bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of early visual outcomes after low-energy SMILE, high-energy SMILE, and LASIK for myopia and myopic astigmatism in the United States
Authors: Hamilton D. Rex , Chen Angela C. , Khorrami Roxana , Nutkiewicz Max , Nejad Mitra
Published: August 2020

Purpose:

To compare uncorrected distance visual acuities (UDVAs) and induced higher-order aberrations (HOAs) in the early postoperative period between low-energy (LE) small-incision lenticule extraction (SMILE), high-energy (HE) SMILE, and femtosecond laser–assisted laser in situ keratomileusis (FS-LASIK) procedures.

Setting:

University based refractive surgery center.

Study design:

Retrospective cohort study.

Methods:

Records of patients who underwent SMILE or FS-LASIK were retrospectively reviewed. SMILE patients were separated into 2 groups: HE settings (125 nJ, 3.0 μm spot spacing) and LE settings (125-130 nJ, 4.5 μm spot spacing). UDVA was measured at postoperative day (POD) 1. Corneal HOAs and UDVA were measured at postoperative month (POM) 1. Induced spherical aberration, vertical coma, horizontal coma, total coma, and total HOAs were calculated.

Results:

The study included 147 eyes of 106 patients, 49 in each group. For SMILE patients, the difference in mean UDVA at POD1 was highly statistically significant in favor of the LE group (−0.003 vs 0.141, P < .0001). No significant difference in mean UDVA at POD1 was noted between the LE group and FS-LASIK group (−0.003 vs −0.011, P = .498). Induced change in spherical aberration was less in LE SMILE than that in FS-LASIK (0.136 vs 0.186 μm, P = .02) at POM1. No significant differences in POM1 mean UDVA (−0.033 vs −0.036) or induced change in all other HOAs were noted between LE SMILE and FS-LASIK.

Conclusions:

LE settings were associated with significantly improved POD1 UDVA. POD1 and POM1 UDVA were comparable with those of FS-LASIK. Spherical aberration induction was less with LE SMILE than that with FS-LASIK, whereas all other induced HOAs were comparable with FS-LASIK.
Corneal transillumination: technique to detect big bubble in deep anterior lamellar keratoplasty
Authors: Estrin Diego A. , Szuster Nestor M. , Szuster Erik A.
Published: August 2020

Deep anterior lamellar keratoplasty is a widely adopted technique to treat pathologies of the cornea without endothelial cell involvement. This technique has several advantages including longer graft survival without endothelial rejection and lower doses of steroid administration. A transillumination technique was used to diagnose big bubble formation. A partial-thickness trephination was made, followed by superficial keratectomy and air injection into the stroma. Then, a vitreoretinal endoilluminator was used to illuminate the cornea and check for any signs of “full moon” or “waning moon,” which corresponded to the shine of the big bubble from total internal reflection of light. Once the diagnosis was made, the remnant stroma was removed, and the donor cornea without endothelium was sutured. An advantage of this technique was that it allowed the diagnosis of big bubble even on an opaque or whitish emphysematous cornea when other methods could not be used.
The Effect of Numbered Jerseys on Directed Commands, Teamwork, and Clinical Performance During Simulated Emergencies
Authors: Kim Yekaterina , Dym Akiva A. , Yang Karen , Fein Daniel G. , Bangar Maneesha , Ferenchick Hannah R. B. , Keene Adam , Orsi Deborah , Washington Moses A. , Eisen Lewis A.
Published: August 2020

Communication and teamwork are essential during inpatient emergencies such as cardiac arrest and rapid response (RR) codes. We investigated whether wearing numbered jerseys affect directed commands, teamwork, and performance during simulated codes. Eight teams of 6 residents participated in 64 simulations. Four teams were randomized to the experimental group wearing numbered jerseys, and four to the control group wearing work attire. The experimental group used more directed commands (49% vs. 31%, p < .001) and had higher teamwork score (25 vs. 18, p < .001) compared with control group. There was no difference in time to initiation of chest compression, bag-valve-mask ventilation, and correct medications. Time to defibrillation was longer in the experimental group (190 vs. 140 seconds, p = .035). Using numbered jerseys during simulations was associated with increased use of directed commands and better teamwork. Time to performance of clinical actions was similar except for longer time to defibrillation in the jersey group.
Implementation and Feasibility of the Re-Engineered Discharge for Surgery (RED-S) Intervention: A Pilot Study
Authors: Du Rebecca Y. , Shelton George , Ledet Celia R. , Mills Whitney L. , Neal-Herman Levi , Horstman Molly , Trautner Barbara , Awad Samir , Berger David , Naik Aanand D.
Published: August 2020

Introduction:

Adapting Project Re-Engineered Discharge (Project RED), an intervention for reducing internal medicine hospital readmissions, is a promising option for reducing colorectal surgery readmissions.

