bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Cannabis Use During the Reproductive Cycle: A Retrospective Cross-Sectional Study of Women in States With Recreational and Medical Cannabis Legalization
Authors: Taylor Danica Loralyn , Bell Janice F. , Adams Susan L. , Drake Christiana
Published: June 2021

Introduction

Passage of cannabis laws may impact cannabis use and the use of other substances. The suggested association is of particular concern in pregnant women where exposure to substances can cause harm to both the pregnant woman and fetus. The present study contributes to the minimal literature on factors associated with cannabis use during the preconception, prenatal, and postpartum periods including state legalization status, concurrent use of tobacco and e-cigarettes and adequacy of prenatal care.

Methods

We conducted a cross-sectional analysis using combined survey data from the 2016–2018 Pregnancy Risk Assessment Monitoring System (PRAMS) collected from 36,391 women. Logistic regression was used to estimate the impact of state-legalization, adequacy of prenatal care, and other substance use on cannabis use during the preconception, prenatal, and post-partum periods.

Results

In the preconception model, residence in a recreationally legal state (OR: 2.37; 95% CI, 2.04–2.75) or medically legal state (OR:3.32; 95% CI, 2.90–3.80) compared to a non-legal state was associated with higher odds of cannabis use. In the prenatal model, residence in a recreationally legal state was associated with higher odds of cannabis use (OR: 1.51; 95% CI, 1.29–1.79) whereas there was no association with residence in a medically legal state. Tobacco use including e-cigarettes and moderate prenatal alcohol use were also significantly associated with cannabis use.

Conclusion

Recreational cannabis legalization is associated with the use of cannabis prior to, during, and after pregnancy. Renewed clinical and policy efforts may be warranted to update prenatal substance use prevention programs, educational campaigns, and provider education as cannabis legalization evolves.
The role of Hashimoto thyroiditis in predicting radioiodine ablation efficacy and prognosis of low to intermediate risk differentiated thyroid cancer
Authors: Albano Domenico , Dondi Francesco , Zilioli Valentina , Panarotto Maria Beatrice , Galani Alessandro , Cappelli Carlo , Bertagna Francesco , Giubbini Raffaele , Casella Claudio
Published: June 2021

Objective

The baseline treatment of differentiated thyroid cancer (DTC) consists of thyroidectomy followed by postoperative risk-adapted radioiodine therapy (RAIT) when indicated. The choice of most appropriate RAI activities to administer with the aim to reach an efficient remnant ablation and reduce the risk of recurrence is yet an open issue and the detection of basal factors that may predict treatment response seems fundamental. The aim of this study was to investigate the potential role of Hashimoto thyroiditis (HT) in predicting 1-year and 5-year treatment response after RAIT and prognosis.

Methods

We retrospectively included 314 consecutive patients (174 low-risk and 140 intermediate-risk) who received thyroidectomy plus RAIT. One-year and 5-year disease status was evaluated according to 2015 ATA categories response based upon biochemical and structural findings.

Results

HT was reported histopathologically in 120 patients (38%). DTC patients with concomitant HT received a higher number of RAITs and cumulative RAI activities. Initial RAIT reached an excellent response in 63% after one year and 84% after 5 years. The rate of excellent response one year and 5-year after first RAIT was significantly lower in HT groups, compared to not HT (p < 0.001). Instead, HT did not have a prognostic role considering PFS and OS; while stimulate thyroglobulin (sTg) at ablation was significantly related to survival.

Conclusions

HT may affect the efficacy of RAIT in low to intermediate risk DTC, particularly reducing the successful rate of excellent response after RAIT. Instead, HT did not have a prognostic impact such as stimulated sTg.
Safety Concerns Emerging from Robots Navigating in Crowded Pedestrian Areas
Authors: Salvini Pericle , Paez-Granados Diego , Billard Aude
Published: June 2021

The slogan “robots will pervade our environment” has become a reality. Drones and ground robots are used for commercial purposes while semi-autonomous driving systems are standard accessories to traditional cars. However, while our eyes have been riveted on dangers and accidents arising from drones falling and autonomous cars’ crashing, much less attention has been ported to dangers arising from the imminent arrival of robots that share the floor with pedestrians and will mix with human crowds. These robots range from semi or autonomous mobile platforms designed for providing several kinds of service, such as assistant, patrolling, tour-guide, delivery, human transportation, etc. We highlight and discuss potential sources of injury emerging from contacts of robots with pedestrians through a set of case studies. We look specifically at dangers deriving from robots moving in dense crowds. In such situations, contact will not only be unavoidable, but may be desirable to ensure that the robot moves with the flow. As an outlook toward the future, we also offer some thoughts on the psychological risks, beyond the physical hazards, arising from the robot’s appearance and behaviour. We also advocate for new policies to regulate mobile robots traffic and enforce proper end user’s training.
Microstructure, Grain Growth and Hardness of Nanostructured Ferritic ODS Steel Powder during Annealing
Authors: Nowik Krzysztof , Oksiuta Zbigniew
Published: June 2021

