bluuebunny/crossref_metadata_2025_split huggingface dataset:
A positive feedback-based mechanism for constriction rate acceleration during cytokinesis inC. elegans
Authors: Khaliullin Renat N. , Green Rebecca A. , Shi Linda Z. , Gomez-Cavazos J. Sebastian , Berns Michael W. , Desai Arshad , Oegema Karen 
Published: July 2017

ABSTRACTDuring cytokinesis, an equatorial actomyosin contractile ring constricts at a relatively constant overall rate despite its progressively decreasing size. Thus, the per-unit-length rate of ring closure increases as ring perimeter decreases. To understand this acceleration, we monitored cortical surface and ring component dynamics during the first division of theC. elegansembryo. We show that the polar cortex expands during ring constriction to provide the cortical surface area required for division. Polar expansion also allows ring myosin to compress cortical surface along the pole-to-pole axis, leading to a continuous flow of cortical surface into the ring. We propose that feedback between ring myosin and compression-driven cortical flow drives an exponential increase in the amount of ring myosin that maintains the high overall closure rate as ring perimeter decreases. We further show that an analytical mathematical formulation of the proposed feedback, called the Compression Feedback model, recapitulates the experimental observations.IMPACT STATEMENTDuring cytokinesis, positive feedback between myosin motors in the contractile ring and compression-driven cortical flow along the axis perpendicular to the ring drives constriction rate acceleration to ensure timely cell separation.MAJOR SUBJECT AREASCell biology, Computational and Systems Biology
Cyanobacterial Growth on Municipal Wastewater Requires Low Temperatures
Authors: Korosh Travis C. , Dutcher Andrew , Pfleger Brian F. , McMahon Katherine D. 
Published: July 2017

ABSTRACTSide-streams in wastewater treatment plants can serve as concentrated sources of nutrients (i.e. nitrogen and phosphorus) to support the growth of photosynthetic organisms that ultimately serve as feedstock for production of fuels and chemicals. However, other chemical characteristics of these streams may inhibit growth in unanticipated ways. Here, we evaluated the use of liquid recovered from municipal anaerobic digesters via gravity belt filtration as a nutrient source for growing the cyanobacteriumSynechococcussp. strain PCC 7002. The gravity belt filtrate (GBF) contained high levels of complex dissolved organic matter (DOM), which seemed to negatively influence cells. We investigated the impact of GBF on physiological parameters such as growth rate, membrane integrity, membrane composition, photosystem composition, and oxygen evolution from photosystem II. At 37°C, we observed an inverse correlation between GBF concentration and membrane integrity. Radical production was also detected upon exposure to GBF at 37°C. However, at 27°C the dose dependent relationship between GBF concentration and lack of membrane integrity was abolished. Immediate resuspension of strains in high doses of GBF showed markedly reduced oxygen evolution rates relative to the control. Together, this suggests that one mechanism responsible for GBF toxicity toSynechococcusis the interruption of photosynthetic electron flow and subsequent phenomena. We hypothesize this is likely due to the presence of phenolic compounds within the DOM.IMPORTANCECyanobacteria are viewed as promising platforms to produce fuels and/or high-value chemicals as part of so-called “bio-refineries”. Their integration into wastewater treatment systems is particularly interesting because removal of the nitrogen and phosphorus in many wastewater streams is an expensive but necessary part of wastewater treatment. In this study, we evaluated strategies for cultivatingSynechococcusstrain PCC 7002 on media comprised of two wastewater streams; treated secondary effluent supplemented with the liquid fraction extracted from sludge following anaerobic digestion. This strain is commonly used for metabolic engineering to produce a variety of valuable chemical products and product precursors (e.g. lactate). However, initial attempts to grow PCC 7002 under otherwise standard conditions of light and temperature failed. We thus systematically evaluated alternative cultivation conditions and then used multiple methods to dissect the apparent toxicity of the media under standard cultivation conditions.
Psychotropic polypharmacy in Australia, 2006 to 2015: a descriptive cohort study
Authors: Brett Jonathan , Daniels Benjamin , Karanges Emily A. , Buckley Nicholas A. , Schneider Carl , Nassir Atheer , McLachlan Andrew J. , Pearson Sallie‐Anne 
Published: July 2017

