bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folate‐appended cyclodextrin carrier targets ovarian cancer cells expressing the proton‐coupled folate transporter
Authors: Saito Shinichi , Koya Yoshihiro , Kajiyama Hiroaki , Yamashita Mamoru , Kikkawa Fumitaka , Nawa Akihiro 
Published: March 2020

AbstractFolate receptor alpha (FRα) is overexpressed in >80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as a first‐line chemotherapeutic agent in combination with platinum‐based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor‐EL, a traditional formulation vehicle that causes significant side effects, including neutropenia. Several years ago, folate‐appended β‐CyD (Fol‐c1‐β‐CyD) was developed as an FRα‐targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol‐c1‐β‐CyD (PTX/Fol‐c1‐β‐CyD) in EOC‐derived cell lines. We found that PTX/Fol‐c1‐β‐CyD killed not only FRα‐expressing cells but also FRα‐negative cells. In the FRα‐negative A2780 cells, knockdown of proton‐coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol‐c1‐β‐CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or proton‐coupled folate transporter (PCFT) decreased the cytotoxicity of PTX/Fol‐c1‐β‐CyD in FRα‐expressing SK‐OV‐3 cells. Furthermore, the cytotoxicity of PTX/Fol‐c1‐β‐CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα‐expressing or PCFT‐expressing EOC cells, intraperitoneal administration of PTX/Fol‐c1‐β‐CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol‐c1‐β‐CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity.
Parathyroid hormone ameliorates temporomandibular joint osteoarthritic‐like changes related to age
Authors: Cui Chen , Zheng Liwei , Fan Yi , Zhang Jun , Xu Ruoshi , Xie Jing , Zhou Xuedong 
Published: March 2020

AbstractObjectivesAgeing could be a contributing factor to the progression of temporomandibular joint osteoarthritis (TMJ OA), whereas its pathogenesis and potential therapeutic strategy have not been comprehensively investigated.Materials and methodsWe generated ageing mouse models (45‐week and 60‐week; 12‐week mice as control) and intermittently injected 45‐week mice with parathyroid hormone (PTH(1‐34)) or vehicle for 4 weeks. Cartilage and subchondral bone of TMJ were analysed by microCT, histological and immunostaining. Western blot, qRT‐PCR, ChIP, ELISA and immunohistochemical analysis were utilized to examination the mechanism of PTH(1‐34)’s function.ResultsWe showed apparent OA‐like phenotypes in ageing mice. PTH treatment could ameliorate the degenerative changes and improve bone microarchitecture in the subchondral bone by activating bone remodelling. Moreover, PTH inhibited phosphorylation level of Smad3, which can combine with p16ink4a gene promoter region, resulting in reduced senescent cells accumulation and increased cellular proliferation of marrow mesenchymal stem cells (MSCs). ELISA also showed relieved levels of specific senescent‐associated secretory phenotype (SASP) in ageing mice after PTH treatment.ConclusionsIn summary, PTH may reduce the accumulation of senescent cells in subchondral bone by inhibiting p16ink4a and improve bone marrow microenvironment to active bone remodelling process, indicating PTH administration could be a potential preventative and therapeutic treatment for age‐related TMJ OA.
Pharmacokinetic and Metabolic Profile of Deutetrabenazine (TEV‐50717) Compared With Tetrabenazine in Healthy Volunteers
Authors: Schneider Frank , Bradbury Margaret , Baillie Thomas A. , Stamler David , Hellriegel Edward , Cox Donna S. , Loupe Pippa S. , Savola Juha‐Matti , Rabinovich‐Guilatt Laura 
Published: March 2020