Nanocrystalline oxide-dispersion strengthened ferritic alloy formation and its annealing behavior were examined through modern X-ray diffraction pattern analysis and supplemented by microhardness and microscopic measurements. The basic microstructure features, with particular emphasis on evolution of domain size distribution and defect content during mechanical and thermal treatment, were quantified via the whole powder pattern modeling approach. The microstructure of the powdered alloy, formed during mechanical alloying, evolved toward nanocrystalline state consisting of narrow dispersion of very fine crystallites with substantial dislocation density, which exhibited relatively high stability against elevated temperature. It was shown that crystallite size is seriously sustained by the grain-boundary strain, therefore coarsening of grains begins only after the density of dislocations drops below certain level. Obtaining correct results for the annealing-related data at specific temperature range required the incorporation of the “double-phase” model, indicating possible bimodal domain size distribution. The dislocation density and grain size were found not to be remarkably affected after consolidation by hot isostatic pressing.
High salinity enhances the adsorption of 17α-ethinyl estradiol by polyethersulfone membrane: isotherm modelling and molecular simulation
Authors: Goh J. Y. , Goh K. S. , Yip Y. M. , Ng C. K.
Published: June 2021

The increasing occurrence of steroidal hormone micropollutant in the aquatic environment and their associated consequences have caused serious environmental concerns globally. Adsorptive removal of hormonal pollutants using polymeric membranes has been suggested but information on their performance in various environmental conditions is lacking. In this study, we examined the effect of salinity on the performance of polyethersulfone (PES) membrane to remove synthetic hormone 17α-ethinyl estradiol (EE2) from water. Our results show that an increase of salinity from 0 to 3% results in higher retention of EE2 onto PES membrane from 79.3 to 98.7%. The experimental results fit the Freundlich isotherm model better as compared to the Langmuir model. The Freundlich parameters n and Kf yielded the highest values at 3% salinity. The molecular simulation results suggest that a high salinity increases the binding energy between EE2 and PES membranes, promoting the PES-EE2 interaction through π–π interaction, hydrogen bonding and hydrophobic interaction. This study provides valuable information for improving design of specialised treatment facilities (in farming, pharmaceutical industries, etc.) to allow better removal of EE2 and other low-polar organic contaminants from water via a membrane-based sorption-elution method, and we recommend the inclusion of salinity as a factor in modelling the adsorption capacity of membranes to prevent the oversaturation of membrane and minimise the release of contaminants into the environment.
Who's Afraid of Sunlight? Explaining Opposition to Transparency in Economic Development
Authors: Jensen Nathan M. , Thrall Calvin
Published: June 2021

Firms and governments often negotiate economic development deals, such as tax abatements, with limited transparency, using exceptions to public records laws or other strategies for nondisclosure. In this article we explore the motivations of firms for keeping economic development deals out of the public eye. We explore legal challenges to public records requests for deal-specific, company-specific participation in a state economic development incentive program. By examining applications for participation in a major state economic program, the Texas Enterprise Fund, we find that a company is more likely to challenge a formal public records request if it has renegotiated the terms of the award to reduce its job-creation obligations. We interpret this as companies challenging transparency when they have avoided being penalized for noncompliance by engaging in nonpublic renegotiations. These results provide evidence regarding those conditions that prompt firms to challenge transparency and illustrate some of the limitations of safeguards such as clawbacks (or incentive-recapture provisions) when such reforms aren't coupled with robust transparency mechanisms. We speculate that the main motivation for these challenges is to limit scrutiny of these deals that could lead to backlashes against future economic development agreements.
Thinking What One is Doing: Knowledge-how, Methods, and Reliability
Authors: Turman John
Published: June 2021

