bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of a pharmacist skill development “work-with” program
Authors: Rourke Wallace , Pagel Kaitlyn , Dumont Zack , Len Suzanne , Roy Caitlin
Published: September 2022

Purpose

Pharmacists’ clinical competency is necessary to ensure patient safety and medication optimization. There are many barriers to the implementation of competency assessments and scant literature on their implementation. We aimed to determine if a competency assessment program for hospital pharmacists is feasible, acceptable, and effective.

Methods

Clinical competency assessments of hospital pharmacists were conducted. During the assessments, pharmacists presented a patient case or completed patient care activities while a leadership team member evaluated them using a competency rubric and provided feedback. A postevaluation electronic survey adapted from validated tools regarding perceptions of program feasibility and acceptability was emailed to the pharmacists following each competency assessment and to evaluators at study conclusion. Feasibility was also measured through reviewing rubrics for completion within the 1.5- to 2-hour assessment timeframe. Effectiveness was captured by comparing results to expected competency levels based on experience.

Results

In total, 20 assessments were completed. Fifty percent of assessments required longer than the allotted timeframe. Most participants surveyed found the competency assessments implementable, possible, doable, and easy to use. The majority also approved of the implemented assessments and found them appealing, likable, and welcomed and commented that they aided in professional development. For 50% of the competencies assessed, most participants aligned with competency expectations based on years of experience.

Conclusion

The implementation of these competency assessments was found to be feasible and acceptable to hospital pharmacists. The rubric used was found to be moderately effective. Major implementation barriers were related to time constraints and criteria for success. Future work will be done to enhance the program’s effectiveness.
Comparison of scRNA-seq data analysis method combinations
Authors: Xu Li , Xue Tong , Ding Weiyue , Shen Linshan
Published: September 2022

Single-cell ribonucleic acid (RNA)-sequencing (scRNA-seq) data analysis refers to the use of appropriate methods to analyze the dataset generated by RNA-sequencing performed on the single-cell transcriptome. It usually contains three steps: normalization to eliminate the technical noise, dimensionality reduction to facilitate visual understanding and data compression and clustering to divide the data into several similarity-based clusters. In addition, the gene expression data contain a large number of zero counts. These zero counts are considered relevant to random dropout events induced by multiple factors in the sequencing experiments, such as low RNA input, and the stochastic nature of the gene expression pattern at the single-cell level. The zero counts can be eliminated only through the analysis of the scRNA-seq data, and although many methods have been proposed to this end, there is still a lack of research on the combined effect of existing methods. In this paper, we summarize the two kinds of normalization, two kinds of dimension reduction and three kinds of clustering methods widely used in the current mainstream scRNA-seq data analysis. Furthermore, we propose to combine these methods into 12 technology combinations, each with a whole set of scRNA-seq data analysis processes. We evaluated the proposed combinations using Goolam, a publicly available scRNA-seq, by comparing the final clustering results and found the most suitable collection scheme of these classic methods. Our results showed that using appropriate technology combinations can improve the efficiency and accuracy of the scRNA-seq data analysis. The combinations not only satisfy the basic requirements of noise reduction, dimension reduction and cell clustering but also ensure preserving the heterogeneity of cells in downstream analysis. The dataset, Goolam, used in the study can be obtained from the ArrayExpress database under the accession number E-MTAB-3321.
APPRIS principal isoforms and MANE Select transcripts define reference splice variants
Authors: Pozo Fernando , Rodriguez José Manuel , Martínez Gómez Laura , Vázquez Jesús , Tress Michael L
Published: September 2022

Motivation

Selecting the splice variant that best represents a coding gene is a crucial first step in many experimental analyses, and vital for mapping clinically relevant variants. This study compares the longest isoforms, MANE Select transcripts, APPRIS principal isoforms, and expression data, and aims to determine which method is best for selecting biological important reference splice variants for large-scale analyses.

Results

Proteomics analyses and human genetic variation data suggest that most coding genes have a single main protein isoform. We show that APPRIS principal isoforms and MANE Select transcripts best describe these main cellular isoforms, and find that using the longest splice variant as the representative is a poor strategy. Exons unique to the longest splice isoforms are not under selective pressure, and so are unlikely to be functionally relevant. Expression data are also a poor means of selecting the main splice variant. APPRIS principal and MANE Select exons are under purifying selection, while exons specific to alternative transcripts are not. There are MANE and APPRIS representatives for almost 95% of genes, and where they agree they are particularly effective, coinciding with the main proteomics isoform for over 98.2% of genes.

Availability and implementation

APPRIS principal isoforms for human, mouse and other model species can be downloaded from the APPRIS database (https://appris.bioinfo.cnio.es), GENCODE genes (https://www.gencodegenes.org/) and the Ensembl website (https://www.ensembl.org). MANE Select transcripts for the human reference set are available from the Ensembl, GENCODE and RefSeq databases (https://www.ncbi.nlm.nih.gov/refseq/). Lists of splice variants where MANE and APPRIS coincide are available from the APPRIS database.

