bluuebunny/crossref_metadata_2025 huggingface dataset:
Health conditions associated with sexual assault in a large hospital population
Authors: Lake Allison M. , Goleva Slavina B. , Samuels Lauren R. , Carpenter Laura M. , Davis Lea K.
Published: April 2022

Objective

To develop a clinical informatics approach to identify patients with a history of sexual assault and to characterize the clinical risk factors and comorbidities of this population in a sex-stratified manner.

Methods

We developed and applied a keyword-based approach to clinical notes to identify patients with a history of sexual assault in the Vanderbilt University Medical Center (VUMC) electronic health record from 1989 to 2021. Using a phenome-wide association study (PheWAS), we then examined diagnoses that co-occurred with evidence of sexual assault. We also examined whether sex assigned at birth modified any of these associations.

Results

Our keyword-based algorithm achieved a positive predictive value of 90.4%, as confirmed by manual patient chart review. Out of 1,703 diagnoses tested across all subgroup analyses, we identified a total of 465 associated with sexual assault, many of which have been previously observed in the literature. Interaction analysis revealed 55 sex-differential phenotypic associations.

Conclusions

In a large hospital setting, disclosures of sexual assault were associated with increased rates of hundreds of health conditions.
Severity and Correlates of Mental Fog in People with Traumatic Brain Injury
Authors: Bell Tyler , Crowe Michael , Novack Thomas , Davis Richard D. , Stavrinos Despina
Published: April 2022

Objective

Alongside objective performance declines, self-reported cognitive symptoms after traumatic brain injury (TBI) abound. Mental fog is one symptom that has been underexplored. The current project investigated mental fog across two studies of individuals with mild traumatic brain injury and moderate-to-severe traumatic brain injury to close our knowledge gap about differences in severity. We then explored the cognitive and affective correlates of mental fog within these groups.

Methods

Using between-groups designs, the first study recruited individuals with acute mild TBI (n = 15) along with a healthy control group (n = 16). Simultaneously, a second study recruited persons with post-acute moderate-to-severe TBI, a stage when self-reports are most reliable (n = 15). Measures across the studies were harmonized and involved measuring mental fog (Mental Clutter Scale), objective cognition (Cogstate® and UFOV®), and depressive symptoms. In addition to descriptive group difference analyses, nonparametric correlations determined associations between mental fog, objective cognition, and depressive symptoms.

Results

Results revealed higher self-reported mental fog in acute mild TBI compared to healthy controls. And though exploratory, post-acute moderate-to-severe TBI also appears characterized by greater mental fog. Correlations showed that mental fog in mild TBI corresponded to greater depressive symptoms (r = .66) but was unrelated to objective cognition. By contrast, mental fog in moderate-to-severe TBI corresponded to poorer working memory (r = .68) and slowed processing speed (r = -.55) but was unrelated to depressive symptoms.

Conclusion

As a common symptom in TBI, mental fog distinguishes individuals with acute mild TBI from uninjured peers. Mental fog also appears to reflect challenges in recovery, including depressive symptoms and objective cognitive problems. Screening for mental fog, in addition to other cognitive symptoms, might be worthwhile in these populations.
Effectiveness of Oral Health Education Interventions on Oral Health Literacy Levels in Adults; A Systematic Review
Authors: Ebrahimi Tayebe , Farokhi Moshtagh R
Published: April 2022

Background

Oral health literacy within the construct of health literacy may be instrumental in decreasing oral health disparities and promoting oral health. Even though current research links oral health literacy to oral health knowledge and education, the impact of educational intervention on oral health literacy remains controversial. We aimed to identify effective health education interventions delivered with a focus on oral health literacy.

Methods

An electronic systematic search in PubMed, Scopus, Web of Science and Cochrane library and gray literatue was performed for relevant studies (1995-2021). Experimental study designs of randomized controlled trials, non-randomized controlled trials, and quasi-experimental studies in which adults aged 18 years or older, male, or female (participants) trained under a health education intervention (intervention) were compared with those with no health education or within the usual care parameters (comparison). An assessment of oral health literacy levels (outcome) were included according to the PICO question. The search was conducted by applying filters for the title, abstract and methodological quality of the data, and English language. Study screening, extraction and critical appraisal was performed by two independent reviewers. Data was extracted from the included studies whereas a meta-analysis was not possible since findings were mostly presented as a narrative format.

Results

Eight studies out of the 2783 potentially eligible articles met the selection criteria for this systematic review. The aim of interventions in these studies was 1) improving oral health literacy as the first outcome or 2) improving oral health behavior and oral health skills as the first outcome and assessing oral health literacy as the second outcome. The strength of evidence from the reviewed articles was high and there was an enormous heterogeneity in the study design, OHL measurement instruments and outcomes measure. Interventions were considerably effective in improving oral health literacy.

