bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent high intraocular pressure after cataract combined with vitrectomy: a case report
Authors: Gao Xianxin , Zhao Rong , Wang Guohua , Liu Xiaonian
Published: December 2024

Introduction and importance:

When pars plana vitrectomy combined with cataract extraction, postoperative intraocular pressure (IOP) elevation is a common complication, especially in cases of incorporated eye trauma.

Case presentation:

A 51-year-old man was admitted to the hospital after sustaining a basketball injury to his right eye, experiencing a persistent dark shadow in his vision for 1 month. An eye examination revealed a visual acuity of 50/100, improving to 80/100 with −1.25DS correction in the right eye, and 100/100 in the left eye. IOP was measured at 25.0 mmHg in the right eye and 15.3 mmHg in the left. The cornea was clear, and the right anterior chamber appeared normal, but aqueous humor flash (++), along with an increase in anterior chamber cells (++). The right pupil was irregularly shaped with a diameter of about 5 mm and had an impaired pupillary light reflex. Lens opacity was noted as C2N2. The vitreous body contained significant blood turbidity, with numerous small dark red hemorrhages at the posterior pole. The patient underwent phacoemulsification and intraocular lens implantation, vitrectomy, gas-liquid exchange, and retinal laser photocoagulation in the right eye. Post-operatively, the patient experienced elevated IOP, which was managed through multiple anterior chamber fluid punctures to control the pressure before discharge.

Clinical discussion:

It is not uncommon for patients with persistent high IOP after cataract combined with vitrectomy. The patient reported in this case was unwilling to undergo further anti-glaucoma surgery. After multiple anterior chamber punctures and drainage, the IOP was finally controlled. There are not many reports in the literature on such patients.

Conclusion:

To investigate the causes of elevated IOP following blunt ocular trauma and vitrectomy, and to provide guidance for clinical diagnosis and treatment.
Exploring Rapport Formation Between Nurses and End-of-Life Patients
Authors: Chang Sung Ok , Jeong Eunhye
Published: December 2024

This study aims to deepen the understanding of rapport formation between nurses and end-of-life patients by synthesizing existing qualitative research. Using meta-ethnography, this research integrates findings from various studies to explore the essence and process of rapport formation from nurses' perspectives. A comprehensive search across MEDLINE, EMBASE, CINAHL, and Web of Science databases in August 2024 identified 13 relevant studies. The quality of these studies was assessed using the Critical Appraisal Skills Programme checklist. The analysis identified 5 key themes in rapport building: “secure acceptance and safety,” “genuine and transparent interaction,” “insight into the patient's world,” “bonding enhanced by professional support,” and “advancing connections within boundaries.” These themes underscore the role of rapport in enhancing the quality of palliative care, providing emotional stability, and improving the nurse-patient relationship. This study offers valuable insights for health care professionals to strengthen nurse-patient interactions, emphasizing the importance of rapport in end-of-life care.
Use of Cholinesterase Inhibitors for Treatment and Prevention of Cognitive Adverse Effects of Electroconvulsive Therapy
Authors: Dylewski Angela , Holder Amanda C. , Brown Jamie N.
Published: December 2024

Although electroconvulsive therapy (ECT) is effective for treating depression, schizophrenia, and mania, cognitive adverse effects may limit use. One possible mechanism for these effects includes cholinergic transmission alterations, supporting potential use of cholinesterase inhibitors for prevention and treatment of these cognitive deficits. The objective of this review is to determine efficacy and safety of cholinesterase inhibitors clinically used for dementia in reducing ECT cognitive adverse effects. PubMed, EMBASE, and CENTRAL were searched in August 2024 for randomized controlled trials using terms and keywords related to cholinesterase inhibitors (acetylcholinesterase inhibitor, cholinesterase inhibitor, donepezil, galantamine, or rivastigmine) and ECT (electroconvulsive therapy, electroconvulsive, electroshock therapy, or ECT). A total of 8 randomized controlled trials were reviewed with mean patient ages ranging from 28.6 to 59.33 years and most common diagnoses including depressive disorders, schizophrenia/psychosis, and bipolar disorder. Six of the 8 trials showed benefits of using cholinesterase inhibitors in patients undergoing ECT. Significant improvements were found in immediate memory after ECT and recovery of personal memory, repetition, alertness, orientation, and impersonal memory compared with placebo. Trials varied in cognitive assessment scales, length of therapy, dosing strategy, ECT schedule, and ECT type/parameters. Cholinesterase inhibitors may be effective for reducing cognitive adverse effects of ECT and appear safe and well tolerated. The most commonly studied medication was donepezil 5 mg daily started shortly before and continued throughout ECT. Additional studies are needed to clarify optimal dosing, titration, duration of therapy, and the role of treatment for older adults, preexisting cognitive impairment, and neurologic comorbidities.
Microthrombi-growth in ADAMTS13 deficiency exacerbated ulcerative colitis via mucosal and endothelial dysfunction
Authors: Tatsuta Kyota , Honkura Naoki , Morooka Nanami , Sakata Mayu , Kurachi Kiyotaka , Sugimoto Ken , Kokame Koichi , Takeuchi Hiroya , Urano Tetsumei , Suzuki Yuko
Published: December 2024

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation and ulceration, with systemic immune dysregulation exacerbating disease progression. While the accumulation of von Willebrand factor (VWF), normally digested by a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) from ultra-large multimers to small molecules, has been implicated in UC pathogenesis, the association between aberrant microthrombus formation and colitis remains unclear.

