bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between recreational cannabis commercialization and cannabis exposures reported to the US National Poison Data System
Authors: Shi Yuyan , Liang Di 
Published: February 2020

AbstractBackground and AimsRecreational cannabis has been legalized in 11 states and District of Columbia (DC) in the United States. Among these, 10 states further permitted retail sale to provide a legal supply to adults. This study examined the associations of cannabis exposures with recreational cannabis legalization and commercialization.DesignSecondary data analysis of state‐quarter level cannabis exposures during 2010–17 in the United States. Linear regressions with a difference‐in‐differences design were used to compare pre‐ and post‐legalization trends in states that legalized recreational cannabis to contemporaneous trends in states that did not legalize recreational cannabis.SettingUnited States, including all 50 states and DC.CasesCannabis exposures reported to the US National Poison Data System.MeasurementsThe primary outcome was state age‐adjusted cannabis exposures reported to the US National Poison Data System per 1 000 000 population per quarter. The two policy variables of interest included (1) the enactment of recreational cannabis legalization (i.e. removing penalties for adults’ possession of cannabis in a small amount for recreational use) and (2) the initiation of recreational cannabis commercialization (i.e. providing a legal supply of cannabis to adults through licensed dispensaries).FindingsThe association between a state's enactment of recreational cannabis legalization and its changes in cannabis exposures was statistically non‐significant overall. After controlling for recreational cannabis legalization, however, the initiation of recreational cannabis commercialization was associated with 5.06–5.80 more exposures per 1 000 000 population per quarter (67–77% increase relative to the pre‐legalization average), depending on the composition of comparison states. The increase associated with commercialization was higher among minors than adults (7.97–9.53 versus 3.83–4.21 more exposures), higher among males than females (6.16–7.56 versus 3.76–3.91 more exposures) and higher among exposures with medical consequences than those without medical consequences (4.09–4.79 versus 0.97–1.01 more exposures).ConclusionAn increase in cannabis exposures reported to the US National Poison Data System was observed following recreational cannabis commercialization in the United States.
Vedolizumab for perianal Crohn’s disease: a multicentre cohort study in 151 patients
Authors: Chapuis‐Biron Constance , Bourrier Anne , Nachury Maria , Nancey Stéphane , Bouhnik Yoram , Serrero Mélanie , Armengol‐Debeir Laura , Buisson Anthony , Tran‐Minh My‐Linh , Zallot Camille , Fumery Mathurin , Bouguen Guillaume , Abitbol Vered , Viennot Stéphanie , Chanteloup Elise , Rajca Sylvie , Dib Nina , Parmentier Anne‐Laure , Peyrin‐Biroulet Laurent , Vuitton Lucine ,   the GETAID BioLAP Study Group
Published: February 2020

SummaryBackgroundThe management of Crohn's disease patients with perianal lesions and anti‐TNF failure is challenging.AimsTo assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real‐life cohort.MethodsWe conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments.ResultsOne hundred and fifty‐one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti‐TNF. The median follow‐up time was 52 weeks. Sixty‐eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04‐0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25‐18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks.ConclusionsWe identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.
Frequent methylation of the tumour suppressor miR‐1258 targeting PDL1: implication in multiple myeloma‐specific cytotoxicity and prognostification
Authors: Wang Lu Q. , Kumar Shaji , Calin George A. , Li Zhenhai , Chim Chor S. 
Published: February 2020