Methods:

We conducted a pilot study for the adaptation and implementation of Project RED with patients admitted for colectomy at a regional VA tertiary care center between July 2014 and January 2015. Implementation was evaluated using adherence to intervention components and results from the Survey of Healthcare Experiences of Patients. The adapted Project RED for Surgery has five components: surgical wound/ostomy-care education, scheduled follow-up appointments, medication reconciliation, an After Hospital Care Plan, and postdischarge phone calls.

Results:

All (n = 21) participants received postoperative wound care education, and 77% of ostomy patients received education. Follow-up appointments were scheduled for 76% with surgery clinic and 67% with primary care. Half received pharmacist-led medication reconciliation. Seventy-five percent received a postdischarge phone call. Ninety five percent of participants reported positive or satisfactory care transitions versus less than 60% of a comparison group of surgery patients from the same institution. We summarized lessons learned from this intervention study to facilitate future dissemination efforts.

Conclusion:

The lessons learned from this pilot can guide quality improvement teams seeking to implement the Re-Engineered Discharge for Surgery intervention within their existing workflows.
Comparison of Documentation on Inpatient Discharge and Ambulatory End-of-Visit Summaries
Authors: Downey Emily , Olds Danielle M.
Published: August 2020

Introduction:

Providing complete pending diagnostic test information and medication lists on inpatient discharge and ambulatory end-of-visit summaries decreases adverse events, reduces medical errors, and improves patient satisfaction. The purpose was to compare inpatient and ambulatory settings regarding percentages of records with documentation of pending diagnostic test result information and medication lists given at discharge/end of visit.

Methods:

Using a cross-sectional, observational design, 2018 NDNQI discharge/end-of-visit data from 133 inpatient and 90 ambulatory units in 20 hospitals were examined. Trained site coordinators reviewed records for documentation of discharge/end-of-visit elements. Mann–Whitney U tests were used to compare inpatient and ambulatory percent of elements completed.

Results:

Across all discharge/end-of-visit elements, there were differences (all p < .001) between inpatient and ambulatory settings. Ambulatory units had a lower percent completion for all medication list and pending diagnostic result elements. Depending on the element, the sample means for documentation in discharge/end-of-visit summaries were 18.6–98.8% for inpatient and 4.5–61.8% for ambulatory settings.

Conclusions:

Discharge instructions and end-of-visit summaries are crucial forms of communication between clinicians and patients. However, many patients are not receiving complete information.

Implications:

In a large nationwide sample, we found substantial opportunities to improve completeness of summaries, particularly in ambulatory settings.
Improving Contagious Disease Reporting in a Medical Examiner's Office
Authors: Rogers Christopher , Sathyavagiswaran Lakshmanan
Published: August 2020

Contagious disease reporting is an important mechanism for public health officials to be informed of emerging and ongoing risks to the community's health. There are several mechanisms for reporting, including automated reporting from computer sources, required reporting from physicians and other health care professionals, and reporting of sales of certain over-the-counter medications such as cold remedies.

Reporting by medical examiners is a significant source of information because contagious disease may first come to the medical examiner by causing sudden unexpected death. This study describes how the Los Angeles County Department of Medical Examiner–Coroner improved contagious disease reporting from coroner's cases. Methods used include computerized transmission to public health of initial coroner's case reports, e-mailed requests to the coroner to obtain cultures, having all results of coroner's cultures come through a single person who reports contagious disease as necessary, and including infectious disease screening in retrospective case review.
Terahertz range resonances of metasurface formed by double-layer grating of microsize graphene strips inside dielectric slab
Authors: Zinenko Tatiana L. , Matsushima Akira , Nosich Alexander I.
Published: August 2020

We analyse, using integral equations and a previously developed in-house numerical algorithm, the scattering and absorption of the
H
-polarized plane wave by a metasurface consisting of a double-layer grating of flat graphene strips placed into a lossless dielectric slab. The algorithm is meshless and its convergence is guaranteed mathematically. It is a version of the method of analytical preconditioning; namely, it uses the set of weighted Chebyshev polynomials as expansion functions in the discretization of a hypersingular electric field integral equation for the on-strip current. Then the computational error is controlled by the matrix size and can be reduced to machine precision. Using this advanced tool, we plot the frequency dependences, in a huge range from 1 GHz to 10 THz, of the transmittance, reflectance and absorbance of such a metasurface. This accurate analysis reveals resonances on several types of natural modes, best understood via visualization of in-resonance near-fields. In addition to plasmon-mode resonances, special attention is paid to the ultra-high-
Q
resonances on the lattice modes, which are absent on the free-standing graphene strip gratings.
Influence of temperature on Turing pattern formation
Authors: Van Gorder Robert A.
Published: August 2020