Methods

Plasma and inflamed colonic tissues from UC patients were analyzed. In the experimental colitis model, we employed an intravital imaging technique to reveal real-time structural dynamics of the mucus layer and the mucosal vasculature. Dextran sulfate sodium (DSS)-induced colitis in wild-type and ADAMTS13-deficient mice was evaluated for disease progression, mucus layer disruption, leukocyte recruitment, and thrombus formation in mucosal vessels using intravital multiphoton excitation microscopy within single-cell spatial resolution.

Results

UC patients exhibited significantly reduced plasma ADAMTS13 activity correlating with disease severity and excessive VWF deposition in inflamed colonic tissues. In DSS-induced colitis mice, ADAMTS13 deficiency showed heightened disease activity and increased mucosal erosion in histochemical analysis compared to wild-type mice. A novel methodology established in this study using intravital microscopy successfully appraised colonic mucus barrier integrity by visualizing fluorescent dextran penetration from the colonic lumen to the crypts. ADAMTS13 deficiency accelerated mucus layer disruption, leukocyte adhesion, and microthrombi formation, particularly close to crypt epithelium regions. Vessel-specific analyses demonstrated that obstructive microthrombi were most prominent in the mucosal layer, contributing to local ischemia and mucosal erosion. Therapeutical usage of recombinant human ADAMTS13 alleviated microthrombus formation, improved mucosal integrity, and mitigated colitis severity in wild-type and ADAMTS13-deficient mice.

Conclusions

Obstructive thrombi formed in mucosal vessels due to impaired ADAMTS13 activity appeared essential in the disease progression of UC. Advanced intravital imaging provided novel insights into single-cell resolution UC pathogenesis.
The selfish yet forgetful brain: Stable cerebral oxygen metabolism during hypoglycemia but impaired memory consolidation
Authors: Bose Antonia , Haschka Stefanie J. , Koehler Johanna , Hesse Felix A. , Martin Santiago , Steinberg Lea , Iakoubov Roman , Riedl Valentin
Published: December 2024

The continuous supply of glucose and oxygen is essential for healthy brain function. Accordingly, the Selfish Brain Theory proposes that the human brain prioritizes its own energy demands, making it less vulnerable to fluctuations in systemic energy availability. Although studies have reported decreases in cerebral glucose metabolism, alternative energy sources other than glucose might be oxidized for ATP production. However, cerebral oxygen metabolism (CMRO2) has never been quantified across the human brain. In this study, we investigated the influence of insulin-induced hypoglycemia on CMRO2in healthy male participants. Additionally, we explored the prolonged effects of hypoglycemia on cognitive function following the restoration of euglycemia. We found that CMRO2remained stable under hypoglycemia, even at blood glucose levels below 49 mg/dL. Interestingly, we detected a significant increase in cerebral blood flow (CBF) of up to 11%, particularly in regions involved in higher cognitive processing. Despite stable rates of oxygen metabolism, we identified a selective impairment in memory consolidation following hypoglycemia, even after normal glucose levels were restored, with no effects observed in memory encoding or attention. In favor of the Selfish Brain Theory, the stability in CMRO2suggests that the brain efficiently shifts to alternate energy pathways under hypoglycemia, potentially using astrocytic glycogen. Despite this metabolic flexibility, our results indicate that prior hypoglycemia imposes long-lasting effects on memory consolidation, possibly linked to glycogen depletion and impaired glutamate synthesis. In summary, our study suggests that clinical states of hypoglycemia pose a critical impact on patients’ brain health and functioning.
Aging disrupts spatiotemporal coordination in the cycling ovary
Authors: Lan Tammy C.T. , Fischer David S. , Kochersberger Alison , Raichur Ruth , Szady Sophia , Simeonova Radiana , Minagar Andrew , Tran Hien , Shalek Alex K. , Sabeti Pardis C. , Kumar Vipin , Marrero Giovanni , Barrera Irving , Mangiameli Sarah , Chen Fei , Garrison Jennifer L. , Chung Hattie
Published: December 2024

