bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute hypoxaemia and vascular function in healthy humans
Authors: Lewis N. C. S. , Bain A. R. , Wildfong K. W. , Green D. J. , Ainslie P. N. 
Published: September 2017

New Findings
What is the central question of this study?
Endothelium‐dependent flow‐mediated dilatation (FMD) is impaired during acute (60 min) exposure to moderate hypoxia. We examined whether FMD is impaired to the same degree during exposure to milder hypoxia. Additionally, we assessed whether smooth muscle vasodilatory capacity [glyceryl trinitrate (GTN)‐induced dilatation] is impaired during acute hypoxic exposure.

What is the main finding and its importance?
A graded impairment in FMD and GTN‐induced dilatation was evident during acute (≤60 min) exposure to mild and moderate hypoxia. This study is the first to document these graded impairments, and provides rationale to examine the relationship between graded increases in sympathetic nerve activity with hypoxia on FMD and GTN‐induced dilatation.

Endothelium‐dependent flow‐mediated dilatation (FMD) and endothelium‐independent dilatation [induced with glyceryl trinitrate (GTN)] are impaired at high altitude (5050 m), and FMD is impaired after acute exposure (<60 min) to normobaric hypoxia equivalent to ∼5050 m (inspired oxygen fraction ∼0.11). Whether GTN‐induced dilatation is impaired acutely and whether FMD is impaired during milder hypoxia are unknown. Therefore, we assessed brachial FMD at baseline and after 30 min of mild (end‐tidal 74 ± 2 mmHg) and moderate (end‐tidal 50 ± 3 mmHg) normobaric hypoxia (n = 12) or normoxia (time‐control trial; n = 10). We also assessed GTN‐induced dilatation after the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared with the normoxic baseline, reductions during mild and moderate hypoxic exposure were evident in FMD (mild versus moderate, −1.2 ± 1.1 versus −3.1 ± 1.7%; P = 0.01) and GTN‐induced dilatation (−2.1 ± 1.0 versus −4.2 ± 2.0%; P = 0.01); the declines in FMD and GTN‐induced dilatation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve, FMD was attenuated in both conditions (mild versus moderate, 0.6 ± 0.9 versus 0.8 ± 0.7%; P ≤ 0.01). After 30 min of normoxic time control, FMD was reduced (−0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental decline in smooth muscle vasodilator capacity (impaired GTN‐induced dilatation). Our findings from the normoxic control study suggest the decline in FMD in acute hypoxia also appears to be influenced by 30 min of supine rest/inactivity.
What is the impact of research champions on integrating research in mental health clinical practice? A quasiexperimental study in South London, UK
Authors: Oduola Sherifat , Wykes Til , Robotham Dan , Craig Tom K J 
Published: September 2017

ObjectivesKey challenges for mental health healthcare professionals to implement research alongside clinical activity have been highlighted, such as insufficient time to apply research skills and lack of support and resources. We examined the impact of employing dedicated staff to promote research in community mental health clinical settings.DesignQuasiexperiment before and after study.SettingSouth London and Maudsley National Health Service Foundation Trust.Participants4455 patients receiving care from 15 community mental health teams between 1 December 2013 and 31 December 2014.Outcome measuresThe proportion of patients approached for research participation in clinical services where research champions were present (intervention group), and where research champions were not present (comparison group).ResultsPatients in the intervention group were nearly six times more likely to be approached for research participation (Adj. OR=5.98; 95% CI 4.96 to 7.22).ConclusionsInvesting in staff that promote and drive research in clinical services increases opportunities for patients to hear about and engage in clinical research studies. However, investment needs to move beyond employing short-term staff.
Effect of anesthesiadepth onpostoperative clinical outcome in patients with supratentorial tumor (DEPTH): study protocol for a randomized controlled trial
Authors: Cui Qianyu , Peng Yuming , Liu Xiaoyuan , Jia Bo , Dong Jia , Han Ruquan 
Published: September 2017

