes. This study presents an integrative multi-omic analysis of proteomic and RNA-seq from proliferating and senescent osteosarcoma cells. This study demonstrates senescence induction in a widely used cell line which can be used as a model system for characterising cancer cell responses to sub-lethal doses of chemotherapeutic agents, and makes available both RNA-seq and proteomic data from proliferating and senescent cells in open access repositories to aid reuse by the community.
Specimen-displacement correction for powder X-ray diffraction in Debye–Scherrer geometry with a flat area detector. Erratum
Authors: Hulbert Benjamin S. , Kriven Waltraud M.
Published: March 2023

An error in Fig. 2(b) in the paper by Hulbert & Kriven [J. Appl. Cryst. (2023), 56, 160–166] is corrected.
FAIR and scalable management of small-angle X-ray scattering data
Authors: Giess Torsten , Itzigehl Selina , Range Jan , Schömig Richard , Bruckner Johanna R. , Pleiss Jürgen
Published: March 2023

A modular research data management toolbox based on the programming language Python, the widely used computing platform Jupyter Notebook, the standardized data exchange format for analytical data (AnIML) and the generic repository Dataverse has been established and applied to analyze small-angle X-ray scattering (SAXS) data according to the FAIR data principles (findable, accessible, interoperable and reusable). The SAS-tools library is a community-driven effort to develop tools for data acquisition, analysis, visualization and publishing of SAXS data. Metadata from the experiment and the results of data analysis are stored as an AnIML document using the novel Python-native pyAnIML API. The AnIML document, measured raw data and plots resulting from the analysis are combined into an archive in OMEX format and uploaded to Dataverse using the novel easyDataverse API, which makes each data set accessible via a unique DOI and searchable via a structured metadata block. SAS-tools is applied to study the effects of alkyl chain length and counterions on the phase diagrams of alkyltrimethylammonium surfactants in order to demonstrate the feasibility and usefulness of a scalable data management workflow for experiments in physical chemistry.
The antecedents of university loyalty: a study of postgraduate students in Malaysia
Authors: Mutum Dilip S. , Hussein Ahmad Hata , Ghazali Ezlika M.
Published: March 2023

Purpose

This study investigates the antecedents of student loyalty towards universities. This study offers new insights into postgraduate loyalty in the context of the Malaysian higher education industry.

Design/methodology/approach

Partial least squares structural equation modelling is used to analyse data obtained from a survey of 231 postgraduate students in Malaysia.

Findings

The findings indicate that there is a significant relationship between price value and both student satisfaction and student loyalty. There are also strong relationships between learning environment and student satisfaction and between student satisfaction and student loyalty. While university prestige showed a significant relationship with student satisfaction, it is not related to student loyalty. Another important finding is that price value has a strong and direct relationship with both student satisfaction and student loyalty.

Originality/value

This study presents an updated empirical model of student loyalty. Contrary to previous studies, the results indicate that service quality is not related to student satisfaction. However, it is found to influence student loyalty towards the University. The results also indicate the important mediating effect of student satisfaction. This is the first study to look specifically at student satisfaction and loyalty of postgraduate students in Malaysia.
Depressive mood and compulsive social media usage: the mediating roles of contingent self-esteem and social interaction fears
Authors: Ali Fayaz , Tauni Muhammd Zubair , Ashfaq Muhammad , Zhang Qingyu , Ahsan Tanveer
Published: March 2023

Purpose

Given the limited literature on depression as a contributing factor to compulsive social media use, the present research examines the role of perceived depressive mood (PDM) in developing compulsive social media use behavior. The authors also identify and hypothesize channels such as contingent self-esteem (CSE), social interaction anxiety (SIA) and fear of negative evaluation (FNE), which may explain how PDM affects compulsive social media use.

Design/methodology/approach

The research model was empirically tested with a survey of 367 Chinese university students using structural equation modeling by drawing on the escape and self-presentation lenses.

Findings

The findings indicate that PDM contributes to compulsive social media use behavior both directly and indirectly through CSE. Furthermore, the impact of CSE on compulsive social media use is mediated by the FNE, whereas SIA fails to mediate this effect.

