bluuebunny/crossref_metadata_2025 huggingface dataset:
A Contemporary Review of the Treatment Landscape and the Role of Predictive and Prognostic Biomarkers in Pancreatic Adenocarcinoma
Authors: Yu Irene S. , Cheung Winson Y.
Published: February 2018

Pancreatic cancer continues to represent one of the leading causes of cancer-related morbidity and mortality in the developed world. Over the past decade, novel systemic therapy combination regimens have contributed to clinically meaningful and statistically significant improvements in overall survival as compared to conventional monotherapy. However, the prognosis for most patients remains guarded secondary to the advanced stages of disease at presentation. There is growing consensus that outcomes can be further optimized with the use of predictive and prognostic biomarkers whereby the former can be enriching for patients who would benefit from therapies and the latter can inform decision-making regarding the need and timing of advanced care planning. One of the challenges of current biomarkers is the lack of standardization across clinical practices such that comparability between jurisdictions can be difficult or even impossible. This inconsistency can impede widespread implementation of their use. In this review article, we provide a comprehensive overview of the contemporary treatment options for pancreatic cancer and we offer some insights into the existing landscape and future directions of biomarker development for this disease.
Health Related Quality of Life among TB Patients: Question Mark on Performance of TB DOTS in Pakistan
Authors: Malik Madeeha , Nasir Rida , Hussain Azhar
Published: February 2018

Due to long duration of treatment and use of several agents, tuberculosis can lead to poor health related quality of life among patients. Objective. The present study was designed to assess health related quality of life among pulmonary tuberculosis patients in Pakistan. Methodology. A descriptive cross-sectional study design was used. SF-36 was self-administered to a sample of 382 pulmonary tuberculosis patients receiving self-administered or directly observed types of treatment, in baseline, initial, or continuous phase of treatment. After data collection, data was cleaned, coded, and statistically analyzed using SPSS version 21.0. Results. The results of the current study highlighted a significant impact on several domains of HRQoL of pulmonary TB patients. Highest HRQoL scores had been observed for the domain of physical functioning (60.03, ±25.779) whereas lowest HRQoL scores were observed for the domain of general health (34.97, ±14.286) perceptions of TB patients followed by bodily pain (43.40, ±24.594). Conclusion. The results of the present study concluded that TB patients had poor HRQoL in spite of the new therapeutic strategies and free availability of medicines. The disease had a negative impact on HRQoL of TB patients across all domains.
Recent Trends in the Recurrence of North Atlantic Atmospheric Circulation Patterns
Authors: Yiou Pascal , Cattiaux Julien , Ribes Aurélien , Vautard Robert , Vrac Mathieu
Published: February 2018

A few types of extreme climate events in the North Atlantic region, such as heatwaves, cold spells, or high cumulated precipitation, are connected to the recurrence of atmospheric circulation patterns. Understanding those extreme events requires assessing long‐term trends of the atmospheric circulation. This paper presents a set of diagnostics of the intra‐ and interannual recurrence of atmospheric patterns. Those diagnostics are devised to detect trends in the stability of the circulation and the return period of atmospheric patterns. We detect significant emerging trends in the winter circulation, pointing towards a potential increased predictability. No such signal seems to emerge in the summer. We find that the winter trends in the dominating atmospheric patterns and their recurrences do not depend of the patterns themselves.
Propositions on the Optimal Number of Q-Graders and R-Graders
Authors: Louzada Pereira Lucas , Carvalho Guarçoni Rogério , Soares de Souza Gustavo , Brioschi Junior Dério , Rizzo Moreira Taís , Schwengber ten Caten Carla
Published: February 2018

Sensory analysis or cup testing has been widely used in the coffee production chain for the validation of final quality. The tasters are responsible for defining the patterns and qualitative profiles of the drink based on the sensorial analysis and according to their gustatory sensibilities, which are often acquired by professional experience. However, the literature has not discussed in detail the relationship between the number of tasters and the consistency of sensorial analysis. Thus, using the bootstrap simulation methodology to estimate the optimum plot size, this study quantifies and proposes a specific number of tasters for the process of sensorial analysis of specialty coffees. The results indicate that the use of 6 tasters is sufficient to conduct sensorial analysis following SCA and BSCA protocol for coffees in the Arabica group, as well as 6 tasters for coil and Conilon coffees. From this number, no gains in precision are observed in the process of sensorial analysis of coffee with addition tasters.
Blood Transfusion Practice among Healthcare Personnel in Nepal: An Observational Study
Authors: Sapkota Abja , Poudel Sabitra , Sedhain Arun , Khatiwada Niru
Published: February 2018

