bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems approach framework for evaluating tree restoration interventions for social and ecological outcomes in rural tropical landscapes
Authors: Pfeifer Marion , Sallu Susannah M. , Marshall Andrew R. , Rushton Stephen , Moore Eleanor , Shirima Deo D. , Smit Josephine , Kioko Esther , Barnes Lauren , Waite Catherine , Raes Leander , Braunholtz Laura , Olivier Pieter I. , Ishengoma Evodius , Bowers Sam , Guerreiro-Milheiras Sergio 
Published: November 2022

The science guiding design and evaluation of restoration interventions in tropical landscapes is dominated by ecological processes and outcomes and lacks indicators and methods that integrate human wellbeing into the restoration process. We apply a new systems approach framework for tree restoration in forest-agricultural landscapes to show how this shortcoming can be addressed. Demonstrating ‘proof of concept’, we tested statistical models underlying the framework pathways with data collected from a case study in Tanzania. Local community perceptions of nature's values were not affected by levels of self-reported wildlife-induced crop damage. But mapped predictions from the systems approach under a tree restoration scenario suggested differential outcomes for biodiversity indicators and altered spatial patterns of crop damage risk, expected to jeopardize human wellbeing. The predictions map anticipated trade-offs in costs and benefits of restoration scenarios, which we have started to explore with stakeholders to identify restoration opportunities that consider local knowledge, value systems and human wellbeing. We suggest that the framework be applied to other landscapes to identify commonalities and differences in forest landscape restoration outcomes under varying governance and land use systems. This should form a foundation for evidence-based implementation of the global drive for forest landscape restoration, at local scales.This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Realizing the potential of restoration science
Authors: Lewis Simon L. 
Published: November 2022

Restoration science is growing fast. The restoration of habitats is increasingly part of the discussion over how to tackle the challenges of climate change, biodiversity loss and rural development. With this increasing role and attendant visibility, restoration science has seen increasing controversy. Here I describe six aspects of robust restoration science that should be kept in mind to help realize its potential: do data-driven studies; focus on robust results; improve reproducibility; contextualize the results; give attention to economics; consider the wider goals of restoration. Realizing the potential of restoration science, via robust scientific studies, will provide society with the knowledge and tools to make better choices about which habitats to restore and where.This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
A physiologically-based model of bile acid metabolism in mice
Authors: Kister Bastian , Viehof Alina , Rolle-Kampczyk Ulrike , Schwentker Annika , Treichel Nicole Simone , Jennings Susan , Wirtz Theresa H. , Blank Lars M. , Hornef Mathias W. , von Bergen Martin , Clavel Thomas , Kuepfer Lars 
Published: November 2022

AbstractBile acid (BA) metabolism is a complex system that includes a wide variety of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases. However, a mechanistic understanding of the relationship between altered BA metabolism and related diseases is lacking. Computational modeling may support functional analyses of the physiological processes involved in the EHC of BAs along the gut-liver axis. In this study, we developed a physiologically-based model of murine BA metabolism describing synthesis, conjugation, microbial transformations, systemic distribution, excretion and EHC of BAs at the whole-body level. For model development, BA metabolism of specific pathogen-free (SPF) mice was characterized in vivo by measuring BA levels and composition in various organs, expression of transporters along the gut and cecal microbiota composition. We found significantly different BA levels between male and female mice that could only be explained by adjusted expression of the hepatic enzymes and transporters in the model. Of note, this finding was in agreement with experimental observations. The model for SPF mice could also describe equivalent experimental data in germ-free mice by specifically switching of microbial activity in the intestine. The here presented model can therefore facilitate and guide functional analyses of BA metabolism in mice, e.g., the effect of pathophysiological alterations on BA metabolism and translation of results from mouse studies to a clinically relevant context through cross-species extrapolation.
Consortium bibliometric analysis of hotspots and frontiers of immunotherapy in pancreatic cancer
Authors: Xu Qiong , Zhou Yan , Zhang Heng , Li Haipeng , Qin Haoren , Wang Hui 
Published: November 2022