Supplementary information

Supplementary data are available at Bioinformatics online.
This is GlycoQL
Authors: Hayes Catherine , Daponte Vincenzo , Mariethoz Julien , Lisacek Frederique
Published: September 2022

Motivation

We have previously designed and implemented a tree-based ontology to represent glycan structures with the aim of searching these structures with a glyco-driven syntax. This resulted in creating the GlySTreeM knowledge-base as a linchpin of the structural matching procedure and we now introduce a query language, called GlycoQL, for the actual implementation of a glycan structure search.

Results

The methodology is described and illustrated with a use-case focused on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein glycosylation. We show how to enhance site annotation with federated queries involving UniProt and GlyConnect, our glycoprotein database.

Availability and implementation

https://glyconnect.expasy.org/glycoql/.
HMI-PRED 2.0: a biologist-oriented web application for prediction of host–microbe protein–protein interaction by interface mimicry
Authors: Lim Hansaim , Tsai Chung-Jung , Keskin Ozlem , Nussinov Ruth , Gursoy Attila
Published: September 2022

HMI-PRED 2.0 is a publicly available web service for the prediction of host–microbe protein–protein interaction by interface mimicry that is intended to be used without extensive computational experience. A microbial protein structure is screened against a database covering the entire available structural space of complexes of known human proteins.

Availability and implementation

HMI-PRED 2.0 provides user-friendly graphic interfaces for predicting, visualizing and analyzing host–microbe interactions. HMI-PRED 2.0 is available at https://hmipred.org/.
Spatial organization of neuron–astrocyte interactions in the somatosensory cortex
Authors: Baraibar Andrés M , Belisle Lindsey , Marsicano Giovanni , Matute Carlos , Mato Susana , Araque Alfonso , Kofuji Paulo
Published: September 2022

Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons. Here, we show that Cannabinoid type 1 receptor (CB1R)-mediated astrocyte activation by neuron-released endocannabinoids elevate astrocyte Ca2+ levels, stimulate ATP/adenosine release as gliotransmitters, and transiently depress synaptic transmission in layer 5 pyramidal neurons at relatively distant synapses (˃20 μm) from the stimulated neuron. This astrocyte-mediated heteroneuronal synaptic depression occurred between pyramidal neurons within a cortical column and was absent in neurons belonging to adjacent cortical columns. Moreover, this form of heteroneuronal synaptic depression occurs between neurons located in particular layers, following a specific connectivity pattern that depends on a layer-specific neuron-to-astrocyte signaling. These results unravel the existence of astrocyte-mediated nonsynaptic communication between cortical neurons and that this communication is column- and layer-specific, which adds further complexity to the intercellular signaling processes in the neocortex.
Rapid Determination of Preservatives in Cosmetics Using a Core–Shell Column
Authors: Tanaka Misa , Doi Takahiro , Takeda Akihiro , Nakamura Akihiko , Azuma Yuki , Kawaguchi Masami , Tagami Takaomi
Published: September 2022

Preservatives are frequently added to cosmetics to maintain product quality. Our laboratory quantifies 11 preservatives in cosmetics each year for regulatory purposes. In laboratories, many manufactures also analyze the preservatives in their products for quality control. To analyze many cosmetic samples, a rapid analysis method is required for efficiency. In this study, we developed a rapid method for the simultaneous determination of 11 regulated preservatives in cosmetics using a core–shell column by high-performance liquid chromatography. In this method, the 11 preservatives were separated within 17 min, which was approximately half the time reported in the previous study. The peak resolution for each preservative was >2.6, the correlation coefficients of the calibration curves were >0.9988, the percent recoveries were 92.0–111.9% and the relative standard deviations were <3.5% (n = 3). The relative standard deviations among 6 researchers were <4.7%. Thus, it is an effective rapid determination method for the analysis of preservatives in cosmetics.
Extraction-HPLC Green Methodology for Determination of Phenolic Compounds from Fruits by using Brij-58 Surfactant
Authors: Kori Shivpoojan , Sharma Shweta
Published: September 2022

A green, simple and cost-effective, validated high-performance liquid chromatographic (HPLC) with UV detector has been developed an analytical method for the simultaneous determination of the most significant phenolic compounds viz. Gallic acid (GA), Quercetin (QC) and Ferulic acid (FA). The detection limit of GA, QC, FA was 0.303, 0.168, 0.0976 μg/mL and quantitation limit was 0.918, 0.051, 0.295 μg/mL, respectively. All parameters of planned validated method were carried out as per the ICH guidelines. This analytical method was applied to determine the phenolic compounds in fruits cultivated in India. Phenolic compounds in fruits extract were quantified using regression equations. This method can be scaled up to determine the alkaloids from several medicinal and poisonous plants samples in pharmaceutical, forensics and industrial areas.
Ideology, political polarisation and agility of policy responses: was weak executive federalism a curse or a blessing for COVID-19 management in the USA?
Authors: Gasulla Óscar , Bel Germà , Mazaira-Font Ferran A
Published: September 2022

