bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on Pregnancy Following Breast Cancer Diagnosis and Treatment
Authors: Perachino Marta , Poggio Francesca , Arecco Luca , Blondeaux Eva , Spinaci Stefano , Marrocco Camilla , Levaggi Alessia , Lambertini Matteo 
Published: May 2022

Abstract
Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor–positive disease and BRCA carriers.
Therapeutic effect of anti-HMGB1 antibody in a mouse model of 4-h middle cerebral artery occlusion: comparison with tissue plasminogen activator
Authors: Nakano Takafumi , Tagashira Yui , Egashira Saki , Morimoto Mayuka , Irie Keiichi , Hosokawa Masato , Hayashi Toshinobu , Egawa Takashi , Hayakawa Kazuhide , Mishima Kenichi 
Published: May 2022

Objective
Delayed tissue plasminogen activator (tPA) treatment increases the risk of intracerebral hemorrhage in patients with ischemic stroke. We previously demonstrated that tPA treatment caused hemorrhagic complications in a 4-h middle cerebral artery occlusion (MCAO) mouse model when administered after reperfusion. In the present study, we administered an anti-high mobility group box 1 (αHMGB1) antibody to 4-h MCAO mice to evaluate the usability of αHMGB1 antibody treatment in the delayed phase of ischemia, beyond the therapeutic time window of tPA.

Methods
αHMGB1 antibody, tPA and control IgG were dissolved in normal saline and administered intravenously into the tail vein of the mice after reperfusion. Infarct volume, hemorrhagic volume, brain swelling, functional outcomes and levels of pro-inflammatory cytokines, such as HMGB1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, were evaluated 24 h after MCAO.

Results
tPA treatment was not only ineffective but also caused a massive intracerebral hemorrhage. Treatment with αHMGB1 antibody reduced the infarct volume and swelling and ameliorated neurologic impairment and motor coordination without hemorrhagic complications by inhibiting HMGB1 activity. Moreover, the αHMGB1 antibody suppressed pathways of secondary inflammatory responses, such as IL-6 and TNF-α, after cerebral ischemia.

Conclusion
These results indicate that αHMGB1 antibody may be therapeutically efficient in the delayed phase of ischemia, where tPA treatment is no longer an eligible option. Treatment with an αHMGB1 antibody may be an effective therapeutic option in patients who exceed the tPA therapeutic time window.
Extracellular application of the N-methyl-D-aspartate receptor allosteric modulator rapastinel acts remotely to regulate Ca2+ inactivation at an intracellular locus
Authors: Zhang Xiao-lei , Berglund Nils A. , Burgdorf Jeffrey S. , Donello John E. , Moskal Joseph R. , Stanton Patric K. 
Published: May 2022

Background
A novel N-methyl-D-aspartate receptor (NMDAR) allosteric modulator, rapastinel (RAP, formerly GLYX-13), elicits long-lasting antidepressant-like effects by enhancing long-term potentiation (LTP) of synaptic transmission. RAP elicits these effects by binding to a unique site in the extracellular region of the NMDAR complex, transiently enhancing NMDAR-gated current in pyramidal neurons of both hippocampus and medial prefrontal cortex.

Methods
We compared efficacy of RAP in modulating Schaffer collateral-evoked NMDAR-currents as a function of kinetics of the Ca2+ chelator in the intracellular solution, using whole-cell patch-clamp recordings. The intracellular solution contained either the slow Ca2+ chelator EGTA [3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecane-1,14-dioic acid, 0.5 mmol/l] or the 40–500-fold kinetically faster, more selective Ca2+ chelator BAPTA {2,2′,2″,2‴-[ethane-1,2-diylbis(oxy-2,1-phenylenenitrilo)] tetraacetic acid, 5 mmol/l}. NMDAR-gated currents were pharmacologically isolated by bath application of the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor antagonist 6-nitro-2,3-dioxo-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (10 μmol/l) plus the GABA receptor blocker bicuculline (20 μmol/l).