Throughout the female reproductive lifespan, the ovary completes hundreds of cycles of follicle development, ovulation, and tissue regeneration1–3. These processes rely on the precise coordination of intricate multicellular interactions across time and space4. How aging disrupts these interactions, leading to the overall decline in reproductive and endocrine functions, remains understudied. To understand the multicellular dynamics that underlie ovarian function and their changes with age, here we use Slide-seq, a near-cellular spatial transcriptomics method, to profile 21 ovaries across reproductive cycles and chronological age, representing 601,831 near-cellular spots across 68 spatial transcriptomic profiles5,6. We develop a segmentation analysis to identify static snapshots of spatial niches that capture folliculogenesisin situ, allowing us to examine the multicellular dynamics of 345 oocytes, 653 follicles, and 234 corpora lutea. We find that aging disrupts both the spatial organization and temporal coordination of folliculogenesis before the cessation of cycling, leading to dysregulation of hormone production and signaling. These disruptions are marked by altered immune cell dynamics, inflammatory signaling, and global tissue disorganization that impair the cyclic remodeling required for ovarian function. Our findings reveal how multicellular niches orchestrate the reproductive and endocrine functions of the ovary and demonstrate how age-related breakdown of tissue organization across time and space precedes reproductive decline.
Investigating the Impacts of Sphingomyelinases on Extracellular Vesicle Cargo Sorting
Authors: Padilla Juan-Carlos A. , Barutcu Seda , Boulais Jonathan , Chen Yiran , Syed Easin , Kwon Eunjeong , Lécuyer Eric
Published: December 2024

Extracellular vesicles (EVs) form through regulated biogenesis processes involving sphingomyelinases (SMases), enzymes that metabolize sphingomyelin to produce ceramide—a lipid influencing membrane rigidity and essential for EV generation. This study explores the impact on EV protein and RNA cargoes resulting from inhibiting neutral SMase (NSM) and acid SMase (ASM) in human MCF7 cells. Our results revealed that NSM inhibition reduces EV nanoparticles and diminishes RNA and protein cargoes, including endosomal, spliceosomal, and translation-related proteins. Conversely, ASM inhibition increased RNA-binding proteins within and enhanced the expression of ribonucleoprotein complex-associated RNA in released EVs, including several snRNAs and 7SL RNA. Intriguingly, ASM-inhibited EVs enhanced the migration and translational activity of recipient MCF10A cells. These findings suggest an important role for SMase-dependent vesiculation in governing RNA and protein trafficking to the extracellular space, unveiling potential implications for cellular communication and function.
Changes in Female Cancer Diagnostic Billing Rates over the COVID-19 Period in the Ontario Health Insurance Plan
Authors: McLeod Deanna , Martins Ilidio , Tinker Anna V. , Selk Amanda , Brezden-Masley Christine , LeVasseur Nathalie , Altman Alon
Published: December 2024

Background and Objectives The initial response to COVID-19 in Ontario included suspension of cancer screening programs and deferral of diagnostic procedures and many treatments. Although the short-term impact of these measures on female cancers is well documented, few studies have assessed the mid- to long-term impacts. We conducted an analysis of Ontario Health Insurance Program (OHIP) claims for female cancer diagnostic codes by comparing annual billing prevalence and incidence rates during the COVID-19 period (2020-2022) to pre-COVID-19 levels (2015-2019). Methods Linear regression analysis was used to fit pre-COVID-19 (2015-2019) data for each OHIP billing code and extrapolate counterfactual values for the years of 2020-2022. Excess billing rates were calculated as the difference between projected and actual rates for each year. Results In 2020, OHIP billing prevalence rates for cervical, breast, uterine and ovarian cancer decreased relative to projected values for that year by -50.7/100k, -13.9/100k, -3.5/100k and -3.8/100k, respectively. The reverse was observed in 2021 with rate increases of 47.8/100k, 59.1/100k, 2.5/100k and 3.7/100k, respectively. In 2022, the excesses were further amplified, especially for cervical and breast cancers (111.2/100k and 78.67/100k, respectively). The net excess patient billing rate for 2020-2022 was largely positive for all female cancers (108.3/100k, 123.7/100k, 5.2/100k, 1.8/100k, respectively). Analysis of billing incidence rates showed similar trends. Conclusion The expected female cancer billing rate decreases in 2020 were followed by large increases in 2021 and 2022, resulting in a cumulative excess during the COVID-19 period. Further research is required to assess the nature of these changes.
Estimating scale-dependent covariate responses using two-dimensional diffusion derived from the SPDE method
Authors: Lindmark Max , Anderson Sean C. , Thorson James T.
Published: December 2024

Species distribution models (SDMs) are widely used to standardize spatially unbalanced data, project climate impacts, and identify habitat for conservation. SDMs typically estimate the impact of local environmental conditions by applying a pointwise basis expansion, thereby estimating a dome-shaped or non-parametric “environmental response function”. However, ecological responses integrate across local habitat conditions, such that the species density depends on habitat at the location of sampling but also at nearby locations.

To address this, we extend methods from the Stochastic Partial Differential Equation (SPDE) method that is widely used in INLA, which approximates spatial correlations based on local diffusion over a finite-element mesh (FEM). We specifically introduce the sparse inverse-diffusion operator on a FEM, and apply this operator to covariates to efficiently calculate a spatially weighted average of local habitat that is then passed through pointwise basis-expansion to predict species densities. We show that this operator has several useful properties, i.e., conservation of mass, linear computational time with spatial resolution, and a uniform stationary distribution, where the latter ensures that estimated responses are invariant to linear (scale and offset) transformations of covariates.

