bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Craniosynostosis in Lethal Perinatal Hypophosphatasia
Authors: Kim Erinn N. , Leung Karen L. , Wong Alvin , McGregor Jyoti , Skolnick Gary B. , Patel Kamlesh B. , Gosman Amanda A.
Published: August 2023

Although perinatal lethal hypophosphatasia (HPP) was once a disease with a universally poor prognosis, it has now become a rare but treatable condition with the advent of enzyme replacement therapy with asfotase alfa. As a result, a greater population of patients with perinatal HPP are presenting with abnormal head shape and craniosynostosis. The authors present here 3 cases of perinatal lethal HPP, 1 treated with traditional open cranial vault remodeling and 2 treated utilizing distraction osteogenesis techniques. All patients demonstrated outcomes comparable to those previously reported with traditional observation or open cranial vault repair. Thorough consideration and discussion between the surgical team and patient’s family is needed to determine a treatment plan that best addresses the goals of patient and family in light of recent advances in medical treatment in this rare patient population in which surgical interventions were previously nearly impossible. This article further supports the safety and efficacy of surgical intervention and explores the utility of distraction osteogenesis to address craniosynostosis in this patient population.
Improving performance of hurdle models using rare-event weighted logistic regression: an application to maternal mortality data
Authors: Awuor Okello Sharon , Otieno Omondi Evans , Odhiambo Collins O.
Published: August 2023

In this paper, performance of hurdle models in rare events data is improved by modifying their binary component. The rare-event weighted logistic regression model is adopted in place of logistic regression to deal with class imbalance due to rare events. Poisson Hurdle Rare Event Weighted Logistic Regression (REWLR) and Negative Binomial Hurdle (NBH) REWLR are developed as two-part models which use the REWLR model to estimate the probability of a positive count and a Poisson or NB zero-truncated count model to estimate non-zero counts. This research aimed to develop and assess the performance of the Poisson and Negative Binomial (NB) Hurdle Rare Event Weighted Logistic Regression (REWLR) models, applied to simulated data with various degrees of zero inflation and to Nairobi county’s maternal mortality data. The study data on maternal mortality were pulled from JPHES. The data contain the number of maternal deaths, which is the outcome variable, and other obstetric and demographic factors recorded in MNCH facilities in Nairobi between October 2021 and January 2022. The models were also fit and evaluated based on simulated data with varying degrees of zero inflation. The obtained results are numerically validated and then discussed from both the mathematical and the maternal mortality perspective. Numerical simulations are also presented to give a more complete representation of the model dynamics. Results obtained suggest that NB Hurdle REWLR is the best performing model for zero inflated count data due to rare events.
Microchimerism as a source of information on future pregnancies
Authors: Úbeda Francisco , Wild Geoff
Published: August 2023

Small numbers of fetal cells cross the placenta during pregnancy turning mothers into microchimeras. Fetal cells from all previous pregnancies accumulate forming the mother’s fetal microchiome. What is significant about microchimeric cells is that they have been linked to health problems including reproductive and autoimmune diseases. Three decades after the discovery of fetal microchimerism, the function of these cells remains a mystery. Here, we contend that the role of microchimeric cells is to inform the fetus about the likelihood that its genes are present in future pregnancies. We argue that, when genes are more likely than average to be in future maternal siblings, fetuses will send a fixed number of cells that will not elicit a maternal immune response against them. However, when genes are less likely to be in future maternal siblings, fetuses will send an ever-increasing number of cells that will elicit an ever-stronger maternal immune response. Our work can explain the observed clinical association between microchimeric cells and pre-eclampsia. However, our work predicts that this association should be stronger in women with a genetically diverse microchiome. If supported by medical tests, our work would allow establishing the likelihood of pregnancy or autoimmune problems advising medical interventions.
Urban birds become less fearful following COVID-19 reopenings
Authors: Diamant Eleanor S. , MacGregor-Fors Ian , Blumstein Daniel T. , Yeh Pamela J.
Published: August 2023

Following the COVID-19 pandemic, many people around the world stayed home, drastically altering human activity in cities. This exceptional moment provided researchers the opportunity to test how urban animals respond to human disturbance, in some cases testing fundamental questions on the mechanistic impact of urban behaviours on animal behaviour. However, at the end of this ‘anthropause', human activity returned to cities. How might each of these strong shifts affect wildlife in the short and long term? We focused on fear response, a trait essential to tolerating urban life. We measured flight initiation distance—at both individual and population levels—for an urban bird before, during and after the anthropause to examine if birds experienced longer-term changes after a year and a half of lowered human presence. Dark-eyed juncos did not change fear levels during the anthropause, but they became drastically less fearful afterwards. These surprising and counterintuitive findings, made possible by following the behaviour of individuals over time, has led to a novel understanding that fear response can be driven by plasticity, yet not habituation-like processes. The pandemic-caused changes in human activity have shown that there is great complexity in how humans modify a behavioural trait fundamental to urban tolerance in animals.
Differences in pMGA1.2 and pMGA1.3 sequences among isolated field strains of Mycoplasma gallisepticum that produce deformed eggs in laying hens.
Authors: Maya-Rodríguez Linda , Gómez-Verduzco Gabriela , Trigo-Tavera Francisco J. , Moreno-Fierros Leticia , Miranda-Morales Rosa Elena
Published: August 2023

