bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and evaluation of a non-invasive brain-spine interface using transcutaneous spinal cord stimulation
Authors: Atkinson Carolyn , Lombardi Lorenzo , Lang Meredith , Keesey Rodolfo , Hawthorn Rachel , Seitz Zachary , Leuthardt Eric C. , Brunner Peter , Seáñez Ismael
Published: September 2024

Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of lower limb movement in the sensorimotor cortex of unimpaired individuals and to quantify the performance of a linear discriminant analysis (LDA) decoder in detecting movement onset from these neural correlates. Our results show that initiation of knee extension was associated with event-related desynchronization in the central-medial cortical regions at frequency bands between 4-44 Hz. Our neural decoder using µ (8-12 Hz), low β (16-20 Hz), and high β (24-28 Hz) frequency bands achieved an average area under the curve (AUC) of 0.83 ± 0.06 s.d. (n = 7) during a cued movement task offline. Generalization to imagery and uncued movement tasks served as positive controls to verify robustness against movement artifacts and cue-related confounds, respectively. With the addition of real-time decoder-modulated tSCS, the neural decoder performed with an average AUC of 0.81 ± 0.05 s.d. (n = 9) on cued movement and 0.68 ± 0.12 s.d. (n = 9) on uncued movement. Our results suggest that the decrease in decoder performance in uncued movement may be due to differences in underlying cortical strategies between conditions. Furthermore, we explore alternative applications of the BSI system by testing neural decoders trained on uncued movement and imagery tasks. By developing a non-invasive BSI, tSCS can be timed to be delivered only during voluntary effort, which may have implications for improving rehabilitation.
Testicular sex cord–stromal tumors in mice with constitutive activation of PI3K and loss of Pten
Authors: Dinevska Marija , Mcaloney Lachlan , Widodo Samuel S. , Filiz Gulay , Anderson Jeremy , Dworkin Sebastian , Windley Simon P. , Wilhelm Dagmar , Mantamadiotis Theo
Published: September 2024

Testicular tumors are the most common malignancy of young men and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressorPten, targeted to nestin expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord–stromal Leydig cell tumors. Single cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+T-cells predominating. Further analysis showed that immune cells preferentially localize to or accumulate within stromal regions.

Graphical Abstract
Density-Dependent Colour Scanning Electron Microscopy (DDC-SEM). Applications in the study of calcified tissues and visual impact
Authors: Tsolaki Elena , Hunter Luke , Chester Adrian H , Bertazzo Sergio
Published: September 2024

Scanning Electron Microscopy (SEM) is widely used as a technique for materials characterization. It has also been successfully applied to the imaging of biological samples, providing invaluable insights into the topography, morphology and composition of biological structures. A particular method combining different SEM detectors, named Density-Dependent Coloured SEM (DDC-SEM), has proven to be most useful for the identification and visualization of minerals in soft tissues. The method consists of a manipulation of original greyscale SEM images to produce coloured images that provide both topography and density information for samples with components of different densities. Here we provide a discussion on how to use DDC-SEM to aid the visualization and intuitive understanding of pathological calcification. This method has become popular not only for its scientific improvement of conventional SEM greyscale images, but also for its aesthetical merits.

Lay summary

Scanning Electron Microscopes (SEM) are widely used tools for examining biological materials such as human tissue. Like other electron microscopes, it only produces images in greyscale. SEM has been useful, for instance, in improving our understanding of calcific diseases. These diseases involve the build-up of mineral in the body’s soft tissues, and frequently affect the heart, kidneys, or eyes. This work provides a discussion on using a SEM technique known as Density-Dependent Colour Scanning Electron Microscopy (DDC-SEM), which enhances SEM images through scanning the same area with different detectors, assigning a unique colour to each detector’s output, and then overlaying these images.
Localization of Albumin with Correlative Super Resolution Light- and Electron Microscopy in the Kidney
Authors: Birtasu Alexandra N. , Ermel Utz H. , Rahm Johanna V. , Seybert Anja , Flottmann Benjamin , Heilemann Mike , Grahammer Florian , Frangakis Achilleas S.
Published: September 2024