We investigate whether weak executive federalism was beneficial or damaging for COVID-19 management in the USA. We formulate a policy response model for subnational governments, considering the national government’s preferred policy, in addition to other factors, with incomplete and with complete information. The hypotheses derived are tested using econometric techniques. Our results suggest that ideological and political biases were more influential in a situation of incomplete information than in one of complete information. As such, weak executive federalism allowed more agile policy responses in Democrat-led states when information was incomplete, thus reducing the rates of incidence and mortality. When information was complete, ideological and political biases were found to be of no relevance at all.
Exploring Patient Perspectives on a 12-Week Online, Stress Reduction Intervention in Inflammatory Bowel Disease
Authors: Watt Makayla , Peerani Farhad , Madsen Karen , Siffledeen Jesse , Kroeker Karen , Lim Allen , Tandon Puneeta , Hyde Ashley
Published: September 2022

Background

Online stress reduction interventions may be useful adjuncts to standard medical therapies for inflammatory bowel disease (IBD). As part of the evaluation of a 12-week randomized control trial (RCT) of an online multicomponent stress reduction program, our aim for the current study was to use qualitative methods to more deeply explore the patient experience with the online programming.

Methods

Upon completion of the 12-week RCT, all intervention participants were invited to participate in semistructured interviews. A qualitative descriptive approach was used. Interviews were analyzed through a theoretical thematic analysis process, whereby transcripts were coded, and codes then grouped into larger categories and themes.

Results

A total of 56 interviews were analyzed with the emergence of 3 main themes: (1) IBD as a source of stress and uncertainty, (2) understanding the positive impacts of the stress reduction program, and (3) suggested strategies to enhance program desirability. IBD was described as causing uncertainty, significant disruptions to daily activities, and stress, which in turn worsened symptoms. The online program was associated with a perceived reduction in IBD symptom burden, an increased ability to manage daily and disease-associated stressors, and a more positive mindset. Variation in program content and fostering connections with others in the IBD community were identified as potential strategies to enhance future programming.

Conclusions

This qualitative companion study highlights the power of the patient voice to deepen our understanding of the impact of IBD, and the potential benefit of an online stress reduction program including suggestions for iterative refinement.
Inferior vena cava filter limb embolization to the right ventricle: a case report
Authors: Knox Abbey , Gimpel Damian , Harjit Singh Rajinder Singh , Burdeniuk Christine , Bennetts Jayme S
Published: September 2022

Background

Inferior vena cava (IVC) filters are used to prevent pulmonary embolism (PE) in patients at a high risk for venous thromboembolism with a contraindication to anticoagulation. Inferior vena cava filters are associated with rare but significant long-term complications such as filter fracture and embolization.

Case summary

We report the case of a 53-year-old female with an IVC filter inserted 8 years back for the management of recurrent bilateral PE resistant to anticoagulation. Imaging revealed an incidental finding of IVC filter limb fracture and migration to the right heart and the hepatic and renal veins. The patient remained asymptomatic with no impairment in cardiac, liver, or renal function. Due to a high operative risk, the broken IVC filter and embolized filter limbs were not retrieved.

Discussion

There is no consensus on the management of intracardiac embolization of IVC filters. Intravascular fragments may be removed by endovascular or surgical approaches, depending on the anatomical location. Following IVC filter insertion, an appropriate follow-up must be put in place to ensure removal and limit clinical sequelae that are otherwise avoidable. A multidisciplinary approach to the management of IVC filter fracture and embolization is recommended.
NESM: a network embedding method for tumor stratification by integrating multi-omics data
Authors: Li Feng , Sun Zhensheng , Liu Jin-Xing , Shang Junliang , Dai Lingyun , Liu Xikui , Li Yan
Published: September 2022

Tumor stratification plays an important role in cancer diagnosis and individualized treatment. Recent developments in high-throughput sequencing technologies have produced huge amounts of multi-omics data, making it possible to stratify cancer types using multiple molecular datasets. We introduce a Network Embedding method for tumor Stratification by integrating Multi-omics data. Network Embedding method for tumor Stratification by integrating Multi-omics pregroup the samples, integrate the gene features and somatic mutation corresponding to cancer types within each group to construct patient features, and then integrate all groups to obtain comprehensive patient information. The gene features contain network topology information, because it is extracted by integrating deoxyribonucleic acid methylation, messenger ribonucleic acid expression data, and protein–protein interactions through network embedding method. On the one hand, a supervised learning method Light Gradient Boosting Machine is used to classify cancer types based on patient features. When compared with other 3 methods, Network Embedding method for tumor Stratification by integrating Multi-omics has the highest AUC in most cancer types. The average AUC for stratifying cancer types is 0.91, indicating that the patient features extracted by Network Embedding method for tumor Stratification by integrating Multi-omics are effective for tumor stratification. On the other hand, an unsupervised clustering algorithm Density-Based Spatial Clustering of Applications with Noise is utilized to divide single cancer subtypes. The vast majority of the subtypes identified by Network Embedding method for tumor Stratification by integrating Multi-omics are significantly associated with patient survival.
The Association Between Midlife Leisure-Time Physical Activity and Hearing Loss in Late Life in the Atherosclerosis Risk in Communities Study
Authors: Martinez-Amezcua Pablo , Garcia Morales Emmanuel , Gabriel Kelley P , Dooley Erin E , Hornikel Bjoern , Coresh Josef , Lin Frank R , Pankow James S , Sharrett A Richey , Schrack Jennifer A , Sullivan Kevin J , Reed Nicholas , Deal Jennifer A , Palta Priya
Published: September 2022

