bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching Mindfulness to Mitigate Burnout in a Pandemic
Authors: Tolouian Audrey , Wholeben Melissa , Rankin Diane
Published: January 2022

BACKGROUND:

Posttraumatic stress syndrome has been on the rise across all nursing specialties. When dealing with high-stress situations in the workplace, it has become clear that health care providers require tools to maintain a healthy environment.

OBJECTIVE:

The purpose of this article is to describe an initiative to provide baccalaureate nursing students with mindfulness techniques to manage their internal reactions to day-to-day events during a pandemic.

METHODS:

This is an innovative classroom initiative reviewing nursing student engagement on a discussion board related to mindfulness reflection questions before and after implementing an 8-week mindfulness program conducted from August to October 2020 in a first-year undergraduate nursing program in Texas.

RESULTS:

A total of 124 student nurses participated in a mindfulness program. The majority of these were women (83.9%), aged 19–50 years, single (78.2%), and Hispanic or Latino (84.7%). Discussion board engagement increased from n = 1,001 posts over 16-week premindfulness program implementation to n = 4,191 over the first 10 weeks of the program implementation.

CONCLUSION:

Nursing implications include providing an atmosphere in which nurses can practice mindfulness skills, such as being in touch with their thoughts and bodies, which will help them transition into the position of trauma nurse. As nurse educators, it is our responsibility to assist in developing tools that students and patients may use to deal with their anxiety and foster an environment that promotes learning, understanding, and compassion.
Costs Associated With Incorporation of Network Approaches Into Sexually Transmitted Disease Program Activities
Authors: Williams Austin M. , Eppink Samuel T. , Guy Jalila N. , Seña Arlene C. , Berruti Andrés A.
Published: January 2022

Background

Network approaches can be used to study sociosexual partnerships and identify individuals at high risk of infection. Little is known about the cost structure of these services and their association with STD diagnoses.

Method

We collected costs associated with using a peer network strategy to recruit men who have sex with men and transwomen of color in 4 counties in North Carolina: Guilford, Forsyth, Durham, and Wake from February through October 2019. We used a comprehensive costing approach to gather detailed retrospective information on the intervention cost, broken down by category and programmatic activity.

Results

The sociosexual networks collected consisted of 31 initial seeds (index cases) and 49 peers of those seeds. In peers, 5 cases of human immunodeficiency virus (HIV) and 10 cases of syphilis were identified. The cost per case (HIV or syphilis) identified was $7325. Personnel costs accounted for 80% of total expenditures, followed by laboratory expenses (12%). Personnel cost was distributed between disease intervention specialist patient navigators (51%), nonclinical (37%), and management (12%) staff. General administration was the costliest programmatic activity (37%), followed by case management and field services (37%), and study activities (11%). The estimated average cost per patient tested was $2242.

Conclusions

Finding positive peer cases in nonclinical settings is costly but may be crucial for limiting the spread of sexually transmitted diseases. The cost of staff was the major driver. This study demonstrates that using a network strategy can be a cost-effective way to identify, test, and refer patients at high risk of syphilis and HIV infections to care.
The Emergence of Hepatitis C Virus Genotype 4d Among Human Immunodeficiency Virus–Infected Patients in Mexico City: A Molecular Epidemiological Study
Authors: Lopez Luis Bruno Ali , Rodríguez-Díaz Roberto , Angulo-Medina Luis , Soto-Ramírez Luis Enrique
Published: January 2022

The recent detection of hepatitis C virus genotype 4 infection in human immunodeficiency virus–infected patients prompted performing molecular characterization of these isolates. All the Mexican isolates belonged to a subcluster within the 4d group and shared a common ancestor with a French isolate. The estimated timing of introduction in Mexico City was as recent as December 2015.
Case Report: Intracorneal Hemorrhages Seen with Scleral Contact Lens Wear and Netarsudil Therapy
Authors: Crum Amanda R. , Srikumaran Divya
Published: January 2022

SIGNIFICANCE

Intracorneal hemorrhages are a rare finding generally associated with surgery or trauma. There is no consensus on preferred management except eliminating or addressing the causative mechanism in hopes of reducing the risk of corneal haze or scarring.

PURPOSE

This case highlights a rare adverse outcome of intracorneal hemorrhages occurring after recent initiation of netarsudil, possibly exacerbated by scleral contact lens wear in a patient with open-angle glaucoma and limbal stem cell deficiency.

CASE REPORT

A 77-year-old man using scleral contact lenses for therapeutic management of limbal stem cell deficiency started netarsudil for open-angle glaucoma. During an annual follow-up to adjust his scleral contact lenses, the patient developed peripheral intracorneal hemorrhages bilaterally. The intracorneal hemorrhages resolved over the course of 10 weeks after minor adjustments were made to the scleral contact lens fit and netasurdil was discontinued. Visual acuity and intraocular pressure remained stable throughout.