Results
When the slow Ca2+ chelator EGTA was in the intracellular solution, RAP elicited significant enhancement of NMDAR-gated current at a 1 μmol/l concentration, and significantly reduced current at 10 μmol/l. In contrast, when recording with the 40–500-fold kinetically faster, more selective Ca2+ chelator BAPTA, NMDAR current increased in magnitude by 84% as BAPTA washed into the cell, and the enhancement of NMDAR current by 1 μmol/l RAP was completely blocked. Interestingly, the reduction in NMDAR current from 10 μmol/l RAP was not affected by the presence of BAPTA in the recording pipette, indicating that this effect is mediated by a different mechanism.

Conclusion
Extracellular binding of RAP to the NMDAR produces a novel, long-range reduction in affinity of the Ca2+ inactivation site on the NMDAR C-terminus accessible to the intracellular space. This action underlies enhancement in NMDAR-gated conductance elicited by RAP.
Hippocampal proteins discovery of diabetes-induced central neuropathy based on proteomics
Authors: Zhao Ying , Huan Shuai , Yang Yang , Gao Weiying , Wang Jie 
Published: May 2022

Objectives
Growing evidence suggests that diabetes can cause multifactorial damage to the central nervous system (CNS) and may lead to dementia. However, the underlying mechanism of diabetes-induced central neuropathy remains sparse. In recent years, proteomics has provided better methods and means in analyzing the molecular mechanisms of disease. We applied proteomics to investigate the changes of hippocampal proteins in diabetic rats, with a view to discover the biomarkers of diabetes-induced central neuropathy and elucidated the potential biological relationships.

Methods
Male Wistar rats were randomly divided into the control group and model group. The model group rats were injected intraperitoneally with streptozotocin. Morris water maze test was performed to evaluate the learning and memory of rats, and the hippocampus was taken out. Proteomics were adopted to investigate the changes of differentially expressed proteins.

Results
Compared with the control group, the escape latency of the diabetic rats was significantly increased (P < 0.01, P < 0.05). It was presented that four differentially expressed proteins might be the potential biomarkers of diabetes-induced central neuropathy: septin 5, GRB2 related binding protein 2 (GAB2), casein kinase 1ε (CK1ε), aquaporin 4 (AQP4). These differentially expressed proteins were mainly involved in the following signaling pathways: apoptosis, glycine/serine/threonine metabolic and GTPase signaling pathway.

Conclusions
These findings provided reference insights into the underlying molecular pathogenesis of diabetes-induced CNS neuropathy.
Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses
Authors: Hagan T. , Gerritsen B. , Tomalin LE. , Fourati S. , Mulè MP. , Chawla DG. , Rychkov D. , Henrich E. , Miller HER. , Diray-Arce J. , Dunn P. , Lee A. ,   The Human Immunology Project Consortium (HIPC), Levy O. , Gottardo R. , Sarwal M. M. , Tsang JS. , Suárez-Fariñas M. , Sékaly RP. , Kleinstein SH. , Pulendran B. 
Published: May 2022

AbstractSystems biology approaches have been used to define molecular signatures and mechanisms of immunity to vaccination. However, most such studies have been done with single vaccines, and comparative analysis of the response to different vaccines is lacking. We integrated temporal transcriptional data of over 3,000 samples, obtained from 820 healthy adults across 28 studies of 13 different vaccines and analyzed vaccination-induced signatures associated with the antibody response. Most vaccines induced similar kinetics of shared transcriptional signatures, including signatures of innate immunity occurring 1-3 days post-vaccination, as well as the canonical plasmablast and cell cycle signatures appearing 7 days post-vaccination. However, the yellow fever vaccine YF-17D uniquely induced an early transient signature of T and B cell activation at Day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at Days 7 and 14-21, respectively. Thus, despite the shared transcriptional response to most vaccines, at any given time point there was no evidence for a “universal signature” that could be used to predict the antibody response to all vaccines. However, accounting for the asynchronous nature of responses led to the identification of a time-adjusted signature that improved prediction antibody of responses across vaccines. These results provide a transcriptional atlas of the human immune response to vaccination and define a common, time-adjusted signature of antibody responses to vaccination.
Unlocking the strength of inducible promoters in gram-negative bacteria
Authors: Carrillo Rincón Andrés Felipe , Farny Natalie G. 
Published: May 2022