Practical implications

The results can advance the authors’ knowledge of the role and process by which depressive mood impacts compulsive social media use. These findings may add insights into psychological treatment and help in, for example, developing counseling programs or coping strategies for depressed people to protect them from using social media excessively.

Originality/value

This research identifies the pathway mechanism between PDM and compulsive use of social media. It also increases the understanding of how CSE and social interaction deficiencies contribute to compulsive social media usage (CSMU).
Role of inter-organizational systems in driving tourism businesses forward in the post-COVID-19 new normal
Authors: Ku Edward C.S.
Published: March 2023

Purpose

This study aims to explore how inter-organizational systems (IOSs) drive tourism businesses to a new normal based on the resource-based view through the supply chain of tourism and information and computer technology used in IOSs.

Design/methodology/approach

Data were collected from the management of tourism businesses, and stratified sampling was used in the study. The authors selected 1,000 travel agencies as the study sample, mailed the research questionnaire to their managers and received 252 completed questionnaires. The authors analyzed the data using the partial least squares approach.

Findings

IOS is seen as a transformational service mechanism that provides a dynamic support weapon for members of the tourism supply chain. Tourism businesses should look for suppliers providing comprehensive services through IOS, excellent quality tourism products and customized tourism products to enhance the competitiveness of tourism businesses in the new normal.

Originality/value

This study provides an industrial marketing research perspective on tourism businesses facing the challenges of the new normal. For tourism businesses, technological innovation allows for changes in the strategies and procedures for their transformation and improves the business model of tourism businesses in the new normal.
Web accessibility of Indian cultural heritage information: an analytical study of museum websites
Authors: Pandey Rahul , Kumar Vinit
Published: March 2023

Purpose

This paper compares the web accessibility of Indian museum websites assessing the level of compliance to the Web Content Accessibility Guidelines 2.1 (WCAG 2.1). The study aims to assess the accessibility of Indian museum websites in terms of their severity.

Design/methodology/approach

The accessibility evaluation of 11 Indian museum websites was conducted using Siteimprove Accessibility Checker (SAC), an automated website testing tool.

Findings

The study results indicate that the mean conformance score for the Indian museum websites for level A was 19.27, while for level AA and AAA, it came out to be 2.63 and 4.09, respectively, with the highest severity scores for error (16.3) followed by review (5.81) criteria and warning (3.81). The major findings indicate that the websites of Indian museums poorly conform to web accessibility guidelines.

Practical implications

The study's findings will assist the museum's website creators, managers and administrators in determining the level of conformity as per standard accessibility guidelines helping them make strategic decisions to improve the accessibility.

Originality/value

Most of the studies available in the field of website accessibility range from the web accessibility of educational institutions, tourism websites, municipal websites and ministerial websites, but there are very few studies investigating the accessibility of museum websites. A quantitative evaluation of different aspects of accessibility was conducted in the study, which can pave the way for the better design of web sites by addressing deficiencies.
Examining the role of personality traits in guestroom technologies
Authors: Demirciftci Tevfik , Bilgihan Anil , Erdem Mehmet , Baloglu Seyhmus
Published: March 2023

Purpose

This study aimed to identify distinctive characteristics of hotel guests and understand their perception of guestroom technologies (GRTs) in hotels by utilizing the theory of consumer innovativeness and the social influence theory.

Design/methodology/approach

The data were collected from 268 hotel guests. The K-means clustering algorithm was employed to identify participants based on their views on the significance of technologies provided in guest rooms. A multivariate analysis of variance was applied to investigate if there were significant differences among clusters regarding social influence on hotel bookings, technology innovativeness and technology expertise and knowledge.

Findings

Two clusters were identified: technology compassionates and casual users of technology. Findings revealed that technology compassionates are more influenced by their friends when booking a hotel compared to casual users of technology. The ability to link up multiple wireless mobile devices, accessible outlets and mobile websites were the most critical GRTs for technology compassionates.

Practical implications

Technology should be considered a crucial part of the hotel guest experience. Hoteliers ought to continue investing in smart technologies to improve their guests' experiences. GRTs can reduce overhead staff costs while giving guests more control over their stay by utilizing everyday items like smartphones and offering them more power over their lodging experience.

