bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability
Authors: Feleke Rahel , Jazayeri Dana , Abouzeid Maya , Powell Kim L , Srivastava Prashant K , O’Brien Terence J , Jones Nigel C , Johnson Michael R
Published: September 2022

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. We assessed the effect of gestational VPA on foetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses that are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied—inbred Genetic Absence Epilepsy Rats from Strasbourg, a model of genetic generalized epilepsy, and inbred non-epileptic control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Foetuses were extracted via C-section on gestational Day 21 (1 day prior to birth) and foetal brains were snap-frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes downregulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic foetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation.
Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci
Authors: Soutar Marc P M , Melandri Daniela , O’Callaghan Benjamin , Annuario Emily , Monaghan Amy E , Welsh Natalie J , D’Sa Karishma , Guelfi Sebastian , Zhang David , Pittman Alan , Trabzuni Daniah , Verboven Anouk H A , Pan Kylie S , Kia Demis A , Bictash Magda , Gandhi Sonia , Houlden Henry , Cookson Mark R , Kasri Nael Nadif , Wood Nicholas W , Singleton Andrew B , Hardy John , Whiting Paul J , Blauwendraat Cornelis , Whitworth Alexander J , Manzoni Claudia , Ryten Mina , Lewis Patrick A , Plun-Favreau Hélène
Published: September 2022

Parkinson’s disease is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies has considerably advanced our understanding of the Parkinson’s disease genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Impaired mitophagy is a key causative pathway in familial Parkinson’s disease, but its relevance to idiopathic Parkinson’s disease is unclear. We used a mitophagy screening assay to evaluate the functional significance of risk genes identified through genome-wide association studies. We identified two new regulators of PINK1-dependent mitophagy initiation, KAT8 and KANSL1, previously shown to modulate lysine acetylation. These findings suggest PINK1-mitophagy is a contributing factor to idiopathic Parkinson’s disease. KANSL1 is located on chromosome 17q21 where the risk associated gene has long been considered to be MAPT. While our data do not exclude a possible association between the MAPT gene and Parkinson’s disease, they provide strong evidence that KANSL1 plays a crucial role in the disease. Finally, these results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration.
The multifaceted role of neurofilament light chain protein in non-primary neurological diseases
Authors: Abu-Rumeileh Samir , Abdelhak Ahmed , Foschi Matteo , D'Anna Lucio , Russo Michele , Steinacker Petra , Kuhle Jens , Tumani Hayrettin , Blennow Kaj , Otto Markus
Published: September 2022

The advancing validation and exploitation of CSF and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarize the state of the art, future perspectives, but also limitations, of neurofilament light chain protein as a CSF and blood biomarker in several medical fields, including intensive care medicine, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurological impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease-19 pandemic and in normal ageing. Altogether, current data outline a multifaceted applicability of CSF and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.
ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy
Authors: Mattison Kari A , Tossing Gilles , Mulroe Fred , Simmons Callum , Butler Kameryn M , Schreiber Alison , Alsadah Adnan , Neilson Derek E , Naess Karin , Wedell Anna , Wredenberg Anna , Sorlin Arthur , McCann Emma , Burghel George J , Menendez Beatriz , Hoganson George E , Botto Lorenzo D , Filloux Francis M , Aledo-Serrano Ángel , Gil-Nagel Antonio , Tatton-Brown Katrina , Verbeek Nienke E , van der Zwaag Bert , Aleck Kyrieckos A , Fazenbaker Andrew C , Balciuniene Jorune , Dubbs Holly A , Marsh Eric D , Garber Kathryn , Ek Jakob , Duno Morten , Hoei-Hansen Christina E , Deardorff Matthew A , Raca Gordana , Quindipan Catherine , van Hirtum-Das Michele , Breckpot Jeroen , Hammer Trine Bjørg , Møller Rikke S , Whitney Andrea , Douglas Andrew G L , Kharbanda Mira , Brunetti-Pierri Nicola , Morleo Manuela , Nigro Vincenzo , May Halie J , Tao James X , Argilli Emanuela , Sherr Elliot H , Dobyns William B ,   Genomics England Research Consortium, Baines Richard A , Warwicker Jim , Parker J Alex , Banka Siddharth , Campeau Philippe M , Escayg Andrew
Published: September 2022

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms.
Tumour necrosis factor blockade after asphyxia in foetal sheep ameliorates cystic white matter injury
Authors: Lear Christopher A , Lear Benjamin A , Davidson Joanne O , Sae-Jiw Jialin , Lloyd Johanna M , Dhillon Simerdeep K , Gunn Alistair J , Bennet Laura
Published: September 2022

Cystic white matter injury is highly associated with severe neurodevelopmental disability and cerebral palsy in preterm infants, yet its pathogenesis remains poorly understood and there is no established treatment. In the present study, we tested the hypothesis that slowly evolving cystic white matter injury after hypoxia-ischaemia is mediated by programmed necrosis initiated by tumour necrosis factor. Tumour necrosis factor blockade was begun 3 days after hypoxia-ischaemia to target the tertiary phase of injury, when most secondary cell death is thought to be complete.