We test this covariate-diffusion method using a simulation experiment, and show that it can correctly recover a non-local environmental response while collapsing to a local (pointwise) response when warranted. We apply it to monitoring data for 25 bottom-associated fishes in the eastern Bering Sea and 20 bird species in the western United States. This application confirms that non-local responses in the eastern Bering Sea case study are parsimonious for 25 species-maturity combinations, while 20 collapse to the null method. Estimates suggest that some species-maturity combinations avoid proximity to the continental slope, beyond what is predicted by local bathymetry in isolation. By contrast, in only 2 of the 20 bird species is the diffused human population density covariate more parsimonious than the original covariate.

The covariate-diffusion method introduced here constitutes a fast and efficient approach to modelling non-local covariate effects. This flexible method may be useful in cases when covariates influence nearby population densities, for instance due to movement of the sampled species or its important biological or physical drivers.
Purifying Selection Shapes the Dynamics of P-element Invasion inDrosophilaPopulations
Authors: Langmüller Anna M. , Haller Benjamin C. , Nolte Viola , Schlötterer Christian
Published: December 2024

Background

Transposable elements (TEs) are DNA sequences that can move within a host genome. Many new TE insertions have deleterious ebects on their host and are therefore removed by purifying selection. The genomic distribution of TEs thus reflects a balance between new insertions and purifying selection. However, the inference of purifying selection against deleterious TE insertions from the patterns observed in natural populations is challenged by the confounding ebects of demographic events, such as population bottlenecks and migration.

Results

We used Experimental Evolution to study the role of purifying selection during the invasion of the P-element, a highly invasive TE, in replicatedDrosophila simulanspopulations under controlled laboratory conditions. Because the change in P-element copy number over time provides information about the transposition rate and the ebect of purifying selection, we repeatedly sequenced the experimental populations to study the P-element invasion dynamics. Based on these empirical data we used Gaussian Process surrogate models to infer parameter values characterizing the observed P-element invasion trajectory. We found that 73% of P-element copies are under purifying selection with a mean selection coebicient of -0.056, highlighting the central role of selection in shaping P-element invasion dynamics.

Conclusion

This study underscores the power of Experimental Evolution as a tool for studying transposable element invasions, and highlights the pivotal role of purifying selection in regulating P-element dynamics.
Continuous Prediction of Mice Lever-Pressing Kinematic Parameters by Background Removed Single-photon Calcium Images
Authors: Li Mingkang , Wang Ruixue , Wan Guihua , Yang Yuqi , Zhang Shaomin
Published: December 2024

Calcium imaging has gained extensive application in neural decoding tasks because of its high precision in observing cortical neural activity. Nevertheless, the immense data volume and complexity of automated signal extraction algorithms in calcium imaging result in significant delays in extracting neuronal calcium fluorescence signals, greatly constraining the efficiency of neural decoding research and its applicability in real-time tasks. Although a few studies have successfully used partial neuronal signals from calcium imaging data for real-time neural decoding and brain-computer interface tasks, they fail to leverage the complete neuronal dataset from experiments, which limits their ability to decode continuous and complex movements. In response to this challenge, we introduce a neural decoding method based on background-removed single-photon calcium images. This approach extracts three-dimensional spatiotemporal representations of neuronal activity via background removal and employs a decoder combining 3D-ResNet and RNN networks to enable continuous and rapid decoding of mouse lever-pressing kinematic parameters. Compared with traditional methods for neural decoding using single-photon calcium imaging, this approach offers higher accuracy and faster speed. Combined with real-time motion correction algorithms, the proposed neural decoding approach meets real-time decoding requirements at a 20Hz acquisition frame rate, achieving single decoding in just 21.8ms. This advancement significantly improves the efficiency of single-photon calcium imaging-based neural decoding, offering solutions for its application in real-time tasks, such as optical brain-computer interfaces.
A population-level analysis of armed conflict and diphtheria at the subnational level in the WHO African Region 2017-2024
Authors: O’Sullivan Tierney , Keegan Lindsay T.
Published: December 2024

Background

Diphtheria has been re-emerging around the world at alarming rates, raising concerns about emergency preparedness when global supplies of life-saving diphtheria antitoxin are insufficient. Outbreaks have occurred in areas with suboptimal coverage of the three-dose diphtheria tetanus and pertussis (DTP3) vaccine and regions experiencing conflict, but systematic studies assessing the association between these variables and the risk of diphtheria emergence are limited. This population-level study aimed to investigate the relationship between fatalities from armed conflict events, childhood DTP3 vaccination coverage, and the presence of reported diphtheria cases in countries in the World Health Organization’s (WHO) African region from 2017-2024.

Methods

The analysis was conducted at the subnational geographic scale of administrative level 1 (ADM1) (N countries=35, N ADM1 regions=541) from March 2017 to March 2024. We first used a univariate logistic regression model to establish a crude relationship between the ADM1 diphtheria status from 2017-2024 and the population-adjusted cumulative conflict-related fatalities from 2013-2024. We then fit three competing generalized logistic models with random effects accounting for weekly repeated measures at the ADM1 and country levels to estimate the relationship between time-varying rates of conflict-related fatalities and diphtheria status, adjusting for diphtheria vaccine coverage estimates.

