bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal exposure to endocrine disrupting-bisphenol A (BPA) alters testicular fatty acid metabolism in the adult offspring: relevance to sperm maturation and quality
Authors: Varma Saikanth , Molangiri Archana , Kona Suryam Reddy , Ibrahim Ahamed , Duttaroy Asim K , Basak Sanjay 
Published: January 2023

AbstractDaily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult offspring is unknown. Pregnant Wistar rats were gavaged from gestational day 4 to 21 with BPA and BPS (0.0, 0.4, 4.0, 40.0 μg/kg bw/d). Despite increased body and testis weight, the total testicular cholesterol, triglyceride, and plasma fatty acids were unaffected in offspring. Lipogenesis was upregulated by increased SCD-1, SCD-2, and expression of lipid storage (ADRP) and trafficking protein (FABP4). The arachidonic acid, 20:4 n-6 (ARA) and docosapentaenoic acid, 22:5 n-6 (DPA) levels were decreased in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPARα, PPARγ proteins and CATSPER2 mRNA were decreased, which are important for energy dissipation and motility of the sperm in the testis. The endogenous conversion of linoleic acid,18:2n-6 (LA), to ARA was impaired by a reduced ARA/LA ratio and decreased FADS1 expression in BPA-exposed testis. Collectively, fetal BPA exposure affected endogenous long-chain fatty acid metabolism and steroidogenesis in the adult testis, which might dysregulate sperm maturation and quality.HighlightsIn utero BPA exposure not BPS affected testicular long-chain n-6 PUFA metabolism in offspringFetal exposure to BPA alters delta-9-desaturase indices in the adult testisBPA exposure reduced fatty acid desaturase1 expression in offspring testisFetal BPA exposure dysregulated lipogenesis in offspring testis
Application of Elastic Net Regression for Modeling COVID-19 Sociodemographic Risk Factors
Authors: Moxley Tristan A. , Johnson-Leung Jennifer , Seamon Erich , Williams Christopher , Ridenhour Benjamin J. 
Published: January 2023

ABSTRACTObjectivesCOVID-19 has been at the forefront of global concern since its emergence in December of 2019. Determining the social factors that drive case incidence is paramount to mitigating disease spread. We gathered data from the Social Vulnerability Index (SVI) along with Democratic voting percentage to attempt to understand which county-level sociodemographic metrics had a significant correlation with case rate for COVID-19.MethodsWe used elastic net regression due to issues with variable collinearity and model overfitting. Our modelling framework included using the ten Health and Human Services regions as submodels for the two time periods 22 March 2020 to 15 June 2021 (prior to the Delta time period) and 15 June 2021 to 1 November 2021 (the Delta time period).ResultsStatistically, elastic net improved prediction when compared to multiple regression, as almost every HHS model consistently had a lower root mean square error (RMSE) and satisfactoryR2coefficients. These analyses show that the percentage of minorities, disabled individuals, individuals living in group quarters, and individuals who voted Democratic correlated significantly with COVID-19 attack rate as determined by Variable Importance Plots (VIPs).ConclusionsThe percentage of minorities per county correlated positively with cases in the earlier time period and negatively in the later time period, which complements previous research. In contrast, higher percentages of disabled individuals per county correlated negatively in the earlier time period. Counties with an above average percentage of group quarters experienced a high attack rate early which then diminished in significance after the primary vaccine rollout. Higher Democratic voting consistently correlated negatively with cases, coinciding with previous findings regarding a partisan divide in COVID-19 cases at the county level. Our findings can assist policymakers in distributing resources to more vulnerable counties in future pandemics based on SVI.
Quality of life in adolescents with chronic non-traumatic knee pain: An analysis of 323 adolescents with Patellofemoral Pain and Osgood-Schlatter Disease
Authors: Djurtoft Chris , Yona Tomer , Roos Ewa Maria , Thorborg Kristian , Hölmich Per , Rasmussen Sten , Olesen Jens Lykkegaard , Rathleff. Michael Skovdal 
Published: January 2023

