bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photoimmunotherapy retains its anti-tumor efficacy with increasing stromal content in heterotypic pancreatic cancer spheroids
Authors: Saad Mohammad A. , Zhung Wonho , Stanley Margaret Elizabeth , Formica Sydney , Grimaldo-Garcia Stacey , Obaid Girgis , Hasan Tayyaba 
Published: November 2021

AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by increased levels of desmoplasia that contributes to reduced drug delivery and poor treatment outcomes. In PDAC, the stromal content can account for up to 90% of the total tumor volume. The complex interplay between stromal components, including pancreatic cancer associated fibroblasts (PCAFs), and PDAC cells in the tumor microenvironment (TME) have a significant impact on prognoses and thus needs to be recapitulated in vitro when evaluating various treatment strategies. This study is a systematic evaluation of photodynamic therapy (PDT) in 3D heterotypic coculture models of PDAC with varying ratios of patient derived PCAFs that simulate heterogenous PDAC tumors with increasing stromal content. The efficacy of antibody-targeted PDT (photoimmunotherapy; PIT) using cetuximab photoimmunoconjugates (PICs) of benzoporphyrin derivative (BPD) is contrasted with that of liposomal BPD (Visudyne®), which is currently in PDT clinical trials for PDAC. We demonstrate that both Visudyne®-PDT and PIT were effective in heterotypic PDAC 3D spheroids with a low stromal content. However, as the stromal content increases above 50% in the 3D spheroids, the efficacy of Visudyne®-PDT is reduced by up to 10-fold, while PIT retains its efficacy. PIT was found to be 10-fold, 19-fold and 14-fold more phototoxic in spheroids with 50%, 75% and 90% PCAFs, respectively, as compared to Visudyne®-PDT. This marked difference in efficacy is attributed to the ability of PICs to penetrate and distribute within spheroids with a higher stromal content, whereas Visudyne® is restricted to the spheroid periphery. This study thus demonstrates how the stromal content in PDAC spheroids directly impacts their responsiveness to PDT and proposes PIT to be a highly suited treatment option for desmoplastic tumors with particularly high degrees of stromal content.
Heterogeneous CaMKII-dependent synaptic compensations in CA1 pyramidal neurons from acute slices with dissected CA3
Authors: Vergara Pablo , Pino Gabriela , Vera Jorge , Sanhueza Magdalena 
Published: November 2021

ABSTRACTProlonged changes in neural activity trigger homeostatic synaptic plasticity (HSP) allowing neuronal networks to operate in functional ranges. Cell-wide or input-specific adaptations can be induced by pharmacological or genetic manipulations of activity, and by sensory deprivation. Reactive functional changes caused by deafferentation may partially share mechanisms with HSP. Acute hippocampal slices constitute a suitable model to investigate relatively rapid (hours) pathway-specific modifications occurring after denervation and explore the underlying mechanisms. As Schaffer collaterals constitute a major glutamatergic input to CA1 pyramidal neurons, we conducted whole-cell recordings of miniature excitatory postsynaptic currents (mEPSCs) to evaluate changes over 12 hours after slice preparation and CA3 dissection. We observed an increment in mEPSCs amplitude and a decrease in decay time, suggesting synaptic AMPA receptor upregulation and subunit content modifications. Sorting mEPSC by rise time, a correlate of synapse location along dendrites, revealed amplitude raises at two separate domains. A specific frequency increase was observed in the same domains and was accompanied by a global, unspecific raise. Amplitude and frequency increments were lower at sites initially more active, consistent with local compensatory processes. Transient preincubation with a specific Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor either blocked or occluded amplitude and frequency upregulation in different synapse populations. Results are consistent with the concurrent development of different known CaMKII-dependent HSP processes. Our observations support that deafferentation causes rapid and diverse compensations resembling classical slow forms of adaptation to inactivity. These results may contribute to understand fast-developing homeostatic or pathological events after brain injury.
Predicting direct physical interactions in multimeric proteins with deep learning
Authors: Gao Mu , Nakajima An Davi , Parks Jerry M. , Skolnick Jeffrey 
Published: November 2021

AbstractAccurate descriptions of protein-protein interactions are essential for understanding biological systems. Remarkably accurate atomic structures have been recently computed for individual proteins by AlphaFold2 (AF2). Here, we demonstrate that the same neural network models from AF2 developed for single protein sequences can be adapted to predict the structures of multimeric protein complexes without retraining. In contrast to common approaches, our method, AF2Complex, does not require paired multiple sequence alignments. It achieves higher accuracy than some complex protein-protein docking strategies and provides a significant improvement over AF-Multimer, a new development of AlphaFold for multimeric proteins. Moreover, we introduce metrics for predicting direct protein-protein interactions between arbitrary protein pairs and validate AF2Complex on some challenging benchmark sets and theE. coliproteome. Lastly, using the cytochromecbiogenesis system I as an example, we present high-confidence models of three sought-after assemblies formed by eight members of this system.
Characterization of scar tissue biomechanics during adult murine flexor tendon healing
Authors: Korcari Antonion , Buckley Mark R. , Loiselle Alayna E. 
Published: November 2021

