bluuebunny/crossref_metadata_2025 huggingface dataset:
Turbulent, pinned superfluids in neutron stars and pulsar glitch recoveries
Authors: Haskell B , Antonopoulou D , Barenghi C
Published: September 2020

Pulsar glitches offer an insight into the dynamics of superfluids in the high-density interior of a neutron star. To model these phenomena, however, one needs to have an understanding of the dynamics of a turbulent array of superfluid vortices moving through a pinning lattice. In this paper, we develop a theoretical approach to describe vortex-mediated mutual friction in a pinned, turbulent and rotating superfluid. Our model is then applied to the study of the post-glitch rotational evolution in the Vela pulsar and in PSR J0537-6910. We show that in both cases a turbulent model fits the evolution of the spin frequency derivative better than a laminar one. We also predict that the second derivative of the frequency after a glitch should be correlated with the waiting time since the previous glitch, which we find to be consistent with observational data for these pulsars. The main conclusion of this paper is that in the post-glitch rotational evolution of these two pulsars we are most likely observing the response to the glitch of a pinned turbulent region of the star (possibly the crust) and not the laminar response of a regular straight vortex array.
CasCollect: targeted assembly of CRISPR-associated operons from high-throughput sequencing data
Authors: Podlevsky Joshua D , Hudson Corey M , Timlin Jerilyn A , Williams Kelly P
Published: September 2020

CRISPR arrays and CRISPR-associated (Cas) proteins comprise a widespread adaptive immune system in bacteria and archaea. These systems function as a defense against exogenous parasitic mobile genetic elements that include bacteriophages, plasmids and foreign nucleic acids. With the continuous spread of antibiotic resistance, knowledge of pathogen susceptibility to bacteriophage therapy is becoming more critical. Additionally, gene-editing applications would benefit from the discovery of new cas genes with favorable properties. While next-generation sequencing has produced staggering quantities of data, transitioning from raw sequencing reads to the identification of CRISPR/Cas systems has remained challenging. This is especially true for metagenomic data, which has the highest potential for identifying novel cas genes. We report a comprehensive computational pipeline, CasCollect, for the targeted assembly and annotation of cas genes and CRISPR arrays—even isolated arrays—from raw sequencing reads. Benchmarking our targeted assembly pipeline demonstrates significantly improved timing by almost two orders of magnitude compared with conventional assembly and annotation, while retaining the ability to detect CRISPR arrays and cas genes. CasCollect is a highly versatile pipeline and can be used for targeted assembly of any specialty gene set, reconfigurable for user provided Hidden Markov Models and/or reference nucleotide sequences.
Read trimming is not required for mapping and quantification of RNA-seq reads at the gene level
Authors: Liao Yang , Shi Wei
Published: September 2020

RNA sequencing (RNA-seq) is currently the standard method for genome-wide expression profiling. RNA-seq reads often need to be mapped to a reference genome before read counts can be produced for genes. Read trimming methods have been developed to assist read mapping by removing adapter sequences and low-sequencing-quality bases. It is however unclear what is the impact of read trimming on the quantification of RNA-seq data, an important task in RNA-seq data analysis. In this study, we used a benchmark RNA-seq dataset and simulation data to assess the impact of read trimming on mapping and quantification of RNA-seq reads. We found that adapter sequences can be effectively removed by read aligner via ’soft-clipping’ and that many low-sequencing-quality bases, which would be removed by read trimming tools, were rescued by the aligner. Accuracy of gene expression quantification from using untrimmed reads was found to be comparable to or slightly better than that from using trimmed reads, based on Pearson correlation with reverse transcriptase-polymerase chain reaction data and simulation truth. Total data analysis time was reduced by up to an order of magnitude when read trimming was not performed. Our study suggests that read trimming is a redundant process in the quantification of RNA-seq expression data.
Association of Early Nasopharyngeal Immune Markers With COVID-19 Clinical Outcome: Predictive Value of CCL2/MCP-1
Authors: Sierra Beatriz , Pérez Ana B , Aguirre Eglis , Bracho Claudia , Valdés Odalys , Jimenez Narciso , Baldoquin Waldemar , Gonzalez Guelsys , Ortega Lilia M , Montalvo Maria C , Resik Sonia , Alvarez Delmis , Guzmán Maria G
Published: September 2020

Early recognition of severe forms of coronavirus disease 2019 (COVID-19) is essential for an opportune and effective intervention, reducing life-risking complications. An altered inflammatory immune response seems to be associated with COVID-19’s pathogenesis and progression to severity. Here we demonstrate the utility of early nasopharyngeal swab samples for detection of the early expression of immune markers and the potential value of CCL2/MCP-1 in predicting disease outcome.
Perceptions of Kinesiophobia in Relation to Physical Activity and Exercise After Myocardial Infarction: A Qualitative Study
Authors: Bäck Maria , Caldenius Victoria , Svensson Leif , Lundberg Mari
Published: September 2020

Objective

Physical activity and exercise are central components in rehabilitation after a myocardial infarction. Kinesiophobia (fear of movement) is a well-known barrier for a good rehabilitation outcome in these patients; however, there is a lack of studies focusing on the patient perspective. The aim of this study was to explore patients’ perceptions of kinesiophobia in relation to physical activity and exercise 2 to 3 months after an acute myocardial infarction.