SummarymiR‐1258 is localised to the first intron of ZNF385B at chromosome 2q31.3. miR‐1258 promoter methylation was studied in 147 samples including 10 normal buffy coat, eight normal bone marrow plasma cells, 16 human myeloma cell lines (HMCLs), 20 MGUS, 63 diagnostic myeloma, and 30 relapsed myeloma samples by methylation‐specific PCR. In myeloma lines, miR‐1258 methylation, verified by pyrosequencing, was detected in 62·5% HMCLs but not normal controls, and expression of miR‐1258 correlated with that of ZNF385B. 5‐Aza‐2′‐deoxycytidine resulted in promoter demethylation and ZNF385B/miR‐1258 re‐expression. Luciferase assay confirmed programmed cell death ligand‐1 (PDL1) as a direct target of miR‐1258. Over‐expression of miR‐1258 in completely methylated myeloma cells led to reduced cellular proliferation and enhanced apoptosis, hence a tumour suppressor role, in addition to repression of PDL1. In primary samples, miR‐1258 methylation, with lower expression of miR‐1258, was detected in 49·2% diagnostic myeloma, imparting an inferior PFS (P = 0·034) in addition to 50·0% relapsed myeloma but not MGUS. Therefore, miR‐1258 is a tumour suppressor miRNA co‐regulated with its host gene, and frequently hypermethylated in active myeloma instead of MGUS, hence acquired during myeloma progression. Methylation‐mediated miR‐1258 silencing led to overexpression of PDL1 and inferior PFS, implicating miR‐1258 in the modulation of myeloma‐specific cytotoxicity.
A low MW inhibitor of CD44 dimerization for the treatment of glioblastoma
Authors: Wang Chongwu , Wang Zhaotao , Chen Chen , Fu Xiaojun , Wang Ji , Fei Xiaowei , Yan Xiaojing , Xu Ruxiang 
Published: February 2020

Background and PurposeAs a hallmark of glioblastoma multiforme (GBM), CD44 plays a crucial role in promoting glioblastoma stem cell (GSC) stemness phenotypes and multiple drug resistance. The therapeutic potential of CD44 has been validated by the clinical successes of several CD44 inhibitors, including antibodies and hyaluronan‐related drugs.Experimental ApproachWe used systemsDock software to predict verbascoside as a candidate CD44 inhibitor. Microscale thermophoresis was used to confirm the interaction between CD44 and verbascoside. Four glioblastoma cell lines and a patient‐derived glioblastoma cell line were used to test the influences of verbascoside on glioblastoma. CD44‐overexpressing and CD44‐knockout cell lines were also used. Real‐time quantitative PCR and western blot analyses were performed. A xenograft mouse model was used to test verbascoside.Key ResultsVerbascoside bound to CD44 and suppressed its dimerization. By inhibiting CD44 dimerization, verbascoside decreased the release of the CD44 intracellular domain (CD44ICD) and suppressed the expression of CD44 downstream genes. Verbascoside treatment suppressed the stemness phenotypes of cells with high CD44 expression. In a mouse model of glioma, verbascoside treatment highly reduced the growth of intracranial tumours and inhibited CD44ICD release. Both stem cell marker and mesenchymal GBM subtype marker genes were down‐regulated in verbascoside‐treated mice.Conclusion and ImplicationsVerbascoside suppressed growth of glioblastoma cells by inhibiting CD44 dimerization. Stem cell‐like cell properties and tumour cell growth were also suppressed by verbascoside, both in vitro and in vivo. Verbascoside significantly prolonged survival of xenografted mice.
The evolution of the human capital of women
Authors: Bowlus Audra , Robinson Chris 
Published: February 2020

AbstractThe labour market attachment of females has increased dramatically over the last half century, converging to a pattern similar to that of males. Human capital theory predicts an associated increase in human capital investment by females and a convergence in the life‐cycle human capital investment profiles of males and females. This paper explores wage‐based and job skills‐based approaches to measuring the increased supply of efficiency units of human capital by females over the last four decades. Results suggest that the magnitude of the contribution of the increased human capital of women to post‐war economic growth is substantially underestimated by conventional methods of measuring human capital and labour inputs. A complete picture of the evolution of the human capital of women requires new approaches to measuring their human capital.
Computational‐based discovery of FAK FERM domain chemical probes that inhibit HER2‐FAK cancer signaling
Authors: Stahl Erik , Nott Rohini , Koessel Karissa , Cance William , Marlowe Timothy 
Published: February 2020