AbstractTendon injuries are very common and result in significant impairments in mobility and quality of life. During healing, tendons produce a scar at the injury site, characterized by abundant and disorganized extracellular matrix and by permanent deficits in mechanical integrity compared to healthy tendon. Although a significant amount of work has been done to understand the healing process of tendons and to develop potential therapeutics for tendon regeneration, there is still a significant gap in terms of assessing the direct effects of therapeutics on the functional and material quality specifically of the scar tissue, and thus, on the overall tendon healing process. In this study, we focused on characterizing the mechanical properties of only the scar tissue in flexor digitorum longus (FDL) tendons during the proliferative and remodeling healing phases and comparing these properties with the mechanical properties of the composite healing tissue. Our method was sensitive enough to identify significant differences in structural and material properties between the scar and tendon-scar composite tissues. To account for possible inaccuracies due to the small aspect ratio of scar tissue, we also applied inverse finite element analysis (iFEA) to compute mechanical properties based on simulated tests with accurate specimen geometries and boundary conditions. We found that the scar tissue linear tangent moduli calculated from iFEA were not significantly different from those calculated experimentally at all healing timepoints, validating our experimental findings, and suggesting the assumptions in our experimental calculations were accurate. Taken together, this study first demonstrates that due to the presence of uninjured stubs, testing composite healing tendons without isolating the scar tissue overestimates the material properties of the scar itself. Second, our scar isolation method promises to enable more direct assessment of how different treatment regimens (e.g., cellular ablation, biomechanical and/or biochemical stimuli, tissue engineered scaffolds) affect scar tissue function and material quality in multiple different types of tendons.
Effects of tendon viscoelasticity in the distribution of forces over sutures in a model tendon-to-bone repair
Authors: Huang Yuxuan , Hoppe Ethan D. , Kurtaliaj Iden , Birman Victor , Thomopoulos Stavros , Genin Guy M. 
Published: November 2021

AbstractTears to the rotator cuff often require surgical repair. These repairs often culminate in re-tearing when sutures break through the tendon in the weeks following repair. Although numerous studies have been performed to identify suturing strategies that reduce this risk by balancing forces across sutures, none have accounted for how the viscoelastic nature of tendon influences load sharing. With the aim of providing insight into this problem, we studied how tendon viscoelasticity, tendon stiffness, and suture anchor spacing affect this balancing of forces across sutures. Results from a model of a three-row sutured re-attachment demonstrated that optimized distributions of suture stiffnesses and of the spacing of suture anchors can balance the forces across sutures to within a few percent, even when accounting for tendon viscoelasticity. Non-optimized distributions resulted in concentrated force, typically in the outermost sutures. Results underscore the importance of accounting for viscoelastic effects in the design of tendon to bone repairs.
Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK
Authors: Campbell Cori , Wang Tingyan , Smith David A , Freeman Oliver , Noble Theresa , Várnai Kinga A , Harris Steve , Salih Hizni , Roadknight Gail , Little Stephanie , Glampson Ben , Mercuri Luca , Papadimitriou Dimitri , Jones Christopher R , Taylor Vince , Chaudhry Afzal , Phan Hang , Borca Florina , Olza Josune , Warricker Frazer , Romão Luis , Ramlakhan David , English Louise , Klenerman Paul , Andersson Monique I. , Collier Jane , Nastouli Eleni , Khakoo Salim I , Gelson William , Cooke Graham S , Woods Kerrie , Davies Jim , Barnes Eleanor , Matthews Philippa C 
Published: November 2021

AbstractBackground and aimsTo determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (ALT and HBV viral load).MethodsWe used anonymised electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK NHS Trusts.ResultsWe report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient.ConclusionsFurther investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.
SARS-CoV-2 RNA is enriched by orders of magnitude in solid relative to liquid wastewater at publicly owned treatment works
Authors: Kim Sooyeol , Kennedy Lauren C. , Wolfe Marlene K. , Criddle Craig S. , Duong Dorothea H. , Topol Aaron , White Bradley J. , Kantor Rose S. , Nelson Kara L. , Steele Joshua A. , Langlois Kylie , Griffith John F. , Zimmer-Faust Amity G. , McLellan Sandra L. , Schussman Melissa K. , Ammerman Michelle , Wigginton Krista R. , Bakker Kevin M. , Boehm Alexandria B. 
Published: November 2021

