bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome
Authors: Larionov Alexey , Dahlke Eileen , Kunke Madlen , Zanon Rodriguez Luis , Schiessl Ina M. , Magnin Jean‐Luc , Kern Ursula , Alli Abdel A. , Mollet Geraldine , Schilling Oliver , Castrop Hayo , Theilig Franziska 
Published: August 2019

AbstractThe NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a proteinuria‐dependent fashion have been made responsible; however, referring to the timeline of symptoms occurring and underlying mechanisms, contradictory results have been published. Characterizing the mouse model of podocyte inactivation of NPHS2 (Nphs2∆pod) with respect to volume handling and proteinuria revealed that sodium retention, hypertension and gross proteinuria appeared sequentially in a chronological order. Detailed analysis of Nphs2∆pod during early sodium retention, revealed increased expression of full‐length ENaC subunits and αENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na+/K+‐ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process αENaC. Renal expression levels of precursor and active cathepsin B were increased and could be localized to glomeruli and intercalated cells. Inhibition of cathepsin B prevented hypertension. With the appearance of gross proteinuria, plasmin occurs in the urine and additional cleavage of γENaC is encountered. In conclusion, characterizing the volume handling of Nphs2∆pod revealed early sodium retention occurring independent to aberrantly filtered plasma proteases. As an underlying mechanism cathepsin B induced αENaC processing leading to augmented channel activity and hypertension was identified.
Hepatic pedicle endometriosis: Case report and review of the literature
Authors: Eychenne Camille , Suc Bertrand , Delchier Marie C. , Vidal Fabien , Rimailho Jacques , Illac Claire , Breibach Florence , Vaysse Charlotte , Chantalat Elodie 
Published: August 2019

AbstractThe localization of endometriotic disease in the hepatic pedicle has never been reported to date. We report the first case of a 67‐year‐old postmenopausal patient having presented an endometriotic lesion in the hepatic pedicle. A surgical biopsy was needed to confirm the diagnosis after a first radiologic biopsy that concluded the presence of a mucinous cystic tumor with low‐grade dysplasia. Medical treatment with aromatase inhibitors was carried out because of the inextirpable nature of the lesion. The diagnosis and therapeutic management of this rarely occurring lesion of atypical localization in a postmenopausal patient is presented here. A review of the literature on this localization could have led to a damaging surgical treatment due to the different diagnoses suggested. Management of endometriosis relies on a multidisciplinary approach that each practitioner must know how to broach with patients of all ages.
Impact of inhaled nitric oxide stewardship programme in a neonatal intensive care unit
Authors: Ahearn Joshua , Panda Malavika , Carlisle Hazel , Chaudhari Tejasvi 
Published: August 2019

AimInhaled nitric oxide (iNO) is the most common, although expensive, therapy for persistent pulmonary hypertension of the newborn and hypoxaemic respiratory failure. With significant variation in iNO delivery practices amongst clinicians, this study aimed to assess the effectiveness of a stewardship programme in increasing clinician compliance with revised, standardised protocols and to measure the impact of compliance on iNO therapy use.MethodsInitiation and weaning protocols for iNO were introduced to the neonatal intensive care unit at The Centenary Hospital on 01 March 2016. A 2‐year stewardship programme was utilised to assess protocol compliance and the resulting iNO usage impacts were measured. A combined retrospective and prospective study from 1 March 2014 to 28 February 2018 was conducted to compare the patterns of iNO utilisation between the pre‐ and post‐stewardship cohorts.ResultsThe pre‐stewardship cohort incorporated 18 neonates, receiving 19 iNO treatment episodes, and 18 neonates, receiving 21 iNO treatment episodes, in the post‐stewardship cohort. No significant difference in patient demographics was determined. Compliance with the protocols improved from 61% in year 1 to 88% in year 2 of the stewardship programme. Significant reductions were observed in median total hours of iNO therapy per patient (P = 0.0014) and in median time from therapy initiation to initial wean (P < 0.0001). The cost of iNO therapy reduced 52% during the stewardship programme with no increase in adverse patient outcomes.ConclusionAn iNO stewardship programme could be safely implemented in any NICU leading to increased protocol compliance with a beneficial reduction in iNO usage and cost.
Melatonin protects mouse oocytes from DNA damage by enhancing nonhomologous end‐joining repair
Authors: Leem Jiyeon , Bai Guang‐Yu , Kim Jae‐Sung , Oh Jeong Su 
Published: August 2019

