bluuebunny/crossref_metadata_2025 huggingface dataset:
VITRECTOMY + TRANSSCLERAL DIODE LASER CYCLOPEXY TREATMENT FOR 360° TRAUMATIC CYCLODIALYSIS AND HYPOTONY MACULOPATHY: CASE REPORT
Authors: Rios-Nequis Geovanni , Flores-Villalobos Erick Omar , Ramirez-Estudillo Abel , Gonzalez-Saldivar Gerardo , Diez-Cattini Gian Franco
Published: September 2020

Background/Purpose:

To report a surgical approach of combined vitrectomy, gas endotamponade, and transscleral diode laser cyclopexy treatment for hypotony maculopathy induced by traumatic cyclodialysis.

Methods:

A case of a 37-year-old male patient with decreased vision in his right eye because of hypotony maculopathy and 360° traumatic cyclodialysis is reported. Patient was initially treated conservatively with topical steroid + cycloplegic eye drops and repeated periocular corticosteroid injections with no improvement in the intraocular pressure and the anatomical defect. The patient underwent 23 G pars plana vitrectomy with 20% SF6 gas endotamponade and supine position. Transscleral 810-nm laser burns were applied at 1.5 mm from the scleral limbus around the cornea in two confluent rows avoiding the horizontal meridians. Parameters used were 700–1,000 mW of power with a 2-second exposure in a continuous wave mode, and postoperative supine positioning of the head was indicated.

Results:

Preoperative intraocular pressure improved from 2 mmHg to 10 mmHg at one week after surgical treatment and achieved 16 mmHg at one month to remain stable during a 6 months follow-up period. Presenting visual acuity was 1.0 logMAR (20/200 Snellen) and improved to 0.3 logMAR (20/40 Snellen) at Month 1 and achieved 0.1 logMAR (20/20 Snellen) at the third month. Complete closure of the cyclodialysis cleft and peripheral anterior synechiae formation were also observed at 3 months after treatment, with complete reattachment of the ciliary body demonstrated by ultrasound biomicroscopy and significant improvement of the macular anatomy demonstrated by spectral-domain optical coherence tomography.

Conclusion:

The combination of pars plana vitrectomy, supine positioning with gas endotamponade, and transscleral laser cyclopexy can successfully improve the visual and anatomical outcomes in patients with hypotony maculopathy and 360° traumatic cyclodialysis.
Impact of Pupil Dilation on Optical Coherence Tomography Angiography Retinal Microvasculature in Healthy Eyes
Authors: Villatoro George , Bowd Christopher , Proudfoot James A. , Manalastas Patricia I.C. , Nguyen Khoa D. , Hou Huiyuan , Penteado Rafaella C. , Li Andrew J. , Moghimi Sasan , Ghahari Elham , Weinreb Robert N. , Zangwill Linda M.
Published: September 2020

Précis:

Small but significant decreases in optical coherence tomography angiography (OCTA)-measured circumpapillary capillary density (cpCD) were observed in healthy eyes dilated with 2.5% phenylephrine/0.5% tropicamide. Although likely clinically insignificant, ophthalmologists should consider these changes when interpreting OCTA results from dilated eyes.

Purpose:

The purpose of this study was to investigate the effect of pupil dilation using 2.5% phenylephrine and 0.5% tropicamide on quantitative assessment of retinal microvasculature using OCTA.

Methods:

OptoVue AngioVue high density (HD) and non-HD OCTA macula and optic nerve head (ONH) images were obtained at 15-minute intervals predilation and postdilation in 26 healthy participants (mean age: 40.0; 95% confidence interval=33.9, 46.1 y). Superficial macular vessel density (VD) was measured in the whole image VD and the parafoveal region VD. ONH capillary density was measured in the whole image capillary density and the cpCD region. Differences between predilation and postdilation densities were assessed using linear mixed effects models to account for within-patient correlation.

Results:

Instillation of dilating drops resulted in a small but statistically significant reduction in non-HD ONH whole image capillary density of 0.6%, from a mean of 45.2% (95% confidence interval=41.9%, 48.4%) to 44.6% (41.4%, 47.8%) (P=0.046). A similar reduction in non-HD ONH cpCD of 0.8% also was observed, from a mean of 49.3% (45.3%, 53.3%) to 48.5% (44.5%, 52.4%) (P=0.025). No postdilation decreases in macular VD or HD ONH capillary density were observed.

Conclusions:

Pupil dilation using topical 2.5% phenylephrine and 0.5% tropicamide results in a small but statistically significant reduction in non-HD ONH whole image and cpCD in healthy eyes. The observed reduction likely is not clinically significant because the observed reduction was within the previously reported range of measurement variability. Further studies should consider investigating these effects in nonhealthy eyes with glaucoma and media opacities, as well as older individuals.
Primary Versus Posttrabeculectomy XEN45 Gel Stent Implantation: Comparison of Success Rates and Intraocular Pressure-lowering Potential in Pseudophakic Eyes
Authors: Widder Randolf A. , Lappas Alexandra , Rennings Corinna , Hild Matthias , Dietlein Thomas S. , Roessler Gernot F.
Published: September 2020

Precis:

The XEN45 Gel Stent can be implanted after failed trabeculectomy without disadvantages compared with primary implantation.