AimsTo describe psychotropic polypharmacy in Australia between 2006 and 2015.MethodsWe used pharmaceutical claims from a national 10% sample of people with complete dispensing histories to estimate the annual prevalence of the combined use (overlap of >60 days exposure) of ≥2 psychotropics overall and within the same class or subclass (class and subclass polypharmacy). We also estimated the proportion of polypharmacy episodes involving one, two, three and four or more unique prescribers.ResultsThe prevalence of class polypharmacy between 2006 and 2015 in people dispensed specific psychotropic classes was 5.9–7.3% for antipsychotics, 2.1–3.7% for antidepressants and 4.3–2.9% for benzodiazepines. The prevalence of antipsychotic polypharmacy was higher than expected given the prevalence of antipsychotic exposure and combinations of sedating agents were notably common. Overall, 26.7% of polypharmacy episodes involved multiple prescribers but having multiple prescribers occurred more frequently for class and subclass polypharmacy and people with four or more concomitant psychotropics.DiscussionPsychotropic polypharmacy is common, despite limited evidence of risks and benefits. Increases in polypharmacy with multiple prescribers may be due to poor communication with patients and between health care professionals.
Intra‐Target Microdosing – A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans
Authors: Burt T , MacLeod D , Lee K , Santoro A , DeMasi DK , Hawk T , Feinglos M , Rowland M , Noveck RJ 
Published: July 2017

AbstractIntra‐Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first‐in‐human (FIH) testing of new molecular entities (NMEs). ITM combines intra‐target drug delivery and “microdosing,” the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic‐level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18F‐fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well‐tolerated. Results are consistent with ITM proof‐of‐concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach.
Identification of OAT1/OAT3 as Contributors to Cisplatin Toxicity
Authors: Hu S , Leblanc AF , Gibson AA , Hong KW , Kim JY , Janke LJ , Li L , Vasilyeva A , Finkelstein DB , Sprowl JA , Sweet DH , Schlatter E , Ciarimboli G , Schellens JHM , Baker SD , Pabla N , Sparreboom A 
Published: July 2017

AbstractCisplatin is among the most widely used anticancer drugs and known to cause a dose‐limiting nephrotoxicity, which is partially dependent on the renal uptake carrier OCT2. We here report a previously unrecognized, OCT2‐independent pathway of cisplatin‐induced renal injury that is mediated by the organic anion transporters OAT1 and OAT3. Using transporter‐deficient mouse models, we found that this mechanism regulates renal uptake of a mercapturic acid metabolite of cisplatin that acts as a precursor of a potent nephrotoxin. The function of these two transport systems can be simultaneously inhibited by the tyrosine kinase inhibitor nilotinib through noncompetitive mechanisms, without compromising the anticancer properties of cisplatin. Collectively, our findings reveal a novel pathway that explains the fundamental basis of cisplatin‐induced nephrotoxicity, with potential implications for its therapeutic management.
Modelling the spatial variation of vital rates: An evaluation of the strengths and weaknesses of correlative species distribution models
Authors: Suárez‐Seoane Susana , Álvarez‐Martínez Jose Manuel , Wintle Brendan A. , Palacín Carlos , Alonso Juan C. 
Published: July 2017

AbstractAimSpecies distribution models based on breeding occurrence data allow for identifying both environmental drivers and geographic areas potentially relevant for breeding. However, the interpretation of model predictions in terms of reproductive performance should be further investigated, as this information is crucial for conservation planning. We evaluated the strengths and weaknesses of a correlative modelling approach based on breeding occurrence data (presence–absence) against another approach based on vital rates’ data (breeding success) for gaining insights on species persistence in the case of Great Bustards (Otis tarda).LocationSpain.MethodsBreeding occurrence and breeding success were independently modelled using generalized linear models and multimodel inference analyses. Sensitivities to the way in which the population parameter (breeding success) was defined were explored by building five versions of the dependent variable. We evaluated differences in model performance and identified areas of congruence for breeding occurrence and breeding success.ResultsThe agreement between the spatial predictions achieved by breeding occurrence and breeding success models differed substantially across databases, with the largest differences in occupied breeding areas. The deviance explained by the breeding occurrence model was 64.98% and ranged from 7.83% to 62.27% for the breeding success models. Model performance was higher for models calibrated within potential than within occupied breeding areas.Main conclusionsThe combination of data on both breeding occurrence and breeding success into a species distribution modelling framework showed the limitations of breeding occurrence models for inferring reproductive parameters. The definition of the population parameter as dependent variable was a key factor that strongly affected the inference of vital rates’ models. The approach allowed for discriminating between areas and landscape attributes necessary for the long‐term species persistence from others that may be relevant, but not so much for reproductive performance.
Deficits of ankle muscle strength not found in children, adolescents and young adults with haemophilic ankle arthropathy
Authors: Lobet S. , Croisier J.‐L. , Lantin A.‐C. , Hermans C. , Peerlinck K. , Vandesande J. , Pialat J.‐B. , Deschamps K. 
Published: July 2017