AbstractMammalian oocytes remain arrested at the first prophase of meiosis in ovarian follicles for an extended period. During this protracted arrest, oocytes are remarkably susceptible to the accumulation of DNA damage. Melatonin (N‐acetyl‐5‐methoxytryptamine), a hormone secreted by the pineal gland, has diverse effects on various physiological processes. However, the effect of melatonin on DNA damage response in mammalian oocytes has not been explored. Here, we showed that melatonin protected mouse oocytes from DNA damage induced by double‐strand breaks (DSBs) during prophase arrest and subsequently improved oocyte quality. We found that DNA damage during prophase arrest impaired subsequent meiotic maturation and deteriorated oocyte quality, increasing chromosome fragmentation, spindle abnormality, mitochondrial aggregation, and oxidative stress. However, melatonin treatment during DNA damage accumulation at prophase improved meiotic maturation and relieved the quality decline of oocytes. In addition, melatonin inhibited the accumulation of DNA damage during prophase arrest by reducing the γ‐H2AX levels. Although activated ATM levels were decreased by melatonin treatment, the effect of melatonin on DNA damage response was not a direct consequence of ATM inhibition. Instead, melatonin enhanced DNA repair via nonhomologous end‐joining (NHEJ) pathway. Interestingly, these actions of melatonin on DNA damage response are receptor‐independent in mouse oocytes. Therefore, our results demonstrated that melatonin protects oocytes from DNA damage during prophase arrest by enhancing DNA repair via NHEJ and subsequently prevents the deterioration of oocyte quality during meiotic maturation.
Nonlinear mixed‐effects pharmacokinetic modeling of the novel COX‐2 selective inhibitor vitacoxib in dogs
Authors: Wang Jianzhong , Schneider Benjamin K. , Sun Pan , Gong Xiaohui , Qiu Jicheng , Li Jing , Seo Yeon‐Jung , Mochel Jonathan P. , Cao Xingyuan 
Published: August 2019

AbstractThe objective of this study was to develop a nonlinear mixed‐effects model of vitacoxib disposition kinetics in dogs after intravenous (I.V.), oral (P.O.), and subcutaneous (S.C.) dosing. Data were pooled from four consecutive pharmacokinetic studies in which vitacoxib was administered in various dosing regimens to 14 healthy beagle dogs. Plasma concentration versus time data were fitted simultaneously using the stochastic approximation expectation maximization (SAEM) algorithm for nonlinear mixed‐effects as implemented in Monolix version 2018R2. Correlations between random effects and significance of covariates on population parameter estimates were evaluated using multiple samples from the posterior distribution of the random effects. A two‐compartment mamillary model with first‐order elimination and first‐order absorption after P.O. and S.C. administration, best described the available pharmacokinetic data. Final parameter estimates indicate that vitacoxib has a low‐to‐moderate systemic clearance (0.35 L hr−1 kg−1) associated with a low global extraction ratio, but a large volume of distribution (6.43 L/kg). The absolute bioavailability after P.O. and S.C. administration was estimated at 10.5% (fasted) and 54.6%, respectively. Food intake was found to increase vitacoxib oral bioavailability by a fivefold, while bodyweight (BW) had a significant impact on systemic clearance, thereby confirming the need for BW adjustment with vitacoxib dosing in dogs.
Japan's nationwide long‐term monitoring survey of seaweed communities known as the “Monitoring Sites 1000”: Ten‐year overview and future perspectives
Authors: Terada Ryuta , Abe Mahiko , Abe Takuzo , Aoki Masakazu , Dazai Akihiro , Endo Hikaru , Kamiya Mitsunobu , Kawai Hiroshi , Kurashima Akira , Motomura Taizo , Murase Noboru , Sakanishi Yoshihiko , Shimabukuro Hiromori , Tanaka Jiro , Yoshida Goro , Aoki Misuzu 
Published: August 2019

