bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative 18F-FDG PET/computed tomography predicts survival following resection for colorectal liver metastases
Authors: Grut Harald , Stern Nadide Mutlukoca , Dueland Svein , Labori Knut Jørgen , Dormagen Johann Baptist , Schulz Anselm
Published: June 2020

Objective

The liver is the most frequent metastatic site from colorectal cancer and about 20% of these patients are treated by surgical resection. However, the 5-year disease-free survival (DFS) following resection is only about 25% and 5-year overall survival (OS) about 38%. The aim of the study was to evaluate the ability of metabolic and volumetric measurements from fluorine-18-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) prior to resection for colorectal liver metastases (CLM) to predict survival.

Patients and methods

Preoperative 18F-FDG PET/CT examinations were assessed. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum, mean and peak standardized uptake values and tumor to background ratio, were obtained for all CLM. Cutoff values were determined for each of these parameters by using receiver operating characteristic analysis dividing the patients into two groups. DFS, liver recurrence-free survival (LRFS), OS and cancer-specific survival (CSS) for patients over and under the cutoff value were compared by using the Kaplan–Meier method and log-rank test.

Results

Twenty-seven patients who underwent 18F-FDG PET/CT prior to resection for CLM were included. Low values of total MTV and TLG were significantly correlated to improved 5-year LRFS (P = 0.016 and 0.006) and CSS (P = 0.034 and 0.008). Patients who developed liver recurrence had significantly higher total MTV and TLG compared to patients without liver recurrence (P = 0.042 and 0.047).

Conclusion

Low values of total MTV and TLG were significantly correlated to improved LRFS and CSS and may improve the risk stratification of patients considered for resection for CLM.
Implementing a Food is Medicine Program to Address Food Insecurity in an Academic Medical Center
Authors: Wynn Nicole , Staffileno Beth A. , Grenier Jennifer M. , Phillips Janice
Published: June 2020

Background:

Food insecurity is a public, social, and health concern.

Local Problem:

A Food is Medicine Program was developed to address food insecurity.

Methods:

A quality improvement initiative was piloted on 3 acute care units.

Interventions:

Patients were screened for Social Determinant of Health (SDoH) needs and if identified as food insecure, linked to community resources and provided with a bag of food on discharge. Education was offered to nursing staff and a pre- and postsurvey was administered to assess SDoH knowledge and confidence.

Results:

Over a 3-month period, 2354 patients were admitted; 2063 (88%) were screened for SDoH and 220 (10%) were positive for food insecurity. Patients (n = 1525, 74%) were linked to community resources. Nearly all (97%) nurses participated in education and demonstrated increased knowledge and confidence (P < .001).

Conclusions:

These data provide preliminary outcomes from the Food is Medicine Program.
Pediatricians as Case Managers Reduce the Exposure to Computerized Tomography in Children Experiencing Minor Head Trauma
Authors: Fishman Yuri , Gross Itai , Hashavya Saar , Benifla Menachem , Tenenbaum Ariel , Rekhtman David
Published: June 2020

Background

Head trauma is one of the most common reasons for pediatric emergency medicine department (PED) visits. Computerized tomography (CT) scan is considered the criterion standard for the diagnosis of traumatic brain injury but was shown to increases the risk of malignancies.

Methods

We retrospectively analyzed collected data of all children (ages 0–16 years) experiencing mild head trauma who were admitted to a single center, from January 1, 2010, to December 31, 2015. Comparison between patients treated by pediatricians/pediatric emergency medicine physicians (PEMP) with those treated by surgeons regarding CT rates and prognosis was done.

Results

During the previously mentioned period, 4232 children presented to the PED after minor head trauma, the average age was 5.4 (±4) years and 67.1% were male. Head CT was done in 7.7%, of which 30.7% had positive findings. Younger children tended to have higher percentage of positive findings on CT scan (60%, 43.8%, 26.6%, P = 0.003, for children up to 5 months, 5–24 months, and older than 24 months, respectively). Pediatricians ordered less CT scans when compared with surgeons (5.4% vs 8.5%, P < 0.001). Moreover, they had higher rates of positive findings on CT scan (52.5% vs 25.8%, P < 0.001). When all other characteristics were similar, if the case manager was a pediatrician, the patient's chances to undergo a CT scan were 4.3 times lower than if the case manager was a surgeon (odds ratio, 4.277; confidence interval, 2.274–7.104). No difference in readmissions or other complications were found between the 2 groups.

Discussion

This study highlights that when the case manager of children with minor head trauma is a pediatrician/PEMP, CT scan rates and thus exposure to radiation are diminished without a failure to detect clinically important traumatic brain injury.

In conclusion, our findings suggest that when possible, all children experiencing minor head trauma should be treated by a pediatrician/PEMP in the PED.
High Concurrent Use of Sulfonylureas and Antimicrobials With Drug Interactions Causing Hypoglycemia
Authors: Pilla Scott J. , Pitts Samantha I. , Maruthur Nisa M.
Published: June 2020

Objectives

Sulfonylureas, the second most common oral diabetes treatment, have interactions with antimicrobials that substantially increase the risk of hypoglycemia. The objectives of this study are to quantify the concurrent use of sulfonylureas and interacting antimicrobial in U.S. ambulatory care and to examine whether interacting antimicrobials are used for an appropriate indication.