Mycoplasmosis in poultry is a chronic disease that causes economic losses in farming and is difficult to eradicate in flocks. Mycoplasma gallisepticum (MG) is one pathogen that causes this disease. This bacterium has many important surface proteins involved in adhesion, transporter activity, and evasion of the immune system, all of which promote infection. The lipoprotein pMGA presents antigenic variability. It includes regions from the pMGA1.2 and pMGA1.3 sequences, which are stable segments with 97% amino acid identity. The aim of this study was to determine the similar and different regions of pMGA1.2 and pMGA1.3 in MG field strains compared with the M83178.1 sequence. We identified 18 MG field strains (16 from eggs, one from an oviduct membrane, and one from an air sac) of laying hen flocks based on the mgc2 gene. We generated six internal primers to amplify six segments that cover the pMGA1.2 and pMGA1.3 sequences; the MGS6 and MSWUV1853 strains served as a positive and negative control, respectively. Segments close to the C-terminal region were amplified more frequently. Interestingly, no field strains presented the same amplification pattern as MGS6. We performed bioinformatics of segments 4 and 6, translating the nucleotide sequences to amino acids. They were compatible with conserved sequences in Myco_haema protein domains in the genus Mycoplasma that belong to Q7NAP3_MYCGA VlhA.3.04. There were differences in the field strains along with a homologous region that suggests genetic transfer has occurred bacterial evolution. The outcomes showed the dynamic variability in pMGA, and these differences could represent an important factor for the development for vaccines to provide protection against MG infection in chickens.
Pseudokordiimonas caeni gen. nov., sp. nov., isolated from activated sludge
Authors: Li Na , Yang Yingxin , Wu Jing , Zhang Hao , Liu Bin , He Jian
Published: August 2023

A bacterial strain designated as LB-31T was isolated from activated sludge. Strain LB-31T was Gram-stain-negative, non-spore-forming and rod-shaped with a single polar flagellum. The isolate grew at 15–37 °C, pH 5.5–8.5 and 0.5–8.5 % (w/v) NaCl. Genome sequencing revealed a genome size of 3.55 Mb, a G+C content of 61.1 mol% and 3222 protein-coding genes. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain LB-31T formed a phyletic lineage that was distinct from the three known genus within the family

Kordiimonadaceae

. The 16S rRNA gene sequence similarity of strain LB-31T to all recognized bacterial species was no more than 94 %. Average nucleotide identity and digital DNA–DNA hybridization values between strain LB-31T and its phylogenetic neighbours were below 72 and 22 %, respectively. The average amino acid identity values for strain LB-31T and its closed phylogenetic neighbours

Kordiimonas

and

Eilatimonas

were below 63%, supporting that strain LB-31T was a member of a novel genus. The predominant respiratory quinone is Q-10, the fatty acid profile predominantly consisted of iso-C17 : 1
 ω9c, iso-C17 : 0, iso-C15 : 0 and summed feature 3 (comprising iso-C15 : 02-OH/C16 : 1
 ω7c), and the major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The combined genotypic and phenotypic data show that strain LB-31T represents a novel species of a novel genus in the family

Kordiimonadaceae

, for which the name Pseudokordiimonas caeni gen. nov., sp. nov. is proposed. The type strain of Pseudokordiimonas caeni is LB-31T (=GDMCC 1.3625T=KCTC 92687T).
Pseudo-neighbourhoods: Approximating the Social Characteristics of Saskatoon’s Locally-Defined Neighbourhoods using Statistics Canada’s Census Profiles
Authors: Marouzi Anousheh , Plante Charles , Neudorf Cory
Published: August 2023

There is a growing desire to use social data to support local evidence-based health planning and decision-making. However, the geographic boundaries which social data are disseminated for do not usually align exactly with boundaries used by local health organizations. In this paper, we propose a method we call “pseudo-geography” to estimate counts for locally-defined geographic boundaries using data on smaller spatial units. We compared six different pseudo-geography methods, using data in Saskatoon, and identified the most accurate one, which incorporates the area-weighted spatial join technique. We further found that the pseudo-geography method can be refined by eliminating the areas with few or no residents before carrying out any spatial joins. We expect this method to be more accurate in larger cities and when the ratio of the locally-defined area to the smaller spatial units gets larger.
An Incognito Standardized Patient Approach for Measuring and Reducing Intersectional Healthcare Stigma
Authors: Smith M. Kumi , Luo Danyang , Meng Siyan , Fei Yunqing , Zhang Wei , Tucker Joseph , Wei Chongyi , Tang Weiming , Yang Ligang , Joyner Benny L , Huang Shujie , Wang Cheng , Yang Bin , Sylvia Sean Y
Published: August 2023

Background

Consistent evidence highlights the role of stigma in impairing healthcare access in people living with HIV (PLWH), men who have sex with men (MSM), and people with both identities. We developed an incognito standardized patient (SP) approach to obtain observations of providers to inform a tailored, relevant, and culturally appropriate stigma reduction training. Our pilot cluster randomized control trial assessed the feasibility, acceptability, and preliminary effects of an intervention to reduce HIV stigma, anti-gay stigma, and intersectional stigma.

