bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualising Emergency Department Wait Times; Rapid Iterative Testing to Determine Patient Preferences for Displays
Authors: Walker Katie , Potter Eden , Hwang Indae , Dwyer Tim , Egerton-Warburton Diana , Joe Keith , Hutton Jennie , Freeman Sam , Flynn Daphne
Published: April 2022

Visualising patient wait times in emergency departments for patients and families is increasingly common, following the development of prediction models using routinely collected patient demographic, urgency and flow data. Consumers of an emergency department wait time display will have culturally and linguistically diverse backgrounds, are more likely to be from under-served populations and will have varied data literacy skills. The wait times are uncertain, the information is presented when people are emotionally and physically challenged, and the predictions may inform high stakes decisions. In such a stressful environment, simplicity is crucial and the visual language must cater to the diverse audience. When wait times are conveyed well, patient experience improves. Designers must ensure the visualisation is patient-centred and that data are consistently and correctly interpreted. In this article, we present the results of a design study at three hospitals in Melbourne, Australia, undertaken in 2021. We used rapid iterative testing and evaluation methodology, with patients and families from diverse backgrounds as participants, to develop and validate a wait time display. We present the design process and the results of this project. Patients, families and staff were eligible to participate if they were awaiting care in the emergency department, or worked in patient reception and waiting areas. The patient-centred approach taken in our design process varies greatly from past work led by hospital administrations, and the resulting visualisations are very distinct. Most currently displayed wait time visualisations could be adapted to better meet end-user needs. Also of note, we found that techniques developed by visualisation researchers for conveying temporal uncertainty tended to overwhelm the diverse audience rather than inform. There is a need to balance precise and comprehensive information presentation against the strong need for simplicity in such a stressful environment.
Patterns of antibiotic cross-resistance by bacterial sample source: a retrospective cohort study
Authors: Cherny Stacey S. , Chowers Michal , Obolski Uri
Published: April 2022

Background and objectives

Antimicrobial resistance is a major healthcare burden, aggravated when it extends to multiple drugs. While cross-resistance is well-studied experimentally, it is not the case in clinical settings, and especially not while considering confounding variables. In addition, bacteria from different sample sources may have undergone different evolutionary trajectories, therefore examining cross-resistance across sources is desirable.

Methodology

We employed additive Bayesian network (ABN) modelling to examine antibiotic cross-resistance in five major bacterial species, obtained from different sources (urine, wound, blood, and sputum) in a clinical setting, collected in a large hospital in Israel over a 4-year period. ABN modelling allowed for examination of the relationship between resistance to different drugs while controlling for major confounding variables.

Results

Patterns of cross-resistance differed across sample sources. All identified links between resistance to different antibiotics were positive, and most were present in several culture sources. However, in 15 of 18 instances, the magnitudes of the links were significantly different between sources compared. For example, E coli exhibited adjusted odds ratios of gentamicin-ofloxacin cross-resistance ranging from 3.0 (95%CI [2.3,4.0]) in urine samples to 11.0 (95%CI [5.2,26.1]) in blood samples.

Conclusions and implications

Our results highlight the importance of considering sample sources when assessing likelihood of antibiotic cross-resistance and determining antibiotic treatment regimens and policies.

Abstract Importance

We examine the patterns of antibiotic resistance of a given bacterial species, obtained from different clinical infection locations, while accounting for potentially relevant clinical variables. We find that such patterns of cross-resistance between pairs of antibiotics vary between culture sources (e.g., urine vs blood samples), indicating different selective pressures. These findings have implications on prescription policies aiming to minimize collateral resistance.
The impact of COVID-19 pandemic on influenza surveillance: a systematic review and meta-analysis
Authors: Sabeena Sasidharanpillai , Ravishankar Nagaraja , Robin Sudandiradas
Published: April 2022

Background

Influenza activity was reported to be below the seasonal levels during the COVID-19 pandemic globally. However, during the SARS-CoV-2 outbreak, the routine real-time surveillance of influenza like illness (ILI) and acute respiratory infection (ARI) was adversely affected due to the changes in priorities, economic constraints, repurposing of hospitals for COVID care and closure of outpatient services.

Methods

A systematic review and meta-analysis were carried out to assess the pooled proportion of symptomatic cases tested for influenza virus before the current pandemic in 2019 and during the pandemic in 2020/21. An electronic search of PubMed/MEDLINE, Scopus and Google Scholar was carried out for the articles reporting the impact of the COVID-19 pandemic on Influenza surveillance among humans using search terms. The study was designed based on PRISMA guidelines and the meta-analysis was performed to synthesise the pooled proportion of patients sampled for influenza with 95% confidence interval (CI).

Results

The nine qualified studies from the WHO-European region, Canada, Japan, Germany, Italy, Spain, South Africa and the United States were pooled by random-effects meta-analysis. The overall pooled proportion of symptomatic cases sampled for influenza surveillance before and during the pandemic was 2.38% (95% CI 2.08%-2.67%) and 4.18% (95% CI 3.8%-4.52%) respectively. However, the pooled proportion of samples tested for influenza before the pandemic was 0.69% (95% CI 0.45-0.92%) and during the pandemic was 0.48% (95% CI 0.28-0.68%) when studies from Canada were excluded.