ObjectivesAdequate management of haemophilia patients requires early detection of joint impairment in relatively asymptomatic patients. This study sought to quantify the impact of the ankle's structural impairment on muscle strength in children, adolescent and young adults with haemophilia (CAAwH).MethodsTwenty‐three CAAwH underwent bilateral magnetic resonance imaging (MRI) assessing the anatomical status of tibiotalar joint (TTJ) and subtalar joint (STJ) using the International Prophylaxis Study Group MRI scale. An isokinetic dynamometer enabled a detailed evaluation of muscle strength at slow and fast speed. In parallel, 10 typically developing healthy boys (TDB) participated in a 1‐week interval test‐retest assessment to assess the test's reliability.ResultsForty‐six MRI ankle scores were obtained, with 11 patients unilaterally affected and one bilaterally. Of the 13 affected feet, nine showed abnormalities at TTJ, three at the posterior STJ and the remaining one at both joints. Muscle strength was not reduced in CAAwH exhibiting TTJ and/or STJ arthropathy, as compared to healthy TDB, nor was there any difference between the CAAwH's affected or unaffected sides.ConclusionContrarily to adult patients, CAAwH with repeated ankle bleeding may be less impaired than current structural evaluations imply, with possibly a latency between the occurrence of structural and functional damage.
Acupuncture Attenuates Hyperglycaemia and Improves Ovarian Function in Female Rats Subjected to Continuous Light Exposure
Authors: Kang Xuezhi , Jia Lina , Li Yaming , Zhang Xu 
Published: July 2017

Objective Exposure to unnatural light cycles is increasingly associated with obesity and the metabolic syndrome. The purpose of this study was to examine the effects of electroacupuncture (EA) on glucose metabolism and ovarian function in female rats subjected to long-term continuous light exposure. Methods Female Sprague-Dawley rats (n=24) were divided into three experimental groups: an LD group that was maintained under a normal light-dark cycle (healthy control); an LL group that was exposed to continuous light for 21 weeks but remained untreated; and an LL+EA group that received EA at ST36 and SP6 during weeks 17 to 21 of continuous light exposure. Results Oestrous cycles of female rats kept in a continuously lit environment for 21 weeks were disordered and polycystic ovarian syndrome (PCOS)-like changes occurred, accompanied by increased fasting blood glucose (6.23±0.33 vs 5.27±0.40 mmol/L in week 17, p=0.015) and reduced fasting levels of serum testosterone (0.07±0.018 vs 0.12±0.058 ng/L, p=0.043) and insulin (0.89±0.20 vs 1.43±0.46 ng/L, p=0.006). After 5 weeks of EA treatment at ST36 and SP6, ovarian cycle disruption was mitigated and blood glucose levels showed a gradual decline (5.18±0.37 vs 5.80±0.55 mmol/L, p=0.017; and 5.73±0.31 vs 6.62±0.13 mmol/L, p=0.004; in the fourth and fifth weeks of EA treatment, respectively). EA also attenuated the reductions otherwise seen in serum insulin and testosterone levels. Conclusion Prolonged exposure to light can lead to a decline in ovarian and pancreatic function. EA at ST36 and SP6 may reduce abnormally elevated blood glucose levels and improve ovarian and pancreatic hormone levels.
Acupuncture for the Treatment of Gastro-Oesophageal Reflux Disease: A Systematic Review and Meta-Analysis
Authors: Zhu Jiajie , Guo Yu , Liu Shan , Su Xiaolan , Li Yijie , Yang Yang , Hou Liwei , Wang Guishu , Zhang Jiaxin , Chen Jiande JD , Wang Qingguo , Wei Ruhan , Wei Wei 
Published: July 2017