AbstractBackgroundPancreatic cancer is one of the most common malignant neoplasms with an increasing incidence, low rate of early diagnosis, and high degree of malignancy. In recent years, immunotherapy has made remarkable achievements in various cancer types including pancreatic cancer, due to the long-lasting antitumor responses elicited in human body. Immunotherapy mainly relies on mobilizing the host’s natural defense mechanisms to regulate the body state and exert anti-tumor effects. However, no bibliometric research about pancreatic cancer immunotherapy has been reported to date. This study aimed to assess research trends and offer possible new research directions in pancreatic cancer immunotherapy.MethodsThe articles and reviews related to the pancreatic cancer immunotherapy were collected from the Web of Science Core Collection. CiteSpace, VOSviewer and an online platform were used to analyse co-authorship, citation, co-citation, and co-occurrence of terms retrieved from literatures highlighting the scientific advances in pancreatic cancer immunotherapy.ResultsWe collected 2475 publications and the number of articles was growing year by year. The United States had a strong presence worldwide with the most articles. The most contributing institution was Johns Hopkins University (103 papers). EM Jaffee was the most productive researcher with 43 papers, L Zheng and RH Vonderheide ranked second and third, with 34 and 29 papers, respectively. All the keywords were grouped into four clusters: “immunotherapy”, “clinical treatment study”, “tumor immune cell expression”, “tumor microenvironment”. In the light of promising hotspots, keywords with recent citation bursts can be summarized into four aspects: immune microenvironment, adaptive immunotherapy, immunotherapy combinations, and molecular and gene therapy.ConclusionsIn recent decades, immunotherapy showed great promise for many cancer types, so various immunotherapy approaches have been introduced to treat pancreatic cancer. Understanding the mechanisms of immunosuppressive microenvironment, eliminating immune suppression and blocking immune checkpoints, and combining traditional treatments will be hotspots for future research.
3MDR, a microcomputer-controlled visual stimulation device for psychotherapy-like treatments of mice
Authors: Jauch Isa , Kamm Jan , Benn Luca , Rettig Lukas , Friederich Hans-Christoph , Tesarz Jonas , Kuner Thomas , Wieland Sebastian 
Published: November 2022

ABSTRACTPost-traumatic stress disorder and other mental disorders can be treated by an established psychotherapy called Eye Movement Desensitization and Reprocessing (EMDR). In EMDR, patients are confronted with traumatic memories while they are stimulated with alternating bilateral stimuli (ABS). How ABS affect the brain and whether ABS could be adapted to different patients or mental disorders is unknown. Interestingly, ABS reduced conditioned fear in mice. Yet, an approach to systematically test complex visual stimuli and compare respective differences in emotional processing based on (semi-)automated behavioral analysis is lacking. We developed 3MDR (Model for MultiModal visual stimulation to Desensitize Rodents) - a novel, open-source, low-cost, customizable device that can be integrated in and TTL-controlled by commercial rodent behavioral setups. 3MDR allows to design and precisely steer multimodal visual stimuli in the head direction of freely-moving mice. Optimized videography allows to semi-automatically analyze rodent behavior during visual stimulation. Detailed building, integration, and treatment instructions along with open-source software provide easy access for inexperienced users. Using 3MDR, we confirmed that EMDR-like ABS persistently improve fear extinction in mice and showed for the first time that ABS-mediated anxiolytic effects strongly depend on physical stimulus properties such as ABS brightness. 3MDR not only enables researchers to interfere with mouse behavior in an EMDR-like setting, but demonstrates that visual stimuli can be used as a noninvasive brain stimulation to differentially alter emotional processing in mice.SIGNIFICANCE STATEMENTAlternating bilateral stimuli (ABS) reduce fear in post-traumatic stress disorder patients and in mice. The mechanism of how classic ABS – typically used in Eye Movement Desensitization and Reprocessing (EMDR) - reduce fear is enigmatic. We provide detailed resources to build a cost-effective, computer-controlled device called 3MDR to perform and semi-automatically analyze EMDR-like treatments in freely-moving mice and to test behavioral effects of multiple ABS variants. Using the 3MDR device, this study confirmed that classic ABS strongly and persistently improve the extinction of conditioned fear in mice – an effect that depended on the brightness of ABS. This novel method may ultimately contribute to a deeper translational and neurobiological understanding of how visual stimuli affect emotional processing in mice.
Enhanced protein synthesis is a defining requirement for neonatal B cell development
Authors: Åkerstrand Hugo , Boldrin Elena , Montano Giorgia , Vanhee Stijn , Olsson Karin , Krausse Niklas , Vergani Stefano , Cieśla Maciej , Bellodi Cristian , Yuan Joan 
Published: November 2022