SUMMARY“Monitoring Sites 1000” – Japan's long‐term monitoring survey was established in 2003, based on the Japanese Government policy for the conservation of biodiversity. Ecological surveys have been conducted on various types of ecosystems at approximately 1000 sites in Japan for 15 years now and are planned to be carried out for 100 years. Since 2008, seaweed communities had been monitored at six sites, featuring the kelp (e.g. Saccharina and Ecklonia; Laminariales) and Sargassum (Fucales) communities in the subarctic and temperate regions of Japan. Annual surveys were carried out during the season when these canopy‐forming seaweeds are most abundant. A non‐destructive quadrat sampling method, with permanent quadrats placed along transects perpendicular to the shoreline, was used to determine species composition, coverage, and vertical distribution of seaweeds at these sites; while destructive sampling was done every 5 years to determine biomass. The occurrence of canopy‐forming species Saccharina japonica (var. japonica) and Ecklonia cava have appeared to be stable at the Muroran (southwestern part of Hokkaido Island) and Shimoda (Pacific coast of middle Honshu Island) sites, respectively; whereas the coverage of Ecklonia radicosa (= Eckloniopsis radicosa) at the Satsuma‐Nagashima site in southern part of Kyushu Island was highly variable until its sudden disappearance from the habitat in 2016. Thalli of E. radicosa lost most of their blades through browsing by herbivorous fish, and thus, this may be one of the causes of the decline. A shift in the community structure related to environmental changes had also been observed at some other sites. Pre‐ and post‐disaster data revealed the impact of the 2011 earthquake and tsunami disasters, including a shift in the vertical distribution of Ecklonia bicyclis (= Eisenia bicyclis) to shallower depths at the Shizugawa site in the Pacific coast of northern Honshu Island, due to seafloor subsidence.
Copper blocks V‐ATPase activity and SNARE complex formation to inhibit yeast vacuole fusion
Authors: Miner Gregory E. , Sullivan Katherine D. , Zhang Chi , Hurst Logan R. , Starr Matthew L. , Rivera‐Kohr David A. , Jones Brandon C. , Guo Annie , Fratti Rutilio A. 
Published: August 2019

AbstractThe accumulation of copper in organisms can lead to altered functions of various pathways and become cytotoxic through the generation of reactive oxygen species. In yeast, cytotoxic metals such as Hg+, Cd2+ and Cu2+ are transported into the lumen of the vacuole through various pumps. Copper ions are initially transported into the cell by the copper transporter Ctr1 at the plasma membrane and sequestered by chaperones and other factors to prevent cellular damage by free cations. Excess copper ions can subsequently be transported into the vacuole lumen by an unknown mechanism. Transport across membranes requires the reduction of Cu2+ to Cu+. Labile copper ions can interact with membranes to alter fluidity, lateral phase separation and fusion. Here we found that CuCl2 potently inhibited vacuole fusion by blocking SNARE pairing. This was accompanied by the inhibition of V‐ATPase H+ pumping. Deletion of the vacuolar reductase Fre6 had no effect on the inhibition of fusion by copper. This suggests that Cu2+ is responsible for the inhibition of vacuole fusion and V‐ATPase function. This notion is supported by the differential effects of chelators. The Cu2+‐specific chelator triethylenetetramine rescued fusion, whereas the Cu+‐specific chelator bathocuproine disulfonate had no effect on the inhibited fusion.
Administration of certain sedative drugs is associated with variation in sonographic and radiographic splenic size in healthy cats
Authors: Auger Mylène , Fazio Constance , de Swarte Marie , Bussières Geneviève , Schaefer Deanna , Springer Cary M. 
Published: August 2019

AbstractUltrasonography and radiography are standard diagnostic tests for cats with suspected splenic disease, however published information on outside sources of variation are currently lacking. The purpose of this prospective, randomized, crossover group study was to evaluate effects of common sedative drugs on the sonographic and radiographic characteristics of the spleen in healthy cats. Fifteen healthy adult research cats were randomly assigned into one of three groups corresponding to different sequences of administration of five sedative drugs/drug combinations (acepromazine; butorphanol; dexmedetomidine; midazolam and butorphanol (MB); and dexmedetomidine, butorphanol, and ketamine (DBK)), administered at 1‐week intervals. At each visit, three‐view abdominal radiographic and ultrasonographic examinations were performed prior to sedation and repeated 15‐30 min and 2‐3 h post sedation. Two board‐certified radiologists (one ACVR and one ACVR/ECVDI) evaluated the anonymized and randomized images. Acepromazine resulted in significantly increased sonographic and radiographic splenic measurements from baseline, which remained significantly increased 2‐3 h post sedation. The mean magnitude of this change ranged from 0.9 mm (tail height, SD 1.4 mm) to 1.8 mm (body height, SD 1.7 mm) for ultrasound, and was 2.2 mm (ventrodorsal width, SD 2.3 mm) for radiographs. With butorphanol, there was no significant change in splenic size. For dexmedetomidine, MB, and DBK, there was a trend toward increased splenic size from baseline to the first post‐sedation timepoint, which was statistically significant for radiographic measurements, although not for ultrasound. Findings indicated that acepromazine should be avoided prior to imaging while butorphanol may be used when sedation is needed in cats presenting for potential splenic disease.
Focused Ultrasound Ablation for the Treatment of Patients With Localized Deformed Breast Cancer: Computer Simulation
Authors: Montienthong Prempreeya , Rattanadecho Phadungsak 
Published: August 2019