Results

Results from the crude model indicate that higher ten-year cumulative rates of conflict-related fatalities are associated with a higher risk of reported diphtheria cases (OR = 1.41, 95% CI: 1.17-1.68). The results from the best-fitting repeated measures model indicate that higher rates of log-transformed conflict-related fatalities are associated with a 17.6-fold increase in diphtheria risk (OR = 17.6, 95% CI: 13.99-22.08), though risk varied widely by state and country. The best-fit model also associated lower estimates of diphtheria risk in areas with high (>80%) and low (<50%) vaccine coverage, though this is possibly due to underreporting of the true burden of disease in low-resource settings.

Conclusions

This exploratory analysis indicates that a history of fatalities from armed conflict is a potentially helpful indicator of subnational diphtheria risk in countries in the WHO African region from 2017-2024. Further, it may be especially useful if estimates of population-level diphtheria immunity are limited.
Inflammation-like environments limit the loss of quorum sensing inPseudomonas aeruginosa
Authors: Fu Taoran , Wright Rosanna C.T. , Gifford Danna R. , Knight Christopher G. , Brockhurst Michael A.
Published: December 2024

Within-host environments are complex and multidimensional, making it challenging to link evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator,lasR, is a common adaptation ofPseudomonas aeruginosaduring chronic infections. Here, we use experimental evolution in host-mimicking media to show that loss of QS is constrained by environmental factors associated with host inflammation. Specifically, environments combining oxidative stress and abundant free amino acids limited loss of QS, whereas QS loss was rapid in the absence of oxidative stress regardless of amino acids. Under oxidative stress,lasRmutations were contingent upon first decoupling regulation of oxidative stress responses from QS via mutations in the promoter region of the primary catalase,katA, or in the oxidative stress regulator,oxyR, enabling maintenance of oxidative stress tolerance. Together, our findings suggest that host inflammatory responses likely delay the loss of QS whilst colonizers undergo stepwise evolution, first adapting to survive lethal stressors before responding to other nutritional selective drivers that favour loss of QS.

Significance Statement

Pseudomonas aeruginosais a common cause of chronic infections characterized by persistent inflammation. Host inflammatory responses alter within-host environments, including by increasing levels of antimicrobial stressors and releasing free amino acids through proteolysis. Here, we show stepwise adaptation of experimentalP. aeruginosapopulations to inflammation-like environments, first adapting to survive lethal stress by decoupling oxidative stress responses from quorum sensing, before then adapting to the nutritional conditions, delaying the loss of quorum sensing. These results highlight the power of using laboratory evolution experiments to disentangle the multidimensional selective forces driving pathogen adaptation in complex within-host environments.
Incomplete adaptation to surface movement during hand reaching
Authors: Balestrucci Priscilla , Bianchi Matteo , Ryan Colleen P. , Daniele Giulia , Flamini Alice , Valente Fanny , Lacquaniti Francesco , Moscatelli Alessandro
Published: December 2024

Humans can effectively adapt to changes in the environment to maintain adequate motor performance in a vast range of situations. However, residual errors tend to persist when stronga prioriassumptions about the statistical regularities of the environment are violated. In our study, we challenged the expectation that inanimate objects are usually at rest. To this end, we used a robotic interface to move a plate over which participants slid their finger while reaching towards a target. We found limited evidence of adaptation after prolonged exposure to this perturbation, and only when visual feedback about hand position was provided. Although participants were aware of the motion of the contact surface, explicit knowledge about its direction was limited. Our results provide important insights on the limits of adaptation to motion perturbation in the somatosensory system, which can inform the design of technology applications such as haptic interfaces and collaborative robots.
Barley disease screening: a multiplex digital droplet PCR approach for the detection ofRamularia collo-cygni, Rhynchosporium graminicolaandPyrenophora teres
Authors: Zia Rabisa , Popper Zoë A. , Kildea Steven
Published: December 2024

Barley is the most widely grown cereal crop in Ireland and faces substantial yield loss annually due to airborne, seed-borne, and soil-borne pathogens. The most prevalent and destructive of these include Ramularia leaf spot, Barley leaf scald and Net blotch, caused byRamularia collo-cygni, Rhynchosporium graminicolaandPyrenophora teresrespectively. Infected seeds are considered as the major source of inoculum for these diseases. The absence of varietal resistance for these fungal pathogens suggests the need for better disease management strategies. Accurate pathogen detection is one of the most widely accepted disease management strategies. Here we demonstrate two digital droplet PCR (ddPCR) assays, based on TaqMan probe chemistry, for the detection of the above pathogens. ddPCR is a third generation of PCR, relying on sample partition into thousands of droplets in which each droplet acts as a reaction unit, enabling pathogen detection at extremely low levels. We developed a multiplex assay capable of detectingR. graminicola, R.collo-cygniandP. teres. ForP. teressamples, a further assay was designed to distinguish between the two economically significant forms ofP. teresi.e.P. teresf. maculata (Ptm; spot form of Net blotch) andP. teresf. teres (Ptt; net form of Net blotch). The assay offers sensitive and selective pathogen detection from barley seeds to pico moles/µl level. Finally, the efficacy of the assay was demonstrated by screening a collection of historical barley seeds.
Bounding phenotype transition probabilities via conditional complexity
Authors: Dingle Kamal , Hagolani Pascal , Zimm Roland , Umar Muhammad , O’Sullivan Samantha , Louis Ard A.
Published: December 2024

