bluuebunny/crossref_metadata_2025 huggingface dataset:
A226 INCIDENTAL FINDING OF A LARGE GASTRIC VARIX ASSOCIATED WITH NEONATAL UMBILICAL VEIN CANALIZATION
Authors: Tsang L , Abraldes J , Wiebe E , Sandha G S , van Zanten S
Published: March 2021

Results

A 41-year old Asian male, who immigrated to Canada many years ago, and who had previously been successfully treated for Helicobacter pylori infection underwent gastroscopy for investigation of dyspepsia. His gastroscopy was normal except for a large subepithelial abnormality that was noted close to the gastroesophageal junction. Routine gastric biopsies from the antrum and body were normal. Subsequent endoscopic ultrasound revealed flow through the anechoic tortuous lesion and confirmed it was a very large isolated gastric varix type 1.

Abdominal CT scan revealed chronic occlusion of the portal vein, splenic vein, and the portal confluence with extensive collateralization in the upper abdomen. There was complete cavernous transformation of the portal vein. Of the numerous varices in the upper abdomen, a very large varix drained into the left renal vein and indented into the posterior wall of the fundus of the stomach which accounted for the endoscopic finding. Multiple mesenteric veins were identified that connected to varices adjacent to the inferior aspect of the pancreas and duodenum. Notably, there was no evidence of cirrhosis or chronic pancreatitis. Liver enzymes, albumin, and INR were normal.

Further collateral history revealed that he was hospitalized as a neonate for pneumonia with catheterization of the umbilical vein, which is known to be associated with thrombosis of the portal vein.

Conclusions

Detection of congenital absence of the portal vein (CAPV) is recognized more often due to advances in diagnostic imaging. Radiologically, the absence of the portal vein in CAPV is distinguished from portal vein thrombosis by the lack of venous collaterals or sequalae of portal hypertension, such as ascites or splenomegaly. A more gradual thrombosis of the portal vein may permit collaterals to develop without acute changes and is not equivalent to portal vein aplasia or agenesis as intrahepatic bile ducts are normal.

The gold standard for diagnosis of CAPV is histologic absence of the portal vein in the liver on catheter angiography. CAPV is associated with abnormal embryologic development of the portal vein and frequently presents with complications of portal hypertension or portosystemic encephalopathy or the sequalae of venous shunts, hepatic or cardiac abnormalities found on imaging.

Our case is an incidentally discovered absence of the portal venous system due to chronic thrombosis with extensive collateralization and an enlarged gastric varix protruding into the proximal stomach. It is well documented that canalization of the umbilical vein in infancy is associated with portal vein thrombosis, with incidences up to 68%. This case highlights the importance of eliciting a childhood hospitalization history in cases of non-cirrhotic portal hypertension.

Funding Agencies

None
A236 LINACLOTIDE IS NOT DETECTABLE IN BREAST MILK OF LACTATING WOMEN: AN OPEN-LABEL, PHASE 1 STUDY
Authors: Crittenden N , McGeeney D , Assouline-Dayan Y , Boutros K , Syrzycka M , Bartolini W , Boinpally R , Andrews C N
Published: March 2021

Background

Linaclotide (LIN) is a guanylate cyclase-C agonist approved to treat adults with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). As LIN is a 14-amino acid peptide, no absorption from the gastrointestinal tract is expected following oral administration. However, LIN levels in human breast milk have not been determined.

Aims

To determine the levels of LIN and its active metabolite, MM-419447, excreted in breast milk after multiple once-daily doses of LIN (72 µg, 145 μg, or 290 μg) in lactating women.

Methods

This was a multicenter, open-label, multidose, Phase 1, milk-only lactation study (NCT02220348) in lactating women aged 18–45 years who were actively breastfeeding or pumping for ≥4 weeks and were already taking LIN 72 μg, 145 μg, or 290 μg therapeutically for IBS-C or CIC. Participants continued their LIN dose once daily for the 3 study days, with breast milk extractions at −1 to 0 hours (pre-dose) on Day 1 and −1 to 0 hours and 0–2, 2–4, 4–8, 8–12, 12–16, and 16–24 hours after dosing on Day 3. The pharmacokinetic endpoints were the cumulative amount of LIN and MM-419447 and the percentage dose of LIN excreted into the breast milk over the dosing interval. Adverse events (AEs) were monitored. The study has institutional review board approval.

Results

Seven women were enrolled in the study (IBS-C, n=1; CIC, n=6) and received LIN (72 μg, n=5; 145 μg, n=1; and 290 μg, n=1). Mean age was 28 (range: 19–35), mean weight was 70 kg (standard deviation [SD]: 12 kg), and mean body mass index was 26 kg/m2 (SD: 4 kg/m2); the majority were white (n=6). Concentrations of LIN and MM-419447 in breast milk samples were below the quantitation limits (<0.25 ng/mL and <1.00 ng/mL, respectively) at all time points for all participants. Cumulative exposure for each dose was 216 μg (72 μg dose), 435 μg (145 μg dose), and 870 μg (290 μg dose). One treatment-emergent AE was reported (mild rash).