Background. The complications associated with errors in transfusion practice can be minimized by assessing transfusion practices. In Nepal, there is no standard protocol on blood transfusion. So, this study was conducted with an aim to assess the blood transfusion practice among healthcare personnel. Methods. A descriptive observational study was conducted in two tertiary hospitals in Kathmandu, Nepal, over a period of 10 months. Bedside blood transfusion procedures were observed using structured checklist. Results. Altogether, 86 observations were made. Time taken from dispatch from the blood bank to transfusion was >2 hours in 53.2% of cases. In majority of the cases, blood was kept in the ward in uncontrolled and unprotected manner by the patients’ relatives. Only 8.2% of the patients and/or the relatives were informed about the reasons, associated probable risks (2.4%), and the benefits of transfusion (4.7%). Assessment of vital signs at 15 minutes of initiation of transfusion was done on about 2 to 4% of cases. Conclusion. We found a suboptimal blood transfusion practice in Nepal, which could be attributable to substantial knowledge gap among healthcare personnel and the absence of quality culture, quality system, and quality management in the area of blood transfusion practices.
Modulation of Molecular Biomarker Expression in Response to Chemotherapy in Invasive Ductal Carcinoma
Authors: Oloomi Mana , Moazzezy Neda , Bouzari Saeid
Published: February 2018

Breast cancer (BC) has varied morphological and biological features and is classified based on molecular and morphological examinations. Molecular classification of BC is based on biological gene-expression profiling. In this study, biomarker modulation was assessed during BC treatment in 30 previously untreated patients. Heterogeneity among patients was pathologically diagnosed and classified into luminal and basal-like immunohistochemical profiles based on estrogen, progesterone, and human epidermal growth factor receptor (ER/PR/HER2) status. Marker heterogeneity was compared with mRNA biomarker expression in patients with BC before and after therapy. Reverse transcription-polymerase chain reaction was performed for molecular characterization. Expression and modulation of biological markers, CK19, hMAM, CEA, MUC, Myc, Ki-67, HER2/neu, ErbB2, and ER, were assessed after treatment, where the expression of the biomarkers CK19, Ki-67, Myc, and CEA was noted to be significantly decreased. Marker expression modulation was determined according to different stages and pathological characteristics of patients; coexpression of three markers (CK19, Ki-67, and Myc) was specifically modulated after therapy. In the histopathologically classified basal-like group, two markers (CK19 and Ki-67) were downregulated and could be considered as diagnostic biomarkers. In conclusion, pathological characteristics and marker variation levels can be evaluated to decide a personalized treatment for patients.
Effect of Zishen Jiangtang Pill, a Chinese Herbal Product, on Rats with Diabetic Osteoporosis
Authors: Li Huilin , Chu Shufang , Zhao Hengxia , Liu Deliang , Liu Xuemei , Qu Xi , Chen Jianpin , Li Zengyin , Li Jinhua
Published: February 2018

Diabetic osteoporosis (DO) is a complication of diabetes. Zishen Jiangtang Pill (ZJP) is a Chinese herbal product which has been used in clinic to maintain blood glucose level and bone density for decades. However, the evidence about its mechanism on diabetes and osteoporosis is still unknown. The aim of this study is to investigate therapeutic effect of ZJP on DO in streptozotocin‐ (STZ‐) induced rats. Rats were randomly assigned to 4 groups: one control group (CON), one model group (MOD), and two ZJP treatment groups (1.5 and 3.0 g/kg/d). All rats were treated for 8 weeks. Results showed that ZJP decreased the blood glucose level during OGTT and prevented the changes of FBG and Fins. Similarly, ZJP inhibited the changes of BCa, P, TRACP‐5b, CTX‐1, BALP, and BGP and the reduction of BMD. In parallel, 1H‐NMR metabolomic studies showed that ZJP significantly altered the metabolic fingerprints of blood and urine level. These findings suggest that ZJP can effectively improve glucose metabolism, abnormal bone metabolism, and metabolic disorders in DO rats, which may be a useful alternative medicine for DO therapy.
The Visualization of Spherical Patterns with Symmetries of the Wallpaper Group
Authors: Liu Shihuan , Leng Ming , Ouyang Peichang
Published: February 2018