Purpose:

We aimed to compare the outcomes of XEN45 Gel Stent implantation in pseudophakic eyes after failed trabeculectomy and in pseudophakic eyes without other previous surgeries.

Patients and Methods:

In this retrospective study, we included 30 pseudophakic eyes of 30 patients who underwent XEN45 Gel Stent implantation after failed trabeculectomy (trabeculectomy group) and 60 eyes of 60 patients with primary XEN45 Gel Stent implantation (control group). The groups were matched for preoperative intraocular pressure (IOP), preoperative medication score, cup-to-disc ratio, follow-up time, visual acuity, and age at a ratio of 1:2. Eyes with concomitant eye diseases, those who had undergone previous surgery, and those with a follow-up duration <6 months were excluded. We compared the success rates on the basis of different criteria: Criteria A (IOP<21 mm Hg, IOP reduction>20%, no repeat surgery); Criteria B (IOP<18 mm Hg, IOP reduction>20%, no repeat surgery); and Criteria C (IOP≤15 mm Hg, IOP reduction≥40%, no repeat surgery).

Results:

After an average follow-up period of 20 months, the mean IOP was reduced from 24.4±5.7 to 14.0±4.1 mm Hg in all the study subjects (90 patients). There were no significant differences between the 2 groups in postoperative IOP, postoperative medication score, revision rate, and repeat surgery rate or success rate.

Conclusions:

XEN45 Gel Stent implantation is a viable option after failed trabeculectomy. According to our results, it has no disadvantage compared with primary XEN45 Gel Stent implantation.
Request for spectacle independence in a 25-year-old patient: September consultation #1
Authors: Nuijts Rudy M.M.A. , Kartal Serdar
Published: September 2020

A 25-year-old woman was seen at our clinic with contact lens (CL) intolerance and a request for spectacle independence. Her medical history included asthma and allergic rhinitis. Because of the allergies, the patient used to extensively rub her eyes. Her hobby is boxing.

The corrected distance visual acuity at presentation was 20/20 with −4.75 −2.50 × 52 and 20/20 with −5.75 −2.00 × 121 in the right and left eyes, respectively. The subjective refraction 6 months later was −5.00 −1.50 × 60 and −4.75 −1.50 × 121 in the right and left eyes, respectively. Her tear breakup time was 3 and 5 seconds and the Schirmer tear test values were 11.0 and 12.0 mm in the right and left eyes, respectively.

The anterior chamber depth (ACD) (measured from the endothelium) was 2.87 mm and 2.89 mm in the right and left eyes, respectively. The corneal thickness was 566 μm and 551 μm of the right and left eyes, respectively. Corneal endothelial cell density was on average 2100 cells/mm2 for both eyes. Slitlamp biomicroscopy showed some slight punctate keratopathy inferiorly of both corneas. Figures 1 to 4

JOURNAL/jcrs/04.03/02158034-202009000-00020/figure1/v/2023-08-19T002553Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202009000-00020/figure2/v/2023-08-19T002553Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202009000-00020/figure3/v/2023-08-19T002553Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202009000-00020/figure4/v/2023-08-19T002553Z/r/image-tiff

show the corneal topography and Belin-Ambrósio maps at presentation and 6 months later of the right and left eyes, respectively.
Treatment of pulmonary exacerbations in cystic fibrosis
Authors: Ng Christabella , Nadig Tejaswi , Smyth Alan R. , Flume Patrick
Published: September 2020

Purpose of review

This review will discuss the challenges of defining a pulmonary exacerbations in cystic fibrosis and the key pathogens, which contribute. It will discuss the treatment options currently available and the importance of preventing pulmonary exacerbations.

Recent findings

The basis for treatment of pulmonary exacerbations remains unchanged over the past 15 years and whilst there have been trials exploring alternative antibiotics, there has been little change. However, there are ongoing studies that are expected to establish a platform for identifying best practices. Chronic cystic fibrosis therapies have been shown to reduce pulmonary exacerbations. In the era of new CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapies, the number of pulmonary exacerbations are expected to be even fewer. However, it is unclear whether the other chronic therapies can be discontinued without losing their benefits in reducing exacerbations.

Although there is no universal definition of a pulmonary exacerbation in cystic fibrosis, proposed definitions have many similarities. We have outlined the current recommendations for treatment of pulmonary exacerbations, including the duration and location of treatments. We have also summarized the key therapies used for prevention of pulmonary exacerbations in cystic fibrosis.
Three-Dimensional Modeling of Complex Pediatric Intracranial Aneurysmal Malformations With a Virtual Reality System
Authors: Yan Eric G. , Rennert Robert C. , Levy Danielle M. , Levy Michael L.
Published: September 2020

Introduction

Surgical simulation is valuable in neurovascular surgery given the progressive rarity of these cases and their technical complexity, but its use has not been well described for pediatric vascular pathologies. We herein review the use of surgical simulation at our institution for complex pediatric aneurysmal malformations.