Methods

We analyzed the 2006–2016 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual probability samples of visits to U.S. office-based physicians. We determined nationally representative estimates of visits for adults with concurrent use of sulfonylureas and 7 antimicrobials with established interactions. We examined whether visit diagnoses included appropriate indications for antibiotics according to national guidelines.

Results

There were 2.5 million visits per year (95% confidence interval [CI] 2.2–2.9) in which sulfonylureas were used with systemic antimicrobials, of which 1 million (95% CI, 0.8–1.2) or 38.0% (95% CI, 32.3%–44.0%) were interacting antimicrobials. Sulfonylurea users had similar odds of interacting antimicrobial use as patients using diabetes medications without antimicrobial interactions (adjusted odds ratio, 1.07; 95% CI, 0.82–1.40). The most common interacting antimicrobials used with sulfonylureas were fluoroquinolones, accounting for 59.9% (95% CI, 50.7%–68.2%) of antimicrobials, and sulfamethoxazole-trimethoprim, accounting for 21.1% (95% CI, 14.8%–29.2%). There was no appropriate antibiotic indication in 69.7% (95% CI, 55.2%–81.1) of visits with interacting antibiotic use.

Conclusions

Sulfonylureas and antimicrobials with potentially hazardous interactions are frequently used together. To reduce resultant hypoglycemic events, there is a need for interventions to increase physician awareness and promote antibiotic stewardship.
Serum Urate Levels of Hemodialyzed Renal Patients Revisited
Authors: Arenas María-Dolores , Soriano Raquel , Andrés Mariano , Pascual Eliseo
Published: June 2020

Objectives

The need of maintaining serum urate (SU)–lowering agents in hemodialysis (HD) patients is an understudied area that requires a review, as it is a common practice. The aims were to assess the SU reduction achieved under HD and to analyze the kinetics of SU in a week of intermittent HD.

Methods

The serum urate levels were determined before and after HD sessions in 96 consecutive patients with end-stage renal disease, and the average SU reduction was assessed. Variables related to HD were analyzed whether they were associated with SU reductions of 80% greater. In addition, a kinetics study was performed on 10 selected patients with hyperuricemia (SU before HD >6.8 mg/dL) throughout intermittent HD sessions in a 1-week period.

Results

The mean ± SD age of the patients was 66.5 ± 13.8 years, and 62 of them were male (64.6%). The mean ± SD time on HD replacement was 7.1 ± 7.2 years, and 16 (16.4%) continued with urate-lowering agents. The mean SU reduction immediately after HD was 80.2% (95% confidence interval, 78.4–82.0); 51 patients (56.7%) showed SU reduction of 80% or greater. In the SU kinetics study, SU levels significantly reduced all over the period and persisted below hyperuricemia threshold (p = 0.015). Noteworthy, 6 patients (60%) were hyperuricemic before session 1, but only 1 (10%) before session 2 and none before session 3.

Conclusions

Under HD replacement therapy, the SU levels effectively reduced and persisted below saturation point, suggesting that the SU-lowering therapy would be unnecessary for patients on HD, but necessary in selected cases. The definition of hyperuricemia under HD needs to be revised.
Ultrasonography Reliability in the Detection of Inflammatory and Structural Abnormalities
Authors: Brites Luisa , Santiago Mariana , Rovisco João , Freitas João , A.P. Silva José , Silva Inês , Teixeira Filipa , Faria Daniela S. , Silva Cândida G. , Falcão Sandra
Published: June 2020

Background

Ultrasonography is an image technique that allows rheumatologists to visualize structural and inflammatory changes within a joint. The objective of this study was to assess the interobserver and intraobserver reliability of musculoskeletal ultrasound (US) in the detection of inflammatory and destructive joint changes in patients with polyarthritis.

Methods

A Delphi exercise was undertaken to standardize and adapt the EULAR-OMERACT elementary US definitions of inflammatory lesions (effusion, synovial hypertrophy, power Doppler, bone erosions, and synovitis) for each joint. Fifteen patients were analyzed, and video clips of 600 joints were collected. Each joint was scored for the presence of each elementary component, on 2 separate occasions, by 6 examiners. Interobserver and intraobserver agreement analysis was assessed through Fleiss κ coefficient (κ).

Results

Considering all patients and all joints, the interobserver values were highest for erosions and lowest for effusion (κ = 0.7314 and κ = 0.6044, respectively). When analyzing different regions, the highest interobserver agreement was for tibiotalar joint (κ = 0.8043) and the lowest for wrist (κ = 0.6767). Intraobserver reliability was excellent for each and all elementary components and anatomical region.