The Turing instability is one of the most commonly studied mechanisms leading to pattern formation in reaction–diffusion systems, yet there are still many open questions on the applicability of the Turing mechanism. Although experiments on pattern formation using chemical systems have shown that temperature differences play a role in pattern formation, there is far less theoretical work concerning the interplay between temperature and spatial instabilities. We consider a thermodynamically extended reaction–diffusion system, consisting of a pair of reaction–diffusion equations coupled to an energy equation for temperature, and use this to obtain a natural extension of the Turing instability accounting for temperature. We show that thermal contributions can restrict or enlarge the set of unstable modes possible under the instability, and in some cases may be used to completely shift the set of unstable modes, strongly modifying emergent Turing patterns. Spatial heterogeneity plays a role under several experimentally feasible configurations, and we give particular consideration to scenarios involving thermal gradients, thermodynamics of chemicals transported within a flow, and thermodiffusion. Control of Turing patterns is also an area of active interest, and we also demonstrate how patterns can be modified using time-dependent control of the boundary temperature.
Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease
Authors: DeMichele-Sweet Mary Ann A. , Klei Lambertus , Creese Byron , Harwood Janet C. , Weamer Elise A. , McClain Lora , Sims Rebecca , Hernandez Isabel , Moreno-Grau Sonia , Tárraga Lluís , Boada Mercè , Alarcón-Martín Emilio , Valero Sergi ,   NIA-LOAD Family Based Study Consortium,   Alzheimer’s Disease Genetics Consortium (ADGC), Liu Yushi , Hooli Basavaraj , Aarsland Dag , Selbaek Geir , Bergh Sverre , Rongve Arvid , Saltvedt Ingvild , K. Skjellegrind Håvard , Engdahl Bo , Stordal Eystein , Andreassen Ole A. , Djurovic Srdjan , Athanasiu Lavinia , Seripa Davide , Borroni Barbara , Albani Diego , Forloni Gianluigi , Mecocci Patrizia , Serretti Alessandro , Ronchi Diana De , Politis Antonis ,   AddNeuroMed Consortium, Williams Julie , Mayeux Richard , Foroud Tatiana , Ruiz Agustin , Ballard Clive , Holmans Peter , Lopez Oscar L. , Kamboh M. Ilyas , Devlin Bernie , Sweet Robert A.
Published: August 2020

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD+P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.
Inhibition of histone readers bromodomain extra-terminal proteins alleviates skin fibrosis in experimental models of scleroderma
Authors: Vichaikul Sirapa , Gurrea-Rubio Mikel , Amin M. Asif , Campbell Phillip L. , Wu Qi , Mattichak Megan N. , Brodie William D. , Palisoc Pamela J. , Ali Mustafa , Muraoka Sei , Ruth Jeffrey H. , Model Ellen N. , Rohraff Dallas M. , Hervoso Jonatan L. , Mao-Draayer Yang , Fox David A. , Khanna Dinesh , Sawalha Amr H. , Tsou Pei-Suen
Published: August 2020

Binding of the bromodomain and extra-terminal domain proteins (BETs) to acetylated histone residues is critical for gene transcription. This study sought to determine the anti-fibrotic efficacy and potential mechanisms of BET inhibition in systemic sclerosis (SSc). Blockade of BETs was done using a pan BET inhibitor JQ1, BRD2 inhibitor BIC1, or BRD4 inhibitors AZD5153 or ARV825. BET inhibition, specifically BRD4 blockade, showed anti-fibrotic effects in an animal model of scleroderma and in patient-derived diffuse cutaneous (dc)SSc fibroblasts. Transcriptome analysis of JQ1-treated dcSSc fibroblasts revealed differentially expressed genes related to extracellular matrix, cell cycle, and calcium signaling. The anti-fibrotic effect of BRD4 inhibition was at least in part mediated by downregulation of Ca2+/calmodulin-dependent protein kinase II α (CaMKII-α) and reduction of intracellular calcium concentrations. These results suggest that targeting calcium pathways or BRD4 might be novel therapeutic approaches for progressive tissue fibrosis.
A Systematic Review of the Cardiovascular Manifestations and Outcomes in the Setting of Coronavirus-19 Disease
Authors: Thakkar Samarthkumar , Arora Shilpkumar , Kumar Ashish , Jaswaney Rahul , Faisaluddin Mohammed , Ammad Ud Din Mohammad , Shariff Mariam , Barssoum Kirolos , Patel Harsh P , Nirav Arora , Jani Chinmay , Savani Sejal , DeSimone Christopher , Mulpuru Siva , Deshmukh Abhishek
Published: August 2020

The impact of coronavirus disease, 2019 (COVID-19), has been profound. Though COVID-19 primarily affects the respiratory system, it has also been associated with a wide range of cardiovascular (CV) manifestations portending extremely poor prognosis. The principal hypothesis for CV involvement is through direct myocardial infection and systemic inflammation. We conducted a systematic review of the current literature to provide a foundation for understanding the CV manifestations and outcomes of COVID-19. PubMed and EMBASE databases were electronically searched from the inception of the databases through April 27th, 2020. A second literature review was conducted to include major trials and guidelines that were published after the initial search but before submission. The inclusion criteria for studies to be eligible were case reports, case series, and observation studies reporting CV outcomes among patients with COVID-19 infection. This review of the current COVID-19 disease and CV outcomes literature revealed a myriad of CV manifestations with potential avenues for treatment and prevention. Future studies are required to understand on a more mechanistic level the effect of COVID-19 on the myocardium and thus provide avenues to improve mortality and morbidity.
The tolerance to hypoxia is defined by a time-sensitive response of the gene regulatory network in sea urchin embryos
Authors: Layous Majed , Khalaily Lama , Gildor Tsvia , de-Leon Smadar Ben-Tabou
Published: August 2020