Background

Hearing loss is highly prevalent in older ages and has several health consequences. Some cardiovascular risk factors are associated with worse hearing at older ages. Still, the role of midlife leisure-time physical activity (PA) as a risk factor for hearing loss is yet to be investigated.

Methods

Among 3 198 participants of the Atherosclerosis Risk in Communities study, we investigated the associations of midlife and change from mid- to late-life PA (assessed via modified Baecke questionnaire) with hearing loss (audiometric battery [worse-ear pure-tone average, and speech-in-noise test]) at older ages. We used regression analyses, adjusted for demographics, medical conditions, and noise exposure, to estimate differences in hearing between those who met and did not meet PA recommendations at midlife and at late life.

Results

A total of 1 386 (43.3%) participants met PA recommendations at midlife. These participants, compared to those who did not meet recommendations, had lower (better) pure-tone average by 1.51 (0.46, 2.55) decibels, identified 0.37 (0.01, 0.74) more words (better score) in the speech-in-noise test, and had a lower relative risk of having hearing loss at older ages (eg, relative risk ratio for severe hearing loss vs normal hearing = 0.70 [0.52, 0.95]). Similarly, those who persistently met PA recommendations from mid- to late life had, compared with those who did not, a better hearing at older ages.

Conclusions

Meeting PA public health recommendations in midlife and mid- to late life was associated with better hearing at older ages and reduced risk of hearing loss. Promoting adequate levels of PA may be an essential component of hearing care.
Angiotensin (1–7) Delivered Orally via Probiotic in Combination With Exercise: Sex-Dependent Influence on Health Span
Authors: Hernandez Abbi , Sun Yi , Banerjee Anisha , Yang YouFeng , Verma Amrisha , Li Qiuhong , Baptista Liliana , Buford Thomas W , Carter Christy S
Published: September 2022

Age-related declines in physical and cognitive function can have tremendous, negative impacts on health span and quality of life. Therefore, we investigated the potential of utilizing a probiotic treatment to target the renin–angiotensin system (RAS) in conjunction with moderate exercise to ameliorate age-related declines in cognitive and physical function in aged rats. Herein we utilized a genetically modified angiotensin (1–7), which activates a “complementary” arm of the RAS through binding Mas (AT7) receptors. This process induces several beneficial physiologic effects, including decreased inflammation and enhanced physical/cognitive function. Thus, in this short research report, we suggest the efficacy of this Ang(1-7) releasing Lactobacillus paracasei (LPA) as either an alternative strategy to exercise, or more likely as an adjuvant to moderate exercise, for the prevention of both physical and cognitive decline especially in female rats.
Blunted Rest–Activity Circadian Rhythm Is Associated With Increased Rate of Biological Aging: An Analysis of NHANES 2011–2014
Authors: Xu Yanyan , Wang Xiaoling , Belsky Daniel W , McCall William V , Liu Yutao , Su Shaoyong
Published: September 2022

Impaired rest–activity circadian rhythm has been associated with increased risk for morbidity and mortality. Animals with mutations in clock genes display accelerated aging and shortened life span. Whether impaired rest–activity circadian rhythm is also associated with processes of aging in humans has not been explored. We analyzed accelerometry and physiological data from 7 539 adults participating in the 2011–2014 waves of the U.S. National Health and Nutrition Examination Surveys. We used accelerometry data to compute rest–activity rhythm measurements. We used physiological data to compute measurements of biological aging according to 3 published algorithms: Klemera–Doubal method (KDM) Biological Age, PhenoAge, and homeostatic dysregulation (HD). In the models adjusting multiple covariates, participants with higher relative amplitude (RA) and interdaily stability (IS) and lower intradaily variability (IV) exhibited less advanced biological aging indexed by KDM and PhenoAge (effect sizes for 1-quantile increase in these rest–activity measurements ranged from 0.54 to 0.57 “years” for RA, 0.24 to 0.28 “years” for IS, and 0.24 to 0.35 “years” for IV, ps < .001). Similar finding was observed for biological aging indexed by HD, but the significance was limited to RA with 1-quantile increase in RA associated with 0.09 log units decrease in HD (p < .001). The results indicate that blunted rest–activity circadian rhythm is associated with accelerated aging in the general population, suggesting that interventions aiming at enhancing circadian rhythm may be a novel approach for the extension of a healthy life span.
Changes in Grandparental Childcare During the Pandemic and Mental Health: Evidence From England
Authors: Di Gessa Giorgio , Bordone Valeria , Arpino Bruno
Published: September 2022

