bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells
Authors: Hom Lisa M. , Sun Seunghoon , Campbell Jamie , Liu Pinyan , Culbert Shannon , Murphy Ireland M. , Schafer Zachary T. 
Published: February 2023

AbstractIn normal tissue homeostasis, bidirectional communication between different cell types can shape numerous biological outcomes. Many studies have documented instances of reciprocal communication between fibroblasts and cancer cells that functionally change cancer cell behavior. However, less is known about how these heterotypic interactions shape epithelial cell function in the absence of oncogenic transformation. Furthermore, fibroblasts are prone to undergo senescence, which is typified by an irreversible cell cycle arrest. Senescent fibroblasts are also known to secrete various cytokines into the extracellular space; a phenomenon that is termed the senescence-associated secretory phenotype (SASP). While the role of fibroblast derived SASP factors on cancer cells has been well studied, the impact of these factors on normal epithelial cells remains poorly understood. We discovered that treatment of normal mammary epithelial cells with conditioned media (CM) from senescent fibroblasts (SASP CM) results in a caspase-dependent cell death. This capacity of SASP CM to cause cell death is maintained across multiple senescence-inducing stimuli. However, the activation of oncogenic signaling in mammary epithelial cells mitigates the ability of SASP CM to induce cell death. Despite the reliance of this cell death on caspase activation, we discovered that SASP CM does not cause cell death by the extrinsic or intrinsic apoptotic pathway. Instead, these cells die by an NLRP3, caspase-1, and gasdermin D (GSDMD)-dependent induction of pyroptosis. Taken together, our findings reveal that senescent fibroblasts can cause pyroptosis in neighboring mammary epithelial cells, which has implications for therapeutic strategies that perturb the behavior of senescent cells.
Macroscale coupling between structural and effective connectivity in the mouse brain
Authors: Benozzo Danilo , Baron Giorgia , Coletta Ludovico , Chiuso Alessandro , Gozzi Alessandro , Bertoldo Alessandra 
Published: February 2023

AbstractHow the emergent functional connectivity (FC) relates to the underlying anatomy (structural connectivity, SC) is one of the biggest questions of modern neuroscience. At the macro-scale level, no one-to-one correspondence between structural and functional links seems to exist. And we posit that to better understand their coupling, two key aspects should be taken into account: the directionality of the structural connectome and the limitations of describing network functions in terms of FC. Here, we employed an accurate directed SC of the mouse brain obtained by means of viral tracers, and related it with single-subject effective connectivity (EC) matrices computed by applying a recently developed DCM to whole-brain resting-state fMRI data. We analyzed how SC deviates from EC and quantified their couplings by conditioning both on the strongest SC links and EC links. We found that when conditioning on the strongest EC links, the obtained coupling follows the unimodal-transmodal functional hierarchy. Whereas the reverse is not true, as there are strong SC links within high-order cortical areas with no corresponding strong EC links. This mismatch is even more clear across networks. Only the connections within sensory motor networks align both in terms of effective and structural strength.
A novel purity analysis method of bovine milk-derived exosomes by two-dimensional high-performance liquid chromatography
Authors: Lu Lu , Han Chunle , Zhang Quan , Wang Miao , Qi Dongli , Gao Mengya , Wang Na , Yin Jianxin , Dong Fengwei , Ge Xiaohu 
Published: February 2023