AbstractThe LIN28B RNA binding protein exhibits a ontogenically restricted expression pattern and is a key molecular regulator of fetal and neonatal B lymphopoiesis. It enhances the positive selection of CD5+ immature B cells early in life through amplifying the CD19/PI3K/c-MYC pathway and is sufficient to reinitiate self-reactive B-1a cell output when ectopically expressed in the adult. In this study, interactome analysis in primary B cell precursors showed direct binding by LIN28B to numerous ribosomal protein transcripts, consistent with a regulatory role in cellular protein synthesis. Induction of LIN28B expression in the adult setting is sufficient to promote enhanced protein synthesis during the small Pre-B and immature B cell stages, but not during the Pro-B cell stage. This stage dependent effect was dictated by IL-7 mediated signaling, which masked the impact of LIN28B through an overpowering stimulation on the c-MYC / protein synthesis axis in Pro-B cells. Importantly, elevated protein synthesis was a distinguishing feature between neonatal and adult B cell development that was critically supported by endogenousLin28bexpression early in life. Finally, we used a ribosomal hypomorphic mouse model to demonstrate that subdued protein synthesis is specifically detrimental for neonatal B lymphopoiesis and the output of B-1a cells, without affecting B cell development in the adult. Taken together, we identify elevated protein synthesis as a defining requirement for early-life B cell development that critically depends onLin28b. Our findings offer new mechanistic insights into the layered formation of the complex adult B cell repertoire.
The impact of culture variables on 3D humanin vitrobone remodeling; a design of experiments approach
Authors: de Wildt Bregje W.M. , Cuypers Lizzy A.B. , Cramer Esther E.A. , Wentzel Annelieke S. , Ito Keita , Hofmann Sandra 
Published: November 2022

AbstractHumanin vitrobone remodeling models, using osteoclast-osteoblast co-cultures, could facilitate the investigation of human healthy (i.e., balanced) and pathological (i.e., unbalanced) bone remodeling while reducing the need for animal experiments. Although currentin vitroosteoclast-osteoblast co-cultures have improved our understanding of bone remodeling, they lack culture method and outcome measurement standardization, which is hampering reproducibility and translatability. Therefore,in vitrobone remodeling models could benefit from a thorough evaluation of the impact of culture variables on functional and translatable outcome measures, with the aim to reach ‘healthy’ balanced osteoclast and osteoblast activity. Using a resolution III fractional factorial design, we identified the main effects of commonly used culture variables on bone turnover markers in a robustin vitrohuman bone remodeling model. Our model was able to capture physiological quantitative resorption – formation coupling along all conditions, whereby remodeling could be enhanced by external stimuli. Especially culture conditions of two runs showed promising results, where conditions of one run could be used as a high bone turnover system and conditions of another run as a self-regulating system as the addition of osteoclastic and osteogenic differentiation factors was not required for remodeling. The results generated with ourin vitromodel allow for better translation betweenin vitrostudies and towardsin vivostudies, for improved preclinical bone remodeling drug development.Graphical abstract
Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
Authors: Totty Michael S. , Ramanathan Karthik R. , Jin Jingji , Peters Shaun E. , Maren Stephen 
Published: November 2022

AbstractTraumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6-9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a novel role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction.
Systematic analysis of cellular crosstalk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease
Authors: Albanus Ricardo D'Oliveira , Finan Gina M , Brase Logan , Chen Shuo , Guo Qi , Kannan Abhirami , Acquarone Mariana , You Shih-Feng , Novotny Brenna C , Ribeiro Pereira Patricia M , Morris John C , Holtzman David M , McDade Eric , Farlow Martin , Chhatwal Jasmeer P ,   Dominantly Inherited Alzheimer Network (DIAN), Mace Emily E , Benitez Bruno A , Piccio Laura , Sutherland Greg T , Ma Qin , Fu Hongjun , Karch Celeste M , Harari Oscar , Kim Tae-Wan 
Published: November 2022

