bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cross-sectional survey of physical strains among offshore wind farm workers in the German exclusive economic zone
Authors: Velasco Garrido Marcial , Mette Janika , Mache Stefanie , Harth Volker , Preisser Alexandra M 
Published: March 2018

ObjectivesTo assess the physical strains of employees in the German offshore wind industry, according to job type and phase of the wind farm (under construction or operation).DesignWeb-based cross-sectional survey.SettingOffshore wind farm companies operating within the German exclusive economic zone.ParticipantsMale workers with regular offshore commitments and at least 28 days spent offshore in the past year (n=268).Outcome measuresPhysical strains (eg, climbing, noise, working overhead, with twisted upper body or in confined spaces, vibration, heavy lifting, humidity, odours).ResultsThe most frequently mentioned physical strain was ’climbing’ with 63.8% of the respondents reporting to be always or frequently confronted with climbing and ascending stairs during offshore work. Work as a technician was associated with a greater exposition to noise, vibrations, humidity, cold, heat, chemical substances, lifting/carrying heavy loads, transport of equipment, working in non-ergonomic positions and in cramped spaces, as well as climbing.Indeed, statistical analyses showed that, after adjusting for phase of the wind farm, age, nationality, offshore experience, work schedule and type of shift, compared with non-technicians, working as a technician was associated with more frequently lifting/carrying of heavy loads (OR 2.58, 95% CI 1.58 to 4.23), transport of equipment (OR 2.06 95% CI 1.27 to 3.33), working with a twisted upper body (OR 2.85 95% CI 1.74 to 4.69), working overhead (OR 2.77 95% CI 1.67 to 4.58) and climbing (OR 2.30 95% CI 1.40 to 3.77). Working in wind farms under construction was strongly associated with increased and decreased exposure to humidity (OR 2.32 95% CI 1.38 to 3.92) and poor air quality (OR 0.58 95% CI 0.35 to 0.95), respectively.ConclusionsWorkers on offshore wind farms constitute a heterogeneous group, including a wide variety of occupations. The degree of exposure to detrimental physical strains varies depending on the type of job. Technicians are more exposed to ergonomic challenges than other offshore workers.
Association between refill adherence to lipid-lowering medications and the risk of cardiovascular disease and mortality in Swedish patients with type 2 diabetes mellitus: a nationwide cohort study
Authors: Karlsson Sofia Axia , Hero Christel , Svensson Ann-Marie , Franzén Stefan , Miftaraj Mervete , Gudbjörnsdottir Soffia , Eeg-Olofsson Katarina , Eliasson Björn , Andersson Sundell Karolina 
Published: March 2018

ObjectivesTo analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus.DesignCohort study.SettingNational population-based cohort of Swedish patients with type 2 diabetes mellitus.Participants86 568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007–2010, 87% for primary prevention.Exposure and outcome measuresRefill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%–40%, 41%–60%, 61%–80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics.ResultsThe hazard ratios for CVD ranged 1.33–2.36 in primary prevention patients and 1.19–1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001).ConclusionsHigher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.
How will South Africa’s mandatory salt reduction policy affect its salt iodisation programme? A cross-sectional analysis from the WHO-SAGE Wave 2 Salt & Tobacco study
Authors: Charlton Karen , Ware Lisa Jayne , Baumgartner Jeannine , Cockeran Marike , Schutte Aletta E , Naidoo Nirmala , Kowal Paul 
Published: March 2018