By constructing invariant mappings associated with wallpaper groups, this paper presents a simple and efficient method to generate colorful wallpaper patterns. Although the constructed mappings have simple form and only two parameters, combined with the color scheme of orbit trap algorithm, such mappings can create a great variety of aesthetic wallpaper patterns. The resulting wallpaper patterns are further projected by central projection onto the sphere. This creates the interesting spherical patterns that possess infinite symmetries in a finite space.
Readout Distance Enhancement of the Passive Wireless Multi-Parameter Sensing System Using a Repeater Coil
Authors: Wang Lifeng , Dong Lei , Huang Qing-an
Published: February 2018

A repeater coil is used to extend the detection distance of a passive wireless multi-parameter sensing system. The passive wireless sensing system has the ability of simultaneously monitoring three parameters by using backscatter modulation together with channel multiplexing. Two different repeater coils are designed and fabricated for readout distance enhancement of the sensing system: one is a PCB (printed circuit board) repeater coil, and the other is a copper wire repeater coil. Under the conditions of fixed voltage and adjustable voltage, the maximum readout distance of the sensing system with and without a repeater coil is measured. Experimental results show that larger power supply voltage can help further increase the readout distance. The maximum readout distance of the sensing system with a PCB repeater coil has been extended 2.3 times, and the one with a copper wire repeater coil has been extended 3 times. Theoretical analysis and experimental results both indicate that the high Q factor repeater coil can extend the readout distance more. With the copper wire repeater coil as well as a higher power supply voltage, the passive wireless multi-parameter sensing system finally achieves a maximum readout distance of 13.5 cm.
Involvement of MrgprC in Electroacupuncture Analgesia for Attenuating CFA‐Induced Thermal Hyperalgesia by Suppressing the TRPV1 Pathway
Authors: Liu Ying-jun , Lin Xiao-xi , Fang Jian-qiao , Fang Fang
Published: February 2018

Mas‐related G‐protein‐coupled receptor C (MrgprC) plays an important role in modulating chronic inflammatory pain. Electroacupuncture (EA) has a satisfactory analgesic effect on chronic pain. This study aimed to investigate the involvement of MrgprC and its transient receptor potential vanilloid 1 (TRPV1) pathway in EA analgesia in chronic inflammatory pain. Chronic inflammatory pain was induced by subcutaneously injecting complete Freund’s adjuvant (CFA) into the left hind paw. EA (2/100 Hz) stimulation was administered. MrgprC siRNAs were intrathecally administered to inhibit MrgprC expression, and bovine adrenal medulla 8‐22 (BAM8‐22) was used to activate MrgprC. The mechanical allodynia was decreased by EA significantly since day 3. The piled analgesic effect of EA was partially blocked by 6 intrathecal administrations of MrgprC siRNA. Both EA and BAM8‐22 could downregulate the expression of TRPV1 and PKC in both the DRG and the SCDH. Both EA and BAM8‐22 could also decrease the TRPV1 translocation and p‐TRPV1 level in both the DRG and the SCDH. The effects of EA on PKCε, TRPV1 translocation, and p‐TRPV1 in both the DRG and the SCDH were reversed by MrgprC siRNA. The results indicated that MrgprC played crucial roles in chronic pain modulation and was involved in EA analgesia partially through the regulation of TRPV1 function at the DRG and SCDH levels.
Vibration Characteristics Analysis of Cylindrical Shell‐Plate Coupled Structure Using an Improved Fourier Series Method
Authors: Cao Yipeng , Zhang Runze , Zhang Wenping , Wang Jinzhao
Published: February 2018