Conclusions

The data collected in this study provide no evidence that breastfeeding infants receive LIN or MM-419447 through breast milk as their concentrations were below the quantitation limit following multiple once-daily doses of LIN 72 μg, 145 μg, or 290 μg.

Funding Agencies

This study was sponsored by Allergan plc, Dublin, Ireland (prior to acquisition by AbbVie Inc.). Writing and editorial assistance were provided to the authors by Stephanie J. Rippon, MBio, Jane Beck, MA, and Rebecca Fletcher, BA(Hons), of Complete HealthVizion, Inc., Chicago, IL, USA and funded by Allergan plc (prior to acquisition by AbbVie Inc.).
Courtship, Mating Behavior, and Ovary Histology of the Nymph Parasitoid Psyllaephagus bliteus (Hymenoptera: Encyrtidae)
Authors: Favoreto A L , Domingues M M , Serrão J E , Ribeiro M F , Silva C A D , Zanuncio J C , Wilcken C F
Published: March 2021

The potential of the parasitoid Psyllaephagus bliteus Riek for the biological control of the eucalyptus pest Glycaspis brimblecombei Moore (Hemiptera: Aphalaridae) nymphs is high. This research sought to analyze the courtship, male competition, and mating behavior of P. bliteus at the proportions of 1:1 and 2:1 males to female in a Petri dish (5 cm diameter), and to describe the ovary histology of virgin and mated females of this parasitoid. At 1:1, males touch the antennae and thorax–abdomen of females during courtship, but females avoid mate attempts before they are 48 h old. At 2:1, the competition between male parasitoids inhibits mating. The histology of ovaries of virgin and mated P. bliteus females is similar, with two well-defined germarium and vitellarium regions, with oocytes at different developmental stages, including mature ones rich in yolk and with eggshell. A clearer understanding of the reproductive behavior and histology of P. bliteus aids in the use of this parasitoid for the biological control of G. brimblecombei.
Four misconceptions about investigative genetic genealogy
Authors: Guerrini Christi J , Wickenheiser Ray A , Bettinger Blaine , McGuire Amy L , Fullerton Stephanie M
Published: March 2021

Investigative genetic genealogy (IGG) is a new technique for identifying criminal suspects that has sparked controversy. The technique involves uploading a crime scene DNA profile to one or more genetic genealogy databases with the intention of identifying a criminal offender’s genetic relatives and, eventually, locating the offender within the family tree. IGG was used to identify the Golden State Killer in 2018 and it is now being used in connection with hundreds of cases in the USA. Yet, as more law enforcement agencies conduct IGG, the privacy implications of the technique have come under scrutiny. While these issues deserve careful attention, we are concerned that their discussion is, at times, based on misunderstandings related to how IGG is used in criminal investigations and how IGG departs from traditional investigative techniques. Here, we aim to clarify and sharpen the public debate by addressing four misconceptions about IGG. We begin with a detailed description of IGG as it is currently practiced: what it is and—just as important—what it is not. We then examine misunderstood or not widely known aspects of IGG that are potentially confusing efforts to have constructive discussions about its future. We conclude with recommendations intended to support the productivity of those discussions.
Occurrence of the Mosquito Aedes triseriatus (Diptera: Culicidae) Beyond Its Most Northwestern Range Limits in Manitoba, Canada
Authors: Koloski Cody W , Drahun Ivan , Cassone Bryan J
Published: March 2021

Native to the Eastern United States and Eastern Canada, Aedes triseriatus (eastern tree hole mosquito) is an important vector of La Crosse virus and dog heartworm. Although its range has been well characterized in the United States, few studies have surveyed its distribution within Canada. In this study, mosquitoes were collected from a variety of urban and rural communities throughout Manitoba, Canada between the years of 2018 and 2020. Aedes triseriatus was identified and confirmed molecularly to be present in 13 communities. This includes localities that expand the species known distribution to new northern and western areas, and suggests that past surveillance efforts have not been comprehensive or environmental factors have caused this mosquito species to be present in areas in which it was not found previously. As Canada is showing signs of a changing climate, this may be driving the broader occurrence of Ae. triseriatus.
Simultaneous modelling of matter power spectrum and bispectrum in the presence of baryons
Authors: Aricò Giovanni , Angulo Raul E , Hernández-Monteagudo Carlos , Contreras Sergio , Zennaro Matteo
Published: March 2021