CONCLUSIONS

There are few reports of intracorneal hemorrhages associated with scleral contact lens use and even fewer associated with the use of netarsudil. This case proposes several possible causes of the intracorneal hemorrhages, including topical rho-associated kinase inhibitors, contact lens wear, and trauma. Further studies are needed to determine if netarsudil is associated with intracorneal hemorrhages, to understand the sequelae of intracorneal hemorrhages in netarsudil therapy, and to recommend management when intracorneal hemorrhages manifest with netarsudil use.
Case Report: Visual Snow Syndrome after Repetitive Mild Traumatic Brain Injury
Authors: Werner Rachel N. , Gustafson Jennifer A.
Published: January 2022

SIGNIFICANCE

Visual snow syndrome is a recently recognized condition with its own diagnostic criteria, evolving pathophysiologic research, and potential treatment options.

PURPOSE

This report documents a rare but likely underdiagnosed condition called visual snow syndrome. A review of the current literature on pathophysiology and treatments is discussed.

CASE REPORT

A 40-year-old Whiteman started experiencing symptoms of constant pulsating pixels throughout his entire visual field approximately 3 weeks after a series of mild concussions. In addition, he experienced a persistence of images and photosensitivity. The patient had normal eye examination results, visual fields, and retinal imaging result. Brain MRI, magnetic resonance angiography, electroencephalography, and cerebrospinal fluid analysis were unremarkable. A positron emission tomography scan demonstrated hypometabolism in the posterior parietal lobes and left posterior cingulate gyrus. Pharmacological treatment with antiepileptic and migraine medications was unsuccessful. Tinted lenses were essentially ineffective with a 10% reduction in symptoms reported with the use of a custom blue-tinted lens.Vision rehabilitation aids with optical character recognition were used for prolonged reading needs.

CONCLUSIONS

Although rare, visual snow syndrome should be considered in all patients reporting continuous pixelations in their vision for more than 3 months, especially when accompanied by at least two of the following: photosensitivity, palinopsia, enhanced entopic phenomena, or nyctalopia. The pathophysiology is still unclear at this point, with evidence suggesting a link to the secondary visual cortex, specifically the lingual gyrus. More studies are needed to determine the exact cause, especially studies that separate visual snow syndrome patients with and without comorbid migraine. Because the pathophysiology is unclear, the treatment course is also unclear. Anecdotal evidence may suggest that tinted lenses may be of some value.
Technical Report: Reducing Lens Fogging Associated with Patient Mask Wearing with Heated Diagnostic Fundoscopy Lenses
Authors: Fabrykowski Marta C. , Schwartz Luke A. , Gupta Rohun R. , Mitchell Jamie R.
Published: January 2022

SIGNIFICANCE

Severe acute respiratory syndrome coronavirus 2 has indirectly created challenges to the ophthalmic retinal examinations because of lens fogging related to patients wearing masks. To date, there are no objective data on the degree of diagnostic ophthalmic lens fogging associated with mask wearing or on the effectiveness of proposed solutions to ophthalmologic lens fogging.

PURPOSE

The purposes of this study were to investigate the degree of ophthalmologic lens fogging in patients wearing masks and to assess the efficacy lens warming in reducing lens fogging and facilitating ophthalmologic retinal examinations.

METHODS

This study quantified the degree of lens fogging in mask-wearing subjects using ImageJ to measure lens surface area fogged in slit-lamp photographs of 90 D lenses before and after the use of a lens warmer. We investigated the clinical relevance of diagnostic lens fogging via a survey study of eye care providers. Subjects rated on a Likert scale their experience with diagnostic lens fogging during retinal examination in mask-wearing patients with and without the use of a lens warming device.

RESULTS

For mask-wearing subjects, the percentage of fogged lens area in a 90 D lens averaged 32.5% using an unheated lens and 1.1% using a heated lens. Survey responders noted significantly less fogging of the 78 and 90 D lenses on retinal examination when using the lens warmer (P < .001) and found that using the lens warmer facilitated their retinal examination (P < .001).

CONCLUSIONS

This study shows that there is significant fogging of ophthalmic slit-lamp lenses associated with patients wearing masks and that using a lens warmer significantly reduces fogging and facilitates retinal examinations. Eye care providers would benefit from the use of a lens warmer to reduce diagnostic lens fogging during retinal examination.
Case Report: Bilateral Cecocentral Visual Field Defect Secondary to Congenital Optic Disc Pit
Authors: Mangum Andrew J.
Published: January 2022

SIGNIFICANCE

Congenital optic disc pits are known to cause complications, commonly maculopathy due to retinoschisis and/or neurosensory retinal detachment. Retinal nerve fiber layer defects with associated visual field defects without maculopathy are another complication and can result in decreased visual function but have rarely been reported in the literature, especially bilaterally.

PURPOSE

This case report describes a patient with bilateral cecocentral visual field defects due to congenital optic nerve pits without associated maculopathy.

CASE REPORT

A 42-year-old Black man presented with blur symptoms at near uncorrected. Of note, there was no history of substance abuse or nutritional deficiencies. Best-corrected acuities were 20/20 in the right eye and 20/30 in the left eye. Clinical examination revealed bilateral focal grayish depression of the temporal optic nerve cup with associated papillomacular retinal nerve fiber layer defects. Optical coherence tomography (OCT) imaging revealed bilateral focal excavation of the temporal cup, temporal thinning of the retinal nerve fiber layer, and correlated binasal thinning of the ganglion cell complex, in the absence of retinoschisis or neurosensory detachment. Threshold visual field testing revealed stable bilateral cecocentral visual field defects. A diagnosis of bilateral cecocentral visual field defect secondary to congenital optic disc pits was made based on the patient's history and clinical examination.