Deoxygenation, the reduction of oxygen level in the oceans induced by global warming and anthropogenic disturbances, is a major threat to marine life. This change in oxygen level could be especially harmful to marine embryos that utilize endogenous hypoxia and redox gradients as morphogens during normal development. Here we show that the tolerance to hypoxic conditions changes between different developmental stages of the sea urchin embryo, due to the structure of the gene regulatory networks (GRNs). We demonstrate that during normal development, bone morphogenetic protein (BMP) pathway restricts the activity of the vascular endothelial growth factor (VEGF) pathway to two lateral domains and by that controls proper skeletal patterning. Hypoxia applied during early development strongly perturbs the activity of Nodal and BMP pathways that affect VEGF pathway, dorsal-ventral (DV) and skeletogenic patterning. These pathways are largely unaffected by hypoxia applied after DV axis formation. We propose that the use of redox and hypoxia as morphogens makes the sea urchin embryo highly sensitive to environmental hypoxia during early development, but the GRN structure provides higher tolerance to hypoxia at later stages.

Summary statement

The use of hypoxia and redox gradients as morphogens makes sea urchin early development sensitive to environmental hypoxia. This sensitivity decreases later, due to the structure of the gene regulatory network.
Long-term exposure to air-pollution and COVID-19 mortality in England: a hierarchical spatial analysis
Authors: Konstantinoudis Garyfallos , Padellini Tullia , Bennett James , Davies Bethan , Ezzati Majid , Blangiardo Marta
Published: August 2020

Background

Recent studies suggested a link between long-term exposure to air-pollution and COVID-19 mortality. However, due to their ecological design, based on large spatial units, they neglect the strong localised air-pollution patterns, and potentially lead to inadequate confounding adjustment. We investigated the effect of long-term exposure to NO2and PM2·5on COVID-19 deaths up to June 30, 2020 in England using high geographical resolution. Methods We included 38 573 COVID-19 deaths up to June 30, 2020 at the Lower Layer Super Output Area level in England (n=32 844 small areas). We retrieved averaged NO2and PM2·5concentration during 2014-2018 from the Pollution Climate Mapping. We used Bayesian hierarchical models to quantify the effect of air-pollution while adjusting for a series of confounding and spatial autocorrelation.

Findings

We find a 0·5% (95% credible interval: −0·2%-1·2%) and 1·4% (−2·1%-5·1%) increase in COVID-19 mortality rate for every 1μg/m3increase in NO2and PM2·5respectively, after adjusting for confounding and spatial autocorrelation. This corresponds to a posterior probability of a positive effect of 0·93 and 0·78 respectively. The spatial relative risk at LSOA level revealed strong patterns, similar for the different pollutants. This potentially captures the spread of the disease during the first wave of the epidemic.

Interpretation

Our study provides some evidence of an effect of long-term NO2exposure on COVID-19 mortality, while the effect of PM2·5remains more uncertain.

Funding

Medical Research Council, Wellcome Trust, Environmental Protection Agency and National Institutes of Health.
A Simultaneous [11C]Raclopride Positron Emission Tomography and Functional Magnetic Resonance Imaging Investigation of Striatal Dopamine Binding in Autism
Authors: Zürcher Nicole R. , Walsh Erin C. , Phillips Rachel D. , Cernasov Paul M. , Tseng Chieh-En J. , Dharanikota Ayarah , Smith Eric , Li Zibo , Kinard Jessica L. , Bizzell Joshua C. , Greene Rachel K. , Dillon Daniel , Pizzagalli Diego A. , Izquierdo-Garcia David , Lalush David , Hooker Jacob M. , Dichter Gabriel S.
Published: August 2020

Background

The social motivation hypothesis of autism suggests that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework posits that impaired mesolimbic dopamine (DA) function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD.

Methods

This study evaluated striatal dopaminergic functioning during incentive processing in ASD using simultaneous positron emission tomography (PET) and fMRI using the D2/D3 dopamine receptor antagonist [11C]raclopride. Using a bolus + infusion protocol, voxel-wise binding potential (BPND) was compared between groups (Controls=12, ASD=10) in the striatum.

Results

Relative to controls, the ASD group demonstrated relatively decreased phasic DA release to incentives in the right and left putamen and left caudate. Striatal clusters showing significant between-group BPNDdifferences were used as seeds in whole-brain fMRI general functional connectivity analyses. This revealed increased connectivity between the PET-derived right putamen seed and clusters in the precuneus and right insula in the ASD group. Within the ASD group, decreased phasic DA release in the left putamen was related to poorer theory-of-mind skills.