We demonstrate that baryonification algorithms, which displace particles in gravity-only simulations according to physically motivated prescriptions, can simultaneously capture the impact of baryonic physics on the two and three-point statistics of matter. Specifically, we show that our implementation of a baryonification algorithm jointly fits the changes induced by baryons on the power spectrum and equilateral bispectrum on scales up to $k = 5\rm h\, {\rm Mpc}^{-1}$ and redshifts 0 ≤ z ≤ 2, as measured in six different cosmological hydrodynamical simulations. The accuracy of our fits is typically $\sim 1{{\ \rm per\ cent}}$ for the power spectrum, and for the equilateral and squeezed bispectra, which somewhat degrades to $\sim 3{{\ \rm per\ cent}}$ for simulations with extreme feedback prescriptions. Our results support the physical assumptions underlying baryonification approaches and encourage their use in interpreting weak gravitational lensing and other cosmological observables.
Relationship between magnetic field properties and statistical flow using numerical simulation and magnetic feature tracking on solar photosphere
Authors: Takahata K , Hotta H , Iida Y , Oba T
Published: March 2021

We perform radiative magnetohydrodynamic calculations for the solar-quiet region to investigate the dependence of statistical flow on magnetic properties and the three-dimensional structure of magnetic patches in the presence of large-scale flow that mimics differential rotation. It has been confirmed that strong magnetic field patches move faster in the longitudinal direction at the solar surface. Consequently, strong magnetic patches penetrate deeper into the solar interior. The motion of the deep-rooted magnetic patches is influenced by the faster differential rotation in the deeper layer. In this study, we perform realistic radiative magnetohydrodynamic calculations using r2d2 code to validate that stronger patches have deeper roots. We also add large-scale flow to mimic the differential rotation. The magnetic patches are automatically detected and tracked, and we evaluate the depth of 30 000 magnetic patches. The velocities of 2.9 million magnetic patches are then measured at the photosphere. We obtain the dependence of these values on the magnetic properties, such as field strength and flux. Our results confirm that strong magnetic patches tend to show deeper roots and faster movement, and we compare our results with observations using the point spread function of instruments at the Hinode and Solar Dynamics Observatory (SDO). Our result is quantitatively consistent with previous observational results of the SDO.
The determination of asteroid H and G phase function parameters using Gaia DR2
Authors: Colazo M , Duffard R , Weidmann W
Published: March 2021

The Gaia mission will provide the scientific community with high-quality observations of asteroids of all categories. The second release of Gaia data (DR2) was published in 2018 and consists of 22 months of observations of 14 099 known Solar system objects, mainly asteroids. The purpose of this work is to obtain a catalogue of phase function parameters (H and G) for all the asteroids that were observed during the Gaia mission and that were published in DR2. For this purpose, we introduce an algorithm capable of building this catalogue from the magnitude and UTC epoch data present in the DR2 data base. Because Gaia will never observe asteroids with a phase angle of 0° (corresponding to opposition), but with phase angles higher than 10°, we added data from ground observations (corresponding to small phase angles) and thus improved the determination of the H and G parameters of the phase function. We also built a catalogue of the parameters of the H, G1 andG2 phase function. We compared our results of the H, G functions with those of the Astorb data base and observed that the level of agreement is satisfactory.
The Counteracting Effects of Demography on Functional Genomic Variation: The Roma Paradigm
Authors: Font-Porterias Neus , Caro-Consuegra Rocio , Lucas-Sánchez Marcel , Lopez Marie , Giménez Aaron , Carballo-Mesa Annabel , Bosch Elena , Calafell Francesc , Quintana-Murci Lluís , Comas David
Published: March 2021

Demographic history plays a major role in shaping the distribution of genomic variation. Yet the interaction between different demographic forces and their effects in the genomes is not fully resolved in human populations. Here, we focus on the Roma population, the largest transnational ethnic minority in Europe. They have a South Asian origin and their demographic history is characterized by recent dispersals, multiple founder events, and extensive gene flow from non-Roma groups. Through the analyses of new high-coverage whole exome sequences and genome-wide array data for 89 Iberian Roma individuals together with forward simulations, we show that founder effects have reduced their genetic diversity and proportion of rare variants, gene flow has counteracted the increase in mutational load, runs of homozygosity show ancestry-specific patterns of accumulation of deleterious homozygotes, and selection signals primarily derive from preadmixture adaptation in the Roma population sources. The present study shows how two demographic forces, bottlenecks and admixture, act in opposite directions and have long-term balancing effects on the Roma genomes. Understanding how demography and gene flow shape the genome of an admixed population provides an opportunity to elucidate how genomic variation is modeled in human populations.
MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors
Authors: Meng Ying , Pople Christopher B , Suppiah Suganth , Llinas Maheleth , Huang Yuexi , Sahgal Arjun , Perry James , Keith Julia , Davidson Benjamin , Hamani Clement , Amemiya Yutaka , Seth Arun , Leong Hon , Heyn Chinthaka C , Aubert Isabelle , Hynynen Kullervo , Lipsman Nir
Published: March 2021

Background

Liquid biopsy is promising for early detection, monitoring of response, and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood from brain tumors, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology. We hypothesized that MRgFUS can enrich the signal of circulating brain-derived biomarkers to aid in liquid biopsy.