Methods

A retrospective review of patients treated for middle cerebral artery aneurysmal malformations with surgical simulation assistance (SuRgical Planner [SRP]; Surgical Theater, Mayfield Village, OH) during a 2-year period at Rady Children's Hospital of San Diego was performed.

Results

In 5 pediatric patients with complex MCA aneurysmal malformations (mean age = 33.2 ± 49.9 months), preoperative 3-dimensional (3D) interactive modeling informed treatment planning and enhanced surgeon understanding of the vascular pathology. Availability of intraoperative simulation also aided real-time anatomical understanding during surgery. Specific benefits of simulation for these cases included characterization of involved perforating vessels, as well as an enhanced understanding of flow patterns within associated complex arteriovenous fistulas and feeding vessel/daughter branch anatomy. Despite the complexity of the lesions treated, use of simulation qualitatively enhanced surgeon confidence. There were no perioperative complications for patients treated with open surgery.

Conclusions

Surgical simulation may aid in the treatment of complex pediatric aneurysmal malformations.
Valproic acid treatment rescues injured tissues after traumatic brain injury
Authors: Biesterveld Ben E. , Pumiglia Luke , Iancu Ariella , Shamshad Alizeh A. , Remmer Henriette A. , Siddiqui Ali Z. , O’Connell Rachel L. , Wakam Glenn K. , Kemp Michael T. , Williams Aaron M. , Pai Manjunath P. , Alam Hasan B.
Published: September 2020

BACKGROUND

No agents that are specifically neuroprotective are currently approved to emergently treat patients with traumatic brain injury (TBI). The histone deacetylase inhibitor, high-dose valproic acid (VPA) has been shown to have cytoprotective potential in models of combined TBI and hemorrhagic shock, but it has not been tested in an isolated TBI model. We hypothesized that VPA, administered after isolated TBI, will penetrate the injured brain, attenuate the lesion size, and activate prosurvival pathways.

METHODS

Yorkshire swine were subjected to severe TBI by cortical impact. One hour later, animals were randomized to VPA treatment (150 mg/kg delivered intravenously for 1 hour; n = 4) or control (saline vehicle; n = 4) groups. Seven hours after injury, animals were sacrificed, and brain lesion size was measured. Mass spectrometry imaging was used to visualize and quantitate brain tissue distribution of VPA. Sequential serum samples were assayed for key biomarkers and subjected to proteomic and pathway analysis.

RESULTS

Brain lesion size was 50% smaller (p = 0.01) in the VPA-treated animals (3,837 ± 948 mm3) compared with the controls (1,900 ± 614 mm3). Endothelial regions had eightfold higher VPA concentrations than perivascular regions by mass spectrometry imaging, and it readily penetrated the injured brain tissues. Serum glial fibrillary acid protein was significantly lower in the VPA-treated compared with the control animals (p < 0.05). More than 500 proteins were differentially expressed in the brain, and pathway analysis revealed that VPA affected critical modulators of TBI response including calcium signaling pathways, mitochondria metabolism, and biosynthetic machinery.

CONCLUSION

Valproic acid penetrates injured brain tissues and exerts neuroprotective and prosurvival effects that resulted in a significant reduction in brain lesion size after isolated TBI. Levels of serum biomarkers reflect these changes, which could be useful for monitoring the response of TBI patients during clinical studies.
Use of fibrinogen concentrate for trauma-related bleeding: A systematic-review and meta-analysis
Authors: Stabler Sarah N. , Li Siying Shari , Karpov Andrei , Vu Erik N.
Published: September 2020

BACKGROUND

Trauma-induced coagulopathy contributes to significant morbidity and mortality in patients who experience trauma-related bleeding. This study aimed to synthesize the evidence supporting the efficacy and safety of preemptive and goal-directed fibrinogen concentrate (FC) in the management of trauma-related hemorrhage.

METHODS

PubMed, Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform were systematically searched. All trial designs, except individual case reports, which evaluated the preemptive or goal-directed use of FC for trauma-related bleeding/coagulopathy, in patients older than 16 years, were included in the systematic review. For the included randomized controlled trials comparing FC with control, meta-analysis was performed and a risk-of bias-assessment was completed using the Cochrane Methodology and Preferred Reporting Items Systematic Reviews and Meta-analysis guidelines.

RESULTS

A total of 2,743 studies were identified; 26 were included in the systematic review, and 5 randomized controlled trials (n = 238) were included in the meta-analysis. For the primary outcome of mortality, there was no statistically significant difference between the groups, with 22% and 23.4% in the FC and comparator arms, respectively (risk ratio, 1.00 [95% confidence interval, 0.39 to 2.56]; p = 0.99). In addition, there was no statistical difference between FC and control in packed red blood cell, fresh frozen plasma, or platelet transfusion requirements, and thromboembolic events. Overall, the quality of evidence was graded as low to moderate because of concerns with risk of bias, imprecision, and inconsistency.

CONCLUSION

Further high-quality, adequately powered studies are needed to assess the impact of FC in trauma, with a focus on administration as early as possible from the point of entry into the trauma system of care.