The functioning of vertebrate life relies on renal filtration of surplus fluid and elimination of low-molecular-weight waste products, while keeping serum proteins in the blood. In disease, however, there is leak of serum proteins and tracing them to identify the leaking position within tissue with a nanometer resolution poses a significant challenge. Correlative microscopy integrates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Using chemical tagging of albumin with synthetic fluorophores we achieve protein-specific labeling that preserve their post-embedding fluorescence after high-pressure freezing and freeze-substitution of murine kidney tissue. Using advanced registration techniques for super-resolution correlative light and electron microscopy, we can localize the labeled albumin with a high precision in the x-y plane of electron micrographs and cartograph its distribution. Thereby we can quantify the albumin concentration and measure a linear reduction gradient across the kidney filtration barrier. Our study shows the feasibility of combining different microscopy contrasts for tracing fluorescently labeled protein markers with super resolution in various tissue samples and opens new perspectives for correlative imaging in volume electron microscopy.
Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell lymphoma
Authors: Herrero Alba Díaz , Pelaez-Prestel Hector Fernando , Massenet-Regad Lucile , Veyssiere Maëva , Calvani Julien , Cristinelli Caterina , Lehmann-Che Jacqueline , Meignin Véronique , Thieblemont Catherine , Blanc Véronique , Soumelis Vassili , Tonnerre Pierre
Published: September 2024

Diffuse Large B-cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin’s lymphoma for which current therapeutic strategies remain insufficient. The diffuse nature of DLBCL, lacking distinct tissue structures, represents a challenge to elucidate the cellular organization and interactions within the tumor microenvironment (TME). In this study, we applied spatial transcriptomics to identify spatially-resolved gene expression profiles in 10 DLBCL tissue samples, identifying distinct immune cell infiltration and colocalization patterns. These profiles were classified into six cellular ecosystems (Cell-Eco) that differ in cellular composition, functional patterns, and neighborhood characteristics. The spatially-resolved Cell-Eco signatures provided prognostic scores that stratified patients with different overall survival rates. We also found that C1q+ tumor-associated macrophages are the primary cells interacting with malignant B cells and influencing the spatial architecture of the TME. This study provides novel biological insights into the complexity of the TME in DLBCL and highlights the potential prognostic value of its spatial organization.

Graphical abstract

Key findings

Spatial transcriptomics classifies DLBCL tissues based on immune cell infiltration and colocalization patterns.

DLBCL tumor microenvironment consists of cellular ecosystems (Cell-Eco) that differ in cellular composition, transcriptomic profiles and neighborhood characteristics.

Spatially-resolved Cell-Eco signatures stratify patients with different overall survival.

C1q+ tumor-associated macrophages primarily interact with malignant B cells and contribute to the spatial organization of the tumor microenvironment.
Peristaltic pump-triggered amyloid formation suggests shear stresses arein vivorisk factors of amyloid nucleation
Authors: Goto Yuji , Ota Tomoki , Yuan Wenlou , Yumen Ikuko , Yamaguchi Keiichi , Matsuda Hirokazu , Yamamoto Suguru , Ogi Hirotsugu
Published: September 2024

Amyloid fibrils, crystal-like fibrillar aggregates of denatured proteins, are formed linked with the breakdown of supersaturation, causing a series of amyloidosis including Alzheimer’s and Parkinson’s diseases. Although varyingin vitrofactors are known,in vivofactors breaking supersaturation are unclear. We found that flowing by a peristaltic pump effectively triggers amyloid formation of hen egg white lysozyme, a model amyloidogenic protein, and, moreover, amyloidosis-associated proteins (i.e. α-synuclein, amyloid β 1-40, and β2-microglobulin). The peristaltic pump-dependent amyloid formation was visualized by a fluorescence microscope with looped flow system, revealing dynamic motions under flow. Among them, amyloid fibrils of amyloid β 1-40 were stickier than others, self-associating, absorbing to loop surfaces, and surging upon flicking the loop, implying early stages of cerebral amyloid angiopathy. On the other hand, β2-microglobulin at a neutral pH showed unique two-step amyloid formation with an oligomeric trapped intermediate, which might mimic amyloid formation in patients. Peristalsis-caused strong shear stresses were considered to mechanically break supersaturation. Shearing stresses occur in vivoat varying levels, suggesting that they break otherwise persistent supersaturation, thus triggering amyloid formation and ultimately leading to amyloidosis. (182 words <200 words)
What influences non-menstruator attitudes and behaviours towards menstruation among Rohingya refugees in Bangladesh? A quantitative analysis
Authors: Hales Georgia , Hutchings Paul , Roelich Katy , Das Mahua , Akram Nowshad , Begum Shajeda , Sultana Zahida
Published: September 2024