Methods

Nine patients were treated in a prospective single-arm, open-label trial to investigate serial MRgFUS and adjuvant temozolomide combination in patients with glioblastoma (NCT03616860). Blood samples were collected as an exploratory measure within the hours before and after sonication, with control samples from non-brain tumor patients undergoing BBB opening (BBBO) alone (NCT03739905).

Results

Brain regions averaging 7.8 ± 6.0 cm3 (range 0.8-23.1 cm3) were successfully treated within 111 ± 39 minutes without any serious adverse events. We found MRgFUS acutely enhanced plasma cfDNA (2.6 ± 1.2-fold, P < .01, Wilcoxon signed-rank test), neuron-derived extracellular vesicles (3.2 ± 1.9-fold, P < .01), and brain-specific protein S100b (1.4 ± 0.2-fold, P < .01). Further comparison of the cfDNA methylation profiles suggests a signature that is disease- and post-BBBO-specific, in keeping with our hypothesis. We also found cfDNA-mutant copies of isocitrate dehydrogenase 1 (IDH1) increased, although this was in only one patient known to harbor the tumor mutation.

Conclusions

This first-in-human proof-of-concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.
Development of Integrated 3-Dimensional Computer Graphics Human Head Model
Authors: Kiyofuji Satoshi , Kin Taichi , Kakizawa Yukinari , Doke Takehito , Masuda Taisuke , Yamashita Juli , Shono Naoyuki , Nakatomi Hirofumi , Morita Akio , Harada Kanako , Saito Nobuhito
Published: March 2021

BACKGROUND

Understanding the complex anatomy of neurostructures is very important in various stages of medical education, from medical students to experienced neurosurgeons, and, ultimately, for the knowledge of human beings.

OBJECTIVE

To develop an interactive computer graphics (CG) anatomic head model and present the current progress.

METHODS

Based on the prior head 3-dimensional CG (3DCG) polygon model, 23 additional published papers and textbooks were consulted, and 2 neurosurgeons and 1 CG technician performed revision and additional polygon modeling. Three independent neurosurgeons scored the clear visibility of anatomic structures relevant to neurosurgical procedures (anterior petrosal and supracerebellar infratentorial approaches) in the integrated 3DCG model (i model) and patients’ radiological images (PRIs) such as those obtained from computed tomography, magnetic resonance imaging, and angiography.

RESULTS

The i model consisted of 1155 parts (.stl format), with a total of 313 763 375 polygons, including 10 times more information than the foundation model. The i model was able to illustrate complex and minute neuroanatomic structures that PRIs could not as well as extracranial structures such as paranasal sinuses. Our subjective analysis showed that the i model had better clear visibility scores than PRIs, particularly in minute nerves, vasculatures, and dural structures.

CONCLUSION

The i model more clearly illustrates minute anatomic structures than PRIs and uniquely illustrates nuclei and fibers that radiological images do not. The i model complements cadaveric dissection by increasing accessibility according to spatial, financial, ethical, and social aspects and can contribute to future medical education.
Transsylvian Insular Glioma Surgery: New Classification System, Clinical Outcome in a Consecutive Series of 79 Cases
Authors: Pitskhelauri David , Bykanov Andrey , Konovalov Alexander , Danilov Gleb , Buklina Svetlana , Sanikidze Alexander , Sufianov Rinat
Published: March 2021

BACKGROUND

Surgery of insular glial tumors remains a challenge because of high incidence of postoperative neurological deterioration and the complex anatomy of the insular region.

OBJECTIVE

To explore the prognostic role of our and Berger-Sanai classifications on the extent of resection (EOR) and clinical outcome.

METHODS

From 2012 to 2017, a transsylvian removal of insular glial tumors was performed in 79 patients. The EOR was assessed depending on magnetic resonance imaging scans performed in the first 48 h after surgery.

RESULTS

The EOR ≥90% was achieved in 30 (38%) cases and <90% in 49 (62.0%) cases. In the early postoperative period, the new neurological deficit was observed in 31 (39.2%) patients, and in 5 patients (6.3%), it persisted up to 3 mo.

We proposed a classification of insular gliomas based on its volumetric and anatomical characteristics. A statistically significant differences were found between proposed classes in tumor volume before and after surgery (P < .001), EOR (P = .02), rate of epileptic seizures before the surgical treatment (P = .04), and the incidence of persistent postoperative complications (P = .03).

In the logistic regression model, tumor location in zone II (Berger-Sanai classification) was the predictor significantly related to less likely EOR of ≥90% and the maximum rate of residual tumor detection (P = .02).

