bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial proximity and asynchronous refuge sharing networks both explain patterns of tick genetic relatedness among lizards, but in different years
Authors: Wohlfeil Caroline K. , Godfrey Stephanie S. , Leu Stephan T. , Clayton Jessica , Gardner Michael G. 
Published: May 2020

AbstractA major question for understanding the ecology of parasite infections and diseases in wildlife populations concerns the transmission pathways among hosts. Network models are increasingly used to model the transmission of infections among hosts – however, few studies have integrated host behaviour and genetic relatedness of the parasites transmitted between hosts. In a study of the Australian sleepy lizard Tiliqua rugosa and its three‐host ixodid tick (Bothriocroton hydrosauri), we asked if patterns of genetic relatedness among ticks were best explained by spatial proximity or the host transmission network. Using synchronous GPS locations of over 50 adult lizards at 10 min intervals across the three‐month activity period, over 2 years, we developed two alternative parasite transmission networks. One alternative was based on the spatial proximity of lizards (at the centre of their home ranges), and the other was based on the frequency of asynchronous shared refuge use between pairs of lizards. In each year, adult ticks were removed from lizards and their genotypes were determined at four polymorphic microsatellite loci. Adult ticks collected from the same host were more related to each other than ticks from different hosts. Similarly, adult ticks collected from different lizards had a higher relatedness if those lizards had a shorter path length connecting them on each of the two networks we explored. The predictors of tick relatedness differed between years. In the first year, the asynchronous shared refuges network was the stronger predictor of tick relatedness, whereas in year two, the spatial proximity‐based network was the stronger predictor of tick relatedness. We speculate on how changing environmental conditions might change the relative importance of alternative processes driving the transmission of parasites.
Disentangling the Social Context of Nonmedical Use of Prescription Stimulants in College Students
Authors: Wilens Timothy E. , Martelon MaryKate , Yule Amy , Kaminski Tamar A. , Burke Colin , Schepis Ty S. , McCabe Sean E. 
Published: May 2020

Background and ObjectivesThe aim of this study was to investigate the social context of nonmedical use of prescription stimulants (NMUPS) among college students who endorsed NMUPS with co‐occurring substance use disorders (SUD) compared with those without co‐occurring SUDs.MethodsPresented here are new analyses based on data previously collected from college students aged 18 to 28 years derived from the Boston metropolitan area who endorsed NMUPS (N = 100) at least once in their lifetime. Differences between those with lifetime history of SUD (N = 46) and without a history of SUD (N = 54) on the Massachusetts General Hospital ADHD Medication Misuse and Diversion Assessment were analyzed using the Student t test, the Pearson χ2 test, and the Wilcoxon rank‐sum test.ResultsCollege students who endorsed NMUPS with co‐occurring SUD were more likely than those without SUD to have bought or traded stimulants, bought or traded in their car, used at parties with drugs/alcohol, or used intranasally (all P < .05). Intranasal administration was common (38% of all students endorsing NMUPS) and was associated with misuse at a party and simultaneous use with cocaine (P = .04), marijuana (P < .001), and alcohol (P < .001), compared with only oral use.Discussion and ConclusionsNotable characteristics were identified among individuals who engaged in NMUPS in the type, amount, cost, and ascertainment of stimulants.Scientific SignificanceThe concurrence of SUD and/or intranasal administration appear to represent a more severe phenotype of NMUPS that should be considered in the implementation of future prevention and intervention protocols on college campuses. (Am J Addict 2020;29:476–484)
Orlistat attenuates obesity‐induced decline in steroidogenesis and spermatogenesis by up‐regulating steroidogenic genes
Authors: Suleiman Joseph Bagi , Nna Victor Udo , Othman Zaidatul Akmal , Zakaria Zaida , Bakar Ainul Bahiyah Abu , Mohamed Mahaneem 
Published: May 2020