Methods

Design of the intervention was informed by the results of a baseline round of incognito visits in which SPs presented standardized cases to consenting doctors. The HIV status and sexual orientation of each case was randomly varied, and stigma was quantified as differences in care across scenarios. Care quality was measured in terms of diagnostic testing, diagnostic effort, and patient-centered care. Impact of the training, which consisted of didactic, experiential, and discussion-based modules, was assessed by analyzing results of a follow-up round of SP visits using linear fixed effects regression models.

Results

Feasibility and acceptability among the 55 provider participants was high. We had a 87.3% recruitment rate and 74.5% completion rate of planned visits (N=238) with no adverse events. Every participant found the training content “highly useful” or “useful.” Preliminary effects suggest that, relative to the referent case (HIV negative straight man), the intervention positively impacted testing for HIV negative MSM (0.05 percentage points [PP], 95% CI,-0.24, 0.33) and diagnostic effort in HIV positive MSM (0.23 standard deviation [SD] improvement, 95% CI, -0.92, 1.37). Patient-centered care only improved for HIV positive straight cases post-training relative to the referent group (SD, 0.57; 95% CI, -0.39, 1.53). All estimates lacked statistical precision, an expected outcome of a pilot RCT.

Conclusions

Our pilot RCT demonstrated high feasibility, acceptability, and several areas of impact for an intervention to reduce enacted healthcare stigma in a low-/middle-income country setting. The relatively lower impact of our intervention on care outcomes for PLWH suggests that future trainings should include more clinical content to boost provider confidence in the safe and respectful management of patients with HIV.
Disrupted excitation-inhibition balance in cognitively normal individuals at risk of Alzheimer’s disease
Authors: Fortel Igor , Zhan Liang , Ajilore Olusola , Wu Yichao , Mackin Scott , Leow Alex
Published: August 2023

Background

Sex differences impact Alzheimer’s disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology.

Objective

Examine how AD risk factors (age, APOE-ɛ4, amyloid-β) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures.

Methods

Individuals from the OASIS-3 cohort (age 42-95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231).

Results

In absence of AD risk factors (APOE-ɛ4/Aβ+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, β = -0.007). Regression modeling including APOE-ɛ4 allele carriers (Aβ-) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, β = 0.014), persisting with inclusion of Aβ+ individuals (p = 0.012, β = 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the trail-making test (p < 0.05).

Conclusion

Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOE-ɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOE-ɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population.
Gender differences in submission behavior exacerbate publication disparities in elite journals
Authors: Basson Isabel , Ni Chaoqun , Badia Giovanna , Tufenkji Nathalie , Sugimoto Cassidy R. , Larivière Vincent
Published: August 2023

Women are particularly underrepresented in journals of the highest scientific impact, with substantial consequences for their careers. While a large body of research has focused on the outcome and the process of peer review, fewer articles have explicitly focused on gendered submission behavior and the explanations for these differences. In our study of nearly five thousand active authors, we find that women are less likely to report having submitted papers and, when they have, to submit fewer manuscripts, on average, than men. Women were more likely to indicate that they did not submit their papers (in general and their subsequently most cited papers) toScience, Nature, orPNASbecause they were advised not to. In the aggregate, no statistically significant difference was observed between men and women in how they rated the quality of their work. Nevertheless, regardless of discipline, women were more likely than men to indicate that their “work was not ground-breaking or sufficiently novel”as a rationale for not submitting to one of the listed prestigious journals. Men were more likely than women to indicate that the “work would fit better in a more specialized journal.” We discuss the implications of these findings and interventions that can serve to mitigate the disparities caused by gendered differences in submission behavior.

