bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative richness patterns of range sizes and life forms of Apocynaceae along forest–savanna transitions in Brazil
Authors: de Deus Vidal João , Schmitt Christine B , Koch Ingrid
Published: September 2023

Brazilian moist forests and savannas are some of the most species-rich biomes in the Neotropics. In the transition zones between these regions, ecotones often accumulate even higher taxonomic diversity. However, whether these ecotonal communities consist of overlapping species widespread from the neighbouring biomes or a specific set of locally adapted species still needs to be clarified. Regional differences in species richness may be influenced by factors such as species' environmental tolerances, life forms, or species’ range sizes. To investigate the species richness found in ecotones, we used the ‘milk-weed’ family (Apocynaceae), which comprises both widespread and narrowly distributed trees, lianas, and shrubs, as a model to evaluate if (i) their observed richness in ecotones is promoted by widespread species or by locally adapted species; (ii) trees, lianas, and shrubs show different richness patterns in savannas, ecotones, and forests; and (iii) species found in ecotones have broader environmental tolerances than other species in the family. We used a taxonomically curated georeferenced dataset to compare the range sizes of 643 species of Apocynaceae from 73 genera listed for Brazil, comprising 298 species with a liana life form and 345 trees, herbs, or shrubs. We recorded 335 predominantly forest species, 56 savanna species, and 152 ecotone species, for which we quantified species richness, areas of occurrence, precipitation, and temperature ranges and tested for differences in range sizes and environmental tolerances between habits and ecoregions. Our results indicate that (i) Apocynaceae species occurring in ecotones have wider geographical ranges than species not occurring in ecotones; (ii) lianas showed higher area-weighted richness in ecotones than other life forms; and (iii) species found in ecotones had broader environmental tolerances than species restricted to moist forests or savannas. These results indicate that the species richness found in ecotones between savannas and moist forests in Brazil is not necessarily a consequence of higher endemism and local adaptation but may also be a result of overlapping ranges of widespread species typically associated with neighbouring biomes. Together, our findings add to our understanding of ecotones and biomes as continuous, gradual biogeographical transitions instead of sharply defined ecological units.
White matter tracts and executive functions: a review of causal and correlation evidence
Authors: Ribeiro Monica , Yordanova Yordanka Nikolova , Noblet Vincent , Herbet Guillaume , Ricard Damien
Published: September 2023

Executive functions are high-level cognitive processes involving abilities such as working memory/updating, set-shifting and inhibition. These complex cognitive functions are enabled by interactions among widely distributed cognitive networks, supported by white matter tracts. Executive impairment is frequent in neurological conditions affecting white matter; however, whether specific tracts are crucial for normal executive functions is unclear. We review causal and correlation evidence from studies that used direct electrical stimulation during awake surgery for gliomas, voxel-based and tract-based lesion-symptom mapping, and diffusion tensor imaging to explore associations between the integrity of white matter tracts and executive functions in healthy and impaired adults. The corpus callosum was consistently associated with all executive processes, notably its anterior segments. Both causal and correlation evidence showed prominent support of the superior longitudinal fasciculus to executive functions, notably to working memory. More specifically, strong evidence suggested that the second branch of the superior longitudinal fasciculus is crucial for all executive functions, especially for flexibility. Global results showed left lateralization for verbal tasks and right lateralization for executive tasks with visual demands. The frontal aslant tract potentially supports executive functions, however, additional evidence is needed to clarify whether its involvement in executive tasks goes beyond the control of language. Converging evidence indicates that a right-lateralized network of tracts connecting cortical and subcortical grey matter regions supports the performance of tasks assessing response inhibition, some suggesting a role for the right anterior thalamic radiation. Finally, correlation evidence suggests a role for the cingulum bundle in executive functions, especially in tasks assessing inhibition. We discuss these findings in light of current knowledge about the functional role of these tracts, descriptions of the brain networks supporting executive functions and clinical implications for individuals with brain tumours.
A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex
Authors: Luppi Andrea I , Girn Manesh , Rosas Fernando E , Timmermann Christopher , Roseman Leor , Erritzoe David , Nutt David J , Stamatakis Emmanuel A , Spreng R Nathan , Xing Lei , Huttner Wieland B , Carhart-Harris Robin L
Published: September 2023

Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy—where it plays a central role in the integrative processes underpinning complex, human-defining cognition—the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression and recent evidence suggests that, during early brain development, 5-HT2AR signalling on neural progenitor cells stimulates their proliferation—a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signalling plays a major role in both human cortical expansion and functioning. Owing to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.
Educational inclusion of deaf children: current policy, practices, and future possibilities
Authors: Oppong Alexander M , Swanwick Ruth , Fobi Daniel
Published: September 2023