Originality/value

This study advances the existing literature on GRTs by identifying which GRTs produce the most customer satisfaction. Moreover, this study explores the impact of social influence, innovativeness as a personality trait and having expert knowledge of technologies on preferences for GRTs.
Increasing global mindset through collaborative online international learning (COIL): internationalizing the undergraduate international business class
Authors: Garcia Fernando , Smith Stephen Ray , Burger Amy , Helms Marilyn
Published: March 2023

Purpose

This study aims to provide a case example of two partner institutions and business faculty who creatively used a collaborative online international learning (COIL) experience during the height of the COVID-19 pandemic and transition to online learning to internationalize an undergraduate business class and use existing technology to offer a case study project to further students’ global mindset.

Design/methodology/approach

Using open-ended qualitative comments from an American college and a Peruvian university, researchers uncovered key themes from a virtual COIL-based learning experience offered as part of an international business class.

Findings

Student end-of-course evaluation comments from both countries validated the success of the learning experience and value of working together with other students and faculty in a virtual setting.

Research limitations/implications

Areas for future research are provided to extend these initial exploratory findings. However, the implications are clear that the methodology is also appropriate in nonpandemic situations and can quickly bring a global mindset to remote corners of the globe and ensure all students experience the “virtual” study abroad, even when there are travel limitations or budget restrictions for students or the institutions.

Practical implications

The implementation detail provided can be easily replicated by other institutions with a global mindset and internationalization goals.

Social implications

The proliferation of COIL-based experiences will impact how study abroad experiences are defined and offered in the future.

Originality/value

While researchers have documented COIL experiences in the academic literature, their use during the COVID-19 pandemic, as often the only solution for on-going internationalization, has not been thoroughly studied or documented. In addition, the class activities further used team-based international workplace pedagogy, authentic engagement and technology.
Cloud-based big data framework towards strengthening disaster risk reduction: systematic mapping
Authors: Mahrin Mohd Naz’ri , Subbarao Anusuyah , Chuprat Suriayati , Abu Bakar Nur Azaliah
Published: March 2023

Purpose

Cloud computing promises dependable services offered through next-generation data centres based on virtualization technologies for computation, network and storage. Big Data Applications have been made viable by cloud computing technologies due to the tremendous expansion of data. Disaster management is one of the areas where big data applications are rapidly being deployed. This study looks at how big data is being used in conjunction with cloud computing to increase disaster risk reduction (DRR). This paper aims to explore and review the existing framework for big data used in disaster management and to provide an insightful view of how cloud-based big data platform toward DRR is applied.

Design/methodology/approach

A systematic mapping study is conducted to answer four research questions with papers related to Big Data Analytics, cloud computing and disaster management ranging from the year 2013 to 2019. A total of 26 papers were finalised after going through five steps of systematic mapping.

Findings

Findings are based on each research question.

Research limitations/implications

A specific study on big data platforms on the application of disaster management, in general is still limited. The lack of study in this field is opened for further research sources.

Practical implications

In terms of technology, research in DRR leverage on existing big data platform is still lacking. In terms of data, many disaster data are available, but scientists still struggle to learn and listen to the data and take more proactive disaster preparedness.

Originality/value

This study shows that a very famous platform selected by researchers is central processing unit based processing, namely, Apache Hadoop. Apache Spark which uses memory processing requires a big capacity of memory, therefore this is less preferred in the world of research.
Disk diffusion‐based method aids in the detection of vanM‐positive Enterococcus faecium with low vancomycin minimum inhibitory concentrations
Authors: Wang Jue , Li Pei , Xin Lin , Xu Xiaogang , Wang Minggui
Published: March 2023