Objectives

Policies aiming at reducing rates of hospitalization and death from coronavirus disease 2019 (COVID-19) encouraged older people to reduce physical interactions. In England, until July 2021, provision of care for grandchildren was allowed only under very limited circumstances. Evidence also suggests that reduced face-to-face interactions took a toll on mental health during the pandemic. This study aims to investigate associations between changes in grandchild care provision during the first 8/9 months of the pandemic and grandparents’ mental health.

Methods

Using prepandemic data from Wave 9 (2018/2019) and the second COVID-19 substudy (November/December 2020) of the English Longitudinal Study of Ageing, we first describe changes in grandchild care provision during the pandemic to then investigate, using regression models, associations between changes in grandchild care provision and mental health (depression, quality of life, life satisfaction), while controlling for prepandemic levels of the outcome variables.

Results

About 10% of grandparents stopped looking after grandchildren altogether during the first 9 months of the pandemic, with 22% reporting an overall decrease in the amount of grandchild care provided. Compared to grandparents who mostly maintained unchanged their grandchild care provision, those who stopped altogether and those who mostly reduced the amount of grandchild care provided were more likely to report poorer mental health, even accounting for prepandemic health.

Discussion

While measures to limit physical contact and shield older people were necessary to reduce the spread of COVID-19, policymakers should acknowledge potential adverse consequences for mental health among grandparents who experienced changes in their roles as grandchild caregivers.
Relationship Quality Change Among Partnered Older Adults During the COVID-19 Pandemic
Authors: Wong Jaclyn S , Zhong Selena , Liu Hui
Published: September 2022

Objectives

The coronavirus disease 2019 (COVID-19) pandemic dramatically changed social life, but we know less about whether partnered relationships changed during this time. Because high-quality intimate relationships are key to many older Americans’ well-being, we explore whether, how, and for whom the pandemic changed relationship quality among partnered older Americans.

Methods

Nationally representative data from 1,642 partnered adults aged 50 and older come from the 2020 National Social Life, Health, and Aging Project COVID-19 Study. Multinomial logistic regression analyses estimate the likelihood of reporting improved, unchanged, or worsened relationship quality since the pandemic began across sociodemographic groups.

Results

Two thirds of respondents reported that relationship quality stayed the same during the pandemic, 22.8% reported their relationship quality got better, and 10.5% reported their relationship quality got worse. Although women and the oldest old were less likely to report improved relationship quality, Black respondents were more likely to do so, even after controlling for explanatory variables.

Discussion

Resilience describes many partnered older adults’ experiences during the first year of the pandemic, suggesting that they were able to protect their partnerships during this public health crisis.
The Dynamics of Daily Life in Custodial Grandmothers
Authors: Infurna Frank J , Castro Saul A , Webster Britney A , Dolbin-MacNab Megan L , Smith Gregory C , Max Crowley D , Musil Carol
Published: September 2022

Objective

Guided by a life-course perspective, we examine the nature of daily life among custodial grandmothers (CGM) through documenting daily positive and negative affect, reporting daily negative and positive events, and emotional reactivity/responsiveness to daily negative and positive events. We also examine whether CGM age, adverse childhood experiences (ACEs), and social relationship quality with grandchild are associated with each indicator.

Methods

We applied multilevel models to 200 CGM (Mage = 61, SD = 5.66) who were recruited from across the United States and completed a daily survey for 14 consecutive days prior to commencing a randomized clinical trial.

Results

Older age and reporting fewer ACEs were associated with better overall and less variability in daily well-being. Positive events were reported on 83% of days and negative events were reported on 56% of days. Daily well-being was lower when a negative event was reported and higher when a positive event was reported. Reporting more ACEs was associated with greater exposure to daily negative events and stronger gains in daily well-being when a daily positive event was reported. Older age was associated with lesser declines in daily well-being on days when a negative event was reported.