Non-menstruators play an important yet overlooked role in shaping menstrual health. They may be the family budget holders who purchase menstrual materials, receive health information outside the household, or preserve social stigmas. In response, World Vision, supported by UNICEF, implemented a programme to influence non-menstruators among the Rohingya population living in Kutupalong refugee camp, Bangladesh. The intention was to ensure non-menstruators recognise their important role in supporting family members to improve their menstrual health. We evaluated this intervention using a baseline and endline survey of 150 participants based on the Risk-Attitudes-Norms-Ability-Self-regulation (RANAS) approach to behaviour change. Based on the responses, we categorised participants into ‘doers’ and ‘non-doers’ of positive behaviours. We then performed multiple linear regression analyses and ANOVA comparison of means tests to understand how psychosocial and contextual factors influence the population’s attitudes and behaviours towards menstruation before and after intervention. The regression analyses showed eight psychosocial and contextual factors that had a significant relationship with the desired behaviours. These were the block they lived in, marital status, already having learnt about menstruation from World Vision, how they were introduced to menstruation, who they discuss menstruation with, family members’ reaction, perceptions of their role, and their commitment. Additionally, the ANOVA comparison of means between doers and non-doers showed doers were more likely to be confident to carry out the behaviour, perceive their role as important, and discuss menstruation with family. They were also more likely to be married, older, and have first learnt about menstruation from their family. This is the first study to identify which psychosocial and contextual factors significantly influence positive non-menstruator attitudes and conducive behaviours towards menstruation and menstruators. Humanitarian organisations can use these factors to improve the design and targeting of behaviour change programmes to improve menstrual health.

Highlights

Menstrual health is often limited in refugee settings

Non-menstruators can enable and constrain menstrual health

Menstrual health intervention among Rohingya refugees shows positive change in non-menstruator behaviour

Behavioural determinants for non-menstruators related to marriage, commitment, and family reaction

‘Doers’ more likely to be confident, perceive role as important, and discuss menstruation with family
Biomarkers of atrial fibrillation-related pathways and left atrial structure and function in an overweight and obese population
Authors: Li Linzi , Romaguera Dora , Alonso-Gómez Angel M. , Toledo Estefanía , Shah Amit J. , Mora Marta Noris , Tojal-Sierra Lucas , Martinez-Gonzalez Miguel Angel , Mas-Llado Caterina , Razquin Cristina , Estruch Ramón , Fitó Montserrat , Alonso Alvaro
Published: September 2024

Background

Exploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis.

Methods

We studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models.

Results

The participants in this analysis had a mean age of 65.0 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years.

Conclusion

In an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.
Development and validation of a 5-year risk model using mammogram risk scores generated from screening digital breast tomosynthesis
Authors: Jiang Shu , Bennett Debbie L. , Colditz Graham A.
Published: September 2024

Screening digital breast tomosynthesis (DBT) aims to identify breast cancer early when treatment is most effective leading to reduced mortality. In addition to early detection, the information contained within DBT images may also inform subsequent risk stratification and guide risk-reducing management. We obtained a 5-year area under the curve (AUC) = 0.78 (95% confidence interval (CI) = 0.75 – 0.80) in the internal validation. The model validated in external data (n=6,553 women; AUC = 0.77 (95% CI, 0.74 – 0.80). There was no change in the AUC when age and BI-RADS density are added to the synthetic DBT image. The model significantly outperforms the Tyrer-Cuzick model (p<0.01). Our model extends risk prediction applications to synthetic DBT, provides 5-year risk estimates, and is readily calibrated to national risk strata for clinical translation and application in the setting of US risk management guidelines. The model could be implemented within any digital mammography program.

One Sentence Summary

We develop and externally validate a 5-year risk prediction model for breast cancer using synthetic digital breast tomosynthesis and demonstrate clinical utility by calibrating to the national risk strata.
Reactogenicity and immunogenicity against MPXV of the intradermal administration of Modified Vaccinia Ankara compared to the standard subcutaneous route
Authors: Mazzotta Valentina , Piselli Pierluca , Lepri Alessandro Cozzi , Matusali Giulia , Cimini Eleonora , Esvan Rozenn , Colavita Francesca , Gagliardini Roberta , Notari Stefania , Oliva Alessandra , Meschi Silvia , Casetti Rita , Micheli Giulia , Bordi Licia , Giacinta Alessandro , Grassi Germana , Tekle Saba Gebremeskel , Cimaglia Claudia , Paulicelli Jessica , Caioli Alessandro , Gallì Paola , Duca Giulia Del , Lichtner Miriam , Sarmati Loredana , Tamburrini Enrica , Mastroianni Claudio , Latini Alessandra , Faccendini Paolo , Fontana Carla , Nicastri Emauele , Siddu Andrea , Barca Alessandra , Vaia Francesco , Girardi Enrico , Maggi Fabrizio , Antinori Andrea ,   MPOX Vaccine Lazio Study Group
Published: September 2024