We first reported the vanM vancomycin resistance gene in enterococci in Shanghai, China in 2006 and later found it to be the predominant van gene in vancomycin‐resistant enterococci (VRE). In this study, we successively collected 1292 Enterococcus faecium and Enterococcus faecalis strains from in‐ and outpatients at Huashan Hospital, Fudan University and found that nearly all of the isolates (1290/1292) were vancomycin‐sensitive determined by the VITEK 2 system. However, using a modified macromethod‐based disk diffusion test, 10 E. faecium isolates that were previously determined to be vancomycin‐sensitive by the VITEK 2 system were found to have colonies in the vancomycin disk inhibition zone. Pulse‐field gel electrophoresis results showed that each randomly selected colony in the inhibition zone belonged to the same clone as the original strain. All 10 isolates were later found to be vanM‐positive. The disk diffusion‐based method may aid in the detection of vanM‐positive E. faecium with low vancomycin minimum inhibitory concentrations and prevent missing the detection of vancomycin sensitivity‐variable enterococci.
COVID‐19 and the fiscal and monetary challenges to implementing Our Common Agenda
Authors: Sowels Nicholas
Published: March 2023

This contribution examines the fiscal and monetary policy legacies of the COVID‐19 pandemic. Thanks to exceptional support from governments and central banks, the world economy returned rapidly to growth following the dramatic global lockdowns of spring 2020. However, the huge fiscal and monetary interventions involved raise significant challenges for future growth and financial stability, especially given the sharp rise in inflation from mid‐2021. These challenges make implementing the ambitious Common Agenda of the United Nations difficult, especially as the war in Ukraine has greatly weakened international cooperation.
Self‐reported alcohol use versus phosphatidylethanol in behavioral trials: A study of people living with HIV in Tshwane, South Africa
Authors: Parry Charles D. H. , Myers Bronwyn , Londani Mukhethwa , Shuper Paul A. , Nkosi Sebenzile , Hahn Judith A. , Kekwaletswe Connie , Morojele Neo K.
Published: March 2023

Background

Accurately quantifying alcohol use among persons with HIV (PWH) is important for validly assessing the efficacy of alcohol reduction interventions.

Methods

We used data from a randomized controlled trial of an intervention to reduce alcohol use among PWH who were receiving antiretroviral therapy in Tshwane, South Africa. We calculated agreement between self‐reported hazardous alcohol use measured by the Alcohol Use Disorders Identification Test (AUDIT; score ≥8) and AUDIT‐Consumption (AUDIT‐C; score ≥3 for females and ≥4 for males), heavy episodic drinking (HED) in the past 30 days, and heavy drinking in the past 7 days with a gold standard biomarker‐‐phosphatidylethanol (PEth) level (≥50 ng/mL)‐‐among 309 participants. We used multiple logistic regression to assess whether underreporting of hazardous drinking (AUDIT‐C vs. PEth) differed by sex, study arm, and assessment time point.

Results

Participants' mean age was 40.6 years, 43% were males, and 48% were in the intervention arm. At 6 months, 51% had PEth ≥50 ng/mL, 38% and 76% had scores indicative of hazardous drinking on the AUDIT and AUDIT‐C, respectively, 11% reported past 30‐day HED, and 13% reported past 7‐day heavy drinking. At 6 months, there was low agreement between AUDIT‐C scores and past 7‐day heavy drinking relative to PEth ≥50 (sensitivities of 83% and 20% and negative predictive values of 62% and 51%, respectively). Underreporting of hazardous drinking at 6 months was associated with sex (OR = 3.504. 95% CI: 1.080 to 11.364), with odds of underreporting being greater for females.

Conclusions

Steps should be taken to decrease underreporting of alcohol use in clinical trials.
Case series: Voluntary discontinuation of sublingual buprenorphine treatment for opioid use disorder using extended‐release buprenorphine
Authors: Rodriguez Claudia P. , Suzuki Joji
Published: March 2023

Background and Objectives

Despite its efficacy, patients may still seek to voluntarily discontinue sublingual (SL) buprenorphine treatment, but little guidance exist on how to safely conduct a taper. We, therefore, report on the use of extended‐release buprenorphine (XR‐BUP) to facilitate voluntary treatment discontinuation.

Methods

A case series (n = 4).