LEVEL OF EVIDENCE

Systematic review and Meta-analysis, level II.
Paucihalobacter ruber gen. nov., sp. nov., isolated from a haloalkaline lake sediment sample
Authors: Wu Shu-ge , Wang Jing-jing , Wang Jia-ning , Chen Qi , Du Zong-jun , Li Yue-zhong
Published: September 2020

A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped bacterium, designated CWB-1T, was isolated from a haloalkaline lake sediment sample collected from the bottom of Chaiwopu Lake, Urumchi, Xinjiang Province, PR China. Strain CWB-1T grew at 4–40 °C (optimum, 30–35 °C), pH 6.5–9.0 (optimum, pH 6.5–7.0) and with 0.5–5.5 % (w/v) NaCl (optimum, 2.5–3.0 %). Phylogenetic analyses based on the 16S rRNA gene sequence and the whole genome sequence both revealed that strain CWB-1T belonged to the family

Flavobacteriaceae

. The strain had the highest similarity of the 16S rRNA gene sequence to

Psychroserpens jangbogonensis

PAMC 27130T (92.8 %). The genome of strain CWB-1T was 3 548 011 bp long with 36.3 % DNA G+C content. The predominant fatty acids (>10 %) in the CWB-1T cells were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 1 (iso-C15 : 1 H/C13 : 0 3-OH). The major respiratory quinone was menaquinone-6 and the major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and two unidentified lipids. Based on the phylogenetic analyses, as well as the phenotypic characteristics, a novel genus and species of the family

Flavobacteriaceae

, Paucihalobacter ruber gen. nov., sp. nov., is proposed. The type strain is CWB-1T (=KCTC 72450T=CGMCC 1.17149T).
Flaviflexus ciconiae sp. nov., isolated from the faeces of the oriental stork, Ciconia boyciana
Authors: Lee Jae-Yun , Kang Woorim , Kim Pil Soo , Lee So-Yeon , Shin Na-Ri , Sung Hojun , Lee June-Young , Yun Ji-Hyun , Jeong Yun-Seok , Han Jeong Eun , Jung Mi-Ja , Hyun Dong-Wook , Kim Hyun Sik , Tak Euon Jung , Bae Jin-Woo
Published: September 2020

A novel Gram-stain-positive, non-motile, non-spore-forming, coccobacillus-shaped, strictly aerobic bacterium, designated strain H23T48T, was isolated from the faecal sample of an oriental stork collected from the Seoul Grand Park Zoo in Seoul, Republic of Korea. Optimal growth of strain H23T48Twas observed at 30–37 °C, pH 8 and with 3 % (w/v) NaCl. 16S rRNA gene sequence-based phylogenetic analysis revealed that strain H23T48Twas closely related to the genusFlaviflexus, with 97.0 and 96.7 % sequence similarities toFlaviflexus salsibiostraticolaEBR4-1-2TandFlaviflexus huanghaiensisH5T, respectively. Strain H23T48Tpossessed MK-9(H4) as the major menaquinone and C16 : 0(42.4 %), C18 : 1 ω9c(31.3 %) and C14 : 0(17.7 %) as the major cellular fatty acids. The polar lipids included phosphatidylglycerol, two unidentified lipids, six unidentified phospholipids and two unidentified glycophospholipids. The amino acid composition of the cell-wall peptidoglycan wasl-alanine,l-lysine,d-glutamic acid,l-aspartic acid and glycine. The genomic G+C content of strain H23T48Tis 59.5 mol% and the average nucleotide identity value between H23T48TandF. salsibiostraticolaKCT C33148T(=EBR4-1-2T) is 75.5 %. Based on the obtained data, strain H23T48Trepresents a novel species of the genusFlaviflexus, for which the nameFlaviflexus ciconiaesp. nov. is proposed. The type strain is H23T48T(=KCTC 49253T=JCM 33282T).
Depsipeptide nucleic acids: prebiotic formation, oligomerization, and self-assembly of a new candidate proto-nucleic acid
Authors: Fialho David M. , Karunakaran Suneesh C. , Greeson Katherine W. , Martínez Isaac , Schuster Gary B. , Krishnamurthy Ramanarayanan , Hud Nicholas V.
Published: September 2020

The mechanism by which genetic polymers spontaneously formed on the early Earth is currently unknown. The RNA World hypothesis implies that RNA oligomers were produced prebiotically, but the demonstration of this process has proven challenging. Alternatively, RNA may be the product of evolution and some, or all, of its chemical components may have been preceded by functionally analogous moieties that were more readily accessible under plausible early-Earth conditions. We report a new class of nucleic acid analog, depsipeptide nucleic acid, which displays several properties that make it an attractive candidate for the first informational polymer to arise on the Earth. The monomers of depsipeptide nucleic acids can form under plausibly prebiotic conditions. These monomers oligomerize spontaneously when dried from aqueous solutions to form nucleobase-functionalized depsipeptides. Once formed, these depsipeptide nucleic acid oligomers are capable of complementary self-assembly, and are resistant to hydrolysis in the assembled state. These results suggest that the initial formation of primitive, self-assembling, informational polymers may have been relatively facile.
Reduced risk-taking behavior during frontal oscillatory theta band neurostimulation
Authors: Dantas Aline M. , Sack Alexander T. , Bruggen Elisabeth , Jiao Peiran , Schuhmann Teresa
Published: September 2020

Background

Most of our decisions involve a certain degree of risk regarding the outcomes of our choices. People vary in the way they make decisions, resulting in different levels of risk-taking behavior. These differences have been linked to prefrontal theta band activity. However, a direct functional relationship between prefrontal theta band activity and risk-taking has not yet been demonstrated.