The recent resurgence of Mpox in central Africa has been declared again a Public Health Emergency of International Concern (PHEIC) requiring coordinated international responses. Vaccination is a priority to expand protection and enhance control strategies, but the vaccine’s need exceeds the currently available doses. Intradermal administration of one-fifth of the standard Modified-Vaccinia-Ankara (MVA-BN) dose was temporarily authorized during the 2022 PHEIC. Studies conducted before 2022 provided evidence about the humoral response against the Vaccinia virus (VACV) after vaccination but not against the Mpox virus (MPXV). Moreover, no data are available on the T-cell response elicited by MVA-BN administered subcutaneously or intradermally. Here, we compare the two vaccine administration routes according to reactogenicity and immunogenicity based on data from 943 vaccine recipients during the 2022 vaccination campaign in Rome, Italy. We found that the intradermal route elicited slightly higher titers of MPXV-specific IgG and nAbs than the subcutaneous one. At the same time, no differences in cellular response were detected. MVA-BN was globally well tolerated despite higher reactogenicity for the intradermal than the subcutaneous route, especially for the reactions at the local injection site. The intradermal dose-sparing strategy was proven safe and immunogenic and would make vaccination available to more people.
De novovariant analysis of childhood-onset obsessive-compulsive disorder in the French-Canadian population
Authors: Bornais Kate , Ross Jay P. , Schmilovich Zoe , Medeiros Miranda , Spiegelman Dan , Boileau Bernard , Marier Jean-Jacques , Laurin Ghislain , Dion Patrick A. , Rouleau Guy A.
Published: September 2024

Childhood-onset obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with a strong genetic component.De novovariants (DNVs) have been shown to have a role in childhood-onset OCD, but to date, no DNV analysis has been performed in patients from a genetically isolated population. Here, we aimed to investigate the impact of rarede novosingle nucleotide variants (dnSNVs) on childhood-onset OCD risk in the French-Canadian population. In a cohort of 36 French-Canadian trios comprised of 36 probands with childhood-onset OCD and 72 unaffected parents, we identified 34 dnSNVs harboured in 34 different genes. We found that four of these genes were previously associated with OCD, replicating their contribution to its risk. We also observed complete overlap between our 34 candidate genes and genes associated with 11 related neuropsychiatric disorders, supporting a shared underlying genetic susceptibility across psychopathologies. Among genes harbouring DNVs across three childhood-onset OCD cohorts, we observed an overrepresentation of genes involved in clathrin-dependent endocytosis (GO:0072583;p-adj= 0.0498) and phosphatidylinositol binding (GO:0035091;p-adj= 0.0431), offering potential biological mechanisms underlying childhood-onset OCD. No association was found between the number of dnSNVs in childhood-onset OCD probands and OCD symptom severity. Altogether, this study offers a framework for performing DNV analyses of complex disorders in genetically isolated populations. We have provided the first list of candidate childhood-onset OCD genes in the French-Canadian population.
Pre-chronic kidney disease -- Serial creatinine tracks glomerular filtration rate decline above 60 mL/min
Authors: Burke Cyril O. , Toffaletti John G. , Burke Leanne M. , Tanzer Joshua Ray
Published: September 2024

OBJECTIVES

To allow primary clinicians to detect early decline in glomerular filtration rates above 60 milliliters per minute, before stage-three chronic kidney disease.

METHODS

We re-examine a standard reference that found low tubular secretion of creatinine at glomerular filtration rates above 80 milliliters per minute and suggested “observation of subtle changes in serum creatinine levels”. We explain why that method extends to the 80 to 60 milliliters per minute range by(1)fitting a hyperbolic curve,(2)expanding the Y-axis (to reflect accuracy of modern creatinine assays), and(3)showing reasonable continuity down to 60 milliliters per minute. We summarize why equations estimating glomerular filtration rate are unsuitable above 60 milliliters per minute.

RESULTS

Four patient cases show how serum creatinine referenced to an individual’s historical maximum can suggest increased risk, triggering investigation to separate benign processes that alter serum creatinine from true decline in glomerular filtration rate of prechronic kidney disease.

CONCLUSIONS

At glomerular filtration rates above 60 milliliters per minute, serial creatinine is more reliable than estimating equations and appears practical for clinical monitoring and early intervention.

STRENGTHS OF THIS STUDY

Includes serial creatinine proof-of-concept cases that show preCKD

Reviews properties that favor serial creatinine for early kidney disease

Addresses mathematical limitations of GFR estimating equations

Re-analyzes a 40-year-old standard reference that still influences research, showing its overlooked importance for early kidney diagnosis
Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program
Authors: Lorman Vitaly , Bailey L. Charles , Song Xing , Rao Suchitra , Hornig Mady , Utidjian Levon , Razzaghi Hanieh , Mejias Asuncion , Leikauf John Erik , Brill Seuli Bose , Allen Andrea , Bunnell H Timothy , Reedy Cara , Mosa Abu Saleh Mohammad , Horne Benjamin D , Geary Carol Reynolds , Chuang Cynthia H. , Williams David A , Christakis Dimitri A , Chrischilles Elizabeth A , Mendonca Eneida A , Cowell Lindsay G. , McCorkell Lisa , Liu Mei , Cummins Mollie R , Jhaveri Ravi , Blecker Saul , Forrest Christopher B.
Published: September 2024

