bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Obesity on Plastic Surgery Outcomes: A Systematic Review and Meta-analysis
Authors: Bigarella Lucas Goldmann , Ballardin Ana Carolina , Couto Luísa Serafini , de Ávila Ana Carolina Porciuncula , Ballotin Vinícius Remus , Ingracio Anderson Ricardo , Martini Matheus Piccoli
Published: January 2022

Background

Obesity is a potential risk factor for complications in plastic surgeries. However, the data presented by primary studies are contradictory.

Objectives

The aim of this study was to summarize and clarify the divergences in the literature to provide a better understanding of the impact of obesity in different plastic surgery procedures.

Methods

We conducted a systematic review and meta-analysis of the impact of obesity on plastic surgery outcomes. Searches were conducted in MEDLINE, LILACS, SciELO, Scopus, Embase, Web of Science, Opengrey.eu, and the Cochrane Database of Systematic Reviews. The primary outcomes assessed were surgical complications, medical complications, and reoperation rates. The secondary outcome assessed was patient satisfaction. Subgroup analysis was performed to investigate the impact of each BMI category on the outcomes.

Results

Ninety-three articles were included in the qualitative synthesis, and 91 were used in the meta-analysis. Obese participants were 1.62 times more likely to present any of the primary outcomes (95% CI, 1.48-1.77; P < 0.00001). The highest increase in risk among plastic surgery types was observed in cosmetic procedures (risk ratio [RR], 1.80; 95% CI, 1.43-2.32; P < 0.00001). Compared with normal-weight participants, overweight participants presented a significantly increased RR for complications (RR, 1.16; 95% CI, 1.07-1.27; P = 0.0004). Most authors found no relation between BMI and overall patient satisfaction.

Conclusions

Obesity leads to more complications and greater incidence of reoperation compared with nonobese patients undergoing plastic surgeries. However, this effect is not evident in reconstructive surgeries in areas of the body other than the breast.
Unraveling the potential of phenomic selection within and among diverse breeding material of maize (Zea mays L.)
Authors: Weiß Thea Mi , Zhu Xintian , Leiser Willmar L , Li Dongdong , Liu Wenxin , Schipprack Wolfgang , Melchinger Albrecht E , Hahn Volker , Würschum Tobias
Published: January 2022

Genomic selection is a well-investigated approach that facilitates and supports selection decisions for complex traits and has meanwhile become a standard tool in modern plant breeding. Phenomic selection has only recently been suggested and uses the same statistical procedures to predict the targeted traits but replaces marker data with near-infrared spectroscopy data. It may represent an attractive low-cost, high-throughput alternative but has not been sufficiently studied until now. Here, we used 400 genotypes of maize (Zea mays L.) comprising elite lines of the Flint and Dent heterotic pools as well as 6 Flint landraces, which were phenotyped in multienvironment trials for anthesis-silking-interval, early vigor, final plant height, grain dry matter content, grain yield, and phosphorus concentration in the maize kernels, to compare the predictive abilities of genomic as well as phenomic prediction under different scenarios. We found that both approaches generally achieved comparable predictive abilities within material groups. However, phenomic prediction was less affected by population structure and performed better than its genomic counterpart for predictions among diverse groups of breeding material. We therefore conclude that phenomic prediction is a promising tool for practical breeding, for instance when working with unknown and rather diverse germplasm. Moreover, it may make the highly monopolized sector of plant breeding more accessible also for low-tech institutions by combining well established, widely available, and cost-efficient spectral phenotyping with the statistical procedures elaborated for genomic prediction - while achieving similar or even better results than with marker data.
Caenorhabditis elegans transposable elements harbor diverse transcription factor DNA-binding sites
Authors: Garrigues Jacob M , Pasquinelli Amy E
Published: January 2022

Transposable elements are powerful agents of evolution that can diversify transcriptional programs by distributing transcription factor DNA-binding sites throughout genomes. To investigate the extent that transposable elements provide transcription factor-binding motifs in Caenorhabditis elegans, we determined the genomic positions of DNA-binding motifs for 201 different transcription factors. Surprisingly, we found that almost all examined transcription factors have binding motifs that reside within transposable elements, and all types of transposable elements have at least 1 instance of a transcription factor motif, demonstrating that transposable elements provide previously unappreciated numbers of transcription factor-binding motifs to the C. elegans genome. After determining the occurrence of transcription factor motifs in transposable elements relative to the rest of the genome, we identified DNA-binding motifs for 45 different transcription factors that are greater than 20-fold enriched within transposable elements compared to what would be expected by chance. Consistent with potential functional roles for these transposable element-enriched transcription factor-binding sequences, we determined that all transcription factor motif types found in transposable elements have instances of residing within accessible chromatin sites associated with transcription factor binding. The overwhelming majority of transcription factor-binding motifs located within transposable elements associate with their cognate transcription factors, suggesting extensive binding of transcription factors to sequences within transposable elements. In addition, transposable elements with accessible or transcription factor-bound motifs reside in the putative promoter regions of approximately 12% of all protein-coding genes, providing widespread possibilities for influencing gene expression. This work represents the first comprehensive analysis of transposable element–transcription factor interactions in C. elegans and demonstrates that transposable element-provided transcription factor-binding sites are prevalent in this important model organism.
Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston
Authors: Seligman Benjamin J , Berry Sarah D , Lipsitz Lewis A , Travison Thomas G , Kiel Douglas P
Published: January 2022