Objective

We used noninvasive brain stimulation to test the functional relevance of prefrontal oscillatory theta activity for the regulatory control of risk-taking behavior.

Methods

In a within-subject experiment, 32 healthy participants received theta [4-8 Hertz (Hz)], gamma (30-50 Hz), and sham transcranial alternating current stimulation (tACS) over the left prefrontal cortex (lPFC). During stimulation, participants completed a task assessing their risk-taking behavior as well as response times and sensitivity to value and outcome probabilities. Electroencephalography (EEG) was recorded before and immediately after stimulation.

Results

Theta-band, but not gamma-band or sham, tACS led to a significant reduction in risk-taking behavior, indicating a frequency-specific effect of prefrontal brain stimulation on the modulation of risk-taking behavior. Moreover, theta-band stimulation led to increased response times and decreased sensitivity to reward values. EEG data analyses did not show an increase in power in the stimulated frequencies.

Conclusion

These findings provide direct empirical evidence for the effects of prefrontal theta-band stimulation on behavioral risk-taking regulation.
Human uniqueness illustrated by life history diversity among small-scale societies and chimpanzees
Authors: Davison Raziel J. , Gurven Michael D.
Published: September 2020

Background

We compare life histories and selection forces among chimpanzees and human subsistence societies in order to identify the age-specific vital rates that best explain fitness variation, selection pressures and species divergence.

Methods

We employ Life Table Response Experiments that quantify vital rate contributions to population growth rate differences. Although widespread in ecology, these methods have not been applied to human populations or to look at species differences among humans and chimpanzees. We also estimate correlations between vital rate elasticities and life history traits to investigate differences in selection pressures and test predictions of life history theory.

Results

Chimpanzees’ earlier maturity and higher adult mortality drive species differences, whereas infant mortality and fertility variation drive differences among humans. Human fitness is decoupled from longevity by postreproductive survival, while chimpanzees forfeit higher potential lifetime fertility due to adult mortality attrition. Infant survival is often lower among humans, but lost fitness is recouped via short birth spacing and high peak fertility, thereby reducing selection on infant survival. Lastly, longevity and delayed maturity reduce selection on child survival, but among humans, recruitment selection is unexpectedly highest in longer-lived populations, which are also faster-growing due to high fertility.

Conclusion

Humans differ from chimpanzees more because of delayed maturity and adult mortality than child mortality or fertility rates. In both species, high child mortality reflects bet-hedging costs of quality/quantity tradeoffs borne by offspring, with high and variable child mortality likely regulating human population growth over evolutionary history. Among human subsistence societies, positive correlations between survival and natural fertility lead selection pressures in human subsistence societies to differ from modern populations undergoing demographic transition, due in part to positive correlations between longevity and natural fertility and negative correlations between recruitment elasticity and reproductive effort.
Genome-wide association study of skin and soft tissue infection susceptibility
Authors: Rogne Tormod , Liyanarachi Kristin V , Rasheed Humaira , Thomas Laurent F , Flatby Helene M , Løset Mari , Gill Dipender , Burgess Stephen , Willer Cristen J , Hveem Kristian , Åsvold Bjørn O , Brumpton Ben M , DeWan Andrew T , Solligård Erik , Damås Jan K
Published: September 2020

Background

Skin and soft tissue infections (SSTIs) are common worldwide, but little is known about the genetic susceptibility and the causal effect of cardiometabolic risk factors. We therefore conducted the first genome-wide association study (GWAS) of SSTIs, with downstream analyses including Mendelian randomization analyses.

Methods

The GWAS was conducted using the UK Biobank as discovery cohort, with 6,107 cases and 399,239 controls, and the Trøndelag Health Study (HUNT) as replication cohort with 1,657 cases and 67,522 controls. Cases and controls were those who had or had not been hospitalized with an SSTI diagnosis, respectively.

Findings

One locus, lead single-nucleotide polymorphism rs3749748 in LINC01184/SLC12A2, was associated with SSTIs in the UK Biobank (odds ratio [OR] 1.19, p-value = 7.6e-16) and replicated in HUNT (OR 1.15, p-value = 6.3e-4). Meta-analysis confirmed the lead variant (OR 1.18, p-value = 4.4e-18), as well as suggested two additional loci close to genome-wide significance (rs2007361 in PSMA1, OR 0.91, p-value = 5.1e-8; and rs78625038 in GAN, OR 1.86, p-value = 5.9e-8). Gene-based association tests identified four genes linked to SSTIs: SLC12A2, PSMA1, GAN, and IL6R. The minor allele of rs3749748 reduced the gene expression of SLC12A2 primarily in monocytes and macrophages. Mendelian randomization analyses showed that increasing body mass index and lifetime smoking habits increased risk of SSTIs.