Conclusion

The meta-analysis concludes that globally there was a decline in influenza surveillance during the COVID-19 pandemic except in Canada.

Key Messages

The nine observational studies from Europe, Canada, Japan, South Africa and the United States were qualified for the meta-analysis

A steep decline in the seasonal influenza activity in both northern and southern hemispheres was observed

Almost double the number of symptomatic cases were sampled as part of influenza surveillance during the current pandemic in Canada

Except in Canada, a decline in influenza surveillance globally during the COVID-19 pandemic was observed
If you build it, will they use it? Use of a Digital Assistant for Self-Reporting of COVID-19 Rapid Antigen Test Results during Large Nationwide Community Testing Initiative
Authors: Herbert Carly , Shi Qiming , Kheterpal Vik , Nowak Chris , Suvarna Thejas , Durnam Basyl , Schrader Summer , Behar Stephanie , Naeem Syed , Tarrant Seanan , Kalibala Ben , Singh Aditi , Gerber Ben , Barton Bruce , Lin Honghuang , Cohen-Wolkowiez Michael , Corbie-Smith Giselle , Kibbe Warren , Marquez Juan , Baek Jonggyu , Hafer Nathaniel , Gibson Laura , O’Connor Laurel , Broach John , Heetderks William , McManus David , Soni Apurv
Published: April 2022

Importance

Wide-spread distribution of rapid-antigen tests is integral to the United States’ strategy to address COVID-19; however, it is estimated that few rapid-antigen test results are reported to local departments of health.

Objective

To characterize how often individuals in six communities throughout the United States used a digital assistant to log rapid-antigen test results and report them to their local Department of Health.

Design

This prospective cohort study is based on anonymously collected data from the beneficiaries of The Say Yes! Covid Test program, which distributed 3,000,000 rapid antigen tests at no cost to residents of six communities between April and October 2021. We provide a descriptive evaluation of beneficiaries’ use of digital assistant for logging and reporting their rapid antigen test results.

Main Outcome and Measures

Number and proportion of tests logged and reported to the Department of Health through the digital assistant

Results

A total of 178,785 test kits were ordered by the digital assistant, and 14,398 households used the digital assistant to log 41,465 test results. Overall, a small proportion of beneficiaries used the digital assistant (8%), but over 75% of those who used it reported their rapid antigen test results to their state public health department. The reporting behavior varied between communities and was significantly different for communities that were incentivized for reporting test results (p < 0.001). In all communities, positive tests were less reported than negative tests (60.4% vs 75.5%; p<0.001).

Conclusions and Relevance

These results indicate that app-based reporting with incentives may be an effective way to increase reporting of rapid tests for COVID-19; however, increasing the adoption of the digital assistant is a critical first step.
The HIV and STI syndemic following mass scale-up of combination HIV interventions in Uganda: a population-based cross-sectional study
Authors: Grabowski M. Kate , Mpagazi Josephine , Kiboneka Stephen , Ssekubugu Robert , Kereba John Baptiste , Nakayijja Annet , Tukundane Julius , Jackson Jade , Peer Austin D. , Kennedy Caitlin , Kigozi Godfrey , Galiwango Ronald M. , Manabe Yuka , Chang Larry W. , Kalibala Sarah , Gray Ronald H , Wawer Maria J , Reynolds Steven J , Tobian Aaron AR , Serwadda David , Gaydos Charlotte A. , Kagaayi Joseph , Quinn Thomas C
Published: April 2022

Background

Combination HIV interventions (CHIs) have led to significant declines in HIV incidence in sub-Saharan Africa; however, population-level data on non-HIV sexually transmitted infection (STI) burden in the context of CHIs are rare. We aimed to assess STI burden in Uganda following mass scale-up of CHIs, including universal HIV treatment.

Methods

The Sexually Transmitted Infection Prevalence Study (STIPS) was a cross-sectional study nested within the Rakai Community Cohort Study (RCCS), a population-based cohort among inland agrarian and Lake Victoria fishing populations in southern Uganda. STIPS enrolled consenting participants, 18-49 years, between May and October 2019 and measured prevalence ofChlamydia trachomatis(chlamydia),Neisseria gonorrhoeae(gonorrhea),Trichomonas vaginalis(trichomonas), syphilis, and herpes simplex virus type 2 (HSV-2).

Findings

STIPS enrolled 1,825 participants, including 965 women (53%), of whom 9% (n=107) were pregnant. Overall, there was 9.8% prevalence of chlamydia (95%CI:8.5-11%), 6.7% gonorrhea (95%CI:5.7-8.0%), and 11% trichomonas (95%CI:9.5-12%). In the fishing population, syphilis reactivity was 24% (95%CI:22-27%), with 9.4% (95%CI:7.7-11%) having high titer (RPR ≥ 1:8) infection, including 17% (95%CI:12-24%) of HIV-positive men. Prevalence of ≥ 1 curable STI (chlamydia, gonorrhea, trichomonas, or high titer syphilis) was 44% higher among HIV-positive persons (adjusted prevalence risk ratio [adjPRR]=1.44,95%CI:1.22-1.71), with no differences by HIV treatment status. HIV-positive pregnant women were more likely than HIV-negative pregnant women to have a curable STI (adjPRR=1.87, 95%CI: 1.08-3.23).