AbstractExosomes have been implicated in many biological processes as intercellular communication carriers. Because exosomes are increasingly explored as natural vehicles for cell and gene therapies, and drug delivery applications, it is critical to have high-quality samples. Protein:particle ratio, ELISA, western blotting, polymerase chain reaction, and size-exclusion high-performance liquid chromatography are the main methods that have been extensively applied to analyze exosomes purity in recent years. However, there is currently no well-established method that is convenient for routine quality analysis of small-size impurities in exosomes samples. Here, a size-exclusion high-performance liquid chromatography (SE-HPLC), an ion-exchange high-performance liquid chromatography (IEX-HPLC), and a novel two-dimensional high-performance liquid chromatography (2D-HPLC) method were used to detect the purity of bovine milk-derived exosomes with different processes of exosome isolation in detail. The results showed that the 2D-HPLC method could enhance the accuracy of detecting exosomal purity with higher precision and accuracy of instrumental, reduced personal error and experimental cost, shortened analysis time greatly, and more automation. The 2D-HPLC method is rapid, exhibits high selectivity, and has good sensitivity, thus making it well-suited for application in the pharmaceutical and toxicological analysis of exosomes.
Synthesis, structure, in vitro pharmacology, and in vivo activity of trans‐3,4‐dichloro‐N‐[[1‐(dimethylamino)‐4‐phenylcyclohexyl]methyl]‐benzamide (AP01; 4‐phenyl‐AH‐7921), a novel mixed μ‐/κ‐opioid
Authors: Krstenansky John L. , Bacsa John , Zambon Alexander 
Published: February 2023

AbstractAnalogs of non‐fentanyl novel synthetic opioids (NSO) with modifications that fall outside of established structure–activity relationships (SARs) for that class of drugs create the question whether or not it should be considered an analog, as defined by 21 U.S.C. §802(32)(A), which is important for its inclusion in the US system of drug scheduling. AH‐7921 is a US Schedule I drug and an example of the 1‐benzamidomethyl‐1‐cyclohexyldialkylamine class of NSO. The SARs regarding substitution of the central cyclohexyl ring have not been well characterized in the literature. Therefore, in order to expand the SAR surrounding AH‐7921 analogs, trans‐3,4‐dichloro‐N‐[[1‐(dimethylamino)‐4‐phenylcyclohexyl]methyl]‐benzamide (AP01; 4‐phenyl‐AH‐7921) has been synthesized, analytically characterized, and tested in vitro and in vivo pharmacologically. Using methods described in the original patents for this class of NSO, it was found that the single trans geometric isomer was obtained. The proton nuclear magnetic resonance, mass spectrum, infrared spectrum, and Raman spectrum are reported along with the melting point of the hydrochloride salt. In vitro binding to a battery of 43 central nervous system receptors showed it to be a high‐affinity μ‐opioid receptor (MOR) and κ‐opioid receptor (KOR) ligand (60 nM and 34 nM, respectively). AP01 also had a 4 nM affinity for the serotonin transporter (SERT), which is a higher level of potency at this receptor than most other opioids. In rats, it exhibited antinociception in the acetic acid writhing test. Therefore, the 4‐phenyl modification results in an active NSO, but carries with it potential toxicities beyond those expected for currently approved opioid drugs.
Myopericytomatosis: A rare entity mimicking other vascular tumours and malformations
Authors: Zhang Lois , Kang Mina , Kossard Steven , Parsi Kurosh 
Published: February 2023

AbstractMyopericytoma is a rare tumour which typically presents as a benign lesion that mimics features of other more common vascular tumours and malformations. We present a case of a symptomatic diffuse myopericytomatosis of the left abdomen presenting as multiple subcutaneous vascular tumours detected on ultrasound and treated with ultrasound‐guided sclerotherapy.
Spatial mismatch between wild bee diversity hotspots and protected areas
Authors: Casanelles‐Abella Joan , Fontana Simone , Meier Eliane , Moretti Marco , Fournier Betrand 
Published: February 2023