Methods

This qualitative study design used individual semi-structured interviews. Face-to-face interviews were conducted with 21 patients post-myocardial infarction who were screened for kinesiophobia (≥32 on the Tampa Scale for Kinesiophobia Heart). The interviews were transcribed and analyzed according to an inductive content analysis.

Results

An overarching theme was defined as “coping with fear of movement after a myocardial infarction—a dynamic process over time” comprising 2 subthemes and explaining how coping with kinesiophobia runs in parallel processes integrating the patient’s internal process and a contextual external process. The 2 processes are described in a total of 8 categories. The internal process was an iterative process governed by a combination of factors: ambivalence, hypervigilance, insecurity about progression, and avoidance behavior. The external process contains the categories of relatives’ anxiety, prerequisites for feeling safe, information, and the exercise-based cardiac rehabilitation program.

Conclusion

Coping with fear of movement after a myocardial infarction is a dynamic process that requires internal and external support. To further improve cardiac rehabilitation programs, person-centered strategies that support the process of each person—as well as new treatment strategies to reduce kinesiophobia—need to be elaborated.

Impact

Patients with a myocardial infarction were found to be ambivalent about how they expressed their fear of movement; therefore, it is crucial for physical therapists to acknowledge signs of fear by listening carefully to the patient’s full story in addition to using adequate self-reports and tests of physical fitness. These results will inform the design, development, and evaluation of new treatment strategies, with the overall aim of reducing kinesiophobia and increasing physical activity and participation in exercise-based cardiac rehabilitation.
Elaboration of a new synovial predictive score of septic origin for acute arthritis on the native joint (RESAS)
Authors: Coiffier Guillaume , Berthoud Olivia , Albert Jean David , Robin François , Goussault Claire , Gougeon-Jolivet Anne , Bendavid Claude , Guggenbuhl Pascal
Published: September 2020

Objective

To establish a new predictive score for the diagnosis of septic arthritis (SA) according to different synovial fluid (SF) variables.

Methods

First, we analysed the different clinical, biological and SF variables associated with the diagnosis of SA (according to the Newman’s criteria) in a monocentric cohort of acute arthritis (<30 days) (n = 233) (SYNOLACTATE cohort). A new score predictive of SA (RESAS) was created using the independent discriminant variables after multivariate analysis. A value was attributed to each variable of the score according to the weighting based on their likelihood ratio for the diagnosis of SA. RESAS performance was then tested on the first cohort (internal validation) and then checked on a second independent cohort (n = 70) (external validation).

Results

After multivariate analysis, four independent variables of the SF were included for RESAS: (i) purulent SF or white blood cells count ≥70 000/mm3; (ii) absence/presence of crystals; (iii) lactate; and (iv) glucose synovial level. RESAS ranged between −4 and +13 points. The performance of RESAS to predicted SA was excellent with area under the curve (AUC)=0.928 (0.877–0.980) in internal validation and AUC=0.986 (0.962–1.00) in external validation. For a RESAS threshold ≥+4, SA was diagnosed with Se=56.0% (0.371–0.733), Sp=98.1% (0.952–0.993), LR+=29.1 (10.4–81.6) in the first cohort and with Se=91.7% (0.646–0.985), Sp=98.3% (0.909–0.997), LR+=53.2 (7.56–373) in the second cohort.

Conclusion

RESAS is a new composite score of four SF variables with excellent performance to predicted SA in acute arthritis population.
Effects of Bacillus subtilis PB6 and/or chromium propionate supplementation on serum chemistry, complete blood count, and fecal Salmonella spp. count in high-risk cattle during the feedlot receiving and finishing periods1,2
Authors: Smock Taylor M , Samuelson Kendall L , Wells Jim E , Hales Kristin E , Hergenreder Jerilyn E , Rounds P Whitney , Richeson John T
Published: September 2020

