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ABSTRACT Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals’ respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation—in part driven by Candida colonization—and blunted interferon signaling represent a common feature of severe COVID-19 infection.IMPORTANCEIn this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.

HemoCue analyzers are standard point-of-care devices for measuring blood hemoglobin concentration ([Hb]). The utility of these photometers has been demonstrated for all vertebrate lineages including birds, yet because most vertebrates except mammals possess nucleated red-blood cells, their [Hb] readings are inflated upward in these taxa and require a correction factor relative to the reference calibration. We field tested the newest of these analyzers, Hb801, against its predecessor, the Hb201+. Because of differences in the photometry methods, these two analyzers were not found to be equivalent for taxa with nucleated red-blood cells, such as birds. Whereas a correction factor of 1.0–1.4 g/dL is required for the Hb201+, it may be that no correction factor is required for the Hb801. Further study of the Hb801 relative to a gold-standard reference in non-mammalian lineages is warranted.

As with the broad field of deep learning, autonomy is a research topic that has experienced a heavy explosion in attention from both the scientific and commercial industries due to its potential for the advancement of humanity in many cross-cutting disciplines. Recent advancements in computer vision-based autonomy has highlighted the potential for the realization of increasingly sophisticated autonomous ground vehicles for both commercial and non-traditional applications, such as grocery delivery. Part of the success of these technologies has been a boon in the abundance of training data that is available for training the autonomous behaviors associated with their autonomy software. These data abundance advantage is quickly diminished when an application moves from structured environments, i.e., well-defined city road networks, highways, street signage, etc., into unstructured environments, i.e., cross-country, off-road, non-traditional terrains. Herein, we aim to present insights, from a dataset perspective, into how the scientific community can begin to expand autonomy into unstructured environments, while highlighting some of the key challenges that are presented with such a dynamic and ever-changing environment. Finally, a foundation is laid for the creation of a robust off-road dataset being developed by the Engineer Research and Development Center and Mississippi State University’s Center for Advanced Vehicular Systems.

Background:. Hidradenitis suppurativa (HS) is an understudied disease, and current HS studies have focused on participants already connected to dermatologic care. Objective:. We surveyed participants in online HS support communities to gain a comprehensive understanding of how provider type impacts HS disease management and the issues individuals with HS face when accessing care. Methods:. From June 13 to June 30, 2021, we administered an anonymous cross-sectional online survey to HS Facebook support group participants who had a self-confirmed diagnosis of HS. Survey items assessed respondent demographics, primary HS provider, and barriers to HS care and pain management. Descriptive analyses are presented. Results:. The survey was viewed 5,168 times and 1,040 surveys met eligibility criteria (20.1%). Survey participants were 97% female and 72% White. Seventy-two percentage resided in the United States and 22% in Europe. Forty-seven percentage reported having a dermatologist as their primary HS provider, 38% reported a nondermatologist, and 15% reported no HS provider. We found that Asian race, full-time employment, private health insurance, and urban setting were each associated with higher rates of having a dermatologist as a primary HS provider. However, 43.7% of those with a dermatologist reported biologic use, as compared with 14.5% with nondermatologist HS providers. Our cohort was notably more severely impacted by comorbid diseases; 55.9% of our cohort had anxiety, 53.6% had depression, and 50.7% had obesity. Overall, 74.2% of our cohort reported experiencing stigma while accessing care for their HS. Limitations:. Participant recruitment via social media platform facilitates recruitment of individuals across the spectrum of healthcare access, but may introduce selection bias and favor well-resourced areas. Self-reported data may be subject to recall bias. Conclusion:. Our study provides unique insights into the characteristics and experiences of individuals with HS across the spectrum of health care access.

BackgroundHidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk.ObjectiveTo provide evidence-based screening recommendations for comorbidities linked to HS.MethodsSystematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria.ResultsScreening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity.LimitationsScreening recommendations represent one component of a comprehensive care strategy.ConclusionsDermatologists should support screening efforts to identify comorbid conditions in HS.