There has been renewed interest over the last twenty years in Ryle's claims and arguments about knowledge-how. Elzinga (2018) and Löwenstein (2017) have both recently defended independent Ryle-inspired accounts of knowledge-how. In what follows, I will propose and defend an amendment to accounts of knowledge-how like those of Elzinga and Löwenstein. I argue that this amendment provides an additional needed distinction between the performance robustness provided by certain performance methods (or styles), and the robustness of an agent's ability to perform according to such methods (or styles). Additionally, the proposed amendment, if adopted, will make the amended views even more Rylean. I argue for this, in part, through original exegetical work on an under-discussed theme in Ryle's philosophy of mind: the relation between semi-hypothetical statements, methodological act-description, and knowledge-how.
Attributable mortality of vancomycin resistance in ampicillin-resistant Enterococcus faecium bacteremia in Denmark and the Netherlands: A matched cohort study
Authors: Rottier Wouter C. , Pinholt Mette , van der Bij Akke K. , Arpi Magnus , Blank Sybrandus N. , Nabuurs-Franssen Marrigje H. , Ruijs Gijs J.H.M. , Tersmette Matthijs , Ossewaarde Jacobus M. , Groenwold Rolf H. , Westh Henrik , Bonten Marc J.M. ,   for the Dutch VRE Bacteremia Investigators,   the Danish Collaborative Bacteraemia Network (DACOBAN)
Published: June 2021

Objective:

To study whether replacement of nosocomial ampicillin-resistant Enterococcus faecium (ARE) clones by vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineages, increases mortality in patients with E. faecium bacteremia, and to evaluate whether any such increase is mediated by a delay in appropriate antibiotic therapy.

Design:

Retrospective, matched-cohort study.

Setting:

The study included 20 Dutch and Danish hospitals from 2009 to 2014.

Patients:

Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed.

Methods:

The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors.

Results:

The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06–2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of the increased mortality risk.

Conclusions:

Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.
Prediction of type 2 diabetes mellitus based on nutrition data
Authors: Katsimpris Andreas , Brahim Aboulmaouahib , Rathmann Wolfgang , Peters Anette , Strauch Konstantin , Flaquer Antònia
Published: June 2021

Numerous predictive models for the risk of type 2 diabetes mellitus (T2DM) exist, but a minority of them has implemented nutrition data so far, even though the significant effect of nutrition on the pathogenesis, prevention and management of T2DM has been established. Thus, in the present study, we aimed to build a predictive model for the risk of T2DM that incorporates nutrition data and calculates its predictive performance. We analysed cross-sectional data from 1591 individuals from the population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013–14) and used a bootstrap enhanced elastic net penalised multivariate regression method in order to build our predictive model and select among 193 food intake variables. After selecting the significant predictor variables, we built a logistic regression model with these variables as predictors and T2DM status as the outcome. The values of area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of our predictive model were calculated. Eleven out of the 193 food intake variables were selected for inclusion in our model, which yielded a value of area under the ROC curve of 0⋅79 and a maximum PPV, NPV and accuracy of 0⋅37, 0⋅98 and 0⋅91, respectively. The present results suggest that nutrition data should be implemented in predictive models to predict the risk of T2DM, since they improve their performance and they are easy to assess.
Where in the cell is my protein?
Authors: DeRosier David J.
Published: June 2021

The application of cryo-correlative light and cryo-electron microscopy (cryo-CLEM) gives us a way to locate structures of interest in the electron microscope. In brief, the structures of interest are fluorescently tagged, and images from the cryo-fluorescent microscope (cryo-FM) maps are superimposed on those from the cryo-electron microscope (cryo-EM). By enhancing cryo-FM to include single-molecule localization microscopy (SMLM), we can achieve much better localization. The introduction of cryo-SMLM increased the yield of photons from fluorophores, which can benefit localization efforts. Dahlberg and Moerner (2021, Annual Review of Physical Chemistry, 72, 253–278) have a recent broad and elegant review of super-resolution cryo-CLEM. This paper focuses on cryo(F)PALM/STORM for the cryo-electron tomography community. I explore the current challenges to increase the accuracy of localization by SMLM and the mapping of those positions onto cryo-EM images and maps. There is much to consider: we need to know if the excitation of fluorophores damages the structures we seek to visualize. We need to determine if higher numerical aperture (NA) objectives, which add complexity to image analysis but increase resolution and the efficiency of photon collection, are better than lower NA objectives, which pose fewer problems. We need to figure out the best way to determine the axial position of fluorophores. We need to have better ways of aligning maps determined by FM with those determined by EM. We need to improve the instrumentation to be easier to use, more accurate, and ice-contamination free. The bottom line is that we have more work to do.
Migraine: interactions between brain’s trait and state
Authors: Szabo Edina , Green Stephen , Karunakaran Keerthana Deepti , Sieberg Christine B. , Elman Igor , Burstein Rami , Borsook David
Published: June 2021