Significance

Publishing in high-impact scholarly journals has a significant effect on researchers’ careers. Our findings identify factors that affect submission toScience, Nature, and theProceedings of the National Academy of Sciences of the United States of America(PNAS) and explore whether there is a relationship between gender and desk rejections or submission rates. We found no relationship between gender and reported desk rejection and a relationship between gender and reported submissions. Women were more likely than men to indicate that their “work was not ground-breaking or sufficiently novel” for the listed prestigious journals and that they were advised against submitting to these venues. Men were more likely to indicate that the “work would fit better in a more specialized journal.”
Gills are not used for gas exchange in the suspension-feeding hemichordateProtoglossus graveolens
Authors: Sackville Michael A. , Cameron Christopher B. , Brauner Colin J.
Published: August 2023

The gills are hypothesized to play a key role in early vertebrate evolution by replacing the skin as the primary site of gas exchange. In this scenario, water flow across the gills used for suspension feeding in ancestral deuterostomes was coopted for breathing in stem vertebrates to facilitate the evolution of larger, active fishes. This hypothesis is supported by a stem-vertebrate origin for structures that increase gill capacity for breathing. However, these structures might have instead enhanced an already dominant capacity at the gills of invertebrate deuterostomes rather than mark a shift from the skin. To test this, we characterized gill function for gas exchange in the suspension-feeding hemichordate acorn wormProtoglossus graveolens. We measured oxygen uptake and ammonia excretion in whole worms and worm halves with or without gills at 10°C and during an acute thermal challenge at 20°C to maximize gill recruitment. Gills did not enhance oxygen uptake or ammonia excretion, suggesting they are not a primary site of gas exchange. This is the first test of gill function for gas exchange in a suspension-feeding invertebrate deuterostome, and it provides essential support for the long-hypothesized vertebrate origin of breathing at gills and its role in early vertebrate evolution.
Actomyosin-mediated apical constriction promotes physiological germ cell death inC. elegans
Authors: Kohlbrenner Tea , Berger Simon , Aegerter-Wilmsen Tinri , Laranjeira Ana Cristina , deMello Andrew , Hajnal Alex
Published: August 2023

Germ cell apoptosis inC. eleganshermaphrodites is a physiological process eliminating around 60% of all cells in meiotic prophase to maintain tissue homeostasis. In contrast to programmed cell death in theC. eleganssoma, the selection of germ cells undergoing apoptosis is stochastic.

By live-tracking individual germ cells at the pachytene stage, we found that germ cells smaller than their neighbors are selectively eliminated through apoptosis before differentiating into oocytes. Thus, cell size is a strong predictor of physiological germ cell death. The RAS/MAPK and ECT/RHO/ROCK pathways together regulate germ cell size by controlling actomyosin constriction at the apical rachis bridges, which are cellular openings connecting the syncytial germ cells to a shared cytoplasmic core. Enhancing apical constriction reduces germ cell size and increases the rate of cell death while inhibiting the actomyosin network in the germ cells prevents their death. We propose that actomyosin contractility at the rachis bridges of the syncytial germ cells amplifies intrinsic disparities in cell size. Through this mechanism, animals can adapt the rate of germ cell death and differentiation to changing environmental conditions.
Associations between sex, systemic iron and inflammatory status and subcortical brain iron
Authors: Spence Holly , Mengoa-Fleming Stephanie , Sneddon Alan A. , McNeil Christopher J. , Waiter Gordon D.
Published: August 2023

Key Points

Differences in subcortical brain iron levels were observed between males and females

Females exhibited more associations between brain iron and systemic markers for iron than males.

Males exhibited more associations between brain iron and systemic markers for inflammation than females.

Background

Brain iron is increased in several neurodegenerative diseases, with studies demonstrating relationships between increased subcortical iron and disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron and systemic iron and inflammatory status to improve our understanding of brain iron accumulation.

Methods

Brain MRI scans and blood plasma samples were collected from cognitively healthy females (n=176, mean age = 61.4 ± 4.5 y, age range = 28 - 72 y) andmales (n=152, mean age = 62.0 ± 5.1 y, age range = 32 - 74 y). Quantitative susceptibility mapping was used to quantify regional brain iron. To assess systemic iron, haematocrit, plasma ferritin and plasma soluble transferrin receptor (sTfR) were measured and total body iron index (TBI) was calculated. To assess systemic inflammation, C-reactive protein (CRP), Neutrophil/Lymphocyte ratio (NLR), plasma macrophage colony stimulating factor 1 (MCSF), plasma interleukin 6 (IL6) and plasma interleukin 1β (IL1β) were measured.

Results

Females exhibited associations between TBI and iron levels in the left and right caudate and right pallidum. Females also exhibited associations between haematocrit and iron levels in the right pallidum and left putamen. However, in males, the only association between brain iron and iron status was a positive correlation between iron in the right caudate and ferritin. In males, positive associations were observed between CRP levels and iron in the right thalamus and between IL6 levels and iron in the right amygdala and right pallidum. Males also exhibited a negative association between IL6 levels and iron in the left caudate. Positive associations between iron in the left thalamus and NLR were observed in both sexes.