The study objective was to determine the effects of Bacillus subtilis PB6 and/or chromium propionate supplementation on serum chemistry, complete blood count, and fecal Salmonella spp. count in high-risk beef cattle during a 56-d feedlot receiving period and the subsequent finishing period. Four truckload blocks of crossbred beef bulls (n = 300) and steers [n = 84; total n = 384; average initial body weight (BW) = 220 ± 16.2 kg] were sourced from regional auction markets and assigned randomly to treatments arranged in a 2 × 2 factorial. Blood samples were collected from two bulls nearest to the median BW on arrival in each pen (n = 96) and fecal samples were collected from cattle in block 3 (n = 96). The generalized complete block design consisted of 12 pen replications per treatment with pen as the experimental unit. Treatments were: 1) negative control (CON); 2) 13 g per animal daily of prepared B. subtilis PB6 product (CST); 3) 450 ppb dry matter (DM) chromium propionate (CHR); and 4) 13 g per animal daily of prepared B. subtilis PB6 product and 450 ppb DM chromium propionate (CST + CHR). Treatments were top dressed in feed bunks daily using 0.45 kg per animal ground corn carrier immediately following feed delivery. Data were analyzed using mixed models with repeated measures. Day affected all serum chemistry variables (P ≤ 0.03) except total CO2 (P = 0.34) and all complete blood count variables during receiving (P ≤ 0.02) except percentage basophils (P ≥ 0.12). During the overall receiving period, serum calcium was decreased (P = 0.02) by CHR. Cattle fed CHR had greater total leukocyte count (P = 0.04) and neutrophil count (P = 0.02) during the overall receiving period. Fecal Salmonella spp. count was markedly reduced in cattle fed CST on day 28 (P = 0.01) and overall (P = 0.07). Overall, these data provide metabolic and hematologic insight into the unique challenges presented by lightweight, high-risk feeder cattle. Notably, CST was found to be effective in mitigating fecal enumeration and presumably replication of Salmonella spp. in the gastrointestinal tract.
Pediatric Patient Surge: Evaluation of an Alternate Care Site Quality Improvement Initiative
Authors: De Leon Eric , Enriquez Oscar , Rodriguez Debra , Higginbotham Eric , Fredeboelling Elizabeth , Lewis Kimberly A.
Published: September 2020

Background:

Pediatric Level I trauma centers often experience patient volume surges. The increase stresses the emergency department, and usual patient care areas become inadequate. The purpose of this quality improvement study is to describe the implementation and analysis of an alternate care site to facilitate patient flow during seasonal patient volume surges.

Methods:

This initiative used a nonequivalent historical control group posttest-only design. An alternate care site was selected because of its size, temporary nature, low cost, and proximity to the emergency department. The alternate care site was activated between January and March 2019 using the following criteria: the total number of patients in waiting room 30 or more and wait times 2.5 hr or more. Outcome metrics include total census, length of stay—admissions, length of stay—discharges, left without being seen, hours per patient visit, patient satisfaction scores, and process metrics. Descriptive statistics and t tests were used to determine differences between groups.

Results:

A total of 180 patients were analyzed with n = 90 from 2018 and n = 90 from 2019. The alternate care site was activated five times over one season. The alternate care site decreased median waiting times, length of stay—admissions, length of stay—discharges, and left without being seen as compared with the previous year. Hours per patient visit and patient satisfaction scores remained constant as compared with the previous year.

Conclusions:

The creation of an alternate care site within the emergency department allowed quick mobilization, response, and treatment of patients. The alternate care site decreased median length of stay for admissions, discharges, and who left without being seen while keeping hours per patient visit and patient satisfaction constant. Future studies should confirm findings by testing the alternate care site in other hospitals and settings and should consider formally evaluating staff satisfaction.
Implementation of an Abusive Head Trauma Prevention Program Through Interdisciplinary Collaboration: A Pilot Study
Authors: McInerney Susan , Nanassy Autumn D. , Lavella Heather , Thompson Rochelle , Sandhu Rebecca , Meyer Loreen K.
Published: September 2020

Background:

Shaken baby syndrome/abusive head trauma (SBS/AHT) is the leading cause of child abuse death. Our institution piloted an evidence-based educational program to increase nurse and caregiver knowledge about SBS/AHT.

Methods:

Nurses participated in a pretest survey, completed online implementation training, and then were given a posttest survey to determine the change in SBS/AHT knowledge. Once trained, nurses disseminated information to caregivers with children younger than 6 months. Caregivers (N = 87) watched an educational video, reviewed information in a booklet with a nurse, and participated in teach-back related to key points of the intervention in both a hospital and the community setting.

Results:

Prior to the education, nurses (n = 115) scored 8.03 out of 10.00 on the SBS/AHT assessment. Following the intervention, nurses (n = 120) scored 9.00 out of 10.00 on the assessment, t(233) = −6.61, p < .001. During education, caregivers (n = 69) were able to recall 8.55 out of 12 key educational components. In the community setting, caregivers (n = 18) worked together to recall 12 out of the 12 key components. Caregivers were most likely to recall ways to comfort their crying baby (94%) and why shaking a baby is dangerous (93%).

Conclusion:

This pilot study significantly increased nurses' knowledge of SBS/AHT and provided education to caregivers about SBS/AHT.
Pediatric Seat Belt Use in Motor Vehicle Collisions: The Need for Driver Education Programs
Authors: Elkbuli Adel , Dowd Brianna , Spano Paul J. , McKenney Mark
Published: September 2020

Background:

By statute, pediatric passengers transported in motor vehicles need to be appropriately restrained. The National Highway Traffic Safety Administration (NHTSA) estimates that currently only 2% of children do not wear safety restraints. This study aimed primarily to evaluate the use of pediatric restraints (seat belts) in motor vehicle collisions (MVCs) transported to our Level I pediatric trauma center (PTC) compared with historical NHTSA controls.