AbstractWild bees are critical for multiple ecosystem functions but are currently threatened. Understanding the determinants of the spatial distribution of wild bee diversity is a major research gap for their conservation. We modeled wild bee α and β taxonomic and functional diversity in Switzerland to uncover countrywide diversity patterns and determine the extent to which they provide complementary information, assess the importance of the different drivers structuring wild bee diversity, identify hotspots of wild bee diversity, and determine the overlap between diversity hotspots and the network of protected areas. We used site‐level occurrence and trait data from 547 wild bee species across 3343 plots and calculated community attributes, including taxonomic diversity metrics, community mean trait values, and functional diversity metrics. We modeled their distribution with predictors describing gradients of climate, resource availability (vegetation), and anthropogenic influence (i.e., land‐use types and beekeeping intensity). Wild bee diversity changed along gradients of climate and resource availability; high‐elevation areas had lower functional and taxonomic α diversity, and xeric areas harbored more diverse bee communities. Functional and taxonomic β diversities diverged from this pattern, with high elevations hosting unique species and trait combinations. The proportion of diversity hotspots included in protected areas depended on the biodiversity facet, but most diversity hotspots occurred in unprotected land. Climate and resource availability gradients drove spatial patterns of wild bee diversity, resulting in lower overall diversity at higher elevations, but simultaneously greater taxonomic and functional uniqueness. This spatial mismatch among distinct biodiversity facets and the degree of overlap with protected areas is a challenge to wild bee conservation, especially in the face of global change, and calls for better integrating unprotected land. The application of spatial predictive models represents a valuable tool to aid the future development of protected areas and achieve wild bee conservation goals.
Use of the FreeStyle Libre system and diabetes treatment progression in T2DM: Results from a retrospective cohort study using a Canadian private payer claims database
Authors: Harris Stewart B. , Levrat‐Guillen Fleur 
Published: February 2023

AbstractBackgroundUp to one‐third of Canadians are estimated to be living with prediabetes or diabetes. A retrospective study using Canadian private drug claims data was conducted to investigate whether flash glucose monitoring using the FreeStyle Libre system (FSL) among people with type 2 diabetes mellitus (T2DM) in Canada can be associated with changes in treatment intensification when compared with blood glucose monitoring (BGM) alone.Materials and MethodsUsing a Canadian national private drug claims database comprising approximately 50% coverage of insured individuals in Canada, cohorts of people with T2DM using FSL or BGM were identified algorithmically based on treatment history and followed over a 24‐month study period, tracking their progression in diabetes treatment therapy. The Andersen‐Gill model for recurrent time‐to‐event data was used to evaluate whether the rate of treatment progression differs between the FSL and BGM treatment cohorts. The survival function was used to calculate comparative treatment progression probabilities between the cohorts.ResultsIn total, 373 871 people with T2DM met the inclusion criteria. Across treatment (FSL) and control (BGM) groups, people using FSL had a higher probability of treatment progression compared with BGM alone, with a relative risk ranging between 1.86 and 2.81 (p < .001). A higher probability of treatment progression was independent of the diabetes treatment at the enrolment date (index date) or the patient status, and independent of whether patients were treatment naïve or on established diabetes therapy. Assessment of the ending treatment relative to the starting therapy indicated that dynamic treatment changes were most evident for patients in the FSL cohort and that the FSL cohort had a much greater portion of patients who ended with insulin treatment (when they started with non‐insulin treatment) compared with the BGM cohort.ConclusionsPeople with T2DM using FSL had a greater probability for treatment progression compared with BGM alone, irrespective of the starting therapy, which may suggest that FSL can be used to support escalation of diabetes therapy to improve therapeutic inertia in T2DM.
Rosmarinic acid alleviates ultraviolet‐mediated skin aging via attenuation of mitochondrial and ER stress responses
Authors: Gupta Divya , Sharma Raghu Rai , Rashid Haroon , Bhat Aalim Maqsood , Tanveer Malik Ahmad , Abdullah Sheikh Tasduq 
Published: February 2023