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients’ clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.
Subcallosal Cingulate structural connectivity as biomarker for chronic low back pain
Authors: Tsolaki Evangelia , Wei Wenxin , Ward Michael , Bari Ausaf , Pouratian Nader
Published: September 2024

Background

Chronic low back pain (CLBP) poses a significant challenge, contributing significantly to the ongoing opioid crisis while also being a leading cause of disability. Although spinal cord stimulation (SCS) stands as the primary FDA-endorsed method for neuromodulatory therapy in CLBP, there remains a subset of patients unresponsive to SCS and others who experience insufficient pain relief over time. In view of the evidence suggesting the critical role of subcallosal cingulate cortex (SCC) connectivity in pain processing, in the current study we investigated the role of the baseline SCC structural as a potential neuroimaging predictive biomarker to identify patients that are likely to benefit from SCS.

Methods

Diffusion magnetic resonance imaging scans were acquired in 8 patients with CLBP (mean (SD) age = 70 (10) years; 6 female/2 male, 6 UCLA site, 2 UTSW) before their initial SCS trial. Probabilistic tractography from subject-specific anatomically defined SCC seed regions to the ventral striatum (VS), anterior cingulate cortex (ACC), uncinate fasciculus (UCF) and bilateral medial prefrontal cortex (mPFC) was used to calculate FSL structural probabilistic connectivity in the target network. To explore cross-sectional variations in SCC connectivity related to SCS trial response, we employed a general linear model (GLM) using the SCC probability of connectivity as dependent variable, and the response to the SCS trial as independent variable. We used Pearson correlation to evaluate further the relationships between the critical SCC probability of connectivity and the change in VAS score after the SCS trial. Finally, the role of depression in the treatment outcome was evaluated.

Results

Responders to SCS had significantly lower ipsilateral SCC connectivity to mPFC (F1,8 =8.19, p = 0.03) and VS (F1,8 =17.48, p=0.01) on the left hemisphere compared to non-responders. Pearson correlation analysis showed that decreased ipsilateral SCC baseline connectivity to left mPFC (p=0.03) and VS (p=0.01) was correlated with higher improvement in VAS scores. The baseline depression severity did not significantly influence the change in VAS score following the SCS trial. On the other hand, baseline SCC-VS connectivity on the left hemisphere was a significant predictor of change in VAS score (p=0.02).

Conclusions

Our study highlights the important role of SCC connectivity that can serve as a potential biomarker for CLBP stratification and prediction to SCS treatment. These results can reshape our perspective on CLBP management and can serve as early indicator of response to the treatment providing a personalized approach based on the individual’s underlying SCC connectivity.
Gaps in protection toAnophelesexposure in high malaria endemic regencies of Papua Province, Indonesia
Authors: Rozi Ismail E , Syahrani Lepa , Permana Dendi H , Asih Puji B S , Sumiwi Maria E , Lobo Neil F , Hawley William A , Syafruddin Din
Published: September 2024

Background

Malaria in eastern Indonesia remains high despite significant reductions and local elimination in other parts of the country. Malaria control activities that have been implemented include early diagnosis and prompt treatment, provision of Long-lasting insecticide-treated nets (LLINs), and indoor residual spraying (IRS). To expedite malaria elimination in this region, a rapid entomological assessment combined with human behaviour observations (HBOs) were conducted in eight high malaria endemic regencies in Papua Province, Indonesia. The present study focuses on identifying gaps in protection against mosquito biting indoors and outdoors that may contribute to the sustained transmission and persistently high endemicity.

Methods

This study was conducted alongside a rapid entomologic assessment, including human landing catches (HLCs) of adult mosquitoes. Human behavior was documented by direct observations during HLCs. HBO data focused on temporal (over the night) and spatial (domestic or peri-domestic) presence, alongside bed net usage and sleeping patterns. Household questionnaires, also conducted during entomological collections, documented data on house structure materials, practices against mosquito bites, livestock presence, as well as intervention usage.

Results

Analysis of human behaviors in each regency identified several indoor and outdoor gaps in protection against mosquito biting. Human exposure to mosquito bites was driven by ITN usage, IRS coverage, indoor presence without protection prior to sleeping, absence of mosquito house screens, and outdoor presence without protection.