Results

Four individuals interested in voluntary discontinuation of sublingual buprenorphine treatment were transitioned to varying durations of XR‐BUP, after which all were able to discontinue buprenorphine with minimal withdrawal symptoms. One individual had a brief recurrence to illicit opioid use. All remained engaged in treatment.

Discussion and Conclusions

The use of XR‐BUP, given its long terminal half‐life, may be a helpful option for individuals who are interested in voluntary buprenorphine discontinuation. Collaboration with the patient must include information about the risk of lapse to use and overdose following discontinuation.

Scientific Significance

The cases reported here provide preliminary support for the use of XR‐BUP to help individuals discontinue buprenorphine treatment. There is only one other case series showing the use of XR‐BUP in helping individuals successfully discontinue buprenorphine treatment. Buprenorphine discontinuation is clinically relevant and there is little guidance in the current literature.
Comparative validation of HAS‐BLED, GARFIELD‐AF and ORBIT bleeding risk scores in Asian people with atrial fibrillation treated with oral anticoagulant: A report from the COOL‐AF registry
Authors: Chichareon Ply , Winijkul Arjbordin , Lip Gregory Y. H. , Krittayaphong Rungroj
Published: March 2023

Aims

Comparative data between the HAS‐BLED, GARFIELD‐AF and ORBIT score are limited in anticoagulated Asian patients with atrial fibrillation (AF). We compared the performance of the 3 scores in a nationwide registry.

Methods

AF patients treated with oral anticoagulants in the COOL‐AF registry were studied. We fitted the variables of the HAS‐BLED, GARFIELD‐AF and ORBIT score to major bleeding in Cox model. We explored a modified HAS‐BLED by addition of sex and body weight. Discrimination, calibration, net reclassification index (NRI) and decision curve analysis were used to compare the performance of the 3 models.

Results

Of 3402 patients in the registry, 2568 patients who received oral anticoagulant at baseline were studied. Majority of patients (91.1%) received warfarin. The rate of major bleeding was 2.11 per 100 person‐years. The C‐statistics of the GARFIELD‐AF, HAS‐BLED, modified HAS‐BLED and ORBIT score were 0.65 (95% confidence interval [CI] 0.63–0.67), 0.66 (95%CI 0.64–0.68), 0.69 (95%CI 0.67–0.71) and 0.64 (95%CI 0.62–0.66) respectively. There was good agreement between predicted and observed bleeding in the deciles of HAS‐BLED and GARFIELD‐AF scores, while the modified HAS‐BLED score and ORBIT score overestimated the risk in the last decile. The modified HAS‐BLED score had superior NRI than the HAS‐BLED score (26.9%, 95%CI 9.7%–42.2%) and the ORBIT score (31.9%, 95%CI 9.0–53.6%). The NRI between the modified HAS‐BLED and GARFIELD‐AF score was similar. The net benefit curve of the 4 models were overlapping among different thresholds.

Conclusions

The clinical utility for bleeding prediction of GARFIELD‐AF, HAS‐BLED, modified HAS‐BLED and ORBIT scores were similar in anticoagulated Asian patients with AF participating in the COOL‐AF registry. We found no advantage of the ORBIT over HAS‐BLED score for bleeding risk prediction, even in direct oral anticoagulant users.
Trustworthiness as information: Satisfying the understanding condition of valid consent
Authors: Martin Robert K.
Published: March 2023

Within medical ethics, there is widespread agreement that morally valid consent includes an understanding condition. Disagreement centers on what is meant by that understanding condition. Tom Dougherty proposed that this understanding condition should be divided into the two mutually exclusive categories of descriptive information and contextual information. Further, Dougherty argues that each type of information is necessary to satisfy the understanding condition. In contrast, I argue that when the deontic aspect of valid consent is in view, each type of information can be sufficient to satisfy the understanding condition on its own. Moreover, by analyzing delegation, which is conceptually related to consent since both are morally transformative actions, I show that delegation often depends not on descriptive or contextual information but on trust. So, I argue that trustworthiness can also be a type of information that does the same work as descriptive and contextual information in satisfying the understanding condition for valid consent.
The ambiguities of coercion: Mapping adolescents' experiences of coercion in institutional everyday life
Authors: Henriksen Ann-Karina , Øye Christine
Published: March 2023