Deutetrabenazine (Austedo, Teva Pharmaceuticals) is a deuterated form of tetrabenazine. It is the first deuterated drug to receive US regulatory approval and is approved for treatment of chorea in Huntington’s disease and tardive dyskinesia. Two oral single dose studies comparing deutetrabenazine (25 mg) with tetrabenazine (25 mg) in healthy volunteers evaluated the impact of deuteration on pharmacokinetics of the active metabolites, alpha‐dihydrotetrabenazine (α‐HTBZ) and beta‐dihydrotetrabenazine (β‐HTBZ), metabolite profile, safety, and tolerability. In the two‐way, cross‐over study, the mean elimination half‐life of deuterated total (α + β)‐HTBZ was doubled compared with nondeuterated total (α + β)‐HTBZ, with a twofold increase in overall mean exposure (area under the concentration‐time curve from zero to infinity (AUC0–inf)) and a marginal increase in mean peak plasma concentration (Cmax). In the mass balance and metabolite profiling study, there were no novel plasma or urinary metabolites of [14C]‐deutetrabenazine relative to [14C]‐tetrabenazine. Specific deuteration in deutetrabenazine resulted in a superior pharmacokinetic profile and an increased ratio of active‐to‐inactive metabolites, attributes considered to provide significant benefits to patients.
Developing outreach events that impact underrepresented students: Are we doing it right?
Authors: Gall Andrew J. , Vollbrecht Peter J. , Tobias Tristan 
Published: March 2020

AbstractMany outreach programs share the common goals of serving underrepresented groups in STEM and improving public attitudes toward science. To meet these goals, scientists must find ways to both reach the appropriate audience and communicate the importance of science in meaningful and accessible ways. This requires careful consideration of the outreach method being used. Two common outreach methods include in‐school visits (scientist in the classroom) and science fairs or open houses. Here, we compare the effectiveness of these two outreach methods in meeting the goals of reaching underrepresented students and/or students with less initial interest in science. We have found that in‐school visits reached more underrepresented students and that initial attitudes toward science scores were lower for in‐school visit participants than for open house event participants. Importantly, positive attitudes toward science increased significantly after in‐school outreach events. Taken together, these data suggest that outreach events that are taken out into the community will reach a less enthusiastic but more diverse audience and can have a positive impact on attitudes toward science within these populations. These studies highlight the importance of knowing the goals of your outreach program and choosing the method that is best suited to meeting those goals.
Opinions and clinical practices related to diagnosing and managing functional (psychogenic) movement disorders: changes in the last decade
Authors: LaFaver K. , Lang A. E. , Stone J. , Morgante F. , Edwards M. , Lidstone S. , Maurer C. W. , Hallett M. , Dwivedi A. K. , Espay A. J. 
Published: March 2020

Background and purposeThere is large variability in the diagnostic approach and clinical management in functional movement disorders (FMD). This study aimed to examine whether opinions and clinical practices related to FMD have changed over the past decade.MethodsAdapted from a 2008 version, we repeated the survey to members of the International Parkinson and Movement Disorder Society (MDS).ResultsIn all, 864/7689 responses (denominator includes non‐neurologists) were received from 92 countries. Respondents were more often male (55%), younger than 45 (65%) and from academic practices (85%). Although the likelihood of ordering neurological investigations prior to delivering a diagnosis of FMD was nearly as high as in 2008 (47% vs. 51%), the percentage of respondents communicating the diagnosis without requesting additional tests increased (27% vs. 19%;P = 0.003), with most envisioning their role as providing a diagnosis and coordinating management (57% vs. 40%;P < 0.001). Compared to patients with other disorders, 64% of respondents were more concerned about missing a diagnosis of another neurological disorder. Avoiding iatrogenic harm (58%) and educating patients about the diagnosis (53%) were again rated as the most effective therapeutic options. Frequent treatment barriers included lack of physician knowledge and training (32%), lack of treatment guidelines (39%), limited availability of referral services (48%) and cultural beliefs about psychological illnesses (50%). The preferred term for communication favored ‘functional’ over ‘psychogenic’ (P < 0.001).ConclusionsAttitudes and management of FMDs have changed over the past decade. Important gaps remain in access to treatment and in the education of neurologists about the inclusionary approach to FMD diagnosis.
Effect of bioactive glass air‐abrasion on the wettability and osteoblast proliferation on sandblasted and acid‐etched titanium surfaces
Authors: Abushahba Faleh , Tuukkanen Juha , Aalto‐Setälä Laura , Miinalainen Ilkka , Hupa Leena , Närhi Timo O. 
Published: March 2020