Age-associated changes in DNA methylation have been implicated as 1 mechanism to explain the development of frailty; however, previous cross-sectional studies of epigenetic age acceleration (eAA) and frailty have had inconsistent findings. Few longitudinal studies have considered the association of eAA with change in frailty. We sought to determine the association between eAA and change in frailty in the MOBILIZE Boston cohort. Participants were assessed at 2 visits 12–18 months apart. Intrinsic, extrinsic, GrimAge, and PhenoAge eAA were assessed from whole-blood DNA methylation at baseline using the Infinium 450k array. Frailty was assessed by a continuous frailty score based on the frailty phenotype and by frailty index (FI). Analysis was by correlation and linear regression with adjustment for age, sex, smoking status, and body mass index. Three hundred and ninety-five participants with a frailty score and 431 with an FI had epigenetic and follow-up frailty measures. Mean (standard deviation) ages were 77.8 (5.49) and 77.9 (5.47) for the frailty score and the FI cohorts respectively, and 232 (58.7%) and 257 (59.6%) were female. All participants with epigenetic data identified as White. Baseline frailty score was not correlated with intrinsic or extrinsic eAA, but was correlated with PhenoAge and, even after adjustment for covariates, GrimAge. Baseline FI was correlated with extrinsic, GrimAge, and PhenoAge eAA with and without adjustment. No eAA measure was associated with change in frailty, with or without adjustment. Our results suggest that no eAA measure was associated with change in frailty. Further studies should consider longer periods of follow-up and repeated eAA measurement.
Have the 1999 Izmit–Düzce earthquakes influenced the motion and seismicity of the Anatolian microplate?
Authors: Martin de Blas J , Iaffaldano G , Calais E
Published: January 2022

In the current plate tectonics paradigm, relative plate motions are assumed to remain unperturbed by temporal stress changes occurring during the seismic cycle, whereby stress slowly built up along tectonic plate boundaries is suddenly released by rapid fault slip during earthquakes. However, direct observations that could challenge such a tenet have not been identified so far. Here we show that the rigid motion of the whole Anatolian microplate, measured using space geodetic techniques, was altered by the stress released during the 1999 Izmit–Düzce earthquakes, which ruptured along the North Anatolian Fault. This kinematic change requires a torque change that is in agreement with the torque change imparted upon the Anatolian microplate by the Izmit–Düzce coseismic stress release. This inference holds across realistic ranges of data noise and controlling parameters, and is not hindered by active deformation in western Anatolia. These results suggest the existence of a whole-plate kinematic signal associated with the stress released by large earthquakes.
Prevalence of doravirine cross-resistance in HIV-infected adults who failed first-line ART in China, 2014–18
Authors: Sun Zhuoqun , Lan Yun , Liang Shujia , Wang Jing , Ni Mingjian , Zhang Xia , Yu Fengting , Chen Meiling , Zhang Hanxi , Yan Liting , Cai Weiping , Lan Guanghua , Ma Ye , Zhang Fujie
Published: January 2022

Objectives

To evaluate the prevalence and characteristics of doravirine resistance and cross-resistance in patients who failed first-line ART in China.

Methods

From 2014 to 2108, 4132 patients from five provinces were tested for drug resistance by genotypic resistance testing. Drug resistance mutations were assessed using the Stanford HIVdb algorithm Version 9.0. Sequences classified as having low-level, intermediate and high-level resistance were defined as having drug resistance.

Results

Overall, the prevalence of doravirine and other NNRTIs cross-resistance was 69.5%, with intermediate and high-level resistance accounting for 56.4%. Doravirine resistance highly correlated with efavirenz (r = 0.720) and nevirapine (r = 0.721) resistance and moderately correlated with etravirine (r = 0.637) and rilpivirine (r = 0.692) resistance. The most frequent doravirine-associated resistance mutations were V106M (8.7%), K101E (6.8%) and P225H (5.1%). High-level resistance was mainly due to Y188L (3.2%) and M230L (2.7%). There were significant differences between genotypes and provinces. Compared with CRF01_AE, CRF07_BC (OR = 0.595, 95% CI = 0.546–0.648) and CRF08_BC (OR = 0.467, 95% CI = 0.407–0.536) were associated with lower risks of doravirine resistance. Conversely, genotype A (OR = 3.003, 95% CI = 1.806–4.991) and genotype B (OR = 1.250, 95% CI = 1.021–1.531) were associated with higher risks of doravirine resistance. The risk of doravirine resistance was significantly lower in Xinjiang compared with other provinces.