CONCLUSIONS

A cecocentral visual field defect, unrelated to maculopathy, is a less common complication of congential optic disc pits that can cause decreased visual function. This case report provides evidence of this bilateral ocular condition and reviews the reported clinical, OCT, and threshold visual field manifestations of the disease. Specifically, spectral-domain OCT ganglion cell analysis seems useful in localizing the visual field defect.
Prognostic Significance of Cancer Stem Cell Markers in Patients With Salivary Gland Carcinomas
Authors: Sadeghi Hanieh , Saffar Hana , Taheri Pardis , Yazdani Farzad , Etebarian Arghavan
Published: January 2022

Objectives:

Cancer stem cells (CSCs) are a small group of cells resistant to therapy and play a major role in tumor progression, recurrence, and poor clinical outcomes of patients. This study aimed to evaluate the association of CSC markers with clinicopathologic features and survival in patients with salivary gland carcinomas (SGCs).

Materials and Methods:

The medical records of 48 patients affected by mucoepidermoid carcinoma (MEC) and 47 patients with adenoid cystic carcinoma (AdCC) were reviewed retrospectively. SOX2, CD133, and CD44 expression was appraised by immunohistochemistry and statistically analyzed to weigh the correlation between these markers and patients’ clinicopathologic features and tumor outcomes.

Results:

In AdCC patients showing poor outcomes, a trend toward a high expression of CD133 and CD44 and low expression of SOX2 was observed, while in MEC patients experiencing the same outcomes, there was a trend toward a high expression of CD44 and low expression of CD133 and SOX2. Only the increase of MEC histopathologic grade was statistically significant with decreased SOX2 expression. Distant metastasis in AdCC patients, tumor grade, lymph node involvement, and local recurrence in MEC patients had significant correlations with patients’ survival.

Conclusion:

Besides the significant association between low SOX2 expression and higher grades of MEC, we found no statistically significant correlation between the studied CSC markers and patients’ survival or clinicopathologic features. Therefore, a larger sample size with long-term follow-up is beneficial for thorough investigations toward the main role of CSCs in patients with SGCs.
Discordant Metabolic Response on 18F-FDG PET/CT in Synchronous Primary Gastric Lymphoma and Gastric Adenocarcinoma
Authors: Hao Wanting , Li Yaming , Du Bulin , Li Xuena
Published: January 2022

An 84-year-old man presented with dysphagia for 20 days. The biopsies of the multiple lesions through gastroscopy revealed gastric diffuse large B-cell lymphoma and gastric adenocarcinoma. Staging 18F-FDG PET/CT showed multiple hypermetabolic lesions in the stomach, abdomen, and pelvis. After 4 courses of chemotherapy, except for the lesion of biopsy-proven gastric adenocarcinoma, other hypermetabolic lesions in stomach and other sites returned to normal on posttherapy 18F-FDG PET/CT. This case indicated that 18F-FDG PET/CT can track differential treatment response of synchronous gastric tumors and guide subsequent therapy.
Application of Multimodal Imaging Biomarker in the Differential Diagnosis of Ovarian Mass
Authors: Bang Ji-In , Kim Ji-Young , Choi Min Chul , Lee Ho-Young , Jang Su Jin
Published: January 2022

Purpose

The aim is to investigate the diagnostic performance of multimodal imaging with 18F-FDG PET/CT, MRI, and contrast-enhanced CT (CECT) in cases with unilateral or bilateral ovarian mass without ancillary findings of malignancy.

Methods

Retrospectively, 307 patients who had unilateral or bilateral ovarian masses and underwent preoperative FDG PET/CT and/or MRI/CECT were included. The criterion standard for the ovarian mass was the final pathology. The peak standardized uptake value (SULpeak) among benign tumors (BTs), borderline ovarian tumors (BoTs), and malignant ovarian tumors (MTs) were compared. The cutoff value of SULpeak to discriminate between BT/BoT and MT was determined from the training (n = 200) and validation (n = 131) cohorts. Diagnostic performances of SULpeak, Ovarian-Adnexal Reporting Data System (O-RADS) MRI score, CECT findings, and combination of multimodal imagings were analyzed.

Results

SULpeak of MT was significantly higher than that of BT or BoT (P < 0.05). There was no significant difference in SULpeak between BT and BoT (P = 0.147). The cutoff value of SULpeak for discriminating between BT/BoT and MT was 1.76 (sensitivity, 87.0%; specificity, 83.0%). Diagnostic performance for BT/BoT versus MT of O-RADS MRI, CECT, FDG PET/CT plus O-RADS MRI score, and FDG PET/CT plus CECT yielded the respective sensitivities of 100%, 94%, 95%, and 82%, and specificities of 43%, 46%, 88%, and 91%, respectively.