Conclusions

The present study showed either a good or excellent US interobserver and intraobserver reliability in elementary elements and anatomical region. This kind of US reliability exercises are important for standardization of exploration in everyday practice by reducing the variability associated with this imaging technique, and ensuring a greater degree of homogeneity and future comparability in the assessment of disease activity in polyarthritis patients.
A Meta-analysis and Systematic Review of Valvular Heart Disease in Systemic Lupus Erythematosus and Its Association With Antiphospholipid Antibodies
Authors: Hussain Kifah , Gauto-Mariotti Estefania , Cattoni Hugo Macchi , Arif Abdul Wahab , Richardson Carrie , Manadan Augustine , Yadav Neha
Published: June 2020

Background

Valvular heart disease (VHD) is a known cardiac manifestation of systematic lupus erythematosus (SLE). This systematic review aims to pool data from studies to estimate the frequency of valvular lesions in SLE patients. It also aims to demonstrate the association between VHD in SLE and antiphospholipid antibodies positivity.

Methods

We included 27 studies after identifying relevant abstracts from PubMed, Scopus, and Google Scholar from the time of inception of database to 2019. Inclusion criteria consisted of English-language case-control and cohort studies. Three reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale for assessing risk for bias.

Results

For VHD in SLE patients, the most commonly involved valve was the mitral valve, with 19.7% lesions being mitral regurgitation. In terms of morphological lesions, valve thickening (11.06%) and vegetations (11.76%) were among the most prevalent. Other commonly encountered lesions were mitral valve prolapse and tricuspid regurgitation in 9.25% and 10.86% of patients, respectively. A meta-analysis of 21 studies with 2163 SLE patients, of which 23.3% had valvular lesions, showed a significant association of anticardiolipin antibodies positivity with VHD (relative risk, 1.55; confidence interval, 1.10–2.18).

Conclusions

Systemic lupus erythematosus is associated with VHD, and it should be considered a clinical manifestation of SLE in the absence of other valvular pathologies. There is a clear association between VHD in SLE and immunoglobulin G anticardiolipin antibodies positivity. This association suggests that this subgroup of SLE patients might benefit from a screening echocardiogram.
Prevalence and Financial Impact of Claustrophobia, Anxiety, Patient Motion, and Other Patient Events in Magnetic Resonance Imaging
Authors: Nguyen Xuan V. , Tahir Sana , Bresnahan Brian W. , Andre Jalal B. , Lang Elvira V. , Mossa-Basha Mahmud , Mayr Nina A. , Bourekas Eric C.
Published: June 2020

Claustrophobia, other anxiety reactions, excessive motion, and other unanticipated patient events in magnetic resonance imaging (MRI) not only delay or preclude diagnostic-quality imaging but can also negatively affect the patient experience. In addition, by impeding MRI workflow, they may affect the finances of an imaging practice. This review article offers an overview of the various types of patient-related unanticipated events that occur in MRI, along with estimates of their frequency of occurrence as documented in the available literature. In addition, the financial implications of these events are discussed from a microeconomic perspective, primarily from the point of view of a radiology practice or hospital, although associated limitations and other economic viewpoints are also included. Efforts to minimize these unanticipated patient events can potentially improve not only patient satisfaction and comfort but also an imaging practice's operational efficiency and diagnostic capabilities.
Complementary and Alternative Medicine in Radiotherapy
Authors: Borm Kai J. , Schiller Kilian , Asadpour Rebecca , Combs Stephanie E.
Published: June 2020

Complementary and alternative medicine (CAM) approaches are widely used by patients throughout a broad range of medical fields and diseases, and often self-administered by patients without the involvement of physicians or other members of the health care team. CAM use is well documented in cancer and chronic illnesses, and emerging data in radiation oncology show CAM usage of 26% to 97% in radiation therapy patients. No information is, however, available on CAM usage in radiology and in the imaging procedure fields. This article reviews the fundamental principles and the experience with the wide spectrum of CAM in radiation oncology—a field that shares many parallels with radiology, such as prevalence of imaging, procedural requirements, and cooperation demanded from patients.

CAM is defined as “approaches and practices that are typically not part of conventional medical care,” and includes the use of mind- and body-based practices (eg, meditation, massage, acupuncture), natural products (eg, herbs, vitamins, minerals), and other interventions. Supplements are used frequently to alleviate side effects of therapy and promote overall well-being. Specifically, the mindfulness/meditation approaches of CAM are known to reduce anxiety and enhance physical and emotional wellbeing in patients with chronic diseases, such as cancer or neurologic diseases, through physiological, psychological, and perhaps placebo mechanisms. Such patients often require repetitive and invasive imaging examinations or procedures, such as for cancer treatment, cancer surveillance/follow-up, or monitoring of chronic diseases, for example, surveillance MRI in multiple sclerosis. Such parallels suggest that the vastly understudied area of CAMs deserve further investigation in both the radiation oncology and the imaging fields. Further research on CAM is needed to develop refined recommendations and national/and international guidelines on its use.
Adenoid Cystic Carcinoma of Lacrimal Gland with Bone Remodeling
Authors: Parlak Safak , Bulut Elif Gunay
Published: June 2020