Chronically instrumented preterm foetal sheep (0.7 gestation) received 25 min of hypoxia-ischaemia induced by complete umbilical cord occlusion or sham-umbilical cord occlusion (controls, n = 10), followed by intracerebroventricular infusion of the soluble TNF inhibitor, Etanercept, at 3, 8 and 13 days after umbilical cord occlusion (n = 9) or vehicle (n = 9). Foetal brains were processed for histology at 21 days after umbilical cord occlusion.

Umbilical cord occlusion with vehicle was associated with a spectrum of macroscopic white matter degeneration, including white matter atrophy, ventriculomegaly and overt temporal lobe cystic white matter injury. Oligodendrocyte maturational arrest and impaired labelling of myelin proteins, characteristic of diffuse white matter injury, was observed in the parietal lobe and surrounding the cystic lesions in the temporal lobe. Etanercept markedly attenuated cystic white matter injury on the side of the intracerebroventricular infusion, with partial contralateral protection. Further, Etanercept improved oligodendrocyte maturation and labelling of myelin proteins in the temporal and parietal lobes.

The present study shows that cystic white matter injury reflects late-onset tertiary cell death mediated by delayed neuroinflammation through the tumour necrosis factor pathway. Delayed tumour necrosis factor blockade markedly attenuated cystic white matter injury and restored oligodendrocyte maturation and deficits in myelin protein expression. These data suggest that delayed tumour necrosis factor blockade may represent a viable therapeutic strategy to reduce the risk of cystic and diffuse white matter injury and potentially cerebral palsy after preterm birth, with a surprisingly wide therapeutic window.
Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons With Human Immunodeficiency Virus (HIV): The Swiss HIV Cohort Study
Authors: Schoepf Isabella C , Thorball Christian W , Kovari Helen , Ledergerber Bruno , Buechel Ronny R , Calmy Alexandra , Weber Rainer , Kaufmann Philipp A , Nkoulou René , Schwenke Johannes M , Braun Dominique L , Fellay Jacques , Tarr Philip E ,   for the Swiss HIV Cohort Study, Abela I , Aebi-Popp K , Anagnostopoulos A , Battegay M , Bernasconi E , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Hachfeld A , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Kusejko K , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nemeth J , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Wandeler G , Yerly S
Published: September 2022

Background

In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown.

Methods

In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population.

Results

We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval [CI], 1.18–5.67), and a CAC OR = 3.95 (95% CI, 1.45–10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75–59.11), and a CAC-OR = 65.07 (95% CI, 18.48–229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively).

Conclusions

In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.
Long-term variation in psoas muscle mass index is affected by short-term loss after esophagectomy in survivors of esophageal cancer
Authors: Nishimura Erica , Kawakubo Hirofumi , Matsuda Satoru , Fukuda Kazumasa , Nakamura Rieko , Kitagawa Yuko
Published: September 2022

Changes in muscle mass may be an objective approach toward measuring the quality of life after surgery, but long-term changes due to surgery without the effect of cachexia remain unclear. Patients with esophageal cancer who underwent esophagectomy and did not experience cancer recurrence for 3 years were analyzed. The psoas muscle mass index (PMI) was assessed before surgery and 7 days, 1 year, and 3 years after surgery. Patients with no change or increased PMI within 7 days after surgery were categorized into the Nondecreasing-PMI group, whereas those with decreased PMI were categorized into the Decreasing-PMI group. Eighty-four and 51 patients were categorized into the Nondecreasing- and Decreasing-PMI groups, respectively. The Decreasing-PMI group had a higher incidence rate of anastomotic leakage than the Nondecreasing-PMI group (25% vs. 12%, respectively; P = 0.042). Moreover, the Decreasing-PMI group showed a significantly greater decrease in the PMI 1 year after surgery than the Nondecreasing-PMI group (−9.2% vs. −4.0%, respectively; P = 0.048). However, although the Decreasing-PMI group had a greater decrease in the PMI than the Nondecreasing-PMI group, no significant difference was observed 3 years after surgery (−9.8% vs. −5.3%, respectively; P = 0.115). A decrease in PMI in the acute phase after esophagectomy may contribute to a long-term decrease in the PMI. Intensive interventions may be beneficial for these patients to improve their long-term quality of life.
Incidence, Prevalence, Disease Course, and Treatment Strategy of Crohn’s Disease Patients from the Veszprem Cohort, Western Hungary: A Population-based Inception Cohort Study Between 2007 and 2018
Authors: Gonczi Lorant , Lakatos Laszlo , Kurti Zsuzsanna , Golovics Petra A , Pandur Tunde , David Gyula , Erdelyi Zsuzsanna , Szita Istvan , Lakatos Peter L
Published: September 2022