Conclusions

Multimodal imaging biomarkers including FDG PET/CT and MR/CECT could provide additional information to differentiate ovarian masses.
Measuring dominance certainty and assessing its impact on individual and societal health in a nonhuman primate model: a network approach
Authors: McCowan Brenda , Vandeleest Jessica , Balasubramaniam Krishna , Hsieh Fushing , Nathman Amy , Beisner Brianne
Published: January 2022

The notion of dominance is ubiquitous across the animal kingdom, wherein some species/groups such relationships are strictly hierarchical and others are not. Modern approaches for measuring dominance have emerged in recent years taking advantage of increased computational power. One such technique, named Percolation and Conductance (Perc), uses both direct and indirect information about the flow of dominance relationships to generate hierarchical rank order that makes no assumptions about the linearity of these relationships. It also provides a new metric, known as ‘dominance certainty’, which is a complimentary measure to dominance rank that assesses the degree of ambiguity of rank relationships at the individual, dyadic and group levels. In this focused review, we will (i) describe how Perc measures dominance rank while accounting for both nonlinear hierarchical structure as well as sparsity in data—here we also provide a metric of dominance certainty estimated by Perc, which can be used to compliment the information dominance rank supplies; (ii) summarize a series of studies by our research team reflecting the importance of ‘dominance certainty’ on individual and societal health in large captive rhesus macaque breeding groups; and (iii) provide some concluding remarks and suggestions for future directions for dominance hierarchy research.

This article is part of the theme issue ‘The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies’.
High seroprevalence of SARS-CoV-2 in white-tailed deer (Odocoileus virginianus) at one of three captive cervid facilities in Texas
Authors: Roundy Christopher M. , Nunez Chase M. , Thomas Logan F. , Auckland Lisa D. , Tang Wendy , Richison Jack J. , Green Breanna R. , Hilton Clayton D. , Cherry Michael J. , Pauvolid-Correa Alex , Hamer Gabriel L. , Cook Walter E. , Hamer Sarah A.
Published: January 2022

Free-ranging white-tailed deer (Odocoileus virginanus) across the United States are increasingly recognized as involved in SARS-CoV-2 transmission cycles. Through a cross-sectional study of 80 deer at three captive cervid facilities in central and southern Texas, we provide evidence of 34 of 36 (94.4%) white-tailed deer at a single captive cervid facility seropositive for SARS-CoV-2 by neutralization assay (PRNT90), with endpoint titers as high as 1280. In contrast, all tested white-tailed deer and axis deer (Axis axis) at two other captive cervid facilities were seronegative, and SARS-CoV-2 RNA was not detected in respiratory swabs from deer at any of the three facilities. These data support transmission among captive deer that cannot be explained by human contact for each infected animal, as only a subset of the seropositive does had direct human contact. The facility seroprevalence was more than double of that reported from wild deer, suggesting that the confined environment may facilitate transmission. Further exploration of captive cervids and other managed animals for their role in the epizootiology of SARS-CoV-2 is critical for understanding impacts on animal health and the potential for spillback transmission to humans or other animal taxa.

Importance

As SARS-CoV-2 vaccine coverge of the human population increases and variants of concern continue to emerge, identification of the epidemiologic importance of animal virus reservoirs is critical. We found that nearly all (94.4%) of the captive white-tailed deer at a cervid facility in central Texas had neutralizing antibodies for SARS-CoV-2. This seroprevalence is over double than that which has been reported from free-ranging deer from other regions of the US. Horizontal transmission among deer may be facilitated in confinement. Tracking new infections among wild and confined deer is critical for understanding the importance of animal reservoirs for both veterinary and human health.
Dissecting conformational rearrangements and allosteric modulation in metabotropic glutamate receptor activation
Authors: Lecat-Guillet Nathalie , Quast Robert B. , Liu Hongkang , Møller Thor C. , Rovira Xavier , Soldevila Stéphanie , Lamarque Laurent , Trinquet Eric , Liu Jianfeng , Pin Jean-Philippe , Rondard Philippe , Margeat Emmanuel
Published: January 2022

Selective allosteric modulators bear great potential to fine-tune neurotransmitter-induced brain receptor responses. Promising targets are metabotropic glutamate (mGlu) receptors, which are associated to different brain diseases. These multidomain class C GPCRs experience concerted structural rearrangements and rely on allosteric modulation of agonist action to be fully activated. Here we establish live cell compatible fluorescence labeling of mGlu2 by click chemistry through genetic code expansion. Using lanthanide resonance energy transfer, we establish multiple FRET sensors to monitor ligand effects on conformational changes in mGlu2 extracellular domain and subsequently dissect the underlying conformational states by smFRET. Using three distinct FRET sensors, we demonstrate that mGlu activation relies on a ligand-induced sampling of three conformational states. Orthosteric agonists act by promoting the closure of the mGlu2 ligand binding domains, leading to an equilibrium between an inactive intermediate and the active state. Allosteric modulator further push this equilibrium toward the active state, promoting and stabilizing the relative reorientation of the mGlu protomers. These results underline the complex and dynamic nature of such type of neuroreceptors, pointing out that ligands fine-tune activation by differentially acting on the equilibria between multiple states.
WhyD tailors surface polymers to prevent bacteriolysis and direct cell elongation in Streptococcus pneumoniae
Authors: Flores-Kim Josué , Dobihal Genevieve S. , Bernhardt Thomas G. , Rudner David Z.
Published: January 2022