Conclusion

Health education that is tailored to the needs and addresses patients’ barrier to care can improve their oral health literacy level.
Influence of Illustrator’s Intentions and Visual Description Techniques of Medical Illustrations on Generating Interest and Boosting Comprehension of Medical Information
Authors: Haragi Makiko , Onozuka Ryo , Nishida Ryosuke , Koyama Shimpei
Published: April 2022

In this study, an exploratory online survey was conducted to clarify points that have not been clarified so far in the medical illustration research field. If several illustrators make an illustration of the same information, does a match of intentions and techniques affect the impression or comprehension of the information? The aim is to further the utilization of medical illustration in actual practice (n=1104).

First, we selected Autosomal Dominant Polycystic Kidney Disease (ADPKD) as the medical condition about which information had to be disseminated. Then, we asked 32 art professionals to make six illustrations with three detail types (high, middle, and low) and two purposes (“getting interested” and “boosting comprehension”). Thereafter, we selected six different types of art professionals’ illustrations for the questionnaire to ask the participants about the intentions of the illustrations and comprehension of the content. We found that if the illustrator’s intentions and visual description techniques match with the recipients, the match of intentions could help generate interest in the content, and the match of visual description techniques could enhance the comprehension of the information.
Domain specific need assessment for Hospital Disaster Preparedness: a systematic review and critical interpretative synthesis
Authors: Pawar Neeraj , Gumashta Raghvendra , Gupta Girjesh , Mahore Rajendra , Gumashta Jyotsna
Published: April 2022

Background

During disasters, the most pressing demands are those related to health, and hospital preparedness is an area that require special attention. Hospitals are viewed as resources that must be proactively utilized in the event of a disaster. If national and local systems, particularly health systems, are unprepared to deal with disasters, the vulnerability of both individuals and communities is amplified. The unexpected surge in demand for important health services caused by disasters frequently overwhelms health systems and institutions, leaving them unable to perform the life-saving measures that are required. This study aims to understand various domains of hospital disaster preparedness by critically synthesizing qualitative evidence from selected research on the topic.

Methods

Electronic data base from PubMed, Google Scholar, key hospital disaster related journals was explored with search syntax focusing on hospital related disaster preparedness. Peer reviewed English articles published from January 2011 were systematically selected and critical interpretative qualitative synthesis was done to have comprehensive understanding of the said phenomenon.

Results

A total of 29 articles were included in the systematic review. Major resultant domains describing disaster preparedness were Human Resource, Logistics And Finance, Response, Communication, Coordination, Patient Care, Evacuation and Personal Protection. Some domains were more emphasised than others, this information can help prioritizing the action based on need especially in the times of disaster.

Conclusion

Disaster preparedness needs a comprehensive approach including context specific optimization with the effective use of available resources.
Hematopoietic and Lung Platelet Biogenesis as a Prognostic Indicator in Idiopathic Pulmonary Fibrosis (IPF)
Authors: Saito Shigeki , Chung Cheng Han H. , Jacob Alex , Nuradin Nebil , Meyer Amy E. , Saito Toshie , Yang Haoran , Kolls Jay K. , Thannickal Victor J. , Liu Yao-Zhong , Lasky Joseph A.
Published: April 2022

Rationale and objectives

The role of human lung megakaryocytes in homeostasis and their dynamics in disease states remain unknown. We sought to investigate whether megakaryocyte/platelet gene signatures are altered in IPF.

Methods

We analyzed publicly available transcriptome datasets of lung tissue, bronchoalveolar lavage (BAL) cells, and peripheral whole blood from IPF patients and healthy controls. Enrichment of megakaryocyte and platelet gene signatures in those datasets were estimated using xCell, a novel computational method. Furthermore, we analyzed whether mean platelet volume (MPV) and platelet counts in peripheral blood are associated with lung transplant-free survival in our IPF cohort.

Results

In lung tissue, megakaryocyte gene signature enrichment scores were significantly lower in IPF than in controls. In BAL cells, platelet gene signature enrichment scores were significantly lower in IPF than in controls, and lower platelet scores were associated with lower lung transplant-free survival in IPF. In contrast, in blood, megakaryocyte scores were significantly higher in IPF than in controls, and higher megakaryocyte scores were associated with lower disease progression-free survival in IPF. Furthermore, higher MPV was associated with lower transplant-free survival in our IPF cohort, independent of age, sex, forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO).

Conclusions

In IPF, megakaryocyte/platelet gene signatures were altered in a compartment-specific manner. Moreover, those signatures and MPV in blood were associated with important clinical outcomes such as transplant-free survival. These findings provide new insights into altered megakaryocyte/platelet biogenesis in IPF and suggest the potential utility of megakaryocyte/platelet-based biomarkers in IPF.
Sustained patient use and improved outcomes with digital transformation of a COPD service: RECEIVER trial and DYNAMIC-SCOT COVID-19 scale-up response
Authors: Taylor A , Cushing A , Dow M , Anderson J , McDowell G , Lua S , Manthe M , Padmanabhan S , Burns S , McGinness P , Lowe DJ , Carlin C
Published: April 2022

Introduction

LenusCOPD has been co-designed to enable digital transformation of COPD services for proactive preventative care. Patient-facing progressive web application, clinician dashboard and support website integrate patient-reported outcomes (PROs), self-management resources, structured clinical summary, wearable and home NIV data with asynchronous patient-clinician messaging. We commenced the implementation-effectiveness observational cohort RECEIVER trial in September 2019, with the primary endpoint of sustained patient usage and secondary endpoints including admissions, mortality, exacerbations, service workload and quality of life. We paused recruitment in March 2021 and provided LenusCOPD as routine care in the “DYNAMIC-SCOT” COVID-19 response service scale-up.