AbstractBackgroundSteroidogenesis decline is reported to be one of the mechanisms associated with obesity‐induced male factor subfertility/infertility.ObjectivesWe explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity‐induced steroidogenesis and spermatogenesis decline.Materials and methodsTwenty‐four adult maleSprague Dawleyrats weighing 250‐300 g were randomized into four groups (n = 6/group), namely; normal control, high‐fat diet, high‐fat diet plus orlistat preventive group and high‐fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high‐fat diet for 12 weeks (high‐fat diet plus orlistat preventive group) or administered from week 7‐12 post‐ high‐fat diet feeding (high‐fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.ResultsObesity increased serum leptin and decreased adiponectin levels, decreased serum and intra‐testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase were significantly decreased in the testes of the high‐fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high‐fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high‐fat diet‐induced obese male rats, with the preventive group (high‐fat diet plus orlistat preventive group) having better results relative to the treatment group (high‐fat diet plus orlistat treatment group).Discussion and ConclusionOrlistat attenuated impaired spermatogenesis and steroidogenesis decline by up‐regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.
Evaluation of a novel database for quality assurance at a head and neck service in New Zealand: an audit of free flap head and neck reconstruction
Authors: Marinone Lares Silvia G. , Clark Sita , Mathy Jon A. , Chaplin John , McIvor Nick 
Published: May 2020

AbstractBackgroundClinical audit is a critical quality improvement exercise, yet efficient audit tools are lacking. The main objective of this study was to evaluate a recently deployed database in facilitating the process of clinical audit, and the secondary objective was to evaluate the outcomes of free flap reconstruction of the head and neck at our centre.MethodsA head and neck cancer‐specific database was customized to suit the needs of our head and neck multidisciplinary team. Data has been entered prospectively into this database since March of 2018. An audit of free flap reconstruction of the head and neck over a 12‐month period was performed using the database and analysed as a case study to examine its efficacy as a clinical audit tool. Additionally, the outcomes of free flap reconstruction at our centre were compared to those reported in the international literature.ResultsThe database allows flexible and specific queries, analysis and export of data, and can provide immediate results. However, issues with data quality and completeness were identified. In this audit, the overall 30‐day complication rate and 30‐day mortality in patients undergoing free flap reconstruction of the head and neck were 58% and 3%, respectively.ConclusionThe database is fit for its intended purpose as an audit tool. Outcomes of free flap reconstruction of the head and neck at our centre are comparable to those of institutions overseas.
Evolution and clinical adoption of the Autologs system: An automated analysis for enhanced patient management in MCS
Authors: Brown Michael C. , Ramos Veronica , Voskoboynikov Neil 
Published: May 2020

AbstractThe Medtronic Autologs System allows real‐time clinician review of HeartWare HVAD System logfiles, providing supplemental pump data to aid in patient management. In its first year of availability, Autologs generated a 70% increase in logfile submissions, with 73% of all logfile requests being sent to Autologs. Within a month of its launch, Autologs submissions outnumbered the amount of logfiles submitted for manual review. Following the v1.1 release, there was a 20% increase in logfile submissions, with 77% of all logfile requests being Autologs. With the introduction of v1.2, there was another 35% increase in logfile submissions, with nearly 90% of all logfile requests being Autologs. The widespread adoption and utility of the Autologs System highlights the need for clinician access to real‐time data analysis in the field of Mechanical Circulatory Support.
Big Data Analytics and Other Emerging Technologies: The Impact on the Australian Audit and Assurance Profession
Authors: Kend Michael , Nguyen Lan Anh 
Published: May 2020