Conclusions

ASD was characterized by impaired striatal phasic DA release and abnormally increased functional connectivity, providing support for the social motivation hypothesis of autism. PET measures of dopamine receptor target occupancy may be suitable to evaluate novel ASD therapeutics targeting the striatal dopamine system.
Effectiveness of booster BCG vaccination in preventing Covid-19 infection
Authors: Amirlak lradj , Haddad Rifat , Hardy John Denis , Khaled Naief Suleiman , Chung Michael H. , Amirlak Bardia
Published: August 2020

Introduction

The evidence that BCG (bacille Calmette-Guerin) vaccine may increase the ability of the immune system to fight off pathogens other than tuberculosis has been studied in the past. This nonspecific immunity gained our interest, especially after initial reports of less cases in countries with universal BCG vaccination. In hopes of possible protective immunity, all staff of the Emirates International Hospital (United Arab Emirates) were offered a booster BCG vaccine in early March 2020. All the hospital staff were then tested for Covid-19 infection by the end of June 2020.

Methodology

We divided the subjects into two groups: booster vaccinated, versus unvaccinated. The rate of Covid-19 infection was compared between the groups. Criteria included all staff who were offered the vaccine.

Results

71 subjects received the booster vaccination. This group had zero cases of positive COVID 19 infection. 209 subjects did not receive the vaccination, with 18 positive PCR confirmed COVID 19 cases The infection rate in the unvaccinated group was 8.6% versus zero in the booster vaccinated group. (Fisher’s exact test p-value=0.004).

Conclusion

Our findings demonstrated the potential effectiveness of the booster BCG vaccine, specifically the booster in preventing Covid-19 infections in an elevated-risk healthcare population.
Temporal changes in the gut microbiota in farmed Atlantic cod (Gadus morhua) outweigh the response to diet supplementation with macroalgae
Authors: Keating C. , Bolton-Warberg M. , Hinchcliffe J. , Davies R. , Whelan S. , Wan A.H.L. , Fitzgerald R. D. , Davies S. J. , Ijaz U. Z. , Smith C. J.
Published: August 2020

Background

Aquaculture successfully meets global food demands for many fish species. However, aquaculture production of Atlantic cod (Gadus morhua) is modest in comparison to market demand. For cod farming to be a viable economic venture specific challenges on how to increase growth, health and farming productivity need to be addressed. Feed ingredients play a key role here. Macroalgae (seaweeds) have been suggested as a functional feed supplement with both health and economic benefits for terrestrial farmed animals and fish. The impact of such dietary supplements to cod gut integrity and microbiota, which contribute to overall fish robustness is unknown. The objective of this study was to supplement the diet of juvenile Atlantic cod with macroalgae and determine the impacts on fish condition and growth, gut morphology and hindgut microbiota composition (16S rRNA amplicon sequencing). Fish were fed one of three diets: control (no macroalgal inclusion), 10% inclusion of either egg wrack (Ascophyllum nodosum) or sea lettuce (Ulva rigida) macroalgae in a 12-week trial.

Results

The results demonstrated there was no significant difference in fish condition, gut morphology or hindgut microbiota between theU. rigidasupplemented fish group and the control group at any time-point. This contrasts with theA. nodosumtreatment. Fish within this group were further categorised as either ‘Normal’ or ‘Lower Growth’. ‘Lower Growth’ individuals found the diet unpalatable resulting in reduced weight and condition factor combined with an altered gut morphology and microbiome relative to the other treatments. Excluding this group, our results show that the hindgut microbiota was largely driven by temporal pressures with the microbial communities becoming more similar over time irrespective of dietary treatment. The core microbiome at the final time-point consisted of the ordersVibrionales(VibrioandPhotobacterium),Bacteroidales(BacteroidetesandMacellibacteroides) andClostridiales(Lachnoclostridium).

Conclusions

Our study indicates thatU. rigidamacroalgae can be supplemented at 10% inclusion levels in the diet of juvenile farmed Atlantic cod without any impact on fish condition or hindgut microbial community structure. We also conclude that 10% dietary inclusion ofA. nodosumis not a suitable feed supplement in a farmed cod diet.
Heat-treated virus inactivation rate depends strongly on treatment procedure: illustration with SARS-CoV-2
Authors: Gamble Amandine , Fischer Robert J. , Morris Dylan H. , Yinda Kwe Claude , Munster Vincent J. , Lloyd-Smith James O.
Published: August 2020

Decontamination helps limit environmental transmission of infectious agents. It is required for the safe re-use of contaminated medical, laboratory and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval: [0.09, 1.77]) in closed vials in a heat block to 37.00 min ([12.65, 869.82]) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature temperature-dependent coronavirus stability and found that specimen containers, and whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines.