This paper examines policies and practices of inclusive education for young deaf children in Ghana. Though existing Government policy promotes the principles and implementation of educational inclusion of all children in Ghana, caregivers often encounter significant challenges ensuring access to early years’ education for their deaf children. We used Bronfenbrenner’s (2005) bioecological systems theory and interviewed 15 educators of deaf children and 9 hearing-health clinicians, to capture different knowledge, experience, and perspectives on policy, practice, and inclusive approaches to deaf children’s education. We ask: (a) How do teachers, clinicians, and caregivers connect to promote early childhood care education (ECCE) for young deaf preschoolers in Ghana? and (b) What resources and precarities are available to educators of deaf children and hearing-health clinicians in sustaining inclusive educational practices across urban and rural contexts in Ghana? We address these unanswered questions about the potential pathway to bring about changes in policy and practice in promoting successful inclusive education for deaf children in Ghana. Implications for national and international policy and practice of ECCE for deaf children are discussed and recommendations are made.
Mitigating the Risk of Tofacitinib-induced Adverse Events in the Elderly Population with Ulcerative Colitis
Authors: Viola Anna , Li Voti Raffaele , Bivacqua Chiara , De Francesco Clara , Muscianisi Marco , Costantino Giuseppe , Fries Walter
Published: September 2023

Background and Aims

Older patients with ulcerative colitis treated with tofacitinib are at risk for major cardiovascular events, thromboembolism, herpes zoster, and malignancies and, accordingly, its use is limited by the regulatory authorities. The aim of the present study was to evaluate the occurrence of adverse events and potential preventive measures.

Methods

We retrospectively evaluated patients treated with tofacitinib, divided into two groups according to comorbidities and age. Patient- and disease-related variables were recorded [primary non-response, loss of response, and persistence], together with deviations from the recommended induction regimen, ie, dose reduction, and concomitant treatments with anti-thrombotic therapy.

Results

The age-adjusted Charlson comorbidity index of Group 1 [n = 30] was ≥2 and that of Group 2 [n = 37] was ≤ 1. No differences were observed for primary or secondary treatment failures. Both groups achieved comparable steroid-free remission rates at 12 months [53% and 46%, respectively]. Herpes zoster occurred in two patients per group, and no more cases occurred after strict recombinant zoster vaccination. No major cardiovascular event or thromboembolism was registered. Half of patients in Group 1 were treated with a reduced induction dose of 5 mg twice daily and 47% were on concomitant anti-thrombotic therapy. Malignancies were registered in two patients from Group 1 and one patient from Group 2.

Conclusions

Modulation of induction dose and anti-thrombotic therapy may have contributed to prevent cardiological events and thromboembolism. The introduction of zoster vaccine virtually eliminated zoster risk after the first cases. Potential malignancies deserve a careful work-up of older patients before treatment start.
Long-term outcomes of functional single ventricles associated with heterotaxy syndrome
Authors: Tanimoto Kazuki , Hoashi Takaya , Shibagaki Keisuke , Ono Yoshikazu , Komori Motoki , Okuda Naoki , Imai Kenta , Iwai Shigemitsu , Ichikawa Hajime
Published: September 2023

OBJECTIVES

The goal of this study was to determine the long-term surgical outcomes of patients with functional single ventricles associated with heterotaxy syndrome, risk factors for mortality and factors associated with Fontan stage completion.

METHODS

Overall, 279 patients with a functional single ventricle associated with heterotaxy syndrome who underwent an initial surgical procedure at our institute between 1978 and 2021 were grouped into 4 “eras” based on the surgical year during which the initial procedure was performed: era 1 (1978–1989, n = 71), era 2 (1990–1999, n = 98), era 3 (2000–2009, n = 64) and era 4 (2010–2021, n = 46). Neonatal surgery was more frequent in eras 3 and 4 than in eras 1 and 2.

RESULTS

Overall, 228 patients had right atrial isomerism; 120 patients (43.0%) had a total anomalous pulmonary venous connection; and 58 patients (20.8%) underwent an initial procedure as neonates. Overall survival rates at 10, 20 and 30 years after the initial procedure were 47.1%, 40.6% and 36.1%, respectively. Neonatal surgery (P < 0.001), total anomalous pulmonary venous connection repair at the initial procedure (P < 0.001) and early era (P < 0.001) were identified as risk factors for mortality, with the last 2 variables being negatively associated with Fontan stage completion (P < 0.001 for both).

CONCLUSIONS

Although era had a favourable effect on survival, total anomalous pulmonary venous connection with intrinsic pulmonary vein obstruction was associated with both mortality and Fontan stage completion.