One of the earliest neurobiological findings in autism has been the differences in the thalamocortical pathway connectivity, suggesting the vital role thalamus plays in human experience. The present functional MRI study investigated resting-state functional connectivity of the thalamus in 49 (autistic, ADHD, and neurotypical) young adults. All participants underwent structural MRI and eyes-open resting state functional MRI scans. After preprocessing the imaging data using Conn’s connectivity toolbox, a seed-based functional connectivity analysis was conducted using bilateral thalamus as primary seeds. Autistic participants showed stronger thalamic connectivity, relative to ADHD and neurotypical participants, between the right thalamus and right precentral gyrus, right pars opercularis-BA44, right postcentral gyrus, and the right superior parietal lobule (RSPL). Autistic participants also showed significantly increased connectivity between the left thalamus and the right precentral gyrus. Furthermore, regression analyses revealed a significant relationship between autistic traits and left thalamic-precentral connectivity (R2 = 0.1113), as well as between autistic traits and right postcentral gyrus and RSPL connectivity (R2 = 0.1204) in autistic participants compared to ADHD. These findings provide significant insights into the role of thalamus in coordinating neural information processing and its alterations in neurodevelopmental disorders.

Hidradenitis suppurativa is a chronic inflammatory disease that disproportionately affects women of childbearing age. Hidradenitis suppurativa is characterized by painful nodules, abscesses, draining dermal tunnels, and scarring with a predilection for intertriginous sites, such as the axilla, groin, and breast regions. Delay in diagnosis and treatment of hidradenitis suppurativa often results in long-term sequelae leading to significant morbidity, and rarely mortality, in these patients. This clinical opinion suggests that obstetrician-gynecologists are uniquely poised to recognize early signs of hidradenitis suppurativa during routine well-woman examinations and initiate treatment or referral to dermatology. Herein, we provide clinical pearls for obstetrician-gynecologists caring for female patients with hidradenitis suppurativa, including strategies for comprehensive management and recommendations to improve the comfort of patients with hidradenitis suppurativa during examinations.

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

Cutaneous dysbiosis is implicated in hidradenitis suppurativa (HS) pathogenesis. Previous studies reveal skin microbiota shifts in HS lesional skin. In their report, Riverain-Gillet et al. (2020) extended these findings and reported skin microbiota shifts in unaffected HS skinfolds as well. Their study suggests that skin microbial shifts may precede clinical lesions and draws attention to study methods important for skin microbiome research.

Easily accessible office-based procedures that require minimal resources may facilitate timely surgical management of hidradenitis suppurativa (HS). This review focuses on excision and unroofing as two surgical HS treatments that can be tailored to the outpatient setting. Fifty-five articles were included in our review, representing 3914 patients. The majority were retrospective studies (58%, n = 32), and the studies reported data both across patients and by number of treated lesions. Recurrence rates for unroofing (14.5%) were found to be half that of excision (30%) across patients (p = 0.015) and slightly lower across lesions [20% recurrence vs 26% for excision (p = 0.023)]. Complication rates at the lesion level were also significantly associated with procedure, with rates after excision more than double those after roofing (26% vs. 12%, p

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

Background/Study Context: Memory for specific, verbatim details tends to decline with age, and reliance on gist-based information increases. However, instructions that direct attention toward certain types of information can benefit memory accuracy for that information. Previous work has examined gist-based and verbatim memory for images, but little work has utilized stimuli that participants may study in their daily lives, such as a weather forecast.MethodsThe current study examined how younger and older adults recall both general, gist-based information and specific, verbatim details of a weather forecast, and whether differences in the task instructions to focus on gist-based information may affect recall. Two study-test cycles with different forecasts were used to determine whether experience with the task may affect performance.ResultsWhile there was no effect of additional gist-based instructions on recall of gist-based information, participants who received the additional instructions recalled fewer verbatim details than those who did not. There were no age-related differences in recall of the gist of the forecast, but younger adults correctly recalled more verbatim details than older adults did.ConclusionEnvironmental support and use of gist-based processing can allow both younger and older adults to remember information that can be useful in their daily lives. The current study informs future research on prospective memory and memory for everyday information.

In November 2017, a formal debate on the role of bacteria in the pathogenesis of hidradenitis suppurativa (HS) was held at the 2nd Symposium on Hidradenitis Suppurativa Advances (SHSA) in Detroit, Michigan. In this report, we present both sides of the argument as debated at the SHSA meeting and then discuss the potential role of bacteria as classic infectious pathogens versus an alternative pathogenic role as activators of dysregulated commensal bacterial-host interactions. Although there was consensus that bacteria play a role in pathogenesis and thus are pathogenic, there was a compelling discussion about whether bacteria in HS incite an infectious disease as we classically understand it or whether bacteria might play a different role in HS pathogenesis.

The 2nd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 03-05 November 2017 in Detroit, Michigan, USA. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF Inc.) founded in the USA, and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This was the second annual meeting of the SHSA with experts from different disciplines arriving from North America, Europe and Australia, in a joint aim to discuss most recent innovations, practical challenges and potential solutions to issues related in the management and care of Hidradenitis Suppurativa patients. The last session involved clinicians, patients and their families in an effort to educate them more about the disease.