The article presents a metasynthesis of qualitative studies, which have described and analysed adolescents' experiences of coercion in institutional contexts such as psychiatric care, child welfare and juvenile justice. The study finds that coercion is an ambiguous practice, mainly used for protection and treatment purposes, while it is often experienced as punitive. Acknowledging the ambiguities of coercion can contribute to a more nuanced understanding of practice and experience, which is useful for reducing the harmful effects of coercion and strengthening participatory methods of care and treatment.
Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test
Authors: Ekström Ola , Ström Kristoffer , Mir Bilal Ahmad , Laurila Esa , Wessman Ylva , Lehtovirta Mikko , Eriksson Karl‐Fredrik , Hansson Ola
Published: March 2023

Aim

Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum.

Methods

Thirty‐nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme‐linked immunosorbent assay.

Results

After the Wingate test, serum TNC increased on average by 23% [15–33], median [interquartile range]; PWilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO2max. TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue.

Conclusion

TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation.
Lactate and ammonia measurements during cardiopulmonary exercise testing and its recovery phase—Consideration of age and sex in its interpretation
Authors: Ratia Nadja , Lantto Hanna , Rotgers Emmi , Kouri Vesa‐Petteri , Auranen Mari , Luukkonen Ritva , Piirilä Päivi
Published: March 2023

Background

Cardiopulmonary exercise testing with lactate and ammonia samples is used in the diagnostics of metabolic myopathies. As the effect of age and sex on the exercise lactate and ammonia levels are incompletely characterized for clinical associations, our aim was to assess the effects of these factors on healthy subjects to improve the test's interpretation.

Methods

Seventy‐three subjects (34 men and 39 women; age < 35 years, n = 26, 35–50 years, n = 23 and >50 years, n = 24) performed cardiopulmonary exercise tests with venous blood gases, plasma lactate and ammonia analyses at rest, during exercise, and 2, 4, 6, 10, 20 and 30 min into recovery.

Results

The lactate (p = 0.021–0.044) and ammonia values (p = 0.002–0.038) differed between men and women measured during recovery and between three age groups point‐by‐point in maximal exercise and the recovery phase and also longitudinally, most notably between <35‐ and >50‐year‐groups (lactate p = <0.001–0.040, ammonia p = 0.002–0.03). In the linear model, the yearly reduction of lactate was maximally −0.119 mmol/L and that of ammonia −1.514 µmol/L. The yearly reduction of lactate was greater in women than in men (−0.131 vs.−0.099 2 min into recovery), but for ammonia, the results were not as clear.

Conclusions

Plasma lactate and ammonia concentrations measured during cardiopulmonary exercise were lower in older age groups, and their yearly reduction was also influenced by sex. These data give new information on lactate and ammonia levels and the effect of aging on them during exercise and recovery and may help assess cardiopulmonary exercise testing results.
Infection‐related mortality after HLA‐identical and haploidentical hematopoietic cell transplantation using reduced‐intensity conditioning in an outpatient setting
Authors: Jaime‐Pérez José Carlos , Meléndez‐Flores Jesús D. , Ramos‐Dávila Eugenia M. , Gutiérrez‐Aguirre César Homero , Cantú‐Rodríguez Olga G. , Marfil‐Rivera Luis Javier , Áncer‐Rodríguez Jesús , Gómez‐Almaguer David
Published: March 2023

Background

Despite the improvements in supportive care for allogeneic‐hematopoietic cell transplantation (allo‐HCT) recipients, infectious complications and infection‐related mortality (IRM) continue to be a major issue for transplantation centers.

Methods

We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo‐HCT) or HLA‐identical HCT at a tertiary referral center during 2013‐2020. Patients in the haplo‐HCT group received post‐transplant cyclophosphamide (PT‐Cy), and all received reduced‐intensity conditioning regimens.

Results

More haplo‐HCT recipients presented severe infections in the pre‐engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100‐day and 2‐year cumulative incidence of IRM was 15% and 21% for the haplo‐HCT and 5.6% and 17% for the HLA‐identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002).