AbstractChronic exposure to Ultraviolet B radiation (UV‐B) evokes a myriad of toxic signalling events in the irradiated skin. One of such response is ER stress, which is known to exacerbate photodamage responses. Also, recent literature has highlighted the adverse impact of environmental toxicants on mitochondrial dynamics and mitophagy. Impaired mitochondrial dynamics escalates oxidative damage and causes apoptosis. There have been evidences that support crosstalk between ER stress and mitochondrial dysfunction. However, mechanistic clarification is still needed to verify the interactions between UPR responses and mitochondrial dynamics impairment in UV‐B‐induced photodamage models. Lastly, plant‐based natural agents have garnered attention as therapeutic agents against skin photodamage. Thus, gaining mechanistic insights of plant‐based natural agents is required for their application and feasibility in clinical settings. With this aim in view, this study was performed in primary human dermal fibroblasts (HDFs) and Balb/C mice. Different parameters regarding mitochondrial dynamics, ER stress, intracellular damage and histological damage were analyzed using western blot, rt‐PCR and microscopy. We demonstrated that UV‐B exposure leads to induction of UPR responses, upregulation of Drp‐1 and inhibition of mitophagy. Further, 4‐PBA treatment leads to reversal of these noxious stimuli in irradiated HDF cells, thereby, indicating an upstream role of UPR induction in mitophagy inhibition. Also, we explored the therapeutic effect of Rosmarinic acid (RA) against ER stress and impaired mitophagy in photodamage models. RA prevents intracellular damage via alleviation of ER stress and mitophagic responses in HDFs and irradiated Balb/C mice skin. The current study summarizes the mechanistic insights into UVB‐mediated intracellular damage and role of natural plant‐based agent (RA) in ameliorating these toxic responses.
Effects of litter placement, soil moisture and temperature on soil carbon dioxide emissions in a sandy grassland soil
Authors: Hosseiniaghdam Elnazsadat , Yang Haishun , Mamo Martha , Kaiser Michael , Schacht Walter H. , Eskridge Kent M. , Abagandura Gandura O. 
Published: February 2023

AbstractSemiarid grasslands contribute significantly to global soil carbon (C) storage. Carbon loss from these systems via microbial decomposition is controlled by abiotic and biotic factors such as soil moisture and temperature and C input. Plant litter in these systems can be present above the soil surface or mixed with surface soil by trampling, especially in intensively grazed areas. A quantitative understanding of abiotic factors' interactive effect is critical for predicting soil C dynamics in response to grassland management and environmental conditions changes. Therefore, we conducted a 3‐month laboratory incubation experiment to quantify the impact of litter placement and soil moisture on soil carbon dioxide (CO2) emissions under three controlled temperatures. The treatments including three litter placements (no litter, litter on top and litter mixed with surface soil) and three soil moisture levels (23%, 37% and 50% water‐filled pore space [WFPS]) were incubated at three temperatures (10°C, 20°C and 30°C). Carbon dioxide fluxes were measured every 2 weeks. Soil CO2 fluxes were higher for all moisture and litter treatments initially and declined overtime at 20°C and 30°C. Mixing litter with soil increased the cumulative CO2 emissions by 24% and 19.5% at 20°C and 30°C, respectively, compared to no litter. Also, soil‐litter mixing compared with litter on top showed a 14.3% and 21.6% increase in cumulative CO2 emissions at temperatures of 20°C and 30°C, respectively. At all temperatures, 37% and 50% WFPS resulted in similar cumulative CO2 emissions. The results from this study indicate that rising temperatures from 10°C to 30°C accelerate the effect of soil litter mixing on increasing CO2 emissions compared to litter on top and no litter.
Ion migration study in acid‐leached soda–lime–silica glass by thermally stimulated depolarization current analysis
Authors: Nieves Cesar A. , Ogrinc Andrew L. , Kim Seong H. , Furman Eugene , Lanagan Michael T. 
Published: February 2023

AbstractIonic conductivity in silicate glasses is a major issue in the energy sector due to its detrimental effect on electric energy generation and storage and has received increasing attention over the past years. In this study, surface modification of soda–lime–silica (SLS) float glass via acid‐leaching treatment (pH 1) was implemented to understand the impact on ionic transport. The acid‐leaching treatment created a sodium‐depleted “silica‐like” structure in the near‐surface region with depths of 110 ± 20 nm for the air‐side and 93 ± 2 nm for the tin‐side of the SLS glass. Using the thermally stimulated depolarization current technique, two thermally activated relaxation peaks were found to be associated with different ion migration mechanisms. The first peak (P1) with activation energy of ∼0.85 eV was attributed to dc conduction of Na+ ions through the glass bulk. A second overlapping peak (P2) at a higher temperature was found to be related to a more limited Na+ ion migration through the acid‐leached structure, due to H+ conduction, or a coupled contribution of both mechanisms.
How does government policy influence the employment and training of nurse practitioners and physician assistants? A realist analysis using qualitative interviews
Authors: Dankers‐de Mari Ellen J. C. M. , Thijssen Marjolein C. E. , Van Hees Suzanne G. M. , Albertus Job , Batenburg Ronald , Jeurissen Patrick P. T. , Van Vught Anneke J. A. H. 
Published: February 2023