Interpretation

STI burden remains extremely high in Uganda, particularly among HIV-positive persons. There is an urgent need to integrate STI diagnostic testing and treatment with HIV services in African settings.

Funding

National Institutes of Health
Latent Factors of Language Disturbance and Relationships to Quantitative Speech Features
Authors: Tang Sunny X. , Hänsel Katrin , Cong Yan , Nikzad Amir H. , Mehta Aarush , Cho Sunghye , Berretta Sarah , Behbehani Leily , Pradhan Sameer , John Majnu , Liberman Mark Y.
Published: April 2022

Background and Hypothesis

Quantitative acoustic and textual measures derived from speech (“speech features”) may provide valuable biomarkers for psychiatric disorders, particularly schizophrenia spectrum disorders (SSD). We sought to identify cross-diagnostic latent factors for speech disturbance with relevance for SSD and computational modeling.

Study Design

Clinical ratings for speech disturbance were generated across 14 items for a cross-diagnostic sample (N=343), including SSD (n=97). Speech features were quantified using an automated pipeline for brief recorded samples of free-speech. Factor models for the clinical ratings were generated using exploratory factor analysis, then tested with confirmatory factor analysis in the cross-diagnostic and SSD groups. Relationships among factor scores, speech features and other clinical characteristics were examined using network analysis.

Study Results

We found a 3-factor model with good fit in the cross-diagnostic group and acceptable fit for the SSD subsample. The model identifies an impaired expressivity factor and two interrelated disorganized factors for inefficient and incoherent speech. Incoherent speech was specific to psychosis groups, while inefficient speech and impaired expressivity showed intermediate effects in people with nonpsychotic disorders. Network analysis showed that the factors had distinct relationships with speech features, and that the patterns were different in the cross-diagnostic versus SSD groups.

Conclusions

We report a cross-diagnostic 3-factor model for speech disturbance which is supported by good statistical measures, intuitive, applicable to SSD, and relatable to linguistic theories. It provides a valuable framework for understanding speech disturbance and appropriate targets for modeling with quantitative speech features.
Hippocampal CA1 represents action and reward events instantly compared to the superficial and deep layers of the lateral entorhinal cortex
Authors: Soma Shogo , Ohara Shinya , Nonomura Satoshi , Yoshida Junichi , Suematsu Naofumi , Pastalkova Eva , Sakai Yutaka , Tsutsui Ken-Ichiro , Isomura Yoshikazu
Published: April 2022

The entorhinal cortex (EC) is the main interface between the hippocampus and the neocortex. The EC plays a critical role in learning and memory. We investigated the neuronal representation of behavioral events during operant learning in the hippocampal-entorhinal circuit of head-fixed rats. Both CA1 and lateral entorhinal cortex (LEC) neurons develop task-related activities after learning. Among diverse task-related activities, we compared the transient peak activities that represent action and reward and found a distinct difference in the timing of behavioral event representation between CA1 and LEC. CA1 represents action and reward events in close to real-time, whereas both the superficial and deep layers of the LEC showed delayed representation of those events. Our results suggest that subpopulations exist within which CA1 and LEC neurons process the information in a different order from the anatomically defined hippocampal-entorhinal circuit.
Antibody evolution to SARS-CoV-2 after single-dose Ad26.COV2.S vaccine
Authors: Cho Alice , Muecksch Frauke , Wang Zijun , Tanfous Tarek Ben , DaSilva Justin , Raspe Raphael , Johnson Brianna , Bednarski Eva , Ramos Victor , Schaefer-Babajew Dennis , Shimeliovich Irina , Dizon Juan , Yao Kai-Hui , Schmidt Fabian , Millard Katrina G. , Turroja Martina , Jankovic Mila , Oliveira Thiago Y. , Gazumyan Anna , Gaebler Christian , Caskey Marina , Hatziioannou Theodora , Bieniasz Paul D. , Nussenzweig Michel C.
Published: April 2022

The single dose Ad.26.COV.2 (Janssen) vaccine elicits lower levels of neutralizing antibodies and shows more limited efficacy in protection against infection than either of the available mRNA vaccines. In addition, the Ad.26.COV.2 has been less effective in protection against severe disease during the Omicron surge. Here, we examined the memory B cell response to single dose Ad.26.COV.2 vaccination. Compared to mRNA vaccines, Ad.26.COV.2 recipients had significantly lower numbers of RBD-specific memory B cells 1.5 or 6 months after vaccination. Memory antibodies elicited by both vaccine types show comparable neutralizing potency against SARS-CoV-2 and Delta. However, the number of memory cells producing Omicron neutralizing antibodies was somewhat lower after Ad.26.COV.2 than mRNA vaccination. The data help explain why boosting Ad.26.COV.2 vaccine recipients with mRNA vaccines is effective, and why the Janssen vaccine appears to have been less protective against severe disease during the Omicron surge than the mRNA vaccine.