Background and Aims

The number of prospective population-based studies on Crohn’s disease[CD] is still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD cohort. Our aim was to analyse incidence, prevalence, disease phenotype, treatment strategy, disease course, and surgical outcomes in a prospective population-based inception cohort including CD patients diagnosed between 2007 and 2018.

Methods

A total of 421 consecutive inception patients were included [male/female:237/184; mean age at diagnosis: 33.3 ± 16.2years]. Both in-hospital and outpatient records were collected and comprehensively reviewed. Demographic data were derived from the Hungarian Central Statistical Office.

Results

Mean incidence rate was 9.9 [95% CI: 9.0-10.9]/105 person-years in this 12-year period. Prevalence rate was 236.8 [95% CI: 220.8-252.8] in 2015; 17.6% and 20.0% of the patients had stenosing[B2] and penetrating[B3] disease behavior at diagnosis,respectively. The probability of disease behaviour progression from luminal to B2/B3 phenotype was 14.7% (standard error [SE]: 2.2) at 5 years after diagnosis. Distribution of maximal therapeutic steps during the total follow-up (8.5 years [8.5y], standard deviation [SD]: 3.3) was 5-aminosalicylic acid [5-ASA] in 15.7%, corticosteroids in 14.3%, immunosuppressives in 42.5%, and biologic therapy in 26.2%. The probability of receiving biologictherapy after diagnosis was 20.9% [SE: 2.0] at 5 years. The probability of first resective surgery was 20.7% [SE: 2.0] at 1 year, 26.1% [SE: 2.2] at 5 years, and 30.7% [SE: 2.4] at 10 years. The perianal surgery rate was 31.3% among patients with perianal involvement.

Conclusions

The incidence of CD in Hungary was high, similar to high-incidence areas in Western Europe. Treatment strategies are reflecting the biologic era. Disease behaviour progression was lower, as well as long-term [10y] surgery rates decreasing compared with data from previous decades.
Beyond the White Pill: Advocating for Racial Diversity in IBD Trials
Authors: Wong Emily C L , Moayyedi Paul , Narula Neeraj
Published: September 2022

Although inflammatory bowel disease [IBD] affects an increasingly diverse patient population, most patients in IBD clinical trials are White. Acknowledging current barriers and taking meaningful action is required at multiple levels to improve racial diversity across clinical trials in IBD. Ultimately, improving racial diversity in trials can in turn improve the care received by the diverse patients seen in clinical practice.
Econometric Issues in Prospective Economic Evaluations Alongside Clinical Trials: Combining the Nonparametric Bootstrap With Methods That Address Missing Data
Authors: Jalali Ali , Tamimi Rulla M , McPherson Sterling M , Murphy Sean M
Published: September 2022

Prospective economic evaluations conducted alongside clinical trials have become an increasingly popular approach in evaluating the cost-effectiveness of a public health initiative or treatment intervention. These types of economic studies provide improved internal validity and accuracy of cost and effectiveness estimates of health interventions and, compared with simulation or decision-analytic models, have the advantage of jointly observing health and economics outcomes of trial participants. However, missing data due to incomplete response or patient attrition, and sampling uncertainty are common concerns in econometric analysis of clinical trials. Missing data are a particular problem for comparative effectiveness trials of substance use disorder interventions. Multiple imputation and inverse probability weighting are 2 widely recommended methods to address missing data bias, and the nonparametric bootstrap is recommended to address uncertainty in predicted mean cost and effectiveness between trial interventions. Although these methods have been studied extensively by themselves, little is known about how to appropriately combine them and about the potential pitfalls and advantages of different approaches. We provide a review of statistical methods used in 29 economic evaluations of substance use disorder intervention identified from 4 published systematic reviews and a targeted search of the literature. We evaluate how each study addressed missing data bias, whether the recommended nonparametric bootstrap was used, how these 2 methods were combined, and conclude with recommendations for future research.
Antimicrobial volatiles emitted by members of the nest microbiome of social spiders
Authors: Lammers Alexander , Nazipi Seven , Zweers Hans , Bilde Trine , Schramm Andreas , Garbeva Paolina , Lalk Michael
Published: September 2022