AbstractWastewater-based epidemiology has gained attention throughout the world for detection of SARS-CoV-2 RNA in wastewater to supplement clinical testing. Methods have been developed using both the liquid and the solid fraction of wastewater, with some studies reporting higher concentrations in solids. To investigate this relationship further, we collaborated with six other laboratories to conduct a study across five publicly owned treatment works (POTWs) where both primary solids and raw wastewater influent samples were collected and quantified for SARS-CoV-2 RNA. Solids and influent samples were processed by participating laboratories using their respective methods and retrospectively paired based on date of collection. SARS-CoV-2 RNA concentrations by mass (gene copies per gram) were higher in solids than in influent by approximately three orders of magnitude. Concentrations in matched solids and influent were positively and significantly correlated at all five POTWs. RNA concentrations in both solids and influent were correlated to COVID-19 incidence rates in the sewershed and thus representative of disease burden; the solids methods appeared to produce a comparable relationship between SARS-CoV-2 RNA concentration measurements and incidence rates across all POTWs. Solids and influent methods showed comparable sensitivity, N gene detection frequency, and calculated empirical incidence rate lower limits. Analysis of solids has the advantage of using less sample volume to achieve similar sensitivity to influent methods.
Gut microbiome composition is predictive of incident type 2 diabetes
Authors: Ruuskanen Matti O. , Erawijantari Pande P. , Havulinna Aki S. , Liu Yang , Méric Guillaume , Inouye Michael , Jousilahti Pekka , Salomaa Veikko , Jain Mohit , Knight Rob , Lahti Leo , Niiranen Teemu J. 
Published: November 2021

AbstractOBJECTIVETo examine the previously unknown long-term association between gut microbiome composition and incident type 2 diabetes in a representative population cohort.RESEARCH DESIGN AND METHODSWe collected fecal samples of 5 572 Finns (mean age 48.7 years, 54.1% women) in 2002 who were followed up for incident type 2 diabetes until Dec 31st, 2017. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome compositions and incident diabetes using multivariable-adjusted Cox regression models. We first used the Eastern Finland sub-population to obtain initial findings and validated these in the Western Finland sub-population.RESULTSAltogether 432 cases of incident diabetes occurred over the median follow-up of 15.8 years. We detected 4 species and 2 clusters consistently associated with incident diabetes in the validation models. These 4 species wereClostridium citroniae(HR, 1.21; 95% CI, 1.04-1.42),C. bolteae(HR, 1.20; 95% CI, 1.04-1.39),Tyzzerella nexilis(HR, 1.17; 95% CI, 1.01-1.36), andRuminococcus gnavus(HR = 1.17; 95% CI, 1.01-1.36). The positively associated clusters, cluster 1 (HR, 1.18; 95% CI, 1.02-1.38) and cluster 5 (HR, 1.18; 95% CI, 1.02-1.36), mostly consisted of these same species.CONCLUSIONSWe observed robust species-level taxonomic features predictive of incident type 2 diabetes over a long-term follow-up. These findings build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome. The gut microbiome could potentially be used to improve risk prediction and to uncover novel therapeutic targets for diabetes.
Survey of residential indoor Particulate Matter measurements 1990-2019
Authors: Ilacqua Vito , Scharko Nicole , Zambrana Jordan , Malashock Daniel 
Published: November 2021

AbstractWe surveyed literature on measurements of indoor particulate matter in all size fractions, in residential environments free of solid fuel combustion. Data from worldwide studies from 1990-2019 were assembled into the most comprehensive collection to date. Out of 2,752 publications retrieved, 538 articles from 433 research projects met inclusion criteria and reported unique data, from which more than 2,000 unique sets of indoor PM measurements were collected. Distributions of mean concentrations were compiled, weighted by study size. Long-term trends, the impact of non-smoking, air cleaners, and the influence of outdoor PM were also evaluated. Similar patterns of indoor PM distributions for North America and Europe could reflect similarities in the indoor environments of these regions. Greater observed variability for all regions of Asia may reflect greater heterogeneity in indoor conditions, but also low numbers of studies for some regions. Indoor PM concentrations of all size fractions were mostly stable over the survey period, with the exception of observed declines in PM2.5in European and North American studies, and in PM10in North America. While outdoor concentrations were correlated with indoor concentrations across studies, indoor concentrations had higher variability, illustrating a limitation of using outdoor measurements to approximate indoor PM exposures.Practical implicationsResidential indoor PM concentration ranges for several size fractions measured in different worldwide regions are provided and may inform future public health research and practice, including PM exposure and risk assessment, and evaluation of IAQ-related interventions and consumer products, such as portable air cleaners.This long-term indoor PM concentration record provides insights regarding the degree of change in observed indoor PM concentrations by world region and some of the factors contributing to increasing or decreasing temporal trends.Outdoor air pollution remains a major influence on indoor concentrations of PM of all sizes.Greater variability of indoor concentrations of PM relative to outdoor concentrations demonstrate the potential for exposure misclassification when using outdoor concentrations to estimate indoor exposures and risk.IAQ interventions, including removing environmental tobacco smoke or using filtration-based portable air cleaners, can produce major improvements in IAQ through reduced indoor particle concentrations.
NEMoE: A nutrition aware regularized mixture of experts model addressing diet-cohort heterogeneity of gut microbiota in Parkinson’s disease
Authors: Xu Xiangnan , Lubomski Michal , Holmes Andrew J. , Sue Carolyn M. , Davis Ryan L. , Muller Samuel , Yang Jean Y.H. 
Published: November 2021