CONCLUSION

The proposed classification of the insular gliomas was an independent predictor of the EOR and persistent postoperative neurological deficit. According to Berger-Sanai classification, zone II was a predictor of less EOR through the transsylvian approach.
Ascorbate–glutathione pathways mediated by cytokinin regulate H2O2 levels in light-controlled rose bud burst
Authors: Porcher Alexis , Guérin Vincent , Leduc Nathalie , Lebrec Anita , Lothier Jérémy , Vian Alain
Published: March 2021

Rosebush (Rosa “Radrazz”) plants are an excellent model to study light control of bud outgrowth since bud outgrowth only arises in the presence of light and never occurs in darkness. Recently, we demonstrated high levels of hydrogen peroxide (H2O2) present in the quiescent axillary buds strongly repress the outgrowth process. In light, the outgrowing process occurred after H2O2 scavenging through the promotion of Ascorbic acid–Glutathione (AsA–GSH)-dependent pathways and the continuous decrease in H2O2 production. Here we showed Respiratory Burst Oxidase Homologs expression decreased in buds during the outgrowth process in light. In continuous darkness, the same decrease was observed although H2O2 remained at high levels in axillary buds, as a consequence of the strong inhibition of AsA–GSH cycle and GSH synthesis preventing the outgrowth process. Cytokinin (CK) application can evoke bud outgrowth in light as well as in continuous darkness. Furthermore, CKs are the initial targets of light in the photocontrol process. We showed CK application to cultured buds in darkness decreases bud H2O2 to a level that is similar to that observed in light. Furthermore, this treatment restores GSH levels and engages bud burst. We treated plants with buthionine sulfoximine, an inhibitor of GSH synthesis, to solve the sequence of events involving H2O2/GSH metabolisms in the photocontrol process. This treatment prevented bud burst, even in the presence of CK, suggesting the sequence of actions starts with the positive CK effect on GSH that in turn stimulates H2O2 scavenging, resulting in initiation of bud outgrowth.
Independent associations of lymphopenia and neutropenia in patients with systemic lupus erythematosus: a longitudinal, multinational study
Authors: Kandane-Rathnayake Rangi , Louthrenoo Worawit , Golder Vera , Luo Shue-Fen , Wu Yeong-Jian J , Lateef Aisha , Cho Jiacai , Li Zhanguo , An Yuan , Hamijoyo Laniyati , Navarra Sandra , Zamora Leonid , Katsumata Yasuhiro , Harigai Masayoshi , Sockalingam Sargunan , Chan Madelynn , Chen Yi-Hsing , O'Neill Sean , Goldblatt Fiona , Hao Yanjie , Zhang Zhuoli , Kikuchi Jun , Takeuchi Tsutomu , Lau Chak Sing , Nikpour Mandana , Morand Eric , Hoi Alberta ,   for the Asia Pacific Lupus Collaboration
Published: March 2021

Objective

The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort.

Methods

Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses.

Results

Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia.

Conclusion

Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.
SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing
Authors: Moreno Gage K. , Braun Katarina M. , Pray Ian W. , Segaloff Hannah E. , Lim Ailam , Poulson Keith , Meiman Jonathan , Borcher James , Westergaard Ryan P. , Moll Michael K. , Friedrich Thomas C. , O’Connor David H.
Published: March 2021

Background

High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing.

Methods

During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel’s Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks.

Results

In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition.

Conclusions

These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings.

High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.
COVID-19-associated school closures and related efforts to sustain education and subsidized meal programs, United States, February 18–June 30, 2020
Authors: Zviedrite Nicole , Hodis Jeffrey D. , Jahan Ferdous , Gao Hongjiang , Uzicanin Amra
Published: March 2021

Pre-emptive school closures are frontline community mitigation measures recommended by CDC for implementation during severe pandemics. This study describes the spatiotemporal patterns of publicly announced school closures implemented in response to the coronavirus disease 2019 (COVID-19) pandemic and assesses how public K-12 districts adjusted their methods of education delivery and provision of subsidized meals. During February 18–June 30, 2020, we used daily systematic media searches to identify publicly announced coronavirus disease 2019 (COVID-19)–related school closures lasting ≥1 day in the United States (US). We also collected statewide school closure policies from state government websites. Data on distance learning and subsidized meal programs were collected from a stratified sample of 600 school districts. The first COVID-19–associated school closure occurred on February 27, 2020 in Washington state. By March 30, 2020, all but one US public school districts were closed, representing the first-ever nearly synchronous nationwide closure of public K-12 schools in the US. Approximately 100,000 public schools were closed for ≥8 weeks because of COVID-19, affecting >50 million K-12 students. Of 600 districts sampled, the vast majority offered distance learning (91.0%) and continued provision of subsidized meal programs (78.8%) during the closures. Despite the sudden and prolonged nature of COVID-19–associated school closures, schools demonstrated flexibility by implementing distance learning and alternate methods to continue subsidized meal programs.
A quantitative risk estimation platform for indoor aerosol transmission of COVID-19
Authors: Parhizkar Hooman , Van Den Wymelenberg Kevin , Haas Charles , Corsi Richard
Published: March 2021