Microbes produce and respond to a range of structurally and functionally diverse volatiles. Many microbial volatiles have antimicrobial properties. Since volatiles can diffuse through complex 3D systems like spider nests, they are promising pathogen protection for social arthropods. Here, we analyzed the volatilomes of five nest microbiome members of the Namibian, social spider Stegodyphus dumicola, namely the bacteria Massilia sp. IC2-278, Massilia sp. IC2-477, Sphingomonas sp. IC-11, Streptomyces sp. IC-207, and the fungus Aureobasidium sp. CE_32, and tested their antimicrobial activity against two putative spider pathogens, namely Bacillus thuringiensis and Purpureocillium lilacinum. Most nest microbiome members released volatilomes with antibacterial and/or antifungal activities under in vitro conditions. The analysis of their volatilomes using GC/Q-TOF revealed that they include numerous antimicrobial volatiles. We tested the antimicrobial activity of five pure volatile compounds found in the volatilomes and revealed that all of them were antibacterial and/or antifungal. We could not identify the same antimicrobial volatiles as in a previous in situ study, but our results indicate that social spider-associated microorganisms as a source of antimicrobial volatiles are important for pathogen inhibition. Additionally, we showed the influence of the volatilomes on the antibiotic sensitivity of B. thuringiensis offering novel approaches to counter antibiotic resistance.
Using GPS Technologies to Examine Community Mobility in Older Adults
Authors: Crane Breanna M , Moored Kyle D , Rosso Andrea L , Carlson Michelle C
Published: September 2022

Background

Objective measures of community mobility are advantageous for capturing movement outside the home. Compared with subjective, self-reported techniques, global positioning system (GPS) technologies leverage passive, real-time location data to reduce recall bias and increase measurement precision. We developed methods to quantify community mobility among community-dwelling older adults and assessed how GPS-derived indicators relate to clinical measures of physical and cognitive performance.

Methods

Participants (n = 149; M ± standard deviation [SD] = 77.1 ± 6.5 years) from the program to improve mobility in aging (PRIMA) study, a physical therapy intervention to improve walking ability, carried a GPS device for 7 days. Community mobility was characterized by assessing activity space, shape, duration, and distance. Associations between GPS-derived indicators and cognition and physical function were evaluated using Spearman correlations.

Results

In adjusted models, a larger activity space, greater duration (eg, time out-of-home), and greater distance traveled from home were correlated with better 6-Minute Walk Test performance (ρ = 0.17–0.23, p’s < .05). A more circular activity shape was related to poorer performance on the Trail Making Test, Part A (ρ = 0.18, p < .05). More time out-of-home and a larger activity space were correlated with faster times on the Trail Making Test, Part B (ρ = −0.18 to −0.24, p’s < .05). Community mobility measures were not associated with global cognition, skilled walking, or usual gait speed.

Conclusion

GPS-derived community mobility indicators capture real-world activity among older adults and were correlated with clinical measures of executive function and walking endurance. These findings will guide the design of future interventions to promote community mobility.
Multidisciplinary team directed analysis of whole genome sequencing reveals pathogenic non-coding variants in molecularly undiagnosed inherited retinal dystrophies
Authors: Daich Varela Malena , Bellingham James , Motta Fabiana , Jurkute Neringa , Ellingford Jamie M , Quinodoz Mathieu , Oprych Kathryn , Niblock Michael , Janeschitz-Kriegl Lucas , Kaminska Karolina , Cancellieri Francesca , Scholl Hendrik P N , Lenassi Eva , Schiff Elena , Knight Hannah , Black Graeme , Rivolta Carlo , Cheetham Michael E , Michaelides Michel , Mahroo Omar A , Moore Anthony T , Webster Andrew R , Arno Gavin
Published: September 2022