Methods:

A 4-year review utilized our Level I PTC registry for patients younger than 16 years, involved in an MVC. Appropriate booster seat/child restraints were verified by EMS, fire rescue, and patient/family. Odds ratios were used to compare occurrences and χ2 for categorical values with significance defined as p <.05.

Results:

A total of 685 pediatric patients in MVCs were admitted to our PTC during the study period. Only 39 of 685 (5.7%) pediatric patients were in restraints. Based on the NHTSA historical controls, 671 of 685 (98%) children would have been expected to be using restraints (5.7% vs. 98%, p < .01). The odds ratio of lack of use of child restraints or seat belts in pediatric trauma population was markedly higher compared with NHTSA historical controls (odds ratio 793.9, 95% confidence interval: 427.02–1475.98, p < .0001).

Conclusion:

Astonishingly low rates of child restraints and seat belt use in pediatric patients in MVCs, requiring admission to a PTC, indicate the need for better injury prevention programs, and parental or driver education on risks associated with lack of restraints.
Stigma among key populations living with HIV in the Dominican Republic: experiences of people of Haitian descent, MSM, and female sex workers
Authors: Yam Eileen A. , Pulerwitz Julie , Almonte Dulce , García Felipa , del Valle Angel , Colom Alejandra , McClair Tracy L. , Dolores Yordana
Published: September 2020

Objective(s):

To describe stigma among seropositive MSM, female sex workers (FSWs), and Haitian-descent individuals in the Dominican Republic, and to assess whether stigma is associated with HIV treatment outcomes.

Design:

Cross-sectional survey using Stigma Index 2.0.

Methods:

People living with HIV (PLHIV) interviewed seropositive adult MSM, FSWs, Haitian-descent persons, and other PLHIV who did not identify with these communities about experiences of social exclusion, harassment, stigma in healthcare settings, and internalized stigma. Bivariate analyses were conducted to compare experiences between FSWs and other women; MSM and other men; and Haitian-descent participants and non-Haitian PLHIV. Within each community, separate multivariate logistic regression analyses were conducted to examine the association between stigma experiences with viral suppression and with missed antiretroviral doses.

Results:

The 891 participants consisted of 154 MSM, 216 FSWs, 90 Haitian-descent persons, and 447 who did not identify with any of these three communities. Compared with other women, FSWs reported significantly higher levels of harassment due to their HIV status, and those of Haitian descent reported significantly lower levels of social exclusion compared with non-Haitian PLHIV. In adjusted analyses, MSM who experienced more stigma in HIV-specific services had a significantly lower odds of knowing they had undetectable viral load (adjusted odds ratio 0.37, P < 0.05). Higher internalized stigma scores were significantly associated with missing an antiretroviral treatment dose among FSWs (adjusted odds ratio 1.26, P < 0.05).

Conclusion:

For FSWs and MSM, efforts to mitigate HIV-related stigma are necessary to improve treatment adherence and viral suppression. For Haitian-descent PLHIV, interventions must address not only their HIV-specific needs, but also the broader social and legal barriers to care.
Key Features on the 3-Vessel View and 3-Vessel Tracheal View of Isolated Right Aortic Arch Anomalies
Authors: McGahan John P. , James Gina , Hedriana Herman , Sunderji Sherzana
Published: September 2020

Right aortic arch anomalies are a spectrum of malformations that include right aortic arch with mirror image branching, right aortic arch with an aberrant left subclavian artery, and double aortic arch. Although these are rare anomalies, they are of importance as they form vascular rings, which can cause symptoms in the newborn period. These anomalies are not detected with routine cardiac views, and it is only with the 3-vessel, and the 3-vessel tracheal view that they can be identified and characterized. We describe specific sonographic findings of these anomalies on the 3-vessel and the 3-vessel tracheal view.
An Evaluation Using Colored Doppler Ultrasonography of Central Retinal Artery Hemodynamics in the Healthy Eye in Individuals With Late Monocular Blindness
Authors: Ozen Ozkan , Aslan Fatih
Published: September 2020

Structural and functional changes occur in the brain after vision losses. The purpose of the present study was to investigate central retinal artery (CRA) hemodynamics in the healthy eye of individuals developing late monocular blindness (LMB) using colored Doppler ultrasonography.

The CRAs of 13 healthy eyes of 13 patients with LMB and of 13 healthy individuals as a control group were evaluated in this prospective study. Peak systolic velocity, end-diastolic velocity, mean flow velocity, systolic/diastolic velocity ratio, and resistivity and pulsatility index (RI, PI) values in the CRAs were determined using colored Doppler ultrasonography in both groups.

The mean age of all the individuals examined was 39.3 ± 12.3 years, and loss of vision in the LMB patients had been present for a mean 22 ± 13.2 years. The PSH, DHS, and mean flow velocity values in the LMB group were 13.3 ± 2.5 cm/s, 3.1 ± 0.8 cm/s, and 6.5 ± 1.6 cm/s, respectively, significantly lower than in the control group at 18.6 ± 5 cm/s, 5.5 ± 2.8 cm/s, and 10 ± 3.2 cm/s (P < 0.05). The PI, RI, and systolic/diastolic velocity ratio values differences in the both group were not statistically significant (P > 0.05).