Conclusions

In China, the prevalence of doravirine cross-resistance among patients who have failed first-line ART is high. Therefore, doravirine should not be used blindly without genotypic resistance testing and is not recommended for people who have failed first-line NNRTI-based ART.
Self- and Response Efficacy Information in Fear Appeals: A Meta-Analysis
Authors: Bigsby Elisabeth , Albarracín Dolores
Published: January 2022

Fear appeals are designed to inspire intended and actual actions to avert a danger. Although prior meta-analyses report that the average effect of fear appeals is moderately positive, the role of efficacy information is not completely understood. Prior work and fear appeal theories have argued that the presence of both response and self-efficacy information improves fear appeal success but the individual impacts of each have not been properly estimated. A meta-analysis (k = 158, N = 19,736) was conducted to examine the individual and combined effects of response and self-efficacy information contained in fear appeals on behavioral intentions and behaviors. Estimating the impact of fear appeals relative to low and no fear controls, the meta-analysis showed that fear appeals had a stronger influence on behavioral outcomes when they included positive response efficacy information but did not vary as a function of including self-efficacy information or negative response efficacy information.
Practical guidance for telemedicine use in neuro-oncology
Authors: Strowd Roy E , Dunbar Erin M , Gan Hui K , Kurz Sylvia , Jordan Justin T , Mandel Jacob J , Mohile Nimish A , Nevel Kathryn S , Taylor Jennie W , Ullrich Nicole J , Welch Mary R , Wasilewski Andrea , Mrugala Maciej M
Published: January 2022

While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations.
Trimethoprim-Sulfamethoxazole Versus Levofloxacin for Stenotrophomonas maltophilia Infections: A Retrospective Comparative Effectiveness Study of Electronic Health Records from 154 US Hospitals
Authors: Sarzynski Sadia H , Warner Sarah , Sun Junfeng , Matsouaka Roland , Dekker John P , Babiker Ahmed , Li Willy , Lai Yi Ling , Danner Robert L , Fowler Vance G , Kadri Sameer S
Published: January 2022

Background

Trimethoprim-sulfamethoxazole (TMP-SMX) is considered first-line therapy for Stenotrophomonas maltophilia infections based on observational data from small studies. Levofloxacin has emerged as a popular alternative due to tolerability concerns related to TMP-SMX. Data comparing levofloxacin to TMP-SMX as targeted therapy are lacking.

Methods

Adult inpatient encounters January 2005 through December 2017 with growth of S maltophilia in blood and/or lower respiratory cultures were identified in the Cerner Healthfacts database. Patients included received targeted therapy with either levofloxacin or TMP-SMX. Overlap weighting was used followed by downstream weighted regression. The primary outcome was adjusted odds ratio (aOR) for in-hospital mortality or discharge to hospice. The secondary outcome was number of days from index S maltophilia culture to hospital discharge.

Results

Among 1581 patients with S maltophilia infections, levofloxacin (n = 823) displayed statistically similar mortality risk (aOR, 0.76 [95% confidence interval {CI}, .58–1.01]; P = .06) compared to TMP-SMX (n = 758). Levofloxacin (vs TMP-SMX) use was associated with a lower aOR of death in patients with lower respiratory tract infection (n = 1452) (aOR, 0.73 [95% CI, .54–.98]; P = .03) and if initiated empirically (n = 89) (aOR, 0.16 [95% CI, .03–.95]; P = .04). The levofloxacin cohort had fewer hospital days between index culture collection and discharge (weighted median [interquartile range], 7 [4–13] vs 9 [6–16] days; P < .0001).

Conclusions

Based on observational evidence, levofloxacin is a reasonable alternative to TMP-SMX for the treatment of bloodstream and lower respiratory tract infections caused by S maltophilia.
Estimates of Presumed Population Immunity to SARS-CoV-2 by State in the United States, August 2021
Authors: Stoner Marie C D , Angulo Frederick J , Rhea Sarah , Brown Linda Morris , Atwell Jessica E , Nguyen Jennifer L , McLaughlin John M , Swerdlow David L , MacDonald Pia D M
Published: January 2022

Background

Information is needed to monitor progress toward a level of population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sufficient to disrupt viral transmission. We estimated the percentage of the US population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021.

Methods

Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates with a range of population immunity thresholds.

Results

In our main analysis, which was the most optimistic scenario, presumed population immunity varied among states (43.1% to 70.6%), with 19 states with ≤60% of their population having been infected or vaccinated. Four states had presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (≥78%).

Conclusions

The United States remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.
The diagnostic value of sleep and vigilance tests in central disorders of hypersomnolence
Authors: Mathis Johannes , Andres Daniel , Schmitt Wolfgang J , Bassetti Claudio L , Hess Christian W , Schreier David R
Published: January 2022

Study Objectives

This retrospective cross-sectional observational study explored the diagnostic value of selected sleep and vigilance tests (SVT) beyond the multiple sleep latency test to differentiate between various central disorders of hypersomnolence (CDH) and fatigue syndromes.

Methods

Data from patients who underwent the multiple sleep latency test and at least one additional SVT were extracted from the Bern sleep database (1997–2018). One thousand three hundred fifty-two patients with a CDH (106 narcolepsy type 1, 90 narcolepsy type 2, 119 idiopathic hypersomnia, 192 nonorganic hypersomnia, 205 insufficient sleep syndrome), fatigue syndromes (n = 183), and a subgroup of patients with sleep apnea (n = 457) were analyzed. Classification based on SVT parameters was compared with the final clinical diagnosis serving as a reference.