Background Gastro-oesophageal reflux disease (GORD) is one of the most common diseases presenting to gastroenterology clinics. Acupuncture is widely used as a complementary and alternative treatment for patients with GORD. Objective To explore the effectiveness of acupuncture for the treatment of GORD. Methods Four English and four Chinese databases were searched through June 2016. Randomised controlled trials investigating the effectiveness of manual acupuncture or electroacupuncture (MA/EA) for GORD versus or as an adjunct to Western medicine (WM) were selected. Data extraction and quality evaluation were performed by two authors independently and RevMan 5.2.0 was used to analyse data. Results A total of 12 trials involving 1235 patients were included. Meta-analyses demonstrated that patients receiving MA/EA combined with WM had a superior global symptom improvement compared with those receiving WM alone (relative risk (RR) 1.17, 95% CI 1.09 to 1.26; p=0.03; six studies) with no significant heterogeneity (I2=0%, p=0.41). Recurrence rates of those receiving MA/EA alone were lower than those receiving WM (RR 0.42,95% CI 0.29 to 0.61; p<0.001; three studies) with low heterogeneity (I2=7%, p=0.34), while global symptom improvement (six studies) and symptom scores (three studies) were similar (both p>0.05). Descriptive analyses suggested that acupuncture also improves quality of life in patients with GORD. Conclusion This meta-analysis suggests that acupuncture is an effective and safe treatment for GORD. However, due to the small sample size and poor methodological quality of the included trials, further studies are required to validate our conclusions. Trial registration number PROSPERO Systematic review registration no. CRD42016041916.
Late outcomes of gold weights and platinum chains for upper eyelid loading
Authors: Siah We Fong , Nagendran Sonali , Tan Petrina , Ali Ahmad Syed Mustafa , Litwin Andre S , Malhotra Raman 
Published: July 2017

AimTo identify late outcomes of gold weights (GWs) and platinum chains (PCs) for upper eyelid loading in the management of lagophthalmos.MethodsA retrospective case series of upper eyelid GWs and PCs at a single centre over a 10-year period (2004–2013). Two independent, blinded assessors graded standard photographs for any weight-related morbidity (poor upper eyelid contour, weight prominence and migration).ResultsPrimary upper eyelid loading (high-tarsal technique) was performed in 154 eyelids of 136 patients (facial nerve palsy, n=99; non-paralytic, n=37). A total of 127 eyelids of 110 patients had primary GW insertion. Of these, 40.9% (52/127) had revision surgery: exchange of GW for PC (58%), GW repositioning (25%) and removal of GW (17%). Only 22.2% (6/27 eyelids) with primary PCs required revision surgery. In those not requiring revision surgery, photograph grading showed that both GWs and PCs had weight-related morbidity at late follow-up (median=37.5 months, range 12–110 vs median=33.5 month, range 15–106). GWs had significantly higher rate of weight prominence (p=0.001) and migration (p<0.001) compared with PCs. All PC revisions required one procedure only compared with 10% of GWs revisions requiring two or more procedures. Incidence of gold allergy was 7% (8/110 patients). There was no association between the choice of weight material, physical weight or suture material and eyelid morbidities.ConclusionGWs were found to be associated with higher complications and twice more likely to require long-term revision surgery compared with PCs. Despite weight fixation at a high-tarsal location, prominence of PCs can still occur.
Systemic diseases in patients with HTLV-1-associated uveitis
Authors: Nakao Kumiko , Abematsu Noriko , Sakamoto Taiji 
Published: July 2017

BackgroundHuman T-lymphotropic virus type 1 (HTLV-1) carriers may develop severe systemic diseases, such as adult T cell leukaemia (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This study aims to investigate systemic diseases of HTLV-1 carriers who had developed HTLV-1-associated uveitis (HAU).MethodsWe investigated the occurrence of systemic diseases in 200 patients with HAU by performing a retrospective investigation of their medical records and examining the results of a postal survey.ResultsThe mean age of HAU onset was 49 years, and the total person-years from HAU onset was 1627. There were two cases of ATL. Of these, one was diagnosed with smouldering ATL at the time of HAU onset and the other developed acute-type ATL 4 years after HAU onset. There were 26 cases of HAM/TSP; of these, HAM/TSP occurred first in 13 cases and HAU occurred first in 11 cases. The interval between the onset of HAM/TSP and HAU ranged from 6 months to 6 years, with no significant difference observed based on whether HAM/TSP or HAU occurred first. Hyperthyroidism was noted in 45 cases and preceded onset in all cases. HAU onset occurred after starting thiamazole treatment, and in two cases HAU recurred each time thiamazole treatment was restarted.ConclusionHTLV-1 carriers with HAU may develop HAM/TSP more frequently than general carriers. HTLV-1 carriers undergoing treatment for hyperthyroidism may be prone to developing HAU.
Head impact velocities in FIS World Cup snowboarders and freestyle skiers: Do real-life impacts exceed helmet testing standards?
Authors: Steenstrup Sophie E , Mok Kam-Ming , McIntosh Andrew S , Bahr Roald , Krosshaug Tron 
Published: July 2017