Aerosol transmission has played a significant role in the transmission of COVID-19 disease worldwide. We developed a COVID-19 aerosol transmission risk estimation platform to better understand how key parameters associated with indoor spaces and infector emissions affect inhaled deposited dose of aerosol particles that convey the SARS-CoV-2 virus. The model calculates the concentration of size-resolved, virus-laden aerosol particles in well-mixed indoor air challenged by emissions from an index case(s). The model uses a mechanistic approach, accounting for particle emission dynamics, particle deposition to indoor surfaces, ventilation rate, and single-zone filtration. The novelty of this model relates to the concept of “inhaled & deposited dose” in the respiratory system of receptors linked to a dose-response curve for human coronavirus HCoV-229E. We estimated the volume of inhaled & deposited dose of particles in the 0.5 to 4 μm range expressed in picoliters (pL) in a well-documented COVID-19 outbreak in restaurant X in Guangzhou China. We anchored the attack rate with the dose-response curve of HCoV-229E which provides a preliminary estimate of the average SARS-CoV-2 dose per person, expressed in plaque forming units (PFUs). For a reasonable emission scenario, we estimate approximately three PFU per pL deposited, yielding roughly 10 PFUs deposited in the respiratory system of those infected in Restaurant X. To explore the platform’s utility, we tested the model with four COVID-19 outbreaks. The risk estimates from the model fit reasonably well with the reported number of confirmed cases given available metadata from the outbreaks and uncertainties associated with model assumptions.

Practical Implications

The model described in this paper is more mechanistic in nature than standard probabilistic models that fail to account for particle deposition to indoor materials, filtration, and deposition of particles in the respiratory system of receptors. As such, it provides added insights into how building-related factors affect relative infection risk associated with inhaled deposited dose. An online version of this mechanistic aerosol risk estimation platform is available at Safeairspaces.com. Importantly, the modular nature of this approach allows for easy updates when new information is available regarding dose-response relationships for SARS-CoV-2 or its variants.
Engineered Peptide-Functionalized Hydrogels Modulate the RNA Transcriptome of Human Nucleus Pulposus Cells In Vitro
Authors: Barcellona Marcos N. , Speer Julie E. , Jing Liufang , Gupta Munish C. , Buchowski Jacob M. , Kelly Michael P. , Setton Lori A.
Published: March 2021

Degeneration and aging of the nucleus pulposus (NP) of the intervertebral disc (IVD) is accompanied by alterations in NP cell phenotype marked by a shift towards a fibroblast-like, catabolic state. We have recently demonstrated an ability to manipulate the phenotype of human adult degenerative NP cells through 2D culture upon poly(ethylene glycol) (PEG) based hydrogels dually functionalized with integrin- and syndecan-binding laminin-mimetic peptides (LMPs). In the present study, we sought to understand the transcriptomic changes elicited through NP cell interactions with the LMP-functionalized hydrogel system (LMP gel) by examining targets of interesta prioriand by conducting unbiased analysis to identify novel mechanosensitive targets. The results of gene specific analysis demonstrated that the LMP gel promoted adult degenerative NP cells to upregulate 148 genes including several NP markers (e.g. NOG and ITGA6) and downregulate 277 genes, namely several known fibroblastic markers. Additionally, 13 genes associated with G protein-coupled receptors, many of which are known drug targets, were identified as differentially regulated following culture upon the gel. Furthermore, through gene set enrichment analysis we identified over 700 pathways enriched amongst the up- and downregulated genes including pathways related to cell differentiation, notochord morphogenesis, and intracellular signaling. Together these findings demonstrate the global mechanobiological effects induced by the LMP gel and confirm the ability of this substrate to modulate NP cell phenotype.
Multiple classes of bactericidal antibiotics cause DNA double strand breaks inStaphylococcus aureus
Authors: Clarke Rebecca S. , Ha Kam Pou , Edwards Andrew M.
Published: March 2021

Antibiotics inhibit essential bacterial processes, resulting in arrest of growth and in some cases cell death. Many antibiotics are also reported to trigger endogenous production of reactive oxygen species (ROS), which damage DNA and other macromolecules. However, the type of DNA damage that arises and the mechanisms used by bacteria to repair it are largely unclear. We found that several different classes of antibiotic triggered dose-dependent DNA damage inStaphylococcus aureus, including some bacteriostatic drugs. Damage was heterogenous and varied in magnitude between strains. However, antibiotic-triggered DNA damage led to double strand breaks, the processing of which by the RexAB helicase/nuclease complex triggered the SOS response and reduced staphylococcal susceptibility to most of the antibacterials tested. In most cases, DNA DSBs occurred under aerobic but not anaerobic conditions, suggesting a role for ROS. We conclude that DNA double strand breaks are a common occurrence during bacterial exposure to several different antibiotic classes and that repair of this damage by the RexAB complex promotes bacterial survival.
RNA modulation of transport properties and stability in phase separated condensates
Authors: Tejedor Andrés R. , Garaizar Adiran , Ramírez Jorge , Espinosa Jorge R.
Published: March 2021