In conclusion, the absence of a significant difference in RI and PI values between the 2 groups revealed that vascular resistance did not develop in the CRA hemodynamics of healthy eyes of individuals with LMB, although the low velocity values showed an increase in CRA width.
Relationship Between Cognitive Functions and Insulin-degrading Enzyme in Individuals With Prediabetes
Authors: Saçmaci Hikmet , Ozan Zeynep , Özcan Seda , Meşe Emine , Ercan Müjgan , İnan Levent
Published: September 2020

Background:

Individuals with diabetes can develop cognitive impairment due to dysfunction of glucose metabolism; however, it remains unclear whether cognition becomes altered in the prediabetic stage. Substantial evidence links cognitive impairment in diabetes to aberrant serum insulin-degrading enzyme (s[IDE]) levels. This relationship remains to be investigated in individuals with prediabetes.

Objective:

To investigate the relationship between cognitive function and s[IDE] levels in individuals with prediabetes.

Method:

The study group consisted of 47 individuals who had been diagnosed with prediabetes and 41 healthy controls. Cognitive functions were evaluated using the Montreal Cognitive Assessment (MoCA), and s[IDE] levels were measured using enzyme-linked immunosorbent assay.

Results:

The MoCA total scores and s[IDE] levels of the individuals with prediabetes were significantly lower (P = 0.001, 0.006) than those of the controls, and the MoCA Attention measure of the individuals with prediabetes was also very low (P = 0.001). To determine cognitive impairment, we divided the prediabetics into two subgroups according to the MoCA cutoff value. Scores on all of the MoCA tests were significantly lower in the group with mild cognitive impairment (P < 0.05). There was no correlation between MoCA scores and s[IDE] levels (P > 0.05), but serum-fasting glucose levels showed a negative correlation with MoCA scores (P < 0.05, ρ = –0.287).

Conclusion:

Evidence of mild cognitive impairment was high in the individuals with prediabetes and showed a negative correlation with serum-fasting glucose levels but not with s[IDE] levels.
Diversity During Recruitment At An Internal Medicine Residency Program
Authors: Kumar Sarwan , Gupta Deepak
Published: September 2020

Background

The right problem for graduate medical education (GME) program directors is whether diversity in their GME programs is as good as diversity in feeder entities to their GME programs. Generally, the feeder entities to GME residency programs are their affiliated medical schools. However, the specific feeder entities to GME residency programs are the unfiltered applicants’ pool who apply to these programs through Electronic Residency Application Service® (ERAS®).

Objectives

To analyze associations in diversity among the GME applicants, the GME interviewees and the GME residents within an internal medicine residency program assuming that unfiltered applicants’ pool is the specific feeder entity to the analyzed GME program.

Methods

We analyzed associations in age-group, gender, ethnicity and race diversity among the GME applicants, the GME interviewees and the GME residents within an internal medicine residency program for ERAS® 2018-2020 seasons to decipher Cramer’s V as association coefficients (“diversity scores”).

Results

The only significant finding was that among Not Hispanic or Latino ethnicity applications, race of ERAS® applicants had a very weak association with them being called for interviews or them becoming residents during ERAS® 2019 season as well as during the entire three-season-period (2018-2020).

Conclusion

Race of Not Hispanic or Latino ethnicity ERAS® applicants had a very weak association with them being called for interviews or them becoming residents at the analyzed internal medicine residency program.
An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output
Authors: Stec Natalia , Doerfel Katja , Hills-Muckey Kelly , Ettorre Victoria M. , Ercan Sevinc , Keil Wolfgang , Hammell C. M.
Published: September 2020

While precise tuning of gene expression levels is critical for most developmental pathways, the mechanisms by which the transcriptional output of dosage-sensitive molecules is established or modulated by the environment remain poorly understood. Here, we provide a mechanistic framework for how the conserved transcription factor BLMP-1/Blimp1 operates as a pioneer factor to decompact chromatin near its target loci hours before transcriptional activation and by doing so, regulates both the duration and amplitude of subsequent target gene transcription. This priming mechanism is genetically separable from the mechanisms that establish the timing of transcriptional induction and functions to canalize aspects of cell-fate specification, animal size regulation, and molting. A key feature of the BLMP-1-dependent transcriptional priming mechanism is that chromatin decompaction is initially established during embryogenesis and maintained throughout larval development by nutrient sensing. This anticipatory mechanism integrates transcriptional output with environmental conditions and is essential for resuming normal temporal patterning after animals exit nutrient-mediated developmental arrests.
Estimating the number of COVID-19 cases being introduced into British Higher Education Institutions during Autumn 2020
Authors: Pérez-Reche Francisco J. , Strachan Norval J.C.
Published: September 2020

