bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue pharmacokinetics of DHP107, a novel lipid‐based oral formulation of paclitaxel, in mice and patients by positron emission tomography
Authors: Moon Byung Seok , Park Hyun Soo , Sunwoo Jung , Lee In‐Hyun , Kim Anhye , Moon Seol Ju , Lee Heechan , Son Min Hee , Kim Su Bin , Park Sun Mi , Woo Sang‐Keun , Jang Jun‐Hee , Kim Bom Sahn , Kim Jee Hyun , Kim Sang Eun , Lee Howard 
Published: June 2021

AbstractDHP107 is a newly developed lipid‐based oral formulation of paclitaxel. We evaluated the in vivo tissue pharmacokinetics (PKs) of DHP107 in mice and patients using positron emission tomography (PET). Radioisotope‐labeled [3H]DHP107 and [18F]DHP107 for oral administration were formulated in the same manner as the manufacturing process of DHP107. In vivo tissue PK were assessed in healthy ICR mice and breast cancer xenografted SCID mice. Two patients with metastatic breast cancer were clinically evaluated for absorption at the target lesion after internal absorbed dose estimation. Whole‐body PET/computed tomography data were acquired in healthy and xenografted mice and in patients up to 10–24 h after administration. Tissue [18F]DHP107 signals were plotted against time and PK parameters were determined. The amounts of radioactivity in various organs and excreta were determined using a beta‐counter and are expressed as the percentage of injected dose (ID). Oral [18F]DHP107 was well‐absorbed and reached the target lesion in mice and patients with breast cancer. Significant amounts of radioactivity were found in the stomach, intestine, and liver after oral administration of [3H]‐ and [18F]DHP107 in healthy mice. The [18F]DHP107 reached a peak distribution of 0.7–0.8%ID in the tumor at 5.6–7.3 h in the xenograft model. The [18F]DHP107 distribution in patients with metastatic breast cancer was the highest at 3–4 h postadministration. Systemic exposures after administration of a DHP107 therapeutic dose were comparable with those in previous studies. PET using radioisotope‐labeled drug candidates is useful for drug development and can provide valuable information that can complement plasma PK data, particularly in early phase clinical trials.
Agricultural Persistence and Potentials on the Edge of Northern Ontario
Authors: Finnis Elizabeth 
Published: June 2021

AbstractDrawing on farmers’ lived experiences, I explore factors that shape agricultural persistence in the Parry Sound District, Ontario, Canada. Local farming is embedded in broader contexts and is place‐based and specific. Agricultural persistence and resilience are shaped in part through individual factors, such as flexibility in response to change, the valuing of local agricultural heritage, and the determination to farm. However, attention to specific agricultural needs is critically necessary to help ensure agricultural futures in the district. I demonstrate the ways that attention to place‐based experiences pinpoints the need for localized understandings and supports to ensure agricultural viability and contribute to diverse and valued visions of agriculture and food production within the province.
A long‐brewing crisis: The historical antecedents of major alcohol policy change in Ireland
Authors: Lesch Matthew , McCambridge Jim 
Published: June 2021

AbstractIntroductionThe Public Health (Alcohol) Act 2018 in Ireland has been hailed as a world‐leading package of alcohol policy reforms. Existing studies have identified the events that led to alcohol emerging onto the high‐level policy agenda in Ireland, particularly after 2009. Using policy feedback theory, this study specifically investigates the political consequences of accumulating alcohol‐related health and social harms for processes of policy change prior to 2009.MethodsThe study traces the development of alcohol policy in Ireland over the past three decades. It draws on primary documents, secondary literature and interviews with public health advocates, medical doctors, public health experts and key decision‐makers.ResultsThe study documents a decades‐long struggle to have alcohol recognised as a public health issue in Ireland. We identify 2008/2009 as the key turning point, where policy conditions decisively shifted in a public health direction. We show how insufficient institutional authority and the accumulation of the effects of earlier policy failures helped foster this dynamic. These two factors elevated the visibility of alcohol‐related harm for key stakeholders, helping spur greater demand for major policy change.Discussion and ConclusionsNot acting on the population health harms caused by alcohol can produce significant societal costs, particularly when consumption is rising, and entail subsequent political consequences. Understanding of innovations in alcohol policy decision making requires an appreciation of the historical context, including earlier policy failures.
Static species distribution models in the marine realm: The case of baleen whales in the Southern Ocean
Authors: El‐Gabbas Ahmed , Van Opzeeland Ilse , Burkhardt Elke , Boebel Olaf 
Published: June 2021

AbstractAimInformation on the spatio‐temporal distribution of marine species is essential for developing proactive management strategies. However, sufficient information is seldom available at large spatial scales, particularly in polar areas. The Southern Ocean (SO) represents a critical habitat for various species, particularly migratory baleen whales. Still, the SO’s remoteness and sea ice coverage disallow obtaining sufficient information on baleen whale distribution and niche preference. Here, we used presence‐only species distribution models to predict the circumantarctic habitat suitability of baleen whales and identify important predictors affecting their distribution.LocationThe Southern Ocean (SO).MethodsWe used Maxent to model habitat suitability for Antarctic minke, Antarctic blue, fin and humpback whales. Our models employ extensive circumantarctic data and carefully prepared predictors describing the SO’s environment and two spatial sampling bias correction options. Species‐specific spatial‐block cross‐validation was used to optimize model complexity and for spatially independent model evaluation.ResultsModel performance was high on cross‐validation, with generally little predicted uncertainty. The most important predictors were derived from sea ice, particularly seasonal mean and variability of sea ice concentration and distance to the sea ice edge.Main conclusionsOur models support the usefulness of presence‐only models as a cost‐effective tool in the marine realm, particularly for studying the migratory whales’ distribution. However, we found discrepancies between our results and (within) results of similar studies, mainly due to using different species data quality and quantity, different study area extent and methodological reasons. We further highlight the limitations of implementing static distribution models in the highly dynamic marine realm. Dynamic models, which relate species information to environmental conditions contemporaneous to species occurrences, can predict near‐real‐time habitat suitability, necessary for dynamic management. Nevertheless, obtaining sufficient species and environmental predictors at high spatio‐temporal resolution, necessary for dynamic models, can be challenging from polar regions.
Optical diagnosis of colorectal polyps using novel blue light imaging classification among trainee endoscopists
Authors: Koehn Christopher , Rex Douglas K. , Allen Jimmy , Bhatti Umer , Bhavsar‐Burke Indira , Thoguluva Chandrasekar Viveksandeep , Challa Abhishek , Duvvuri Abhiram , Dakhoul Lara , Ha John , Hamade Nour , Hicks S. Bradley , Jansson‐Knodell Claire , Krajicek Edward , Das Kundumadam Shanker , Nutalapati Venkat , Phatharacharukul Parkpoom “Peter” , Razmdjou Shadi , Saito Akira , Sarkis Fayez , Sutton Richard , Wehbeh Antonios , Sharma Prateek , Desai Madhav 
Published: June 2021

BackgroundBlue light imaging (BLI) has been shown to improve the characterization of colorectal polyps among the endoscopy experts. We aimed to determine if this technology could be taught to endoscopy trainees while maintaining high accuracy and interobserver agreement.MethodsTwenty‐one gastroenterology trainees (fellows) from two academic institutions participated in this prospective study. Each trainee completed a web‐based learning comprising four modules: pre‐test, didactic videos explaining the BLI Adenoma Serrated International Classification (BASIC), interactive examples, and post‐test assessment. The pre‐ and post‐test modules consisted of reviewing video images of colon polyps in high definition white light imaging and BLI and then applying the BASIC classification to determine if the polyps were likely to be adenomatous. Confidence in adenoma identification (rated ‘1’ to ‘5’), accuracy in polyp (adenoma vs. non‐adenoma) identification, and agreement in characterization per BASIC criteria were derived.ResultsTrainee accuracy in the adenoma diagnosis improved from 74.7% (pre‐test) to 85.4% (post‐test) (P < 0.01). There was a trend towards higher accuracy in polyp characterization with subsequent years of training (1st year fellows 77.4%, 2nd year 88.5%, and final year 94.0%) with consistent improvements after the e‐learning across years of trainees. Overall, trainees were able to identify adenoma with a high sensitivity of 86.9%, specificity 83.9%, positive predictive value of 84.4%, and negative predictive value of 86.5%. However, their interobserver agreement in adenoma diagnosis was moderate (k = 0.52).ConclusionThe novel BLI classification can be easily taught to gastroenterology trainees using an online module and accuracy improves with years of training reaching >90% for colorectal polyp characterization.
Synthetic resin acid derivatives selectively open the hKV7.2/7.3 channel and prevent epileptic seizures
Authors: Ottosson Nina E. , Silverå Ejneby Malin , Wu Xiongyu , Estrada‐Mondragón Argel , Nilsson Michelle , Karlsson Urban , Schupp Melanie , Rognant Salomé , Jepps Thomas Andrew , Konradsson Peter , Elinder Fredrik 
Published: June 2021

AbstractObjectiveAbout one third of all patients with epilepsy have pharmacoresistant seizures. Thus there is a need for better pharmacological treatments. The human voltage‐gated potassium (hKV) channel hKV7.2/7.3 is a validated antiseizure target for compounds that activate this channel. In a previous study we have shown that resin acid derivatives can activate the hKV7.2/7.3 channel. In this study we investigated if these channel activators have the potential to be developed into a new type of antiseizure drug. Thus we examined their structure‐activity relationships and the site of action on the hKV7.2/7.3 channel, if they have unwanted cardiac and cardiovascular effects, and their potential antiseizure effect.MethodsIon channels were expressed in Xenopus oocytes or mammalian cell lines and explored with two‐electrode voltage‐clamp or automated patch‐clamp techniques. Unwanted vascular side effects were investigated with isometric tension recordings. Antiseizure activity was studied in an electrophysiological zebrafish‐larvae model.ResultsFourteen resin acid derivatives were tested on hKV7.2/7.3. The most efficient channel activators were halogenated and had a permanently negatively charged sulfonyl group. The compounds did not bind to the sites of other hKV7.2/7.3 channel activators, retigabine, or ICA‐069673. Instead, they interacted with the most extracellular gating charge of the S4 voltage‐sensing helix, and the effects are consistent with an electrostatic mechanism. The compounds altered the voltage dependence of hKV7.4, but in contrast to retigabine, there were no effects on the maximum conductance. Consistent with these data, the compounds had less smooth muscle–relaxing effect than retigabine. The compounds had almost no effect on the voltage dependence of hKV11.1, hNaV1.5, or hCaV1.2, or on the amplitude of hKV11.1. Finally, several resin acid derivatives had clear antiseizure effects in a zebrafish‐larvae model.SignificanceThe described resin acid derivatives hold promise for new antiseizure medications, with reduced risk for adverse effects compared with retigabine.
Hidradenitis suppurativa in skin of colour
Authors: Zouboulis Christos C. , Goyal Mankul , Byrd Angel S. 
Published: June 2021

AbstractHidradenitis suppurativa/acne inversa (HS) more prevalent and disproportionally affects African American females. Although there are limited studies in HS skin of colour populations in the USA, there is more scarcity of HS skin of colour studies in other countries, which limits the overall understanding of the disease among these patients. Herein, our overview of the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference provided a crude example of the limited number of skin of colour physicians, physician scientists and inclusion of skin of colour patients highlighting the need to increase awareness of this important issue. We summarized the epidemiology, pathogenesis, clinical picture and focused on treatment options from southeast Asia and Africa. Our outlined general recommendations for diagnosis will render better clinical care and outcomes for diverse patient populations.
Visible light and human skin pigmentation: The importance of skin phototype
Authors: Moreiras Hugo , O'Connor Clare , Bell Mike , Tobin Desmond J. 
Published: June 2021

AbstractMelanin is synthesised within melanocytes and transferred to keratinocytes in human skin, thereby regulating skin colour and protecting skin cells against UVR‐induced damage. We commonly divide human skin into six phototypes (SPT)‐I to ‐VI (Fitzpatrick scale) according to the skin's tanning response to UVR. In this pilot study, we investigated the impact of UVR (maximum 311nm), blue (peak 450nm) and green visible light (peak 530nm) on melanin production and type in healthy human skin histocultures (SPT‐I, ‐II and ‐III). UVR, blue and green light stimulated a surface tanning response in SPT‐II and ‐III, but not SPT‐I. Using the Warthin‐Starry stain for sensitive melanin detection, all three light treatments induced melanogenesis in SPT‐II and ‐III skin. Surprisingly, blue and green light (but not UVR) stimulated melanin synthesis in SPT‐I skin. Moreover, melanin synthesis induced by blue and green visible light in SPT‐I, SPT‐II, and SPT‐III skin was not associated with a detectable increase in DNA damage or cell apoptosis. By contrast, both responses were detected after UVR. These data suggest that blue and green visible light can stimulate melanin production in fair‐skinned individuals without, at least some of, the harmful consequences of UVR‐induced pigmentation. We are currently examining the molecular basis of UVR‐independent melanogenesis in fair skin.
Nutrients control reproductive traits of hygrophytic bryophytes
Authors: Fernández‐Martínez Marcos , Preece Catherine , Corbera Jordi , Cano Oriol , Garcia‐Porta Joan , Bogdziewicz Michał , Sardans Jordi , Janssens Ivan A. , Sabater Francesc , Peñuelas Josep 
Published: June 2021

Abstract

Nutrient economy and plant nutrient concentrations have been suggested as important selective pressures of reproductive traits in vascular plants. However, evidence supporting that the reproduction of bryophytes and their reproductive traits have also been conditioned by nutrient availability is lacking.

We here analysed the nutrient (N, P, K, and Fe) concentration of 35 aquatic and semi‐aquatic bryophytes and the chemistry of the spring water in which they lived to determine whether bryophyte nutrient concentrations were correlated with the frequency of sexual reproduction, main reproductive mode (sexual vs. asexual), dioicy, and spore diameter, while controlling for climate and nutrient concentrations in the spring water.

Water nutrient concentrations, except for K, had a small but positive influence on bryophyte nutrient concentrations. P‐rich and K‐poor species produced sporophytes more often and were more likely to reproduce sexually and be monoicous. Spore diameter was smaller in P‐ and Fe‐rich mosses but larger in N‐rich mosses living in humid climates. P‐rich species thus produced more and smaller spores and were able to propagate more extensively.

Overall, our results suggest that nutrient economy, especially P economy, has played an important role in shaping the reproductive traits of bryophytes.
Mice with an autism‐associated R451C mutation in neuroligin‐3 show a cautious but accurate response style in touchscreen attention tasks
Authors: Burrows Emma L. , May Carlos , Hill Thomas , Churliov Leonid , Johnson Katherine A. , Hannan Anthony J. 
Published: June 2021

AbstractOne of the earliest identifiable features of autism spectrum disorder (ASD) is altered attention. Mice expressing the ASD‐associated R451C mutation in synaptic adhesion protein neuroligin‐3 (NL3) exhibit impaired reciprocal social interactions and repetitive and restrictive behaviours. The role of this mutation in attentional abnormalities has not been established. We assessed attention in male NL3R451C mice using two well‐established tasks in touchscreen chambers. In the 5‐choice serial reaction task, rodents were trained to attend to light stimuli that appear in any one of five locations. While no differences between NL3R451C and WT mice were seen in accuracy or omissions, slower response times and quicker reward collection latencies were seen across all training and probe trials. In the rodent continuous‐performance test, animals were required to discriminate, and identify a visual target pattern over multiple distractor stimuli. NL3R451C mice displayed enhanced ability to attend to stimuli when task‐load was low during training and baseline but lost this advantage when difficulty was increased by altering task parameters in probe trials. NL3R451C mice made less responses to the distractor stimuli, exhibiting lower false alarm rates during all training stages and in probe trials. Slower response times and quicker reward latencies were consistently seen in NL3R451C mice in the rCPT. Slower response times are a major cognitive phenotype reported in ASD patients and are indicative of slower processing speed. Enhanced attention has been shown in a subset of ASD patients and we have demonstrated this phenotype also exists in the NL3R451C mouse model.
miR‐29c‐3p regulates TET2 expression and inhibits autophagy process in Parkinson's disease models
Authors: Wang Ruili , Yao Jie , Gong Fuhua , Chen Songsheng , He Ya , Hu Chunting , Li Chen 
Published: June 2021

AbstractAutophagy in dopamine (DA) neurons is concerned to be associated with Parkinson's disease (PD), but the detailed mechanism remains unknown. Herein, we aimed to investigate the function of microRNA (miR)‐29c‐3p in autophagy in PD models. Intraperitoneal injection of MPTP (20 mg/kg) was given to C57BL/6 mice to establish PD mouse model. SH‐SY5Y cells were treated with MPP+ (1 mmol/L) to establish in vitro PD model. The results indicated that in the substantia nigra pars compacta (SNpc) DA neurons of PD mice, autophagy was activated accompanied by down‐regulated miR‐29c‐3p and up‐regulated ten‐eleven translocation 2 (TET2) expression. Up‐regulation of miR‐29c‐3p inhibited TET2 expression and SNpc (including DA neurons) autophagy in PD mice. In vitro PD model confirmed that MPP+ treatment markedly down‐regulated miR‐29c‐3p expression and up‐regulated TET2 expression in SH‐SY5Y cells in a dose/time‐dependent manner. Moreover, miR‐29c‐3p up‐regulation also inhibited autophagy and TET2 expression in vitro. Additionally, TET2 was proved to be targeted and down‐regulated by miR‐29c‐3p. TET2 knockdown inhibited MPP+‐induced autophagy, whereas TET2 over‐expression reversed the effects of miR‐29c‐3p over‐expression on SH‐SY5Y cell autophagy. Overall, miR‐29c‐3p over‐expression inhibits autophagy in PD models, which may be mediated by TET2. Our finding may provide new insights for regulating autophagy to improve PD progression.
Polyvinylpyrrolidone in hemodialysis membranes: Impact on platelet loss during hemodialysis
Authors: Zawada Adam M. , Melchior Pascal , Erlenkötter Ansgar , Delinski Dirk , Stauss‐Grabo Manuela , Kennedy James P. 
Published: June 2021

AbstractIntroductionHydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into the patient's blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We investigated the content of PVP and its elution from the blood‐side surface from commercially available dialyzers, including the novel FX CorAL, with PVP‐enriched and α‐tocopherol‐stabilized membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility.MethodsSix synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta [B. Braun]) were investigated in the present study. The content of PVP on blood‐side surface was determined with X‐ray photoelectron spectroscopy (XPS). The amount of elutable PVP was measured photometrically after 5 h recirculation. The level of platelet loss was evaluated in an ex vivo recirculation model with human blood.FindingsHighest PVP content on the blood‐side surface was found for the polysulfone‐based FX CorAL (26.3%), while the polyethersulfone‐based THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for the autoclave steam‐sterilized THERANOVA (9.1 mg/1.6 m2 dialyzer) and Polyflux (9.0 mg/1.6 m2 dialyzer), while the lowest PVP elution was found for the INLINE steam sterilized FX CorAL and FX CorDiax (<0.5 mg/1.6 m2 dialyzer, for both). Highest platelet loss was found for xevonta (+164.4% compared to the reference) and the lowest for the FX CorAL (−225.2%) among the polysulfone‐based dialyzers; among the polyethersulfone‐based dialyzers, THERANOVA (+95.5%) had the highest and ELISIO (−52.1%) the lowest platelet loss.DiscussionPolyvinylpyrrolidone content and elution differ between commercially available dialyzers and were found to be linked to the membrane material and sterilization method. The amount of non‐eluted PVP on the blood‐side surface may be an important determinant for the biocompatibility of dialyzers.
Coronary artery bypass grafting versus percutaneous coronary intervention in end‐stage kidney disease: A systematic review and meta‐analysis of clinical studies
Authors: Kanbay Mehmet , Tapoi Laura , Ureche Carina , Bulbul Mustafa C. , Kapucu Irem , Afsar Baris , Basile Carlo , Covic Adrian 
Published: June 2021

AbstractThe most significant complication of end‐stage kidney disease (ESKD) is cardiovascular disease, mainly coronary artery disease (CAD). Although the effective treatment of CAD is an important prognostic factor, whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is better for treating CAD in this group of patients is still controversial. We searched Pubmed/Medline, Web of Science, Embase, the Cochrane Central Register of Controlled Trials articles that compared the outcomes of CABG versus PCI in patients with ESKD requiring dialysis. A total of 10 observational studies with 39,666 patients were included. Our analysis showed that when compared to PCI, CABG had lower risk of need for repeat revascularization (relative risk [RR] = 2.25, 95% confidence interval [CI] 2.1–2.42, p < 0.00001) and cardiovascular death (RR = 1.19, 95% CI 1.14–1.23, p < 0.00001) and higher risk for short‐term mortality (RR = 0.43, 95% CI 0.38–0.48, p < 0.00001). There was no statistically significant difference between the PCI and CABG groups in the risk for late mortality (RR = 1.05, 95% CI 0.97–1.14, p = 0.25), myocardial infarction (RR = 1.05, 95% CI 0.46–2.36, p = 0.91) or stroke (RR = 1.02, 95% CI 0.64–1.61, p = 0.95). This meta‐analysis showed that in ESKD patients requiring dialysis, CABG was superior to PCI in regard to cardiovascular death and need for repeat revascularization and inferior to PCI in regard to short term mortality. However, this meta‐analysis has limitations and needs confirmation with large randomized controlled trials.