One-Sentence Summary

Ad.26.COV.2 vaccine results in lower quantity but comparable quality of protective memory B cells compared to mRNA vaccines.
Convergence of immune escape strategies highlights plasticity of SARS-CoV-2 spike
Authors: Yu Xiaodi , Juraszek Jarek , Rutten Lucy , Bakkers Mark J. G. , Blokland Sven , van den Broek Niels J.F. , Verwilligen Annemiek Y.W. , Abeywickrema Pravien , Vingerhoets Johan , Neefs Jean-Marc , Mohamed Bakhash Shah A. , Roychoudhury Pavitra , Greninger Alex , Sharma Sujata , Langedijk Johannes P. M.
Published: April 2022

The SARS-CoV-2 spike protein is the target of neutralizing antibodies and the immunogen used in all currently approved vaccines. The global spread of the virus has resulted in emergence of lineages which are of concern for the effectiveness of immunotherapies and vaccines based on the early Wuhan isolate. Here we describe two SARS-CoV-2 isolates with large deletions in the N-terminal domain (NTD) of the spike. Cryo-EM structural analysis showed that the deletions result in complete reshaping of the antigenic surface of the NTD supersite. The remodeling of the NTD affects binding of all tested NTD-specific antibodies in and outside of the NTD supersite for both spike variants. A unique escape mechanism with high antigenic impact observed in the ΔN135 variant was based on the loss of the Cys15-Cys136 disulfide due to the P9L-mediated shift of the signal peptide cleavage site and deletion of residues 136-144. Although the observed large loop and disulfide deletions are rare, similar modifications became independently established in several other lineages, highlighting the possibility of a general escape mechanism via the NTD supersite. The observed plasticity of the NTD foreshadows its broad potential for immune escape with the continued spread of SARS-CoV-2.
Different olfactory neuron classes use distinct temporal and molecular programs to complete synaptic development
Authors: Aimino Michael A. , DePew Alison T. , Restrepo Lucas , Mosca Timothy J.
Published: April 2022

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphological maturation. Moreover, it remains unknown if neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and using identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage of the Drosophila antennal lobe, a model olfactory circuit with remarkable genetic access and synapse-level resolution. Using tissue-specific genetic labeling of active zones, we performed a quantitative analysis of synapse formation in multiple classes of neurons throughout development and adulthood. We found that olfactory receptor neurons (ORNs), projection neurons (PNs), and local interneurons (LNs) each have unique time-courses of synaptic development, addition, and refinement, demonstrating that each class follows a distinct developmental program. This raised the possibility that these classes may also have distinct molecular requirements for synapse formation. We genetically altered neuronal activity in each neuronal subtype and observed differing effects on synapse number based on the neuronal class examined. Silencing neuronal activity in ORNs, PNs, and LNs impaired synaptic development but only in ORNs did enhancing neuronal activity influence synapse formation. ORNs and LNs demonstrated similar impairment of synaptic development with enhanced activity of a master kinase, GSK-3β, suggesting that neuronal activity and GSK-3β kinase activity function in a common pathway. ORNs also, however, demonstrated impaired synaptic development with GSK-3β loss-of-function, suggesting additional activity-independent roles in development. Ultimately, our results suggest that the requirements for synaptic development are not uniform across all neuronal classes with considerable diversity existing in both their developmental timeframes and molecular requirements. These findings provide novel insights into the mechanisms of synaptic development and lay the foundation for future work determining their underlying etiologies.
History of previous midlife estradiol treatment permanently alters interactions of brain insulin-like growth factor-1 signaling and hippocampal estrogen synthesis to enhance cognitive aging in a rat model of menopause
Authors: Baumgartner Nina E. , McQuillen Shannon M. , Perry Samantha F. , Miller Sangtawan , Gibbs Robert , Daniel Jill M
Published: April 2022

Across species, including humans, elevated levels of brain estrogen receptor (ER) α are associated with enhanced cognitive aging even in the absence of circulating estrogens. In rodents, short-term estrogen treatment—such as that commonly used in the menopausal transition—results in long-term increases in levels of ERα in the hippocampus, leading to enhanced memory long after termination of estrogen treatment. However, mechanisms by which increased levels of brain ERα enhances cognitive aging remain unclear. Here we show that in the hippocampus, insulin-like growth factor-1 (IGF-1)—which can activate ER via ligand-independent mechanisms—requires concomitant synthesis of brain-derived neuroestrogens to phosphorylate ERα via MAPK signaling, ultimately resulting in enhanced memory. In a rat model of menopause involving long-term ovarian hormone deprivation, hippocampal neuroestrogen activity decreases, altering IGF-1 activity and resulting in impaired memory. However, this process is reversed by short-term estradiol treatment. Forty-days of estradiol exposure following ovariectomy results in maintenance of neuroestrogen levels that persist beyond the period of hormone treatment, allowing for continued interactions between IGF-1 and neuroestrogen signaling, elevated levels of hippocampal ERα, and ultimately enhanced memory. Collectively, results demonstrate that short-term estradiol use following loss of ovarian function has long-lasting effects on hippocampal function and memory by dynamically regulating cellular mechanisms that promote activity of ERα in the absence of circulating estrogens. Translational impacts of these findings suggest lasting cognitive benefits of short-term estrogen use near menopause and highlight the importance of hippocampal ERα—independent from the role of circulating estrogens—in regulating memory in aging females.