Objectives: Maternal socioeconomic status (SES) is an important predictor of adverse birth outcomes and postnatal health across global populations. Chronic inflammation is implicated in cardiometabolic disease risk in high‐income contexts and is a potential pathway linking maternal adversity to offspring health trajectories. To clarify how socioeconomic inequality shapes pregnancy inflammation in middle‐income settings, we investigated SES as a predictor of inflammatory cytokines in late gestation in a sample from the Cebu Longitudinal Health Nutrition Survey in Cebu, Philippines. Methods: We used multiple regression to evaluate maternal SES, reflected in household assets, as a predictor of general inflammation (C‐reactive protein), inflammatory cytokines (interleukin‐6, interleukin‐10), and inflammatory balance (n = 407). Inflammatory markers were measured at 29.9 weeks gestation in dried blood spots, and a measure reflecting relative balance of IL6 and IL10 was calculated to capture pro‐ versus anti‐inflammatory skewed immune profiles. Results: Greater household assets significantly predicted lower IL6 concentration (p < 0.001), with a trend toward lower IL6 relative to IL10 (p = 0.084). C‐reactive protein and IL10 were not individually related to SES. Conclusions: The inverse relationship between SES and pregnancy inflammation in Cebu is consistent with results from high‐income settings. These findings further highlight the influence of socioeconomic conditions on immune regulation during pregnancy. Given the evidence that gestational inflammation impacts offspring fetal growth, our results suggest that social and economic effects on immune function may be an important pathway for the intergenerational transmission of health disparities. [ABSTRACT FROM AUTHOR]

Mixed‐conducting perovskites are workhorse electrochemically active materials, but typical high‐temperature processing compromises their catalytic activity and chemo‐mechanical integrity. Low‐temperature pulsed laser deposition of amorphous films plus mild thermal annealing is an emerging route to form homogeneous mixed conductors with exceptional catalytic activity, but little is known about the evolution of the oxide‐ion transport and transference numbers during crystallization. Here the coupled evolution of ionic and electronic transport behavior and structure in room‐temperature‐grown amorphous (La,Sr)(Ga,Fe)O3‐x films as they crystallize is explored. In situ ac‐impedance spectroscopy with and without blocking electrodes, simultaneous capturingsynchrotron‐grazing‐incidence X‐ray diffraction, dc polarization, transmission electron microscopy, and molecular dynamics simulations are combined to evaluate isothermal and non‐isothermal crystallization effects and the role of grain boundaries on transference numbers. Ionic conductivity increases by ≈2 orders of magnitude during crystallization, with even larger increases in electronic conductivity. Consequently, as crystallinity increases, LSGF transitions from a predominantly ionic conductor to a predominantly electronic conductor. The roles of evolving lattice structural order, microstructure, and defect chemistry are examined. Grain boundaries appear relatively nonblocking electronically but significantly blocking ionically. The results demonstrate that ionic transference numbers can be tailored over a wide range by tuning crystallinity and microstructure without having to change the cation composition. [ABSTRACT FROM AUTHOR]

As with the broad field of deep learning, autonomy is a research topic that has experienced a heavy explosion in attention from both the scientific and commercial industries due to its potential for the advancement of humanity in many cross-cutting disciplines. Recent advancements in computer vision-based autonomy has highlighted the potential for the realization of increasingly sophisticated autonomous ground vehicles for both commercial and non-traditional applications, such as grocery delivery. Part of the success of these technologies has been a boon in the abundance of training data that is available for training the autonomous behaviors associated with their autonomy software. These data abundance advantage is quickly diminished when an application moves from structured environments, i.e., well-defined city road networks, highways, street signage, etc., into unstructured environments, i.e., cross-country, off-road, non-traditional terrains. Herein, we aim to present insights, from a dataset perspective, into how the scientific community can begin to expand autonomy into unstructured environments, while highlighting some of the key challenges that are presented with such a dynamic and ever-changing environment. Finally, a foundation is laid for the creation of a robust off-road dataset being developed by the Engineer Research and Development Center and Mississippi State University's Center for Advanced Vehicular Systems. [ABSTRACT FROM AUTHOR]

The 5th Scientific Conference of the International Pemphigus and Pemphigoid Foundation (IPPF), "Pemphigus and Pemphigoid: A New Era of Clinical and Translational Science" was held in Orlando, Florida, on May 15-16, 2018. Scientific sessions covered recent, ongoing, and future clinical trials in pemphigus and bullous pemphigoid, disease activity and quality of life instruments, and the IPPF Natural History Study. Furthermore, the meeting provided an opportunity to hear firsthand from patients, investigators, and industry about their experience enrolling for clinical trials.