Methods

83 RECEIVER trial participants and 142 DYNAMIC-SCOT participants had completed minimum 1 year follow-up when we censored data on 31st August 2021. We established a control cohort with 5 patients matched per RECEIVER participant from de-identified contemporary routine clinical data.

Results

Sustained patient app utilisation was noted in both cohorts. Median time to admission or death was 43 days in control, 338 days in RECEIVER and 400 days in DYNAMIC-SCOT participants who had had a respiratory-related admission in the preceding year. The 12-month risk of admission or death was 74% in control patients, 53% in RECEIVER and 47% in the DYNAMIC-SCOT sub-cohort participants. There was a median of 2.5 COPD exacerbations per patient per year with stable quality of life across follow up and a manageable workload for clinical users.

Conclusions

A high proportion of people continued to use the co-designed LenusCOPD application during extended follow-up. Outcome data supports scale-up of this digital service transformation.

Key messages

What is the key question?

Can sustained patient interaction and improved patient outcomes be achieved with digital transformation of a COPD service?

What is the bottom line?

Participants continue to use the LenusCOPD patient app, with an average of 3-3.5 interactions per person per week sustained >1-year post-onboarding. COPD- related hospital admissions and occupied bed days were reduced following LenusCOPD onboarding in participants with a history of a severe exacerbation in the previous year, with a median time to readmission of 380 days compared with 50 days in a contemporary matched control patient cohort.

Why read on?

Feasibility and utility results support scale-up adoption of these digital tools, to support optimised co-management of COPD and other long-term conditions within a continuous implementation-evaluation framework. This will establish a test-bed infrastructure for additional innovations including artificial intelligence-insights for MDT decision support.
Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study
Authors: Bouton Tara C. , Atarere Joseph , Turcinovic Jacquelyn , Seitz Scott , Sher-Jan Cole , Gilbert Madison , White Laura , Zhou Zhenwei , Hossain Mohammad M. , Overbeck Victoria , Doucette-Stamm Lynn , Platt Judy , Landsberg Hannah E. , Hamer Davidson H. , Klapperich Catherine , Jacobson Karen R. , Connor John H.
Published: April 2022

Background

In January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown.

Methods

We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture.

Results

Among 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively.

Conclusions

The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation.

Main Point

Beyond day 5, 17% of our Delta and Omicron-infected cohort were culture positive. We saw no significant impact of booster vaccination on within-host Omicron viral dynamics. Additionally, we found that rapid antigen testing may provide reassurance of lack of infectiousness.
Screening of SARS-CoV-2 Antivirals Through a Cell-Based RNA-Dependent RNA Polymerase (RdRp) Reporter Assay
Authors: Uppal Timsy , Tuffo Kai , Khaiboullina Svetlana , Reganti Sivani , Pandori Mark , Verma Subhash C.
Published: April 2022

COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) continues to pose international public health threat and thus far, has resulted in greater than 5.6 million deaths worldwide. Vaccines are critical tools to limit COVID-19 spread, but antiviral drug development is an ongoing global priority due to fast spreading COVID-19 variants that may elude vaccines efficacies. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is an essential enzyme of viral replication and transcription machinery complex. Therefore, the RdRp is an attractive target for the development of effective anti-COVID-19 therapeutics. In this study, we developed a cell-based assay to determine the enzymatic activity of SARS-CoV-2 RdRp through luciferase reporter system. The SARS-CoV-2 RdRp reporter assay was validated using a known inhibitors of RdRp polymerase, remdesivir along with other anti-virals including ribavirin, penciclovir, rhoifolin, 5’CT, and dasabuvir. Among these inhibitors, dasabuvir (FDA-approved drug) exhibited promising RdRp inhibitory activity. Anti-viral activity of dasabuvir was also tested on the replication of SARS-CoV-2 through infection of Vero E6 cells. Dasabuvir inhibited the replication of SARS-CoV-2, USA-WA1/2020 as well as B.1.617.2 (delta variant) in Vero E6 cells in a dose-dependent manner with IC50 values 9.47 μM and 10.48 μM, for USA-WA1/2020 and B.1.617.2 variants, respectively). Our results suggests that dasabuvir can be further evaluated as a therapeutic drug for COVID-19. In addition, our assays provide robust, target-specific, and high-throughput screening compatible (z- and z’-factors of > 0.5) platforms that will be a valuable tool for the screening SARS-CoV-2 RdRp inhibitors.