AbstractInducible promoters, such as the lac and tet promoters, are ubiquitous biotechnology tools. Inducible bacterial promoters have a consistent architecture including two key elements: the operator region recognized by the transcriptional regulator proteins (e.g., LacI and TetR, and the -10 and -35 consensus sequences required to recruit the sigma (σ) subunits of RNA polymerase to initiate transcription. Despite their widespread use in molecular biology, there remain problems with current inducible expression systems. Leaky transcription in the OFF state remains a particular challenge. Here we have updated the architecture of the lac and tet expression systems to improve their strength, control, and portability. We modified the genetic architecture of the lac and tet expression systems to contain consensus -10 and -35 sequence boxes to be strongly targeted by σ70, to incorporate of a strong ribosome binding site recognized broadly by gram-negative bacteria, and to independently control of the transcriptional regulators by optimized constitutive promoters. To test the promoters, we use the far-red fluorescent protein mCardinal, which we demonstrate significantly improves the signal-to-background ratio of promoter measurement assays over widely utilized green fluorescent proteins. We validate the improvement in OFF state control and inducibility by demonstrating production of the toxic and aggregate-prone cocaine esterase enzyme CocE. We further demonstrate portability of the promoters to additional gram-negative species Pseudomonas putida and Vibrio natriegens. Our results represent a significant improvement over existing protein expression systems that will enable advances in protein production for various biotechnology applications.SignificanceMany of the latest advances in pharmaceuticals, materials, and foods involve the production of recombinant proteins from bacterial hosts. However, the regulated production of enzymes and functional protein products that are toxic to their microbial hosts remains a challenge. Our work provides new tools that enable tight control over expression of protein products in bacterial host strains. We show that our tools function not only in the broadly utilized Escherichia coli, but also in other gram-negative bacteria including the soil organism Pseudomonas putida and the marine bacterium Vibrio natriegens. Our technology will facilitate more efficient production of a broader range of protein products in diverse microbial hosts.
Predicting individual skill learning, a cautionary tale
Authors: Abeles Dekel , Hertzage Jasmine , Shahar Moni , Censor Nitzan 
Published: May 2022

AbstractPeople show vast variability in skill learning. What determines a person’s individual learning ability? In this study we explored the possibility to predict participants’ future learning, based on their behavior during initial skill acquisition. We recruited a large online multi-session sample of participants performing a sequential tapping skill learning task. We trained machine learning models to predict future skill learning from raw data acquired during initial skill acquisition, and from engineered features calculated from the raw data. While the models did not explain learning, strong correlations were observed between initial and final performance. In addition, the results suggest that in correspondence with other empirical fields testing human behavior, canonical experimental tasks developed and selected to detect average effects may constrain insights regarding individual variability, relevant for real-life scenarios. Overall, implementing machine learning tools on large-scale data sets may provide a powerful approach towards revealing what differentiates between high and low innate learning abilities, paving the way for learning optimization techniques which may generalize beyond motor skill learning to broad learning abilities.
Mating strategy predicts gene presence/absence patterns in a genus of simultaneously hermaphroditic flatworms
Authors: Wiberg R. Axel W. , Viktorin Gudrun , Schärer Lukas 
Published: May 2022