It is estimated that 81% of the 163 UK Higher Educational Institutes (HEIs) have more than a 50% chance of having at least one COVID-19 case arriving on campus when considering all staff and students. Across all HEIs it is estimated that there will be a total of approximately 700 COVID-19 cases (95% CI: 640 – 750) arriving on campus of which 380 are associated from UK students, 230 from international and 90 from staff. This assumes all students will return to campus and that student numbers and where they come from are similar to previous years. According to the current UK government guidance approximately 237,370 students arriving on campus will be required to quarantine because they come from countries outwith designated travel corridors. Assuming quarantining is 100% efficient this will potentially reduce the overall number of cases by approximately 20% to 540 (95% CI: 500 – 590). Universities must plan for COVID-19 cases to arrive on campus and facilitate mitigations to reduce the spread of disease. It is likely that the first two weeks will be crucial to stop spread of introduced cases. Following that, the risk of introduction of new cases onto campus will be from interactions between students, staff and the local community as well as students travelling off campus for personal, educational or recreational reasons.
PI3K/mTOR and topoisomerase inhibitors with potential activity against SARS-CoV-2 infection
Authors: White James Robert , Foote Michael Bonner , Jee Justin , Argilés Guillem , Wan Jonathan C.M. , Diaz Luis Alberto
Published: September 2020

There is an urgent need to identify therapies to prevent and treat SARS-CoV-2 infection. We performed a statistical evaluation of in vitro gene expression profiles reflecting exposure to 1,835 drugs, and found topoisomerase inhibitors and PI3K/mTOR pathway inhibitors among the strongest candidates for reduced expression of ACE2, a host gene associated with SARS-CoV-2 infection. Retrospective clinical data suggest that patients on these agents may be less likely to test positive for SARS-CoV-2.
Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19
Authors: Liu Di , Yang Jingyun , Feng Bowen , Lu Wenjin , Zhao Chuntao , Li Lizhuo
Published: September 2020

Objectives

COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear.

Methods

We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19.

Results

In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (β [SE] = 0.42 [0.09], P = 4.75×10−06 and β [SE] = –0.48 [0.11], P = 6.76×10−06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation.

Conclusions

We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.
Reducing variance in a mouse defect healing model: Real-time Finite Element Analysis allows homogenization of tissue scale strains
Authors: Paul Graeme R. , Wehrle Esther , Tourolle Duncan C. , Kuhn Gisela A. , Müller Ralph
Published: September 2020

Mechanical loading allows both investigation into the mechano-regulation of fracture healing as well as interventions to improve fracture-healing outcomes such as delayed healing or non-unions. However, loading is seldom individualised or even targeted to an effective mechanical stimulus level within the bone tissue. In this study, we use micro-finite element analysis to demonstrate the result of using a constant loading assumption for all mouse femurs in a given group. We then contrast this with the application of an adaptive loading approach, denoted real time Finite Element (rtFE) adaptation, in which micro-computed tomography images provide the basis for micro-FE based simulations and the resulting strains are manipulated and targeted to a reference distribution. Using this approach, we demonstrate that individualised femoral loading leads to a better-specified strain distribution and lower variance in tissue mechanical stimulus across all mice, both longitudinally and cross-sectionally, while making sure that no overloading is occurring leading to refracture of the femur bones.
Triplet-Triplet Annihilation PLGA-Nanoparticles for Cancer Bioimaging
Authors: Vepris Olena , Eich Christina , Feng Yansong , Zhang Hong , Kaijzel Eric. L. , Cruz Luis J.
Published: September 2020

Triplet-triplet annihilation upconversion (TTA-UC) nanoparticles (NPs) have emerged as imaging probes and therapeutic probes in recent years due to their excellent optical properties. In contrast to lanthanide ions-doped inorganic materials, highly efficient TTA-UC can be generated by low excitation power density, which makes it suitable for clinical applications. In the present study, we used biodegradable poly(lactic-co-glycolic acid) (PLGA)-NPs as delivery vehicle for TTA-UC based on the heavy metal porphyrin Platinum(II) octaethylporphyrin (PtOEP) and the polycyclic aromatic hydrocarbon 9,10-diphenylanthracene (DPA) as photosensitizer/emitter pair. TTA-UC-PLGA-NPs were successfully synthesized according to an oil-in-water emulsion and solvent evaporation method. After physicochemical characterization, UC-efficacy of TTA-UC-PLGA-NPs was assessedin vitroandex vivo. TTA-UC could be detected in the tumor area 96 hours afterin vivoadministration of TTA-UC-PLGA-NPs, confirming the integrity and suitability of PLGA-NPs as TTA-UCin vivodelivery system. Thus, this study provides proof-of-concept that the advantageous properties of PLGA can be combined with the unique optical properties of TTA-UC for the development of advanced nanocarriers for simultaneousin vivomolecular imaging and drug delivery.
Recombinant Paraprobiotics as a New Paradigm for Treating Gastrointestinal Nematode Parasites of Humans
Authors: Li Hanchen , Abraham Ambily , Gazzola David , Hu Yan , Beamer Gillian , Flanagan Kelly , Soto Ernesto , Rus Florentina , Mirza Zeynep , Draper Austin , Vakalapudi Sridhar , Stockman Cheryl , Bain Perry , Urban Joseph F. , Ostroff Gary R. , Aroian Raffi V.
Published: September 2020