AbstractThe aim of this exploratory research study is to obtain the views of relevant stakeholders in relation to the impact big data analytics (BDA), artificial intelligence (AI) and robotics have had in Australia on the audit and assurance services market. Views are also sought on the impact or potential for impact of blockchain technologies. This paper reports findings from interviews and/or focus groups with 20 individuals representing key stakeholders in the market for audit and assurance services in Australia. Via a synthesis of these stakeholder perceptions and a review of the relevant accounting literature, the study finds that, overall, the impact of BDA, robotics and AI on auditing is seen as positive. BDA takes auditors away from manual, intensive tasks, and gives them more time to apply their minds and skills to more critical evaluation‐type work or key audit judgements. Participants also highlighted the need for regulators and standard setters to keep on track with the fast‐paced IT, automation evolution in the auditing field. Finally, and surprisingly given the attention surrounding blockchain technologies, the participants in this study seemed unconvinced of the application of blockchain technologies in auditing practice.
A novel statistical method for modeling covariate effects in bisulfite sequencing derived measures of DNA methylation
Authors: Zhao Kaiqiong , Oualkacha Karim , Lakhal‐Chaieb Lajmi , Labbe Aurélie , Klein Kathleen , Ciampi Antonio , Hudson Marie , Colmegna Inés , Pastinen Tomi , Zhang Tieyuan , Daley Denise , Greenwood Celia M.T. 
Published: May 2020

AbstractIdentifying disease‐associated changes in DNA methylation can help us gain a better understanding of disease etiology. Bisulfite sequencing allows the generation of high‐throughput methylation profiles at single‐base resolution of DNA. However, optimally modeling and analyzing these sparse and discrete sequencing data is still very challenging due to variable read depth, missing data patterns, long‐range correlations, data errors, and confounding from cell type mixtures. We propose a regression‐based hierarchical model that allows covariate effects to vary smoothly along genomic positions and we have built a specialized EM algorithm, which explicitly allows for experimental errors and cell type mixtures, to make inference about smooth covariate effects in the model. Simulations show that the proposed method provides accurate estimates of covariate effects and captures the major underlying methylation patterns with excellent power. We also apply our method to analyze data from rheumatoid arthritis patients and controls. The method has been implemented in R package SOMNiBUS.
Prognostic indices in diffuse large B‐cell lymphoma in the rituximab era: an analysis of the UK National Cancer Research Institute R‐CHOP 14 versus 21 phase 3 trial
Authors: Gleeson Mary , Counsell Nicholas , Cunningham David , Lawrie Anthony , Clifton‐Hadley Laura , Hawkes Eliza , McMillan Andrew , Ardeshna Kirit M. , Burton Cathy , Chadwick Nick , Gambell Joanna , Smith Paul , Mouncey Paul , Pocock Christopher , Radford John , Davies John , Turner Deborah , Kruger Anton , Johnson Peter , Linch David 
Published: May 2020

SummaryWe compared the International Prognostic Index (IPI), Revised (R)‐IPI and age‐adjusted (aa)‐IPI as prognostic indices for patients with diffuse large B‐cell lymphoma (DLBCL) in the UK National Cancer Research Institute (NCRI) R‐CHOP 14 versus 21 trial (N = 1080). The R‐IPI and aa‐IPI showed no marked improvement compared to the IPI for overall and progression‐free survival, in terms of model fit or discrimination. Similar results were observed in exploratory analyses incorporating the Grupo Español de Linfomas/Transplante de Médula Ósea (GELTAMO)‐IPI, where baseline β2‐microglobulin data were available (N = 655). Although our findings support current use of the IPI, a novel prognostic tool to better delineate a high‐risk DLBCL group in the rituximab era is needed.
Ferroptosis at the crossroads of infection, aging and cancer
Authors: Toyokuni Shinya , Yanatori Izumi , Kong Yingyi , Zheng Hao , Motooka Yashiro , Jiang Li 
Published: May 2020