AbstractGene repertoire turnover is a characteristic of genome evolution. However, we lack well-replicated analyses of presence/absence patterns associated with different selection contexts. Here, we study ∼100 transcriptome assemblies across Macrostomum, a genus of simultaneously hermaphroditic flatworms exhibiting multiple convergent shifts in mating strategy and associated reproductive morphologies. Many species mate reciprocally, with partners donating and receiving sperm at the same time. Other species convergently evolved to mate by hypodermic injection of sperm into the partner. We find that for orthologous transcripts annotated as expressed in the body region containing the testes, sequences from hypodermically inseminating species diverge more rapidly from the model species, M. lignano, and have a lower probability of being observed in other species. For other annotation categories, simpler models with a constant rate of similarity decay with increasing genetic distance from M. lignano match the observed patterns well. Thus, faster rates of sequence evolution for hypodermically inseminating species in testis-region genes result in higher rates of homology detection failure, yielding a signal of rapid evolution in sequence presence/absence patterns. Our results highlight the utility of considering appropriate null models for unobserved genes, as well as associating patterns of gene presence/absence with replicated evolutionary events in a phylogenetic context.
A generic risk assessment model for animal disease entry through wildlife: The example of highly pathogenic avian influenza and African swine fever in The Netherlands
Authors: Counotte Michel J. , Petie Ronald , van Klink Ed G. M. , de Vos Clazien J. 
Published: May 2022

SummaryAnimal diseases can enter countries or regions through movements of infected wildlife. A generic risk model would allow to quantify the risk of entry via this introduction route for different diseases and wildlife species, despite the vast variety in both, and help policy-makers to make informed decisions. Here, we propose such a generic risk assessment model and illustrate its application by assessing the risk of entry of African swine fever (ASF) through wild boar and highly pathogenic avian influenza (HPAI) through wild birds for the Netherlands between 2014-2021. We used disease outbreak data and abstracted movement patterns to populate a stochastic risk model. We found that the entry risk of HPAI fluctuated between the years with a peak in 2021. In that year, we estimated the number of infected birds to reach the Dutch border by wild bird migration at 273 (95% uncertainty interval: 254-290). The probability that ASF outbreaks that occurred between 2014 and 2021, reached the Dutch border through wild boar movement was very low throughout the whole period; only the upper confidence bound indicated a small entry risk. On a yearly scale, the predicted entry risk for HPAI correlated well with the number of observed outbreaks. In conclusion, we present a generic and flexible framework to assess the entry risk of disease through wildlife. The model allows rapid and transparent estimation of the entry risk for diverse diseases and wildlife species. The modular structure of the model allows to add nuance and complexity, when required or when more data becomes available.
Advancing terrestrial biodiversity monitoring with satellite remote sensing in the context of the Kunming-Montreal global biodiversity framework
Authors: Timmermans Joris , Kissling W. Daniel 
Published: May 2022

AbstractSatellite remote sensing (SRS) provides huge potential for tracking progress towards conservation targets and goals, but SRS products need to be tailored towards the requirements of ecological users and policymakers. In thisviewpointarticle, we propose to advance SRS products with a terrestrial biodiversity focus for tracking the goals and targets of the Kunming-Montreal global biodiversity framework (GBF). Of 371 GBF biodiversity indicators, we identified 58 unique indicators for tracking the state of terrestrial biodiversity, spanning 2 goals and 8 targets. Thirty-six shared enough information to analyse their underlying workflows and spatial information products. We used the concept of Essential Biodiversity Variables (EBV) to connect spatial information products to different dimensions of biodiversity (e.g. species populations, species traits, and ecosystem structure), and then counted EBV usage across GBF goals and targets. Combined with published scores on feasibility, accuracy, and immaturity of SRS products, we identified a priority list of terrestrial SRS products representing opportunities for scientific development in the next decade. From this list, we suggest two key directions for advancing SRS products and workflows in the GBF context using current instruments and technologies. First, existing terrestrial ecosystem distributions and live cover fraction SRS products (of above-ground biomass, ecosystem fragmentation, ecosystem structural variance, fraction of vegetation cover, plant area index profile, and land cover) need to be refined using a co-design approach to achieve harmonized ecosystem taxonomies, reference states and improved thematic detail. Second, new SRS products related to plant physiology and primary productivity (e.g. leaf area index, chlorophyll content & flux, foliar N/P/K content, and carbon cycle) need to be developed to better estimate plant functional traits, especially with deep learning techniques, radiative transfer models and multi-sensor frameworks. Advancements along these two routes could greatly improve the tracking of GBF target 2 (‘improve connectivity of priority terrestrial ecosystems), target 3 (‘ensure management of protected areas’), target 6 (‘control the introduction and impact of invasive alien species’), target 8 (‘minimize impact of climate change on biodiversity’), target 10 (‘increase sustainable productivity of agricultural and forested ecosystems’) and target 12 (‘increase public urban green/blue spaces’). Such improvements can have secondary benefits for other EBVs, e.g. as predictor variables for modelling species distributions and population abundances (i.e. data that are required in several GBF indicators). We hope that ourviewpointstimulates the advancement of biodiversity monitoring from space and a stronger collaboration among ecologists, SRS scientists and policy experts.
Hydroquinone, a cigarette smoke compound, affects cartilage homeostasis through activation of the aryl hydrocarbon receptor pathway
Authors: Heluany Cintia Scucuglia , de Palma Anna , Day Nicholas , Poliselli Farsky Sandra Helena , Nalesso Giovana 
Published: May 2022