A simple yet accurate solution procedure based on the improved Fourier series method (IFSM) is applied to the vibration characteristics analysis of a cylindrical shell‐circular plate (S‐P) coupled structure subjected to various boundary conditions. By applying four types of coupling springs with arbitrary stiffness at the junction of the coupled structure, the mechanical coupling effects are completely considered. Each of the plate and shell displacement functions is expressed as the superposition of a two‐dimensional Fourier series and several supplementary functions. The unknown series‐expansion coefficients are treated as the generalized coordinates and determined using the familiar Rayleigh‐Ritz procedure. Using the IFSM, a unified solution for the S‐P coupled structure with symmetrical and asymmetrical boundary conditions can be derived directly without the need to change either the equations of motion or the expressions of the displacements. This solution can be verified by comparing the current results with those calculated by the finite‐element method (FEM). The effects of several significant factors, including the restraint stiffness, the coupling stiffness, and the situation of coupling, are presented. The forced vibration behaviors of the S‐P coupled structure are also illustrated.
Acute Isolated Hyperbilirubinemia as a Presentation of Alcoholic Liver Disease: A Case Report and Literature Review
Authors: Hossain Muhammad Rajib , Pandey Ramesh Kumar , Islam Mohammad Faridul , Datar Praveen , Gayam Vijay , Puri Pradeep , Malar Thwin
Published: February 2018

Isolated hyperbilirubinemia as a manifestation of alcoholic liver disease without significant liver abnormalities is seen very rarely. We report such a case where a patient with chronic alcoholism presented to the ER with acute jaundice with bilirubin of 24.8 mg/dl, predominantly conjugated in nature along with mild elevation of AST (76 IU/L). There were no other abnormalities of the liver function. The patient underwent extensive laboratory and imaging tests that excluded extrahepatic cholestasis, viral and autoimmune hepatitis, ischemic hepatitis, and so forth. Liver biopsy excluded hemochromatosis, dysplasia, or malignancy and other differentials. Bilirubin gradually trended down to 7.3 mg/dl when alcohol consumption was stopped.
The Prevalence and Underreporting of Needlestick Injuries among Dental Healthcare Workers in Pakistan: A Systematic Review
Authors: Pervaiz Mehak , Gilbert Ruth , Ali Nasreen
Published: February 2018

Needlestick injuries (NSIs) are a major occupational health problem among dental healthcare workers (HCWs) in Pakistan, which places them at a significant risk of acquiring blood-borne infections. However, not all NSIs are reported, leading to an underestimation of the actual prevalence. The harmful impacts of NSIs on the healthcare delivery necessitate an urgent need to measure its actual prevalence.Objectives. The aim of this study was to review literature to estimate the prevalence and reporting rates of NSIs among dental-HCWs in Pakistan.Methods. 713 potentially relevant citations were identified by electronic databases and hand searching of articles. Nine primary studies were subsequently identified to be included in the review.Results. The results of the included studies indicate that the prevalence of NSIs among Pakistani dental-HCWs was between 30% and 73%. The rate of reporting of NSIs was between 15% and 76%, and the most common reason was found to be the lack of awareness regarding the reporting system, or of the need to report NSIs.Conclusion. It is evident from the review of the included studies that there is a significantly high prevalence and a low rate of reporting of NSIs among dental-HCWs in Pakistan, suggesting the need to setup an occupational health department in dental settings, for preventing, managing, recording, and monitoring NSIs.
Oncogenic Kinase–Induced PKM2 Tyrosine 105 Phosphorylation Converts Nononcogenic PKM2 to a Tumor Promoter and Induces Cancer Stem–like Cells
Authors: Zhou Zhifen , Li Min , Zhang Lin , Zhao Hong , Şahin Özgür , Chen Jing , Zhao Jean J. , Songyang Zhou , Yu Dihua
Published: February 2018