The purpose of this paper is to identify likely pathogenic non-coding variants in inherited retinal dystrophy (IRD) genes, using genome sequencing (GS). Patients with IRD were recruited to the study and underwent comprehensive ophthalmological evaluation and GS. The results of GS were investigated through virtual gene panel analysis, and plausible pathogenic variants and clinical phenotype evaluated by the multidisciplinary team (MDT) discussion. For unsolved patients in whom a specific gene was suspected to harbor a missed pathogenic variant, targeted re-analysis of non-coding regions was performed on GS data. Candidate variants were functionally tested by messenger RNA analysis, minigene or luciferase reporter assays. Previously unreported, likely pathogenic, non-coding variants in 7 genes (PRPF31, NDP, IFT140, CRB1, USH2A, BBS10 and GUCY2D), were identified in 11 patients. These were shown to lead to mis-splicing (PRPF31, IFT140, CRB1 and USH2A) or altered transcription levels (BBS10 and GUCY2D). MDT-led, phenotype-driven, non-coding variant re-analysis of GS is effective in identifying the missing causative alleles.
Step in Time: Conservation of Circadian Clock Genes in Animal Evolution
Authors: Stanton Daniel , Justin Hannah S , Reitzel Adam M
Published: September 2022

Over the past few decades, the molecular mechanisms responsible for circadian phenotypes of animals have been studied in increasing detail in mammals, some insects, and other invertebrates. Particular circadian proteins and their interactions are shared across evolutionary distant animals, resulting in a hypothesis for the canonical circadian clock of animals. As the number of species for which the circadian clockwork has been described increases, the circadian clock in animals driving cyclical phenotypes becomes less similar. Our focus in this review is to develop and synthesize the current literature to better understand the antiquity and evolution of the animal circadian clockwork. Here, we provide an updated understanding of circadian clock evolution in animals, largely through the lens of conserved genes characterized in the circadian clock identified in bilaterian species. These comparisons reveal extensive variation within the likely composition of the core clock mechanism, including losses of many genes, and that the ancestral clock of animals does not equate to the bilaterian clock. Despite the loss of these core genes, these species retain circadian behaviors and physiology, suggesting novel clocks have evolved repeatedly. Additionally, we highlight highly conserved cellular processes (e.g., cell division, nutrition) that intersect with the circadian clock of some animals. The conservation of these processes throughout the animal tree remains essentially unknown, but understanding their role in the evolution and maintenance of the circadian clock will provide important areas for future study.
Encountering Cover Versions of Songs Derived from Personal Music-Listening History Data: a Design and Field Trial of Musée in Homes
Authors: Jang Sangu , Lee Woojin , Kim Beom , Odom William , Park Young-Woo
Published: September 2022

We designed and implemented Musée to capture the novel experience of interpreting cover versions of music, which contain both familiar and unfamiliar musical components and are curated based on the user’s music-streaming history data. Musée is a tangible music player that enables users to explore and listen to professional or amateur covers of songs (via YouTube) in two categories: covers of songs from users’ most-liked artists and covers of users’ most-played songs. To investigate its potential value in situ, we conducted field trials of Musée in four households for 1 month. Findings showed that unfamiliar musical elements in cover music provided a sense of ‘freshness’ to past songs and helped the listener appreciate over-consumed music in new ways. In addition, restricting detailed information about cover songs that were playing helped users focus on the sound, thus priming them to infer and reflect on the original song and their memories associated with it. Our findings point to new insights for the design of interfaces that use historical personal data to expand users’ experience beyond solely revisiting prior tastes.
The effects of dietary ellagic acid supplementation on growth performance, immune response, antioxidant activity, digestive enzyme activities, and intestinal functions in yellow-feathered broilers
Authors: Wang Fang , Chen Jiashun , Yin Yexin , Yang Mei , Xiao Yintao , Cheng Ying , Yin Lichen , Fu Chenxing
Published: September 2022