Conclusions

This study demonstrates differential relationships between systemic iron and inflammation markers and brain iron in females and males. These results suggest differing iron regulation mechanisms in older age between sexes which could lead towards an understanding of the differences in neurodegenerative disease prevalence in males and females.
The effects of human population density on trophic interactions are contingent upon latitude
Authors: Hernandez-Aguero Juan Antonio , Ruiz-Tapiador Ildefonso , Garibaldi Lucas A. , Kozlov Mikhail V. , Mantyla Elina , Nacif Marcos E. , Salinas Norma , Cayuela Luis
Published: August 2023

Aim: Studies conducted at a global scale are necessary to make general conclusions on the effect of urbanization on trophic interactions and explore how these effects change along latitudinal gradients. Since biotic interactions are more intense at lower latitudes, we predict that the intensity of trophic interactions will decrease in response to urbanization (quantified by human population density), with higher impacts of urbanization at higher latitudes.

Location: Global (881 study sites).

Time period: 2000-2021.

Major taxa studied: Birds, arthropods and woody plants.

Methods: We compiled global data on insect herbivory and bird predation from individual studies using similar methodologies, and fitted generalized linear mixed models to test the effect of human population density, latitude and their interaction on these two response variables.

Results: The intensity of herbivory and predation decreased with the increase of human population density at lower latitudes, remained unaffected at intermediate latitudes, and increased at higher latitudes.

Main conclusions: The effect of human population density on insect herbivory and bird predation consistently varies across latitudes, with a reversal of the pattern at high versus low latitudes.
Geogenomic predictors of genetree heterogeneity in an Amazonian bird (Thamnophilus aethiops)
Authors: Musher Lukas J. , Del-Rio Glaucia , Marcondes Rafael S. , Brumfield Robb T. , Bravo Gustavo A. , Thom Gregory
Published: August 2023

Can knowledge about genome architecture inform biogeographic and phylogenetic inference? Selection, drift, recombination, and gene flow interact to produce a genomic landscape of divergence wherein patterns of differentiation and genealogy vary nonrandomly across the genomes of diverging populations. For instance, genealogical patterns that arise due to gene flow should be more likely to occur on smaller chromosomes, which experience high recombination, whereas those tracking histories of geographic isolation (reduced gene flow caused by a barrier) and divergence should be more likely to occur on larger and sex chromosomes. In Amazonia, populations of many bird species diverge and introgress across rivers, resulting in reticulated genomic signals. Herein, we used reduced representation genomic data to disentangle the evolutionary history of four populations of an Amazonian antbird,Thamnophilus aethiops,whose biogeographic history was associated with the dynamic evolution of the Madeira River Basin. Specifically, we evaluate whether a large river capture event ca. 200 kya, gave rise to reticulated genealogies in the genome by making spatially explicit predictions about isolation and gene flow based on knowledge about genomic processes. We first estimated chromosome-level phylogenies and recovered two primary topologies across the genome. The first topology (T1) was most consistent with predictions about population divergence, and was recovered for the Z chromosome. The second (T2), was consistent with predictions about gene flow upon secondary contact. To evaluate support for these topologies, we trained a convolutional neural network to classify our data into alternative diversification models and estimate demographic parameters. The best-fit model was concordant with T1 and included gene flow between non-sister taxa. Finally, we modeled levels of divergence and introgression as functions of chromosome length, and found that smaller chromosomes experienced higher gene flow. Given that (1) gene-trees supporting T2 were more likely to occur on smaller chromosomes and (2) we found lower levels of introgression on larger chromosomes (and especially the Z-chromosome), we argue that T1 represents the history of population divergence across rivers and T2 the history of secondary contact due to barrier loss. Our results suggest that a significant portion of genomic heterogeneity arises due to extrinsic biogeographic processes such as river capture interacting with intrinsic processes associated with genome architecture. Future biogeographic studies would benefit from accounting for genomic processes, as different parts of the genome reveal contrasting, albeit complementary histories, all of which are relevant for disentangling the intricate geogenomic mechanisms of biotic diversification.
Predicted Versus Observed Activity of PCB Mixtures Toward the Ryanodine Receptor
Authors: Griffin Justin A. , Li Xueshu , Lehmler Hans-Joachim , Holland Erika B.
Published: August 2023

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs, and similar compounds, towards RyR1 activation and related neurotoxicity.
Macrophage-targeted DNA methyltransferase inhibitor SGI-1027 decreases atherosclerosis in ApoE-null mice
Authors: Márquez-Sánchez Ana Cristina , Manzanares-Guzmán Alejandro , Carriles-Jaimes Ramón , Sánchez-Segura Lino , Colín-Castelán Dannia , Kamen Dan , Koltsova Ekaterina K. , Martínez-Antonio Agustino , Rodríguez-Ríos Dalia , del Carmen Romo-Morales Gloria , Lund Gertrud , Zaina Silvio
Published: August 2023

Background and aims

Correction of vascular DNA hypermethylation may slow atherogenesis. We tested the anti-inflammatory and anti-atherogenic activity of macrophage-targeted DNA methyltransferase (DNMT) inhibitor SGI-1027.