AbstractThe N‐terminal FERM domain of focal adhesion kinase (FAK) contributes to FAK scaffolding and interacts with HER2, an oncogene and receptor tyrosine kinase. The interaction between HER2 and FAK drives resistance to FAK‐kinase domain inhibitors through FAK Y397 transphosphorylation and FAK re‐activation upon inhibition. As such, FAK FERM remains an attractive drug discovery target. In this report, we detail an alternative approach to targeting FAK through virtual screening‐based discovery of chemical probes that target FAK FERM. We validated the binding interface between HER2 and FAK using site‐directed mutagenesis and GST pull‐down experiments. We assessed the ligandability of key‐binding residues of HER2 and FAK utilizing computational tools. We developed a virtual screening method to screen ~200,000 compounds against the FAK FERM domain, identifying 20 virtual chemical probes. We performed GST pull‐down screening on these compounds, discovering two hits, VS4 and VS14, with nanomolar IC50s in disrupting HER2‐FAK. We performed further testing, including molecular docking, immunofluorescence, phosphorylation, and cellular invasion assays to evaluate the compounds’ biological effects. One probe, VS14, was identified with the ability to block both auto‐ and transphosphorylation of Y397. In all, these studies identify two new probes that target FAK FERM, enabling future investigation of this domain.
The potential of marginal coastal nursery habitats for the conservation of a culturally important Caribbean marine species
Authors: Stieglitz Thomas C. , Dujon Antoine M. , Peel Joanne R. , Amice Erwan 
Published: February 2020

AbstractAimIdentifying the potential of marginal habitats for species conservation is of key importance when their core high‐quality habitats are under substantial disturbances and threats. However, there is currently a knowledge gap on how useful marine marginal habitats may be for conserving endangered marine species. Here, we investigate the potential of groundwater‐fed coastal areas for the conservation of the queen conch, an economically and culturally important marine gastropod.LocationThe inlet of Xel‐Há, typical of groundwater‐fed coastal areas widely distributed along the Yucatan Peninsula coast in Mexico and partially protected by a network of marine protected areas.MethodsWe tracked 66 queen conchs (Lobatus gigas) using acoustic telemetry over a period of 3.5 years. We investigated for ontogenetic niche shift using a network analysis and by modelling their growth.ResultsThe queen conchs exhibited the same ontogenetic niche shift required to complete their life cycle in this marginal habitat as they do in offshore core habitats. A total of 33 individuals departed the inlet and migrated from shallow groundwater‐affected nursery grounds to deeper marine habitats more suitable for breeding aggregation.Main conclusionsAs the broad‐scale movement behaviour of queen conch in this inlet is similar to that observed on the overfished core habitats, our findings suggest that groundwater‐fed coastal areas should be included in conservation planning for an effective management of this species within a network of marine protected areas.
Edge effects on insect–plant food webs: assessing the influence of geographical orientation and microclimatic conditions
Authors: Bernaschini María Laura , Valladares Graciela , Salvo Adriana 
Published: February 2020