Adenoid cystic carcinoma is the most common type of malignancy seen in the lacrimal glands and is generally characterized by invasive malignant appearance with irregular margins and associated bone erosion or destruction. The authors report an unusual patient with a large expansile, well-circumscribed lacrimal adenoid cystic carcinoma with adjacent bone remodeling, radiologically mimicking a benign lesion.
Prognosis of Patient With Resorbable Plates and Screws Under the Incision Site
Authors: Shin Jin Yong , Roh Si-Gyun , Chang Suk Choo , Lee Nae-Ho
Published: June 2020

Various resorbable plates and screws were used for facial bone fractures because of several strengths. However, there are few studies on their clinical course and long-term follow-up concerning their degradation and resorption time. The authors present rare case of long term follow-up of resorbable plates and screws under the incision site.
Breast Cancer Metastases to the Paranasal Sinuses Mimicking Inflammatory Sinus Disease
Authors: Harb Jennifer L. , Shah Ameer T. , O’Leary Miriam A. , Rebeiz Elie E.
Published: June 2020

Introduction:

Breast cancer is one of the most common cancers in women. Metastatic disease is a leading cause of morbidity and mortality. It frequently metastasizes to bone, lungs, regional lymph nodes, liver and brain. Metastasis to the orbit and paranasal sinuses is uncommon. Patients presenting with sinus pain, nasal congestion, or visual disturbance can be misdiagnosed with an infectious process.

Methods:

The authors describe 2 patients with metastatic breast cancer to the paranasal sinuses presenting with signs and symptoms of sinusitis and orbit pathology unresponsive to antibiotics. The authors discuss diagnostic strategy and perform a literature review. Both patients had biopsy-proven metastatic breast adenocarcinoma lesions, and subsequently underwent various treatment options.

Results:

A literature review reveals that metastatic breast adenocarcinoma lesions to the paranasal sinuses are a rare entity that commonly denotes a very poor prognosis. These lesions can significantly affect one's quality of life, and can cause blurry vision, diplopia, proptosis, sinus pressure and pain, nasal congestion, mandibular misalignment or difficulty with mastication. However, early diagnosis and treatment of these lesions can lead to prolonged survival and improved quality of life. If the lesion is surgically resectable, endoscopic sinus surgery is generally considered to be the optimal treatment. However, radiotherapy, chemotherapy, and immunotherapy can potentially play a role in controlling the symptomatology.

Conclusion:

Metastatic lesions to the paranasal sinuses are a rare entity that should be considered in the appropriate clinical setting in order to expedite the proper treatment modality for improved morbidity and mortality
Development and Validation of a HIV Disease–Specific Nutrition Screening Tool
Authors: Wright Lauri , Epps James B.
Published: June 2020

The Rapid Nutrition Screening for HIV disease (RNS-H) was developed and used by case managers to screen for nutrition risk status at an AIDS clinic. A registered dietitian nutritionist (RDN) completed a comprehensive nutritional assessment on all clients screened and assigned a nutrition risk status. A total of 96 clients participated. Analyses showed a very high degree of association between the dietitians' and case mangers' nutrition risk ratings (Kendall τ = 0.973, P < .00008
Evaluation of Dietetic Interns' Research Skills in an Online, Non-Thesis Master's Program
Authors: Arts Jennifer , Paulin Chelsea , Lofgren Ingrid E. , Woodland Barbara , English Catherine
Published: June 2020

Research is the foundation of dietetics. As programs are designed to meet the 2024 entry-level education requirement, innovative approaches are needed to ensure that master's level registered dietitian nutritionists (RDNs) have strong research skills. The MS Dietetics Program is a new, 14-month, online, non-thesis program completed during the Sodexo Dietetic Internship. The objective was to determine whether an online research curriculum impacted research skills. Students evaluated their skills using a 22-question survey and reported significant improvements from baseline in 8 of the 11 research skills. A future investigation should examine whether increased research involvement among master's level RDNs continues after graduation.
Estimation of SARS-CoV-2 aerosol emissions from simulated patients with COVID-19 and no to moderate symptoms
Authors: Riediker Michael , Tsai Dai-Hua
Published: June 2020

Importance

Cases of the coronavirus disease 2019 (COVID-19) with no or mild symptoms were reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome virus (SARS-COV-2) was found at very high concentrations in swab and sputum of such cases.

Objective

We aimed to estimate in a mathematical modeling study the virus release from such cases into different aerosol sizes by normal breathing and coughing, and what exposure can result from this in a room shared with such as case.

Data Sources and Model

We combined the size-distribution of exhaled breath microdroplets for coughing and normal breathing with viral sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50 m3, the size of a small office or medical exam room.

Results

The estimated viral load in microdroplets emitted by simulated patients while breathing normally was on typical 0.0000049 copies/cm3 and could go up to 0.637 copies/cm3. The corresponding numbers for coughing simulated patients were 0.277 copies/cm3 and 36,030/cm3, respectively, per cough. The resulting concentrations in a room with a coughing emitter were always very high, up to 7.44 million copies/m3. However, also regular breathing microdroplets from high emitters was modelled to lead to 1248 copies/m3.