Results

An overall model predicted the final diagnosis in 49.5% of patients. However, for the pairwise differentiation of two clinically suspected diagnoses, many SVT parameters showed a sensitivity and specificity above 70%. While the overall discrimination power of the multiple sleep latency test was slightly better than the one of the maintenance of wakefulness test, the latter differentiated best between narcolepsy and idiopathic hypersomnia with prolonged sleep need. Disproportionally poor results in reaction tests (e.g. steer clear test), despite comparable or lower sleepiness levels (SLAT, WLAT), were valuable for differentiating nonorganic hypersomnia from idiopathic hypersomnia/sleep insufficiency syndrome.

Conclusion

This study demonstrates how the combination of a careful clinical assessment and a selection of SVTs can improve the differentiation of CDH, whereas it was not possible to establish an overall prediction model based on SVTs alone.
Order matters: sleep spindles contribute to memory consolidation only when followed by rapid-eye-movement sleep
Authors: Strauss Mélanie , Griffon Lucie , Van Beers Pascal , Elbaz Maxime , Bouziotis Jason , Sauvet Fabien , Chennaoui Mounir , Léger Damien , Peigneux Philippe
Published: January 2022

Sleep is known to benefit memory consolidation, but little is known about the contribution of sleep stages within the sleep cycle. The sequential hypothesis proposes that memories are first replayed during nonrapid-eye-movement (NREM or N) sleep and then integrated into existing networks during rapid-eye-movement (REM or R) sleep, two successive critical steps for memory consolidation. However, it lacks experimental evidence as N always precedes R sleep in physiological conditions. We tested this sequential hypothesis in patients with central hypersomnolence disorder, including patients with narcolepsy who present the unique, anti-physiological peculiarity of frequently falling asleep in R sleep before entering N sleep. Patients performed a visual perceptual learning task before and after daytime naps stopped after one sleep cycle, starting in N or R sleep and followed by the other stage (i.e. N-R vs. R-N sleep sequence). We compared over-nap changes in performance, reflecting memory consolidation, depending on the sleep sequence during the nap. Thirty-six patients who slept for a total of 67 naps were included in the analysis. Results show that sleep spindles are associated with memory consolidation only when N is followed by R sleep, that is in physiologically ordered N-R naps, thus providing support to the sequential hypothesis in humans. In addition, we found a negative effect of rapid-eye-movements in R sleep on perceptual consolidation, highlighting the complex role of sleep stages in the balance to remember and to forget.
C

0,
α

boundary regularity for the pressure in weak solutions of the 2
d
Euler equations
Authors: Bardos Claude W. , Titi Edriss S.
Published: January 2022

The purpose of this article is to give a complete proof of a

C

0
,
α

regularity result for the pressure for weak solutions of the two-dimensional ‘incompressible Euler equations’ when the fluid velocity enjoys the same type of regularity in a compact simply connected domain with

C
2

boundary. To accomplish our result, we realize that it is compulsory to introduce a new weak formulation for the boundary condition of the pressure, which is consistent with, and equivalent to, that of classical solutions.

This article is part of the theme issue ‘Scaling the turbulence edifice (part 1)’.
Psychrobacter halodurans sp. nov. and Psychrobacter coccoides sp. nov., two new slightly halophilic bacteria isolated from marine sediment
Authors: Shang Dan-Dan , Yang Gui-Jun , Chen Guan-Jun , Du Zong-Jun
Published: January 2022

In this study, two bacterial strains designated F2608T and F1192T, isolated from marine sediment sampled in Weihai, PR China, were characterized using a polyphasic approach. Strains were aerobic, Gram-stain-negative and motile. According to the results of phylogenetic analyses based on their 16S rRNA genes, these two strains should be classified under the genus

Psychrobacter

and they both show <98.5% sequence similarity to their closest relative,

Psychrobacter celer

JCM 12601T. Moreover, strain F2608T showed 97.5% sequence similarity to strain F1192T. Strain F2608T grew at 4–37 °C (optimum, 30–33 °C) and at pH 6.0–9.0 (optimum, pH 6.5–7.0) in the presence of 0–12% (w/v) NaCl (optimum, 4.0–5.0%). Strain F1192T grew at 4–37 °C (optimum, 30 °C) and at pH 5.5–9.0 (optimum, pH 7.0–7.5) in the presence of 0.5–12% (w/v) NaCl (optimum, 3.0–4.0%). The genomic DNA G+C contents of strain F2608T and strain F1192T were 47.4 and 44.9 %, respectively. Genomic characteristics including average nucleotide identity and digital DNA–DNA hybridization values clearly separated strain F2608T from strain F1192T. The sole isoprenoid quinone in these two strains was ubiquinone 8 and the major cellular fatty acids (>10.0%) were C18:1
ω9c and C17:1
ω8c. The major polar lipids of these two strains were phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. Based on the results of polyphasic analysis, the two strains represent two novel species of the genus

Psychrobacter

, for which the names Psychrobacter halodurans sp. nov. and Psychrobacter coccoides sp. nov. are proposed. The type strains are F2608T (=MCCC 1K05774T=KCTC 82766T) and F1192T (=MCCC 1K05775T=KCTC 82765T), respectively.
Real-time multiplex PCR assay reveals the increased prevalence of Campylobacter spp and diarrhoeagenic Escherichia coli in humans from Vellore, South India
Authors: Lakshmi SS Jaya , Prabaa MS Dhiviya , Murugan Dhivya , Anandan Shalini , Veeraraghavan Balaji
Published: January 2022

Introduction. Bacterial dysentery is one of the greatest causes of morbidity and mortality worldwide.