Significance statement

Declines in ovarian hormones following menopause coincide with increased risk of cognitive decline. Due to potential health risks, current recommendations are that menopausal estrogen therapy be limited to a few years. Long-term consequences for the brain and memory of this short-term midlife estrogen therapy are unclear. Here, in a rodent model of menopause, we determined mechanisms by which short-term midlife estrogen exposure can enhance hippocampal function and memory with cognitive benefits and molecular changes enduring long after termination of estrogen exposure. Our model indicates long-lasting benefits of maintaining hippocampal estrogen receptor function in the absence of ongoing estrogen exposure and suggests potential strategies for combating age-related cognitive decline.
An Open and Continuously Updated Fern Tree of Life
Authors: Nitta Joel H. , Schuettpelz Eric , Ramírez-Barahona Santiago , Iwasaki Wataru
Published: April 2022

1

Ferns, with about 12,000 species, are the second most diverse lineage of vascular plants after angiosperms. They have been the subject of numerous molecular phylogenetic studies, resulting in the publication of trees for every major clade and DNA sequences from nearly half of all species. Global fern phylogenies have been published periodically, but as molecular systematics research continues at a rapid pace, these become quickly outdated.

Here, we develop a mostly automated, reproducible, open pipeline to generate a continuously updated fern tree of life (FTOL) from DNA sequence data available in GenBank. Our tailored sampling strategy combines whole plastomes (few taxa, many loci) with commonly sequenced plastid regions (many taxa, few loci) to obtain a global, species-level fern phylogeny with high resolution along the backbone and maximal sampling across the tips. We use a curated reference taxonomy to resolve synonyms in general compliance with the community-driven Pteridophyte Phylogeny Group I classification.

The current FTOL includes 5,582 species, an increase of ca. 40% relative to the most recently published global fern phylogeny. Using an updated and expanded list of 51 fern fossil constraints, we find estimated ages for most families and deeper clades to be considerably older than earlier studies.

FTOL and its accompanying datasets, including the fossil list and taxonomic database, will be updated on a regular basis and are available via a web portal (https://fernphy.github.io) and R packages, enabling immediate access to the most up-to-date, comprehensively sampled fern phylogeny. FTOL will be useful for anyone studying this important group of plants over a wide range of taxonomic scales, from smaller clades to the entire tree. We anticipate FTOL will be particularly relevant for macroecological studies at regional to global scales and will inform future taxonomic systems with the most recent hypothesis of fern phylogeny.
Direct and indirect impacts of positive selection on genomic variation in Drosophila serrata
Authors: Wang Yiguan , Reddiex Adam J. , Allen Scott L. , Chenoweth Stephen F.
Published: April 2022

Understanding the extent to which microevolutionary adaptation relies on novel beneficial mutations, as opposed to previously neutral standing genetic variation, is an important goal of evolutionary genetics. Progress towards this goal has been enhanced during the genomic era through the study of selective sweeps. Selective sweeps fall into two categories: hard sweeps via new mutations and soft sweeps via pre-existing mutations. However, data are currently lacking on the relative frequency of these two types of selective sweep. In this study, we examined 110 whole genome sequences from Drosophila serrata sampled from eastern Australia and searched for hard and soft sweeps using a deep learning algorithm (diploS/HIC). Analyses revealed that approximately 15% of the D. serrata genome was directly impacted by soft sweeps, and that 46% of the genome was indirectly influenced via linkage to these soft sweeps. In contrast, hard sweep signatures were very rare, only accounting for 0.1% of the scanned genome. Gene ontology enrichment analysis further supported our confidence in the accuracy of sweep detection as several traits expected to be under frequent selection due to evolutionary arms races (e.g. immunity and sperm competition) were detected. Within soft sweep regions and those flanking them, there was an over-representation of SNPs with predicted deleterious effects, suggesting positive selection drags deleterious variants to higher frequency due to their linkage with beneficial loci. This study provides insight into the direct and indirect contributions of positive selection in shaping genomic variation in natural populations.
A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease
Authors: Solomon Joshua J. , Danoff Sonye , Woodhead Felix , Hurwitz Shelley , Maurer Rie , Glaspole Ian , Dellaripa Paul F. , Gooptu Bibek , Vassallo Robert , Cox P. Gerald , Flaherty Kevin R. , Adamali Huzaifa I. , Gibbons Michael A. , Troy Lauren , Forrest Ian , Lasky Joseph A. , Spencer Lisa G. , Golden Jeffrey , Scholand Mary Beth , Chaudhuri Nazia , Perella Mark A. , Lynch David , Chambers Daniel C. , Kolb Martin , Spino Cathie , Raghu Ganesh , Goldberg Hilary , Rosas Ivan O. ,   the TRAIL1 Network Investigators
Published: April 2022

Background

Interstitial lung disease (ILD) is a known complication of rheumatoid arthritis (RA) with a lifetime risk in any individual of 7.7%. The TRAIL1 trial was a randomized, double-blinded, placebo-controlled, phase 2 study of safety, tolerability, and efficacy of pirfenidone for the treatment of patients with RA-ILD.