Conclusions

No differences in IRM were observed based on allo‐HCT type, with more haplo‐HCT patients suffering from severe infections in the pre‐engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.
Venous thromboembolism in metastatic pancreatic cancer
Authors: Laderman Lauren , Sreekrishnanilayam Krishnalatha , Pandey Ramesh K. , Handorf Elizabeth , Blumenreich Aryeh , Sorice Kristen A. , Lynch Shannon M. , Cheema Khadija , Nagappan Lavanya , Sosa Iberia R. , Dotan Efrat , Vijayvergia Namrata
Published: March 2023

Background

Pancreatic cancer (PC) carries a high risk of venous thromboembolism (VTE). Several risk assessment models (RAMs) predict benefit of thromboprophylaxis in solid tumors; however, none are verified in metastatic pancreatic cancer (mPC).

Methods

A retrospective mPC cohort treated at an academic cancer center from 2010 to 2016 was investigated for VTE incidence (VTEmets). Multivariable regression analysis was used to assess multiple VTE risk factors. Overall survival (OS) was compared between mPC groups with and without VTE. Survival was analyzed using Kaplan–Meier survival plots and Cox proportional hazards regressions.

Results

400 mPC patients (median age 66; 52% males) were included. 87% had performance status of ECOG 0–1; 70% had advanced stage at PC diagnosis. Incidence of VTEmets was 17.5%; median time of occurrence 3.48 months after mPC diagnosis. Survival analysis started at median VTE occurrence. Median OS was 10.5 months in VTEmets vs. 13.4 in non‐VTE group. Only advanced stage (OR 3.7, p = .001) correlated with increased VTE risk.

Conclusions

The results suggest mPC carries a significant VTE burden. VTE predicts poor outcomes from the point of median VTE occurrence. Advanced stage disease is the strongest risk factor. Future studies are needed to define risk stratification, survival benefit, and choice of thromboprophylaxis.
Adverse impact of a highCD4/CD8ratio in the allograft may be overcome by methotrexate‐ but not mycophenolate‐ or post‐transplant cyclophosphamide‐based graft versus host disease prophylaxis
Authors: Nikoloudis A. , Buxhofer‐Ausch V. , Aichinger C. , Binder M. , Hasengruber P. , Kaynak E. , Wipplinger D. , Milanov R. , Strassl I. , Stiefel O. , Machherndl‐Spandl S. , Petzer A. , Weltermann A. , Clausen J.
Published: March 2023

Introduction

A high CD4/CD8 T cell ratio in hematopoietic stem cell transplant (HSCT) allografts was observed to predict graft‐versus‐host disease (GVHD) and nonrelapse mortality (NRM) but has not been comparatively examined in settings of various GVHD‐prophylaxis regimens.

Methods

This retrospective monocentric study included all consecutive HSCT performed with peripheral blood stem cells between January 2000 and June 2021. The impact of the graft CD4/CD8 ratio was analyzed in three cohorts with different GVHD‐prophylaxis platforms.

Results

In the cyclosporine/mycophenolate‐mofetil (CSA/MMF) cohort (n = 294, HLA‐matched HSCT), a high (>75th percentile) CD4/CD8 ratio was associated with increased overall mortality (HR: 1.56;p = .01), increased NRM (HR: 1.85;p = .01) and GVHD‐associated mortality (HR: 2.13;p = .005). In the post‐transplant cyclophosphamide (PTCy)/tacrolimus/MMF cohort (n = 113, haploidentical‐related or mismatched‐unrelated HSCT), a high CD4/CD8 ratio was associated with increased overall mortality (HR 2.07;p = .04) and aGVHD3‐4 (HR: 2.24;p = .02). By contrast, in the CSA/methotrexate (CSA/MTX) cohort (n = 185, HLA‐matched HSCT) the CD4/CD8 ratio had no significant impact on any of the investigated endpoints.

Conclusion

A high CD4/CD8 ratio in the allograft has an adverse impact on GVHD and survival in CSA/MMF‐ and PTCy‐based HSCT, while MTX‐based prophylaxis may largely alleviate this important risk factor.