Campylobacter

spp. and diarrhoeagenic

Escherichia coli

(DEC) are recognised as the most common causes of bacterial enteritis in developing countries including India.

Hypothesis/Gap statement. Rapid and accurate identification of dysentery causing organisms using molecular methods is essential for better disease management, epidemiology and outbreak investigations.

Aim. In view of the limited information available on the dysentery causing agents like

Campylobacter

spp., enterohemorrhagic

E. coli

(EHEC)/enteropathogenic

E. coli

(EPEC) and enteroinvasive

E. coli

(EIEC)/

Shigella

in India, this study was undertaken to investigate the presence of these pathogens in human and poultry stool samples by molecular methods.

Methodology. In total, 400 human stool samples and 128 poultry samples were studied. Microaerophilic culture along with real-time multiplex PCR with the targets specific to the genus

Campylobacter

,

Campylobacter jejuni

,

Campylobacter coli

, EHEC, EPEC and EIEC/

Shigella

was performed. Further species confirmation was done using MALDI-TOF MS.

Results. On microaerophilic culture,

C. coli

was isolated in one human sample and two

C. jejuni

and one

C. fetus

in poultry samples. On PCR analysis, among human stool samples, typical EPEC (42%) was predominantly seen followed by

Campylobacter

spp. (19%) and EIEC/

Shigella

(10%). In contrast,

Campylobacter

spp. (41%) was predominant in poultry samples, followed by typical EPEC (26%) and EIEC/

Shigella

(9%). Poly-infections with

Campylobacter

spp. and DEC were also observed among both sources.

Conclusion. The present study documented the increased prevalence of

Campylobacter

spp. in humans compared with the results of previous studies from India. Typical EPEC was found to be predominant in children less than 5 years of age in this study. The high prevalence of coinfections in the current study indicates that a multiple aetiology of diarrhoea is common in our settings.
The immunopeptidome from a genomic perspective: Establishing immune-relevant regions for cancer vaccine design
Authors: Bedran Georges , Wang Tongjie , Pankanin Dominika , Weke Kenneth , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O’Neill Robert , Brennan Paul M. , Symeonides Stefan , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: January 2022

A longstanding disconnect between the growing number of MHC Class I immunopeptidomic studies and genomic medicine hinders cancer vaccine design. We develop COD-dipp to genomically map the full spectrum of detected canonical and non-canonical (non-exonic) MHC Class I antigens from 26 cancer studies. We demonstrate that patient mutations in regions overlapping physically identified antigens better predict immunotherapy response when compared to neoantigen predictions. We suggest a vaccine design approach using 140,966 highly immune-visible regions of the genome annotated by their expression and haplotype frequency in the human population. These regions tend to be highly conserved, mutated in cancer and harbor 7.8 times more immunogenicity. Intersecting pan-cancer mutations with these immune surveilled regions revealed a potential to create off-the-shelf multi-epitope vaccines against public neoantigens. Here we release COD-dipp, a cancer vaccine toolkit as a web-application (https://www.proteogenomics.ca/COD-dipp) and open-source high-throughput resource.
Maternal immune activation accelerates puberty initiation and alters mechanical allodynia in male and female C57BL6/J mice
Authors: Zhao Xin , Erickson Mary , Mohammed Ruqayah , Kentner Amanda C.
Published: January 2022

The mechanisms that link maternal immune activation (MIA) with the onset of neurodevelopmental disorders remain largely unclear. Accelerated puberty is also associated with a heightened risk for psychopathology in later life but there is a dearth of evidence on the impacts of maternal infection on pubertal timing. We examined the effects of MIA on reproductive development, mechanical allodynia, and sensorimotor gating in juvenile, adolescent, and adult male and female mice. Moreover, we investigated hypothalamic neural markers associated with the reproductive and stress axes. Finally, we tested the mitigating effects of environmental enrichment (EE), which has clinical relevancy in human rehabilitation settings. Our results show that administration of polyinosinic-polycytidylic acid (poly(I:C)) on gestational day 12.5 led to early preputial separation, vaginal openings, and age of first estrus in offspring. MIA exposure altered pain sensitivity across development and modestly altered prepulse inhibition. The downregulation ofNr3c1andOprkmRNA in the hypothalamus of juvenile mice suggests that MIA’s effects may be mediated through disruption of hypothalamic-pituitary-adrenal axis activity. In contrast, life-long housing with EE rescued many of these MIA-induced consequences. Overall, our findings suggest that accelerated puberty may be associated with the deleterious effects of infection during pregnancy and the onset of psychopathology.
Automated atlas-based multi-label fetal cardiac vessel segmentation in Congenital Heart Disease
Authors: Gilliland Paula Ramirez , Uus Alena , van Poppel Milou P.M. , Grigorescu Irina , Steinweg Johannes K. , Lloyd David F.A. , Pushparajah Kuberan , King Andrew P. , Deprez Maria
Published: January 2022

Congenital heart disease (CHD) is the most commonly diagnosed birth defect. T2w black blood MRI provides optimal vessel visualisation, aiding prenatal CHD diagnosis. Common clinical practice involves manual segmentation of fetal heart and vessels for visualisation and reporting purposes.