Methods

The TRAIL1 was a phase 2 trial intended to enroll 270 adult patients (18 to 85 years) with established RA-ILD at 33 sites in 4 countries. Patients were randomly assigned (1:1) to 2,403 mg oral pirfenidone or placebo daily. The primary endpoint was the incidence of the composite endpoint of decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or greater or death during the 52-week treatment period. Key secondary endpoints included change in absolute and FVC% over 52 weeks.

Findings

The trial was stopped early due to slow recruitment and soon after the shutdown of clinical trials as a consequence of the coronavirus disease 2019 (COVID-19) pandemic. Data from 123 patients enrolled were analyzed. The primary endpoint was met by 11.1% on pirfenidone vs. 15% on placebo [OR=0.67 (0.22, 2.03), p=0.48]. Subjects receiving pirfenidone had a slower rate of decline in lung function as measured by estimated annual change in FVC(ml) (−66 vs. -146, p=0.0082) and FVC(%) (−1.02 vs. -3.21, p=0.0028). This effect on decline was also seen when analyzed within participants with baseline usual interstitial pneumonia (UIP) pattern on HRCT (FVC(ml) (−43 vs. -169, p=0.0014) and FVC% (−0.2 vs. -3.81, p=0.0002)). There was no significant difference in the rate of treatment-emergent serious adverse events.

Interpretation

Due to early termination of the study, results should be interpreted with caution. Despite being underpowered to evaluate the primary endpoint, pirfenidone slowed the rate of decline of FVC over time in subjects with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials.

Funding

Funding for this investigator initiated trial was provided by Genentech, Inc. to Ivan O. Rosas, MD, on behalf of the TRAIL1 Investigators.
Long-term performance assessment of fully automatic biomedical glottis segmentation at the point of care
Authors: Groh René , Dürr Stephan , Schützenberger Anne , Semmler Marion , Kist Andreas M.
Published: April 2022

Deep Learning has a large impact on medical image analysis and lately has been adopted for clinical use at the point of care. However, there is only a small number of reports of long-term studies that show the performance of deep neural networks (DNNs) in such a clinical environment. In this study, we measured the long-term performance of a clinically optimized DNN for laryngeal glottis segmentation. We have collected the video footage for two years from an AI-powered laryngeal high-speed videoendoscopy imaging system and found that the footage image quality is stable across time. Next, we determined the DNN segmentation performance on lossy and lossless compressed data revealing that only 9% of recordings contain segmentation artefacts. We found that lossy and lossless compression are on par for glottis segmentation, however, lossless compression provides significantly superior image quality. Lastly, we employed continual learning strategies to continuously incorporate new data to the DNN to remove aforementioned segmentation artefacts. With modest manual intervention, we were able to largely alleviate these segmentation artefacts by up to 81%. We believe that our suggested deep learning-enhanced laryngeal imaging platform consistently provides clinically sound results, and together with our proposed continual learning scheme will have a long-lasting impact in the future of laryngeal imaging.
Uptake of COVID-19 vaccines among pregnant women: a systematic review and meta-analysis
Authors: Galanis Petros , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsiroumpa Aglaia , Kaitelidou Daphne
Published: April 2022

Background

Mass vaccination against the COVID-19 is essential to control the pandemic. COVID-19 vaccines are recommended now during pregnancy to prevent adverse outcomes.

Objective

To evaluate the evidence from the literature regarding the uptake of COVID-19 vaccination among pregnant women.

Methods

We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched PubMed, Medline, Scopus, ProQuest, Web of Science, CINAHL, and a pre-print service (medRxiv) from inception to March 23, 2022. We included quantitative studies reporting COVID-19 vaccination uptake among pregnant women, studies that examine predictors of COVID-19 vaccination uptake and studies that examine reasons for decline of vaccination. We performed meta-analysis to estimate the overall proportion of vaccinated pregnant women against the COVID-19.

Results

We found 11 studies including 703,004 pregnant women. The overall proportion of vaccinated pregnant women against the COVID-19 was 27.5% (95% CI: 18.8-37.0%). The pooled proportion for studies that were conducted in Israel was higher than the proportion for studies that were conducted in USA and other countries. Predictors of COVID-19 vaccination uptake were older age, ethnicity, race, trust in COVID-19 vaccines, and fear of COVID-19 during pregnancy. On the other hand, mistrust in the government, diagnosis with COVID-19 during pregnancy, and worry about the safety and the side effects of the COVID-19 vaccines were reasons for decline of vaccination.