ObjectiveThe WHO’s global targets for non-communicable disease reduction recommend consumption of<5 g salt/day. In 2016, South Africa was the first country to legislate maximum salt levels in processed foods. South Africa’s salt iodisation fortification programme has successfully addressed iodine deficiency but information is dated. Simultaneous monitoring of sodium reduction and iodine status is required to ensure compatibility of the two public health interventions.Design/setting/participantsA nested cohort design within WHO’s 2015 Study on global AGEing and adult health (n=2887) including individuals from households across South Africa. Randomly selected adults (n=875) provided 24-hour and spot urine samples for sodium and iodine concentration analysis (the primary and secondary outcome measures, respectively). Median 24-hour urinary iodine excretion (UIE) and spot urinary iodine concentrations (UIC) were compared by salt intakes of <5g/day, 5–9g/dayand >9 g/day.ResultsMedian daily sodium excretion was equivalent to 6.3 g salt/day (range 1–43 g/day); 35% had urinary sodium excretion values within the desirable range (<5 g salt/day), 37% had high values (5–9 g salt/day) and 28% had very high values (>9 g salt/day). Median UIC was 130 µg/L (IQR=58–202), indicating population iodine sufficiency (≥100 µg/L). Both UIC and UIE differed across salt intake categories (p<0.001) and were positively correlated with estimated salt intake (r=0.166 and 0.552, respectively; both p<0.001). Participants with salt intakes of <5 g/day were not meeting the Estimated Average Requirement for iodine intake (95 µg/day).ConclusionsIn a nationally representative sample of South African adults, the association between indicators of population iodine status (UIC and UIE) and salt intake, estimated using 24-hour urinary sodium excretion, indicate that low salt intakes may compromise adequacy of iodine intakes in a country with mandatory iodisation of table salt. The iodine status of populations undergoing salt reduction strategies needs to be closely monitored to prevent re-emergence of iodine deficiency.
Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy
Authors: Zhao Yue , Shuen Timothy Wai Ho , Toh Tan Boon , Chan Xue Ying , Liu Min , Tan Sue Yee , Fan Yong , Yang Hechuan , Lyer Shridhar Ganpathi , Bonney Glenn Kunnath , Loh Eva , Chang Kenneth Tou En , Tan Thiam Chye , Zhai Weiwei , Chan Jerry Kok Yen , Chow Edward Kai-Hua , Chee Cheng Ean , Lee Guan Huei , Dan Yock Young , Chow Pierce Kah-Hoe , Toh Han Chong , Lim Seng Gee , Chen Qingfeng 
Published: March 2018

ObjectiveAs the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.DesignPatient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg−/−(NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.ResultsSimilar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.ConclusionsOur work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.
Relationship between stroke recurrence, infarct pattern, and vascular distribution in patients with symptomatic intracranial stenosis
Authors: Raghuram Karthikram , Durgam Aditya , Kohlnhofer Jennifer , Singh Ayush 
Published: March 2018

ObjectiveIn view of recent literature suggesting that stroke recurrence and risks related to intervention may be related to plaque physiology/instability, our study sought to discern the pattern of stroke and rates of stoke recurrence as they relate to the anatomy and presentation of the underlying stenosis.MethodsRetrospective chart as well as CT and MR angiographic imaging review of patients in the institutional stroke database was performed, including identification of patient risk factors, medical therapeutic optimization, compliance, serum cholesterol (low density lipoprotein) levels, blood pressure, physical therapy referrals, follow-up clinical status (using the modified Rankin Scales), and rate of recurrent stroke. 39 patients met the inclusion criteria. We evaluated infarct pattern (embolic, adjacent perforator, or watershed) and vascular distribution.ResultsBasilar artery stenosis was most likely to present as a perforator stroke and least likely to recur. Patients discharged with suboptimal medical therapy were twice as likely to have a recurrent stroke. Among patients with optimized medical therapy, no recurrent strokes were seen in patients with an embolic infarct pattern, while a 57% recurrence rate was seen in patients with a watershed infarct pattern.ConclusionsOur results suggest that hemodynamic intracranial vascular stenoses may be less responsive to medical therapy, while stenotic lesions caused by plaque destabilization or in perforator territories may benefit from aggressive medical management with delayed or staged endovascular therapy. Recurrence of stroke may be affected both by vascular territory and by aggressive risk factor control, although the latter remains difficult to evaluate.
Clinical presentation of CIED infection following initial implant versus reoperation for generator change or lead addition
Authors: Harper Mariko W , Uslan Daniel Z , Greenspon Arnold J , Baddour Larry M , Carrillo Roger G , Danik Stephan B , Tolosana Jose M , Le Katherine , Miro Jose M , Naber Christoph K , Peacock James , Sohail Muhammad Rizwan , Vikram Holenarasipur R , Prutkin Jordan M 
Published: March 2018

ObjectiveTo explore differences in clinical manifestations and outcomes in those patients who develop infection after undergoing initial implantation versus reoperation.MethodsWe compared cases of cardiac implantable electronic device (CIED) infection based on initial implantation versus reoperation from 11 centres.ResultsThere were 432 patients with CIED infection, 178 occurring after initial device placement and 254 after repeat reoperation. No differences were seen in age, sex or device type. Those with infection after initial implant had a higher Charlson Comorbidity Score (median 3 (IQR 2–6) vs 2 (IQR 1–4), p<0.001), shorter time since last procedure (median 8.9 months (IQR 0.9–33.3) vs 19.5 months (IQR 1.1–62.9), p<0.0001) and fewer leads (2.0±0.6vs 2.5±0.9, p<0.001). Pocket infections were more likely to occur after a reoperation (70.1%vs48.9%, p<0.001) and coagulase negative staphylococci (CoNS) was the most frequently isolated organism in this group (p=0.029). In contrast, initial implant infections were more likely to present with higher white cell count (10.5±5.1 g/dL vs 9.5±5.4 g/dL, p=0.025), metastatic foci of infection (16.9%vs8.7%, p=0.016) and sepsis (30.9%vs19.3%, p=0.006). There were no differences in in-hospital (7.9%vs5.2%, p=0.31) or 6-month mortality (21.9%vs14.0%, p=0.056).ConclusionsCIED infections after initial device implant occur earlier, more aggressively, and often due toStaphylococcus aureus. In contrast, CIED infections after reoperation occur later, are due to CoNS, and have more indolent manifestations with primary localisation to the pocket.
Ocular hypertension in a diabetic acromegalic dog
Authors: Pugh Benjamin Marc , Losowski Claudine 
Published: March 2018