Conclusions and Relevance

In this modelling study, breathing and coughing were estimated to release large numbers of viruses, ranging from thousands to millions of virus copies/m3 in a room with an emitter having a high viral load, depending on ventilation and microdroplet formation process. These findings suggest that strict respiratory protection may be needed when there is a chance to be in the same room with a patient - whether symptomatic or not - especially for a prolonged time.

Key Points

Question

How much SARS-CoV-2 virus is released from a case by breathing and coughing, and what is the resulting concentration in a room?

Finding

In this mathematical modelling study, both, breathing and coughing were estimated to release large numbers of viruses, which can lead to millions of virus copies/m3 in a poorly ventilated room with a coughing emitter.

Meaning

These results may explain the important rate of transmissions and implies the need for strict respiratory protection when people are in the same room with a case with COVID-19.
TBDB – A database of structurally annotated T-box riboswitch:tRNA pairs
Authors: Marchand Jorge A. , Smela Merrick D. Pierson , Jordan Thomas H. H. , Narasimhan Kamesh , Church George M.
Published: June 2020

T-box riboswitches constitute a large family of tRNA-binding leader sequences that play a central role in gene regulation in many gram-positive bacteria. Accurate inference of the tRNA binding to T-boxes is critical to predict their cis-regulatory activity. However, there is no central repository of information on the tRNA binding specificities of T-box riboswitches andde novoprediction of binding specificities requires advance knowledge of computational tools to annotate riboswitch secondary structure features. Here we presentT-boxannotationDatabase (TBDB,https://tbdb.io), an open-access database with a collection of 23,497 T-box sequences, spanning the major phyla of 3,621 bacterial species. Among structural predictions, the TBDB also identifies specifier sequences, cognate tRNA binding partners, and downstream regulatory target. To our knowledge, the TBDB presents the largest collection of feature, sequence, and structural annotations carried out on this important family of regulatory RNA.
Social media reveals consistently disproportionate tourism pressure on a threatened marine vertebrate
Authors: Papafitsoros Kostas , Panagopoulou Aliki , Schofield Gail
Published: June 2020

Establishing how wildlife viewing pressure is distributed across individual animals within a population can inform the management of this activity, and ensure targeted individuals or groups are sufficiently protected. Here, we used social media data to quantify whether tourism pressure varies in a loggerhead sea turtle (Caretta caretta) population and elucidate potential implications. Laganas Bay (Zakynthos, Greece) supports both breeding (migratory, and hence transient) and foraging (resident) turtles, with turtle viewing representing a major component of the tourism industry. Social media entries spanning two seasons (April to November, 2018 and 2019) were evaluated, and turtles were identified via photo-identification. For both years, 1684 and 2105 entries of 139 and 122 unique turtles were obtained from viewings, respectively (boats and underwater combined). However, while residents represented less than one-third of uniquely identified turtles, they represented 81.9% and 87.9% of all entries. Even when the seasonal breeding population was present (May to July), residents represented more than 60% entries. Of note, the same small number of resident turtles (<10), mostly males, were consistently viewed in both years; however, different individuals were targeted by boats versus underwater. Thus, turtles appear to use and remain in the area despite high viewing intensity, possibly indicating low disturbance. However, photo-identification records revealed a high risk of propeller and boat strike to residents (30%) leading to trauma and mortality. To reduce this threat and ease viewing pressure, we recommend the compulsory use of propeller guards for all boats and the creation of temporary “refuge” zones for resident animals at viewing hotspots, with these suggestions likely being relevant for other wildlife with similar population dynamics. In conclusion, social media represents a useful tool for monitoring individuals at a population scale, evaluating the pressure under which they are placed, and providing sufficient data to refine wildlife viewing guidelines and/or zoning.
Coupled Dynamics of Behavior and Disease Contagion Among Antagonistic Groups
Authors: Smaldino Paul E. , Jones James Holland
Published: June 2020

Disease transmission and behavior change are both fundamentally social phenomena. Behavior change can have profound consequences for disease transmission, and epidemic conditions can favor the more rapid adoption of behavioral innovations. We analyze a simple model of coupled behavior-change and infection in a structured population characterized by homophily and outgroup aversion. Outgroup aversion slows the rate of adoption and can lead to lower rates of adoption in the later-adopting group or even behavioral divergence between groups when outgroup aversion exceeds positive ingroup influence. When disease dynamics are coupled to the behavior-adoption model, a wide variety of outcomes are possible. Homophily can either increase or decrease the final size of the epidemic depending on its relative strength in the two groups and onR0for the infection. For example, if the first group is homophilous and the second is not, the second group will have a larger epidemic. Homophily and outgroup aversion can also produce dynamics suggestive of a “second wave” in the first group that follows the peak of the epidemic in the second group. Our simple model reveals dynamics that are suggestive of the processes currently observed under pandemic conditions in culturally and/or politically polarized populations such as the United States.
Outdoor Atmospheric Microbial Diversity is Associated with Urban Landscape Structure and Differs from Indoor-Transit Systems as Revealed by Mobile Monitoring and Three-Dimensional Spatial Analysis
Authors: Stewart JD , Kremer P. , Shakya K.M. , Conway M. , Saad A.
Published: June 2020