Methods, Results

SGI-1027 was encapsulated into human serum albumin (HSA) nanoparticles (HSANP) functionalized with the PP1 peptide, a macrophage scavenger receptor 1 ligand, fused to a FLAG epitope (S-HSANP-FLAGPP1). Nanoparticle physico-chemical characteristics predicted good marginalization towards the vascular wall, although SGI-1027 encapsulation efficiency was relatively low (∼23%). S-HSANP-FLAGPP1 were rapidly internalized compared to non-functionalized and, surprisingly, functionalized void controls, and induced a shift towards an anti-inflammatory profile of secreted cytokines in human THP-1 macrophages. S-HSANP-FLAGPP1 colonized the atheroma and induced a significant ∼44% reduction of atherosclerosis burden in the aortic tree of ApoE-null mice compared to controls. A reduction in aortic root atherosclerosis was observed, although primarily induced by HSANP irrespective of loading or functionalization. No alteration of body weight, non-vascular tissue gross histology, plasma glucose, triglyceride or cholesterol were observed. HSA whether free or structured in nanoparticles, induced a 3-4-fold increase in HDL compared to vehicle.

Conclusions

We confirm that DNMT inhibition is anti-atherogenic and provide proof of principle that targeted HSANP are effective carriers for those molecules. SGI-1027 displayed a novel anti-inflammatory activity that is independent of cell proliferation and therefore likely unrelated to DNMT inhibition. HDL elevation may represent an additional advantage of HSA-based nanocarriers.
Spheroid architecture strongly induces miR-221/222 expression and promotes oxidative phosphorylation and survival of mobile tumor cells through a mechanism that includes restriction of miR-9 expression
Authors: Ward Avery S. , Hall Cody N. , Tree Maya O. , Kohtz D. Stave
Published: August 2023

Tumor cell spheroids are three dimensional multicellular structures that form during the expansive growth of carcinoma cells. Spheroids support tumor metastasis as vehicles of dissemination, promoting growth and survival of bulk tumor and cancer stem cells within the mobile tumor cell population. Deciphering how spheroid architecture affects tumor cell phenotype will be essential for the development of therapeutics to inhibit transperitoneal metastasis and the development of peritoneal carcinomatosis by ovarian cancers. We investigated how spheroid formation directly affects OXPHOS activity and microRNA expression in a cultured ovarian carcinoma cell system. The rate of oxidative phosphorylation/respiration per cell in spheroids was nearly double that of the same cell type growing in suspension as single cells. Cells growing as spheroids showed greatly enhanced expression of miR-221/222, an oncomiR that targets multiple tumor suppressor genes, promotes invasion, as well as reduced expression of miR-9, which targets mitochondrial tRNA-modification enzymes and inhibits OXPHOS. Consistent with the greater efficiency of ATP generation afforded by OXPHOS phosphorylation, tumor cells growing as spheroids injected into the nutrient-poor environment of the murine peritoneum survived longer than the cells growing in suspension as loosely associated aggregates. The data suggest that in addition to the reported effects of spheroid formation on cancer cell growth and phenotype, including promotion of stem cell generation, spheroid architecture increases the OXPHOS activity of constituent tumor cells. During the mobile phase of metastasis, when ovarian tumor cells disperse through nutrient-poor environments such as the peritoneum, enhanced OXPHOS activity afforded by spheroid architecture would enhance survival and thereby contribute to metastatic potential.
Navigational systems in the human brain dynamically code for past, present, and future trajectories
Authors: Cheng You (Lily) , Ling Sam , Stern Chantal E. , Chrastil Elizabeth R.
Published: August 2023

Navigational trajectory planning requires the interaction of systems that include spatial orientation and memory. Here, we used a complex navigation task paired with fMRI pattern classification to examine head and travel direction tuning throughout the human brain. Rather than a single, static network, we report multiple simultaneous subnetworks that 1) have strong connections with both allocentric (world-centered) and egocentric (viewer-centered) movement trajectories, 2) change during the course of exploration, 3) code for past and future movements as well as the present direction, and 4) are strongest for individuals who convert their trajectories into egocentric movements once they have learned the environment. These findings shift our understanding of the neural processes underlying navigation from static structure-function relationships to a dynamic understanding of the multiple brain networks that support active navigation. The insights into the nature of individual navigation abilities uncovered here challenge the dominant framework of largely allocentric coding for successful navigation in complex environments, and replace this with a new framework that relies on multiple co-existing dynamic computations.
multiDGD: A versatile deep generative model for multi-omics data
Authors: Schuster Viktoria , Dann Emma , Krogh Anders , Teichmann Sarah A.
Published: August 2023