AbstractThe microbiome plays a fundamental role in human health and diet is one of the strongest modulators of the gut microbiome. However, interactions between microbiota and host health are complex and diverse. Understanding the interplay between diet, the microbiome and health state could enable the design of personalized intervention strategies and improve the health and wellbeing of affected individuals. A common approach to this is to divide the study population into smaller cohorts based on dietary preferences in the hope of identifying specific microbial signatures. However, classification of patients based solely on diet is unlikely to reflect the microbiome-host health relationship or the taxonomic microbiome makeup. To this end, we present a novel approach, the Nutrition-Ecotype Mixture of Experts (NEMoE) model, for establishing associations between gut microbiota and health state that accounts for diet-specific cohort variability using a regularized mixture of experts model framework with an integrated parameter sharing strategy to ensure data driven diet-cohort identification consistency across taxonomic levels. The success of our approach was demonstrated through a series of simulation studies, in which NEMoE showed robustness with regard to parameter selection and varying degrees of data heterogeneity. Further application to real-world microbiome data from a Parkinson’s disease cohort revealed that NEMoE is capable of not only improving predictive performance for Parkinson’s Disease but also for identifying diet-specific microbiome markers of disease. Our results indicate that NEMoE can be used to uncover diet-specific relationships between nutritional-ecotype and patient health and to contextualize precision nutrition for different diseases.
Disparities in COVID-19 Fatalities among Working Californians
Authors: Cummings Kristin J. , Beckman John , Frederick Matthew , Harrison Robert , Nguyen Alyssa , Snyder Robert , Chan Elena , Gibb Kathryn , Rodriguez Andrea , Wong Jessie , Murray Erin L. , Jain Seema , Vergara Ximena 
Published: November 2021

AbstractBackgroundInformation on the occupational distribution of COVID-19 mortality is limited.ObjectiveTo characterize COVID-19 fatalities among working Californians.DesignRetrospective study of laboratory-confirmed COVID-19 fatalities with dates of death from January 1 to December 31, 2020.SettingCalifornia.ParticipantsCOVID-19 accounted for 8,050 (9.9%) of 81,468 fatalities among Californians 18-64 years old. Of these decedents, 2,486 (30.9%) were matched to state employment records and classified as “confirmed working.” The remainder were classified as “likely working” (n=4,121 [51.2%]) or “not working” (n=1,443 [17.9%]) using death certificate and case registry data.MeasurementsWe calculated age-adjusted overall and occupation-specific COVID-19 mortality rates using 2019 American Community Survey denominators.ResultsConfirmed and likely working COVID-19 decedents were predominantly male (76.3%), Latino (68.7%), and foreign-born (59.6%), with high school or less education (67.9%); 7.8% were Black. The overall age-adjusted COVID-19 mortality rate was 30.0 per 100,000 workers (95% confidence interval [CI], 29.3-30.8). Workers in nine occupational groups had mortality rates higher than this overall rate, including those in farming (78.0; 95% CI, 68.7-88.2); material moving (77.8; 95% CI, 70.2-85.9); construction (62.4; 95% CI, 57.7-67.4); production (60.2; 95% CI, 55.7-65.0); and transportation (57.2; 95% CI, 52.2-62.5) occupations. While occupational differences in mortality were evident across demographic groups, mortality rates were three-fold higher for male compared with female workers and three- to seven-fold higher for Latino and Black workers compared with Asian and White workers.LimitationsThe requirement that fatalities be laboratory-confirmed and the use of 2019 denominator data may underestimate the occupational burden of COVID-19 mortality.ConclusionCalifornians in manual labor and in-person service occupations experienced disproportionate COVID-19 mortality, with the highest rates observed among male, Latino, and Black workers.