Microbes are abundant inhabitants of the near-surface atmosphere in urban areas. The distribution of microbial communities may benefit or hinder human wellbeing and ecosystem function. Surveys of airborne microbial diversity are uncommon in both natural and built environments and those that investigate diversity are stationary in the city, thus missing continuous exposure to microbes that covary with three-dimensional urban structure. Individuals in cities are generally mobile and would be exposed to diverse urban structures outdoors and within indoor-transit systems in a day. We used mobile monitoring of microbial diversity and geographic information system spatial analysis, across Philadelphia, Pennsylvania, USA in outdoor and indoor-transit (subways and train cars) environments. This study identifies to the role of the three-dimensional urban landscape in structuring atmospheric microbiomes and employs mobile monitoring over ~1920 kilometers to measure continuous biodiversity. We found more diverse communities outdoors that significantly differ from indoor-transit air in microbial community structure, function, likely source environment, and potentially pathogenic fraction of the community. Variation in the structure of the urban landscape was associated with diversity and function of the near-surface atmospheric microbiome in outdoor samples.

Importance

Global nutrient cycling and human health depend on the rich biodiversity of microorganisms. The influence of the urban environment on microbiomes remains poorly described despite cities being the fastest growing ecosystems. All life is exposed to the atmosphere and thus discerning what microbes are present and what their functions may be is critical to create resistant and resilient cities under climate change. This study combines a spatially explicit analysis of urban structure with mobile monitoring of the atmospheric microbiome.
Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs
Authors: Vesga Omar , Valencia Andres F. , Mira Alejandro , Ossa Felipe , Ocampo Esteban , Agudelo Maria , Čiuoderis Karl , Perez Laura , Cardona Andres , Aguilar Yudy , González Javier M. , Cataño Juan C. , Agudelo Yuli , Hernández-Ortiz Juan P. , Osorio Jorge E.
Published: June 2020

Molecular tests for viral diagnostics are essential to confront the COVID-19 pandemic, but their production and distribution cannot satisfy the current high demand. Early identification of infected people and their contacts is the key to being able to isolate them and prevent the dissemination of the pathogen; unfortunately, most countries are unable to do this due to the lack of diagnostic tools. Dogs can identify, with a high rate of precision, unique odors of volatile organic compounds generated during an infection; as a result, dogs can diagnose infectious agents by smelling specimens and, sometimes, the body of an infected individual. We trained six dogs of three different breeds to detect SARS-CoV-2 in respiratory secretions of infected patients and evaluated their performance experimentally, comparing it against the gold standard (rRT-PCR). Here we show that viral detection takes one second per specimen. After scent-interrogating 9,200 samples, our six dogs achieved independently and as a group very high sensitivity, specificity, predictive values, accuracy, and likelihood ratio, with very narrow confidence intervals. The highest metric was the negative predictive value, indicating that with a disease prevalence of 7.6%, 99.9% of the specimens indicated as negative by the dogs did not carry the virus. These findings demonstrate that dogs could be useful to track viral infection in humans, allowing COVID-19 free people to return to work safely.
Structural mimicry confers robustness in the cyanobacterial circadian clock
Authors: Heisler Joel , Swan Jeffrey A. , Palacios Joseph G. , Sancar Cigdem , Ernst Dustin C. , Spangler Rebecca K. , Bagshaw Clive R. , Tripathi Sarvind , Crosby Priya , Golden Susan S. , Partch Carrie L. , LiWang Andy
Published: June 2020

The histidine kinase SasA enhances robustness of circadian rhythms in the cyanobacteriumS. elongatusby temporally controlling expression of the core clock components,kaiBandkaiC. Here we show that SasA also engages directly with KaiB and KaiC proteins to regulate the period and enhance robustness of the reconstituted circadian oscillatorin vitro, particularly under limiting concentrations of KaiB. In contrast to its role regulating gene expression, oscillator function does not require SasA kinase activity; rather, SasA uses structural mimicry to cooperatively recruit the rare, fold-switched conformation of KaiB to the KaiC hexamer to form the nighttime repressive complex. Cooperativity gives way to competition with increasing concentrations of SasA to define a dynamic window by which SasA directly modulates clock robustness.

One Sentence Summary

SasA controls the assembly of clock protein complexes through a balance of cooperative and competitive interactions.
Structural Consequences of the Villin Headpiece Interaction with a Carbon Nitride Polyaniline (C3N) Nanosheet
Authors: Gu Zonglin , Perez-Aguilar Jose Manuel , Zhou Ruhong
Published: June 2020