AbstractIntroductionWe aimed to describe Quality of life (QoL) among adolescents with Patellofemoral Pain (PFP) and Osgood-Schlatter Disease (OSD) according to the QoL subscale of The Knee injury and Osteoarthritis Outcome Score (KOOS) and the EuroQol 5-dimensions (EQ-5D) and to investigate the characteristics associated with QoL.MethodsThis individual participant analysis included data from three clinical trials on adolescents diagnosed with PFP or OSD. We relabeled individual data and constructed a single dataset.ResultsWe included 323 adolescents with PFP or OSD. Total score of KOOS-QoL was 51±18 and total index score for the EQ5D was 0.67±0.21. KOOS-QoL subscale showed that 59% reported being aware of their knee problems daily or constantly, 37% reported severe to extreme lack of confidence in their knees, 27% reported severe to extreme difficulty with their knees, and 20% reported severely or totally modifying their lifestyle to avoid potentially damaging activities to their knee. EQ-5D showed that 77% experienced problems with everyday activities, 47% reported mobility problems, 17% felt worried, sad, or unhappy, and 7% reported problems looking after themselves. Older participants (age 17-19) reported worse QoL than younger participants. None of the other characteristics were associated with QoL.ConclusionsA high proportion of adolescents with chronic non-traumatic knee pain experience low QoL. More than half were aware of their knee problems at least daily, one in three reported a severe lack of confidence in their knee, and one in six felt worried, sad, or unhappy. QoL was lowest among older adolescents.Highlights-One in every three adolescents with PFP or OSD reported a severe lack of confidence in their knee.-Many adolescents reported being sad or worried, and modified their usual activities due to their knee pain.-Clinicians may extend the scope and include pain management strategies to address psychological perspectives when managing adolescents diagnosed with PFP or OSD.-Modifiable targets such as adolescents understanding of pain may be a beneficial management strategy to consider in rehabilitation for PFP or OSD.
The scheduling of adolescence with Netrin-1 and UNC5C
Authors: Hoops Daniel , Kyne Robert F. , Salameh Samer , MacGowan Del , Avramescu Radu G. , Ewing Elise , He Alina T. , Orsini Taylor , Durand Anais , Popescu Christina , Zhao Janet M. , Schatz Kelcie C. , Li LiPing , Carroll Quinn E. , Liu Guofa , Paul Matthew J. , Flores Cecilia 
Published: January 2023

AbstractDopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters;Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.
Quantitative proteomics combined with network pharmacology analysis unveils the biological basis of Schisandrin B in treating diabetic nephropathy
Authors: Song Jianying , Zhang Bo , Lyu Xudong , Zhang Huiping , Cheng Wenbo , Liu Peiyuan , Kang Jun 
Published: January 2023

AbstractBackgroundDiabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN.ObjectiveWe aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats.MethodsStreptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis.ResultsHigh dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified.ConclusionSch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.
Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Progression
Authors: Savchuk Solomiia , Gentry Kaylee , Wang Wengang , Carleton Elana , Yalçın Belgin , Liu Yin , Pavarino Elisa C. , LaBelle Jenna , Toland Angus M. , Woo Pamelyn J. , Qu Fangfei , Filbin Mariella G. , Krasnow Mark A. , Sabatini Bernardo L. , Sage Julien , Monje Michelle , Venkatesh Humsa S. 
Published: January 2023

SummaryNeural activity is increasingly recognized as a critical regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses, while perisynaptic neurotransmitter signaling drives breast cancer brain metastasis growth. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression. However, the extent to which the nervous system regulates lung cancer progression, either in the lung or when metastatic to brain, is largely unexplored. Small cell lung cancer (SCLC) is a lethal high-grade neuroendocrine tumor that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that, similar to glioma, metastatic SCLC cells in the brain co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. Optogenetic stimulation of cortical neuronal activity drives proliferation and invasion of SCLC brain metastases. In the brain, SCLC cells exhibit electrical currents and consequent calcium transients in response to neuronal activity, and direct SCLC cell membrane depolarization is sufficient to promote the growth of SCLC tumors. In the lung, vagus nerve transection markedly inhibits primary lung tumor formation, progression and metastasis, highlighting a critical role for innervation in overall SCLC initiation and progression. Taken together, these studies illustrate that neuronal activity plays a crucial role in dictating SCLC pathogenesis in both primary and metastatic sites.
A haptic illusion created by gravity
Authors: Opsomer Laurent , Delhaye Benoit , Théate Vincent , Thonnard Jean-Louis , Lefèvre Philippe 
Published: January 2023