Clinical registration number

R19092
Familial central precocious puberty due to DLK1 deficiency: novel genetic findings and relevance of serum DLK1 levels
Authors: Montenegro Luciana , Seraphim Carlos , Tinano Flávia , Piovesan Maiara , Canton Ana P M , McElreavey Ken , Brabant Severine , Boris Natalia P , Magnuson Melissa , Carroll Rona S , Kaiser Ursula B , Argente Jesús , Barrios Vicente , Brito Vinicius N , Brauner Raja , Latronico Ana Claudia
Published: September 2023

Background

Several rare loss-of-function mutations of delta-like noncanonical notch ligand 1 (DLK1) have been described in non-syndromic children with familial central precocious puberty (CPP).

Objective

We investigated genetic abnormalities of DLK1 gene in a French cohort of children with idiopathic CPP. Additionally, we explored the pattern of DLK1 serum levels in patients with CPP and in healthy children at puberty, as well as in wild-type female mice.

Patients and Methods

Genomic DNA was obtained from 121 French index cases with CPP. Automated sequencing of the coding region of the DLK1 gene was performed in all cases. Serum DLK1 levels were measured by enzyme linked immunosorbent assay (ELISA) in 209 individuals, including 191 with normal pubertal development and in female mice during postnatal pubertal maturation.

Results

We identified 2 rare pathogenic DLK1 allelic variants: A stop gain variant (c.372C>A; p.Cys124X) and a start loss variant (c.2T>G; p.Met1?, or p.0) in 2 French girls with CPP. Mean serum DLK1 levels were similar between healthy children and idiopathic CPP children. In healthy individuals, DLK1 levels correlated with pubertal stage: In girls, DLK1 decreased between Tanner stages III and V, whereas in boys, DLK1 decreased between Tanner stages II and V (P = .008 and .016, respectively). Serum levels of Dlk1 also decreased in wild-type female mice.

Conclusions

Novel loss-of-function mutations in DLK1 gene were identified in 2 French girls with CPP. Additionally, we demonstrated a pattern of dynamic changes in circulating DLK1 serum levels in humans and mice during pubertal stages, reinforcing the role of this factor in pubertal timing.
Nutrient Metabolites Associated With Low D3Cr Muscle Mass, Strength, and Physical Performance in Older Men
Authors: Hetherington-Rauth Megan , Johnson Eileen , Migliavacca Eugenia , Parimi Neeta , Langsetmo Lisa , Hepple Russell T , Grzywinski Yohan , Corthesy John , Ryan Terence E , Ferrucci Luigi , Feige Jérôme N , Orwoll Eric S , Cawthon Peggy M
Published: September 2023

Background

The relationship between amino acids, B vitamins, and their metabolites with D3-creatine (D3Cr) dilution muscle mass, a more direct measure of skeletal muscle mass, has not been investigated. We aimed to assess associations of plasma metabolites with D3Cr muscle mass, as well as muscle strength and physical performance in older men from the Osteoporotic Fractures in Men cohort study.

Methods

Out of 1 425 men (84.2 ± 4.1 years), men with the lowest D3Cr muscle mass (n = 100), slowest walking speed (n = 100), lowest grip strength (n = 100), and a random sample (n = 200) serving as a comparison group to the low groups were included. Metabolites were analyzed using liquid chromatography–tandem mass spectrometry. Metabolite differences between the low groups and random sample and their relationships with the muscle outcomes adjusted for confounders and multiple comparisons were assessed using t-test/Mann–Whitney–Wilcoxon and partial correlations, respectively.

Results

For D3Cr muscle mass, significant biomarkers (p < .001) with ≥10% fold difference and largest partial correlations were tryptophan (Trp; r = 0.31), kynurenine (Kyn)/Trp; r = −0.27), nicotinamide (Nam)/quinolinic acid (Quin; r = 0.21), and alpha-hydroxy-5-methyl-tetrahydrofolate (hm-THF; r = −0.25). For walking speed, hm-THF, Nam/Quin, and Quin had the largest significance and fold difference, whereas valine (r = 0.17), Trp (r = 0.17), HKyn/Xant (r = −0.20), neopterin (r = −0.17), 5-methyl-THF (r = −0.20), methylated folate (r = −0.21), and thiamine (r = −0.18) had the strongest correlations. Only hm-THF was correlated with grip strength (r = −0.21) and differed between the low group and the random sample.