Significance

SARS-CoV-2 has caused a major public crisis world has seen in recent history. Development of vaccines and emergency use authorization of anti-virals are helping in reducing the burden of SARS-CoV-2 caused hospitalization and deaths. However, there is still need for optimal anti-viral(s) that can efficiently block viral propagation, and targeting viral polymerase (RdRp) is an among the most suitable targets for clamping viral replication. In this study, we developed a cell-based assay to screen potential compounds capable of blocking RdRp activity. The efficacy of our assay was validated by using already approved anti-virals, which reduced RdRp activity and slowed the replication of two SARS-CoV-2 variants (WA1 USA-WA1/2020 and B.1.617.2) in a cell culture model. This confirmed that our system can be used for identifying potential anti-SARS-CoV-2 anti-virals.
Description of Halopseudomonas maritima sp. nov., based on phylogenomic analysis
Authors: Kujur Ritu Rani Archana , Das Subrata K
Published: April 2022

A novel bacterium, strain RR6T of the genus Halopseudomonas, was isolated from the sea sand from Paradip port area, India. Cells are Gram-stain-negative, rod-shaped, aerobic, non-sporulating and motile. The major cellular fatty acids of RR6T were C10:0 3OH, C12:0, C16:1 w7c/16:1 w6c, 18:1 w7c and/or 18:1 w6c and C16:0. The predominant polar lipids were phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), unidentified phospholipid (PL) and unidentified lipids (L1-L2). The genome size of the strain RR6 was 3.93 Mb. The genomic G+C content was 61.3%. Gene ontology study showed a significant fraction of genes were associated with biological processes (53%), followed by molecular function (36%) and cellular components (11%). Comparisons of 16S rRNA gene sequences revealed 99.73 - 99.87 % sequence similarity with the closely related type strains of the genus Halopseudomonas. The average nucleotide identity (ANI) and average amino acid identity (AAI) of RR6T with reference strains of closely related species of the genus Halopseudomonas were below 95–96, and the corresponding in-silico DNA–DNA hybridization (DDH) values were below 70 %. A phylogenomic tree based on core genome analysis supported these results. Genotypic and phenotypic characteristics of RR6T indicate that the strain represents a novel species of the genus Halopseudomonas and the name Halopseudomonas maritima sp. nov. is proposed. The type strain is RR6T (= NBRC 115418T = TBRC 15628T).
Have deaths of despair risen during the COVID-19 pandemic? A rapid systematic review
Authors: Rahimi-Ardabili Hania , Feng Xiaoqi , Nguyen Phi-Yen , Astell-Burt Thomas
Published: April 2022

Objective

To systematically review the literature on the impact of the COVID-19 pandemic on deaths of despair (suicide, overdoses and drug-related liver diseases).

Methods

Five electronic databases were searched using search terms on deaths of despair and COVID-19.

Results

The review of 70 publications included indicates that there is no change or a decline in the suicide rate during the pandemic compared to the pre-pandemic period. Drug-related deaths such as overdose deaths and liver diseases, however, have been increased compared to the pre-pandemic rate. Findings are mainly from middle-high- and high-income countries and data from low-income countries are lacking. Synthesis of data from subgroup analysis indicates that some groups such as Black people, women and younger age groups would be more vulnerable to socioeconomic disruption during the pandemic.

Conclusion

Studies included in this review were preliminary and suffered from methodological limitations such as lack of inferential analysis or using provisional data. Further high-quality studies are needed considering the contribution of factors such as disease prevalence, government intervention and environmental characteristics.
Single-neuron bursts encode pathological oscillations in Parkinson’s disease and essential tremor
Authors: Scherer Maximilian , Steiner Leon A , Kalia Suneil K , Hodaie Mojgan , Kühn Andrea A , Lozano Andres M , Hutchison William D , Milosevic Luka
Published: April 2022

Deep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Herein, we address the relationship between singleneuron and aggregate-level (local field potential; LFP) activities in the subthalamic nucleus (STN) and thalamic ventral intermediate nucleus (Vim) of patients with Parkinson’s disease (n=19) and essential tremor (n=16), respectively. Both disorders have been characterized by pathologically elevated LFP oscillations, as well as an increased tendency for neuronal bursting. Our findings suggest that periodic single-neuron bursts encode both pathophysiological beta (13-33Hz; STN) and tremor (4-10Hz; Vim) LFP oscillations, evidenced by strong time-frequency and phase-coupling relationships between the bursting and LFP signals. Spiking activity occurring outside of bursts had no relationship to the LFP. In STN, bursting activity most commonly preceded the LFP oscillation, suggesting that neuronal bursting generated within STN may give rise to an aggregate-level LFP oscillation. In Vim, LFP oscillations most commonly preceded bursting activity, suggesting that neuronal firing may be entrained by periodic afferent inputs. In both STN and Vim, the phasecoupling relationship between LFP and high-frequency oscillation (HFO) signals closely resembled the relationships between the LFP and single-neuron bursting. This suggests that periodic singleneuron bursting is likely representative of a higher spatial and temporal resolution readout of periodic increases in the amplitude of HFOs, which themselves may be a higher resolution readout of aggregate-level LFP oscillations. Overall, our results may reconcile “rate” and “oscillation” models of Parkinson’s disease and shed light onto the single-neuron basis and origin of pathophysiological oscillations in movement disorders.