Carbon nitride polyaniline (C3N) nanosheets shared a similar structure with graphene and have been utilized in biomedical applications since its recent successful synthesis. However, limited information was known about the interaction of this next-generation nanomaterial with biomolecules, which might hamper its applications in living tissues. Here, by using all-atom molecular dynamics (MD) simulations, we investigated the interaction between a C3N nanosheet and the prototypical protein villin headpiece (HP35), in order to identify the mechanistic determinants of such interaction; this knowledge will provide guidelines about C3N’s biocompatibility. Our MD simulations revealed that the C3N-based nanomaterial caused the partial denaturation of HP35 once the protein was bound on its surface. That is, upon adsorption, we observed the loss of the protein’s interior hydrogen bonds and the native contacts, which were related with unwinding events in the protein’s helices. The protein/C3N nanosheet interacting process was dominated by vdW contributions to the energy and the stepwise changes observed in the values of this energy term suggested a gradual unfolding pattern of HP35 during the absorption event. Furthermore, we also found that the interaction energy showed a linear correlation with the native Q ratio of HP35, suggesting that the degree of HP35 unfolding was linearly time-dependent to the interaction energy. Our findings shed light on the underlying molecular mechanism of the potential consequences of C3N-based nanostructures to proteins, which might delineate the future applications of these nanomaterials in biomedicine.
GLP-1R agonist NLY01 reduces retinal inflammation, astrocyte reactivity, and retinal ganglion cell death secondary to ocular hypertension
Authors: Sterling Jacob K. , Adetunji Modupe , Guttha Samyuktha , Bargoud Albert , Uyhazi Katherine , Ross Ahmara G. , Dunaief Joshua L. , Cui Qi N.
Published: June 2020

Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by the death of retinal ganglion cells. Reduction of intraocular pressure (IOP) is the only therapeutic mechanism available to slow disease progression. However, glaucoma can continue to progress despite normalization of IOP. New treatments are needed to reduce vision loss and improve outcomes for patients who have exhausted existing therapeutic avenues. Recent studies have implicated neuroinflammation in the pathogenesis of neurodegenerative diseases of both the retina and the brain, including glaucoma and Parkinson’s disease. Pro-inflammatory A1 astrocytes contribute to neuronal cell death in multiple disease processes and have been targeted therapeutically in mouse models of Parkinson’s disease. Microglial release of pro-inflammatory cytokines C1q, IL-1α, and TNF-α is sufficient to drive the formation of A1 astrocytes. The role of A1 astrocytes in glaucoma pathogenesis has not been explored. Using a mouse model of glaucoma, we demonstrated that IOP elevation was sufficient to trigger production of C1q, IL-1α, and TNF-α by infiltrating macrophages followed by resident microglia. These three cytokines drove the formation of A1 astrocytes in the retina. Furthermore, cytokine production and A1 astrocyte transformation persisted following IOP normalization. Ablation of this pathway, by either genetic deletions of C1q, IL-1α, and TNF-α, or treatment with glucagon-like peptide-1 receptor agonist NLY01, reduced A1 astrocyte transformation and RGC death. Together, these results highlight a new neuroinflammatory mechanism behind glaucomatous neurodegeneration that can be therapeutically targeted by NLY01 administration.
Identification of enzymes for lignocellulose degradation in the genome and transcriptome of the aquatic hyphomyceteClavariopsis aquatica
Authors: Heeger Felix , Bourne Elizabeth C. , Wurzbacher Christian , Funke Elisabeth , Lipzen Anna , He Guifen , Ng Vivian , Grigoriev Igor V. , Schlosser Dietmar , Monaghan Michael T.
Published: June 2020

Fungi are ecologically important decomposers of lignocellulose. Basidiomycetes use peroxidases, laccases, and enzymes of the cytochrome P450 superfamily for cometabolic lignin degradation in order to access cellulose and hemicellulose as carbon sources. Limited lignin modification capabilities have also been reported for some terrestrial ascomycetes. Here we newly sequenced the genome of an exclusively aquatic ascomycete,Clavariopsis aquatica, documented the presence of genes for the modification of lignocellulose and its constituents, and compared differential gene expression betweenC. aquaticacultivated on lignocellulosic and sugar-rich substrates. We identified potential peroxidases, laccases, and cytochrome P450 monooxygenases several of which were differentially expressed when experimentally grown on different substrates. Additionally, we found regulation of pathways for cellulose and hemicellulose degradation. Our results suggest thatC. aquaticais able to modify lignin, detoxify aromatic lignin constituents, or both. This may facilitate the use of carbohydrate components of lignocellulose as carbon and energy sources.
Reward processing electrophysiology in schizophrenia: Effects of age and illness phase
Authors: Abram Samantha V. , Roach Brian J. , Holroyd CB , Paulus MP , Ford Judith M. , Mathalon Daniel H. , Fryer Susanna L.
Published: June 2020

Background

Reward processing abnormalities may underlie characteristic pleasure and motivational impairments in schizophrenia. Some neural measures of reward processing show strong age-related modulation, highlighting the importance of considering age effects on reward sensitivity. We compared event-related potentials (ERPs) reflecting reward anticipation (stimulus-preceding negativity, SPN) and evaluation (reward positivity, RewP; late-positive potential, LPP) across individuals with schizophrenia (SZ) and healthy controls (HC), with an emphasis on examining effects of chronological age, brain age (i.e., predicted age based on neurobiological measures), and illness phase.