One of the key mechanisms employed by cells to control their spatiotemporal organization is the formation and dissolution of phase-separated condensates. The balance between condensate assembly and disassembly can be critically regulated by the presence of RNA. In this work, we use a novel sequence-dependent coarse-grained model for proteins and RNA to unravel the impact of RNA in modulating the transport properties and stability of biomolecular condensates. We explore the phase behavior of several RNA-binding proteins such as FUS, hnRNPA1 and TDP-43 proteins along with that of their corresponding prion-like domains and RNA-recognition motifs, from absence to moderately high RNA concentration. By characterising the phase diagram, key molecular interactions, surface tension and transport properties of the condensates, we report a dual RNA-induced behavior: On the one hand, RNA enhances phase separation at low concentration as long as the RNA radius of gyration is comparable to that of the proteins, whilst at high concentration it inhibits the ability of proteins to self-assemble independently of its length. On the other hand, along with the stability modulation, the viscosity of the condensates can be considerably reduced at high RNA concentration as long as the length of the RNA chains is shorter than that of the proteins. Conversely, long RNA strands increase viscosity, even at high concentration, but barely modify protein self-diffusion, which mainly depends on RNA concentration and on its own effect on droplet density. On the whole, our work rationalizes the different routes by which RNA can regulate phase separation and condensate dynamics, as well as the subsequent aberrant rigidification implicated in the emergence of various neuropathologies and age-related diseases.
HOXA9acts as a regulatory switch in acute myeloid leukaemia and myeloproliferative neoplasms
Authors: Talarmain Laure , Clarke Matthew A. , Shorthouse David , Fisher Jasmin , Hall Benjamin A
Published: March 2021

Blood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events initiating abnormal growth ultimately determine the cancer subtype and subsequent clinical outcome. HOXA9 plays an important role in acute myeloid leukaemia (AML) prognosis by promoting blood cell expansion and altering differentiation; however, the function of HOXA9 in other blood malignancies is still unclear. Here, we demonstrate the importance of this gene in chronic myeloproliferative neoplasms (MPN) and highlight the biological switch and prognosis marker properties of HOXA9 in AML and MPN. This binary switch function can explain the clinical stratification of these two blood disorders. First, we establish the ability of HOXA9 to stratify AML patients with distinct cellular and clinical outcomes. Then, through the use of a computational network model of MPN, we show that the self-activation of HOXA9 and its relationship to JAK2 and TET2 can explain the branching progression of JAK2/TET2 mutant MPN patients towards divergent clinical characteristics. Finally, we predict a connection between the RUNX1 and MYB genes and a suppressive role for the NOTCH pathway in MPN diseases.
Fungal taste for minerals: the ectomycorrhizal fungusPaxillus involutustriggers specific genes when extracting potassium from different silicates
Authors: Pinzari F. , Jungblut A.D. , Cuadros J.
Published: March 2021

Silicates make up about 90% of the Earth’s crust and constitute the main source of mineral nutrients for microorganisms and plants. Fungi can actively weather silicates to extract nutrients. However, it is unclear whether they are able to obtain the same amounts of nutrients and use the same mechanisms when tapping into different mineral sources. We performed a microcosm experiment using the ectomycorrhizal basidiomycetesPaxillus involutusand the silicates K-vermiculite, muscovite and phlogopite as only potassium sources, as they show a different resistance for the removal of K cations from the mineral structure. A combination of transcriptomic, elemental and SEM analyses showed that different minerals stimulated specific weathering mechanisms and led to a change in fungal genes expression. The differential expression of the fungal genes generated alternative chemical attacks on the minerals, resulting in a tailored dissolution and selective uptake of chemical elements according to the leachability of K from the silicate mineral. The K uptake capacity of the fungus was highest with vermiculite in comparison to growth on phlogopite and muscovite. The findings provide new insights into fungal-mineral interactions that will help to interpret key processes for the homeostasis of soil environments.
SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection
Authors: Bashor Laura , Gagne Roderick B. , Bosco-Lauth Angela , Bowen Richard , Stenglein Mark , VandeWoude Sue
Published: March 2021

SARS-CoV-2 spillback from humans into domestic and wild animals has been well-documented. We compared variants of cell culture-expanded SARS-CoV-2 inoculum and virus recovered from four species following experimental exposure. Five nonsynonymous changes in nsp12, S, N and M genes were near fixation in the inoculum, but reverted to wild-type sequences in RNA recovered from dogs, cats and hamsters within 1-3 days post-exposure. Fourteen emergent variants were detected in viruses recovered from animals, including substitutions at spike positions H69, N501, and D614, which also vary in human lineages of concern. The rapidity of in vitro and in vivo SARS-CoV-2 selection reveals residues with functional significance during host-switching, illustrating the potential for spillback reservoir hosts to accelerate evolution, and demonstrating plasticity of viral adaptation in animal models.