Discussion

In accordance with the life-course perspective, our findings illustrate how the timing of being a CGM (age) and the cumulative nature of development (ACEs) affect daily well-being and negative and positive events for CGM. Our discussion focuses on resources to consider when building resilience-focused interventions for promoting the health and well-being of CGM.
Second Medical Use Patents and Compensation for the Delay in Marketing Authorisations: The Curious Case of Vietnam
Authors: Le Van Anh
Published: September 2022

There has been a concern that developing countries which join new-generation FTAs might jeopardise their population’s access to medicines because those FTAs mandate TRIPS-plus patent standards. This article, however, argues that Vietnam, through its unusual legislative steps, has avoided increasing patent protection for medicines without (yet) violating international obligations. Its practice is examined via two specific patent-related issues: second medical uses and compensation for the delay in marketing authorisations. Regarding the first issue, the author finds that the law is deliberately ambiguous, as it neither rejects nor allows second medical use inventions. Regarding the second issue, Vietnam’s newly amended law in 2022 has arguably adopted a unique form of compensation: it waives the patent maintenance fees instead of extending the patent term. The paper concludes that because of the country’s sluggish local industry as well as its legislators’ struggle to keep pace with increasingly changing IP standards in the new FTAs, language ambiguity and lip service have become Vietnam’s weapons of choice.
Social progress and corporate culture
Authors: Gorton Gary B , Zentefis Alexander K
Published: September 2022

Social progress through improved treatment of minority groups (e.g., forbidding racial or sexual harassment) may or may not spread to corporate cultures through competition. We provide a theory of corporate culture, and we show that emergent, progressive corporate cultures can displace existing, regressive ones when the prevailing wage gap is large between majority and minority groups. The model provides testable predictions on racial and gender wage gaps across firms.
Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Shedding and Predictors of Viral Culture Positivity on Vaccinated Healthcare Workers With Mild Coronavirus Disease 2019
Authors: Luna-Muschi Alessandra , Noguera Saidy Vásconez , Borges Igor C , De Paula Anderson V , Côrtes Marina Farrel , Larocca Carolina , Mari Julia Ferreira , Guimarães Lara Silva Pereira , Torres Pablo Munoz , Scaccia Nazareno , Villas-Boas Lucy S , da Silva Almir Ribeiro , Andrade Pâmela S , Teixeira Juliana C , Escadafal Camille , de Oliveira Vitor Falcão , Tozetto-Mendoza Tania R , Mendes-Correa Maria Cássia , Levin Anna S , Sabino Ester C , Costa Silvia F
Published: September 2022

In this prospective cohort of 30 vaccinated healthcare workers with mild Omicron variant infection, we evaluated viral culture, rapid antigen test (RAT), and real-time reverse-transcription polymerase chain reaction (RT-PCR) of respiratory samples at days 5, 7, 10, and 14. Viral culture was positive in 46% (11/24) and 20% (6/30) of samples at days 5 and 7, respectively. RAT and RT-PCR (Ct ≤35) showed 100% negative predictive value (NPV), with positive predictive values (PPVs) of 32% and 17%, respectively, for predicting viral culture positivity. A lower RT-PCR threshold (Ct ≤24) improved culture prediction (PPV = 39%; NPV = 100%). Vaccinated persons with mild Omicron infection are potentially transmissible up to day 7. RAT and RT-PCR might be useful tools for shortening the isolation period.
Soleris® Automated System for the Rapid Detection of Burkholderia cepacia Complex in Cosmetic Products
Authors: Zhang Lei , Tolan Jerry , Lavigne Nicholas , Montei Carolyn , Donofrio Robert , Biswas Preetha
Published: September 2022

Background

Burkholderia cepacia complex (Bcc) has emerged as an important opportunistic pathogen with rising concern in pharmaceuticals and cosmetic products. The Bcc supplement (S2-BCC-S) was purposely developed and used with the Pseudomonas vial (PD-109) for the detection of Bcc through the Soleris® Next Generation automated instrument system.

Objective

This study aimed to evaluate the performance of the Soleris Bcc testing method for cosmetic products.

Method

Inclusivity and exclusivity were assessed with the Soleris Bcc method and the United States Pharmacopeia (USP) method in three enrichment broths. Matrix testing was conducted using 28 cosmetic products to compare the equivalency of the Soleris Bcc method to that of the USP reference method. Repeatability of the Soleris Bcc assay, method robustness, product stability, and lot-to-lot consistency of the Soleris reagents were also assessed.

Results

Both the Soleris Bcc and the USP methods supported the growth of all 26 inclusivity strains, except the USP method missed one inclusivity strain in one broth. For exclusivity, 0–6% was presumptive positive with the Soleris Bcc method, and 42–48% was presumptive positive with the reference method. Kappa index was 0.96 for the matrix testing, indicating a good agreement between the Soleris Bcc assay and the reference method for testing Bcc in cosmetics. Repeatability results showed the coefficient of variation was less than 4%. The robustness and ruggedness study yielded detection times within 1 h differences when small variations were introduced. The lot-to-lot study showed consistent results among four lots of the Bcc reagents.

Conclusions

The automated Soleris method was successfully demonstrated to be robust, sensitive, and specific for Bcc detection in cosmetic products.