We propose an automated multi-label fetal cardiac vessels deep learning segmentation approach for T2w black blood MRI. Our network is trained using single-label manual segmentations obtained through current clinical practice, combined with a multi-label anatomical atlas with desired multi-label segmentation protocol. Our framework combines deep learning label propagation with 3D residual U-Net segmentation to produce high-quality multi-label output well adapted to the individual subject anatomy.

We train and evaluate the network using forty fetal subjects with suspected coarctation of the aorta, achieving a dice score of 0.79 ± 0.02 for the fetal cardiac vessels region. The proposed network outperforms the label propagation and achieves a statistically equivalent performance to a 3D residual U-Net trained exclusively on manual single-label data (p-value>0.05). This multi-label framework therefore represents an advancement over the single-label approach, providing label-specific anatomical information, particularly useful for assessing specific anomaly areas in CHD.
Activity of Estrogen Receptor β Agonists in Therapy-Resistant Estrogen Receptor-Positive Breast Cancer
Authors: Datta Jharna , Willingham Natalie , Manouchehri Jasmine M. , Schnell Patrick , Sheth Mirisha , David Joel J. , Kassem Mahmoud , Wilson Tyler A. , Radomska Hanna S. , Coss Christopher C. , Bennett Chad E. , Ganju Ramesh K. , Sardesai Sagar D. , Lustberg Maryam , Ramaswamy Bhuvaneswari , Stover Daniel G. , Cherian Mathew A.
Published: January 2022

Background

Among women, breast cancer is the leading cause of cancer-related death worldwide. Estrogen receptor α positive (ERα+) breast cancer accounts for 70% of all breast cancer subtypes. Although ERα+ breast cancer initially responds to estrogen deprivation or blockade, resistance emergence compelling the use of more aggressive therapies. While ERα is a driver in ERα+ breast cancer, ERβ plays an inhibitory role in several different cancer types. To date, the lack of highly selective ERβ agonists without ERα activity has limited the exploration of ERβ activation as a strategy for ERα+ breast cancer.

Methods

We measured expression levels of ESR1 and ESR2 genes in immortalized mammary epithelial cells and different breast cancer cell lines. The viability of ERα+ breast cancer cell lines upon treatments with specific ERβ agonists, including OSU-ERb-12 and LY500307 was assessed. The specificity of the ERβ agonists, OSU-ERb-12 and LY500307, was confirmed by reporter assays. The effects of the agonists on cell proliferation, cell cycle, apoptosis, colony formation, cell migration, and expression of tumor suppressor proteins were analyzed. The expression of ESR2 and genes containing ERE-AP1 composite response elements was examined in ERα+ human breast cancer samples to determine the correlation between ESR2 expression and overall survival and that of putative ESR2 regulated genes.

Results

In this study, we demonstrate the efficacy of highly selective ERβ agonists in ERα+ breast cancer cell lines and drug-resistant derivatives. ERβ agonists blocked cell proliferation, migration and colony formation; and induced apoptosis and S and/or G2/M cell cycle arrest of ERα+ breast cancer cell lines. Also, increases in the expression of the key tumor suppressors FOXO1 and FOXO3a were noted. Importantly, the strong synergy between ERβ agonists and ERα antagonists suggested that the efficacy of ERβ agonists is maximized by combination with ERα blockade. Lastly, ESR2 (ERβ gene) expression was negatively correlated with ESR1 (ERα gene) and CCND1 RNA expression in human metastatic ER+/HER2-breast cancer samples.

Conclusion

Our results demonstrate that highly selective ERβ agonists attenuate the viability of ERα+ breast cancer cell lines in vitro and suggest that this therapeutic strategy merits further evaluation for ERα+ breast cancer.
In vivo Biomechanical Assessment of Iridial Deformations and Muscle Contractions in Human Eyes
Authors: Safa Babak N. , Fard Mohammad Reza Bahrani , Ethier C. Ross
Published: January 2022

The iris is a muscular organ whose deformations can cause primary angle-closure glaucoma (PACG), a leading cause of blindness. PACG risk assessment does not consider iridial biomechanical factors, despite their expected influence on iris deformations. Here we exploited an existing biometric data set consisting of near-infrared movies acquired during the pupillary light reflex (PLR) as a unique resource to study iris biomechanics. The PLR caused significant (>100%) and essentially spatially uniform radial strains in the iris in vivo, consistent with previous findings. Inverse finite element modeling showed that sphincter muscle tractions were c. 5-fold greater than iridial stroma stiffness (range 4- to 13-fold, depending on sphincter muscle size). This muscle traction is greater than has been previously estimated, which may be due to methodological differences and/or to different patient populations in our study (European descent) vs. previous studies (Asian); the latter possibility is of particular interest due to differential incidence rates of PACG in these populations. Our methodology is fast and inexpensive and may be a useful tool in understanding biomechanical factors contributing to PACG.
Extant Sequence Reconstruction: The accuracy of ancestral sequence reconstructions evaluated by extant sequence cross-validation
Authors: Sennett Michael A. , Theobald Douglas L.
Published: January 2022