Significance

In surgical patients with Parkinson’s disease and essential tremor, we leverage intracranial recordings to establish a link between pathophysiological phenomena across various scales of observation (spatio-temporal resolutions). We provide insights and reconcile theories about aberrant neurocircuit phenomena which underly theses debilitating, medically refractory movement disorders. Furthermore, our connectivity analyses between single-neuron and local field potential activities may shed light on the origin of the deleterious neural oscillations underlying these disorders. Ultimately, our findings may aid in the development or investigation of targeted therapies to address or correct underlying neurocircuit dysfunction, which can include neuropharmaceuticals, but also novel neuromodulatory strategies like closed-loop deep brain stimulation targeting pathophysiological oscillations and phase-dependent stimulation methods seeking to stimulate “at the right time/phase.”
Revealing determinants of translation efficiency via whole-gene codon randomisation and machine learning
Authors: Nieuwkoop Thijs , Terlouw Barbara , de Ridder Dick , van der Oost John , Claassens Nico J.
Published: April 2022

Codon usage refers to the occurrence of synonymous codons in protein-coding genes. It is known for decades that codon usage contributes to translation efficiency and hence to protein production levels. However, its role in protein synthesis is still only partly understood. This lack of understanding hampers the design of synthetic genes for efficient protein production. In this study, we developed a method to generate a large, synonymous codon library of the gene encoding the red fluorescent protein (RFP). After expression in Escherichia coli, 1459 clones of this library were selected of which we measured protein production levels and determined the full coding sequences. Using different machine learning approaches, this data was used to reveal correlations between codon usage and protein production. Interestingly, protein production levels can be relatively accurately predicted (Pearson correlation of 0.762) by a Random Forest model, which only relies on the sequence information for the first 8 codons. This study clearly demonstrated the key role of codons at the start of the coding sequence. As such, it provides not only important fundamental insights on the influence of codon usage on protein production but also relevant clues on optimising the design of efficiently translated synthetic genes.
Architectural experience: clarifying its central components and their relation to core affect with a set of first-person-view videos
Authors: Gregorians Lara , Velasco Pablo Fernández , Zisch Fiona , Spiers Hugo J.
Published: April 2022

When studying architectural experience in the lab, it is of paramount importance to use a proxy as close to real-world experience as possible. Whilst still images visually describe real spaces, and virtual reality allows for dynamic movement, each medium lacks the alternative attribute. To merge these benefits, we created and validated a novel dataset of valenced videos of first-person-view travel through built environments. This dataset was then used to clarify the relationship of core affect (valence and arousal) and architectural experience. Specifically, we verified the relationship between valence and fascination, coherence, and hominess - three key psychological dimensions of architectural experience which have previously been shown to explain aesthetic ratings of built environments. We also found that arousal is only significantly correlated with fascination, and that both are embedded in a relationship with spatial complexity and unusualness. These results help to clarify the nature of fascination, and to distinguish it from coherence and hominess when it comes to core affect. Moreover, these results demonstrate the utility of a video dataset of affect-laden spaces for understanding architectural experience.

Highlights

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Developed a video database of first-person-view journeys through built environments

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We explored how core affect and architectural experience relate through the videos

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Previous results are supported: valence ties to fascination, coherence and hominess

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Arousal correlates only with fascination, and not coherence or hominess

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Arousal and fascination are tied to spatial complexity and unusualness
Development of ultra-low-input nanoRibo-seq enables quantification of translational control, revealing broad uORF translation by subtype-specific neurons
Authors: Froberg John E. , Durak Omer , Macklis Jeffrey D.
Published: April 2022

While increasingly powerful approaches enable investigation of transcription using small samples of RNA, approaches to investigate translational regulation in small populations of specific cell types, and/or (sub)-cellular contexts are lacking. Comprehensive investigation of mRNAs actively translated into proteins from ultra-low input material would provide important insight into molecular machinery and mechanisms underlying many cellular, developmental, and disease processes in vivo. Such investigations are limited by the large input required for current state-of-the-art Ribo-seq. Here, we present an optimized, ultra-low input “nanoRibo-seq” approach using 102 – 103-fold less input material than standard approaches, demonstrated here in subtype-specific neurons. nanoRibo-seq requires as few as 2.5K neurons, and exhibits rigorous quality control features: 1) strong enrichment for CDS versus UTRs and non-CDS; 2) narrow, distinct length distributions over CDS; 3) ribosome P-sites predominantly in-frame to annotated CDS; and 4) sufficient ribosome-protected fragment (RPF) coverage across thousands of mRNAs. As proof-of-concept, we calculate translation efficiencies from paired Ribo-seq and alkaline fragmented control libraries from “callosal projection neurons” (CPN), revealing divergence between mRNA abundance and RPF abundance for hundreds of genes. Intriguingly, we identify substantial translation of upstream ORFs in the 5’ UTRs of genes involved in axon guidance and synapse assembly. nanoRibo-seq enables previously inaccessible investigation of translational regulation by small, specific cell populations in normal or perturbed contexts.
Evolution of Delta variant by non-Spike signature co-appearing mutations: trailblazer of COVID-19 disease outcome
Authors: Banerjee Anindita , Mazumder Anup , Roy Jayita , Majumdar Agniva , Chatterjee Ananya , Biswas Nidhan K , Sarkar Mamta Chawla , Maitra Arindam , Dutta Shanta , Das Saumitra
Published: April 2022