The role of pyruvate kinase M2 isoform (PKM2) in tumor progression has been controversial. Previous studies showed that PKM2 promoted tumor growth in xenograft models; however, depletion of PKM2 in the Brca1-loss–driven mammary tumor mouse model accelerates tumor formation. Because oncogenic kinases are frequently activated in tumors and PKM2 phosphorylation promotes tumor growth, we hypothesized that phosphorylation of PKM2 by activated kinases in tumor cells confers PKM2 oncogenic function, whereas nonphosphorylated PKM2 is nononcogenic. Indeed, PKM2 was phosphorylated at tyrosine 105 (Y105) and formed oncogenic dimers in MDA-MB-231 breast cancer cells, whereas PKM2 was largely unphosphorylated and formed nontumorigenic tetramers in nontransformed MCF10A cells. PKM2 knockdown did not affect MCF10A cell growth but significantly decreased proliferation of MDA-MB-231 breast cancer cells with tyrosine kinase activation. Multiple kinases that are frequently activated in different cancer types were identified to phosphorylate PKM2-Y105 in our tyrosine kinase screening. Introduction of the PKM2-Y105D phosphomimetic mutant into MCF10A cells induced colony formation and the CD44hi/CD24neg cancer stem–like cell population by increasing Yes-associated protein (YAP) nuclear localization. ErbB2, a strong inducer of PKM2-Y105 phosphorylation, boosted nuclear localization of YAP and enhanced the cancer stem–like cell population. Treatment with the ErbB2 kinase inhibitor lapatinib decreased PKM2-Y105 phosphorylation and cancer stem–like cells, impeding PKM2 tumor-promoting function. Taken together, phosphorylation of PKM2-Y105 by activated kinases exerts oncogenic functions in part via activation of YAP downstream signaling to increase cancer stem–like cell properties.

Significance: These findings reveal PKM2 promotes tumorigenesis by inducing cancer stem-like cell properties and clarify the paradox of PKM2′s dichotomous functions in tumor progression. Cancer Res; 78(9); 2248–61. ©2018 AACR.
Molecular Characterization of Renal Cell Carcinoma: A Potential Three-MicroRNA Prognostic Signature
Authors: Lokeshwar Soum D. , Talukder Asif , Yates Travis J. , Hennig Martin J.P. , Garcia-Roig Michael , Lahorewala Sarrah S. , Mullani Naureen N. , Klaassen Zachary , Kava Bruce R. , Manoharan Murugesan , Soloway Mark S. , Lokeshwar Vinata B.
Published: February 2018

Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach.

Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241).

Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2–4-fold) and miR-192 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21+194; miR-21+142-5p+194) significantly predicted metastasis and/or disease-specific mortality; miR-21+142-5p+194 (for metastasis): P = 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75–0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21+142-5p+194: P < 0.0001; OR, 0.37; 95% CI, 0.58–0.23).

Conclusions: The interconnected discovery–validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients.

Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464–72. ©2018 AACR.
Endo-/Epicardial Catheter Ablation of Atrial Fibrillation
Authors: Piorkowski Christopher , Kronborg Mads , Hourdain Jerome , Piorkowski Judith , Kirstein Bettina , Neudeck Sebastian , Wechselberger Simon , Päßler Ellen , Löwen Anastasia , El-Armouche Ali , Mayer Julia , Ulbrich Stefan , Pu Liying , Richter Utz , Gaspar Thomas , Huo Yan
Published: February 2018

Background:

Until today, catheter interventional mapping and ablation of atrial fibrillation (AF) has been limited to the right and left atrial endocardium. We report feasibility, electrophysiological findings, and clinical outcome using a combined endo-/epicardial catheter approach for mapping and ablation of AF.

Methods and Results:

Fifty-nine patients with permanence of pulmonary vein isolation and further symptomatic recurrences of paroxysmal AF, persistent AF, or atrial tachycardia underwent reablation using biatrial endo-/epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. Using continuous monitoring and a 3-month blanking period, freedom from AF/atrial tachycardia ≥2 minutes was defined as primary end point. In all patients, endo-/epicardial mapping and ablation was feasible using standard technologies of catheter access, 3-dimensional mapping, and radiofrequency ablation. Epicardial mapping and ablation did not add procedural risks. Exclusively epicardial low voltage substrates were found in 14% of the patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human AF patients (19% of the cohort). Epicardial ablation was needed in 80% of the patients. Over 23±10 months of follow-up freedom from arrhythmia recurrences measured 73%.

Conclusions:

Catheter-based endo-/epicardial mapping and ablation of AF was feasible and safe. Epicardial mapping provided new insights into AF mechanisms. Epicardial ablation increased transmurality of ablation lesions. Clinical outcome in this cohort of complex AF patients was favorable, indicating potential further development of current AF treatment.
Altered Repolarization Reserve in Failing Rabbit Ventricular Myocytes
Authors: Hegyi Bence , Bossuyt Julie , Ginsburg Kenneth S. , Mendoza Lynette M. , Talken Linda , Ferrier William T. , Pogwizd Steven M. , Izu Leighton T. , Chen-Izu Ye , Bers Donald M.
Published: February 2018

Background:

Electrophysiological remodeling and increased susceptibility for cardiac arrhythmias are hallmarks of heart failure (HF). Ventricular action potential duration (APD) is typically prolonged in HF, with reduced repolarization reserve. However, underlying K
+
current changes are often measured in nonphysiological conditions (voltage clamp, low pacing rates, cytosolic Ca
2+
buffers).