Conclusions

Data demonstrates multiple gaps in protection against mosquito exposure in all eight regencies of Papua evaluated. Indoor interventions require optimization, while current vector control activities do not presently address outdoor exposure. Measured spatial and temporal exposure may be utilized to understand protective vector interventions that may function in these spaces while also pointing to continued exposure. Additional interventions, such as community-based larval source management, may reduce exposure overall, while novel interventions like spatial repellents may fill some gaps in protection – alongside optimized case detection and treatment. Results suggest that the present strategy may be insufficient to eliminate malaria in the region, and a rethought evidence-based and adaptive strategy is required.
Executive Function and Adherence in Children and Adolescents Living with HIV: Evidence from the HIV-associated Neurocognitive Disorders in Zambia (HANDZ) Study
Authors: Mwanza-Kabaghe Sylvia , Sportiello Kristen , Shah Mina , Adams Heather R. , Mbewe Esau G. , Kabundula Pelekelo P. , Schneider Colleen , Mweemba Milimo , Birbeck Gretchen L. , Bearden David R.
Published: September 2024

Introduction

Executive function (EF) may be impaired in people with human immunodeficiency virus (HIV) infection, and poor EF may affect medication adherence. However, there is little data on EF in children with HIV in sub-Saharan Africa.

Methods

208 children/adolescents with perinatally acquired HIV and 208 HIV-exposed uninfected controls were recruited in Zambia for this prospective cohort study. EF was measured using performance-based, self-report, and parental report measures. Adherence over one year of follow-up was assessed through questionnaires and viral load measurement.

Results

Children with HIV performed significantly worse on all three measures of EF. Lower parental rating of EF was associated with poorer antiretroviral therapy adherence (OR: 1.5, 95% CI = 1.02 – 2.2, p = 0.04).

Conclusion

Children with HIV have EF impairments which may lead to consequences like poor medication adherence and treatment failure. Interventions to improve EF or compensate for impaired EF may be necessary in this population.
Socio-medical Factors Associated with Neurodevelopmental Disorders on the Kenyan Coast
Authors: Kipkemoi Patricia , Savage Jeanne E. , Gona Joseph , Rimba Kenneth , Kombe Martha , Mwangi Paul , Kipkoech Collins , Chepkemoi Eunice , Ngombo Alfred , Mkubwa Beatrice , Rehema Constance , Kariuki Symon M. , Posthuma Danielle , Donald Kirsten A. , Robinson Elise , Abubakar Amina , Newton Charles R
Published: September 2024

Background

Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism, intellectual disability and attention deficit hyperactivity disorder (ADHD). Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental risk factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast that did not overlap.

Methods and Findings

We included 172 of the study participants from the Kilifi Autism Study and 151 from the NeuroDev Study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression analysis. Univariable analysis in the Kilifi Autism Study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 (95%CI 4.04 – 27.41) for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, and maternal bleeding) OR: 3.17 (95%CI 1.61 – 6.23). In the NeuroDev study sample, labour and birth complications (OR: 7.30 (2.17 – 24.61)), neonatal jaundice (OR: 5.49 (95%CI 1.61 – 18.72)) and infection during pregnancy (OR: 5.31 (1.56 – 18.11)) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs.

Conclusion

Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed.
Inositol polyphosphates regulate resilient mechanisms in the green algaChlamydomonas reinhardtiito adapt to extreme nutrient conditions
Authors: Bedera-García Rodrigo , García-Gómez María Elena , Personat José María , Couso Inmaculada
Published: September 2024

In the actual context of climate changing environments, photosynthetic organisms need to adapt to more extreme conditions. Microalgae can be excellent organisms to understand molecular mechanisms that activate survival strategies under stress.Chlamydomonas reinhardtiisignaling mutants are extremely useful to decipher which strategies they use to cope with changeable environments. In this study, we conducted prolonged starvation in wild type andvip1-1 Chlamydomonascells. The mutantvip1-1has an altered profile of pyroinositol polyphosphates (PP-InsPs) which are signaling molecules present in all eukaryotes. These molecules have been connected to P signaling in other organisms including plants but their implications in other nutrient signaling is still under evaluation. After prolonged starvation, WT andvip1-1showed important differences in the levels of chlorophyll and photosystem II (PSII) activity. We also performed a metabolomic analysis under these conditions and found an overall decrease in different organic compounds such as amino acids including arginine and its precursors and tryptophan which is considered as a signaling molecule itself in plants. In addition, we observed significant differences in RNA levels of genes related to nitrogen assimilation that are under the control of NIT2 transcription factor. Overall our data indicate an important role of PP-InsPs in the regulation of nutrient starvation especially regarding N assimilation and C distribution. These data are of great importance for the generation of resilient strains to be used in open ponds and high capacity bioreactors.
The mechanism of peptidoglycan O-acetylation in Gram-negative bacteria typifies bacterial MBOAT-SGNH acyltransferases
Authors: Anderson Alexander C. , Schultz Bailey J. , Snow Eric D. , Brott Ashley S. , Stangherlin Stefen , Malloch Tyler , London Jalen R. , Walker Suzanne , Clarke Anthony J.
Published: September 2024