Importance

Heat is a powerful weapon against most infectious agents. It is widely used for decontamination of medical, laboratory and personal protective equipment, and for biological samples. There are many methods of heat treatment, and methodological details can affect speed and efficacy of decontamination. We applied four different heat-treatment procedures to liquid specimens containing SARS-CoV-2. Our results show that the container used to store specimens during decontamination can substantially affect inactivation rate: for a given initial level of contamination, decontamination time can vary from a few minutes in closed vials to several hours in uncovered plates. Reviewing the literature, we found that container choices and heat treatment methods are only rarely reported explicitly in methods sections. Our study shows that careful consideration of heat-treatment procedure — in particular the choice of specimen container, and whether it is covered — can make results more consistent across studies, improve decontamination practice, and provide insight into the mechanisms of virus inactivation.
Arabidopsis thalianaZn2+-efflux ATPases HMA2 and HMA4 are required for resistance to the necrotrophic fungusPlectosphaerella cucumerinaBMM
Authors: Escudero Viviana , Castro-León Álvaro , Sánchez Darío Ferreira , Abreu Isidro , Bernal María , Krämer Ute , Grolimund Daniel , González-Guerrero Manuel , Jordá Lucía
Published: August 2020

Zinc is an essential nutrient at low concentrations, but toxic at slightly higher ones. This could be used by plants to fight pathogens colonization.

Elemental distribution inArabidopsis thalianaleaves inoculated with the necrotrophic fungusPlectosphaerella cucumerinaBMM (PcBMM) was determined and compared to mock-inoculated ones. Infection assays were carried out in wild type and long-distance zinc trafficking double mutanthma2hma4, defective in root-to-shoot zinc partitioning. Expression levels of genes involved in zinc homeostasis or in defence phytohormone-mediated pathways were determined.

Zinc and manganese levels increased at the infection site. Zinc accumulation was absent inhma2hma4. HMA2 and HMA4transcription levels were upregulated uponPcBMMinoculation. Consistent with a role of these genes in plant immunity,hma2hma4mutants were more susceptible toPcBMMinfection, phenotype rescued upon zinc supplementation. Transcript levels of genes involved in the salicylic acid, ethylene and jasmonate pathways were constitutively upregulated inhma2hma4plants.

These data are consistent with a role of zinc in plant immunity not only of hyperaccumulator plants, but also of plants containing ordinary levels of zinc. This new layer of immunity seems to run in parallel to the already characterized defence pathways, and its removal has a direct effect on pathogen resistance.
Dysregulation of the secretory pathway connects Alzheimer’s disease genetics to aggregate formation
Authors: Kuo Chih-Chung , Chiang Austin WT , Baghdassarian Hratch M. , Lewis Nathan E.
Published: August 2020

A hallmark of amyloid disorders, such as Alzheimer’s disease, is aggregation of secreted proteins. However, it is largely unclear how the hundreds of secretory pathway proteins contribute to amyloid formation. We developed a systems biology framework that integrates expression data with protein-protein interaction networks to successfully estimate a tissue’s fitness for producing specific secreted proteins. Using this framework, we analyzed the fitness of the secretory pathway of various brain regions and cell types for synthesizing the Alzheimer’s disease-associated amyloid-precursor protein (APP). While none of the key amyloidogenic pathway components were differentially expressed in AD brain, we found the deposition of Aβ is associated with repressed expression of the secretory pathway components proximal to APP. Concurrently, we detected systemic up-regulation of the secretory pathway components proximal to β- and γ-secretases in AD brains. Our analyses suggest that perturbations from 3 high confidence AD risk genes cascade through the secretory machinery support network for APP and into the endocytosis pathway. Thus, we present a model where amyloidogenesis is associated with dysregulation of dozens of secretory pathway components supporting APP, which could yield novel therapeutic targets for the treatment of AD.
Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies from human serum samples
Authors: Mazzini Livia , Martinuzzi Donata , Hyseni Inesa , Lapini Giulia , Benincasa Linda , Piu Pietro , Trombetta Claudia Maria , Marchi Serena , Razzano Ilaria , Manenti Alessandro , Montomoli Emanuele
Published: August 2020

A newly identified coronavirus, named SARS-CoV-2, emerged in December 2019 in Hubei Province, China, and quickly spread throughout the world; so far, it has caused more than 18 million cases of disease and 700,000 deaths. The diagnosis of SARS-CoV-2 infection is currently based on the detection of viral RNA in nasopharyngeal swabs by means of molecular-based assays, such as real-time RT-PCR. Furthermore, serological assays aimed at detecting different classes of antibodies constitute the best surveillance strategy for gathering information on the humoral immune response to infection and the spread of the virus through the population, in order to evaluate the immunogenicity of novel future vaccines and medicines for the treatment and prevention of COVID-19 disease. The aim of this study was to determine SARS-CoV-2-specific antibodies in human serum samples by means of different commercial and in-house ELISA kits, in order to evaluate and compare their results first with one another and then with those yielded by functional assays using wild-type virus. It is important to know the level of SARS-CoV-2-specific IgM, IgG and IgA antibodies in order to predict population immunity and possible cross-reactivity with other coronaviruses and to identify potentially infectious subjects. In addition, in a small sub-group of samples, we performed a subtyping Immunoglobulin G ELISA. Our data showed an excellent statistical correlation between the neutralization titer and the IgG, IgM and IgA ELISA response against the receptor-binding domain of the spike protein, confirming that antibodies against this portion of the virus spike protein are highly neutralizing and that the ELISA Receptor-Binding Domain-based assay can be used as a valid surrogate for the neutralization assay in laboratories which do not have Biosecurity level-3 facilities.
Whole-Brain Longitudinal Profiling of Serotonergic Reuptake Inhibition
Authors: Ioanas Horea-Ioan , Saab Bechara John , Rudin Markus
Published: August 2020