IntroductionPrior to the 2013–2014 season, the International Ski Federation (FIS) increased the helmet testing speed from a minimum requirement of 5.4 to 6.8 m/s for alpine downhill, super-G and giant slalom and for freestyle ski cross, but not for the other freestyle disciplines or snowboarding. Whether this increased testing speed reflects impact velocities in real head injury situations on snow is unclear. We therefore investigated the injury mechanisms and gross head impact biomechanics in four real head injury situations among World Cup (WC) snowboard and freestyle athletes and compared these with helmet homologation laboratory test requirements. The helmets in the four cases complied with at least European Standards (EN) 1077 (Class B) or American Society for Testing and Materials (ASTM) F2040.MethodsWe analysed four head injury videos from the FIS Injury Surveillance System throughout eight WC seasons (2006–2014) in detail. We used motion analysis software to digitize the helmet’s trajectory and estimated the head’s kinematics in two dimensions, including directly preimpact and postimpact.ResultsAll four impacts were to the occiput. In the four cases, the normal-to-slope preimpact velocity ranged from 7.0(±SD 0.2) m/s to 10.5±0.5 m/s and the normal-to-slope velocity change ranged from 8.4±0.6 m/s to 11.7±0.7 m/s. The sagittal plane helmet angular velocity estimates indicated a large change in angular velocity (25.0±2.9 rad/s to 49.1±0.3 rad/s).ConclusionThe estimated normal-to-slope preimpact velocity was higher than the current strictest helmet testing rule of 6.8 m/s in all four cases.
Association of the DASH dietary pattern with insulin resistance and diabetes in US Hispanic/Latino adults: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Corsino Leonor , Sotres-Alvarez Daniela , Butera Nicole M , Siega-Riz Anna María , Palacios Cristina , Pérez Cynthia M , Albrecht Sandra S , Espinoza Giacinto Rebecca A , Perera Marisa Judith , Horn Linda Van , Avilés-Santa M. Larissa 
Published: July 2017

ObjectiveTo examine the association between diet quality and both diabetes status and insulin resistance in Hispanic/Latino adults, and the extent to which differences in diet quality contribute to differences in outcomes across Hispanic/Latino heritage.Research design and methodsCross-sectional study. Data are from 15 942 individuals enrolled in the Hispanic Community Health Study/Study of Latinos. Diet was ascertained using two 24-hour dietary recalls, and diet quality was measured using the Dietary Approaches to Stop Hypertension (DASH) score (range: 0–80, lowest to highest). Diabetes status was defined based on self-reported diagnosis, use of antihyperglycemic medications, or unrecognized diabetes (determined by baseline laboratory measures). Insulin resistance was determined using homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR). The association between DASH and diabetes status was examined using multinomial logistic regression. The association between DASH and HOMA-IR was assessed using linear regression, and we tested whether the association was modified by Hispanic/Latino heritage or diabetes status.ResultsDASH score was highest in those with self-reported diabetes (controlled) and no medications (44.8%). A higher DASH score was associated with a lower HOMA-IR, and the association was the same regardless of diabetes status (p>0.8 for the interaction).ConclusionsThe association between DASH and diabetes status was strongest for those with controlled self-reported diabetes and who were not taking antihyperglycemic medications. A higher DASH score was associated with less insulin resistance among Hispanics/Latinos. Differences in DASH scores by Hispanic/Latino heritage did not explain the differences in prevalence of diabetes and insulin resistance reported in the diverse Hispanic/Latino population.Clinical trial numberNCT02060344