Bacterial cell envelope polymers are commonly modified with acyl groups that provide fitness advantages. Many polymer acylation pathways involve pairs of membrane-boundO-acyltransferase (MBOAT) and SGNH family proteins. As an example, the MBOAT protein PatA and the SGNH protein PatB are required in Gram-negative bacteria for peptidoglycan O-acetylation. The mechanism for how MBOAT-SGNH transferases move acyl groups from acyl-CoA donors made in the cytoplasm to extracellular polymers is unclear. Using the peptidoglycanO-acetyltransferase proteins PatAB, we explore the mechanism of MBOAT-SGNH pairs. We find that the MBOAT protein PatA catalyzes auto-acetylation of an invariant Tyr residue in its conserved C-terminal hexapeptide motif. We also show that PatB can use a synthetic hexapeptide containing an acetylated tyrosine to donate an acetyl group to a peptidoglycan mimetic. Finally, we report the structure of PatB, finding that it has structural features that shape its activity as anO-acetyltransferase and distinguish it from other SGNH esterases and hydrolases. Taken together, our results support a model for peptidoglycan acylation in which a tyrosine-containing peptide at the MBOAT’s C-terminus shuttles an acyl group from the MBOAT active site to the SGNH active site, where it is transferred to peptidoglycan. This model likely applies to other systems containing MBOAT-SGNH pairs, such as those that O-acetylate alginate, cellulose, and secondary cell wall polysaccharides. The use of an acyl-tyrosine intermediate for MBOAT-SGNH acyl transfer is also shared with AT3-SGNH proteins, a second major group of acyltransferases that modify cell envelope polymers.
Molecular activity mediates the composition and assembly of dissolved organic matter in lake sediments
Authors: Wen Shuailong , Hu Ang , Dini-Andreote Francisco , Han Lei , Jiang Shuyu , Jiang Kyoung-Soon , Wang Jianjun
Published: September 2024

Lake sediments are hotspots for carbon transformation and burial, where dissolved organic matter (DOM) interacts with microorganisms to regulate global carbon cycling. The potential for individual DOM molecules to undergo biochemical transformations, i.e., their activity, is a critical molecular trait affecting DOM turnover in environment. However, the composition of sediment DOM and how its assembly mechanisms are related to molecular activity remains poorly understood. Here, 63 freshwater sediments were collected from tropical to cold temperate climatic zones in China. We explored the molecular composition and assembly of sediment DOM and the underlying mechanisms driven by climate, physicochemical factors, and microbes along the molecular activity gradient. Sediment DOM was dominated by lipid- (34.8%) and lignin-like compounds (33.01%), and the latter were enriched as molecular activity of DOM increased. Besides, DOM composed of more active molecules had greater compositional similarity across different climatic zones, and was inclined to assemble deterministically. This was supported by the fact that as potential transformations of molecular assemblages increased from 0.4 to 14, the assembly of these molecules was structured by a shift from stochastic to deterministic processes, with the latter accounting for ≥ 75% thereafter. Overall, the molecular assemblage was primarily structured by physicochemical factors, including sediment total organic carbon and electrical conductivity. As molecular activity increased, however, assemblage was increasingly affected by climate and bacterial communities, consistent with the enhanced complexity of bacterial-molecular networks. Collectively, our study highlights that the intrinsic activity of DOM molecules determines their fate through distinct biotic and abiotic mechanisms.
RIPK1 is essential for Herpes Simplex Virus-triggered ZBP1-dependent necroptosis in human cells
Authors: Amusan Oluwamuyiwa T. , Wang Shuqi , Yin Chaoran , Koehler Heather S. , Li Yixun , Tenev Tencho , Wilson Rebecca , Bellenie Benjamin , Zhang Ting , Wang Jian , Liu Chang , Seong Kim , Poorbaghi Seyedeh L. , Yates Joseph , Shen Yuchen , Upton Jason W. , Meier Pascal , Balachandran Siddharth , Guo Hongyan
Published: September 2024