IntroductionRecent studies have shown that deep anaesthesia is associated with poor outcomes. However, no randomised controlled trials have been conducted to test the causality in patients undergoing brain tumour resection.Methods and analysisDEPTH is a multicenter, randomised, parallel-group, blind trial. The depth of general anaesthesia will be monitored using the bispectral index (BIS). Patients elected for supratentorial tumour resection will be randomly allocated to the deep or the light anaesthesia group in which the target BIS value is 35 or 50, respectively. BIS will be maintained at the target value for more than 90% of the total anaesthesia period. The primary outcome is the disability-free survival rate at postoperative 30 days and 1 year. The secondary outcomes are the mortality and morbidity within 30 days after surgery.Ethics approval and disseminationEthical approval has been granted by the Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medicine University. The reference number is KY2016-059-02. The results of this study will be disseminated through presentations at scientific conferences and publication in scientific journals.Trial registrationNCT03033693.
Acid-fast bacterium detection and identification from paraffin-embedded tissues using a PCR-pyrosequencing method
Authors: Bao Jian R , Clark Richard B , Master Ronald N , Shier Kileen L , Eklund Lynn L 
Published: September 2017

AimsAcid-fast bacterium (AFB) identification from formalin-fixed paraffin-embedded (FFPE) tissues is challenging and may not be readily available to the clinical laboratory. A method to detect and identify AFB from FFPE tissues using PCR and pyrosequencing (PCR-Seq) was developed and evaluated.MethodsThe method was validated using spiked cell-clotted paraffin blocks before use with patients’ specimens. DNA was extracted from tissue sections, and a 16S rRNA gene fragment was amplified and a signature sequence was produced on a PyroMark ID system. Sequences were aligned to established databases for AFB identification. Additional tissue sections were stained and examined for AFB.ResultsBoth sensitivity and specificity were 100% on spiked cell-clotted blocks without cross-reactivity with non-AFB. Of 302 FFPE tissues from patients, 116 (38%) were AFB-stain positive; 83 (72%) of these had AFB identified. The 21 AFB identified includedMycobacterium tuberculosiscomplex (14 cases),Mycobacterium leprae(3),Mycobacterium genavense(2),Mycobacterium marinum-ulceransgroup (3) and 17 other AFB (61). Thirteen cases were AFB-stain indeterminate and 4 were positive by the PCR-Seq method. Of the AFB stain-negative cases, 167 were negative and 6 were positive by PCR-Seq.ConclusionsThe PCR-Seq method provided specific identification of various AFB species or complexes from FFPE tissues.
Steroids administered after vacuum-assisted biopsy in the management of idiopathic granulomatous mastitis
Authors: Deng J Q , Yu L , Yang Y , Feng X J , Sun J , Liu J , Fan F S , Liao L Q 
Published: September 2017

AimsThe aetiology and treatment options for idiopathic granulomatous mastitis (IGM) are controversial. The aim was to study the clinical and diagnostic features and discuss medical and surgical treatment for IGM in our patients.MethodsSixty-five patients who met the histological criteria for IGM were retrospectively studied. The diagnosis of IGM was confirmed using Mammotome (an ultrasound-guided, vacuum-assisted biopsy system), core needle biopsy, quadrantectomy or segmental resection. Forty-five patients were treated with prednisolone (69.2%). Immunohistochemical (IHC) staining for immune-related antigens (CD3, CD4, CD8, CD79a, IgG, and IgM) was performed.ResultsUltrasonography (USG) was carried out in all patients. Among them, 61 were considered to have an inflammatory mass and 15 had accompanying liquefaction. In four patients, the findings mimicked breast carcinoma (6.2%). The IHC results showed CD3, CD4, CD8 and CD79a lymphocytes diffusely distributed in the lesion. Stains for IgG and IgM were negative. Prednisolone was administered to the patients diagnosed with IGM. The success rate was 53 (81.5%) and the whole recurrence was 12 (18.5%). The median follow-up period was 12 months (range 4–42 months).ConclusionsThe aetiology of IGM remains uncertain. The disease has no propensity for the right or left breast. It is a local autoimmune disease, involving humoral and cell-mediated immunity. Hyperprolactinaemia may play a role in some patients. Corticosteroids administered after complete removal of the IGM lesion using the Mammotome biopsy system is an effective treatment option.
Effect of faecal calprotectin assay variability on the management of inflammatory bowel disease and potential role of faecal S100A12
Authors: Whitehead Simon John , Ford Clare , Gama Rousseau Mariano , Ali Ala , McKaig Brian , Waldron Jenna Louise , Steed Helen , Brookes Matthew James 
Published: September 2017