Interpretation

LINC0118/SLC12A2 was robustly associated with SSTI incidence and may exert its effect through reduced gene expression in monocytes and macrophages. Reducing tobacco smoking, overweight and obesity in the population may reduce the incidence of SSTIs.
A Harmonized Atlas of Spinal Cord Cell Types and Their Computational Classification
Authors: Russ Daniel E. , Patterson Cross Ryan B. , Li Li , Koch Stephanie C. , Matson Kaya J.E. , Levine Ariel J.
Published: September 2020

Single cell sequencing is transforming many fields of science but the vast amount of data it creates has the potential to both illuminate and obscure underlying biology. To harness the exciting potential of single cell data for the study of the mouse spinal cord, we have created a harmonized atlas of spinal cord transcriptomic cell types that unifies six independent and disparate studies into one common analysis. With the power of this large and diverse dataset, we reveal spinal cord cell type organization, validate a combinatorial set of markers for in-tissue spatial gene expression analysis, and optimize the computational classification of spinal cord cell types based on transcriptomic data. This work provides a comprehensive resource with unprecedented resolution of spinal cord cell types and charts a path forward for how to utilize transcriptomic data to expand our knowledge of spinal cord biology.
The dirty north: Evidence for multiple colonisations and Wolbachia infections shaping the genetic structure of the widespread butterflyPolyommatus icarusin the British Isles
Authors: Arif Saad , Gerth Michael , Hone-Millard William G. , Nunes Maria D. S. , Dapporto Leonardo , Shreeve Timothy G.
Published: September 2020

The paradigm of differentiation in southern refugia during glacial periods followed by expansions during interglacials, producing limited genetic diversity and population sub-division in northern areas, dominates European phylogeography. However, the existence of complex structured populations in formerly glaciated areas, and on islands connected to mainland areas during glacial maxima, call for alternative explanations. Here, we reconstruct the mtDNA phylogeography of the widespreadPolyommatus icarusbutterfly over its native range, with an emphasis on the formerly glaciated and connected British Isles. We found distinct geographical structuring ofCO1 mitotypes, with an ancient lineage restricted to the marginal European areas, including Northern Scotland and Outer Hebrides. We detected perfect mtDNA-Wolbachiaassociations in Northern Britain that support the possibility of at least two post-glacialWolbachia-mediated sweeps, suggesting a series of sequential replacement of mtDNA in the British Isles and potentially in Europe. Population genomic analysis, using ddRADSeq genomic markers, also reveal unexpected genetic structuring within Britain. However, weak mito-nuclear concordance suggests the potential for independent histories of nuclearversusmitochondrial genomes. We found clustering of genomic SNPs of French samples, with respect to those in the British Isles, is not consistent with a scenario of a single recolonisation. Taken together our mtDNA and ddRADseq observations are consistent with a history of at least two distinct colonisations, a phylogeographic scenario previously put forth to explain diversity and structuring in other British flora and fauna. Additionally, we also present preliminary evidence thatWolbachia-induced feminization may be occurring in the isolated population in the Outer Hebrides.
Benchmarking of numerical integration methods for ODE models of biological systems
Authors: Städter Philipp , Schälte Yannik , Schmiester Leonard , Hasenauer Jan , Stapor Paul L.
Published: September 2020

Ordinary differential equation (ODE) models are a key tool to understand complex mechanisms in systems biology. These models are studied using various approaches, including stability and bifurcation analysis, but most frequently by numerical simulations. The number of required simulations is often large, e.g., when unknown parameters need to be inferred. This renders efficient and reliable numerical integration methods essential. However, these methods depend on various hyperparameters, which strongly impact the ODE solution. Despite this, and although hundreds of published ODE models are freely available in public databases, a thorough study that quantifies the impact of hyperparameters on the ODE solver in terms of accuracy and computation time is still missing. In this manuscript, we investigate which choices of algorithms and hyperparameters are generally favorable when dealing with ODE models arising from biological processes. To ensure a representative evaluation, we considered 167 published models. Our study provides evidence that most ODEs in computational biology are stiff, and we give guidelines for the choice of algorithms and hyperparameters. We anticipate that our results will help researchers in systems biology to choose appropriate numerical methods when dealing with ODE models.
Multimodal imaging brain markers in early adolescence are linked with a physically active lifestyle
Authors: Salvan Piergiorgio , Wassenaar Thomas , Wheatley Catherine , Beale Nicholas , Cottaar Michiel , Papp Daniel , Bastiani Matteo , Fitzgibbon Sean , Duff Euguene , Andersson Jesper , Winkler Anderson M. , Douaud Gwenaëlle , Nichols Thomas E. , Smith Stephen , Dawes Helen , Johansen-Berg Heidi
Published: September 2020

The World Health Organization (WHO) promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and brain development are not fully understood. Here, we asked whether a brain – physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7-days physical activity, body-mass index, heart rate, and blood pressure. Using canonical correlation analysis we unravel a latent mode of brain – physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater grey matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity, covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence.