The serotonergic system is widely implicated in affect regulation, and a common target for psychopharmacological interventions. Selective Serotonin Reuptake Inhibitors (SSRIs) are the foremost drug class for treating depression, as well as anxiety, phobia and other affective disorders. However, the functional mechanisms determining SSRI efficacy remain elusive, hindering the targeted further development of serotonergic system interventions. Assays for longitudinal whole-brain interrogation of the serotonergic system are unavailable, yet such techniques are essential for identifying differential intervention effects across projection areas. We present a novel longitudinal opto-fMRI assay suitable for imaging longitudinal drug treatment effects on the mouse serotonergic system — within-subject and with sub-millimetre spatial resolution. We apply this assay to a longitudinal fluoxetine treatment, and document reliable segmentation of brain-wide treatment effects, including identification of a brainstem cluster with a highly significant longitudinal trajectory, constituting a novel neurophenotype for psychopharmacological interventions. We differentiate serotonergic neuron activation from projection area activation, and offer brain-wide fMRI evidence for the prominent autoinhibition down-regulation theory of SSRI effects. Further, we show that given the sensitivity of the assay, SSRI treatment produces no persistent effects after treatment cessation in healthy subjects.
Ap2s1mutation in mice causes familial hypocalciuric hypercalcemia type 3
Authors: Hannan Fadil M. , Stevenson Mark , Bayliss Asha L. , Stokes Victoria J. , Stewart Michelle , Kooblall Kreepa G. , Gorvin Caroline M. , Codner Gemma , Teboul Lydia , Wells Sara , Thakker Rajesh V.
Published: August 2020

Mutations of the adaptor protein-2 sigma subunit (AP2S1) gene which encodes AP2σ2, a component of the ubiquitous AP2 heterotetrameric complex involved in endosomal trafficking of the calcium-sensing receptor (CaSR), cause familial hypocalciuric hypercalcemia type 3 (FHH3). FHH3 patients have heterozygousAP2S1missense Arg15 mutations (p.Arg15Cys, p.Arg15His or p.Arg15Leu) with marked hypercalcemia and occasional hypophosphatemia and osteomalacia. To further characterise the phenotypic spectrum and calcitropic pathophysiology of FHH3, we used CRISPR/Cas9 genome editing to generate mice harboring theAP2S1p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. Heterozygous (Ap2s1+/L15) mice were viable, and had marked hypercalcemia, hypermagnesemia, hypophosphatemia, and increased plasma concentrations of parathyroid hormone, fibroblast growth factor 23 and alkaline phosphatase activity, but normal pro-collagen type 1 N-terminal pro-peptide and 1,25 dihydroxyvitamin D. Homozygous (Ap2s1L15/L15) mice invariably died perinatally. TheAP2S1p.Arg15Leu mutation impaired protein-protein interactions between AP2σ2 and the other AP2 subunits, and the CaSR. Cinacalcet, a CaSR allosteric activator, ameliorated the hypercalcemia and elevated PTH concentrations, but not the diminished AP2σ2-CaSR interaction. Thus, our studies have established a mouse model with a germline loss-of-functionAP2S1mutation that is representative for FHH3 in humans, and demonstrated that cinacalcet corrects the abnormalities of plasma calcium and PTH.
Rhizosphere Microbiomes in a Historical Maize/Soybean Rotation System respond to Host Species and Nitrogen Fertilization at Genus and Sub-genus Levels
Authors: Meier Michael A. , Lopez-Guerrero Martha G. , Guo Ming , Schmer Marty R. , Herr Joshua R. , Schnable James C. , Alfano James R. , Yang Jinliang
Published: August 2020