Penicillin and related antibiotics disrupt cell wall synthesis in bacteria and induce lysis by misactivating cell wall hydrolases called autolysins. Despite the clinical importance of this phenomenon, little is known about the factors that control autolysins and how penicillins subvert this regulation to kill cells. In the pathogenStreptococcus pneumoniae(Sp), LytA is the major autolysin responsible for penicillin-induced bacteriolysis. We recently discovered that penicillin treatment ofSpcauses a dramatic shift in surface polymer biogenesis in which cell wall-anchored teichoic acids (WTAs) increase in abundance at the expense of lipid-linked lipoteichoic acids. Because LytA binds to these polymers, this change recruits the enzyme to its substrate where it cleaves the cell wall and elicits lysis. In this report, we identify WhyD (SPD_0880) as a new factor that controls the level of WTAs inSpcells to prevent LytA misactivation and lysis. We show that WhyD is a WTA hydrolase that restricts the WTA content of the wall to areas adjacent to active PG synthesis. Our results support a model in which the WTA tailoring activity of WhyD directs PG remodeling activity required for proper cell elongation in addition to preventing autolysis by LytA.
Dynamic changes in mRNA nucleocytoplasmic localization in the nitrate response of Arabidopsis roots
Authors: Fonseca Alejandro , Moyano Tomás C. , Rosa Stefanie , Gutiérrez Rodrigo A.
Published: January 2022

Nitrate (NO3-) is a signaling molecule that regulates gene expression in plants. The nitrate response has been extensively characterized at the transcriptome level. However, we know little about RNA nucleocytoplasmic dynamics during nitrate response. To understand the role of mRNA localization during the nitrate response, we isolated mRNA from the nucleus, cytoplasm, and whole-cells from nitrate-treated Arabidopsis roots and performed RNA-seq. We identified 402 differentially localized transcripts (DLTs) in response to nitrate. DLTs were enriched in GO-terms related to metabolism, response to stimulus, and transport. DLTs showed five localization patterns: nuclear reduction, cytoplasmic reduction, nuclear accumulation, cytoplasmic accumulation, or delayed-cytoplasmic accumulation in response to nitrate. DLTs exhibited large changes in RNA polymerase II occupancy of cognate genes and high mRNA turnover rates, indicating these are rapidly replaced mRNAs. The NITRATE REDUCTASE 1 (NIA1) transcript exhibited the largest changes in synthesis and decay. Using single-molecule RNA FISH, we showed that NIA1 nuclear accumulation occurs mainly at transcription sites. The decay profiles for NIA1 showed a higher half-life when the transcript accumulated in the nucleus than in the cytoplasm. We propose that regulating nucleocytoplasmic mRNA distribution allows tuning transcript availability of fastly replaced mRNAs, controlling plants’ adaptive response to nitrogen nutrient signals.
Controlling periodic long-range signalling to drive a morphogenetic transition
Authors: Ford Hugh Z , Manhart Angelika , Chubb Jonathan R
Published: January 2022

Cells use signal relay to transmit information across tissue scales. However, the production of information carried by signal relay remains poorly characterised. To determine how the coding features of signal relay are generated, we used the classic system for long-range signalling: the periodic cAMP waves that drive Dictyostelium collective migration. Combining imaging and optogenetic perturbation of cell signalling states, we find that migration is triggered by an increase in wave frequency generated at the signalling centre. Wave frequency is regulated by cAMP wave circulation, which organises the long-range signal. To determine the mechanisms modulating wave circulation, we combined mathematical modelling, the general theory of excitable media and mechanical perturbations to test competing models. Models in which cell density and spatial patterning modulate the wave frequency cannot explain the temporal evolution of signalling waves. Instead, our evidence leads to a model where wave circulation increases the ability for cell to relay the signal, causing further increase in the circulation rate. This implies that information driving a morphogenetic transition gradually unfolds due to positive feedback between cell signalling state and signalling pattern. This demonstrates how the coding properties of a long-range signal arise from self-organised wave dynamics at the signalling centre.
A novel mouse model based on intersectional genetics enables unambiguous in vivo discrimination between plasmacytoid and other dendritic cells and their comparative characterization
Authors: Valente Michael , Collinet Nils , Manh Thien-Phong Vu , Naciri Karima , Bessou Gilles , Gil Laurine , Milpied Pierre , Tomasello Elena , Dalod Marc
Published: January 2022