One-Sentence Summary

SARS-CoV-2 variants rapidly arise in non-human hosts, revealing viral evolution and potential risk for human reinfection.
Optimal Time Lags from Causal Prediction Model Help Stratify and Forecast Nervous System Pathology
Authors: Bermperidis Theodoros , Rai Richa , Ryu Jihye , Zanotto Damiano , Agrawal Sunil K , Lalwani Anil K. , Torres Elizabeth B
Published: March 2021

Traditional clinical approaches diagnose disorders of the nervous system using standardized observational criteria. Although aiming for homogeneity of symptoms, this method often results in highly heterogeneous disorders. A standing question thus is how to automatically stratify a given random cohort of the population, such that treatment can be better tailored to each cluster’s symptoms, and severity of any given group forecasted to provide neuroprotective therapies. In this work we introduce new methods to automatically stratify a random cohort of the population composed of healthy controls of different ages and patients with different disorders of the nervous systems. Using a simple walking task and measuring micro-fluctuations in their biorhythmic motions, we combine non-linear causal network connectivity analyses in the temporal and frequency domains with stochastic mapping. The methods define a new type of internal motor timings. These are amenable to create personalized clinical interventions tailored to self-emerging clusters signaling fundamentally different types of gait pathologies. We frame our results using the principle of reafference and operationalize them using causal prediction, thus renovating the theory of internal models for the study of neuromotor control.
Trp53ablation fails to prevent microcephaly in mouse pallium with impaired minor intron splicing
Authors: White Alisa K. , Baumgartner Marybeth , Lee Madisen F. , Drake Kyle D. , Aquino Gabriela S. , Kanadia Rahul N.
Published: March 2021

Mutations in minor spliceosome component RNU4ATAC, a small nuclear RNA (snRNA), are linked to primary microcephaly. We have reported that in the conditional knockout (cKO) mice forRnu11, another minor spliceosome snRNA, minor intron splicing defect in minor intron-containing genes (MIGs) regulating cell cycle resulted in cell cycle defects, with a concomitant increase in γH2aX+ cells and p53-mediated apoptosis.Trp53ablation in theRnu11cKO mice did not prevent microcephaly. However, RNAseq analysis of the double knockout (dKO) pallium reflected transcriptomic shift towards the control from the Rnu11 cKO. We found elevated minor intron retention and alternative splicing across minor introns in the dKO. Disruption of these MIGs resulted in cell cycle defects that were more severe and detected earlier in the dKO, but with delayed detection of γH2aX+ DNA damage. Thus, p53 might also play a role in causing DNA damage in the developing pallium. In all, our findings further refine our understanding of the role of the minor spliceosome in cortical development and identify MIGs underpinning microcephaly in minor spliceosome-related diseases.
Dynamic Training of a Novelty Classifier Algorithm for Real-Time Early Seizure Onset Detection
Authors: Ehrens Daniel , Cervenka Mackenzie C. , Bergey Gregory K. , Jouny Christophe C.
Published: March 2021

The objective of this study was to develop an adaptive framework for seizure detection in real-time that is practical to use in the Epilepsy Monitoring Unit (EMU) as a warning signal, and whose output helps characterize epileptiform activity. Our framework uses a one-class Support Vector Machine (SVM) that is being trained dynamically according to past activity in all available channels. This is done to evaluate the novelty of the current instance according to previous activity. Our algorithm was tested on intracranial EEG from human epilepsy patients that are admitted to the EMU for presurgical evaluation. In this study, we compared multiple configurations for using a one-class SVM to assess if there is significance over specific neural features or electrode locations. Our results show our algorithm is capable of running in real-time and achieving a high performance for early seizure-onset detection with a low false-positive rate and robustness to different types of seizure-onset patterns as well as to the number of channels used. This algorithm offers a solution to warning systems in the EMU as well as a tool for seizure characterization during post-hoc analysis of intracranial EEG data for surgical resection of the epileptogenic network.

Highlights

This study proposes a dynamic training algorithm that efficiently detects sudden novel changes in intracranial electroencephalographic activity, creating a reliable seizure onset detection algorithm that does not need prior training.

The algorithm described has the capability to be implemented in real-time, independently of the number of channels that are being analyzed.

The presented detector shows high performance and reliability to be easily implemented in the Epilepsy Monitoring Unit to quickly alert clinical staff of seizure events.
A novel Rab11-Rab3a cascade required for lysosome exocytosis
Authors: Escrevente Cristina , Bento-Lopes Liliana , Ramalho José S , Barral Duarte C
Published: March 2021

Lysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood.

Here, we identify Rab11a and Rab11b as regulators of calcium-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis independently of the exocyst complex, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) and also Rab3a, which we described previously as a regulator of the positioning and exocytosis of lysosomes.

Thus, our studies suggest that Rab11-positive vesicles transport GRAB to activate Rab3a on lysosomes, establishing a Rab11-Rab3 cascade that is essential for lysosome exocytosis.