A seven‐year eight‐month‐old, female entire, Staffordshire Bull Terrier presented with bilateral third eyelid protrusion, polyuria, polydipsia and respiratory stridor. Diabetes mellitus and acromegaly were diagnosed, suspected to be secondary to elevated circulating endogenous progestogen levels. These elevated levels occur during the luteal phase of the oestrus cycle. The finding of bilateral ocular hypertension is proposed to be secondary to the acromegaly. The ocular hypertension resolved post‐ovariohysterectomy and mammary mass removal, along with the resolution of the acromegaly.This case highlights an unusual presentation for acromegaly and demonstrates the value of tonometry even in cases where glaucoma seems unlikely. To the authors’ knowledge, this is the first report of ocular hypertension secondary to acromegaly in the dog.
Human muscle-specific A-kinase anchoring protein polymorphisms modulate the susceptibility to cardiovascular diseases by altering cAMP/PKA signaling
Authors: Suryavanshi Santosh V. , Jadhav Shweta M. , Anderson Kody L. , Katsonis Panagiotis , Lichtarge Olivier , McConnell Bradley K. 
Published: March 2018

One of the crucial cardiac signaling pathways is cAMP-mediated PKA signal transduction, which is regulated by a family of scaffolding proteins, i.e., A-kinase anchoring proteins (AKAPs). Muscle-specific AKAP (mAKAP) partly regulates cardiac cAMP/PKA signaling by binding to PKA and phosphodiesterase 4D3 (PDE4D3), among other proteins, and plays a central role in modulating cardiac remodeling. Moreover, genetics plays an incomparable role in modifying the risk of cardiovascular diseases (CVDs). Single-nucleotide polymorphisms (SNPs) in various proteins have especially been shown to predispose individuals to CVDs. Hence, we hypothesized that human mAKAP polymorphisms found in humans with CVDs alter the cAMP/PKA pathway, influencing the susceptibility of individuals to CVDs. Our computational analyses revealed two mAKAP SNPs found in cardiac disease-related patients with the highest predicted deleterious effects, Ser 1653 Arg (S1653R) and Glu 2124 Gly (E2124G). Coimmunoprecipitation data in human embryonic kidney-293T cells showed that the S1653R SNP, present in the PDE4D3-binding domain of mAKAP, changed the binding of PDE4D3 to mAKAP and that the E2124G SNP, flanking the 3′-PKA binding domain, changed the binding of PKA before and after stimulation with isoproterenol. These SNPs significantly altered intracellular cAMP levels, global PKA activity, and cytosolic PDE activity compared with the wild type before and after isoproterenol stimulation. PKA-mediated phosphorylation of pathological markers was found to be upregulated after cell stimulation in both mutants. In conclusion, human mAKAP polymorphisms may influence the propensity of developing CVDs by affecting cAMP/PKA signaling, supporting the clinical significance of PKA-mAKAP-PDE4D3 interactions. NEW & NOTEWORTHY We found that single-nucleotide polymorphisms in muscle-specific A-kinase anchoring protein found in human patients with cardiovascular diseases significantly affect the cAMP/PKA signaling pathway. Our results showed, for the first time, that human muscle-specific A-kinase anchoring protein polymorphisms might alter the susceptibility of individuals to develop cardiovascular diseases with known underlying molecular mechanisms.
Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans
Authors: Vermeulen Tyler D. , Boulet Lindsey M. , Stembridge Mike , Williams Alexandra M. , Anholm James D. , Subedi Prajan , Gasho Chris , Ainslie Philip N. , Feigl Eric O. , Foster Glen E. 
Published: March 2018

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4–18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.
Specific circulating microRNAs display dose-dependent responses to variable intensity and duration of endurance exercise
Authors: Ramos Anna E. , Lo Claire , Estephan Leonard E. , Tai Yi-Yin , Tang Ying , Zhao Jingsi , Sugahara Masataka , Gorcsan John , Brown Marcel G. , Lieberman Daniel E. , Chan Stephen Y. , Baggish Aaron L. 
Published: March 2018

Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.