Plasmacytoid dendritic cells (pDC) were identified about 20 years ago, based on their unique ability to rapidly produce copious amounts of all subsets of type I and type III interferon (IFN-I/III) upon virus sensing, while being refractory to infection. Yet, the identity and physiological functions of pDC are still a matter of debate, in a large part due to their lack of specific expression of any single cell surface marker or gene that would allow to track them in tissues and to target them in vivo with high specificity and penetrance. Indeed, recent studies showed that previous methods that were used to identify or deplete pDC also targeted other cell types, including pDC-like cells and transitional DC (tDC) that were proposed to be responsible for all the antigen presentation ability previously attributed to steady state pDC. Hence, improving our understanding of the nature and in vivo choreography of pDC physiological functions requires the development of novel tools to unambiguously identify and track these cells, including in comparison to pDC-like cells and tDC. Here, we report successful generation of a pDC-reporter mouse model, by using an intersectional genetic strategy based on the unique co-expression of Siglech and Pacsin1 in pDC. This pDC-Tomato mouse strain allows specific ex vivo and in situ detection of pDC. Breeding them with Zbtb46GFP mice allowed side-by-side purification and transcriptional profiling by single cell RNA sequencing of bona fide pDC, pDC-like cells and tDC, in comparison to type 1 and 2 conventional DC (cDC1 and cDC2), both at steady state and during a viral infection, revealing diverging activation patterns of pDC-like cells and tDC. Finally, by breeding pDC-Tomato mice with Ifnb1EYFP mice, we determined the choreography of pDC recruitment to the micro-anatomical sites of viral replication in the spleen, with initially similar but later divergent behaviors of the pDC that engaged or not into IFN-I production. Our novel pDC-Tomato mouse model, and newly identified gene modules specific to combinations of DC types and activations states, will constitute valuable resources for a deeper understanding of the functional division of labor between DC types and its molecular regulation at homeostasis and during viral infections.
Time-adaptive Unsupervised Auditory Attention Decoding Using EEG-based Stimulus Reconstruction
Authors: Geirnaert Simon , Francart Tom , Bertrand Alexander
Published: January 2022

The goal of auditory attention decoding (AAD) is to determine to which speaker out of multiple competing speakers a listener is attending based on the brain signals recorded via, e.g., electroencephalography (EEG). AAD algorithms are a fundamental building block of so-called neuro-steered hearing devices that would allow identifying the speaker that should be amplified based on the brain activity. A common approach is to train a subject-specific stimulus decoder that reconstructs the amplitude envelope of the attended speech signal. However, training this decoder requires a dedicated ‘ground-truth’ EEG recording of the subject under test, during which the attended speaker is known. Furthermore, this decoder remains fixed during operation and can thus not adapt to changing conditions and situations. Therefore, we propose an online time-adaptive unsupervised stimulus reconstruction method that continuously and automatically adapts over time when new EEG and audio data are streaming in. The adaptive decoder does not require ground-truth attention labels obtained from a training session with the end-user and instead can be initialized with a generic subject-independent decoder or even completely random values. We propose two different implementations: a sliding window and recursive implementation, which we extensively validate on three independent datasets based on multiple performance metrics. We show that the proposed time-adaptive unsupervised decoder outperforms a time-invariant supervised decoder, representing an important step toward practically applicable AAD algorithms for neuro-steered hearing devices.
Analysis of historical selection in winter wheat
Authors: Yang Chin Jian , Ladejobi Olufunmilayo , Mott Richard , Powell Wayne , Mackay Ian
Published: January 2022

Winter wheat is a major crop with a rich selection history in the modern era of crop breeding. Genetic gains across economically important traits like yield have been well characterized and are the major force driving its production. Winter wheat is also an excellent model for analyzing historical genetic selection. As a proof of concept, we analyze two major collections of winter wheat varieties that were bred in western Europe from 1916 to 2010, namely the Triticeae Genome (TG) and WAGTAIL panels, which include 333 and 403 varieties respectively. We develop and apply a selection mapping approach, Regression of Alleles on Years (RALLY), in these panels, as well as in simulated populations. RALLY maps loci under sustained historical selection by using a simple logistic model to regress allele counts on years of variety release. To control for drift-induced allele frequency change, we develop a hybrid approach of genomic control and delta control. Within the TG panel, we identify 22 significant RALLY quantitative selection loci (QSLs) and estimate the local heritabilities for 12 traits across these QSLs. By correlating predicted marker effects with RALLY regression estimates, we show that alleles whose frequencies have increased over time are heavily biased towards conferring positive yield effect, but negative effects in flowering time, lodging, plant height and grain protein content. Altogether, our results (1) demonstrate the use of RALLY to identify selected genomic regions while controlling for drift, and (2) reveal key patterns in the historical selection in winter wheat and guide its future breeding.

Key Message

Modelling of the distribution of allele frequency over year of variety release identifies major loci involved in historical breeding of winter wheat.
Orally administered antigen can reduce or exacerbate pathology in an animal model of inflammatory arthritis dependent upon the timing of administration
Authors: Meehan Gavin R , McInnes Iain B , Brewer James M , Garside Paul
Published: January 2022

Currently, treatments for rheumatoid arthritis (RA) are focussed on treatment of disease symptoms rather than addressing the cause of disease, which could lead to remission and cure. Central to disease development is the induction of autoimmunity through a breach of self-tolerance. There is considerable research in RA focussed on antigens and approaches to re-establish antigen specific tolerance. A crucial step in this research is to employ appropriate animal models to test prospective antigen specific immunotherapies, preferably in the context of joint inflammation.

In this short communication, we use our previously developed model of antigen specific inflammatory arthritis in which OVA-specific TcR tg T cells drive breach of tolerance to endogenous antigens to determine the impact that the timing of therapy administration has upon disease progression. Using antigen feeding to induce tolerance we demonstrate that administration prior to articular challenge results in a reduced disease score as evidenced by pathology and serum antibody responses. By contrast, feeding antigen after articular challenge had the opposite effect and resulted in the exacerbation of pathology.