Gastrointestinal nematodes (GINs) of humans,e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole (BZ) anthelmintics. However, BZ efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold chain, and massively scalable.Bacillus thuringiensis(Bt) crystal protein 5B (Cry5B) has anthelmintic properties that could fill this void. Here we develop an API (Active Pharmaceutical Ingredient) form of Bt Cry5B compatible with MDA. We expressed Cry5B in asporogenous Bt during vegetative phase, forming cytosolic crystals. TheseBacteria withCytosolicCrystals (BaCC) were rendered inviable (inactivated BaCC or IBaCC) with food-grade essential oils. IBaCC potency was validatedin vitroagainst nematodes. IBaCC was also potentin vivoagainst human hookworm infections in hamsters. IBaCC production was successfully scaled to 350 liters at a contract manufacturing facility. A simple fit-for-purpose formulation to protect against stomach digestion and powdered IBaCC were successfully made and used against GINS in hamsters and mice. A pilot histopathology study and blood chemistry workup showed that five daily consecutive doses of 200 mg/kg Cry5B IBaCC (the curative single dose is 40 mg/kg) was non-toxic and completely safe. IBaCC is a safe, inexpensive, highly effective, easy-to-manufacture, and scalable anthelmintic that is practical for MDA and represents a new paradigm for treating human GINs.
Representational content of oscillatory brain activity during object recognition
Authors: Reddy Leila , Cichy Radoslaw Martin , VanRullen Rufin
Published: September 2020

Numerous theories propose a key role for brain oscillations in visual perception. Most of these theories postulate that sensory information is encoded in specific oscillatory components (e.g., power or phase) of specific frequency bands. These theories are often tested with whole-brain recording methods of low spatial resolution (EEG or MEG), or depth recordings that provide a local, incomplete view of the brain. Opportunities to bridge the gap between local neural populations and whole-brain signals are rare. Here, using representational similarity analysis we ask which MEG oscillatory components (power and phase, across various frequency bands) correspond to low or high-level visual object representations, using brain representations from fMRI, or layer-wise representations in Deep Neural Networks (DNNs) as a template for low/high-level object representations. The results showed that around stimulus onset and offset, most transient oscillatory signals correlated with low-level brain patterns (V1). During stimulus presentation, sustained beta (∼20Hz) and gamma (>60Hz) power best correlated with V1, while oscillatory phase components correlated with IT representations. Surprisingly, this pattern of results did not always correspond to low- or high-level DNN layer activity. In particular, sustained beta-band oscillatory power reflected high-level DNN layers, suggestive of a feed-back component. These results begin to bridge the gap between whole-brain oscillatory signals and object representations supported by local neuronal activations.
Principles of organelle membrane bridging established using cytosolic tether mimics
Authors: Kamal Mohammad Arif , Janeš Josip Augustin , Li Long , Thibaudau Franck , Smith Ana-Suncana , Sengupta Kheya
Published: September 2020

The interactions between different intra-cellular organelles, including the endoplasmic reticulum, have recently been in focus thanks to the tremendous progress in imaging them using cryogenic transmission electron microscopy. However, they are still difficult to study in cellulo, and reconstituting these systems has been a standing challenge. Here we achieve this task using a giant unilamellar vesicle (GUV) and supported lipid bilayer (SLB) system. The tethers, which may reside in the cytosol when unbound, are mimicked by single (or double) stranded DNA sequences of two different lengths with ends that are self-sticky, and with terminal cholesterol moieties which insert into GUV or SLB membranes. The DNA-tethers, bound by their sticky-end, can exist in two possible states - either with both cholesterols in the same membrane or each cholesterol in a different membrane, the latter conformation leading to adhesion. Exchange of tether-molecules between the membranes occurs through the aqueous phase. By developing theoretical arguments that are supported in our experiments, we show that this possibility of exchange and the relative difference in the projected area between the two states drives the adhesion due to collective entropic considerations, rather than the usually considered enthalpy of binding. The establishment of this fundamentally different interaction between two membranes suggests that in physiological conditions, the regulation of contact formation inside cells may be very different from the case of the much studied ligand-receptor pairing on the external cell membrane.
Genome sequence and characterization of five bacteriophages infectingStreptomyces coelicolorandStreptomyces venezuelae: Alderaan, Coruscant, Dagobah, Endor1 and Endor2
Authors: Hardy Aël , Sharma Vikas , Kever Larissa , Frunzke Julia
Published: September 2020