It is well established that migraine is a multifactorial disorder. A deep understanding of migraine should be based upon both the underlying traits and the current states affected by different physiological, psychological, and environmental factors. At this point, there is no framework fully meeting these criteria. Here, we describe a broader view of the migraine disorder defined as a dysfunctional brain state and trait interaction. In this model, we consider events that may enhance or diminish migraine responsivity based on an individual’s trait and state. This could provide an expanded view for considering how migraine attacks are sometimes precipitated by “triggers” and sometimes not, how these factors only lead to migraine attacks in migraine patients, or how individuals with an increased risk for migraine do not show any symptoms at all. Summarizing recent studies and evidence that support the concept of migraine as a brain state–trait interaction can also contribute to improving patient care by highlighting the importance of precision medicine and applying measures that are able to capture how different traits and states work together to determine migraine.
2,4-D and dicamba removal from the surface of plastic mulch using overhead irrigation: analytical analysis and cucurbit bioassay crop response
Authors: Hand Lavesta C. , Eason Kayla M. , Randell Taylor M. , Grey Timothy L. , Culpepper A. Stanley
Published: June 2021

Glyphosate and paraquat are effective preplant burndown herbicide options for multicrop vegetable production that uses plastic mulch, but problematic weeds such as wild radish, cutleaf evening primrose, annual morningglory, or horseweed may not be adequately controlled with these herbicides alone. The herbicides 2,4-D and dicamba could help control these troublesome weeds prior to planting if they can be removed from plastic mulch and thus avoid crop damage. Treatments included 2,4-D (1,065 and 2,130 g ae ha−1) and dicamba (560 and 1,120 g ae ha−1) applied broadcast over plastic mulch a day before transplanting. Just before transplanting, treatments received either 0.76 cm of water via overhead irrigation or no irrigation. Plastic mulch samples were collected at application and planting to determine herbicide presence using analytical techniques, and cantaloupe and zucchini squash were subsequently transplanted on the plastic beds. Analytical ultra-high performance liquid chromatography revealed that 88% to 99% of the initial herbicide concentration was present at crop planting when irrigation was not implemented. At most, a 1/50 rate of dicamba and a 1/500 rate of 2,4-D was present at planting when overhead irrigation was applied prior to transplanting. Maximum cantaloupe and squash injury from 2,4-D with irrigation was 10% and did not influence plant growth, biomass, or yield. For dicamba with overhead irrigation, cantaloupe injury was 35%, vine lengths were reduced by 24%, and maturity was delayed, whereas squash injury ranged from 9% to 12%, with no influence on growth or yield. Without irrigation to wash herbicides from the mulch prior to planting, 60% to 100% injury of both crops occurred with both herbicides. Zucchini squash was more tolerant to dicamba than cantaloupe. Results demonstrated that 2,4-D can be adequately removed from the surface of plastic mulch with irrigation, whereas a single irrigation event was not sufficient to remove dicamba.
Climate Impacts on Source Contributions and Evaporation to Flow in the Snake River Basin Using Surface Water Isoscapes (δ2H and δ18O)
Authors: Windler Grace , Brooks J. Renée , Johnson Henry M. , Comeleo Randy L. , Coulombe Rob , Bowen Gabriel J.
Published: June 2021

Rising global temperatures are expected to decrease the precipitation amount that falls as snow, causing greater risk of water scarcity, groundwater overdraft, and fire in areas that rely on mountain snowpack for their water supply. Streamflow in large river basins varies with the amount, timing, and type of precipitation, evapotranspiration, and drainage properties of watersheds; however, these controls vary in time and space making it difficult to identify the areas contributing most to flow and when. In this study, we separate the evaporative influences from source values of water isotopes from the Snake River basin in the western United States to relate source area to flow dynamics. We developed isoscapes (δ2H and δ18O) for the basin and found that isotopic composition of surface water in small watersheds is primarily controlled by longitude, latitude, and elevation. To examine temporal variability in source contributions to flow, we present a 6‐years record of Snake River water isotopes from King Hill, Idaho, after removing evaporative influences. During periods of low flow, source water values were isotopically lighter indicating a larger contribution to flow from surface waters in the highest elevation, eastern portion of the basin. River evaporation increases were evident during summer likely reflecting climate, changing water availability, and management strategies within the basin. Our findings present a potential tool for identifying critical portions of basins contributing to river flow as climate fluctuations alter flow dynamics. This tool can be applied in other continental‐interior basins where evaporation may obscure source water isotopic signatures.
Probing the Southern Cascadia Plate Interface With the Dense Amphibious Cascadia Initiative Seismic Array
Authors: Alongi T. , Schwartz S. Y. , Shaddox H. R. , Small D. T.
Published: June 2021