Although preliminary, these data suggest that the timing of antigen administration may be key to the success of tolerogenic immunotherapies. This has important implications for the timing of potential tolerogenic therapies in patients.
Towards a unified model of naive T cell dynamics across the lifespan
Authors: Rane Sanket , Hogan Thea , Lee Edward S. , Seddon Benedict , Yates Andrew J.
Published: January 2022

Naive CD4 and CD8 T cells are cornerstones of adaptive immunity, but the dynamics of their establishment early in life and how their kinetics change as they mature following release from the thymus are poorly understood. Further, due to the diverse signals implicated in naive T cell survival, it has been a long-held and conceptually attractive view that they are sustained by active homeostatic control as thymic activity wanes. Here we employ multiple experimental systems to identify a unified model of naive CD4 and CD8 T cell population dynamics across the mouse lifespan. We infer that both subsets divide rarely and progressively increase their survival capacity with cell age. Strikingly, this simple model captures naive CD4 T cell dynamics throughout life. In contrast, we find that newly generated naive CD8 T cells are lost more rapidly during the first 3–4 weeks of life, likely due to increased recruitment into memory. We find no evidence for elevated division rates in neonates, or for feedback regulation of naive T cell numbers at any age. We show how confronting mathematical models with diverse datasets can reveal a quantitative and remarkably simple picture of naive T cell dynamics from birth into old age.
Interspecies transfer of syntenic RAMOSA1 orthologs and promoter cis sequences impacts maize inflorescence architecture
Authors: Strable Josh , Unger-Wallace Erica , Raygoza Alejandro Aragón , Briggs Sarah , Vollbrecht Erik
Published: January 2022

Grass inflorescences support floral structures that each bear a single grain, where variation in branch architecture directly impacts yield. The maize RAMOSA1 (ZmRA1) transcription factor acts as a key regulator of inflorescence development by imposing branch meristem determinacy. Here, we show RA1 transcripts accumulate in boundary domains adjacent to spikelet meristems in Sorghum bicolor (Sb) and Setaria viridis (Sv) inflorescences similar as in the developing maize tassel and ear. To evaluate functional conservation of syntenic RA1 orthologs and promoter cis sequences in maize, sorghum and setaria, we utilized interspecies gene transfer and assayed genetic complementation in a common inbred background by quantifying recovery of normal branching in highly ramified ra1-R mutants. A ZmRA1 transgene that includes endogenous upstream and downstream flanking sequences recovered normal tassel and ear branching in ra1-R. Interspecies expression of two transgene variants of the SbRA1 locus, modeled as the entire endogenous tandem duplication or just the non-frameshifted downstream copy, complemented ra1-R branching defects and induced novel fasciation and branch patterns. The SvRA1 locus lacks conserved, upstream noncoding cis sequences found in maize and sorghum; interspecies expression of an SvRA1 transgene did not or only partially recovered normal inflorescence forms. Driving expression of the SvRA1 coding region by the ZmRA1 upstream region, however, recovered normal inflorescence morphology in ra1-R. These data leveraging interspecies gene transfer suggest that cis-encoded temporal regulation of RA1 expression is a key factor in modulating branch meristem determinacy that ultimately impacts grass inflorescence architecture.
Compartmentalized Cell Envelope Biosynthesis in Mycobacterium tuberculosis
Authors: Puffal Julia , Sparks Ian L. , Brenner James R. , Li Xuni , Leszyk John D. , Hayashi Jennifer M. , Shaffer Scott A. , Morita Yasu S.
Published: January 2022

The intracellular membrane domain (IMD) is a metabolically active and laterally discrete membrane domain initially discovered in Mycobacterium smegmatis. The IMD correlates both temporally and spatially with the polar cell envelope elongation in M. smegmatis. Whether or not a similar membrane domain exists in pathogenic species remains unknown. Here we show that the IMD is a conserved membrane structure found in Mycobacterium tuberculosis. We used two independent approaches, density gradient fractionation of membrane domains and visualization of IMD-associated proteins through fluorescence microscopy, to determine the characteristics of the plasma membrane compartmentalization in M. tuberculosis. Proteomic analysis revealed that the IMD is enriched in metabolic enzymes that are involved in the synthesis of conserved cell envelope components such as peptidoglycan, arabinogalactan, and phosphatidylinositol mannosides. Using a fluorescent protein fusion of IMD-associated proteins, we demonstrated that this domain is concentrated in the polar region of the rod-shaped cells, where active cell envelope biosynthesis is taking place. Proteomic analysis further revealed the enrichment of enzymes involved in synthesis of phthiocerol dimycocerosates and phenolic glycolipids in the IMD. We validated the IMD association of two enzymes, α1,3-fucosyltransferase and fucosyl 4- O-methyltransferase, which are involved in the final maturation steps of phenolic glycolipid biosynthesis. Taken together, these data indicate that functional compartmentalization of membrane is an evolutionarily conserved feature found in both M. tuberculosis and M. smegmatis, and M. tuberculosis utilizes this membrane location for the synthesis of its surface- exposed lipid virulence factors.