AimsTo prospectively evaluate whether between-assay variability of different faecal calprotectin (f-Cp) assays influences diagnostic accuracy for inflammatory bowel disease (IBD) in a cohort of patients with confirmed IBD and irritable bowel syndrome (IBS). To also evaluate the diagnostic accuracy of faecal S100A12 (f-S100A12) against f-Cp in the same patient cohort and assess whether f-S100A12 offers additional diagnostic value.MethodsF-Cp using four commercially available f-Cp assays, f-S100A12 and blood biomarkers were measured in patients, recruited from the local IBD clinic, who had established IBS or active ulcerative colitis (UC) and Crohn’s disease (CD). Diagnostic sensitivities and specificities for each assay and biomarker were calculated and compared.ResultsMedian f-Cp levels in all assays were significantly higher in UC (347–884 µg/g; n=28) and CD (377–838 µg/g; n=15) compared with IBS (6–27 µg/g; n=17). Sensitivities and specificities at 50 µg/g were 94%–100% and 82%–100%, respectively. Median f-S100A12 levels were significantly higher in UC (81.0 µg/g; IQR 38.3–159.8) and CD (47.2 µg/g; IQR 5.3–108.9) compared with IBS (0.7 µg/g; IQR 0.5–0.8). At 2.8 µg/g, f-S100A12 had a sensitivity of 97% and specificity of 94%. The blood biomarkers demonstrated sensitivities and specificities of 44%–63% and 80%–92%, respectively.ConclusionsThe diagnostic sensitivity of the calprotectin assays was similar despite inter-kit variability in absolute values. There is a need for f-Cp assay standardisation, but in its absence assay-specific cut-off values may optimise their diagnostic performance. F-S100A12 demonstrated comparable sensitivity and specificity to f-Cp and although a research tool at present, may have a future role to play in the diagnosis and management of these patients.
Serotonin transporter binding and anxiety symptoms in Parkinson’s disease
Authors: Joling Merijn , van den Heuvel Odile A , Berendse Henk W , Booij Jan , Vriend Chris 
Published: September 2017

BackgroundAnxiety is a common neuropsychiatric symptom in Parkinson’s disease (PD), yet the neural mechanisms have been scarcely investigated. Disturbances in dopaminergic and serotonergic signalling may play a role in its pathophysiology. 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) is a single-photon emission CT radiotracer, and its binding in striatal and extrastriatal subcortical brain areas represents predominant binding to the presynaptic dopamine transporter (DAT) and the serotonin transporter (SERT), respectively. Availability of DAT and SERT may thus provide an in vivo measure for the integrity of both dopamine and serotonin neurons.MethodsWe studied the association between anxiety symptoms, measured with an affective subscale of the Beck Anxiety Inventory, and (extra)striatal 123I-FP-CIT binding in 127 non-demented patients with PD with a median disease duration of 2.55 (IQR 2.90) years. We conducted the analyses on patients currently on or not on dopamine replacement therapy (DRT).ResultsSeverity of anxiety symptoms showed a significant negative association with 123I-FP-CIT binding ratios in the right thalamus (β=−0.203, p=0.019; ΔR2=0.040) (multiple testing pcorr <0.020). In the subgroup of patients not on DRT (n=81), we found a significant negative association between anxiety and thalamic 123I-FP-CIT binding ratios bilaterally (right: β=−0.349, p=0.001, ΔR2=0.119; left: β=−0.269, p=0.017, ΔR2=0.071) (pcorr <0.020).ConclusionThis study shows that higher levels of anxiety in patients with PD are associated with lower thalamic 123I-FP-CIT binding, pointing towards a contribution of serotonergic degeneration to anxiety symptoms in PD.
Enhancement in specific heat by nanocrystallization: Softening of phonon frequencies mechanism
Authors: Choudhary K. K. , Mishra Dron , Sharma Uttam , Kaurav N. 
Published: September 2017