Fault coupling is vital in determining the amount of strain that is accumulated along faults. The magnitude and location of stored elastic strain energy in highly coupled regions has important implications for understanding the full range of slip behavior at plate boundary faults, as well as earthquake and tsunami hazards. We use the temporary dense amphibious array of seismometers offered by the Cascadia Initiative to create a high‐resolution catalog of events to examine the spatio‐temporal behavior of earthquakes near the plate interface. The data show that in southern Cascadia the plate interface updip of the geodetically locked region is nearly devoid of seismicity, therefore likely highly coupled and accumulating strain. The catalog reveals events that are clustered at the downdip edge of the highly coupled megathrust that correlate in time with nearby strain transient observations. Template matching of events in the cluster using permanent stations of the Northern California Seismic Network over a 10‐year period between 2010 and 2020 indicates that this cluster is unique in space and time. Its activity only during the strain transient provides support for the utility of seismic observations in the identification of strain transients.
Cocaine induces paradigm-specific changes to the transcriptome within the ventral tegmental area
Authors: Campbell Rianne R. , Chen Siwei , Beardwood Joy H. , López Alberto J. , Pham Lilyana V. , Keiser Ashley M. , Childs Jessica E. , Matheos Dina P. , Swarup Vivek , Baldi Pierre , Wood Marcelo A.
Published: June 2021

During the initial stages of drug use, cocaine-induced neuroadaptations within the ventral tegmental area (VTA) are critical for drug-associated cue learning and drug reinforcement processes. These neuroadaptations occur, in part, from alterations to the transcriptome. Although cocaine-induced transcriptional mechanisms within the VTA have been examined, various regimens and paradigms have been employed to examine candidate target genes. In order to identify key genes and biological processes regulating cocaine-induced processes, we employed genome-wide RNA-sequencing to analyze transcriptional profiles within the VTA from male mice that underwent one of four commonly used paradigms: acute home cage injections of cocaine, chronic home cage injections of cocaine, cocaine-conditioning, or intravenous-self administration of cocaine. We found that cocaine alters distinct sets of VTA genes within each exposure paradigm. Using behavioral measures from cocaine self-administering mice, we also found several genes whose expression patterns corelate with cocaine intake. In addition to overall gene expression levels, we identified several predicted upstream regulators of cocaine-induced transcription shared across all paradigms. Although distinct gene sets were altered across cocaine exposure paradigms, we found, from Gene Ontology (GO) term analysis, that biological processes important for energy regulation and synaptic plasticity were affected across all cocaine paradigms. Coexpression analysis also identified gene networks that are altered by cocaine. These data indicate that cocaine alters networks enriched with glial cell markers of the VTA that are involved in gene regulation and synaptic processes. Our analyses demonstrate that transcriptional changes within the VTA depend on the route, dose and context of cocaine exposure, and highlight several biological processes affected by cocaine. Overall, these findings provide a unique resource of gene expression data for future studies examining novel cocaine gene targets that regulate drug-associated behaviors.
PKCδ-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs
Authors: Chen Chia-Hung , Wang Bo-Wei , Hsiao Yu-Chun , Wu Chun-Yi , Cheng Fang-Ju , Hsia Te-Chun , Chen Chih-Yi , Wang Yihua , Weihua Zhang , Chou Ruey-Hwang , Tang Chih-Hsin , Chen Yun-Ju , Wei Ya-Ling , Hsu Jennifer L. , Tu Chih-Yen , Hung Mien-Chie , Huang Wei-Chien
Published: June 2021

The tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have been widely used for non-small cell lung cancer (NSCLC) patients, but the development of acquired resistance remains a therapeutic hurdle. The reduction of glucose uptake has been implicated in the anti-tumor activity of EGFR TKIs. In this study, the upregulation of the active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with the poorer clinical outcome of the NSCLC patients who received EGFR TKI treatment. Blockade of SGLT1 overcame this resistance in vitro and in vivo by reducing glucose uptake in NSCLC cells. Mechanistically, SGLT1 protein was stabilized through the interaction with PKCδ-phosphorylated (Thr678) EGFR in the TKI-resistant cells. Our findings revealed that PKCδ/EGFR axis-dependent SGLT1 upregulation was a critical mechanism underlying the acquired resistance to EGFR TKIs. We suggest co-targeting PKCδ/SGLT1 as a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.
A bioinspired and chemically defined alternative to dimethyl sulfoxide for the cryopreservation of human hematopoietic stem cells
Authors: Gilfanova Renata , Callegari Andrea , Childs Adam , Yang Gaomai , Luarca Miranda , Gutierrez Alan G. , Medina Karla I. , Mai Justin , Hui Alvin , Kline Mark , Wei Xiaoxi , Norris Philip J. , Muench Marcus O.
Published: June 2021