IMPORTANCE

M. tuberculosis remains an important public health threat, with more than one million deaths every year. The pathogen’s ability to survive in the human host for decades highlights the importance of understanding how this bacterium regulates and coordinates its metabolism, cell envelope elongation, and growth. The IMD is a membrane structure that associates with the subpolar growth zone of actively growing mycobacteria, but its existence is only known in a non- pathogenic model, M. smegmatis. Here, we demonstrated the presence of the IMD in M. tuberculosis, making the IMD an evolutionarily conserved plasma membrane compartment in mycobacteria. Furthermore, our study revealed that the IMD is the factory for synthesizing phenolic glycolipids, virulence factors produced by slow-growing pathogenic species.
SARS-CoV-2-positive patients display considerable differences in proteome diversity in urine, nasopharyngeal, gargle solution and bronchoalveolar lavage fluid samples
Authors: Okendo Javan , Musanabaganwa Clarisse , Mwangi Peter , Nyaga Martin , Onywera Harris
Published: January 2022

Background

Proteome profile changes post-severe acute respiratory syndrome coronavirus 2 (post-SARS-CoV-2) infection in different body sites of humans remains an active scientific investigation whose solutions stand a chance of providing more information on what constitutes SARS-CoV-2 pathogenesis. While proteomics has been used to understand SARS-CoV-2 pathogenesis, there are limited data about the status of proteome profile in different human body sites infected by the sarscov2 virus. To bridge the gap, our study aims to profile the proteins secreted in urine, bronchoalveolar lavage fluid (BALF), gargle solution, and nasopharyngeal samples and assess the proteome differences in these body samples collected from SARS-CoV-2-positive patients.

Materials and methods

We downloaded publicly available proteomic data from (https://www.ebi.ac.uk/pride/). The data we downloaded had the following identifiers: i) PXD019423, n=3 from Charles Tanford Protein Center in Germany. ii) PXD018970, n=15 from Beijing Proteome Research Centre, China. iii)PXD022085, n=5 from Huazhong University of Science and Technology, China, and iv) PXD022889, n=18 from Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905 USA. MaxQuant was used for the peptide spectral matching using humans, and SARS-CoV-2 was downloaded from the UniProt database (access date 13th October 2021).

Results

The individuals infected with SARS-CoV-2 viruses displayed a different proteome diversity from the different body sites we investigated. Overall, we identified 1809 proteins across the four different sample types we compared. Urine and BALF samples had significantly more abundant SARS-CoV-2 proteins than the other body sites we compared. Urine samples had 257(33.7%) unique proteins, followed by nasopharyngeal with 250(32.8%) unique proteins. Garage solution and BALF had 38(5%) and 73(9.6%) unique proteins.

Conclusions

Urine, gargle solution, nasopharyngeal, and bronchoalveolar lavage fluid samples have different protein diversity in individuals infected with SARS-CoV-2. Moreover, our data demonstrated that a given body site is characterized by a unique set of proteins in SARS-CoV-2 seropositive individuals.
A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron
Authors: Lai Eric , Becker David , Brzoska Pius , Cassens Tyler , Davis-Turak Jeremy , Diamond Evan , Furtado Manohar , Gandhi Manoj , Gort Dale , Greninger Alexander L. , Hajian Pooneh , Hayashibara Kathleen , Kennedy Emily B. , Laurent Marc , Lee William , Leonetti Nicole A. , Lozach Jean , Lu James , Nguyen Jason M. , O’Donovan K. M. Clair , Peck Troy , Radcliffe Gail E. , Ramirez Jimmy M. , Roychoudhury Pavitra , Sandoval Efren , Walsh Brian , Weinell Marianne , Wesselman Cassandra , Wesselman Timothy , White Simon , Williams Stephen , Wong David , Yu Yufei , Creager Richard S.
Published: January 2022

The rapid emergence of new SARS-CoV-2 variants raises a number of public health questions including the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to better understand patterns of transmission and possible load on healthcare resources. Next-Generation Sequencing (NGS) is the primary method for detecting and tracing the emergence of new variants, but it is expensive, and it can take weeks before sequence data is available in public repositories. Here, we describe a Polymerase Chain Reaction (PCR)-based genotyping approach that is significantly less expensive, accelerates reporting on SARS-CoV-2 variants, and can be implemented in any testing lab performing PCR.

Specific Single Nucleotide Polymorphisms (SNPs) and indels are identified that have high positive percent agreement (PPA) and negative percent agreement (NPA) compared to NGS for the major genotypes that circulated in 2021. Using a 48-marker panel, testing on 1,128 retrospective samples yielded a PPA and NPA in the 96.3 to 100% and 99.2 to 100% range, respectively, for the top 10 most prevalent lineages. The effect on PPA and NPA of reducing the number of panel markers was also explored.

In addition, with the emergence of Omicron, we also developed an Omicron genotyping panel that distinguishes the Delta and Omicron variants using four (4) highly specific SNPs. Data from testing demonstrates the capability to use the panel to rapidly track the growing prevalence of the Omicron variant in the United States in December 2021.