The temperature-dependent specific heat C[Formula: see text](T) of nanocrystalline (NC) Cu (8 nm) and Pd (6 nm) is theoretically analyzed and compared with the specific heat of their corresponding bulk materials in the temperature range from 150 K to 300 K. It is revealed that the C[Formula: see text] values of NC Cu (Pd) are about 10% (40%) higher as compared to that of their corresponding bulk form, the softening of phonon frequencies at interfaces in NC materials is argumented as the main mechanism responsible for enhancement in C[Formula: see text] in the present work. Lattice (phonon) specific heat is obtained following an overlap repulsive potential using Debye model. In NC materials having large interface volume ratio, the phonon frequencies and Debye temperature are comparatively less at the interfaces than at the core of nanocrystal. The contributions to specific heat due to atoms present at interfaces (C[Formula: see text]) and those present at the core of nanocrystal (C[Formula: see text]) are estimated separately by estimating the characteristic Debye temperature ([Formula: see text]) from elastic force constant ([Formula: see text]). The temperature derivative of the internal energy yields the electronic contribution to specific heat (C[Formula: see text]). The present investigation based on the softening of phonon frequencies mechanism is successful to explain the enhancement in specific heat by nanocrystallization.
Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling
Authors: Chaudhuri Aadel A. , Chabon Jacob J. , Lovejoy Alexander F. , Newman Aaron M. , Stehr Henning , Azad Tej D. , Khodadoust Michael S. , Esfahani Mohammad Shahrokh , Liu Chih Long , Zhou Li , Scherer Florian , Kurtz David M. , Say Carmen , Carter Justin N. , Merriott David J. , Dudley Jonathan C. , Binkley Michael S. , Modlin Leslie , Padda Sukhmani K. , Gensheimer Michael F. , West Robert B. , Shrager Joseph B. , Neal Joel W. , Wakelee Heather A. , Loo Billy W. , Alizadeh Ash A. , Diehn Maximilian 
Published: September 2017

Abstract
Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here, we apply cancer personalized profiling by deep sequencing (CAPP-seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I–III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the first posttreatment blood sample, indicating reliable identification of MRD. Posttreatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months, and 53% of patients harbored ctDNA mutation profiles associated with favorable responses to tyrosine kinase inhibitors or immune checkpoint blockade. Collectively, these results indicate that ctDNA MRD in patients with lung cancer can be accurately detected using CAPP-seq and may allow personalized adjuvant treatment while disease burden is lowest.
Significance: This study shows that ctDNA analysis can robustly identify posttreatment MRD in patients with localized lung cancer, identifying residual/recurrent disease earlier than standard-of-care radiologic imaging, and thus could facilitate personalized adjuvant treatment at early time points when disease burden is lowest. Cancer Discov; 7(12); 1394–403. ©2017 AACR.
See related commentary by Comino-Mendez and Turner, p. 1368.
This article is highlighted in the In This Issue feature, p. 1355
Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus
Authors: Kim Young-Gun , Yoon Dukyong , Park Sooyoung , Han Seung Jin , Kim Dae Jung , Lee Kwan-Woo , Park Rae Woong , Kim Hae Jin 
Published: September 2017

Background:
The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas.

Methods and Results:
A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015. Incident users of sulfonylurea and DPP-4i who were not prescribed the comparator drug in the year before treatment initiation were included. DPP-4i–treated and sulfonylurea-treated patients were matched on propensity score, calculated with >40 variables. The risk of hospitalization for HF was evaluated with a Cox proportional hazards model in 255 691 matched pairs. Analyses were conducted in the total patient population and in both strata divided by the presence of cardiovascular disease during the baseline period. The hazard ratios (HRs) of hospitalization for HF for DPP-4i–treated patients were 0.78 (95% confidence interval [CI], 0.67–0.86) in all of the patients, 0.77 (95% CI, 0.68–0.79) in patients with baseline cardiovascular disease, and 0.71 (95% CI, 0.56–0.90) in patients without baseline cardiovascular disease compared with HRs for sulfonylurea-treated patients. Sitagliptin and linagliptin showed statistically lower risk for hospitalization for HF (HR, 0.76; 95% CI, 0.67–0.86 for sitagliptin-prescribed patients; HR, 0.74; 95% CI, 0.59–0.92 for linagliptin-prescribed patients) than for sulfonylurea. The HRs for hospitalization for myocardial infarction and stroke with the use of a DPP-4i versus sulfonylurea were HR, 0.76 (95% CI, 0.67–0.87) and HR, 0.63 (95% CI, 0.60–0.67), respectively.