Abstract
This paper is carried out on the computer simulation of breast cancer treated using a high intensity focused ultrasound (HIFU). The mathematical models consist of the pressure acoustics equation, bioheat equation, heat transfer in a blood vessel, momentum equations in a blood vessel, and mechanical deformation equation. In the numerical simulation, these mathematical models are solved by using an axisymmetric finite element method (FEM) with time-dependent, thermal and acoustic properties to describe the temperature distribution and the total displacement in tissue. The comparison of the simulated results in the model with two sizes of the cancer tumor and two frequencies of ultrasound are also considered in order to approach realistic tissue modeling. The results show that the breast cancer model with deformation, which is the more accurate way to simulate the physical characteristics of therapeutic breast cancer compared to the literature results, hence leads to more useful in the medical approach and this study was conducted to prevent errors caused by inaccurate focal points.
Preliminary Evidence That Motor Planning Is Slower and More Difficult for Children With Autism Spectrum Disorder During Motor Cooperation
Authors: Studenka Breanna E. , Myers Kodey 
Published: August 2019

Children with autism spectrum disorder (ASD) exhibit impairment in helping someone else with a motor action, which may arise from impairment in selecting and preparing motor responses. Five children with ASD and five typically developing children performed a cooperative motor planning task that required them to reach for, lift, and hand an object (hammer or stick) to a researcher. The response, movement, and grasp time were measured. Children with ASD grasped the object longer on trials where they helped, indicating that the action was planned in sequence versus as a whole (i.e., prior to the onset of movement). The hammer object elicited a quicker response than the stick, suggesting the facilitation of planning by tools with inherent action properties. Finally, the increased helping of children with ASD was not mirrored by changes in the response, movement, or grasp time.
Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study
Authors: Cerani Agustin , Zhou Sirui , Forgetta Vincenzo , Morris John A , Trajanoska Katerina , Rivadeneira Fernando , Larsson Susanna C , Michaëlsson Karl , Richards J Brent 
Published: August 2019

Abstract

Objective
To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures.

Design
Mendelian randomisation study.

Setting
Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics).

Participants
A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association meta-analysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed.

Results

A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm
2
, 95% confidence interval −0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects.

Conclusions
Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.
Fish and marine fatty acids intakes, theFADSgenotypes and long-term weight gain: a prospective cohort study
Authors: Huang Tao , Wang Tiange , Heianza Yoriko , Wiggs Janey , Sun Dianjianyi , Choi Hyon-Kyoo , Chai Jin Fang , Sim Xueling , Khor Chiea Chuen , Friedlander Yechiel , Chan Andrew T , Curhan Gary , Vivo Immaculata De , van Dam Rob Martinu , Heng Chew Kiat , Fuchs Charles , Pasquale Louis R , Yuan Jian-min , Hu Frank B , Koh Woon Puay , Qi Lu 
Published: August 2019

ObjectiveWe tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI).DesignThreeFADSvariants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies.SettingPopulation based study.Participants11 323 women from the Nurses’ Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women’s Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS).Main outcomesLong-term (~10 years) changes in BMI and body weight.ResultsIn the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with theFADSrs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of theFADSrs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of theFADSrs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m2per g, p=3×10−5) than the rs174570 non-T carriers (beta=0.16 kg/m2per g, p=0.08). Similar results were observed for fish intake.ConclusionsOur hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with theFADSvariant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.