AbstractHaptic force estimation is a critical aspect of human dexterity. To manipulate objects or interact with a haptic interface successfully, the normal and tangential components of the contact forces produced by our fingertips must be carefully coordinated. The tight coupling between tangential and normal contact forces observed during voluntary movements indicates that the nervous system can estimate these forces with high accuracy. Here, we examined the influence of gravity on manual force production in an isometric task. We trained participants to produce isometric tangential forces with the thumb and index finger on a dynamometer held in precision grip. They were tasked with reproducing these forces in a normal gravitational environment (1g) and during parabolic maneuvers creating phases of micro- (0g) and hypergravity (1.6g). The isometric task results showed that arm weight biases estimation of the forces exerted by the fingertips. Reproduced tangential forces were consistently larger downward than upward in 1g. This asymmetry was reduced under microgravity and increased under hypergravity. Critically, the normal forces did not reflect this asymmetry, demonstrating that tangential forces were misestimated and pointing to a haptic illusion created by gravity. This gravitational effect on haptic force estimation may have implications for the design of prostheses incorporating force feedback, haptic devices for teleoperations, or haptic supports aimed at improving sensorimotor performance in space.
Dissecting unsupervised learning through hidden Markov modelling in electrophysiological data
Authors: Masaracchia Laura , Fredes Felipe , Woolrich Mark W. , Vidaurre Diego 
Published: January 2023

ABSTRACTUnsupervised, data-driven methods are commonly used in neuroscience to automatically decompose data into interpretable patterns. These patterns differ from one another depending on the assumptions of the models. How these assumptions affect specific data decompositions in practice, however, is often unclear, which hinders model applicability and interpretability. For instance, the hidden Markov model (HMM) automatically detects characteristic, recurring activity patterns (so-calledstates) from time series data. States are defined by a certain probability distribution, whose state-specific parameters are estimated from the data. But what specific features, from all of those that the data contain, do the states capture? That depends on the choice of probability distribution and on other model hyperparameters. Using both synthetic and real data, we aim at better characterizing the behavior of two HMM types that can be applied to electrophysiological data. Specifically, we study which differences in data features (such as frequency, amplitude or signal-to-noise ratio) are more salient to the models and therefore more likely to drive the state decomposition. Overall, we aim at providing guidance for an appropriate use of this type of analysis on one or two-channel neural electrophysiological data, and an informed interpretation of its results given the characteristics of the data and the purpose of the analysis.NEW & NOTEWORTHYCompared to classical supervised methods, unsupervised methods of analysis have the advantage to be freer of subjective biases. However, it is not always clear what aspects of the data these methods are most sensitive to, which complicates interpretation. Focusing on the Hidden Markov Model, commonly used to describe electrophysiological data, we explore in detail the nature of its estimates through simulations and real data examples, providing important insights about what to expect from these models.
Acoustically Targeted Noninvasive Gene Therapy in Large Brain Regions
Authors: Nouraein Shirin , Lee Sangsin , Saenz Vidal A. , Del Mundo Huckie C. , Yiu Joycelyn , Szablowski Jerzy O. 
Published: January 2023

ABSTRACTFocused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such disorders often affect large brain regions. Moreover, the applicability of FUS-BBBO in the treatment of brain-wide genetic disorders has not yet been evaluated. Herein, we evaluated the transduction efficiency and safety of opening up to 105 sites simultaneously. Increasing the number of targeted sites increased gene delivery efficiency at each site. We achieved transduction of up to 60% of brain cells with comparable efficiency in the majority of the brain regions. Furthermore, gene delivery with FUS-BBBO was safe even when all 105 sites were targeted simultaneously without negative effects on animal weight, neuronal loss, or astrocyte activation. To evaluate the application of multi-site FUS-BBBO for gene therapy, we used it for gene editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, and found effective gene editing, but also a loss of neurons at the targeted sites. Overall, this study provides a brain-wide map of transduction efficiency and the first example of gene editing after site-specific noninvasive gene delivery to a large brain region.
Honey bee drones are synchronously hyperactive inside the nest
Authors: Neubauer Louisa C. , Davidson Jacob D. , Wild Benjamin , Dormagen David M. , Landgraf Tim , Couzin Iain D. , Smith Michael L. 
Published: January 2023