AbstractCellular crosstalk, mediated by membrane receptors and their ligands, is crucial for brain homeostasis and can contribute to neurodegenerative diseases such as Alzheimer’s disease (AD). To discover crosstalk dysregulations in AD, we reconstructed crosstalk networks from single-nucleus transcriptional profiles from 67 clinically and neuropathologically well-characterized controls and AD brain donors. We predicted a significant role for TREM2 and additional AD risk genes mediating neuron-microglia crosstalk in AD. The gene sub-network mediating SEMA6D-TREM2 crosstalk is activated near Aβ plaques andSEMA6D-expressing cells and is disrupted in late AD stages. Using CRISPR-modified human induced pluripotent stem cell-derived microglia, we demonstrated that SEMA6D induces microglial activation in aTREM2-dependent manner. In summary, we demonstrate that characterizing cellular crosstalk networks can yield novel insights into AD biology.One Sentence SummaryWe investigate cell-to-cell communication in Alzheimer’s disease to characterize disease biology and suggest new avenues for therapeutic intervention.
Biomimetic microstimulation of sensory cortices
Authors: Hughes Christopher , Kozai Takashi 
Published: November 2022

AbstractBackgroundIntracortical microstimulation (ICMS) is an emerging approach to restore sensation to people with neurological injury or disease. Biomimetic microstimulation, or stimulus trains that mimic neural activity in the brain through encoding of onset and offset transients, could improve the utility of ICMS for BCI applications, but how biomimetic microstimulation affects neural activation is not understood. Stimulus induced depression of neural activity (decreases in evoked intensity over time) is also a potential barrier to clinical implementation of sensory feedback, and biomimetic microstimulation may reduce this effect.ObjectiveWe evaluated how biomimetic trains change the calcium response, spatial distribution, and depression of neurons in the somatosensory and visual cortices.MethodsCalcium responses of neurons were measured in Layer 2/3 of visual and somatosensory cortices of anesthetized GCaMP6s mice in response to ICMS trains with fixed amplitude and frequency (Fixed) and three biomimetic ICMS trains that increased the stimulation intensity during the onset and offset of stimulation by modulating the amplitude (BioAmp), frequency (BioFreq), or amplitude and frequency (BioBoth). ICMS was provided for either 1-s with 4-s breaks (Short) or for 30-s with 15-s breaks (Long).ResultsBioAmp and BioBoth trains evoked distinct onset and offset transients in recruited neural populations, while BioFreq trains evoked population activity similar to Fixed trains. Individual neurons had heterogeneous responses primarily based on how quickly they depressed to ICMS, where neurons farther from the electrode depressed faster and a small subpopulation (1-5%) were modulated by BioFreq trains. Neurons that depressed to Short trains were also more likely to depress to Long trains, but Long trains induced more depression overall due to the increased stimulation length. Increasing the amplitude during the hold phase resulted in an increase in recruitment and intensity which resulted in more depression and reduced offset responses. Biomimetic amplitude modulation reduced stimulation induced depression by 14.6±0.3% for Short and 36.1±0.6% for Long trains. Ideal observers were 0.031±0.009 s faster for onset detection and 1.33±0.21 s faster for offset detection with biomimetic amplitude encoding.ConclusionsBiomimetic amplitude modulation evokes distinct onset and offset transients, reduces depression of neural calcium activity, and decreases total charge injection for sensory feedback in brain-computer interfaces by lowering recruitment of neurons during long maintained periods of ICMS. In contrast, biomimetic frequency modulation evokes distinct onset and offset transients in a small subpopulation of neurons but also reduces depression in recruited neurons by reducing the rate of activation.
Monkey-to-human transfer of brain-computer interface decoders
Authors: Rizzoglio Fabio , Altan Ege , Ma Xuan , Bodkin Kevin L. , Dekleva Brian M. , Solla Sara A. , Kennedy Ann , Miller Lee E. 
Published: November 2022

ABSTRACTIntracortical brain-computer interfaces (iBCIs) enable paralyzed persons to generate movement, but current methods require large amounts of both neural and movement-related data to be collected from the iBCI user for supervised decoder training. We hypothesized that the low-dimensional latent neural representations of motor behavior, known to be preserved across time, might also be preserved across individuals, and allow us to circumvent this problem. We trained a decoder to predict the electromyographic (EMG) activity for a “source” monkey from the latent signals of motor cortex. We then used Canonical Correlation Analysis to align the latent signals of a “target” monkey to those of the source. These decoders were as accurate across monkeys as they were across sessions for a given monkey. Remarkably, the same process with latent signals from a human participant with tetraplegia was within 90% of the with-monkey decoding across session accuracy. Our findings suggest that consistent representations of motor activity exist across animals and even species. Discovering this common representation is a crucial first step in designing iBCI decoders that perform well without large amounts of data and supervised subject-specific tuning.