AbstractExposure to cigarette smoke has a proven detrimental impact on different aspects of human health. Increasing evidences link smoking to degeneration of joint tissues. However, the toxic mechanisms elicited by the different components of cigarette smoke have not been fully elucidated yet. We have previously shown that exposure to hydroquinone (HQ), a pro-oxidant chemical present in cigarette smoke, can promote joint tissue degradation in murine models of rheumatoid arthritis through the activation of the aryl hydrocarbon receptor (AhR) pathway. Osteoarthritis (OA) is a chronic debilitating articular disease characterized by progressive degradation of the articular cartilage, whose onset and progression have also been associated with smoking. In this work we aimed to investigate the effect of HQ exposure on articular chondrocytes and how it affects cartilage homeostasis. Cell viability, gene expression, oxidative stress and inflammatory parameters were quantified in primary articular chondrocytes exposed to HQ in presence or absence of IL-1β pre-stimulation. HQ stimulation downregulated phenotypic markers genes such as SOX-9 and Col2a1, whereas upregulated the expression of the catabolic enzymes MMP-3 and ADAMTS5. HQ also promoted oxidative stress and reduced proteoglycan content. HQ exacerbated the pro-inflammatory effects mediated by the IL-1β co-stimulation. Finally, we showed that HQ-degenerative effects were mediated by the activation of AhR. Together, our findings address the harmful effects of HQ in the articular cartilage health, providing novel evidence surrounding the toxic mechanisms of environmental pollutants underlying the onset of articular diseases.
From retina to motoneurons: a substrate for visuomotor transformation in salamanders
Authors: Flaive Aurélie , Ryczko Dimitri 
Published: May 2022

AbstractThe transformation of visual input into motor output is essential to approach a target or avoid a predator. In salamanders, visually-guided orientation behaviors have been extensively studied during prey capture. However, the neural circuitry involved is not resolved. Using salamander brain preparations, calcium imaging and tracing experiments, we describe a neural substrate through which retinal input is transformed into spinal motor output. We found that retina stimulation evoked responses in reticulospinal neurons of the middle reticular nucleus, known to control steering movements in salamanders. Microinjection of glutamatergic antagonists in the optic tectum (superior colliculus in mammals) decreased the reticulospinal responses. Using tracing we found that retina projected to the dorsal layers of the contralateral tectum, where the dendrites of neurons projecting to the middle reticular nucleus were located. In slices, stimulation of the tectal dorsal layers evoked glutamatergic responses in deep tectal neurons retrogradely labelled from the middle reticular nucleus. We then examined how tectum activation translated into spinal motor output. Tectum stimulation evoked motoneuronal responses, which were decreased by microinjections of glutamatergic antagonists in the contralateral middle reticular nucleus. Reticulospinal fibers anterogradely labelled from tracer injection in the middle reticular nucleus were preferentially distributed in proximity with the dendrites of ipsilateral motoneurons. Our work establishes a neural substrate linking visual and motor centers in salamanders. This retino-tecto-reticulo-spinal circuitry is well positioned to control orienting behaviors. Our study bridges the gap between the behavioral studies and the neural mechanisms involved in the transformation of visual input into motor output in salamanders.