Methods and Results:

We measured the major K
+
currents (
I
Kr
,
I
Ks
, and
I
K1
) and their Ca
2+
- and β-adrenergic dependence in rabbit ventricular myocytes in chronic pressure/volume overload–induced HF (versus age-matched controls). APD was significantly prolonged only at lower pacing rates (0.2–1 Hz) in HF under physiological ionic conditions and temperature. However, when cytosolic Ca
2+
was buffered, APD prolongation in HF was also significant at higher pacing rates. Beat-to-beat variability of APD was also significantly increased in HF. Both
I
Kr
and
I
Ks
were significantly upregulated in HF under action potential clamp, but only when cytosolic Ca
2+
was not buffered. CaMKII (Ca
2+
/calmodulin-dependent protein kinase II) inhibition abolished
I
Ks
upregulation in HF, but it did not affect
I
Kr
.
I
Ks
response to β-adrenergic stimulation was also significantly diminished in HF.
I
K1
was also decreased in HF regardless of Ca
2+
buffering, CaMKII inhibition, or β-adrenergic stimulation.

Conclusions:

At baseline Ca
2+
-dependent upregulation of
I
Kr
and
I
Ks
in HF counterbalances the reduced
I
K1
, maintaining repolarization reserve (especially at higher heart rates) in physiological conditions, unlike conditions of strong cytosolic Ca
2+
buffering. However, under β-adrenergic stimulation, reduced
I
Ks
responsiveness severely limits integrated repolarizing K
+
current and repolarization reserve in HF. This would increase arrhythmia propensity in HF, especially during adrenergic stress.
Noninvasive Immunometabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance
Authors: Lewis Andrew J.M. , Miller Jack J. , Lau Angus Z. , Curtis Mary K. , Rider Oliver J. , Choudhury Robin P. , Neubauer Stefan , Cunningham Charles H. , Carr Carolyn A. , Tyler Damian J.
Published: February 2018

Rationale:

Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping.

Objective:

To determine whether hyperpolarized MR using [1-
13
C]pyruvate can assess the local cardiac inflammatory response after MI.

Methods and Results:

We performed hyperpolarized [1-
13
C]pyruvate MR studies in small and large animal models of MI and in macrophage-like cell lines and measured the resulting [1-
13
C]lactate signals. MI caused intense [1-
13
C]lactate signal in healing myocardial segments at both day 3 and 7 after rodent MI, which was normalized at both time points after monocyte/macrophage depletion. A near-identical [1-
13
C]lactate signature was also seen at day 7 after experimental MI in pigs. Hyperpolarized [1-
13
C]pyruvate MR spectroscopy in macrophage-like cell suspensions demonstrated that macrophage activation and polarization with lipopolysaccharide almost doubled hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose in activated cells normalized lactate label flux rates and markedly inhibited the production of key proinflammatory cytokines. Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1-
13
C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines. Cine MRI demonstrated improvements in systolic function in 2-DG (2-deoxyglucose)–treated rats at 3 months.

Conclusions:

Hyperpolarized MR using [1-
13
C]pyruvate provides a novel method for the assessment of innate immune cell-driven inflammation in the heart after MI, with broad potential applicability across other cardiovascular disease states and suitability for early clinical translation.
“Malignant” Left Ventricular Hypertrophy Identifies Subjects at High Risk for Progression to Asymptomatic Left Ventricular Dysfunction, Heart Failure, and Death: MESA (Multi‐Ethnic Study of Atherosclerosis)
Authors: Peters Matthew N. , Seliger Stephen L. , Christenson Robert H. , Hong‐Zohlman Susie N. , Daniels Lori B. , Lima Joao A.C. , de Lemos James A. , Neeland Ian J. , deFilippi Christopher R.
Published: February 2018

Background

As heart failure (
HF
)‐associated morbidity and mortality continue to escalate, enhanced focus on prevention is increasingly important. “Malignant” left ventricular (LV) hypertrophy (
LVH
):
LVH
combined with an elevated cardiac biomarker reflecting either injury (high‐sensitivity cardiac troponin T), or strain (amino‐terminal pro‐B‐type natriuretic peptide) has predicted accelerated progression to
HF
. We sought to determine whether malignant
LVH
identified community‐dwelling adults initially free of cardiovascular disease at high risk of asymptomatic decline in
LV
ejection fraction or a clinical cardiovascular event.