Abstract Background Patients with high‐intermediate risk endometrial cancer (H‐IR EMCA) have an elevated risk of recurrence compared to low‐risk counterparts. Many H‐IR EMCA patients are treated with radiation or chemotherapy, but their overall survival is not significantly impacted by treatment. The objective of this study was to compare molecular profiles of H‐IR EMCA patients with disease recurrence to those without to identify characteristics that could better predict patient outcomes. Methods Tissue was acquired from H‐IR EMCA patients with disease recurrence (n=15) and without disease recurrence (n=15) who had not received adjuvant therapy and performed DNA and RNA analyses. Results In recurrent population, 5 patients had matchingrecurrent and initial tumor tissues. Of note, 5/7 (71%) African Americanpatients had disease recurrence compared to 10/23 (43%) White patients. Inaddition, several new mutations were found in individual patient’s recurrentcompared to initial tumors. Conclusions Currently the treatment ofendometrial cancer is rapidly changing with molecular profiling becoming partof the standard of care. Additionally, it and is being incorporated intoclinical trials in this group of patients. The specific gene mutations and RNAexpression signatures that were observed in our small cohort need to bevalidated in larger cohorts to determine their impact.

In order to accurately parse the visual scene into distinct surfaces, it is essential to determine whether a local luminance edge is caused by a boundary between two surfaces or a shadow cast across a single surface. Previous studies have demonstrated that local chromatic cues may help to distinguish edges caused by shadows from those caused by surface boundaries, but the information potentially available in local achromatic cues like contrast, texture, and penumbral blur remains poorly understood. In this study, we develop and analyze a large database of hand-labeled achromatic shadow edges to better understand what image properties distinguish them from occlusion edges. We find that both the highest contrast as well as the lowest contrast edges are more likely to be occlusions than shadows, extending previous observations based on a more limited image set. We also find that contrast cues alone can reliably distinguish the two edge categories with nearly 70% accuracy at 40x40 resolution. Logistic regression on a Gabor Filter bank (GFB) modeling a population of V1 simple cells separates the categories with nearly 80% accuracy, and furthermore exhibits tuning to penumbral blur. A Filter-Rectify Filter (FRF) style neural network extending the GFB model performed at better than 80% accuracy, and exhibited blur tuning and greater sensitivity to texture differences. We compare human performance on our edge classification task to that of the FRF and GFB models, finding the best human observers attaining the same performance as the machine classifiers. Several analyses demonstrate both classifiers exhibit significant positive correlation with human behavior, although we find a slightly better agreement on an image-by-image basis between human performance and the FRF model than the GFB model, suggesting an important role for texture.

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Protonic ceramic electrolysis cells (PCECs) are an attractive green H2 production technology, given their intermediate-temperature operating range and ability to produce dry H2. However, PCECs will benefit from development of more efficient and durable "triple conducting" anodes where steam is split, H incorporated, and oxygen evolved. In this work, we evaluated the kinetics of the steam-splitting/H incorporation reaction on BaPr0.9Y0.1O3−δ (BPY) in comparison to the benchmark Ba1−xCo0.4Fe0.4Zr0.1Y0.1O3−δ (BCFZY) composition, replacing most of the transition metal elements (Co, Fe, Zr) with the lanthanide Pr. We prepared geometrically well-defined perovskite BPY and BCFZY thin films by pulsed laser deposition and performed simultaneous optical transmission relaxation and electrical conductivity relaxation measurements at 400–500 °C in 0.21 atm O2 during switching of the steam partial pressure to isolate and compare their proton surface exchange coefficients (k). The k values of BPY were comparable to those of BCFZY and more stable over time. According to angle-resolved XPS and STEM-EDS mapping of FIB cross-sections, the surface of BPY exhibited Ba enrichment, Pr deficiency, and Si contamination. In contrast, BCFZY exhibited Ba deficiency throughout, no obvious surface segregation, and less Si contamination. The Ba segregation on the BPY film appears to have promoted steam splitting/H incorporation kinetics even though the more basic surface reacted with the acidic environmental SiOxHy. Faster kinetics observed on stoichiometric BCFZY vs. Ba-deficient BCFZY confirmed the benefit of a high A-site Ba concentration. This result contrasts with most work on perovskites applied in solid oxide electrolysis cell anodes, in which A-site segregation is considered deleterious for surface reaction kinetics. [ABSTRACT FROM AUTHOR]