Streptomycesare well-known antibiotic producers, and are also characterized by a complex morphological differentiation.Streptomyces, like all bacteria, are confronted with the constant threat of phage predation, which in turn shapes bacterial evolution. However, despite significant sequencing efforts recently, relatively few phages infectingStreptomyceshave been characterized compared to other genera. Here, we present the isolation and characterization of five novelStreptomycesphages. All five phages belong to theSiphoviridaefamily, based on their morphology as determined by transmission electron microscopy. Genome sequencing revealed that four of them were temperate phages, while one had a lytic lifestyle. Moreover, one of the newly sequenced phages shows very little homology to already described phages, highlighting the still largely untapped viral diversity. Altogether, this study expands the number of characterized phages ofStreptomycesand sheds light on phage evolution and phage-host dynamics inStreptomyces.
Multi-tissue Multi-omics Nutrigenomics Indicates Context-specific Effects of DHA on Rat Brain
Authors: Zhang Guanglin , Meng Qingying , Blencowe Montgomery , Rahul Agrawal , Gomez-Pinilla Fernando , Yang Xia
Published: September 2020

Scope

We explored the influence of DHA on cardiometabolic and cognitive phenotypes, and multiomic alterations in the brain under two metabolic conditions to understand context-specific nutritional effects.

Methods and Results

Rats were randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduced serum triglyceride and improved insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affected genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA altered immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling revealed context-specific regulators of DHA effects, includingKlf4andDusp1for chow condition andLum, Fn1, andCol1a1for fructose condition in hippocampus, as well asCyr61, JunB, Ier2, andPitx2under chow condition andHcar1, Cdh1, andOsr1under fructose condition in hypothalamus.

Conclusion

DHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.
Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells
Authors: Cool Taylor , Worthington Atesh , Poscablo Donna , Hussaini Adeel , Forsberg E. Camilla
Published: September 2020

Respiratory diseases are a leading cause of death worldwide, with highly varied vulnerability to disease between individuals. The underlying reasons of disease susceptibility are unknown, but often include a variable immune response in lungs. Recently, we identified a surprising novel role of the interleukin 7 receptor (IL7R), a primarily lymphoid-associated regulator, in fetal-specified, lung-resident macrophage development. Here, we report that traditional, hematopoietic stem cell-derived myeloid cells in the adult lung, peripheral blood, and bone marrow also depend on IL7R expression. Using single and double germline knockout models, we found that eosinophil numbers were reduced upon deletion of IL7Rα. We then employed two Cre recombinase models in lineage tracing experiments to test whether these cells developed through an IL7Rα+ pathway. Despite the impact of IL7Rα deletion, IL7R-Cre labeled only a minimal fraction of eosinophils. We therefore examined the intrinsic versus extrinsic requirement for IL7R in the production of eosinophils using reciprocal hematopoietic stem cell transplantation assays. These assays revealed that extrinsic, but not eosinophil-intrinsic, IL7R is required for eosinophil reconstitution by HSCs in the adult lung. To determine which external factors may be influencing eosinophil development and survival, we performed a cytokine array analysis between wild-type and IL7Rα-deficient mice and found several differentially regulated proteins. These findings expand upon our previous publication that IL7R is required not only for proper lymphoid cell development and homeostasis, but also for myeloid cell homeostasis in tissues.

Highlights

Loss of IL7Rα resulted in significantly fewer eosinophils in adult mice

IL7R-Cre lineage tracing revealed minimal labeling of eosinophils

IL7Rα-deficient HSCs robustly reconstituted eosinophils in a WT host

WT HSCs failed to fully reconstitute eosinophils in IL7Rα-/-hosts

Several cytokines are differentially expressed in WT and IL7Rα-deficient mice
Predictive modeling of material properties for aircraft control cables
Authors: Yavuz Hande
Published: September 2020

Purpose

This study aims to investigate the relationship between material properties and alloying elements of carbon steels through predictive modeling. Aircraft control cables are usually made of steel materials and subjected to deformation because of the motion of control surfaces such as aileron, rudder, elevator and trailing edge flaps. Investigation of the relationship between material properties and alloying elements would therefore be explored.

Design/methodology/approach

This study is focused on the modeling of mechanical properties of carbon steels concerning the content of alloying elements by using response surface methodology with false discovery rate (FDR) correction approach. SAS Institute JMP data analysis software was used to develop response and argument relationships in various carbon steels without including thermomechanical treatment effect. Mechanical properties were considered as tensile strength, yield strength, ductility, and Brinell hardness. Carbon (0.28 Wt.%-0.46 Wt.%) and manganese (0.7 Wt.%-0.9 Wt.%) proportions were gathered fromASM Handbook. Linear regression models were tested for the statistical adequacy by using analysis of variance and statistical significance analysis. A posterior probability, which refers to Benjamini–Hochberg FDR (BH-FDR), was embedded as multiple testing corrections of thet-testp-values.

Findings

Predictive modeling of the material properties for aircraft control cables was successfully achieved by using the response surface method with BH-FDR significance level of 0.05.

Originality/value

The effect of statistically developed graphical interactions of alloying elements on the common mechanical properties of such steels would provide prompt comparison to material suppliers and part manufacturers except those subjected to thermomechanical treatment applications.