Ancestral sequence reconstruction (ASR) is a phylogenetic method widely used to analyze the properties of ancient biomolecules and to elucidate mechanisms of molecular evolution. Despite its increasingly widespread application, the accuracy of ASR is currently unknown, as it is generally impossible to compare resurrected proteins to the true ancestors. Which evolutionary models are best for ASR? How accurate are the resulting inferences? Here we answer these questions using a cross-validation method to reconstruct each extant sequence in an alignment with ASR methodology, a method we term “extant sequence reconstruction” (ESR). We thus can evaluate the accuracy of ASR methodology by comparing ESR reconstructions to the corresponding known true sequences.

We find that a common measure of the quality of a reconstructed sequence, the average probability, is indeed a good estimate of the fraction of correct amino acids when the evolutionary model is accurate or overparameterized. However, the average probability is a poor measure for comparing reconstructions from different models, because, surprisingly, a more accurate phylogenetic model often results in reconstructions with lower probability. While better (more predictive) models may produce reconstructions with lower sequence identity to the true sequences, better models nevertheless produce reconstructions that are more biophysically similar to true ancestors. In addition, we find that a large fraction of sequences sampled from the reconstruction distribution may have fewer errors than the single most probable (SMP) sequence reconstruction, despite the fact that the SMP has the lowest expected error of all possible sequences. Our results emphasize the importance of model selection for ASR and the usefulness of sampling sequence reconstructions for analyzing ancestral protein properties. ESR is a powerful method for validating the evolutionary models used for ASR and can be applied in practice to any phylogenetic analysis of real biological sequences. Most significantly, ESR uses ASR methodology to provide a general method by which the biophysical properties of resurrected proteins can be compared to the properties of the true protein.
A giant virus genome is densely packaged by stable nucleosomes within virions
Authors: Bryson Terri D. , De Ioannes Pablo , Valencia-Sánchez Marco Igor , Henikoff Jorja G. , Talbert Paul B. , Scola Bernard La , Armache Karim-Jean , Henikoff Steven
Published: January 2022

The two doublet histones of Marseillevirus are distantly related to the four eukaryotic core histones and wrap 121 basepairs of DNA to form remarkably similar nucleosomes. By permeabilizing Marseillevirus virions and performing genome-wide nuclease digestion, chemical cleavage and mass spectrometry assays, we find that the higher-order organization of Marseillevirus chromatin fundamentally differs from that of eukaryotes. Marseillevirus nucleosomes fully protect DNA within virions as closely abutted 121-bp DNA wrapped cores without linker DNA or phasing along genes. Likewise, we observed that a large fraction of the nucleosomes reconstituted onto multi-copy tandem repeats of a nucleosome positioning sequence are tightly packed. Dense promiscuous packing of fully wrapped nucleosomes rather than “beads-on-a-string” with genic punctuation represents a new mode of DNA packaging by histones. We suggest that doublet histones have evolved for viral genome protection and may resemble an early stage of histone differentiation leading to the eukaryotic octameric nucleosome.
Divergent selection predating the Last Glacial Maximum mainly acted on macro-phenotypes in Norway spruce
Authors: Tiret M. , Olsson L. , Grahn T. , Karlsson B. , Milesi P. , Lascoux M. , Lundqvist S.-O. , García-Gil M.R.
Published: January 2022

The current distribution and population structure of many species were, to a large extent, shaped by cycles of isolation in glacial refugia and subsequent population expansions. Isolation in, and post-glacial expansion through heterogeneous environments led to either neutral or adaptive divergence. Norway spruce is no exception, and its current distribution is the consequence of a constant interplay between evolutionary and demographic processes. We investigated population differentiation and adaptation of Norway spruce for juvenile growth, diameter of the stem, wood density and tracheid traits at breast height. Data from 4,461 phenotyped and genotyped Norway spruce from 396 half-sib families in two progeny tests were used to test for divergent selection in the framework of QSTvs FST. We show that the macroscopic resultant trait (stem diameter), unlike its microscopic components (tracheid dimensions) and juvenile growth, was under divergent selection that predated the Last Glacial Maximum. Altogether, the current variation in these phenotypic traits in Norway spruce is better explained by local adaptation to ancestral environments than to current ones, where populations were partly pre-adapted, mainly through growth-related traits.
Operational status of the X-ray powder diffraction beamline at the SESAME synchrotron
Authors: Abdellatief Mahmoud , Najdawi Mohammad Al , Momani Yazeed , Aljamal Basil , Abbadi Anas , Harfouche Messaoud , Paolucci Giorgio
Published: January 2022