The cryopreservation of hematopoietic cells using dimethyl sulfoxide (DMSO) and serum is a common procedure used in transplantation. However, DMSO has clinical and biological side effects due to its toxicity, and serum introduces variation and safety risks. Inspired by natural antifreeze proteins, a novel class of ice-interactive cryoprotectants was developed. The corresponding DMSO-, protein-, and serum-free cryopreservation media candidates were screened through a series of biological assays using human cell lines, peripheral blood cells, and bone marrow cells. XT-Thrive-A and XT-Thrive-B were identified as lead candidates to rival cryopreservation with 10% DMSO in serum based on post-thaw cell survival and short-term proliferation assays. The effectiveness of the novel cryopreservation media in freezing hematopoietic stem cells from human whole bone marrow was assessed by extreme limiting dilution analysis in immunodeficient mice. Stem cell frequencies were measured 12 weeks after transplant based on bone marrow engraftment of erythroid, myeloid, B-lymphoid, and CD34+progenitors measured by flow cytometry. The recovered numbers of cryopreserved stem cells were similar among XT-Thrive A, XT-Thrive B, and DMSO with serum groups. These findings show that cryoprotectants developed through biomimicry of natural antifreeze proteins offers a substitute for DMSO-based media for the cryopreservation of hematopoietic stem cells.
Tumour irradiation combined with vascular-targeted photodynamic therapy enhances antitumour effects in pre-clinical prostate cancer
Authors: Sjoberg Hanna T. , Philippou Yiannis , Magnussen Anette L. , Tullis Iain D. C. , Bridges Esther , Chatrian Andrea , Lefebvre Joel , Tam Ka Ho , Murphy Emma A. , Rittscher Jens , Preise Dina , Agemy Lilach , Yechezkel Tamar , Smart Sean C. , Kinchesh Paul , Gilchrist Stuart , Allen Danny P. , Scheiblin David A. , Lockett Stephen J. , Wink David A. , Lamb Alastair D. , Mills Ian G. , Harris Adrian , Muschel Ruth J. , Vojnovic Boris , Scherz Avigdor , Hamdy Freddie C. , Bryant Richard J.
Published: June 2021

Background

There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy for low-risk low-volume localised PCa, which rapidly disrupts targeted tumour vessels. There is interest in expanding the use of VTP to higher-risk disease. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. FRT alters the tumour microenvironment and promotes transient ‘vascular normalisation’. We hypothesised that multimodality therapy combining fractionated radiotherapy (FRT) and VTP could improve PCa tumour control compared against monotherapy with FRT or VTP.

Methods

We investigated whether sequential delivery of FRT followed by VTP 7 days later improves flank TRAMP-C1 PCa tumour allograft control compared to monotherapy with FRT or VTP.

Results

FRT induced ‘vascular normalisation’ changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast-enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP, and improved overall survival.

Conclusion

Combining FRT and VTP may be a promising multimodal approach in PCa therapy. This provides proof-of-concept for this multimodality treatment to inform early phase clinical trials.
A small RNA regulates pprM, a modulator of pleiotropic proteins promoting DNA repair, in Deinococcus radiodurans under ionizing radiation
Authors: Villa Jordan K. , Han Runhua , Tsai Chen-Hsun , Chen Angela , Sweet Philip , Franco Gabriela , Vaezian Respina , Tkavc Rok , Daly Michael J. , Contreras Lydia M.
Published: June 2021

Networks of transcriptional and post-transcriptional regulators are critical for bacterial survival and adaptation to environmental stressors. While transcriptional regulators provide rapid activation and/or repression of a wide-network of genes, post-transcriptional regulators, such as small RNAs (sRNAs), are also important to fine-tune gene expression. However, the mechanisms of sRNAs remain poorly understood, especially in less-studied bacteria. Deinococcus radiodurans is a gram-positive bacterium resistant to extreme levels of ionizing radiation (IR). Although multiple unique regulatory systems (e.g., the Radiation and Desiccation Response (RDR)) have been identified in this organism, the role of post-transcriptional regulators has not been characterized within the IR response. In this study, we have characterized an sRNA, PprS (formerly Dsr2), as a post-transcriptional coordinator of IR recovery in D. radiodurans. PprS showed differential expression specifically under IR and knockdown of PprS resulted in reduced survival and growth under IR, suggesting its importance in regulating post-radiation recovery. We determined a number of potential RNA targets involved in several pathways including translation and DNA repair. Specifically, we confirmed that PprS binds within the coding region to stabilize the pprM (DR_0907) transcript, a RDR modulator. Overall, these results are the first to present an additional layer of sRNA-based control in DNA repair pathways associated with bacterial radioresistance.
Distinct effects of heterogeneity and noise on gamma oscillation in a model of neuronal network with different reversal potential
Authors: Zheng Tianyi , Kotani Kiyoshi , Jimbo Yasuhiko
Published: June 2021