Highlights

The Soleris Bcc method is user-friendly. It shows the results in real time and generates the report automatically. Implementation of this method for detection of Bcc in cosmetics would save significant time and resources.
Microextraction by Packed Sorbent as a Clean-up Approach for the Determination of Ketamine and Norketamine in Hair by Gas Chromatography--Tandem Mass Spectrometry
Authors: Simão A Y , Oliveira P , Rosendo L M , Rosado T , Andraus M , Barroso M , Gallardo E
Published: September 2022

The use of new psychoactive substances has been increasing and constitutes a social and public health problem, and hence, toxicological analysis has become of utmost importance for the detection of such substances. In this article, we present the development and full validation of a simple, user and environmentally friendly, cheap and suitable method for the determination of ketamine and its main metabolite norketamine in hair samples. The procedure included using a miniaturized procedure—microextraction by packed sorbent with mixed-mode sorbent—for sample clean-up. Organic solvents use was minimal, and it was possible to obtain a linear method (0.05–10 ng/mg for both analytes). The extraction efficiency ranged from 32 to 61%, which did not impair sensitivity. The method proved to be selective, precise, accurate and suitable for routine analysis for the determination of said compounds in 50-mg hair samples.
P018 Susceptibility profile of Candida albicans causing bloodstream infections against azole antifungals over 5 years: A prospective observational study
Authors: Sharma Megha , Ahmad Raees , Ghosh Anup , Rudramurthy Shivaprakash , Chakrabarti Arunaloke
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

To study the drug susceptibility profile of Candida albicans isolated from bloodstream infection (BSI) against azole anti-fungal agents (fluconazole, itraconazole, voriconazole, and posaconazole) in a tertiary care hospital over 5 years.

Methods

All blood culture bottles from patients attending our tertiary care hospital between January 2017 to December 2021 and growing Candida albicans were included in the analysis. All blood culture bottles were continuously monitored automatically inside BACTEC 9240 (BD Becton Dickinson, USA). Beep-positive bottles were further processed by preparation of Gram stain smears, sub-culture onto 5% sheep blood agar and MacConkey agar and spot inoculation onto Sabouraud's Dextrose agar (SDA). Isolates were identified as C. albicans using MALDI-TOF MS (Bruker Daltoniks, Bremen, Germany). Broth microdilution (BMD) was performed to determine minimum inhibitory concentration (MIC) of fluconazole, itraconazole, voriconazole, and posaconazole, in accordance with CLSI document M27-A3 and CLSI M27-S4. Representative isolates were further processed to determine the genetic basis of azole resistance (results will be shared at the conference).

Results

A total of 889 C. albicans were isolated from BSI over 5 years. The rates of resistant were 0.9%, 4.3%, and 1.4%; and that of susceptible dose dependent were 0.8%, 28.5%, and 0.4% for fluconazole, itraconazole, and voriconazole respectively (Fig. 1). The MIC90 of the isolates to fluconazole, itraconazole, voriconazole, and posaconazole were 2 μg/ml, 0.25 μg/ml, 0.5 μg/ml and 0.25 μg/ml, respectively (Fig. 2).

Conclusion

Azole antifungals continue to retain favorable MIC90 against C. albicans BSI isolates. Flucanozole continues to be the favored drug of choice due to low side-effects, cost-effectiveness, and least resistant rates.
P056 Oral Ibrexafungerp outcomes by fungal disease in patients from an interim analysis of a Phase 3 Open-label Study (FURI)
Authors: Prattes Juergen , King Thomas , Azie Nkechi , Angulo David
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Background

There are limited oral treatment options for patients with fungal infections who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of, or with fungal disease refractory to, standard antifungal therapy. We present an interim analysis of patient outcomes from the FURI study by fungal disease type.

Methods

FURI patients are eligible for enrollment if they have proven or probable: severe mucocutaneous candidiasis, invasive candidiasis, chronic or invasive aspergillosis, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options (e.g., due to susceptibility), and continued IV antifungal therapy is clinically undesirable or unfeasible.

Results

An independent Data Review Committee (DRC) provided an assessment of treatment response for 113 enrolled patients in the FURI study from 27 centers in US, UK, and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016-2021. A total of 56 patients (49.5%) had invasive candidiasis/candidemia, 32 (28.3%) had mucocutaneous candidiasis, 14 (12.4%) had vulvovaginal candidiasis (VVC), and 11 (9.7%) patients had aspergillosis.

Upon DRC review, the percentage of patients with complete or partial response, or for VVC, clinical improvement (defined as vulvovaginal signs and symptoms score ≤ 1) was 58.4%; stable disease was 23.9%; and 11.5% had disease progression (including 2 VVC patients not meeting the criteria for clinical improvement). There was one death due to underlying causes, and six outcomes were indeterminate. Table 1 shows outcomes by disease type.

Conclusions

Analysis of 113 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options.
P060 A preliminary in vitro and in vivo evaluation of the effect and action mechanism of 17-AAG combined with azoles against azole-resistant Candida spp.
Authors: Liu Md Luyao
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Invasive candidiasis is the primary reason for the increasing cases of mortality in a medical environment. The resistance spectra of Candida species to antifungal drugs, among which Candida auris is the most prominent, have gradually expanded.