AbstractDespite significant developments and persistent efforts by scientists, cancer is one of the primary causes of human death worldwide. No form of life on Earth can survive without iron, although some species can live without oxygen. Iron presents a double‐edged sword. Excess iron is a risk for carcinogenesis, while its deficiency causes anemia, leading to oxygen shortage. Every cell is eventually destined to death, either through apoptosis or necrosis. Regulated necrosis is recognized in distinct forms. Ferroptosis is defined as catalytic Fe(II)‐dependent regulated necrosis accompanied by lipid peroxidation. The main observation was necrosis of fibrosarcoma cells through inhibition of cystine/glutamate antiporter with erastin, which reduced intracellular cysteine and, thus, glutathione levels. Our current understanding of ferroptosis is relative abundance of iron (catalytic Fe[II]) in comparison with sulfur (sulfhydryls). Thus, either excess iron or sulfur deficiency causes ferroptosis. Cell proliferation inevitably requires iron for DNA synthesis and energy production. Carcinogenesis is a process toward iron addiction with ferroptosis resistance. Conversely, ferroptosis is associated with aging and neurodegeneration. Ferroptosis of immune cells during infection is advantageous for infectious agents, whereas ferroptosis resistance incubates carcinogenic soil as excess iron. Cancer cells are rich in catalytic Fe(II). Directing established cancer cells to ferroptosis is a novel strategy for discovering cancer therapies. Appropriate iron regulation could be a tactic to reduce and delay carcinogenesis.
New variant (Val597Ile) in transmembrane region of the TSH receptor with human chorionic gonadotropin hypersensitivity in familial gestational hyperthyroidism
Authors: Caron Philippe , Broussaud Stéphanie , Galano‐Frutos Juan José , Sancho Javier , Savagner Frédérique 
Published: May 2020

AbstractObjectivesOnly two mutations at the lysine 183 amino acid in the extracellular N‐terminal domain of human TSH receptor (hTSHR) have been associated with hypersensitivity to hCG and familial gestational hyperthyroidism.DesignDescribe a new variant of the TSHR gene with hCG hypersensitivity found in two women of the same family diagnosed with gestational hyperthyroidism.PatientsA 38‐year‐old woman was seen during the first trimester of her second pregnancy for thyrotoxicosis with increased fT3 and fT4 concentrations and low TSH levels without anti‐TSH receptor antibody. Thyrotoxicosis improved spontaneously during the 2nd trimester and persisted at the 3rd trimester. Similar clinical symptoms (weight loss, nausea, vomiting) were also reported during the first trimester of her first pregnancy and the first pregnancy of her mother.ResultsDNA sequencing of the hTSHR gene of this woman and her mother identifies a heterozygous variant changing valine to isoleucine residue at codon 597 in the transmembrane domain (TMD) of this receptor. In vitro functional studies of this variant showed increased constitutive activity in regard to the basal level of cAMP and IP3 production and to the low cell‐surface expression, while response to TSH was reduced compared to that of the wild‐type receptor. The Val597Ile variant presented a dose‐dependent increase in cAMP response to hGC and human luteinizing hormone (hLH). Simulation of the protein dynamics showed a high structural impact of the Val597Ile variant on helices 3 (TMH3) and 5 (TMH5) of the transmembrane domain participating to constitutive activity and hCG sensitivity.ConclusionWe describe a new variant in the transmembrane region of the hTSHR gene with increased constitutive activity and hCG hypersensitivity in familial gestational hyperthyroidism.
Perihematomal brain tissue iron concentration measurement by MRI in patients with intracerebral hemorrhage
Authors: Wei Jialiang , Novakovic Nemanja , Chenevert Thomas L. , Xi Guohua , Keep Richard F. , Pandey Aditya S. , Chaudhary Neeraj 
Published: May 2020

AbstractAimsOver the past two decades, animal intracerebral hemorrhage (ICH) model studies have indicated that iron, released after hemoglobin degradation, is neurotoxic. Iron phantom and animal experiments have shown that magnetic resonance imaging (MRI) relaxivity maps correlate with iron concentration. This study expands this into patients.MethodsEighteen human subjects with ICH underwent MRI at 3, 14, and 30 days. R2* relaxivity maps were used to calculate perihematomal iron concentrations and T2 imaging to determine hematoma and edema volumes.ResultsPerihematomal iron concentrations were increased at all three time points and decreased with distance from the hematoma. While perihematomal iron concentrations did not vary with hematoma size, the total iron overload (increased iron concentration x volume of affected tissue) did. Total iron overload correlated with edema volume.ConclusionsThese results demonstrate the feasibility of measuring perihematomal iron in ICH patients which may be important for monitoring treatment strategies and assessing efficacy noninvasively.
A mortality analysis of septic shock, vasoplegic shock and cryptic shock classified by the third international consensus definitions (Sepsis‐3)
Authors: Yang Won S. , Kang Hui D. , Jung Sang K. , Lee You J. , Oh Se H. , Kim Youn‐Jung , Sohn Chang H. , Kim Won Y. 
Published: May 2020