Methods and Results

A total of 4985 of 6814 individuals without prevalent
cardiovascular disease
underwent baseline cardiac magnetic resonance for
LVH
in combination with measurement of plasma high‐sensitivity cardiac troponin T and amino‐terminal pro‐B‐type natriuretic peptide as part of MESA (Multi‐Ethnic Study of Atherosclerosis) and were subsequently divided into 4 groups: (1) No
LVH
, no elevated biomarkers (n=2206; 44.3%); (2) No
LVH
, ≥1 elevated biomarkers (n=2275; 45.7%); (3)
LVH
, no elevated biomarkers (n=153; 3.0%); and (4)
LVH
, ≥1 elevated biomarkers (malignant
LVH
; n=351; 7.0%).
Cardiac magnetic resonance
was repeated 10 years later (n=2831) for assessment of
LV ejection fraction
<50%. Median follow‐up was 12.2 years. Malignant
LVH
was associated with 7.0‐, 3.5‐, and 2.6‐fold adjusted increases in incidence of
HF
,
cardiovascular
death, and asymptomatic
LV
dysfunction, respectively, versus group 1. New‐onset
HF
was predominately
HF
with reduced ejection fraction (9.5‐fold increase).

Conclusions

Malignant
LVH
is predictive of progression to asymptomatic
LV
dysfunction,
HF
(particularly
HF
with reduced ejection fraction), and
cardiovascular
death. Consequently, malignant
LVH
represents a high‐risk phenotype among individuals without known
cardiovascular disease
, which should be targeted for increased surveillance and more‐aggressive therapies.
Bilateral Transcutaneous Electrical Nerve Stimulation Improves Lower‐Limb Motor Function in Subjects With Chronic Stroke: A Randomized Controlled Trial
Authors: Kwong Patrick W. H. , Ng Gabriel Y. F. , Chung Raymond C. K. , Ng Shamay S. M.
Published: February 2018

Background

Transcutaneous electrical nerve stimulation (
TENS
) has been used to augment the efficacy of task‐oriented training (
TOT
) after stroke. Bilateral intervention approaches have also been shown to be effective in augmenting motor function after stroke. The purpose of this study was to compare the efficacy of bilateral
TENS
combined with
TOT
versus unilateral
TENS
combined with
TOT
in improving lower‐limb motor function in subjects with chronic stroke.

Methods and Results

Eighty subjects were randomly assigned to bilateral
TENS
+
TOT
or to unilateral
TENS
+
TOT
and underwent 20 sessions of training over a 10‐week period. The outcome measures included the maximal strength of the lower‐limb muscles and the results of the Lower Extremity Motor Coordination Test, Berg Balance Scale, Step Test, and Timed Up and Go test. Each participant was assessed at baseline, after 10 and 20 sessions of training and 3 months after the cessation of training. The subjects in the bilateral
TENS
+
TOT
group showed greater improvement in paretic ankle dorsiflexion strength (β=1.32;
P
=0.032) and in the completion time for the Timed Up and Go test (β=−1.54;
P
=0.004) than those in the unilateral
TENS
+
TOT
group. However, there were no significant between‐group differences for other outcome measures.

Conclusions

The application of bilateral
TENS
over the common peroneal nerve combined with
TOT
was superior to the application of unilateral
TENS
combined with
TOT
in improving paretic ankle dorsiflexion strength after 10 sessions of training and in improving the completion time for the Timed Up and Go test after 20 sessions of training.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02152813.
Age at Menarche and Cardiometabolic Health: A Sibling Analysis in the Scottish Family Health Study
Authors: Magnus Maria C. , Lawlor Debbie A. , Iliodromiti Stamatina , Padmanabhan Sandosh , Nelson Scott M. , Fraser Abigail
Published: February 2018

Background

Previous studies of age at menarche and cardiometabolic health report conflicting findings, and only a few could account for childhood characteristics. We aimed to estimate the associations of age at menarche with cardiovascular risk factors in unrelated women and within sister groups, under the assumption that within‐sibship estimates will be better adjusted for shared genetics and early life environment.