By linking genetic sequences to phenotypic traits, genotype-phenotype maps represent a key layer in biological organisation. Their structure modulates the effects of genetic mutations, shaping evolutionary outcomes. Recent work based on algorithmic information theory introduced an upper bound on the likelihood of a random genetic mutation causing a transition between two phenotypes, using only the conditional complexity between them. Here we evaluate how well this bound works for a range of biologically relevant genotype-phenotype maps, including a differential equation model for circadian rhythm, a matrix-multiplication model of gene regulatory networks, a developmental model of tooth morphologies for ringed seals, a polyomino-tile shape model of biological self-assembly, and the HP lattice protein model. By assessing three levels of predictive performance, we find that the bound provides meaningful estimates of transition probabilities across these complex systems. These results suggest that transition probabilities can be predicted to some degree directly from the phenotypes themselves, without needing detailed knowledge of the underlying genotype-phenotype map. This offers a powerful approach for understanding evolutionary dynamics in complex biological systems.
Accelerating Wound Healing Through Deep Reinforcement Learning: A Data-Driven Approach to Optimal Treatment
Authors: Lu Fan , Zlobina Ksenia , Baniya Prahbat , Li Houpu , Rondoni Nicholas , Asefifeyzabadi Narges , Hee Wan Shen , Tebyani Maryam , Schorger Kaelan , Franco Celeste , Bagood Michelle , Teodorescu Mircea , Rolandi Marco , Isseroff Rivkah , Gomez Marcella
Published: December 2024

Advancements in bioelectronic sensors and actuators have paved the way for real-time monitoring and control of wound healing progression. Real-time monitoring allows for precise adjustment in treatment strategies that align with an individual’s unique biological response. However, due to the complexities of human-drug interactions and a lack of predictive models it is challenging to determine just how one should adjust drug dosage to achieve the desired biological response. This work proposes an adaptive closed-loop control framework that integrates deep learning, optimal control, and reinforcement learning to update treatment strategies in real-time with the goal of accelerating wound closure. The proposed approach eliminates the need for mathematical modeling of complex nonlinear wound healing dynamics. We demonstrate the convergence of the controller via anin silicoexperimental setup, where the proposed approach successfully accelerates the wound healing process by 17.71%. Finally, we share the experimental setup and results of anin vivoimplementation to highlight the translational potential of our work. Our data-driven model estimates a 40% acceleration in wound closure.
Marine fishes exhibit exceptional variation in biofluorescent emission spectra
Authors: Carr Emily M. , Thurman Mason M. , Martin Rene P. , Sparks Tate S. , Sparks John S.
Published: December 2024

Biofluorescence is a phylogenetically widespread phenomenon among marine fishes, yet the phenotypic diversity in fluorescent emission wavelengths (e.g., green, red) remains poorly studied across the broad diversity of marine teleosts. In this study we investigate the fluorescent emission spectra from a diverse array of 18 teleost families and record fluorescent emission peaks over multiple body regions. Our results show that fluorescent emission spectra are remarkably diverse among teleost families, as well as within genera. Fluorescent emissions also varied across different body regions within some individuals. We show that members of the families Gobiidae, Oxudercidae, and Bothidae, exhibit at least six distinct, non-overlapping fluorescent emission peaks. Nine of the 18 families examined in this study were found to have at least four distinct and non-overlapping fluorescent emission peaks. Further, we find that several families exhibit multiple discrete emission peaks for a single fluorescent color (i.e., wavelength range), including multiple distinct peaks within the green and red portions of the spectrum. This exceptional degree of phenotypic variation in fluorescent emissions highlights the potential for a diverse, even species-specific, fluorescent signaling system in certain teleost families. The interplay between different fluorescent emission wavelengths and notable variation in the distribution of fluorescence on the body could allow for a wide array of fluorescent patterns to be produced by an individual or among closely related species. Our results reveal far more diversity in both fluorescent emission wavelengths (colors) and in the distribution of fluorescent molecules on the body than had previously been reported in the literature. We characterize this novel variation in fluorescent emissions across an array of teleost families that exhibit biofluorescence and discuss the potential functional implications of this exceptional phenotypic variability.
The gut microbiome promotes mitochondrial respiration in the brain of a Parkinson’s disease mouse model
Authors: Morais Livia H. , Stiles Linsey , Freeman Milla , Oguienko Anastasiya D. , Hoang Jonathan D. , Jones Jeff , Quan Baiyi , Devine Jack , Bois Justin S. , Chou Tsui-Fen , Trinh Joanne , Picard Martin , Gradinaru Viviana , Mazmanian Sarkis K.
Published: December 2024