1. Geographical orientation affects the magnitude of microclimatic edge effects, mainly by altering the exposure to solar radiation. There is considerable evidence available concerning the influence of microclimatic edge effects on organisms at the population level, although little is known about effects at the community level, and variations with edge geographical orientation have barely been addressed. The present study investigated the influence of microclimatic conditions at the forest interior and edges with different geographical orientation on plant–leafminer–parasitoid food webs in the fragmented Chaco Serrano forest located in Central Argentina.2. Microclimatic variables were measured in three locations: interior, north, and south‐facing edges of six forest fragments. In each location, plant resource availability was assessed and mined leaves were collected to investigate plant–leafminer–parasitoid communities by rearing leafminer and parasitoid adults.3. The results obtained revealed changes in the specific composition of plant, leafminer and parasitoid communities among locations, although they failed to detect location influences on most variables linked to abundance (except for leafminers), richness or food web structure. Leafminer abundance was negatively related to temperature, whereas their richness was related, also negatively, to moisture. Instead, parasitoids were favoured by higher temperatures and light levels, stronger winds, and lower humidity.4. The results of the present study indicate that the effects of microclimatic conditions may depend on the trophic level considered. Moreover, the findings suggest that possible trade‐offs between direct and indirect effects (such as plant quality, floral resources, etc.) of microclimatic conditions could influence plant and insect responses to location.
Modulation change detection in human auditory cortex: Evidence for asymmetric, non‐linear edge detection
Authors: Kim Seung‐Goo , Poeppel David , Overath Tobias 
Published: February 2020

AbstractChanges in modulation rate are important cues for parsing acoustic signals, such as speech. We parametrically controlled modulation rate via the correlation coefficient (r) of amplitude spectra across fixed frequency channels between adjacent time frames: broadband modulation spectra are biased toward slow modulate rates with increasing r, and vice versa. By concatenating segments with different r, acoustic changes of various directions (e.g., changes from low to high correlation coefficients, that is, random‐to‐correlated or vice versa) and sizes (e.g., changes from low to high or from medium to high correlation coefficients) can be obtained. Participants listened to sound blocks and detected changes in correlation while MEG was recorded. Evoked responses to changes in correlation demonstrated (a) an asymmetric representation of change direction: random‐to‐correlated changes produced a prominent evoked field around 180 ms, while correlated‐to‐random changes evoked an earlier response with peaks at around 70 and 120 ms, whose topographies resemble those of the canonical P50m and N100m responses, respectively, and (b) a highly non‐linear representation of correlation structure, whereby even small changes involving segments with a high correlation coefficient were much more salient than relatively large changes that did not involve segments with high correlation coefficients. Induced responses revealed phase tracking in the delta and theta frequency bands for the high correlation stimuli. The results confirm a high sensitivity for low modulation rates in human auditory cortex, both in terms of their representation and their segregation from other modulation rates.
Predicting soil test phosphorus decrease in non‐P‐fertilized conditions
Authors: Appelhans Stefania C. , Carciochi Walter D. , Correndo Adrian , Gutierrez Boem Flavio H. , Salvagiotti Fernando , Garcia Fernando O. , Melchiori Ricardo J.M. , Barbagelata Pedro A. , Ventimiglia Luis A. , Ferraris Gustavo N. , Vivas Hugo S. , Caviglia Octavio P. , Ciampitti Ignacio A. 
Published: February 2020

AbstractMonitoring the availability of phosphorus (P) in soil under continuous cropping facilitates finding deficiency in crops and contributes to improving crop growth and nutrient management models. Soil P availability for crops is usually estimated by soil test P (STP), such as Bray‐1. This is widely used in the Americas. The relationship between the decrease of STP Bray‐1 and cumulative removal of P was evaluated in non‐P‐fertilized areas in long‐term studies. This removal was the sum of annual P removal over the study period as P exported in grains/crop outside the soil. The objectives were to: (a) quantify changes in STP as a function of cumulative P removal, (b) assess the relationship between relative decrease rate of STP and soil variables as well as annual removal of P by crops, and (c) develop a model to predict decrease of STP Bray‐1. Exponential decay functions were used to describe annual cumulative removal of P and STP from soil over time for 12 long‐term studies where no addition of P fertilizer was carried out. Changes in the relative rate of decrease of STP, relative to the initial STP Bray‐1 value at the onset of the experiment, were predicted by the ratio of soil organic matter to clay and silt and the average annual P removal by exponential decay (R2adj = 0.64; RMSE = 3.2 mg kg−1). We propose this predictive model as suitable to provide estimates of the relative decrease rate of STP by Bray‐1 and thereby improve management of P for optimizing crop yield.Highlights
STP Bray‐1 decrease and cumulative P removal were related by exponential decay functions.
Relative decrease rate of STP Bray‐1 was related to SOM/(clay+silt) ratio and annual P removal.
A predictive model of the relative decrease rate of STP Bray‐1 was fitted and validate.
Our model is a useful tool to help predict soil P availability and nutrient management.
Same same but different: A Web‐based deep learning application revealed classifying features for the histopathologic distinction of cortical malformations
Authors: Kubach Joshua , Muhlebner‐Fahrngruber Angelika , Soylemezoglu Figen , Miyata Hajime , Niehusmann Pitt , Honavar Mrinalini , Rogerio Fabio , Kim Se‐Hoon , Aronica Eleonora , Garbelli Rita , Vilz Samuel , Popp Alexander , Walcher Stefan , Neuner Christoph , Scholz Michael , Kuerten Stefanie , Schropp Verena , Roeder Sebastian , Eichhorn Philip , Eckstein Markus , Brehmer Axel , Kobow Katja , Coras Roland , Blumcke Ingmar , Jabari Samir 
Published: February 2020