Conclusions:
Our findings suggest that DPP-4i use did not increase the risk of HF compared with sulfonylurea. In addition, the risks for cardiovascular outcomes were not elevated in DPP-4i–treated patients compared with sulfonylurea-treated patients.
Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging
Authors: Ivanov Alexander , Dabiesingh Devindra S. , Bhumireddy Geetha P. , Mohamed Ambreen , Asfour Ahmed , Briggs William M. , Ho Jean , Khan Saadat A. , Grossman Alexandra , Klem Igor , Sacchi Terrence J. , Heitner John F. 
Published: September 2017

Background—
Presence of prominent left ventricular trabeculation satisfying criteria for left ventricular noncompaction (LVNC) on routine cardiac magnetic resonance examination is frequently encountered; however, the clinical and prognostic significance of these findings remain elusive. This registry aimed to assess LVNC prevalence by 4 current criteria and to prospectively evaluate an association between diagnosis of LVNC by these criteria and adverse events.

Methods and Results—
There were 700 patients referred for cardiac magnetic resonance: 42% were women, median age was 70 years (range, 45–71 years), mean left ventricular ejection fraction was 51% (±17%), and 32% had late gadolinium enhancement on cardiac magnetic resonance. The cohort underwent diagnostic assessment for LVNC by 4 separate imaging criteria—referenced by their authors as Petersen, Stacey, Jacquier, and Captur, with LVNC prevalence of 39%, 23%, 25% and 3%, respectively. Primary clinical outcome was combined end point of time to death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, and heart failure hospitalization. Secondary clinical outcomes were (1) all-cause mortality and (2) time to the first occurrence of any of the following events: cardiac death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, or heart failure hospitalization. During a median follow-up of 7 years, there were no statistically significant differences in assessed outcomes noted between patients with and without LVNC irrespective of the applied criteria.

Conclusions—
Current criteria for the diagnosis of LVNC leads to highly variable disease prevalence in patients referred for cardiac magnetic resonance. The diagnosis of LVNC, by any current criteria, was not associated with adverse clinical events on nearly 7 years of follow-up. Limited conclusions can be made for Captur criteria due to low observed prevalence.
Transfusion of Polynitroxylated Pegylated Hemoglobin Stabilizes Pial Arterial Dilation and Decreases Infarct Volume After Transient Middle Cerebral Artery Occlusion
Authors: Cao Suyi , Zhang Jian , Ma Li , Hsia Carleton J. C. , Koehler Raymond C. 
Published: September 2017

Background
Polynitroxylation of hemoglobin confers superoxide dismutase–mimetic and peroxidase activity and may protect from reperfusion injury in addition to facilitating oxygen transport. We determined whether transfusion of polynitroxylated PEGylated hemoglobin (PNPH) is protective in the rat filament model of 2 hours of middle cerebral artery occlusion (MCAO).

Methods and Results

Transfusion of 10 mL/kg of PNPH at 20 minutes of MCAO reduced infarct volume by over 70% (n=10). To determine whether PNPH might act by promoting vasodilation, pial arteriolar diameter in the distal MCA border region was measured in closed cranial windows. With no transfusion, MCAO induced an initial dilation (36±2% ±SE) that subsided by 2 hours (5±4%; n=8). With PNPH transfusion at 20 minutes of MCAO, the initial dilation (31±3%) was better maintained at 2 hours (21±4%; n=7;
P
<0.02). Delaying PNPH transfusion until 90 minutes of MCAO increased perfusion in the border region from 48±6% of the preischemic baseline to 67±8% (n=8;
P
<0.005). The effect of PNPH transfusion after reperfusion was also tested. Compared with the control median hemispheric infarct volume of 22% (13% to 34% interquartiles; n=15), infarct volume was reduced to 7% (3% to 13%; n=14
P
<0.05) when PNPH was transfused at 4 hours after MCAO (2 hours of reperfusion) but not significantly when transfused at 6 hours (8%; 3% to 35%; n=14) or at 8 hours (12%; 10% to 25%; n=14) after MCAO.

Conclusions
PNPH transfusion has a significant therapeutic window for protection during and after transient MCAO and may act, in part, by stabilizing vascular function and improving collateral blood flow.