The high transmissibility and infectivity of a SARS-CoV-2 variant is usually ascribed to the Spike mutations, while emerging non-spike mutations might be a serious threat to the current Spike-recombinant vaccines. In addition to mutations in structural Spike glycoprotein, rapid accumulation of mutations across non-structural genes is leading to continuous virus evolution, altering its pathogenicity. We performed whole genome sequencing of SARS-CoV-2 positive samples collected from different clinical groups from eastern India, during the second pandemic wave (April-May, 2021). In addition to the several common spike mutations in Delta variant, two mutually explicit signature constellations of non-spike co-appearing mutations were identified, driving symptomatic and asymptomatic infections. We attempted to correlate these unique signatures of non-Spike co-appearing mutations to COVID-19 disease outcome. Results revealed that the Delta strains harboring a unique constellation of 9 non-spike co-appearing mutations could be the wheeler and dealer of symptomatic infection, even post vaccination. The strains predominantly driving asymptomatic infection possessed 7 non-spike co-appearing mutations, which were mutually exclusive in contrast to the set of mutations causing symptomatic disease. Phylodynamic analysis depicted high probability of emergence of these unique sub-clusters within India, with subsequent spread worldwide. Interestingly, some mutations of this signature were selected in Omicron and IHU variants, which suggest that gradual accumulation of such co-existing mutations may lead to emergence of more “vaccine-evading variants” in future. Hence, unfaltering genome sequencing and tracking of non-Spike mutations might be significant in formulation of any future vaccines against emerging SARS-CoV-2 variants that might evade the current vaccine-induced immunity.
Goal-directed recruitment of Pavlovian biases through selective visual attention
Authors: Algermissen Johannes , den Ouden Hanneke E.M.
Published: April 2022

Prospective outcomes bias behavior in a “Pavlovian” manner: Reward prospect invigorates action, while punishment prospect suppresses it. Theories have posited Pavlovian biases as global action “priors” in unfamiliar or uncontrollable environments. However, this account fails to explain the strength of these biases—causing frequent action slips—even in well-known environments. We propose that Pavlovian control is additionally useful if flexibly recruited by instrumental control. Specifically, instrumental action plans might shape selective attention to reward/ punishment information and thus the input to Pavlovian control. In two eye-tracking samples (N = 35/ 64), we observed that Go/ NoGo action plans influenced when and for how long participants attended to reward/ punishment information, which in turn biased their responses in a Pavlovian manner. Participants with stronger attentional effects showed higher performance. Thus, humans appear to align Pavlovian control with their instrumental action plans, extending its role beyond action defaults to a powerful tool ensuring robust action execution.
Can the Insect Path Integration Memory be a Bump Attractor?
Authors: Pisokas Ioannis , Kudryashova Nina , Hennig Matthias H.
Published: April 2022

Many animal species are able to return to their nest after a foraging excursion without using familiar visual cues to guide them. They accomplish this by using a navigation competence known as path integration, which is vital in environments that do not have prominent visual features. To perform path integration, an animal maintains a running estimate of the distance and direction to its origin as it moves. This distance and direction estimate needs to be maintained in memory until the animal uses it to return to its nest. However, the neural substrate of this memory remains uncertain. A common hypothesis is that the information is maintained in a bump attractor’s state. We test the bump attractor hypothesis and find that its predictions are inconsistent with the path integration behaviour of ants, thus highlighting the need for alternative models of path integration memory.
Fragmented habitat compensates for the adverse effects of genetic bottleneck
Authors: Löytynoja Ari , Rastas Pasi , Valtonen Mia , Kammonen Juhana , Holm Liisa , Olsen Morten Tange , Paulin Lars , Jernvall Jukka , Auvinen Petri
Published: April 2022