Objectives

Hsp90 plays a protective role in the stress response of fungi and facilitates their virulence. In contrast, Hsp90 inhibitors can improve the resistance of fungi to antifungal drugs by regulating the heat resistance of Hsp90 and thereby destroying the integrity of the fungal cell walls. Therefore, we used Hsp90 inhibitor in combination with different antifungal drugs to explore its antifungal effect and mechanism.

Methods

The drugs tested for the resistance included itraconazole, voriconazole, posaconazole, fluconazole, and 17-AAG. A total of 20 clinical strains of Candida were investigated. The broth microdilution checkerboard technique, as adapted from the CLSI M27-A4 method, was applied in this study. At the same time, the effect of 17-AAG combined with antifungal drugs on the formation of Candida biofilm was observed, and the animal experiment of C. mellonella was carried out in vivo. Moreover, we determined that with the use of rhodamine 6 G to detect drug efflux and that of dihydrorhodamine-123 to detect intracellular reactive oxygen species (ROS).

Results

We found that 17-AAG alone exerted limited antifungal activity against all tested strains. The MIC range of 17-AAG was 8 to >32 μg/ml. The synergy among 17-AAG and itraconazole, voriconazole, and posaconazole was observed against 10 (50%), 7 (35%), and 13 (65%) of all isolates, respectively. Moreover, the synergy between 17-AAG and fluconazole was observed against 5 (50%) stains of azole-resistant Candida. However, no antagonism was recorded. In vivo test, the combination group also significantly prolonged the infection event and improved the survival of larvae. Treatment with 17-AAG combined with azole drugs inhibited the efflux pump of fungi and promoted the accumulation of ROS in the fungal cells.

Conclusion

Our result adequately verifies the influence of 17-AAG on the formation of Candida spp. biofilm. The mechanism of 17-AAG combined with azoles could kill fungi by inhibiting drug efflux and increasing intracellular reactive oxygen species. These results thereby provide a new idea to further explore drugs against drug-resistant Candida spp.
P116 Cutaneous fungal infections in elderly population from Bhopal
Authors: Venkatesan Sevitha , Tadepalli Karuna , Asati Dinesh P. , Maurya Anand K. , Bhadade Arati , Gupta Aditi , Saxena Gaurav , Badal Rahul
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

Methods

Hospital-based cross-sectional study for 5-year duration January 2017-December 2021. Study location is the department of Microbiology AIIMS, Bhopal. Elderly patients (60 years and above) visiting as Outpatient and Inpatient of dermatology and venereology, General Medicine, and other departments with cutaneous infections suspected to be of fungal etiology and fulfilling the inclusion criteria comprised the study population. Patients already on antifungals topical or systemic were excluded. Data extraction was based on predesigned proforma for a detailed history and clinical examination entries. Necessary ethical approval and patient consent were obtained. Samples of skin, hair, nail, and exudates were processed for direct microscopy, culture isolation in suitable media, and identification phenotypically.

Results

A total of 480 elderly patients clinically suspected of cutaneous fungal infections were included in the study. Majority of the suspected cases were in 60–70 years age group 360/480 (75%). Males were 349/480 (72.71%) and females were 131/480 (27.29%) of the total suspected cases. Male to female ratio in study population was 2.66: 1. Tinea corporis 140/480 cases (29.17%) was most common clinical type followed by onychomycosis 64/480 cases (13.33%), ulcerations 62/480 (12.92%), T. cruris 56/480 (11.67%), T. pedis 35/480 (7.29%), T. mannum 25/480 (5.21%), and T. facei 12/480 (2.50%) in suspected cases of cutaneous fungal infection. Majority of cases were found in non-dependent 253/480 (52.70%) population. Out of 480 clinically suspected cases of cutaneous fungal infection was demonstrated in 193 cases (40.20%) either by direct microscopy and/or culture.

A total of 176/480 cases (36.67%) were KOH positive and 113(23.54%) cases were culture positive.

Taking culture as a gold standard sensitivity and specificity of KOH in diagnosing fungal infection was 84.96% and 78.2% respectively. Among 113 culture isolates dermatophytes 53.10% (60/113) were most common mold isolates followed by non-dermatophyte molds 28.3% (32/113), and yeasts 18.59% (21/113). Trichophyton mentagrophytes most common 21.24% followed by T. tonsurans 9.73%, and T. violaceum 7.96% are the common dermatophyte isolates. Aspergillus species is the most common non-dermatophyte mold isolated.

Diabetes was the most common comorbid condition in culture-confirmed cases followed by hypertension and thyroid disorder.

Conclusion

This study showed the prevalence of cutaneous fungal infection among elderly visiting AIIMS, Bhopal as 23.54% (113/480). With increase in elderly population, changing environmental conditions, and association with non-communicable diseases it becomes important that all elderly patients visiting hospital OPD and those hospitalized for long should be evaluated for fungal infections especially cutaneous.