The pathophysiology of Parkinson’s disease (PD) involves gene-environment interactions that impair various cellular processes such as autophagy, lysosomal function, or mitochondrial dysfunction. Specifically, mitochondria-associated gene mutations increase PD risk, mitochondrial respiration is altered in the PD brain, and mitochondrial-damaging toxins cause PD-like motor and gastrointestinal symptoms in animal models. The gut microbiome is altered in PD patients and represents an environmental risk, however a relationship between mitochondrial function and the microbiome in PD has not been previously established. Herein, we report that striatal mitochondria are functionally overactive in α-synuclein-overexpressing (ASO) mice, a model of PD, and that microbiome depletion restores respiration and mitochondria-associated gene expression patterns to wild-type levels. ASO mice harboring a complex microbiome produce increased reactive oxygen species in the striatum whereas germ-free counterparts express elevated levels of antioxidant proteins that may buffer against oxidative damage. Indeed, antioxidant treatment improves motor performance in ASO mice and, remarkably, blocking oxidant scavenging in germ-free mice induces α-synuclein-dependent motor deficits. Thus, the gut microbiome increases mitochondrial respiration and oxidative stress in the brain, which enhances motor symptoms in a mouse model of PD.
IMPACT OF BK POLYOMAVIRUS INFECTION IN CHILDREN AFTER KIDNEY TRANSPLANT IN A REFERENCE CENTER IN SALVADOR – BAHIA, BRAZIL
Authors: Fucs Machado Mariana Perdiz , Costa Mattoso Ricardo José
Published: December 2024

Introduction

BK Polyomavirus infection has a high incidence in the post-renal transplant phase and is considered a significant cause of premature graft failure after transplantation. Pediatric renal patients undergo relatively more potent immunosuppression; however, despite the large number of studies conducted in adult renal recipients, there is limited information on BKPyV infection in the pediatric population.

Objective

To estimate the incidence of BK Polyomavirus infection after kidney transplantation in pediatric patients undergoing immunosuppressive therapy at a referral center.

Methodology

Observational descriptive study, with data collection based on medical records of children undergoing kidney transplantation at Hospital Ana Nery, Salvador-BA, from 2009 to 2017.

Results

Forty-one children were evaluated, of which 21 (51.2%) were female. The mean age of the sample was 11 ± 3, with a higher frequency of patients in the age range of 13-17 years (43.9%). Regarding the presence of BKPyV infection, most patients were not infected (56.1%). Regarding the type of antiproliferative and calcineurin inhibitor, Mycophenolate Mofetil was used in 37 (90.2%) patients and Tacrolimus in 40 (97.6%). When comparing the groups with the presence or absence of BKPyV infection, there was no statistically significant difference between the variables: sex (p = 0.890), age (p = 0.829) and type of antiproliferative used (p = 0.187). In the analysis of renal function, an increase in creatinine was observed in 38.9% of infected patients, while among the uninfected patients, only 13% presented an increase in the period of one year. The difference between these two groups (p = 0.05) therefore demonstrated an association between worsening renal function and the presence of BKPyV infection.

Conclusion

The incidence of BK Polyomavirus infection in pediatric patients undergoing kidney transplantation, in the period of one year after the surgical procedure, is almost 50%. No differences could be demonstrated between the groups with and without BKPyV infection and established risk factors, such as sex, age and immunosuppressive therapy used. Furthermore, a worsening of renal function was evidenced among infected patients, when compared to the uninfected group, in this period of one year.
Spruce hybrids show superior cumulative growth and intermediate response to climate anomalies, as compared to their ecologically divergent parental species
Authors: Reed-Métayer Edouard , Depardieu Claire , Lenz Patrick , Bousquet Jean , Perron Martin
Published: December 2024

Climate change brings new constraints to which trees will have to adapt, including more frequent weather extremes. Black spruce and red spruce are phylogenetically close but adapted to different ecological conditions, and they form a natural hybrid zone where their distributions come into contact. Thus, they represent an interesting model to study the effect of introgressive hybridization in the context of climate change, given that interspecific gene flow could affect their capacity to adapt where their natural distributions overlap. Using a common-garden field test gathering 20-year-old progeny trees resulting from rigorous controlled crosses including previously verified genetic identity of the parents, growth patterns and wood density differences could be observed between species and between them and their F1hybrids. A dendroecological analytical approach relying on wood cores was used and revealed similar wood responses to climatic variations between species, both through lifetime climate sensitivity and through episodic stress response indexes. They were however differentially expressed in early- and latewood between black spruce and red spruce, differences likely driven by diverging cambial phenology adaptations to different growing season lengths. F1hybrids exhibited hybrid vigor for cumulative growth under the test site conditions, but showed intermediate values for traits related to climate response. These results offer new perspectives for understanding the dynamics of adaptation in hybrid zones in the context of climate change, as well as for guiding conservation and genetic improvement efforts.

Highlights

F1cumulative growth is higher than their ecologically contrasted parents.

Hybrids had intermediate climate responses

Parental species responded similarly to climate anomalies, but in various intra-ring part.