Gamma oscillation is crucial in brain functions such as attentional selection, and is inextricably linked to both heterogeneity and noise (or so-called stochastic fluctuation) in neuronal networks. However, under coexistence of these factors, it has not been clarified how the synaptic reversal potential modulates the entraining of gamma oscillation. Here we show distinct effects of heterogeneity and noise in a population of modified theta neurons randomly coupled via GABAergic synapses. By introducing the Fokker-Planck equation and circular cumulants, we derive a set of two-cumulant macroscopic equations. In bifurcation analyses, we find a stabilizing effect of heterogeneity and a nontrivial effect of noise that results in promoting, diminishing, and shifting the oscillatory region, and is largely dependent on the reversal potential of GABAergic synapses. These findings are verified by numerical simulations of a finite-size neuronal network. Our results reveal that slight changes in reversal potential and magnitude of stochastic fluctuations can lead to immediate control of gamma oscillation, which would results in complex spatio-temporal dynamics for attentional selection and recognition.
High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
Authors: Nayler Samuel , Agarwal Devika , Curion Fabiola , Bowden Rory , Becker Esther B. E.
Published: June 2021

Current protocols for producing cerebellar neurons from human pluripotent stem cells (hPSCs) often rely on animal co-culture and mostly exist as monolayers, limiting their capability to recapitulate the complex processes in the developing cerebellum. Here, we employed a robust method, without the need for mouse co-culture to generate three-dimensional cerebellar organoids from hPSCs that display hallmarks of in vivo cerebellar development. Single-cell profiling followed by comparison to human and mouse cerebellar atlases revealed the presence and maturity of transcriptionally distinct populations encompassing major cerebellar cell types. Encapsulation with Matrigel aimed to provide more physiologically-relevant conditions through recapitulation of basement-membrane signalling, influenced both growth dynamics and cellular composition of the organoids, altering developmentally relevant gene expression programmes. We identified enrichment of cerebellar disease genes in distinct cell populations in the hPSC-derived cerebellar organoids. These findings ascertain xeno-free human cerebellar organoids as a unique model to gain insight into cerebellar development and its associated disorders.
Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes
Authors: Shulgach Jonathan A. , Beam Dylan W. , Nanivadekar Ameya C. , Miller Derek M. , Fulton Stephanie , Sciullo Michael , Ogren John , Wong Liane , McLaughlin Bryan L. , Yates Bill J. , Horn Charles C. , Fisher Lee E.
Published: June 2021

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.
Canopy distribution and microclimate preferences of sterile and wild Queensland fruit flies
Authors: Inskeep Jess R. , Allen Andrew P. , Taylor Phillip W. , Rempoulakis Polychronis , Weldon Christopher W.
Published: June 2021

Insects tend to live within well-defined habitats, and at smaller scales can have distinct microhabitat preferences. These preferences are important, but often overlooked, in applications of the sterile insect technique. Different microhabitat preferences of sterile and wild insects may reflect differences in environmental tolerance and may lead to spatial separation in the field, both of which may reduce the control program efficiency. In this study, we compared the diurnal microhabitat distributions of mass-reared (fertile and sterile) and wild Queensland fruit flies, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae). Flies were individually tagged and released into field cages containing citrus trees. We recorded their locations in the canopies (height from ground, distance from canopy center), behavior (resting, grooming, walking, feeding), and the abiotic conditions on occupied leaves (temperature, humidity, light intensity) throughout the day. Flies from all groups moved lower in the canopy when temperature and light intensity were high, and humidity was low; lower canopy regions provided shelter from these conditions. Fertile and sterile mass-reared flies of both sexes were generally lower in the canopies than wild flies. Flies generally fed from the top sides of leaves that were lower in the canopy, suggesting food sources in these locations. Our observations suggest that mass-reared and wild B. tryoni occupy different locations in tree canopies, which could indicate different tolerances to environmental extremes and may result in spatial separation of sterile and wild flies when assessed at a landscape scale.
Few-qubit quantum refrigerator for cooling a multi-qubit system
Authors: Arısoy Onat , Müstecaplıoğlu Özgür E.
Published: June 2021