In the face of human-caused biodiversity crisis, understanding the theoretical basis of conservation efforts of endangered species and populations has become increasingly important. According to population genetics theory, population subdivision helps organisms retain genetic diversity, crucial for adaptation in a changing environment. Habitat shape is thought to be important for generating and maintaining population subdivision, but empirical cases are needed to test this assumption. We studied Saimaa ringed seals, landlocked in a labyrinthine lake and recovering from a drastic bottleneck, by whole-genome sequencing 105 individuals and additional individuals from three other ringed seal subspecies. We analyzed the distribution of variation and genetic relatedness among the individuals in relation to the habitat shape. Despite a severe history of a genetic bottleneck with prevalent homozygosity in Saimaa ringed seals, we found evidence for population structure mirroring the subregions of the lake. Highlighting the significance of habitat connectivity in conservation biology and the power of genomic tools in understanding its impact, genome-wide analyses showed that the subpopulations had retained unique variation and largely complementary patterns of homozygosity. Integration of genetic analyses in conservation decisions gives hope to Saimaa ringed seals and other endangered species in fragmented habitats.
Microclimate is a strong predictor of the native and invasive plant-associated soil microbiota on San Cristóbal Island, Galápagos archipelago
Authors: Schoenborn Alexi A. , Yannarell Sarah M. , MacVicar Caroline T. , Barriga-Medina Noelia N. , Markillie Meng , Mitchell Hugh , Bonham Kevin S. , Leon-Reyes Antonio , Riveros-Iregui Diego , Klepac-Ceraj Vanja , Shank Elizabeth A.
Published: April 2022

Understanding the major drivers that influence soil bacterial and fungal communities is essential to mitigate the impacts of human activity on vulnerable ecosystems, like those found on the Galápagos Islands. Located ~1000 km off the coast of Ecuador, the volcanically formed islands are situated within distinct oceanic currents, which provide seasonal weather patterns and unique microclimates within small spatial scales across the islands. Although much is known about the impacts of human activity, such as climate change and invasive plant species, on above ground biodiversity of the Galápagos Islands, little is known about the resident soil microbial communities and the drivers that shape these communities. Here, our goal was to investigate the bacterial and fungal communities found in soil located in three distinct microclimates: Mirador (arid), Cerro Alto (transition zone), and El Junco (humid), and associated with native and invasive plant types. At each site, we collected soil at three depths (rhizosphere, 5 cm, and 15 cm) associated with the invasive plant,Psidium guajava(guava), and native plant types. We determined that the sampling location (microclimate) was the strongest driver of both bacterial and fungal communities (74 and 38%, respectively), with additional minor but significant impacts from plant type and soil depth. This study highlights the continued need to explore microbial communities across diverse environments and demonstrates the weight of different abiotic and biotic factors impacting soil microbial communities across San Cristóbal Island in the Galápagos archipelago.

IMPORTANCE/SIGNIFICANCE

Human activity such as climate change, pollution, introduction of invasive species, and deforestation, poses a huge threat to biodiverse environments. Soil microbiota are an essential component to maintaining healthy ecosystems. However, a greater understanding of factors that alter these microbial communities is needed in order to find ways to mitigate and reverse the impacts imposed by human activity. The Galápagos Islands are a unique real-world laboratory, in that the islands’ biogeography and physical locations in the Pacific Ocean provide distinct microclimates within small geographic distances. Harnessing these distinct environments allowed us to investigate the influence of microclimates, soil depth, and vegetation cover on bacterial and fungal community composition.
Tracing carbon metabolism with stable isotope metabolomics reveals the legacy of diverse carbon sources in soil
Authors: Wilhelm Roland C. , Barnett Samuel E. , Swenson Tami L. , Youngblut Nicholas D. , Koechli Chantal N. , Bowen Benjamin P. , Northen Trent R. , Buckley Daniel H.
Published: April 2022

Tracking the metabolic activity of whole soil communities can improve our understanding of the transformation and fate of carbon in soils. We used stable isotope metabolomics to trace 13C from nine labeled carbon sources into the water-soluble metabolite pool of an agricultural soil over time. Soil was amended with a mixture of all nine sources, with one source isotopically labeled in each treatment. We compared changes in the 13C-enrichment of metabolites with respects to carbon source and time over a 48-day incubation and contrasted differences between soluble versus insoluble sources. Whole soil metabolite profiles varied singularly by time, while the composition of 13C-labeled metabolites differed primarily by carbon source (R2 = 0.68) rather than time (R2 = 0.07) with source-specific differences persisting throughout incubations. The 13C-labeling of metabolites from insoluble carbon sources occurred at a slower rate than soluble sources but yielded a higher average atom % 13C in metabolite markers of biomass (amino acids and nucleic acids). The 13C-enrichment of metabolite markers of biomass stabilized at between 5 – 15 atom % 13C by the end of incubations. Temporal patterns in the 13C-enrichment of TCA cycle intermediates, nucleobases (uracil and thymine), and by-products of DNA salvage (allantoin) closely tracked microbial activity. Our results demonstrate that metabolite production in soils is driven by the carbon source supplied to the community, and that the fate of carbon in metabolite profiles do not tend to converge over time as a result of ongoing microbial processing and recycling.