Cambial phenology likely drives divergences in wood reaction to climate anomalies
Stability through plasticity: Finding robust memories through representational drift
Authors: Natrajan Maanasa , Fitzgerald James E.
Published: December 2024

Memories are believed to be stored in synapses and retrieved through the reactivation of neural ensembles. Learning alters synaptic weights, which can interfere with previously stored memories that share the same synapses, creating a tradeoff between plasticity and stability. Interestingly, neural representations exhibit significant dynamics, even in stable environments, without apparent learning or forgetting—a phenomenon known as representational drift. Theoretical studies have suggested that multiple neural representations can correspond to a memory, with post-learning exploration of these representation solutions driving drift. However, it remains unclear whether representations explored through drift differ from those learned or offer unique advantages. Here we show that representational drift uncovers noise-robust representations that are otherwise difficult to learn. We first define the non-linear solution space manifold of synaptic weights for a fixed input-output mapping, which allows us to disentangle drift from learning and forgetting and simulate representational drift as diffusion within this manifold. Solutions explored by drift have many inactive and saturated neurons, making them robust to weight perturbations due to noise or continual learning. Such solutions are prevalent and entropically favored by drift, but their lack of gradients makes them difficult to learn and non-conducive to further learning. To overcome this, we introduce an allocation procedure that selectively shifts representations for new information into a learning-conducive regime. By combining allocation with drift, we resolve the tradeoff between learnability and robustness.
Recovery of highly contiguous genomes from complex terrestrial habitats reveals over 15,000 novel prokaryotic species and expands characterization of soil and sediment microbial communities
Authors: Sereika Mantas , Mussig Aaron James , Jiang Chenjing , Knudsen Kalinka Sand , Jensen Thomas Bygh Nymann , Petriglieri Francesca , Yang Yu , Jørgensen Vibeke Rudkjøbing , Delogu Francesco , Sørensen Emil Aarre , Nielsen Per Halkjær , Singleton Caitlin Margaret , Hugenholtz Philip , Albertsen Mads
Published: December 2024

Genomes are fundamental to understanding microbial ecology and evolution. The emergence of high-throughput, long-read DNA sequencing has enabled recovery of microbial genomes from environmental samples at scale. However, expanding the microbial genome catalogue of soils and sediments has been challenging due to the enormous complexity of these environments. Here, we performed deep, long-read Nanopore sequencing of 154 soil and sediment samples collected across Denmark and through an optimised bioinformatics pipeline, we recovered genomes of 15,314 novel microbial species, including 4,757 high-quality genomes. The recovered microbial genomes span 1,086 novel genera and provide the first high-quality reference genomes for 612 previously known genera, expanding the phylogenetic diversity of the prokaryotic tree of life by 8 %. The long-read assemblies also enabled the recovery of thousands of complete rRNA operons, biosynthetic gene clusters and CRISPR-Cas systems, all of which were underrepresented and highly fragmented in previous terrestrial genome catalogues. Furthermore, the incorporation of the recovered MAGs into public genome databases significantly improved species-level classification rates for soil and sediment metagenomic datasets, thereby enhancing terrestrial microbiome characterization. With this study, we demonstrate that long-read sequencing and optimised bioinformatics, allows cost-effective recovery of high-quality microbial genomes from highly complex ecosystems, which remain the largest untapped source of biodiversity for expanding genome databases and filling in the gaps of the tree of life.
Identification ofSENP7andUTF1/VENTXas new loci influencing clustered protocadherin methylation across blood and brain using a genome-wide association study
Authors: Liu Yunfeng , Vukic Maja , Hannon Eilis , Mei Hailiang ,   BIOS Consortium, Mill Jonathan , Daxinger Lucia , Heijmans Bastiaan T.
Published: December 2024

The epigenetic regulation of clustered protocadherin (cPCDH) genes is tightly linked to their function as specific cell surface barcodes for neural self-nonself discrimination. Differential cPCDHDNA methylation in both blood and brain has been implicated in diverse human traits and diseases ranging from BMI, aging, cancer and brain disorders. However, the unique regulation of cPCDHmethylation remains poorly understood. Therefore, we performed a genome-wide association study to evaluate the association of >7 million genetic variants with DNA methylation at 607 cPCDHCpGs measured in whole blood of 3777 individuals and validated findings in prefrontal cortex samples obtained from 523 brain donors. We observed concordant cPCDHmethylation patterns in blood and prefrontal cortex, which switched between hypo-, intermediate and hypermethylation over short distances with the former overlapping with the promoter regions of each cPCDHmember. Through methylation quantitative trait locus (meQTL) analysisin trans, we first confirmed the broad effect of the candidate geneSMCHD1on cPCDHmethylation in blood which validated in prefrontal cortex. Through a genome-wide analysis, we next identified theSENP7andUTF1/VENTXloci to have widespread, subcluster-specific effects on cPCDHmethylation in blood which was validated in prefrontal cortex. WhileSENP7can indirectly affect DNA methylation through the deSUMOylation of the chromatin repressorKAP1,UTF1andVENTXare two genes involved in embryonic development not previously implicated in epigenetic regulation. Our findings shed new light on the processes involved in cPCDHmethylation that may underlie associations with disease.