We propose to use a few-qubit system as a compact quantum refrigerator for cooling an interacting multi-qubit system. We specifically consider a central qubit coupled to N ancilla qubits in a so-called spin-star model to be used as refrigerant by means of short interactions with a many-qubit system to be cooled. We first show that if the interaction between the qubits is of the longitudinal and ferromagnetic Ising model form, the central qubit is colder than the environment. We summarize how preparing the refrigerant qubits using the spin-star model paves the way for the cooling of a many-qubit system by means of a collisional route to thermalization. We discuss a simple refrigeration cycle, considering the operation cost and cooling efficiency, which can be controlled by N and the qubit–qubit interaction strength. Besides, bounds on the achievable temperature are established. Such few-qubit compact quantum refrigerators can be significant to reduce dimensions of quantum technology applications, can be easy to integrate into all-qubit systems, and can increase the speed and power of quantum computing and thermal devices.
Creation of quantum entangled states of Rydberg atoms via chirped adiabatic passage
Authors: Pachniak Elliot , Malinovskaya Svetlana A.
Published: June 2021

Entangled states are crucial for modern quantum enabled technology which makes their creation key for future developments. In this paper, a robust quantum control methodology is presented to create entangled states of two typical classes, the W and the Greenberger–Horne–Zeilinger (GHZ). It was developed from the analysis of a chain of alkali atoms $$^{87}Rb$$

87

R
b

interaction with laser pulses, which leads to the two-photon transitions from the ground to the Rydberg states with a predetermined magnetic quantum number. The methodology is based on the mechanism of the two-photon excitation, adiabatic for the GHZ and non-adiabatic for the W state, induced by the overlapping chirped pulses and governed by the Rabi frequency, the one-photon detuning, and the strength of the Rydberg–Rydberg interactions.
A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
Authors: Lindner Benjamin , Martin Eva , Steininger Monika , Bundalo Aleksandra , Lenter Martin , Zuber Johannes , Schuler Michael
Published: June 2021

Phagocytosis of microbial pathogens, dying or dead cells, and cell debris is essential to maintain tissue homeostasis. Impairment of these processes is associated with autoimmunity, developmental defects and toxic protein accumulation. However, the underlying molecular mechanisms of phagocytosis remain incompletely understood. Here, we performed a genome-wide CRISPR knockout screen to systematically identify regulators involved in phagocytosis ofStaphylococcus(S.)aureusby human monocytic THP-1 cells. The screen identified 75 hits including known regulators of phagocytosis, e.g. members of the actin cytoskeleton regulation Arp2/3 and WAVE complexes, as well as genes previously not associated with phagocytosis. These novel genes are involved in translational control (EIF5A and DHPS) and the UDP glycosylation pathway (SLC35A2, SLC35A3, UGCG and UXS1) and were further validated by single gene knockout experiments. Whereas the knockout of EIF5A and DHPS impaired phagocytosis, knocking out SLC35A2, SLC35A3, UGCG and UXS1 resulted in increased phagocytosis. In addition toS. aureusphagocytosis, the above described genes also modulate phagocytosis ofEscherichia coliand yeast-derived zymosan A. In summary, we identified both known and unknown genetic regulators of phagocytosis, the latter providing a valuable resource for future studies dissecting the underlying molecular and cellular mechanisms and their role in human disease.
Newly diagnosed diabetes has high risk for cardiovascular outcome in ischemic stroke patients
Authors: Cho Kyung-Hee , Kwon Sun U. , Lee Ji Sung , Yu Sungwook , Cho A-Hyun
Published: June 2021

We investigated cardiovascular outcomes in ischemic stroke patients with newly diagnosed diabetes mellitus (DM) compared with those of patients with previously known DM and no DM using the glycosylated hemoglobin (HbA1c) criteria. The relationship between new DM diagnosis and cardiovascular risk remains unclear to date. We performed post hoc analysis using the data of participants from the Prevention of Cardiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO) trial. Newly diagnosed DM was defined as HbA1c of ≥ 6.5% without known DM history. The outcome was the incidence of composite cardiovascular events, including stroke (ischemic and hemorrhagic), myocardial infarction, and cardiovascular death. In total, 1306 patients were included; 38 patients (2.9%) had newly diagnosed DM; 438 patients (33.5%), known DM; and 830 patients (63.6%), no DM. In patients with newly diagnosed DM, known DM, and no DM, the incidence of ischemic stroke was 8.93, 3.79, and 2.64 per 100 person-years (log-rank test; p = 0.0092), while that of composite cardiovascular events was 8.93, 5.92, and 3.87 per 100 person-years (p = 0.025), respectively. Newly diagnosed DM was an important risk factor for ischemic stroke and composite cardiovascular events after ischemic stroke.

Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis
Authors: Ting Darren Shu Jeng , Henein Christin , Said Dalia G. , Dua Harminder S.
Published: June 2021

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (− 4.08 days; 95% CI − 6.27 to − 1.88;p < 0.001) and better UDVA (− 0.26 logMAR; − 0.50 to − 0.02;p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46–1.38;p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (bothp < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable.