bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictions of kelp distribution shifts along the northern coast of Japan
Authors: Sudo Kenji , Watanabe Kentaro , Yotsukura Norishige , Nakaoka Masahiro 
Published: October 2019

AbstractJapanese kelps are important because they perform a valuable ecosystem function of coastal kelp forest formation, and they are important food resources. The present study aimed to predict future shifts in major kelp species in northern Japan under different climate change scenarios. From a database of cold temperate kelp species in Japan, we extracted 1,958 data points to estimate the distribution of 11 kelp species that inhabit the waters around northern Japan. Distributions of the past (1980s) and the future (2040s and 2090s) were estimated using a species distribution model (MaxEnt). Variation in summer and winter sea surface temperatures was the factor most responsible for the estimated distribution patterns for most species; the length of natural rocky coasts and wave height were also important for some species. A forecast of shifts in distributions based on different Intergovernmental Panel on Climate Change scenarios showed that kelp species diversity in Japan would significantly decrease. By the 2090s, their habitat range overall was estimated to decline to 30–51% of that of the 1980s with moderate warming (Representative concentration pathways [RCP] 4.5) and to 0–25% with severe warming (RCP 8.5). The model predicted that 6 of 11 cold temperate kelp species may become extinct around Japan by the 2090s (RCP 8.5). Commercially important species, such as Saccharina japonica, are also expected to decline greatly, which may affect kelp fisheries and aquaculture in northern Japan.
Dry soil determines the pseudoviviparous reproduction in Comanthera nivea (Eriocaulaceae) in the Campos Rupestres in south‐eastern Brazil
Authors: Lombello Juliana C. , Biondi Michel , Teodoro Grazielle S. , Coelho Flávia F. 
Published: October 2019

AbstractPseudovivipary is an asexual reproduction strategy correlated with extreme environments. Comanthera nivea occurs in habitats with low water retention. This study investigated the effect of soil moisture availability on C. nivea pseudoviviparous reproduction and flowering. We established four permanent plots (1 × 1 m), two in a shaded area, in which we marked 15 rosettes in each plot, and two in a full‐sun area, in which we marked 10 rosettes in each plot. We made monthly observations from August 2016 to January 2017, to quantify the number of flower heads and of pseudoviviparous ramets per rosette, and measured soil moisture. Our results showed a high correlation between soil moisture and flowering. Flowering in C. nivea occurs in periods of increased soil moisture, whereas pseudoviviparous reproduction occurs in the driest period. The advantages of a pseudoviviparous canopy‐forming strategy in habitats with scarcity of water in the soil are discussed.
Additive influences of acute early life stress and sex on vulnerability for aversion‐resistant alcohol drinking
Authors: Radke Anna K. , Held Isabel T. , Sneddon Elizabeth A. , Riddle Collin A. , Quinn Jennifer J. 
Published: October 2019

AbstractAcute early life stress (ELS) alters stress system functioning in adulthood and increases susceptibility to posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). The current study assessed the effects of acute, infant ELS on alcohol drinking, including aversion‐resistant drinking, in male and female Long Evans rats. Acute ELS was induced using a stress‐enhanced fear learning (SEFL) protocol that consisted of 15 footshocks delivered on postnatal day (PND) 17. Alcohol drinking during adolescence and adulthood was measured with a two‐bottle choice intermittent alcohol access paradigm. Aversion‐resistant drinking was assessed in adulthood by adding quinine (0.01, 0.1, and 1.0 g/L) to the alcohol bottle after 5 to 6 weeks and 11 to 12 weeks of drinking. ELS had minimal influences on adolescent and adult alcohol consumption and preference. However, ELS, sex, and alcohol exposure history all influenced aversion‐resistant alcohol drinking in an additive fashion. Higher concentrations of quinine were tolerated in females, ELS‐exposed rats, and after 11 to 12 weeks of drinking. Tests of quinine sensitivity in a separate cohort of animals found that rats can detect concentrations of quinine as low as 0.001 g/L in water and that quinine sensitivity is not influenced by sex or ELS exposure. These results agree with reports of sex differences in aversion‐resistant drinking and are the first to demonstrate an influence of ELS on this behavior. Our results also suggest that a single traumatic stress exposure in infancy may be a promising model of comorbid PTSD and AUD and useful in studying the interactions between ELS, sex, and alcohol dependence.
Atypically grown large periradicular cyst affecting adjacent teeth and leading to confounding diagnosis of non‐endodontic pathology
Authors: Ricucci Domenico , Amantea Massimiliano , Girone Christian , Siqueira José F. 
Published: October 2019

AbstractThis article reports a case of a large osteolytic lesion in the mandible, mostly associated with the apices of the premolars, and suspected as having a non‐endodontic origin because the 2 premolars responded positively to the cold sensibility test. The distal border of the lesion reached the mesial root of the first molar, which also had a small lesion in its distal aspect. Cone‐beam computed tomography revealed that the large lesion communicated with the small molar lesion. Because the large lesion was suspected as having a non‐endodontic origin, surgery was scheduled for enucleation and biopsy. The molar was root canal‐retreated, and the 2 premolars treated. Histologic analysis of the premolar pulps showed vitality but advanced degenerative changes. The lesion was histologically diagnosed as an inflammatory periradicular cyst, which originated in the first molar and had an atypical growth to the premolar area. Follow‐up revealed that the affected area healed uneventfully.
Outcomes of women at high familial risk for breast cancer: An 8‐year single‐center experience
Authors: Lammert Jacqueline , Skandarajah Anita R. , Shackleton Kylie , Calder Patricia , Thomas Susan , Lindeman Geoffrey J. , Mann Gregory Bruce 
Published: October 2019

AbstractObjectivesThe value of a high‐risk surveillance program for mutation carriers and women at high familial breast cancer risk has not been extensively studied. A Breast and Ovarian Cancer Risk Management Clinic (BOCRMC) was established at the Royal Melbourne Hospital in 2010 to provide multimodality screening and risk management strategies for this group of women. The aims of this study were to evaluate the program and describe breast cancer diagnoses for BRCA1, BRCA2, and other germline mutation carriers as well as high‐risk noncarriers attending the BOCRMC.MethodsClinical data from mutation carriers and noncarriers with a ≥25% lifetime risk of developing breast cancer who attended between 2010 and 2018 were extracted from clinic records and compared. The pattern and mode of detection of cancer were determined.ResultsA total of 206 mutation carriers and 305 noncarriers attended the BOCRMC and underwent screening on at least one occasion. Median age was 37 years. After a median follow‐up of 34 months, 15 (seven invasive) breast cancers were identified in mutation carriers, with seven (six invasive) breast cancers identified in noncarriers. Of these, 20 (90.9%) were detected by annual screening, whereas two (9.1%) were detected as interval cancers (both in BRCA1 mutation carriers). Median size of the invasive breast cancers was 11 mm (range: 1.5‐30 mm). The majority (76.9%) were axillary node negative. In women aged 25‐49 years, the annualized cancer incidence was 1.6% in BRCA1, 1.4% in BRCA2 mutation carriers, and 0.5% in noncarriers. This compares to 0.06% annualized cancer incidence in the general Australian population.ConclusionsScreening was effective at detecting early‐stage cancers. The incidence of events in young noncarriers was substantially higher than in the general population. This potentially justifies ongoing management through a specialty clinic, although further research to better personalize risk assessment in noncarriers is required.
The VAC regimen for adult rhabdomyosarcoma: Differences between adolescent/young adult and older patients
Authors: Nakano Kenji , Ae Keisuke , Matsumoto Seiichi , Takahashi Shunji 
Published: October 2019

AbstractBackgroundCompared to pediatric patients, adult rhabdomyosarcoma (RMS) patients have poor prognoses, but the differences in prognoses and treatment sensitivity between adolescent/young adult (AYA) patient and older RMS patients have not been established.AimTo evaluate and compare the efficacy and safety of the vincristine/dactinomycin/cyclophosphamide (VAC) regimen, that is, the standard combination chemotherapy regimen for pediatric RMS, in AYA and older patients.MethodsWe retrospectively reviewed the clinical records of adolescent and adult RMS patients treated at our institution and patients treated with the VAC were enrolled in the analyses. The differences in the efficacy and safety of VAC between the AYA patients (15‐39 years old) and older patients (≥40 years old) were compared.ResultsTotal of 23 patients were enrolled (14 AYA patients and nine older patients) were enrolled. With the median follow‐up of 89.4 weeks (range 17.7–263.1 weeks), the median progression‐free survival (PFS) and overall survival (OS) of the VAC regimen were 61.4 weeks (95% CI, 32.6–90.3) and 104.0 weeks (95% CI, 43.8–164.2), respectively, with no significant differences in the PFS or OS between the AYA and older patients. There were no differences in the response rate of the VAC between AYA (64.3%) and older (66.7%), either. Safety profiles were similar between the AYA and older groups, but exposure to antitumor drugs of the VAC tended to be lower in the older group; median number of total cycle of the VAC was 13 in AYA and 10 in older, cumulative cyclophosphamide dose was 16.8 g/m2 in AYA and 12.8 g/m2 in older, and number of vincristine skips was six in AYA and 12 in older, respectively.ConclusionThere were no significant differences in responses to the VAC among AYA and older patients with RMS. With the appropriate dose modification, the VAC regimen could be a feasible treatment option for RMS patients >40 years old.
Time‐Varying Aggregate Short‐Selling in Korea
Authors: Lee Kuan‐Hui , Wang Shu‐Feng 
Published: October 2019

AbstractThis study examines the variation in aggregate short‐selling by foreigners, individuals, and institutional investors in relation to market return and other market‐wide variables in the Korean stock market. First, we find that aggregate short‐selling has strong seasonal components. In contrast to the existing literature, which shows contrarian‐style short‐selling at the stock level, we find momentum‐style short‐selling by foreigners and individual investors at the aggregate level. That is, they significantly increase their short‐selling following a short‐term down market. In addition, we show that past US market return is negatively related to aggregate short‐selling by foreign investors. Vector‐autoregression and impulse‐response analyses reveal that aggregate short‐selling is significantly affected by changes in market return, but not vice versa.
The Impact of Venture Capital Investment on the Performance of Peer‐to‐Peer Lending Platforms: Evidence from China
Authors: Gu Dingwei , Lu Tian , Luo Pinliang , Zhang Chenghong 
Published: October 2019

AbstractThe Chinese peer‐to‐peer (P2P) lending market is expanding quickly but has a relatively poor level of operation. Using panel‐structured data from a leading P2P lending portal in China, we investigate the effects of venture capital (VC) investment on the performance of P2P lending platforms. Specifically, we identify a short‐term signaling effect and a long‐term governance effect of VC investment on platform performance in terms of transaction volume, and numbers of lenders and borrowers. However, we only find a decrease in average interest rates after venture capitalists’ (VCs’) entry in the long run. Moreover, we verify both the effects of investment from listed VCs, but no signaling effect and a weak governance effect of investment from non‐listed VCs. Our analysis provides new insights into how VC investment improves the performance of target firms.
Population pharmacokinetics and pharmacodynamics of dobutamine in neonates on the first days of life
Authors: Hallik Maarja , Ilmoja Mari‐Liis , Standing Joseph F. , Soeorg Hiie , Jalas Tiiu , Raidmäe Maila , Uibo Karin , Köbas Kristel , Sõnajalg Margit , Takkis Kalev , Veigure Rūta , Kipper Karin , Starkopf Joel , Metsvaht Tuuli 
Published: October 2019

AimsTo describe the pharmacokinetics (PK) and concentration‐related effects of dobutamine in critically ill neonates in the first days of life, using nonlinear mixed effects modelling.MethodsDosing, plasma concentration and haemodynamic monitoring data from a dose‐escalation study were analysed with a simultaneous population PK and pharmacodynamic model. Neonates receiving continuous infusion of dobutamine 5–20 μg kg−1 min−1 were included. Left ventricular ejection fraction (LVEF) and cardiac output of right and left ventricle (RVO, LVO) were measured on echocardiography; heart rate (HR), mean arterial pressure (MAP), peripheral arterial oxygen saturation and cerebral regional oxygen saturation were recorded from patient monitors.ResultsTwenty‐eight neonates with median (range) gestational age of 30.4 (22.7–41.0) weeks and birth weight (BW) of 1618 (465–4380) g were included. PK data were adequately described by 1‐compartmental linear structural model. Dobutamine clearance (CL) was described by allometric scaling on BW with sigmoidal maturation function of postmenstrual age (PMA). The final population PK model parameter mean typical value (standard error) estimates, standardised to median BW of 1618 g, were 41.2 (44.5) L h−1 for CL and 5.29 (0.821) L for volume of distribution, which shared a common between subject variability of 29% (17.2%). The relationship between dobutamine concentration and RVO/LVEF was described by linear model, between concentration and LVO/HR/MAP/cerebral fractional tissue oxygen extraction by sigmoidal Emax model.ConclusionIn the postnatal transitional period, PK of dobutamine was described by a 1‐compartmental linear model, CL related to BW and PMA. A concentration–response relationship with haemodynamic variables has been established.
A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicity
Authors: Helsby Nuala A. , Duley John , Burns Kathryn E. , Bonnet Claire , Jeong Soo Hee , Brenman Elliott , Barlow Paula , Sharples Katrina , Porter David , Findlay Michael 
Published: October 2019

AimsA previous study suggested that a thymine (THY) challenge dose could detect aberrant pharmacokinetics in known cases of fluoropyrimidine toxicity compared with healthy volunteers. The preliminary data suggested that urine sampling also could detect this aberrant disposition. The aim of this case–control study was to assess the ability of the urinary THY challenge test to discriminate cases of severe gastrointestinal toxicity in a cohort of patients treated with 5‐fluorouracil or capecitabine.MethodsPatients (n = 37) received a 250 mg (per os) dose of THY and a cumulative urine sample was collected for 0–4 h. The urinary amounts of THY and metabolite dihydrothymine (DHT) were determined by liquid chromatography/mass spectrometry. Genomic DNA was analysed for DPYD gene variants. Renal function was estimated from blood creatinine levels. Cases (n = 9) and noncases (n = 23) of severe (grade ≥ 3) gastrointestinal toxicity were defined based on Common Terminology Criteria for Adverse Events.ResultsThe median THY/DHT ratios were 6.2 (interquartile range 2.9–6.4) in cases, including the 2 patients who were DPYD heterozygous carriers. However, this was not significantly different (P = .07) from the THY/DHT in noncases (median 2.6, interquartile range 2.8–4.2). Although creatinine clearance was lower (P = .001) in cases, renal function could not discriminate cases from noncases. However, logistic regression analysis using both of these explanatory variables could discriminate most cases (receiver operating characteristic area 0.8792, 95% confidence interval 0.72–1.00).ConclusionsThe THY challenge test combined with a patient's renal function may be useful as a phenotypic diagnostic test to detect risk of life‐threatening fluoropyrimidine gastrointestinal toxicity.
Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients
Authors: Bruin Gerard , Hockey Hans‐Ulrich P. , La Stella Phillip , Sigurgeirsson Bárdur , Fu Rong , Patekar Manmath , Charef Pascal , Woessner Ralph , Boutouyrie‐Dumont Bruno 
Published: October 2019

AimsThe aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL.MethodsA phase 1 study in healthy subjects with 6 devices to administer 2 mL injection volumes was conducted to evaluate the serum PK, safety and tolerability of secukinumab following single s.c. injection of 300 mg in the abdomen (either side) or in the thigh (either leg). Primary PK endpoints were maximum observed serum concentration and area under the serum concentration–time curve. The impact of device, site and side of injection on serum exposure was evaluated. In a phase 3 study in psoriasis patients, PK of secukinumab was evaluated following multiple s.c. injections of 300 mg by either 2 × 1‐mL prefilled syringe or 1 × 2‐mL prefilled syringe.ResultsMean serum concentration–time profiles for administration as 2 × 1 mL injections or as 1 × 2 mL injections were similar. With an injection volume of 2 mL, perceived injection pain was not different from 2 × 1 mL injections. A nonclinically significant difference in PK endpoints was observed between thigh and abdomen. Results with a 2 mL prefilled syringe in a 1‐year phase 3 study in patients confirmed PK results observed in the phase 1 study.ConclusionCollective evidence from both studies demonstrated that 2‐mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticeable local reactions.
Sex‐specific behavioural deficits induced at early life by prenatal exposure to the cannabinoid receptor agonist WIN55, 212‐2 depend on mGlu5 receptor signalling
Authors: Manduca Antonia , Servadio Michela , Melancia Francesca , Schiavi Sara , Manzoni Olivier J. , Trezza Viviana 
Published: October 2019

Background and PurposeMarijuana is the illicit drug most commonly used among pregnant and breastfeeding women. Different studies reported long‐term adverse effects induced by in utero exposure to the main component of marijuana, Δ9‐tetrahydrocannabinol (THC), both in rodents and in humans. However, little is known about any potential sex‐dependent effects of marijuana consumption during pregnancy on newborns at early developmental ages.Experimental ApproachWe studied the effects of prenatal exposure to the cannabinoid receptor agonist WIN55,212‐2 (WIN; 0.5 mg·kg−1 from GD5 to GD20) on the emotional reactivity and cognitive performance of male and female rat offspring from infancy through adolescence and tested the role of mGlu5 receptor signalling in the observed effects.Key ResultsPrenatally WIN‐exposed male infant pups emitted less isolation‐induced ultrasonic vocalizations compared with male control pups, when separated from the dam and siblings and showed increased locomotor activity while females were spared. These effects were normalized when male pups were treated with the positive allosteric modulator of mGlu5 receptor CDPPB. When tested at the prepubertal and pubertal periods, WIN‐prenatally exposed rats of both sexes did not show any difference in social play behaviour, anxiety and temporal order memory.Conclusions and ImplicationsWe reveal a previously undisclosed sexual divergence in the consequences of fetal cannabinoids on newborns at early developmental ages, which is dependent on mGlu5 receptor signalling. These results provide new impetus for the urgent need to investigate the functional and behavioural substrates of prenatal cannabinoid exposure in both the male offspring and the female offspring.
Vasodilation of rat skeletal muscle arteries by the novel BK channel opener GoSlo is mediated by the simultaneous activation of BK and Kv7 channels
Authors: Zavaritskaya Olga , Dudem Srikanth , Ma Dongyu , Rabab Kaneez E. , Albrecht Sarah , Tsvetkov Dmitry , Kassmann Mario , Thornbury Keith , Mladenov Mitko , Kammermeier Claire , Sergeant Gerard , Mullins Nicholas , Wouappi Ornella , Wurm Hannah , Kannt Aimo , Gollasch Maik , Hollywood Mark A. , Schubert Rudolf 
Published: October 2019

Background and PurposeBK channels play important roles in various physiological and pathophysiological processes and thus have been the target of several drug development programmes focused on creating new efficacious BK channel openers, such as the GoSlo‐SR compounds. However, the effect of GoSlo‐SR compounds on vascular smooth muscle has not been studied. Therefore, we tested the hypothesis that GoSlo‐SR compounds dilate arteries exclusively by activating BK channels.Experimental ApproachExperiments were performed on rat Gracilis muscle, saphenous, mesenteric and tail arteries using isobaric and isometric myography, sharp microelectrodes, digital droplet PCR and the patch‐clamp technique.Key ResultsGoSlo‐SR compounds dilated isobaric and relaxed and hyperpolarised isometric vessel preparations and their effects were abolished after (a) functionally eliminating K+ channels by pre‐constriction with 50 mM KCl or (b) blocking all K+ channels known to be expressed in vascular smooth muscle. However, these effects were not blocked when BK channels were inhibited. Surprisingly, the Kv7 channel inhibitor XE991 reduced their effects considerably, but neither Kv1 nor Kv2 channel blockers altered the inhibitory effects of GoSlo‐SR. However, the combined blockade of BK and Kv7 channels abolished the GoSlo‐SR‐induced relaxation. GoSlo‐SR compounds also activated Kv7.4 and Kv7.5 channels expressed in HEK 293 cells.Conclusion and ImplicationsThis study shows that GoSlo‐SR compounds are effective relaxants in vascular smooth muscle and mediate their effects by a combined activation of BK and Kv7.4/Kv7.5 channels. Activation of Kv1, Kv2 or Kv7.1 channels or other vasodilator pathways seems not to be involved.