AbstractIntroductionThis study aimed to compare the 28‐day mortality of patients with septic shock, defined by Sepsis‐3 criteria and patients with vasoplegic or cryptic shock who are excluded from this new definition.ObjectivesThis retrospective observational study was performed using a tertiary emergency department's septic shock registry and investigated the records of patients managed between January 2010 and December 2015. In 2,138 total patients, 1004 (47.0%) had septic shock, 476 (22.2%) had vasoplegic shock and 655 (30.6%) had cryptic shock.ResultsThere was significant variation in 28‐day mortality among the three groups: 23.4% for septic shock, 8.8% for vasoplegic shock and 12.2% for cryptic shock (P < .001). In subgroup analysis of cryptic shock or septic shock according to lactate levels (2‐3, 3‐4 and >4 mmol/L), the mortality rate increased as lactate increased (cryptic shock: 9.5%, 14.8% and 18.0%; septic shock: 18.6%, 22.6% and 27.0%, respectively; P < .001). Multivariable analysis revealed odds ratios for mortality of 0.31 (95% CI 0.22‐0.44; P < .001) for vasoplegic shock and 0.46 (95% CI 0.35‐0.61; P < .001) for cryptic shock relative to septic shock. Survival curve analysis showed significant differences among patients with septic shock, vasoplegic shock and cryptic shock (Log rank test: P < .0001).ConclusionThe new septic shock definition may be useful for identifying high‐risk patients requiring intensive care. However, cryptic shock‐associated mortality increased to 18.0% as serum lactate increased, which suggests that some cryptic shock patients may also require intensive management.
The effect of canagliflozin on amputation risk in the CANVAS program and the CREDENCE trial
Authors: Arnott Clare , Huang Yuli , Neuen Brendon L , Di Tanna Gian Luca , Cannon Christopher P. , Oh Richard , Edwards Robert , Kavalam Mary , Rosenthal Norman , Perkovic Vlado , Jardine Meg J , Mahaffey Kenneth , Neal Bruce 
Published: May 2020

AbstractAimTo determine whether there was an explanation as to why the effects of the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor canagliflozin on amputation risk vary between the CANVAS program and the CREDENCE trial.MethodsWe performed a pooled analysis of patient‐level data from the CANVAS program and the CREDENCE trial. Patient characteristics associated with amputation risk were assessed in univariable and multivariable regression models and compared between studies. Effects of canagliflozin on amputation risk were determined from Cox proportional hazards models and compared between studies, subgroups and for a range of amputation outcomes. Effects over time were explored by cumulative event curves.ResultsIn the CANVAS program (n = 10 142; median follow‐up 2.4 years) and CREDENCE trial (n = 4401; median follow‐up 2.5 years), 2.3% and 5.3% of participants, respectively, reported baseline amputation history. Key differences at baseline were the proportions with nephropathy (CREDENCE higher, 100% vs. 17.5%) and cardiovascular disease (CANVAS higher, 66% vs. 50%). There were 133 amputations in CREDENCE (3.0% annual event rate) and 187 amputations in CANVAS (1.8% annual event rate), with prior amputation being the strongest predictor of future amputation in both groups. Effects of canagliflozin on amputation risk were significantly different between trials (Pheterogeneity .02, I2 = 82%), but this was not explained by participant or trial differences. There was no evidence that foot disease management protocols instituted during CREDENCE ameliorated amputation risk.ConclusionsWe identified no explanation for the difference in amputation risk between the CREDENCE trial and the CANVAS program. In the context of null effects of SGLT2 inhibition on amputation in CREDENCE and all other large trials, there is a possibility that the finding in CANVAS was the result of chance.