Significance statement

An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents’ level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain – body relationships in an effort to foster brain health at this crucial stage in development.
Cingulo-Opercular Control Network Supports Disused Motor Circuits in Standby Mode
Authors: Newbold Dillan J. , Gordon Evan M. , Laumann Timothy O. , Seider Nicole A. , Montez David F. , Gross Sarah J. , Zheng Annie , Nielsen Ashley N. , Hoyt Catherine R. , Hampton Jacqueline M. , Ortega Mario , Adeyemo Babatunde , Miller Derek B. , Van Andrew N. , Marek Scott , Schlaggar Bradley L. , Carter Alexandre R. , Kay Benjamin P. , Greene Deanna J. , Raichle Marcus E. , Petersen Steven E. , Snyder Abraham Z. , Dosenbach Nico U.F.
Published: September 2020

Whole-brain resting-state functional MRI (rs-fMRI) during two weeks of limb constraint revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula (1). Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.

Significance

Many studies have examined plasticity in the primary somatosensory and motor cortex during disuse, but little is known about how disuse impacts the brain outside of primary cortical areas. We leveraged the whole-brain coverage of resting-state functional MRI (rs-fMRI) to discover that disuse drives plasticity of distant executive control regions in the cingulo-opercular network (CON). Two complementary analyses, pulse censoring and pulse addition, demonstrated that increased functional connectivity between the CON and disused motor regions was driven by large, spontaneous pulses of activity in the CON and disused motor regions. These results point to a previously unknown role for the CON in supporting motor plasticity and reveal spontaneous activity pulses as a novel mechanism for reorganizing the brain’s functional connections.
A Geometric Theory Integrating Human Binocular Vision with Eye movement
Authors: Turski Jacek
Published: September 2020

Abstract

A theory of the binocular system with asymmetric eyes (AEs) is developed in the framework of bicentric perspective projections. The AE accounts for the eyeball’s global asymmetry produced by the foveal displacement from the posterior pole, the main source of the eye’s optical aberrations, and the crystalline lens’ tilt countering some of these aberrations. In this theory, the horopter curves, which specify retinal correspondence of binocular single vision, are conic sections resembling empirical horopters. This advances the classic model of empirical horopters as conic sections introduced in an ad hoc way by Ogle in 1932. In contrast to Ogle’s theory, here, anatomically supported horopteric conics vary with the AEs’ position in the visual plane of bifoveal fixations and their transformations are visualized in a computer simulation. Integrating horopteric conics with eye movements can help design algorithms for maintaining a stable perceptual world from visual information captured by a mobile robot’s camera-head. Further, this paper proposes a neurophysiologically meaningful definition for the eyes’ primary position, a concept which has remained elusive despite its theoretical importance to oculomotor research. Finally, because the horopteric conic’s shape is dependent on the AE’s parameters, this theory allows for changes in retinal correspondence which is usually considered preformed and stable.
The need for high-quality oocyte mitochondria at extreme ploidy dictates germline development
Authors: Colnaghi Marco , Pomiankowski Andrew , Lane Nick
Published: September 2020

Selection against deleterious mitochondrial mutations is facilitated by germline processes, lowering the risk of genetic diseases. How selection works is disputed: experimental data are conflicting and previous modelling work has not clarified the issues. Here we develop computational and evolutionary models that compare the outcome of selection at the level of individuals, cells and mitochondria. Using realisticde novomutation rates and germline development parameters, the evolutionary model predicts the observed prevalence of mitochondrial mutations and diseases in human populations. We show the importance of organelle-level selection, seen in the selective pooling of mitochondria into the Balbiani body, in achieving high-quality mitochondria at extreme ploidy in mature oocytes. Alternative mechanisms debated in the literature, bottlenecks and follicular atresia, are unlikely to account for the clinical data, because neither process effectively eliminates mitochondrial mutations under realistic conditions. Our findings explain the major features of female germline architecture, notably the longstanding paradox of over-proliferation of primordial germ cells followed by massive loss. The near-universality of these processes across animal taxa makes sense in light of the need to maintain mitochondrial quality at extreme ploidy in mature oocytes, in the absence of sex and recombination.
Single-vessel cerebral blood flow fMRI to map blood velocity by phase-contrast imaging
Authors: Chen Xuming , Jiang Yuanyuan , Choi Sangcheon , Pohmann Rolf , Scheffler Klaus , Kleinfeld David , Yu Xin
Published: September 2020

Current approaches to high-field fMRI provide two means to map hemodynamics at the level of single vessels in the brain. One is through changes in deoxyhemoglobin in venules, i.e., blood oxygenation level-dependent (BOLD) fMRI, while the second is through changes in arteriole diameter, i.e., cerebral blood volume (CBV) fMRI. Here we introduce cerebral blood flow (CBF)-fMRI, which uses high-resolution phase-contrast MRI to form velocity measurements of flow and demonstrate CBF-fMRI in single penetrating microvessels across rat parietal cortex. In contrast to the venule-dominated BOLD and arteriole-dominated CBV fMRI signal, the phase-contrast -based CBF signal changes are highly comparable from both arterioles and venules. Thus, we have developed a single-vessel fMRI platform to map the BOLD, CBV, and CBF from penetrating microvessels throughout the cortex. This high-resolution single-vessel fMRI mapping scheme not only enables the vessel-specific hemodynamic mapping in diseased animal models but also presents a translational potential to map vascular dementia in diseased or injured human brains with ultra-high field fMRI.