Importance

Carbon metabolism in soil remains poorly described due to the inherent difficulty of obtaining information on the microbial metabolites produced by complex soil communities. Our study demonstrates the use of stable isotope probing (SIP) to study carbon metabolism in soil by tracking 13C from supplied carbon sources into metabolite pools and biomass. We show that differences in the metabolism of sources influences the fate of carbon in soils. Heterogeneity in 13C-metabolite profiles corresponded with compositional differences in the metabolically active populations, providing a basis for how microbial community composition is correlated with the quality of soil carbon. Our study demonstrates the application of SIP-metabolomics in studying soils and identifies several metabolite markers of growth, activity, and other aspects of microbial function.
INTERCEPT pathogen reduction of platelet concentrates induces trans-arachidonic acids and affects eicosanoid formation
Authors: Leitner Gerda C. , Hagn Gerhard , Niederstätter Laura , Bileck Andrea , Plessl-Walder Kerstin , Horvath Michaela , Kolovratova Vera , Tanzmann Andreas , Tolios Alexander , Rabitsch Werner , Wohlfarth Philipp , Gerner Christopher
Published: April 2022

Gamma-irradiation of blood products is mandatory to avoid graft versus host disease in patients with immunosuppressed clinical conditions. Pathogen inactivation techniques were implemented to optimize safe blood component supply. The INTERCEPT treatment uses amotosalen together with UVA irradiation. The functional and molecular implications of these essential treatments have not yet been systematically assessed. The irradiation-induced inactivation of nucleic acids may actually be accompanied with modifications of chemically reactive polyunsaturated fatty acids, known to be important mediators of platelet functions. Thus, here we investigated eicosanoids and related fatty acids released upon treatment and during platelet storage for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. In contrast to gamma-irradiation, here we demonstrate that UVA treatment attenuated the formation of ALOX12-products such as 12-HETE and 12-HEPE but induced the formation of trans-arachidonic acids in addition to 11-HETE and HpODEs. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation and clot firmness hardly differed between the two treatment groups. In vitro synthesis of trans-arachidonic acids (trans-AA) out of arachidonic acid in the presence of β-mercaptoethanol suggested that thiol radicals formed by UVA treatment are responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is plausible to assume that trans-AA and other UVA-induced molecules may have specific biological effects on the recipients, which need to be addressed in future studies.

Key points

A previously unrecognized radical mechanisms for the generation of trans-fatty acids by UVA was identified

Irradiation with UVA was found to immediately affect the generation of polyunsaturated fatty acid oxidation products
Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice
Authors: Bedard Madigan L. , Lord Julia Sparks , Perez Patric J. , Bravo Isabel M. , Teklezghi Adonay T. , Tarantino Lisa , Diering Graham , McElligott Zoe A.
Published: April 2022

Opioid misuse has dramatically increased over the last few decades resulting in many people suffering from opioid use disorder (OUD). The prevalence of opioid overdose has been driven by the development of new synthetic opioids, increased availability of prescription opioids, and more recently, the COVID-19 pandemic. Coinciding with increases in exposure to opioids, the United States has also observed increases in multiple Narcan (naloxone) administrations as life-saving measures for respiratory depression, and, thus, consequently, naloxone-precipitated withdrawal. Sleep dysregulation is a main symptom of OUD and opioid withdrawal syndrome, and therefore, should be a key facet of animal models of OUD. Here we examine the effect of precipitated and spontaneous morphine withdrawal on sleep behaviors in C57BL/6J mice. We find that morphine administration and withdrawal dysregulate sleep, but not equally across morphine exposure paradigms. Furthermore, many environmental triggers promote relapse to drug-seeking/taking behavior, and the stress of disrupted sleep may fall into that category. We find that sleep deprivation dysregulates sleep in mice that had previous opioid withdrawal experience. Our data suggest that the 3-day precipitated withdrawal paradigm has the most profound effects on opioid-induced sleep dysregulation and further validates the construct of this model for opioid dependence and OUD.

Highlights

Morphine withdrawal differentially dysregulates the sleep of male and female mice

3-day precipitated withdrawal results in larger changes than spontaneous withdrawal

Opioid withdrawal affects responses to future sleep deprivation differently between sexes
Bis(oxotremorine) fumarate bis(fumaric acid)
Authors: Naeem Marilyn , Chadeayne Andrew R. , Golen James A. , Manke David R.
Published: April 2022

The title compound, bis(oxotremorine) fumarate bis(fumaric acid) {systematic name: 1-[4-(2-oxopyrrolidin-1-yl)but-2-ynyl]pyrrolidinium (2E)-but-2-enedioate bis[(2E)-but-2-enedioic acid]}, 2C12H19N2O+·C4H2O4
2−·2C4H4O4, has a single oxotremorine monocation protonated at the pyrrolidine nitrogen, one fumaric acid molecule and half of a fumarate dianion in the asymmetric unit. The ions and fumaric acid molecules are held together by N—H...O and O–H-...O hydrogen bonds in 40-membered rings with graph-set notation R
6
6(40). The fumarate ions join these rings into infinite chains along [001].