The aim of this study was to evaluate the hydrophilicity, surface free energy, and proliferation and viability of human osteoblast‐like MC3T3‐E1 cells on sandblasted and acid‐etched titanium surfaces after air‐abrasion with 45S5 bioactive glass, zinc‐containing bioactive glass, or inert glass. Sandblasted and acid‐etched titanium discs were subjected to air‐abrasion with 45S5 bioactive glass, experimental bioactive glass (Zn4), or inert glass. Water contact angles and surface free energy were evaluated. The surfaces were studied with preosteoblastic MC3T3‐E1 cells. Air‐abrasion with either type of glass significantly enhanced the hydrophilicity and surface free energy of the sandblasted and acid‐etched titanium discs. The MC3T3‐E1 cell number was higher for substrates air‐abraded with Zn4 bioactive glass and similar to that observed on borosilicate coverslips (controls). Confocal laser scanning microscopy images showed that MC3T3‐E1 cells did not spread as extensively on the sandblasted and acid‐etched and bioactive glass‐abraded surfaces as they did on control surfaces. However, for 45S5‐ and Zn4‐treated samples, the cells spread most at the 24 h time point and changed their morphology to more spindle‐like when cultured further. Air‐abrasion with bioactive glass and inert glass was shown to have a significant effect on the wettability and surface free energy of the surfaces under investigation. Osteoblast cell proliferation on sandblasted and acid‐etched titanium discs was enhanced by air‐abrasion with 45S5 bioactive glass and experimental Zn4 bioactive glass compared with air‐abrasion with inert glass or no air‐abrasion.
P2Y13 and P2X7 receptors modulate mechanically induced adenosine triphosphate release from mast cells
Authors: Shen Dan , Shen Xueyong , Schwarz Wolfgang , Grygorczyk Ryszard , Wang Lina 
Published: March 2020

AbstractSubcutaneous mast cells (MCs) are vulnerable to mechanical stimulation from external environment. Thus, MCs immune function could be modulated by their mechanosensitivity. This property has been identified as the trigger mechanism of needling acupuncture, a traditional oriental therapy. Previously we have demonstrated the release of adenosine triphosphate (ATP), a stress‐responsive signalling molecule, from mechanical‐perturbed MCs. The current work explores its underlying mechanisms. We noticed that propagation of intracellular free Ca2+ occurred among HMC‐1 cells in response to 50% hypotonic shock. Additionally, amplifying cascade of ATP‐induced ATP release was observed in RBL‐2H3 cells stimulated by medium displacement, which could be mimicked by exogenous ATP (exoATP). Secondary ATP liberation induced by low level (50 nmol/L) of exoATP was reduced by inhibiting ecto‐ATPase‐dependent ADP production with ARL67156, or blocking P2 receptors with suramin or PPADS, or with specific P2Y13 receptor antagonist MRS2211, or siRNA. Secondary ATP release induced by higher dose (200 μmol/L) of exoATP, sufficient to stimulate P2X7 receptor, was attenuated by suramin, PPADS or specific P2X7 receptor antagonist BBG, or siRNA. Finally, RT‐PCR confirmed mRNA expression of P2Y13 and P2X7 in RBL‐2H3 cells. Additionally, such secondary ATP release was attenuated by DPCPX, specific antagonist of adenosine A1 receptor, but not by MRS2179, specific inhibitor of P2Y1 receptor. In summary, mechanosensitive ATP release from MCs is facilitated by paracrine/autocrine stimulation of P2Y13 and P2X7 receptors. This multi‐receptor combination could mediate transmission of information from a local site to distal areas, enabling communication with multiple surrounding cells to coordinate and synchronize their function.
Perspectives and challenges of micro/nanoplastics‐induced toxicity with special reference to phytotoxicity
Authors: Maity Sukhendu , Pramanick Kousik 
Published: March 2020