Root associated microbes are key players in plant health, disease resistance, and nitrogen (N) use efficiency. It remains largely unclear how the interplay of biological and environmental factors affects rhizobiome dynamics in agricultural systems. Here, we quantified the composition of rhizosphere and bulk soil microbial communities associated with maize (Zea mays L.) and soybean (Glycine max L.) in a long-term crop rotation study under conventional fertilization and low N regimes. Over two growing seasons, we evaluated the effects of environmental conditions and several treatment factors on the abundance of rhizosphere and soil colonizing microbial taxa. Time of sampling, host plant species and N fertilization had major effects on microbiomes, while no effect of crop rotation was observed. Using variance partitioning as well as 16S sequence information, we further defined a set of 82 microbial genera and sub-genus groups that show distinct responses to treatment factors. We identified taxa that are highly specific to either maize or soybean rhizospheres, as well as taxa that are sensitive to N fertilization in plant rhizospheres and bulk soil. This study provides insights to harness the full potential of soil microbes in maize and soybean agricultural systems through plant breeding and field management.
Distributed harmonic patterns of structure-function dependence orchestrate human consciousness
Authors: Luppi Andrea I. , Vohryzek Jakub , Kringelbach Morten L. , Mediano Pedro A.M. , Craig Michael M. , Adapa Ram , Carhart-Harris Robin L. , Roseman Leor , Pappas Ioannis , Peattie Alexander R.D. , Manktelow Anne E. , Sahakian Barbara J. , Finoia Paola , Williams Guy B. , Allanson Judith , Pickard John D. , Menon David K. , Atasoy Selen , Stamatakis Emmanuel A.
Published: August 2020

Abstract

A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Departing from the predominant location- centric view in neuroimaging, here we provide an alternative perspective on the neural signatures of human consciousness: one that is intrinsically centered on how the distributed network architecture of the human structural connectome shapes functional activation across scales. We decompose cortical dynamics of resting-state functional MRI into fundamental distributed patterns of structure- function association: the harmonic modes of the human structural connectome. We contrast wakefulness with a wide spectrum of states of consciousness, spanning chronic disorders of consciousness but also pharmacological perturbations of consciousness induced with the anaesthetic propofol and the psychoactive drugs ketamine and LSD. Decomposing this wide spectrum of states of consciousness in terms of “connectome harmonics” reveals a generalisable structure-function signature of loss of consciousness, whether due to anaesthesia or brain injury. A mirror-reverse of this harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure. The topology and neuroanatomy of the human connectome are crucial for shaping the repertoire of connectome harmonics into a fine-tuned indicator of consciousness, correlating with physiological and subjective scores across datasets and capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. Overall, connectome harmonic decomposition identifies meaningful relationships between neurobiology, brain function, and conscious experience.
Biodiversity genomics of small metazoans: high qualityde novogenomes from single specimens of field-collected and ethanol-preserved springtails
Authors: Schneider Clément , Woehle Christian , Greve Carola , D’Haese Cyrille A. , Wolf Magnus , Janke Axel , Bálint Miklós , Hüttel Bruno
Published: August 2020

Genome sequencing of all known eukaryotes on Earth promises unprecedented advances in evolutionary sciences, ecology, systematics and in biodiversity-related applied fields such as environmental management and natural product research. Advances in DNA sequencing technologies make genome sequencing feasible for many non-genetic model species. However, genome sequencing today relies on large quantities of high quality, high molecular weight (HMW) DNA which is mostly obtained from fresh tissues. This is problematic for biodiversity genomics of Metazoa as most species are small and yield minute amounts of DNA. Furthermore, briging living specimens to the lab bench not realistic for the majority of species.

Here we overcome those difficulties by sequencing two species of springtails (Collembola) from single specimens preserved in ethanol. We used a newly developed, genome-wide amplification-based protocol to generate PacBio libraries for HiFi long-read sequencing.

The assembled genomes were highly continuous. They can be considered complete as we recovered over 95% of BUSCOs. Genome-wide amplification does not seem to bias genome recovery. Presence of almost complete copies of the mitochondrial genome in the nuclear genome were pitfalls for automatic assemblers. The genomes fit well into an existing phylogeny of springtails. A neotype is designated for one of the species, blending genome sequencing and creation of taxonomic references.

Our study shows that it is possible to obtain high quality genomes from small, field-preserved sub-millimeter metazoans, thus making their vast diversity accessible to the fields of genomics.
Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories
Authors: Kellaway Sophie G , Keane Peter , Edginton-White Benjamin , Kakkad Regha , Kennett Ella , Bonifer Constanze
Published: August 2020

Mutations of the hematopoietic master regulator RUNX1 cause acute myeloid leukaemia, familial platelet disorder and other haematological malignancies whose phenotypes and prognoses depend upon the class of RUNX1 mutation. The biochemical behaviour of these oncoproteins and their ability to cause unique diseases has been well studied, but the genomic basis of their differential action is unknown. To address this question we compared integrated phenotypic, transcriptomic and genomic data from cells expressing four types of RUNX1 oncoproteins in an inducible fashion during blood development from embryonic stem cells. We show that each class of mutated RUNX1 deregulates endogenous RUNX1 function by a different mechanism, leading to specific alterations in developmentally controlled transcription factor binding and chromatin programming. The result is distinct perturbations in the trajectories of gene regulatory network changes underlying blood cell development that are consistent with the nature of the final disease phenotype. The development of novel treatments for RUNX1-driven diseases will therefore require individual consideration.