The Materials Science (MS) beamline at SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East), dedicated to the X-ray powder diffraction technique, started its operational phase in December 2020 by hosting its first users. The MS endstation comprises a two-circle diffractometer coupled with a PILATUS 300K area detector, with which direct beam images are collected and compared with the initial ray-tracing simulation results. We present a detailed description of the beamline components and the experimental characterization of the main instrumental parameters relying on the instrumental profile and the angular resolution. A representative example for microstructure investigations of a nanocrystalline material is demonstrated.
High-speed free-run ptychography at the Australian Synchrotron
Authors: Jones Michael W. M. , van Riessen Grant A. , Phillips Nicholas W. , Schrank Christoph E. , Hinsley Gerard N. , Afshar Nader , Reinhardt Juliane , de Jonge Martin D. , Kewish Cameron M.
Published: January 2022

Over the last decade ptychography has progressed rapidly from a specialist ultramicroscopy technique into a mature method accessible to non-expert users. However, to improve scientific value ptychography data must reconstruct reliably, with high image quality and at no cost to other correlative methods. Presented here is the implementation of high-speed ptychography used at the Australian Synchrotron on the XFM beamline, which includes a free-run data collection mode where dead time is eliminated and the scan time is optimized. It is shown that free-run data collection is viable for fast and high-quality ptychography by demonstrating extremely high data rate acquisition covering areas up to 352 000 µm2 at up to 140 µm2 s−1, with 13× spatial resolution enhancement compared with the beam size. With these improvements, ptychography at velocities up to 250 µm s−1 is approaching speeds compatible with fast-scanning X-ray fluorescence microscopy. The combination of these methods provides morphological context for elemental and chemical information, enabling unique scientific outcomes.
Implementation of wedged-serial protein crystallography at PROXIMA-1
Authors: Chaussavoine Igor , Isabet Tatiana , Lener Robin , Montaville Pierre , Vasireddi Ramakrishna , Chavas Leonard M. G.
Published: January 2022

An approach for serial crystallography experiments based on wedged-data collection is described. This is an alternative method for recording in situ X-ray diffraction data on crystalline samples efficiently loaded in an X-ray compatible microfluidic chip. Proper handling of the microfluidic chip places crystalline samples at geometrically known positions with respect to the focused X-ray interaction area for serial data collection of small wedges. The integration of this strategy takes advantage of the greatly modular sample environment available on the endstation, which allows access to both in situ and more classical cryo-crystallography with minimum time loss. The method represents another optional data collection approach that adds up to the already large set of methods made available to users. Coupled with the advances in processing serial crystallography data, the wedged-data collection strategy proves highly efficient in minimizing the amount of required sample crystals for recording a complete dataset. From the advances in microfluidic technology presented here, high-throughput room-temperature crystallography experiments may become routine and should be easily extended to industrial use.
Scanning structural mapping at the Life Science X-ray Scattering Beamline
Authors: Yang Lin , Liu Jiliang , Chodankar Shirish , Antonelli Stephen , DiFabio Jonathan
Published: January 2022

This work describes the instrumentation and software for microbeam scattering and structural mapping at the Life Science X-ray Scattering (LiX) beamline at NSLS-II. Using a two-stage focusing scheme, an adjustable beam size between a few micrometres and a fraction of a millimetre is produced at the sample position. Scattering data at small and wide angles are collected simultaneously on multiple Pilatus detectors. A recent addition of an in-vacuum Pilatus 900k detector, with the detector modules arranged in a C-shaped configuration, has improved the azimuthal angle coverage in the wide-angle data. As an option, fluorescence data can be collected simultaneously. Fly scans have been implemented to minimize the time interval between scattering patterns and to avoid unnecessary radiation damage to the sample. For weakly scattering samples, an in-vacuum sample environment has been developed here to minimize background scattering. Data processing for these measurements is highly sample-specific. To establish a generalized data process workflow, first the data are reduced to reciprocal coordinates at the time of data collection. The users can then quantify features of their choosing from these intermediate data and construct structural maps. As examples, results from in-vacuum mapping of onion epidermal cell walls and 2D tomographic sectioning of an intact poplar stem are presented.
Knowledge management strategies and organizational improvisation: what changed after the emergence of technological turbulence caused by artificial intelligence?
Authors: Arias-Pérez José , Cepeda-Cardona Juan
Published: January 2022

Purpose

This paper aims to analyze the moderating effect of technological turbulence caused by artificial intelligence on the relationship between the traditional knowledge management strategies of personalization (tacit knowledge) and codification (explicit knowledge), and organizational improvisation, which refers to the firm's ability to generate ideas and respond to changes in the technological environment in real time. Until now, individuals have played a key and indispensable role in organizational improvisation since they are the owners of tacit knowledge and users of explicit knowledge.

Design/methodology/approach

The research model was tested in a sample of firms from sectors in which the adoption of intelligent robots is growing.

Findings

Both personalization and codification have a positive and significant influence on improvisation, the former to a greater extent. Nevertheless, when technological turbulence caused by artificial intelligence occurs, the relationship between personalization and improvisation is weakened, whereas the link between codification and improvisation is strengthened.

Originality/value

Contrary to the pre-digital literature consensus, explicit knowledge is becoming the new major driver of organizational improvisation, while tacit knowledge sharing is losing strength and relevance. This finding may be a first indication that intelligent robots are the new exponents of improvisation for their ability to respond to changes in the environment in real time because of a combination of explicit knowledge, beyond being a mere support tool for humans.