This study was conducted to investigate the effects of dietary supplementation with ellagic acid (EA) on the performance, immune function, antioxidant activity, digestive enzyme activities, and intestinal functions in yellow-feathered broilers. In total, 288 healthy yellow-feathered broilers with an average body weight of 39 ± 0.24 g were randomly divided into four treatment groups. Broilers were given a corn-soybean meal basal diet supplemented with 0 (control group), 100, 200, or 400 mg/kg EA. In the finisher period and the overall period, the inclusion of 100, 200, and 400 mg/kg EA increased the average daily gain (P < 0.05), and the inclusion of 200 or 400 mg/kg EA decreased the feed/gain ratio compared with the control group (P < 0.05). The best immune activity (immunoglobulin G [IgG] and immunoglobulin M [IgM] concentrations) in serum was shown in the 200 mg/kg EA group (P < 0.05). Broilers fed with 200 or 400 mg/kg EA-containing diets exhibited higher serum catalase and glutathione peroxidase activities (P < 0.05) than control broilers. The inclusion of 200 mg/kg EA in the broiler diets increased intestinal chymotrypsin, pepsin, and lipase activities (P < 0.05). Broilers fed 200 mg/kg EA-containing diets had higher villus height in the jejunum and ileum, a higher ratio between villus height and crypt depth in the jejunum, and a deeper crypt in the duodenum compared to control broilers (P < 0.05). EA reduced the diamine oxidase activity and D-lactate concentration in serum. Furthermore, in birds fed EA-containing diets, the abundance of Rikenella and norank_f_norank_o_Clostridia_UCG-014 in cecum were decreased compared with control birds (P < 0.05). Moreover, in birds fed EA-containing diets, the levels of acetate, butyrate, and total short-chain fatty acids in the cecum were higher (P < 0.05) than those in control birds. These findings indicated that dietary EA had ameliorative effects on antioxidant capability, digestive enzyme activity, immune function, and intestinal functions, which led to strengthened growth performance.
Synergistic Use of Novel Technological Advances in Burn Care Significantly Reduces Hospital Length of Stay Below Predicted: A Case Series
Authors: Abla Habib , Brown Elizabeth , Pang Alan , Batchinsky Maria , Raghuram Akshay , Venable Amanda , Kesey Jennifer , Dissanaike Sharmila , Bharadia Deepak , Griswold John
Published: September 2022

Length of stay is an important metric in healthcare systems, primarily because it reflects the cost of care provided. In the United States, as in many countries, inpatient hospital stays are significantly more expensive than outpatient care across all healthcare conditions,1 so earlier discharge and transition to outpatient care is crucial to help control the ever-increasing cost of healthcare. In burn patients, length of stay has traditionally been estimated at 1 day per 1% total body surface area of burn. This estimation was first described in a round table discussion in 1986.2 However, since that time there has been significant evolution in the quality of care available to burn patients, in both the operating room and ICU. The use of new harvesting techniques, synthetic dermal substitution, and autologous epidermal skin cell suspension are allowing large, deep burns to be excised and covered in much quicker time frames than historically were possible. Examples include the skin harvesting and wound debridement device for grafting and excision, biodegradable temporizing matrix as a fully synthetic dermal template, and regenerative epidermal suspension concerning cell harvesting. Although these modalities can all be used separately, we believe that using them in conjunction has allowed us to shorten the length of stay in patients with severe partial and full-thickness burns. We present an initial case series of three patients with anticipated hospital lengths of stay of 54.5, 55, and 51 days, who were ready for discharge in 37, 35, and 43 days, respectively.
Reference genome assembly of the sunburst anemone, Anthopleura sola
Authors: Cornwell Brendan H , Beraut Eric , Fairbairn Colin , Nguyen Oanh , Marimuthu Mohan P A , Escalona Merly , Toffelmier Erin
Published: September 2022

The sunburst anemone Anthopleura sola is an abundant species inhabiting the intertidal zone of coastal California. Historically, this species has extended from Baja California, Mexico to as far north as Monterey Bay, CA. However, recently the geographic range of this species has expanded to Bodega Bay, CA, possibly as far north as Salt Point, CA. This species also forms symbiotic partnerships with the dinoflagellate Breviolum muscatinei, a member of the family Symbiodiniaceae. These partnerships are analogous to those formed between tropical corals and dinoflagellate symbionts, making A. sola an excellent model system to explore how hosts will (co)evolve with novel symbiont populations they encounter as they expand northward. This assembly will serve as the foundation for identifying the population genomic patterns associated with range expansions, and will facilitate future work investigating how hosts and their symbiont partners will evolve to interact with one another as geographic ranges shift due to climate change.
Resilience organizing: a multilevel communication framework
Authors: Doerfel Marya L , Kim Minkyung , Kwestel Melanie , Yoon Hyunsook , Quow Justine
Published: September 2022

This study advances communication-centered resilience theory by examining adaptive capacity of nonprofit networks impacted by Hurricane Harvey in 2017. Data show how formal structures set up conditions for adaptive/informal organizing. This highlights a quandary for disaster planning: improvising emerges from organizations having plans in place. Iterative processes between formal and informal structures expanded capacity, building a foundation for work processes to scaffold from individual to organizational to interorganizational networks. Yet some employees were personally vulnerable, revealing a multilevel dilemma: organizations were resilient even if employees were not. This study also theorizes time as an endogenous mechanism. As workers perceived less urgency, process experts broadened communication across levels, integrating more complex work processes. Resilience differed between organizations that lacked process experts, revealing their critical role across levels. Findings point to a policy-making dilemma: successful resilience processes undermine pressure on policy-makers to mitigate threats that necessitate improving resilience processes to begin with.
A light-cone catalogue from the Millennium-XXL simulation: improved spatial interpolation and colour distributions for the DESI BGS
Authors: Smith Alex , Cole Shaun , Grove Cameron , Norberg Peder , Zarrouk Pauline
Published: September 2022