AbstractPlastic pollution has become a global concern for ecosystem health and biodiversity conservation. Concentrations of plastics are manifold higher in the terrestrial system than the aquatic one. Micro/nanoplastics (M/NP) have the ability to alter soil enzymatic system, soil properties and also affect soil borne microorganisms and earthworms. Despite, the knowhow regarding modulatory effects of plastics are acquired from the study on aquatic system and reports on their phytotoxic potentials are limited. The presence of cell wall that could restrict M/NP invasion into plant roots might be the putative cause of this limitation. M/NP inhibit plant growth, seed germination and gene expression; and they also induce cytogenotoxicity by aggravating reactive oxygen species generation. Dynamic behavior of cell wall; the pores formed either by cell wall degrading enzymes or by plant–pathogen interactions or by mechanical injury might facilitate the entry of into roots M/NP. This review also provides a possible mechanism of large sized microplastics‐induced phytotoxicity especially for those that cannot pass through cell wall pores. As M/NP affect soil microbial community and soil parameters, it is hypothesized that they could have the potential to affect N2fixation and research should be conducted in this direction. Reports on M/NP‐induced toxicity mainly focused only on one polymer type (polystyrene) in spite of the toxicological relevancies of other polymer types like polyethylene, polypropylene etc. So, the assessment of phytotoxic potential of M/NP should be done using other plastic polymers in real environment as they are known to intract with other environmental stressors as well as can alter the the soil–microbe–plant interaction.
Asymmetric patterns and temporal changes in phenology‐based seasonal gross carbon uptake of global terrestrial ecosystems
Authors: Wang Lanhui , Tian Feng , Huang Ke , Wang Yuhang , Wu Zhendong , Fensholt Rasmus 
Published: March 2020

AbstractAimTo study global patterns and temporal changes in the seasonal dynamics (quantity and seasonal distribution) of terrestrial gross carbon uptake in response to global environmental change.LocationGlobal.Time period2000–2016.Major taxa studiedTerrestrial ecosystems.MethodsFollowing a phenology‐based definition of photosynthetic seasonality, we decompose gross primary production (GPP) into three periods, green‐up, maturity and senescence, and derive their corresponding GPP (GPPgp, GPPmp and GPPsp, respectively) from a newly developed time series of satellite‐based global GPP to study spatio‐temporal dynamics of seasonal GPP.ResultsWe find that the global fraction of GPPsp (19.8%) is larger than GPPgp (14.3%), indicating a globally asymmetric seasonal distribution of gross carbon uptake by terrestrial ecosystems. Globally, GPPmp plays a dominant role in shaping spatial patterns and increasing/decreasing trends in GPP, while GPPgp/GPPsp contributes to increasing GPP at the regional scale. Higher fractions of GPPgp/GPPmp (lower of GPPsp), as well as the co‐occurrence of increasing GPP and non‐tree vegetation cover in major croplands, are likely to be caused by agricultural intensification. Global changes in GPPgp and GPPsp are closely related to changes in their seasonal distributions (R = .86/.8, respectively), whereas this relationship is weaker for GPPmp (R = .53). Finally, high correlations are observed between changes in GPPgp and GPPsp and changes in their durations (R = .78/.78, respectively), while GPPmp shows a relatively lower correlation with its duration (R = .67).Main conclusionsThe asymmetric spatio‐temporal patterns in the seasonal dynamics of global terrestrial gross carbon uptake found here have been substantially reshaped by anthropogenic land‐use/cover changes and changes in photosynthetic phenology. Compared to calendar‐based meteorological seasons more suitable for temperate/subpolar ecosystems, our phenology‐based approach is expected to provide an alternative starting point for a better understanding of global spatio‐temporal changes in the seasonal dynamics of terrestrial ecosystem processes and functioning under accelerating global change.
Leaf‐out in northern ecotypes of wide‐ranging trees requires less spring warming, enhancing the risk of spring frost damage at cold range limits
Authors: Zohner Constantin M. , Mo Lidong , Sebald Veronica , Renner Susanne S. 
Published: March 2020