Recent technological advancements in single-cell genomics have enabled joint profiling of gene expression and alternative modalities at unprecedented scale. Consequently, the complexity of multi-omics data sets is increasing massively. Existing models for multi-modal data are typically limited in functionality or scalability, making data integration and downstream analysis cumbersome. We present multiDGD, a scalable deep generative model providing a probabilistic framework to learn shared representations of transcriptome and chromatin accessibility. It shows outstanding performance on data reconstruction without feature selection. We demonstrate on several data sets from human and mouse that multiDGD learns well-clustered joint representations. We further find that probabilistic modelling of sample covatiates enables post-hoc data integration without the need for fine-tuning. Additionally, we show that multiDGD can detect statistical associations between genes and regulatory regions conditioned on the learned representations. multiDGD is available as an scverse-compatible package (https://github.com/Center-for-Health-Data-Science/multiDGD).
Synthesis, characterization and crystal structure of methyl 2-(2-oxo-2H-chromen-4-ylamino)benzoate
Authors: Hollauer Henrique V. P. , Vilas Novas Rachel C. , Guedes Guilherme P. , Buarque Camilla D. , Escobar Lívia B. L.
Published: August 2023

Methyl 2-(2-oxo-2H-chromen-4-ylamino)benzoate, C17H13NO4 (1), was prepared by condensation between 4-hydroxycoumarin and methyl 2-aminobenzoate. It crystallizes in the orthorhombic space group Pca21 at 300 K. The molecule of compound 1 consists of the 2H-chromen-2-one part connected by an amine moiety (–NH–) to the methyl benzoate ring. The supramolecular array is formed by hydrogen bonds between the aromatic ring and the O atoms of the lactone and ester portions. The structural details match the spectroscopic data acquired from NMR and IR spectroscopy.
Country study on drivers and barriers for employee ownership: the case of MONDRAGON group
Authors: Arando-Lasagabaster Saioa , Herce-Lezeta Beñat
Published: August 2023

Purpose

This article analyses how the MONDRAGON Group has overcome the barriers that the literature identifies in the creation of employee owned companies (Mygind and Poulsen, 2021), and how it has managed to grow over the last few decades.

Design/methodology/approach

To this end, based on an analysis of the legislative framework and the internal documentation of the MONDRAGON Group and its cooperatives, the case of what is often considered the most successful and highly developed network of co-operative firms is studied.

Findings

The study leads us to conclude that MONDRAGON has had sufficient capacity to overcome the barriers faced by worker-owned companies and has known how to adapt to the economic and social demands of each moment, despite the fact that at certain times it has had to act flexibly in its principles.

Research limitations/implications

The work is limited to the analysis of the Group's internal documentation. It would be interesting to complement this vision with the perceptions of MONDRAGON's partners.

Practical implications

The MONDRAGON Group's study can show other cooperative experiences what the keys to success are.

Originality/value

MONDRAGON has been analysed from different perspectives, but how it has overcome the specific barriers presented by employee-owned companies has not been specifically studied. This perspective makes it possible to identify some of the group's success factors.
The assertion of reproductive and social control in mid‐twentieth‐century US transgender medicine
Authors: Shuster Stef M.
Published: August 2023

Drawing on archival materials from the Kinsey Institute, including letters of correspondence between medical professionals and transgender people during the 1950s–1970s, this article demonstrates how scientific and medical communities selectively employed old and new eugenics in their work with trans patients seeking hormonal and/or surgical interventions. Old eugenics helped providers control trans people's reproduction and family formations. New eugenics helped providers maintain social control over trans people's lives and solidify an ‘ideal’ patient who demonstrated their ‘value’ by upholding social fitness standards. This work contributes to histories of trans medicine by analysing this era through the lens of eugenics and expanding understandings of how medical and scientific communities sought to assert reproductive and social control over trans people.
Preoperative automatic reminder systems and impact on quality and compliance with colonoscopy preparation: A multicenter randomized controlled trial
Authors: Chen Bo Ru , Zhang Li Hui , Shi Zhao Hong , Ding Xiang Wu , Liu Yi , Wang Ai Xiang , Chen Zu Fang , Yao Li Wen , Gong Rong Rong , Wang Jun Xiao , Wu Lian Lian , Liu Jun , Yu Hong Gang
Published: August 2023

Objectives

Traditional preoperative reminding services have been applied to enhance the quality of bowel preparation for colonoscopy. In this study we aimed to evaluate the effectiveness of an automated electronic reminder system (E‐reminder) on improving bowel preparation and the quality of preoperative education before colonoscopy.

Methods

From August 2021 to March 2022, 833 outpatients aged 50–75 years who underwent colonoscopy were included and randomly assigned to the E‐reminder group and the control group. While the control group received routine preoperative education. The E‐reminder group received automatic phone call, text message reminders and web services regarding the details of bowel preparation before the colonoscopic examination. The quality of bowel preparation was evaluated by the Boston Bowel Preparation Scale (BBPS) score and the previously validated objective evaluation scale of automatic BBPS (e‐BBPS).

Results

In manual assessment, the rate of adequate bowel preparation was improved in the E‐reminder group of intention‐to‐treat population using BBPS (60.7% vs 54.5%, P = 0.01). The percentage of objective evaluated adequate bowel preparation using e‐BBPS in the E‐reminder group of per‐protocol population was significantly higher than that in the control group (76.9% vs 69.2%, P = 0.02).