The use of realistic mock galaxy catalogues is essential in the preparation of large galaxy surveys, in order to test and validate theoretical models and to assess systematics. We present an updated version of the mock catalogue constructed from the Millennium-XXL simulation, which uses a halo occupation distribution method to assign galaxies r-band magnitudes and g − r colours. We have made several modifications to the mock to improve the agreement with measurements from the SDSS and GAMA surveys. We find that cubic interpolation, which was used to build the original halo light cone, produces extreme velocities between snapshots. Using linear interpolation improves the correlation function quadrupole measurements on small scales. We also update the g − r colour distributions so that the observed colours better agree with measurements from GAMA data, particularly for faint galaxies. As an example of the science that can be done with the mock, we investigate how the luminosity function depends on environment and colour, and find good agreement with measurements from the GAMA survey. This full-sky mock catalogue is designed for the ongoing Dark Energy Spectroscopic Instrument Bright Galaxy Survey, and is complete to a magnitude limit r = 20.2.
The EBLM project – IX. Five fully convective M-dwarfs, precisely measured with CHEOPS and TESS light curves
Authors: Sebastian D , Swayne M I , Maxted P F L , Triaud A H M J , Sousa S G , Olofsson G , Beck M , Billot N , Hoyer S , Gill S , Heidari N , Martin D V , Persson C M , Standing M R , Alibert Y , Alonso R , Anglada G , Asquier J , Bárczy T , Barrado D , Barros S C C , Battley M P , Baumjohann W , Beck T , Benz W , Bergomi M , Boisse I , Bonfils X , Brandeker A , Broeg C , Cabrera J , Charnoz S , Collier Cameron A , Csizmadia Sz , Davies M B , Deleuil M , Delrez L , Demangeon O D S , Demory B-O , Dransfield G , Ehrenreich D , Erikson A , Fortier A , Fossati L , Fridlund M , Gandolfi D , Gillon M , Güdel M , Hasiba J , Hébrard G , Heng K , Isaak K G , Kiss L L , Kopp E , Kunovac V , Laskar J , Lecavelier des Etangs A , Lendl M , Lovis C , Magrin D , McCormac J , Miller N J , Nascimbeni V , Ottensamer R , Pagano I , Pallé E , Pepe F A , Peter G , Piotto G , Pollacco D , Queloz D , Ragazzoni R , Rando N , Rauer H , Ribas I , Lalitha S , Santerne A , Santos N C , Scandariato G , Ségransan D , Simon A E , Smith A M S , Steller M , Szabó Gy M , Thomas N , Udry S , Van Grootel V , Walton N A
Published: September 2022

Eclipsing binaries are important benchmark objects to test and calibrate stellar structure and evolution models. This is especially true for binaries with a fully convective M-dwarf component for which direct measurements of these stars’ masses and radii are difficult using other techniques. Within the potential of M-dwarfs to be exoplanet host stars, the accuracy of theoretical predictions of their radius and effective temperature as a function of their mass is an active topic of discussion. Not only the parameters of transiting exoplanets but also the success of future atmospheric characterization relies on accurate theoretical predictions. We present the analysis of five eclipsing binaries with low-mass stellar companions out of a subsample of 23, for which we obtained ultra-high-precision light curves using the CHEOPS satellite. The observation of their primary and secondary eclipses are combined with spectroscopic measurements to precisely model the primary parameters and derive the M-dwarfs mass, radius, surface gravity, and effective temperature estimates using the PYCHEOPS data analysis software. Combining these results to the same set of parameters derived from TESS light curves, we find very good agreement (better than 1 per cent for radius and better than 0.2 per cent for surface gravity). We also analyse the importance of precise orbits from radial velocity measurements and find them to be crucial to derive M-dwarf radii in a regime below 5 per cent accuracy. These results add five valuable data points to the mass–radius diagram of fully convective M-dwarfs.
Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant
Authors: Burrello Jacopo , Monticone Silvia , Burrello Alessio , Bolis Sara , Cristalli Carlotta Pia , Comai Giorgia , Corradetti Valeria , Grange Cristina , Orlando Giuseppe , Bonafè Massimiliano , La Manna Gaetano , Barile Lucio , Bussolati Benedetta
Published: September 2022

Background

A long-standing effort is dedicated towards the identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant.