AbstractAimsThe aim of this study was to develop insights into how and why Dutch government policies on deployment and training of nurse practitioners and physician assistants have effect and under what circumstances.DesignA realist analysis using qualitative interviews.MethodsData analysis of 50 semi‐structured interviews conducted in 2019 with healthcare providers, sectoral and professional associations, and training coordinators. Stratified purposive and snowball sampling were used.ResultsPolicies stimulated employment and training of nurse practitioners and physician assistants by: (1) contributing to the familiarity of participants in the decision‐making process in healthcare providers with and medical doctors' trust in these professions; (2) contributing to participants' motivation in employment and training; and (3) eliminating barriers perceived by medical doctors, managers and directors. The extent to which policies affected employment and training was largely determined by sectoral and organizational circumstances, such as healthcare demand and complexity, and decision‐makers in healthcare providers (medical doctors or managers/directors).ConclusionEffectuating familiarity and trust among participants in the decision‐making process is a crucial first step. Next, policymakers can motivate participants and lower their perceived barriers by extending the scope of practice, creating reimbursement opportunities and contributing to training costs. Theoretical insights into nurse practitioner and physician assistant employment and training have been refined.ImpactThe findings highlight how governments, health insurers, sectoral and professional associations, departments, councils, healthcare providers and professionals can facilitate and support nurse practitioner and physician assistant employment and training by contributing to familiarity, trust and motivation, and by clearing perceived barriers.
Habitat and not topographic heterogeneity constrains the range sizes of African mammals
Authors: Lauer Daniel A. , Shipley Benjamin R. , McGuire Jenny L. 
Published: February 2023

AbstractAimThe extinction risks of species are influenced by their geographical range sizes, as species with smaller ranges are more likely to go extinct following disturbance events. Theoretically, heterogeneous landscapes can maintain small‐ranged species, because they facilitate the coexistence of taxa that are each constrained to distinct abiotic conditions. However, we do not fully understand whether this process is more attributable to variation in habitat types (habitat heterogeneity) or physical elevations (topographic heterogeneity) across landscapes. Here, we compare the influences of habitat versus topographic heterogeneity on mammalian range sizes in Africa.LocationAfrica.TaxonMammalia.MethodsWe built a phylogenetic generalized least squares model to predict the range sizes of 1033 mammalian species from their functional traits and abiotic conditions. We assessed how the performance of the model changed when we incorporated measures of the local habitat and, separately, topographic heterogeneity that species experience.ResultsHabitat and topographic heterogeneity are weakly correlated across Africa (ρ = 0.14). Habitat heterogeneity is inversely related to range size (model coefficient = −0.88). Incorporating habitat heterogeneity significantly decreased the model's AICc, increased its likelihood and increased the proportion of variance that is explained in the range sizes of species. Conversely, topographic heterogeneity is not significantly related to range size and had no impact on the model's AICc, likelihood or predictive performance. This contrast between habitat and topographic heterogeneity is particularly prevalent in carnivorous mammalian clades. Results at multiple spatial resolutions differed minimally.Main ConclusionsOur findings advance ecological theory by demonstrating that a landscape's variation in habitats, and not in elevations, relates inversely with mammalian range size and therefore facilitates the coexistence of small‐ranged mammals. Conservation efforts in regions of high habitat heterogeneity will be critical to prevent extinctions in Africa's biodiverse mammalian species.