Conclusions

The global COVID-19 vaccination prevalence in pregnant women is low. There is a large gap in the literature on the factors influencing the decision of pregnant women to be vaccinated against the COVID-19. Targeted information campaigns are essential to improve trust and build vaccine literacy among pregnant women. Given the ongoing high case rates and the known increased risks of COVID-19 in pregnant women, our findings could help policy makers to improve the acceptance rate of COVID-19 vaccines in pregnant women especially in vulnerable subgroups.
Internet and mental health during the COVID-19 pandemic: Evidence from the UK
Authors: Quintana-Domeque Climent , Zeng Jingya , Zhang Xiaohui
Published: April 2022

With the COVID-19 pandemic, the Internet has become a key player in the daily lives of most people. We investigate the relationship between mental health and internet use frequency and purpose six months after the first lockdown in the UK, September 2020. Using data from the UK Household Longitudinal Study on the 12-item General Health Questionnaire and the Internet use module, and controlling for sociodemographic characteristics and personality traits, we find that older individuals (aged 59 or above) have a lower internet use frequency (twice a day or less). Younger women use the Internet for social purposes more than men do, while younger men use the Internet for leisure-and-learning purposes more than women and older men do. Both high frequency internet use and use for social purposes appear to be a protective factor for social dysfunction. Interestingly, high internet use is a protective factor for social dysfunction among younger women, but a risk factor for psychological distress among younger men. Finally, while leisure-and-learning purpose is a protective factor for social dysfunction among younger women, it is a risk factor for social dysfunction among younger men.
Evidence for feasibility of mobile health and social media-based interventions for early psychosis and clinical high risk
Authors: Franco Olivia H. , Calkins Monica E. , Giorgi Salvatore , Ungar Lyle H. , Gur Raquel E. , Kohler Christian G. , Tang Sunny X.
Published: April 2022

Background

Digital technology, the internet and social media are increasingly investigated as a promising means for monitoring symptoms and delivering mental health treatment. These apps and interventions have demonstrated preliminary acceptability and feasibility, but previous reports suggests that access to technology may still be limited among individuals with psychotic disorders relative to the general population.

Objective

We evaluated and compared access and use of technology and social media in young adults with psychotic disorders (PD), clinical risk for psychosis (CR), and psychosis-free youths (PF).

Methods

Participants were recruited through a coordinated specialty care clinic dedicated towards early psychosis as well as ongoing studies. We surveyed 21 PD, 23 CR, and 15 PF participants regarding access to technology and use of social media, specifically Facebook and Twitter. Statistical analyses were conducted in R. Categorical variables were compared among groups Fisher’s exact test, continuous variables were compared using one-way ANOVA, and multiple linear regressions were used to evaluate for covariates.

Results

Access to technology and social media were similar among PD, CR and PF. Individuals with PD, but not CR, were less likely to post at a weekly or higher frequency compared to psychosis-free individuals. We found that decreased active social media posting was unique to psychotic disorders and did not occur with other psychiatric diagnoses or demographic variables. Additionally, variation in age, sex, Caucasian vs. non-Caucasian race did not affect posting frequency.

Conclusions

For young people with psychosis spectrum disorders, there appears to be no “technology gap” limiting the implementation of digital and mobile health interventions. Active posting to social media was reduced for individuals with psychosis, which may be related to negative symptoms or impairment in social functioning.
Long-term psychological consequences of long Covid: a propensity score matching analysis comparing trajectories of depression and anxiety symptoms before and after contracting long Covid vs short Covid
Authors: Fancourt Daisy , Steptoe Andrew , Bu Feifei
Published: April 2022

Background

There is a growing global awareness of the psychological consequences of long Covid, supported by emerging empirical evidence. However, the mergence and long-term trajectories of psychological symptoms following the infection are still unclear.

Aims

To examine when psychological symptoms first emerge following the infection with SARS-CoV-2, and the long-term trajectories of psychological symptoms comparing long and short Covid groups.

Methods

We analysed longitudinal data from the UCL Covid-19 Social Study (March 2020-November 2021). We included data from adults living in England who reported contracting SARS-CoV-2 by November 2021 (N=3,115). Of these, 15.9% reported having had long Covid (N=495). They were matched to participants who had short Covid using propensity score matching on a variety of demographic, socioeconomic and health covariates (N=962, n=13,325) and data were further analysed using growth curve modelling.

Results

Depressive and anxiety symptoms increased immediately following the onset of infection in both long and short Covid groups. But the long Covid group had substantially greater initial increases in depressive symptoms and heightened levels over 22 months follow-up. Initial increases in anxiety were not significantly different between groups, but only the short Covid group experienced an improvement in anxiety over follow-up, leading to widening differences between groups.

Conclusions

The findings shed light on the psychobiological pathways involved in the development of psychological symptoms relating to long Covid. The results highlight the need for monitoring of mental health and provision of adequate support to be interwoven with diagnosis and treatment of the physical consequences of long Covid.
Use of glycolysis enhancing drugs has less risk of Parkinson’s disease than 5α-reductase inhibitors
Authors: Simmering Jacob E. , Welsh Michael J. , Schultz Jordan , Narayanan Nandakumar S.
Published: April 2022

Background

Terazosin and closely related α1-adrenergic receptor antagonists (doxazosin and alfuzosin; TZ/DZ/AZ) enhance glycolysis and reduce neurodeneration in animal models. Observational evidence in humans from several databases support this finding; however, a recent study has suggested that tamsulosin, the comparator medication, increases risk of Parkinson’s disease. We consider a different comparison group of men taking 5α-reductase inhibitors as a new, independent comparison allowing us to both obtain new estimates of the association between TZ/DZ/AZ and Parkinson’s disease outcomes and validate tamsulosin as an active comparator.