Methods

We characterized 37 surface antigens by flow cytometry, in serum and urine EVs from 58 patients who were evaluated before, and at 10–14 days, 3 months and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year.

Results

Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated with patient outcome at univariate analysis and were able to predict patient outcome at receiver operating characteristics curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome.

Conclusions

An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant.
The Political Sociology of W. E. B. Du Bois
Authors: de Leon Cedric , Rodríguez-Muñiz Michael
Published: September 2022

This handbook and other recent works have claimed W. E. B. Du Bois as foundational to sociology and the social sciences. With few exceptions, however, the recuperation of Du Bois has not extended to political sociology (and politically oriented works in comparative historical sociology). This chapter claims Du Bois as a political sociologist. A wealth of largely unharvested insights in his work awaits the subfield. Here, the focus is on three issues: (1) the entwinement of socio-political processes, (2) the concomitant paradigm shifts implicit in a Du Boisian political sociology for objects of inquiry such as the state and development, and (3) the political exhortation at the heart of these paradigm shifts, which centers on retheorizing democracy and democratization.
Gender, Gender Identity, and Sexual Orientation in Personality and Psychopathology Assessment
Authors: Brabender Virginia
Published: September 2022

The psychological assessor, this chapter puts forth, needs both personality and identity information to understand a client fully. The identity aspects that are brought into focus in this chapter are those related to gender and sexuality. In the beginning of this chapter, basic terminology related to aspects of gender and sexuality are defined and nomothetic efforts to take into account gender differences are described. The chapter then presents an ideographic approach to capturing an individual’s psychology by looking at personality in the context of gender and sexual identities and gender and sexual identities in the context of personality. Two cases are presented, the first of which is that of an individual who enters an assessment for the elucidation of difficulties in social adjustment. Taking into account the individual’s asexual sexual orientation, atypical gender expression, and the stigma that accompanies both statuses was crucial to illumining the individual’s difficulties. In the second case, the assessment of personality features of a young woman who identifies as lesbian assists the assessor in constructing a picture of how she is likely to fare in the coming out process in college. The chapter concludes with an identification of the challenges the assessor is likely to face in figuring gender and sexual identity into a personality assessment and strategies for surmounting them.
Montesquieu, Rhetoric, and Freedom without Equality
Authors: Kingston Rebecca
Published: September 2022

This chapter explores the relation between freedom and inequality in Montesquieu’s work through rhetorical analysis. It begins with a discussion of Montesquieu’s broader conception of the relation between language and regime, demonstrating how his typology of governments is complemented with a typology of rhetorical styles. It then proceeds to discuss Montesquieu’s rather nuanced discussion of equality as related to political regimes and his theory of freedom especially as developed in Book XI, chapter 6 and Book XIX, chapter 27 of The Spirit of the Laws. The chapter suggests that for Montesquieu political liberty in moderate regimes appears to rely on social inequalities. This does not make his theory irrelevant for contemporary purposes but rather offers some tools for unmasking realities underlying contemporary liberal democratic rhetoric.
Marx’s Rhetoric
Authors: Martin James
Published: September 2022

Marx was a radical critic of capitalism and an advocate of its revolutionary overthrow and substitution by communism. An intellectual, polemicist, and propagandist, his political theory was expressed in a variety of rhetorical strategies aimed at illuminating the dynamics of class conflict beneath property relations and at exposing the inadequate and often partial opinions of his adversaries. Marx’s thought was later taken as the foundation of an all-encompassing outlook known as “Marxism,” which, paradoxically, diminished ideas and arguments as factors in political agitation. Yet a closer look at Marx’s rhetoric demonstrates his argumentative versatility across different genres and a distinctive attention to figurative language in illuminating power relations in capitalism.
Rhetoric as Idealization
Authors: Rehg William
Published: September 2022

Jürgen Habermas’s discourse theory includes an epistemic conception of rhetoric that has significant implications for the analysis of political discourse. After situating his remarks about the “rhetorical perspective” in his critical-social project and argumentation theory, this chapter shows how that perspective plays an authoritative role in assessing the cogency of arguments about truth and justice. It then argues that Habermas’s model leads to a deeply social conception of reasonableness, which in turn calls for intellectual humility in political debate. However, contextual differences pose a problem for his model; in response, the chapter briefly sketches a more thoroughly contextualist approach to reasonable moral–political discourse.