Methods

Subjects underwent EEG while completing a slot-machine task for which rewards were not dependent on performance accuracy, speed, or other preparatory demands. Slot-machine task EEG responses were compared between 54 SZ and 54 HC individuals, ages 19 to 65. Reward-related ERPs were analyzed with respect to chronological age, categorically-defined illness phase (early; ESZ versus chronic schizophrenia; CSZ), and were used to model brain age relative to chronological age.

Results

Illness phase-focused analyses indicated there were no group differences in average SPN or RewP amplitudes. However, a group x reward outcome interaction revealed that ESZ differed from HC in later outcome processing, reflected by greater LPP responses following loss versus reward (a reversal of the HC pattern). While brain age estimates did not differ among groups, depressive symptoms in SZ were associated with older brain age estimates while controlling for negative symptoms.

Conclusions

ESZ and CSZ did not differ from HC in reward anticipation or early outcome processing during a cognitively undemanding reward task, highlighting areas of preserved functioning. However, ESZ showed altered later reward outcome evaluation, pointing to selective reward deficits during the early illness phase of schizophrenia. Further, an association between ERP-derived brain age and depressive symptoms in SZ extends prior findings linking depression with reward-related ERP blunting. Taken together, both illness phase and age may impact reward processing in SZ, and brain aging may offer a promising, novel marker of reward dysfunction that warrants further study.
The limited spatial scale of dispersal in soil arthropods revealed with whole-community haplotype-level metabarcoding
Authors: Arribas P , Andújar C , Salces-Castellano A , Emerson BC , Vogler AP
Published: June 2020

Soil mesofauna communities are hyperdiverse and critical for ecosystem functioning. However, our knowledge on spatial structure and underlying processes of community assembly for soil arthropods is scarce, hampered by limited empirical data on species diversity and turnover. We implement a high-throughput-sequencing approach to generate comparative data for thousands of arthropods at three hierarchical levels: genetic, species and supra-specific lineages. A joint analysis of the spatial arrangement across these levels can reveal the predominant processes driving the variation in biological assemblages at the local scale. This multi-hierarchical approach was performed using haplotype-level-COI metabarcoding of entire communities of mites, springtails and beetles from three Iberian mountain regions. Tens of thousands of specimens were extracted from deep and superficial soil layers and produced comparative phylogeographic data for >1000 co-distributed species and nearly 3000 haplotypes. Local assemblages were highly distinctive between grasslands and forests, and within each of them showed strong spatial structures and high endemicity at the scale of a few kilometres or less. The local distance-decay patterns were self-similar for the haplotypes and higher hierarchical entities, and this fractal structure was very similar in all three regions, pointing to a significant role of dispersal limitation driving the local-scale community assembly. Our results from whole-community metabarcoding provide unprecedented insight into how dispersal limitations constrain mesofauna community structure within local spatial settings over evolutionary timescales. If generalized across wider areas, the high turnover and endemicity in the soil locally may indicate extremely high richness globally, challenging our current estimations of total arthropod-diversity on Earth.
Physicochemical characterization, toxicity andin vivobiodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin
Authors: Torgersen Maria Lyngaas , Judge Peter J. , Juarez Juan F. Bada , Pandya Abhilash D. , Fusser Markus , Davies Charlie W. , Maciejewska Matylda K. , Yin Daniel J. , Mælandsmo Gunhild M. , Skotland Tore , Watts Anthony , Sandvig Kirsten
Published: June 2020

Many promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and thein vivoexcretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.
Modified Hypoxia Inducible Factor expression in CD8+ T cells increases anti-tumor efficacy
Authors: Veliça Pedro , Cunha Pedro Pacheco , Vojnovic Nikola , Foskolou Iosifina Petrina , Bargiela David , Gojkovic Milos , Rundqvist Helene , Johnson Randall Scott
Published: June 2020

Adoptive transfer of anti-tumor cytotoxic T cells is a novel form of cancer immunotherapy, and a key challenge is to ensure the survival and function of the transferred T cells. Immune cell survival requires adaptation to different micro-environments, and particularly to the hypoxic milieu of solid tumors. The HIF transcription factors are an essential aspect of this adaptation, and we undertook experiments to define structural determinants of HIF that would potentiate anti-tumor efficacy in cytotoxic T cells. We created retroviral vectors to deliver ectopic expression of HIF-1ɑ and HIF-2ɑ in mouse CD8+ T cells, together or individually, and with or without sensitivity to their oxygen-dependent inhibitors Von Hippel-Lindau (VHL) and Factor Inhibiting HIF (FIH). We found that HIF-2ɑ, but not HIF-1ɑ, drives broad transcriptional changes in CD8+ T cells, resulting in increased cytotoxic differentiation and cytolytic function against tumor targets. We further found that a specific mutation replacing the hydroxyl group acceptor site for FIH in the HIF-2ɑ isoform gives rise to the most effective anti-tumor T cells after adoptive transfer in vivo. Lastly, we show that co-delivering an FIH-insensitive form of HIF-2ɑ with an anti-CD19 chimeric antigen receptor greatly enhances cytolytic function of human CD8+ T cells against lymphoma cells. These experiments provide a means to increase the anti-tumor efficacy of therapeutic CD8+ T cells via ectopic expression of the HIF transcription factor.

Graphical abstract