Methods

Using the Truven Health Analytics Marketscan database, we identified men without Parkinson’s disease, newly started on TZ/DZ/AZ, tamsulosin, or 5α-reductase inhibitors. We followed these matched cohorts to compare the hazard of developing Parkinson’s disease.

Results

We found that men taking TZ/DZ/AZ had a lower hazard of Parkinson’s disease than men taking tamsulosin (HR=0.72, 95% CI: 0.66-0.78, n=239,946) and lower than men taking a 5α-reductase inhibitors (HR=0.81, 95% CI: 0.72-0.92, n=129,320). The hazard for men taking tamsulosin was not statistically significantly different than for men taking 5α-reductase inhibitors (HR=1.10, 95% CI: 1.00-1.22, n=157,490).

Conclusions

These data suggest that men using TZ/DZ/AZ have a lower risk of developing Parkinson’s disease than those using tamsulosin or 5α-reductase inhibitors while users of tamsulosin and 5α-reductase inhibitors have relatively similar survival functions.
A comparative analysis of depression between pregnant and non-pregnant adolescents in a southwestern town in Nigeria
Authors: Mosanya Julianah T. , Adegbite Temilade A. , Adebayo Kazeem O. , Egbewale Bolaji E. , Ijadunola Kayode T.
Published: April 2022

Background

Adolescence constitutes a risk factor for mental health problems, and this may be further complicated by pregnancy. The rate of adolescent pregnancy is still extremely high in the sub-Saharan Africa including Nigeria. Pregnancy and mental health problems during adolescence constitute double vulnerability for negative outcomes for the adolescents and their offspring.

Methodology

The study was cross-sectional in design and it compared prevalence of depression and associated factors among pregnant and non-pregnant adolescents. It was conducted in Osogbo metropolis, Osun State, Southwest, Nigeria. The study population comprised pregnant adolescents (aged 15-19 years) attending antenatal care (ANC) in selected formal and informal health facilities. Non-pregnant adolescents who were equally attending services at the facilities were recruited as the control group. Information was obtained from the adolescents with the use of a structured questionnaire and data was analysed with IBM-SPSS version 21 software.

Results

Three hundred and thirty-four respondents (167 per group) were involved in the study; the pregnant adolescents had a mean age (±SD) of 17.92 (±1.13) years while the non-pregnant adolescents had a mean age of 17.70 (±1.23) years. The prevalence of depression among the pregnant adolescents was 8.4% while that of the non-pregnant adolescents was 3.0%. The result showed a statistically significant association between pregnancy status and depression among the adolescents (p= 0.033). Living arrangement was the only socio-demographic variable that had significant relationship with depression among the pregnant adolescents while living arrangement and employment status had significant relationships with depression among the non-pregnant adolescents. History of mental illness, childhood sexual abuse and anxiety symptoms showed significant relationship with depression among pregnant adolescents, however, only anxiety symptoms showed significant relationship with depression among non-pregnant adolescents.

Conclusion

The study concluded that the prevalence of depression is significantly higher among pregnant adolescents with similarities and differences in the factors associated with depression in the two groups.
Periplasmic oxidized-protein repair during copper stress in E. coli: a focus on the metallochaperone CusF
Authors: Vergnes Alexandra , Henry Camille , Grassini Gaia , Loiseau Laurent , El Hajj Sara , Denis Yann , Galinier Anne , Vertommen Didier , Aussel Laurent , Ezraty Benjamin
Published: April 2022

Methionine residues are particularly sensitive to oxidation by reactive oxygen or chlorine species (ROS/RCS), leading to the appearance of methionine sulfoxide in proteins. This post-translational oxidation can be reversed by omnipresent protein repair pathways involving methionine sulfoxide reductases (Msr). In the periplasm of Escherichia coli, the enzymatic system MsrPQ, whose expression is triggered by the RCS, controls the redox status of methionine residues. Here we report that MsrPQ synthesis is also induced by copper stress via the CusSR two-component system, and that MsrPQ plays a role in copper homeostasis by maintaining the activity of the copper efflux pump, CusCFBA. Genetic and biochemical evidence suggest the metallochaperone CusF is the substrate of MsrPQ and our study reveal that CusF methionines are redox sensitive and can be restored by MsrPQ. Thus, the evolution of a CusSR-dependent synthesis of MsrPQ allows keeping copper homeostasis under aerobic conditions by maintenance of the reduced state of Met residues in copper-trafficking proteins.

AUTHOR SUMMARY

Our study investigates the interconnection between the copper stress response and the methionine redox homeostasis in the Gram-negative bacterium Escherichia coli. We report that the copper-activation of the CusSR two-component system induces the expression of the periplasmic oxidized-protein repair system, MsrPQ. We demonstrate that MsrPQ is crucial for CusCFBA copper efflux pump activity under aerobic conditions as it maintains the periplasmic component CusF in its functional reduced form. Methionine emerges as a critical residue in copper trafficking proteins: however this naturally-selected advantage must be balanced by methionine’s high susceptibility to oxidation. Therefore the induction of MsrPQ by copper allows copper homeostasis under aerobic conditions, illustrating that E. coli has developed an integrated and dynamic circuit for sensing and counteracting stress caused by copper and oxidants, thus allowing bacteria to adapt to host cellular defences.