We established a high-resolution PC-based single-vessel velocity mapping method using the high field MRI. This PC-based micro-vessel velocity measurement enables the development of the single-vessel CBF-fMRI method. In particular, in contrast to the arteriole-dominated CBV and venule-dominated BOLD responses, the CBF-fMRI shows similar velocity changes in penetrating arterioles and venules in activated brain regions. Thus, we have built a noninvasive single-vessel fMRI mapping scheme for BOLD, CBV, and CBF hemodynamic parameter measurements in animals.
Differences in Chemo-signaling Compound-Evoked Brain Activity in Male and Female Young Adults: A Pilot Study in the Role of Sexual Dimorphism in Olfactory Chemo-Signaling
Authors: Ottesen Taylor D. , Davis Kevin C. , Hobbs Landon K. , Muncy Nathan M. , Stevens Nicholas M. , Anderson Malia , Johnson Paula , Doxey Christopher R. , Richter Kent , Wang Haonan , Hartley Randy , Kirwan C. Brock , Wisco Jonathan J.
Published: September 2020

Introduction

Previous studies have shown that putative pheromones 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST) cause activation in the preoptic area/anterior hypothalamus in men and women. Sex differences in neural activation patterns have been demonstrated when participants are subject to pheromone stimulation; however, whether other compounds give rise to similar neural activity has not been completely investigated.

Methods

Twenty-nine young adults [16 female (21.3+/−0.54; mean yrs+/−SE), 13 male (22.85+/−0.42)] participated in a 3-block design, where participants were exposed to a scent (lavender), a synthetic male pheromone (4,16-androstadien-3b-ol; ALD), and a synthetic female pheromone (1,3,5(10),16-Estratetraen-3-ol; EST) via an automated olfactometer. Whole-brain, high-resolution (1.8mm3) functional MRI data from a Siemens Trio 3T MRI scanner were collected during all blocks. Five adults were excluded due to excessive movement. MANOVA analysis, a 2 × 3 multivariate model and analysis of 2×2 effects between sex and subsets of stimuli was done for activation over the whole brain and small volumes involved in olfaction.

Results

Exploratory analysis of 2×2 effects between sex and subsets of stimuli exhibited significant interactions when assessing activations over the whole brain, and small volumes involved in olfaction. The left and right frontal poles (LFP, RFP) shows significant interaction when assessing sex with lavender and EST for whole brain analysis. For small volume analysis, the right orbitofrontal cortex (ROFC) exhibited a sex with lavender and ALD interaction, and a sex with lavender and EST interaction was observed in the left inferior frontal gyrus (LIFG). Main effects of sex, stimulus, or interaction show no differences analyzed using a 2 × 3 multivariate model.

Conclusion

The study shows there is a sexually dimorphic response in the olfactory system to pheromones not previously studied. Scents like lavender do not have this same response. These distinct functional differences in activation patterns may be a result of neural development and maturation differences between sexes. Future studies should expand this pilot study and involve a younger demographic to accurately determine the age at which the olfactory response differentiates between males and females.
Hybrid seed incompatibility in Capsella is connected to chromatin condensation defects in the endosperm
Authors: Dziasek Katarzyna , Simon Lauriane , Placette Clément Lafon , Laenen Benjamin , Wärdig Cecilia , Santos-González Juan , Slotte Tanja , Köhler Claudia
Published: September 2020

Hybridization of closely related plant species is frequently connected to endosperm arrest and seed failure, for reasons that remain to be identified. In this study, we investigated the molecular events accompanying seed failure in hybrids of the closely related species pairCapsella rubellaandC. grandiflora. Mapping of QTLs for the underlying cause of hybrid incompatibility in Capsella revealed three QTLs that were close to pericentromeric regions. This prompted us to investigate whether there are specific changes in heterochromatin associated with interspecific hybridizations. Indeed, we found that chromatin was less condensed in the endosperm, while the embryo was not affected. Loss of chromosome condensation was connected with a strong loss of CHG and CHH methylation and mitotic abnormalities. Genome-wide sequencing of hybrid endosperm revealed that the chromosome loss was random and was likely a consequence of reduced chromatin condensation. Consistent with reduced DNA methylation in hybrid endosperm, we found a disproportionate deregulation of genes located close to pericentromeric regions. Among those deregulated genes there were many potential targets of the AGAMOUS-LIKE transcription factor PHERES1, suggesting that reduced DNA methylation allows PHERES1 to hyperactivate its targets. Since the identified QTLs were also associated with pericentromeric regions, we conclude that relaxation of heterochromatin in response to interspecies hybridization exposes and activates loci leading to hybrid seed failure.