Necroptosis initiated by the host sensor Z-NA Binding Protein-1 (ZBP1) is essential for host defense against a growing number of viruses, including Herpes Simplex Virus-1 (HSV-1). Studies with HSV-1 and other necroptogenic stimuli in murine settings have suggested that ZBP1 triggers necroptosis by directly complexing with the kinase RIPK3. Whether this is also the case in human cells, or whether additional co-factors are needed for ZBP1-mediated necroptosis, is unclear. Here, we show that ZBP1-induced necroptosis in human cells requires RIPK1. We have found that RIPK1 is essential for forming a stable and functional ZBP1-RIPK3 complex in human cells, but is dispensable for the formation of the equivalent murine complex. The RIP Homology Interaction Motif (RHIM) in RIPK3 is responsible for this difference between the two species, because replacing the RHIM in human RIPK3 with the RHIM from murine RIPK3 is sufficient to overcome the requirement for RIPK1 in human cells. These observations describe a critical mechanistic difference between mice and humans in how ZBP1 engages in necroptosis, with important implications for treating human diseases.
De-novo design of actively spinning and gyrating spherical micro-vesicles
Authors: Kaur Veerpal , Khuntia Subhashree S. , Taneja Charu , Chaudhuri Abhishek , Yogendran K. P. , Rakshit Sabyasachi
Published: September 2024

Engineering spherical self-propelled swimmers that exhibit rotation and directed translation has posed a significant experimental challenge in biomedicine design. Often a secondary external field or asymmetric geometry is employed to generate rotation, complicating the design process. In this work, we utilize spherical Giant Unilamellar Vesicles (GUVs) as chassis and enzymes undergoing cyclic, non-reciprocal conformational changes as power units to establish design principles to synthesize autonomous spherical micro-rotors. Leveraging transient interactions, we induce spontaneous symmetry-breaking in enzyme distribution on GUVs, enabling diverse movements from pure spinning to spiral 3D trajectories. With this design, we now open new avenues for advancing self-propelled systems with biocompatible materials, unlocking innovations in biomedical applications.
Brain plasticity for visual words: Elementary school teachers can drive changes in weeks that rival those formed over years
Authors: Wang Fang , Toomarian Elizabeth Y. , Gosavi Radhika S. , Kaneshiro Blair , Norcia Anthony M. , McCandliss Bruce D.
Published: September 2024

This study aims to investigate the impact of vocabulary acquisition through short-term classroom learning and its relation to broader forms of vocabulary learning through long-term exposure in daily life. Through a two week of “learning sprint” in collaboration with a local elementary school and EEG-Steady State Visual Evoked Potentials (EEG-SSVEP) paradigm, we assessed new vocabulary learning in first and second graders within their pedagogical environment. We then compared the results with the word frequency effect, a well-established phenonmenon that reflects long-term vocabulary learning. After two weeks of classroom instruction, newly acquired words elicited neural responses similar to those of high-frequency words, with the effect significantly correlated with children’s phonological decoding skills. Additionally, we successfully replicated the word frequency effect using the SSVEP paradigm for the first time. These findings highlight the potential of the “learning sprint” model for conducting neuroscience research in authentic educational settings, thereby fostering a stronger connection between education and neuroscience.
Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
Authors: Bonnal Sophie , Bajew Simon , Corral Rosa Martinez , Irimia Manuel
Published: September 2024

Microexons are essential for proper functioning of neurons and pancreatic endocrine cells, where their inclusion depends on the splicing factors SRRM3/4. However, in pancreatic cells, lower expression of these regulators limits inclusion to only the most sensitive subset among all neuronal microexons. Although variouscis-acting elements can contribute to microexon regulation, how they determine this differential dose response and high or low sensitivity to SRRM3/4 remains unknown. Here, Massively Parallel Splicing Assays probing 28,535 variants show that sensitivity to SRRM4 is conserved across vertebrates and support a regulatory model whereby high or low microexon sensitivity is largely determined by an interplay between core splicing architecture and length constraints. This conclusion is further supported by distinct spliceosome activities in the absence of SRRM3/4 and by a mathematical model that assumes that the two types of microexons differ only in their efficiency to recruit early spliceosomal components.
Athene cunicularia hypugaeawintering in a central California urban setting arrive later, leave earlier, prefer sheltered micro-habitat, tolerate rain, and contend with diverse predators
Authors: Nicolaus Martin A
Published: September 2024

The wintering phase of the Western Burrowing Owl (Athene cunicularia hypugaea) life cycle has received little attention in the literature. Small numbers of Burrowing Owls have been observed and recorded since 2008 in the winter season in Cesar Chavez Park, a 36-ha peninsula that forms part of the waterfront of the City of Berkeley. The relative ease of observation in this setting allows study of their arrival and departure dates, selection of micro-habitats, tolerance of human presence, behavior in inclement weather, and response to avian and canine predator threats. Viewed over a decade, fewer owls arrived, arrived later, left earlier, and spent less time in residence. Most owls settled in shoreline rip-rap or in tall vegetation; only one fourth settled in short grass. Owls chose exposure to rain for as long as two days. Owls varied widely in tolerance to human proximity. Owls successfully dealt with avian predators, but displayed stress and in some cases became casualties of looseCanis lupus familiaris. Recommendations for habitat management follow.