Conclusions

E‐reminder was an effective tool to improve the quality of bowel preparation and compliance with medical instructions. It may be regarded as an efficient and convenient education tool, improving the quality of medical service.
Parapapillary drusen of the retinal pigment epithelium
Authors: Jonas Jost B. , Jonas Rahul A. , Jonas Shefali B. , Panda‐Jonas Songhomitra
Published: August 2023

Purpose

To describe the occurrence, morphology and associations of parapapillary drusen of the retinal pigment epithelium (RPE‐drusen).

Methods

Using light microscopy, we histomorphometrically examined enucleated human eyes.

Results

The study included 83 eyes (axial length: 25.9 ± 3.2 mm; range: 20.0–35.0 mm). Eyes with parapapillary RPE‐drusen (n = 29 (35%) eyes) as compared to those without drusen had a significantly shorter axial length (24.0 ± 1.8 mm vs 27.0 ± 3.3 mm; p < 0.001), higher prevalence (27/29 vs 12/54; p < 0.001) and longer width (213 ± 125 μm vs 96 ± 282 μm; p < 0.0001) of parapapillary alpha zone, and thicker BM in parapapillary beta zone (8.4 ± 2.7 μm vs 3.9 ± 2.0 μm; p < 0.001) and alpha zone (6.6 ± 3.9 μm vs 4.4 ± 1.5 μm; p = 0.02). Prevalence of parapapillary RPE‐drusen was 27 (69%) out of 39 eyes with alpha zone. Beneath the RPE‐drusen and in total alpha zone, choriocapillaris was open, while it was closed in the central part of parapapillary beta zone. BM thickness was thicker (p = 0.001) in alpha zone than beta zone, where it was thicker (p < 0.001) than in the region outside of alpha/beta zone. BM thickness outside of alpha/beta zone was not correlated with prevalence of parapapillary RPE‐drusen (p = 0.47) or axial length (p = 0.31). RPE cell density was higher in alpha zone than in the region adjacent to alpha zone (22.7 ± 7.3 cells/240 μm vs 18.3 ± 4.1 cells/240 μm; p < 0.001). In the parapapillary RPE‐drusen, RPE cells were connected with a PAS‐positive basal membrane.

Conclusions

Parapapillary RPE‐drusen as fibrous pseudo‐metaplasia of the RPE were associated with shorter axial length, higher prevalence and larger size of alpha zone, and thicker BM in alpha zone and beta zone. The RPE‐drusen may be helpful to differentiate glaucomatous parapapillary beta zone from myopic beta zone.
Detecting and exploiting the circadian clock in rheumatoid arthritis
Authors: Wilantri Siska , Grasshoff Hanna , Lange Tanja , Gaber Timo , Besedovsky Luciana , Buttgereit Frank
Published: August 2023

Over the past four decades, research on 24‐h rhythms has yielded numerous remarkable findings, revealing their genetic, molecular, and physiological significance for immunity and various diseases. Thus, circadian rhythms are of fundamental importance to mammals, as their disruption and misalignment have been associated with many diseases and the abnormal functioning of many physiological processes. In this article, we provide a brief overview of the molecular regulation of 24‐h rhythms, their importance for immunity, the deleterious effects of misalignment, the link between such pathological rhythms and rheumatoid arthritis (RA), and the potential exploitation of chronobiological rhythms for the chronotherapy of inflammatory autoimmune diseases, using RA as an example.
Drivers of jaguar (Panthera onca) and puma (Puma concolor) predation on endangered primates within a transformed landscape in southern Mexico
Authors: Shedden‐González Aralisa , Solórzano‐García Brenda , White Jennifer Mae , Gillingham Phillipa K. , Korstjens Amanda H.
Published: August 2023

Human pressures have increasingly placed keystone species, such as large cats, under threat. Together with forest loss, prey depletion is one of the main threats to the survival of jaguars (Panthera onca) and pumas (Puma concolor) throughout the Neotropics. Generally, primates are not considered main prey for jaguar and puma, and their inclusion in the diet could be indicative of ongoing prey species decline. Here, we investigate the effect of habitat type and disturbance on primate predation by large cats. Surveys took place during the dry seasons (March to June) of 2010 and 2011, covering a total of 608.5 km across 24 localities in the Uxpanapa Valley, Mexico. We found 65 felid scat samples with the aid of a wildlife scat detection dog, and then examined them to identify predator species and classify the prey remains they contained. Primates represented the most frequent prey (35%) for both jaguar and puma in our study site and constituted approximately half of the biomass consumed by these felines in the area. Primate remains were more likely to be found in scats surrounded by the lowest percentage of conserved forest or in areas surrounded by more villages, showing the potential effects of human activities on these species' populations. The high proportion of primates found in scats within our study site could be an early indication that populations of ungulates and other “typical” prey are beginning to collapse, and urgent conservation interventions are needed for both large cats and primates before they become locally extinct.

Abstract in Spanish is available with online material.