1AbstractEusocial insects operate as an integrated collective with tasks allocated among individuals. This applies also to reproduction, through coordinated mating flights between male and female reproductives. While in some species male sexuals take only a single mating flight and never return, in the Western honey bee,Apis mellifera, the male sexuals (drones) live in the colony throughout their lives. Prior research has focused almost exclusively on drone behavior outside of the nest (mating flights), while ignoring the majority of their life, which is spent inside the nest. To understand the in-nest behavior of drones across their lives, we used the BeesBook tracking system to track 192 individually-marked drones continuously for over 20 days, to examine how drones moved and spent time in the nest. In agreement with previous work, we find that drones spend most of their time immobile at the nest periphery. However, we also observe that drones have periods of in-nest hyperactivity, during which they become the most active individuals in the entire colony. This in-nest hyperactivity develops in drones after age 7 days, occurs daily in the afternoon, and coincides with drones taking outside trips. We find strong synchronization across the drones in the start/end of activity, such that the drones in the colony exhibit a “shared activation period”. The duration of the shared activation period depends on the weather; when conditions are suitable for mating flights, the activation period is extended. At the individual-level, we see that the activation order changes from day to day, suggesting that both the external influence of weather conditions, as well as exchange of social information, influences individual activation. Using an accumulation-to-threshold model of drone activation, we show that simulations using social information match experimental observations. These results provide new insight into the in-nest behavior of drones, and how their behavior reflects their role as the male gametes of the colony.
Generation of human alveolar epithelial type I cells from pluripotent stem cells
Authors: Burgess Claire L , Huang Jessie , Bawa Pushpinder , Alysandratos Konstantinos-Dionysios , Minakin Kasey , Morley Michael P , Babu Apoorva , Villacorta-Martin Carlos , Hinds Anne , Thapa Bibek R , Wang Feiya , Matschulat Adeline M , Morrisey Edward E , Varelas Xaralabos , Kotton Darrell N 
Published: January 2023

AbstractIn the distal lung, alveolar epithelial type I cells (AT1s) comprise the vast majority of alveolar surface area and are uniquely flattened to allow the diffusion of oxygen into the capillaries. This structure along with a quiescent, terminally differentiated phenotype has made AT1s particularly challenging to isolate or maintain in cell culture. As a result, there is a lack of established models for the study of human AT1 biology, and in contrast to alveolar epithelial type II cells (AT2s), little is known about the mechanisms regulating their differentiation. Here we engineer a human in vitro AT1 model system through the directed differentiation of induced pluripotent stem cells (iPSC). We first define the global transcriptomes of primary adult human AT1s, suggesting gene-set benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, that are enriched in these cells. Next, we generate iPSC-derived AT2s (iAT2s) and find that activating nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier which produces characteristic extracellular matrix molecules and secreted ligands. Our results indicate a role for Hippo-LATS-YAP signaling in the differentiation of human AT1s and demonstrate the generation of viable AT1-like cells from iAT2s, providing an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s that until now have been challenging to viably obtain from patients.
Immunogenicity and safety in pigs of PHH-1V, a SARS-CoV-2 RBD fusion heterodimer vaccine candidate
Authors: Moros Alexandra , Prenafeta Antoni , Barreiro Antonio , Perozo Eva , Fernández Alex , Cañete Manuel , González Luis , Garriga Carme , Pradenas Edwards , Marfil Silvia , Blanco Julià , Rica Paula Cebollada , Sisteré-Oró Marta , Meyerhans Andreas , Cabañas Teresa Prat , March Ricard , Ferrer Laura 
Published: January 2023

ABSTRACTThe continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ+T-cell response. We conclude that PHH-1V is safe and elicits a robust immune response to SARS-CoV-2 in pigs, a large animal preclinical model.