Conclusions

Future interventions focusing on how the Trp metabolic pathway or hm-THF influences D3Cr muscle mass and physical performance declines in older adults are warranted.
CDKL5-mediated developmental tuning of neuronal excitability and concomitant regulation of transcriptome
Authors: Liao Wenlin , Lee Kun-Ze
Published: September 2023

Cyclin-dependent kinase-like 5 (CDKL5) is a serine–threonine kinase enriched in the forebrain to regulate neuronal development and function. Patients with CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition caused by mutations of CDKL5 gene, present early-onset epilepsy as the most prominent feature. However, spontaneous seizures have not been reported in mouse models of CDD, raising vital questions on the human-mouse differences and the roles of CDKL5 in early postnatal brains. Here, we firstly measured electroencephalographic (EEG) activities via a wireless telemetry system coupled with video-recording in neonatal mice. We found that mice lacking CDKL5 exhibited spontaneous epileptic EEG discharges, accompanied with increased burst activities and ictal behaviors, specifically at postnatal day 12 (P12). Intriguingly, those epileptic spikes disappeared after P14. We next performed an unbiased transcriptome profiling in the dorsal hippocampus and motor cortex of Cdkl5 null mice at different developmental timepoints, uncovering a set of age-dependent and brain region-specific alterations of gene expression in parallel with the transient display of epileptic activities. Finally, we validated multiple differentially expressed genes, such as glycine receptor alpha 2 and cholecystokinin, at the transcript or protein levels, supporting the relevance of these genes to CDKL5-regulated excitability. Our findings reveal early-onset neuronal hyperexcitability in mouse model of CDD, providing new insights into CDD etiology and potential molecular targets to ameliorate intractable neonatal epilepsy.
Albanese Maps for Open Algebraic Spaces
Authors: Schröer Stefan
Published: September 2023

We show that for each algebraic space that is separated and of finite type over a field, and whose affinization is connected and reduced, there is a universal morphism to a para-abelian variety. The latter are schemes that acquire the structure of an abelian variety after some ground field extension. This generalizes classical results of Serre on universal morphisms from algebraic varieties to abelian varieties. Our proof relies on corresponding facts for the proper case, together with the structural properties of group schemes, removal of singularities by alterations, and ind-objects. It turns out that the formation of the Albanese variety commutes with base-change up to universal homeomorphisms. We also give a detailed analysis of Albanese maps for algebraic curves and algebraic groups, with special emphasis on imperfect ground fields.
Crowdfunding as a Market-Fostering Gift System
Authors: Maciel Andre F , Weinberger Michelle F
Published: September 2023

Reward-based crowdfunding has enabled an unprecedented number of consumers to provision capital for commercial and artistic ventures. Each year, consumers use digital platforms to transfer billions of dollars to entrepreneurs and artists to help them develop a wide range of market innovations. Notably, these consumers obtain no financial benefits, no formal guarantee that their money will be used aptly, and no reimbursement options. Under such materially unfavorable conditions, why do consumers transfer their money to these producers? The present research answers this question by introducing the concept of a “market-fostering gift system”: a social contract that entices consumers to fund the creation and enhancement of market offerings by mobilizing the logic and practices of gift-giving. This conceptualization includes the core stakeholders, processes, outcomes, and shortcomings of reward-based crowdfunding, providing theoretical structure to this consequential articulation of platform capitalism. In addition, this conceptualization advances theory about how gift and market economies intersect. Whereas previous research emphasizes the tensions that characterize their interface, this article brings to the fore the complementary, scalable relationship between gift-giving and market exchange.
A reference genome assembly for the continentally distributed ring-necked snake, Diadophis punctatus
Authors: Westeen Erin P , Escalona Merly , Beraut Eric , Marimuthu Mohan P A , Nguyen Oanh , Fisher Robert N , Toffelmier Erin , Shaffer H Bradley , Wang Ian J
Published: September 2023

Snakes in the family Colubridae include more than 2,000 currently recognized species, and comprise roughly 75% of the global snake species diversity on Earth. For such a spectacular radiation, colubrid snakes remain poorly understood ecologically and genetically. Two subfamilies, Colubrinae (788 species) and Dipsadinae (833 species), comprise the bulk of colubrid species richness. Dipsadines are a speciose and diverse group of snakes that largely inhabit Central and South America, with a handful of small-body-size genera that have invaded North America. Among them, the ring-necked snake, Diadophis punctatus, has an incredibly broad distribution with 14 subspecies. Given its continental distribution and high degree of variation in coloration, diet, feeding ecology, and behavior, the ring-necked snake is an excellent species for the study of genetic diversity and trait evolution. Within California, six subspecies form a continuously distributed “ring species” around the Central Valley, while a seventh, the regal ring-necked snake, Diadophis punctatus regalis is a disjunct outlier and Species of Special Concern in the state. Here, we report a new reference genome assembly for the San Diego ring-necked snake, D. p. similis, as part of the California Conservation Genomics Project. This assembly comprises a total of 444 scaffolds spanning 1,783 Mb and has a contig N50 of 8.0 Mb, scaffold N50 of 83 Mb, and BUSCO completeness score of 94.5%. This reference genome will be a valuable resource for studies of the taxonomy, conservation, and evolution of the ring-necked snake across its broad, continental distribution.
Pelvic tilt after Bernese periacetabular osteotomy—a long-term follow-up study
Authors: Heimann Alexander F , Brouze Iris F , Zheng Guoyan , Moosmann Angela M , Schwab Joseph M , Tannast Moritz , Zurmühle Corinne A
Published: September 2023