AbstractObjectiveThe microscopic review of hematoxylin‐eosin–stained images of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex remains challenging. Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. We trained a convolutional neural network (CNN) to classify both entities and visualize the results. Additionally, we propose a new Web‐based deep learning application as proof of concept of how deep learning could enter the pathologic routine.MethodsA digital processing pipeline was developed for a series of 56 cases of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex to obtain 4000 regions of interest and 200 000 subsamples with different zoom and rotation angles to train a neural network. Guided gradient‐weighted class activation maps (Guided Grad‐CAMs) were generated to visualize morphological features used by the CNN to distinguish both entities.ResultsOur best‐performing network achieved 91% accuracy and 0.88 area under the receiver operating characteristic curve at the tile level for an unseen test set. Novel histopathologic patterns were found through the visualized Guided Grad‐CAMs. These patterns were assembled into a classification score to augment decision‐making in routine histopathology workup. This score was successfully validated by 11 expert neuropathologists and 12 nonexperts, boosting nonexperts to expert level performance.SignificanceOur newly developed Web application combines the visualization of whole slide images with the possibility of deep learning–aided classification between focal cortical dysplasia IIb and tuberous sclerosis complex. This approach will help to introduce deep learning applications and visualization for the histopathologic diagnosis of rare and difficult‐to‐classify brain lesions.
Activation of RAW264.7 macrophage by Exopolysaccharide from Aphanothece halaphytica (EPSAH) and the underlying mechanisms
Authors: Ou Yu , Zhu Lei , Xu Shuya , Wei Qingfang 
Published: February 2020

AbstractExopolysaccharide from Aphanothece halophytica (EPSAH), a potent antitumor agent and immunological adjuvant, was investigated for the activation effect on RAW264.7 macrophages and the underlying mechanisms. EPSAH could significantly enhance macrophage phagocytosis and the secretion of nitric oxide, increase the mRNA expression levels of the pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐12, and TNF‐α), anti‐inflammatory cytokine IL‐10, and chemokines (MCP‐1 and MIP‐1α). When RAW264.7 cells were treated with EPSAH, the mRNA expression of TLR4 and its downstream molecules TRAF6 and MyD88 were upregulated. When TLR4 was blocked using a TLR4‐specific neutralizing antibody, nitric oxide secretion from the macrophages was significantly inhibited. EPSAH was further shown to induce phosphorylation of the mitogen‐activated protein kinases (MAPKs) ERK, JNK, and p38, and promote cytoplasmic IκB phosphorylation and increase nuclear NF‐κB p65 levels remarkably in RAW264.7 cells. These data demonstrate the capacity of EPSAH to induce macrophage activation possibly via TLR4/MyD88 pathway, which leads to the activation of its main signaling downstream molecules MAPKs and NF‐κB.