AbstractAimTrees need to avoid frost damage to their young leaves by leafing out after the occurrence of the last frost, yet they also need to start photosynthesis early in the season to achieve sufficient growth. This trade‐off leads to the hypothesis that ‘safety margins’ against spring frost should become shorter, the longer the winter duration, perhaps reaching an asymptotic limit where frost damage would occur in most years. Physiologically, shorter safety margins in high‐latitude ecotypes might be achieved by lower degree‐day requirements for leaf‐out, compared to low‐latitude ecotypes.LocationEurope.Time period1902–2009.Major taxa studiedTemperate trees.MethodsUsing herbarium collections of Acer platanoides, Carpinus betulus, Fagus sylvatica and Prunus spinosa made over 108 years at 40° to 60° N latitude, we related historic leaf‐out dates to winter and spring temperatures (chilling and degree‐days), winter duration, and date of last frost occurrence in the relevant years and locations.ResultsIn all species, frost safety margins decreased towards high‐latitude regions with long winters, with each day increase in winter duration reducing frost safety margins by 0.48 days in Fagus and 0.32–0.21 days in Prunus, Acer and Carpinus. These latitudinal differences correlate with northern ecotypes’ shorter degree‐day requirements for leaf‐out.Main conclusionsThe decline in spring frost safety margins in regions with long winters supports the new hypothesis that species may reach their geographic range limit where they ‘bump up’ against experiencing regular frost injury to their young leaves. Larger datasets are necessary to further corroborate our hypothesis and future efforts should thus be directed toward increasing the latitudinal range of existing phenological databases.
State‐level austerity, education, and large urban labor markets: Evidence from fiscal policy experiments in Kansas and Wisconsin
Authors: Komarek Timothy M. 
Published: March 2020

AbstractIn 2011, Kansas and Wisconsin experimented with fiscal austerity policies. Proponents of the tax and public expenditure cuts argued that they would spur economic growth, while opponents claimed that it would harm vulnerable populations. I use the timing of these policies and the synthetic control method to examine how state‐level austerity affected earnings per worker for high and low education segments of the workforce in major urban areas. The results suggest that the Kansas and Wisconsin fiscal experiments hurt low education workers in some urban areas. The estimates also show heterogeneity in the treatment effect. Notably, Madison, WI, was the only urban area that experienced substantial positive growth in both education segments.
Content validity of psoriatic arthritis screening questionnaires: systematic review
Authors: Landini Enríquez Venecia V. , Jurado Santa‐Cruz Fermín , Peralta‐Pedrero María L. , Morales‐Sánchez Martha‐Alejandra 
Published: March 2020

AbstractBackgroundPsoriatic arthritis (PsA) is the main entity associated with psoriasis (PsO). Consequently, several PsA screening instruments have been developed, most of them are self‐administered questionnaires, known as patient‐reported outcome measures (PROMs).ObjectiveTo identify, summarize, and systematically evaluate the evidence of the content validity of PsA screening PROMs, in patients with PsO, by the dermatologist, based on COSMIN methodology.MethodsA structured literature search was performed, until June 2019, that included development and/or validation studies of a questionnaire for the screening of PsA in patients with PsO. The evaluation was based on the PROMs’ development, relevance, comprehensiveness, and comprehensibility.ResultsEleven PROMs were included in the systematic review with four additional validation studies of the included instruments. Only ToPAS2 (Toronto Psoriatic Arthritis Screen) questionnaire had an adequate content validity. CONTEST (Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis), CEPPA (Center of Excellence for Psoriasis sand Psoriatic Arthritis), and SiPAS (Simple Psoriatic Arthritis Screening questionnaire) qualified as inadequate.ConclusionsDespite the existence of eleven validated PsA screening PROMs, none were supported by very high‐quality evidence of their content validity, which brings the opportunity for the creation of a new proposal PROM for the screening of PsA.
Effects of demographic and obstetric variables with body image on sexual dysfunction in pregnancy: A cross‐sectional and comparative study
Authors: Aksoy Derya Yesim , Gök Uğur Hacer , Özşahin Zeliha 
Published: March 2020

AbstractAimThis study was conducted to determine the effects of demographic and obstetric variables with body image on sexual dysfunction in pregnant women.BackgroundSexual dysfunction is frequent in pregnant women. To what extent body image plays a role is incompletely understood.MethodsIn the research, a cross‐sectional and comparative study was conducted. A personal information form, body image scale, and female sexual function index were applied to 472 pregnant women. Descriptive statistics, the Student t‐test, the χ2 test, and logistic regression analysis were employed for evaluating the data.ResultsSexual dysfunction was found in 54.7%. The frequency of sexual dysfunction in the first trimester was lower. In addition, factors like the place of residence of the pregnant women and number of pregnancies were found to be related to sexual dysfunction in pregnant women. Each unit decrease in body image score resulted in women being 0.98 times more likely to experience sexual dysfunction.ConclusionIt was determined that approximately one in two pregnant women experienced sexual dysfunction, and body image, place of residence, trimester of the pregnancy, and number of pregnancies were important factors affecting sexual function.