Patients with developmental dysplasia of the hip (DDH) are believed to present with increased anterior pelvic tilt to compensate for reduced anterior femoral head coverage. If true, pelvic tilt in dysplastic patients should be high preoperatively and decrease after correction with periacetabular osteotomy (PAO). To date, the evolution of pelvic tilt in long-term follow-up after PAO has not been reported. We therefore asked the following questions: (i) is there a difference in pelvic tilt between patients with DDH and an asymptomatic control group? (ii) How does pelvic tilt evolve during long-term follow-up after Bernese PAO compared with before surgery? This study is a therapeutic study with the level of evidence III. We retrospectively compared preoperative pelvic tilt in 64 dysplastic patients (71 hips) with an asymptomatic control group of 20 patients (20 hips). In addition, immediate postoperative and long-term follow-up (at 18 ± 8 [range 7–34 years) pelvic tilt was assessed and compared. Dysplastic patients had a significantly higher mean preoperative pelvic tilt than controls [2.3 ± 5.3° (−11.2° to 16.4°) versus 1.1 ± 3.0° (−4.9 to 5.9), P = 0.006]. Mean pelvic tilt postoperatively was 1.5 ± 5.3° (−11.2 to 17.0º, P = 0.221) and at long-term follow-up was 0.4 ± 5.7° (range −9.9° to 20.9°, P = 0.002). Dysplastic hips undergoing PAO show a statistically significant decrease in pelvic tilt during long-term follow-up. However, given the large interindividual variability in pelvic tilt, the observed differences may not achieve clinical significance.
Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma
Authors: Papini Chiara , Mirzaei S. Sedigheh , Xing Mengqi , Tonning Olsson Ingrid , de Blank Peter M K , Lange Katharine R , Salloum Ralph , Srivastava Deokumar , Leisenring Wendy M , Howell Rebecca M , Oeffinger Kevin C , Robison Leslie L , Armstrong Gregory T , Krull Kevin R , Brinkman Tara M
Published: September 2023

Background

Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown.

Methods

Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver’s license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided.

Results

Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk = 2.22; task efficiency: relative risk = 1.88; both P < .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (β = 0.06), sensorimotor (β = 0.06), and endocrine (β = 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each β = 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory.

Conclusion

Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions.
Deciphering the protein ubiquitylation system in plants
Authors: Hua Zhihua
Published: September 2023

Protein ubiquitylation is a post-translational modification (PTM) process that covalently modifies a protein substrate with either mono-ubiquitin moieties or poly-ubiquitin chains often at the lysine residues. In Arabidopsis, bioinformatic predictions have suggested that over 5% of its proteome constitutes the protein ubiquitylation system. Despite advancements in functional genomic studies in plants, only a small fraction of this bioinformatically predicted system has been functionally characterized. To expand our understanding about the regulatory function of protein ubiquitylation to that rivalling several other major systems, such as transcription regulation and epigenetics, I describe the status, issues, and new approaches of protein ubiquitylation studies in plant biology. I summarize the methods utilized in defining the ubiquitylation machinery by bioinformatics, identifying ubiquitylation substrates by proteomics, and characterizing the ubiquitin E3 ligase-substrate pathways by functional genomics. Based on the functional and evolutionary analyses of the F-box gene superfamily, I propose a deleterious duplication model for the large expansion of this family in plant genomes. Given this model, I present new perspectives of future functional genomic studies on the plant ubiquitylation system to focus on core and active groups of ubiquitin E3 ligase genes.
Proteomic biomarker evaluation using antibody microarrays: association between analytical methods such as microarray and ELISA
Authors: Gumanova Nadezhda G , Bogdanova Natalya L , Metelskaya Victoria A
Published: September 2023

Objective

To evaluate the associations between analytical methods, such as microarray and enzyme-linked immunosorbent assay (ELISA); expedient cutoffs; and the lowest possible number of microarrays in analysis for target biomarker estimation in case-control studies.

Methods

This study included 321 serum specimens, gathered in different case-control studies to test for atherosclerosis and atrial fibrillation. Among them, 48 serum specimens were analyzed using microarray technology. We used ELISA and commercial kits for confirmation of the results.

Results

Three proteins—cadherin-P, neuronal nitric oxide synthase, and adenovirus fiber—were shown to have distinctly different values in the case group vs the control group. As a result, we used those proteins as the target for confirmation using our alternative analytical method. Also, these protein values represented the limiting range between the highest and lowest differences in case-control groups. The results of microarray assay were confirmed using ELISA and commercial kits in the same specimens, in which microarray profiling was performed, and also in separate large case-control groups.

Conclusions

A 1.5-fold difference in the protein content, as measured using microarray technology, was shown to be sufficient for further investigation of the candidate proteins. As few as 3 microarrays were considered sufficient for perspective evaluation of the target proteins. Microarray serum profiling, therefore, provides semiquantitative determination of protein in serum.
Optimizing an exercise training program in pediatric brain tumour survivors: Does timing postradiotherapy matter?
Authors: Baudou Éloïse , Ryan Jennifer L , Cox Elizabeth , Nham Lisa , Johnston Krista , Bouffet Éric , Bartels Ute , Timmons Brian , de Medeiros Cynthia , Mabbott Donald J
Published: September 2023

Background

While exercise training (ET) programs show positive outcomes in cognition, motor function, and physical fitness in pediatric brain tumor (PBT) survivors, little is known about the optimal timing of intervention. The aim of this work was to explore the feasibility and benefits of ET based on its timing after radiotherapy.

Methods

This retrospective analysis (ClinicalTrials.gov, NCT01944761) analyzed data based on the timing of PBT survivors' participation in an ET program relative to their completion of radiotherapy: <2 years (n = 9), 2–5 years (n = 10), and > 5 years (n = 13). We used repeated measures analysis of variance to compare feasibility and efficacy indicators among groups, as well as correlation analysis between ET program timing postradiotherapy and preliminary treatment effects on cognition, motor function and physical fitness outcomes.

Results

Two to five years postradiotherapy was the optimal time period in terms of adherence (88.5%), retention (100%), and satisfaction (more fun, more enjoyable and recommend it more to other children). However, the benefits of ET program on memory recognition (r = −0.379, P = .047) and accuracy (r = −0.430, P = .032) decreased with increased time postradiotherapy. Motor function improved in all groups, with greater improvements in bilateral coordination (P = .043) earlier postradiotherapy, and in running (P = .043) later postradiotherapy. The greatest improvement in pro-rated work rate occurred in the < 2-year group (P = .008).

Conclusion

Participation in an ET program should be offered as part of routine postradiotherapy care in the first 1–2 years and strongly encouraged in the first 5 years.
The Impact of Infectious Disease Syndromes on Activities During Military Travel
Authors: Boatwright Michael A , Kuo Huai-Ching , Lindholm David A , Griffith Tara , Colombo Rhonda E , Tribble David R , O’Connell Robert , Lalani Tahaniyat
Published: September 2023

Background

We evaluated the impact of infectious disease (ID) syndromes on US active duty (AD) servicemembers returning from overseas deployment (DEP), military training exercises (EXR), or short-term military travel (eg, temporary assignment of duty [TDY]).

Methods

We conducted a survey-based assessment of US AD servicemembers returning from DEP, EXR, or TDY between 2015 and 2019. Subjects completed a post-travel survey capturing symptoms of travelers’ diarrhea (TD), influenza-like illness (ILI), and febrile illness (FI). Risk factors associated with any ID syndrome (ie, either TD, ILI, or FI) that impacted daily activities were assessed using a logistic regression model with backward selection.

Results

One-third of servicemembers (654/1822) experienced an ID syndrome, and 26% (471/1822) reported a ≥50% reduction in activity level due to an ID syndrome (median duration, 3 days). TD was the most common ID syndrome experienced and accounted for 73% (346/471) of ID syndromes impacting daily activities. The greatest impact of ID syndromes was observed in servicemembers on DEP. Compared with servicemembers on EXR or TDY, those on DEP had a longer duration of travel and a delayed period of risk for ID syndromes. Multivariate analysis identified high-risk exposures (ie, environmental exposures, close contact with locals, consuming food from street vendors) and behaviors (ie, inability to sanitize hands before meals) that could be used to inform mitigation strategies.

Conclusions

ID syndromes result in a significant loss of productivity during military travel. Addressing modifiable risk factors and access to TD self-treatment in high-risk settings may help mitigate the impact of ID threats during military travel.
Predator exclosures increase nest success but reduce adult survival and increase dispersal distance of Piping Plovers, indicating exclosures should be used with caution
Authors: Stantial Michelle L , Cohen Jonathan B , Darrah Abigail J , Maslo Brooke
Published: September 2023

Diagnosing unsuccessful population outcomes for endangered species requires understanding relationships among vital rates, ecological conditions, and management variables, including unintended consequences of management actions. The federally threatened Piping Plover (Charadrius melodus) has remained below recovery goals, despite intensive management, including the use of nest exclosures to protect eggs from predation. We studied ecological factors and management actions affecting nest success, survival, site fidelity, and dispersal of the New Jersey, USA population of Piping Plovers over a 7-yr period, focused on evaluating the impact of exclosures on demography. While exclosures increased nest success by 62% over a 34-day period, exclosed nests were 4.7 times more likely to be abandoned, which was likely a consequence of adult mortality. Abandoned nests were associated with lower adult survival, particularly for males, but there was evidence that site fidelity was greater for birds whose last nest was exclosed vs. unexclosed. Regardless of exclosure status, females who abandoned their first nesting attempt dispersed 10 times farther between attempts than those whose first nest attempts were lost to other causes. Moreover, females that abandoned their last nesting attempts dispersed farther than females that lost their last nest to predation or flooding. This difference was more substantial for males. Our results corroborate studies documenting adverse impacts of exclosures on survival, and, for the first time, demonstrate that surviving mates (particularly females) emigrate from the breeding site, resulting in a realized loss of a local breeding pair. Further, we used an online population project model (i.e., PiperEx) to demonstrate that exclosures are not expected to improve growth rates in New Jersey. We conclude that there is a trade-off among increased nest survival, reduced adult survival and increased emigration rates, and we encourage managers to consider whether exclosures are worth the protection of eggs from predators using online decision support tools.
Integrative analysis reveals the recurrent genetic etiologies in idiopathic pulmonary fibrosis
Authors: Guo S , Dong Y , Wang C , Jiang Y , Xiang R , Fan L -L , Luo H , Liu L
Published: September 2023

Background

Idiopathic pulmonary fibrosis (IPF) is increasingly recognized as a chronic, progressive and fatal lung disease with an unknown etiology. Current studies focus on revealing the genetic factors in the risk of IPF, making the integrative analysis of genetic variations and transcriptomic alterations of substantial value.

Aim

This study aimed to improve the understanding of the molecular basis of IPF through an integrative analysis of whole-exome sequencing (WES), bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data.

Methods

WES is a powerful tool for studying the genetic basis of IPF, allowing for the identification of genetic variants that may be associated with the development of the disease. RNA-seq data provide a comprehensive view of the transcriptional changes in IPF patients, while scRNA-seq data offer a more granule view of cell-type-specific alterations.

Results

In this study, we identified a comprehensive mutational landscape of recurrent genomic and transcriptomic variations, including single-nucleotide polymorphisms, CNVs and differentially expressed genes, in IPF populations, which may play a significant role in the development and progression of IPF.

Conclusions

Our study provided valuable insights into the genetic and transcriptomic variations associated with IPF, revealing changes in gene expression that may contribute to disease development and progression. These findings highlight the importance of an integrative approach to understanding the molecular mechanisms underlying IPF and may pave the way for identifying potential therapeutic targets.
Hand joints without radiographic osteoarthritis maintain their joint space width over 4 years despite what’s happening elsewhere in the hand
Authors: Driban Jeffrey B , Vo Nhung , Duryea Jeff , Schaefer Lena F , Haugen Ida K , Eaton Charles B , Roberts Mary B , Lu Bing , McAlindon Timothy
Published: September 2023

Objectives

We aimed to determine whether hand OA is characterized by systemic cartilage loss by assessing if radiographically normal joints had greater joint space width (JSW) loss over 4 years in hands with incident or prevalent OA elsewhere in the hand compared with hands without OA.

Methods

We used semi-automated software to measure JSW in the distal and proximal IP joints of 3368 participants in the Osteoarthritis Initiative who had baseline and 48-month hand radiographs. A reader scored 16 hand joints (including the thumb base) for Kellgren–Lawrence (KL) grade. A joint had OA if scored as KL ≥2. We identified three groups based on longitudinal hand OA status: no hand OA (KL <2 in all 16 joints) at the baseline and 48-month visits, incident hand OA (KL <2 in all 16 joints at baseline and then one or more joints with KL ≥2 at 48 months) and prevalent hand OA (one or more joints with KL ≥2 at baseline and 48 months). We then assessed if JSW in radiographically normal joints (KL 0) differed across these three groups. We calculated unpooled effect sizes to help interpret the differences between groups.

Results

We observed small differences in JSW loss that are unlikely to be clinically important in radiographically normal joints between those without hand OA (n = 1054) and those with incident (n = 102) or prevalent hand OA (n = 2212) (effect size range −0.01–0.24). These findings were robust when examining JSW loss dichotomized based on meaningful change and in other secondary analyses.

Conclusions

Hand OA is not a systemic disease of cartilage.
The impact of the Digital Content Directive on online platforms’ Terms of Service
Authors: Wiśniewska Katarzyna , Pałka Przemysław
Published: September 2023

The Digital Content Directive 2019/770 (the DCD), aiming to foster the Digital Single Market and improve consumer protection, became applicable on 1 January 2022. This article presents the results of the study of 100 Terms of Service (ToS) of online platforms, conducted to evaluate the Directive’s impact. By combining black letter analysis with qualitative and quantitative empirical research, the contribution sheds new light on the Directive’s assumptions, critically assesses its logic, and makes regulatory suggestions for European lawmakers. Our central finding is that a significant number of the studied contracts (28 per cent) do not contain descriptions of the digital content offered. Many of those that do, keep the descriptions extremely vague. Hence, the central institution of the Directive—conformity with the contract—might be less valuable than the lawmakers have assumed. Even though the DCD introduces the concept of ‘objective’ conformity, we show how, in the digital environment, it might lower legal certainty, defeating one of the purposes of the Directive. Moreover, we also demonstrate how the analysed ToS often fail to meet other requirements, such as the right to retrieve one’s content or the protection from unilateral content deletion. This begs the question about the regulatory approach, the efficacy of the chosen enforcement scheme and, more generally, the enforcement schemes used throughout the EU’s private law. To remedy these problems, we suggest engaging in more empirical research when designing future measures to protect consumers online and considering supplementing the existing enforcement schemes with administrative oversight like the one in the Digital Services Act.
Transcriptome and secretome profiling of sensory neurons reveals sex differences in pathways relevant to insulin sensing and insulin secretion
Authors: Moon Sohyun , Alsarkhi Lamyaa , Lin Tai‐Tu , Inoue Ryota , Tahiri Azeddine , Colson Cecilia , Cai Weikang , Shirakawa Jun , Qian Wei‐Jun , Zhao Jerry Yingtao , El Ouaamari Abdelfattah
Published: September 2023

Sensory neurons in the dorsal root ganglia (DRG) convey somatosensory and metabolic cues to the central nervous system and release substances from stimulated terminal endings in peripheral organs. Sex‐biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory–islet crosstalk. However, the molecular underpinnings of these male–female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex‐biased insulin sensing‐ and/or insulin secretion‐modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5‐12 DRG sensory neurons derived from sexually immature 3‐week‐old male and female C57BL/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. The transcriptome analysis identified, among others, higher insulin signaling/sensing capabilities in female DRG neurons; secretome screening uncovered several sex‐specific candidate molecules with potential regulatory functions in pancreatic β cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG–islet crosstalk with implications in sensory feedback loops in the regulation of β‐cell activity in a sex‐biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies/approaches to fathom the role of the sensory–islet axis in the regulation of energy balance in males and females.
Dual Plate Fixation of Periprosthetic Distal Femur Fractures
Authors: Andring Nicholas A , Kaupp Shannon M , Henry Kaitlin A , Helmig Kathryn C , Sharon Babcock , Halvorson Jason J , Pilson Holly T , Carroll Eben A
Published: September 2023

Objectives:

Dual implants for distal femur periprosthetic fractures (DFPF) is a growing area of interest for these challenging fractures with dual plating (DP) emerging as a viable construct for these injuries. In the current study we review our experience with DP constructs.

Design:

Retrospective case series with comparison group

Setting:

Level 1 academic trauma center

Patients/Participants: Adults >50 years old sustaining comminuted OTA/AO 33-A2 or 33-A3 DFPF treated with either DP or a single distal femur locking plating (DFLP). Patients with simple 33-A1 fractures were excluded. Prior to 2018 patients underwent DFLP after which the treatment of choice at our institution became DP. 34 patients treated with DFLP and 38 with DP met inclusion and follow up criteria. The average patient age in the DFLP group was 74.8 +/- 7.3 years compared to 75.9 +/- 11.3 years in the DP group.

Intervention:

Dual plating or single DFLP

Main Outcome Measurements:

Reoperation rate, alignment, and complications

Results:

Average follow up was 18.2 +/- 13.8 months in the DFLP group and 19.8 +/- 16.1 months in the DP group (p=0.339). There were no statistical differences in demographics, fracture morphology, loss of reduction, or reoperation for any cause (p>.05). However, DP patients were more likely to be weight bearing in the twelve-week postoperative period (p <0.001) and return to their baseline ambulatory status (p = 0.004) compared to DFLP patients.

Conclusions:

Dual plating of distal femoral periprosthetic fractures maintained coronal alignment with a low reoperation rate even with immediate weight bearing and these patients regained baseline level of ambulation more reliably as compared to patients treated with a single distal femoral locking plate.