Methods and Results

Our study included 7770 women, from 5984 sibships, participating in the GS:SFHS (Generation Scotland: Scottish Family Health Study). We used fixed‐ and between‐effects linear regression to estimate the associations within sister groups and between unrelated individuals, respectively. Within sibships, the mean difference between sisters with early menarche (≤11 years) and sisters with menarche at 12 to 13 years was 1.73 mm Hg (95% confidence interval [CI], −0.41 to 3.86) for systolic blood pressure, 1.26 mm Hg (95% CI, −0.02 to 2.55) for diastolic blood pressure, −0.06 nmol/L (95% CI, −0.11 to −0.02) for high‐density lipoprotein, 0.20 nmol/L (95% CI, 0.08–0.32) for non–high‐density lipoprotein, −0.34% (95% CI, −1.98 to 1.30) for glucose, 1.60 kg/m
2
(95% CI, 0.92–2.28) for body mass index, and 2.75 cm (95% CI, 1.06–4.44) for waist circumference. There was weak evidence of associations between later menarche (14–15 or ≥16 years) and lower body mass index, waist circumference, and blood pressure. We found no strong evidence that estimates from within‐ and between‐sibship analyses differed (all
P
values >0.1). The associations with other cardiovascular risk factors were attenuated after adjustment for adult body mass index.

Conclusions

Our results suggest that confounding by shared familial characteristics is unlikely to be a major driver of the association between early menarche and adverse cardiometabolic health but do not exclude confounding by individual‐level characteristics.
ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study
Authors: Tastet Lionel , Capoulade Romain , Shen Mylène , Clavel Marie‐Annick , Côté Nancy , Mathieu Patrick , Arsenault Marie , Bédard Élisabeth , Tremblay Alexe , Samson Marilie , Bossé Yohan , Dumesnil Jean G. , Arsenault Benoit J. , Beaudoin Jonathan , Bernier Mathieu , Després Jean‐Pierre , Pibarot Philippe
Published: February 2018

Background

Previous studies reported that middle‐aged patients with atherogenic lipoprotein‐lipid profile exhibit faster progression of aortic valve stenosis (
AS
). The ratio of apolipoprotein B/apolipoprotein A‐I (apoB/apoA‐I) reflects the balance between atherogenic and anti‐atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA‐I ratio and
AS
hemodynamic progression and to determine whether this association varies according to age.

Methods and Results

A total of 159 patients (66±13 years, 73% men) with
AS
were prospectively recruited in the
PROGRESSA
(Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of
AS
was determined by the change in peak aortic jet velocity (V
peak
) measured by Doppler‐echocardiography between baseline and 2‐year follow‐up. Patients in the top tertile of apoB/apoA‐I ratio (≥0.62) had a faster progression rate of
AS
compared with those in the bottom/mid tertiles (V
peak
progression: 0.30 [0.09˗0.49] versus 0.16 [0.01˗0.36] m/s,
P
=0.02). There was a significant interaction (
P
=0.007) between apoB/apoA‐I ratio and age. Among younger patients (ie, aged <70 years; median value of the cohort), those in the top tertile of apoB/apoA‐I ratio had a 3.4‐fold faster
AS
progression compared with those in the bottom/mid tertiles (V
peak
progression: 0.34 [0.13˗0.69] versus 0.10 [−0.03˗0.31] m/s,
P
=0.002), whereas there was no significant difference between tertiles in the subgroup of older patients (
P
=0.83). After comprehensive adjustment, higher apoB/apoA‐I ratio was significantly associated with faster
AS
progression in the subset of younger patients (all, standardized β≥0.36;
P
≤0.01).

Conclusions

Higher apoB/apoA‐I ratio is significantly associated with faster hemodynamic progression of
AS
in the younger patients. These findings suggest that atherogenic lipid factors may play a crucial role in the pathogenesis of
AS
in younger patients, but may be are less important in older patients.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
01679431.
Novel α‐Actin Gene Mutation p.(Ala21Val) Causing Familial Hypertrophic Cardiomyopathy, Myocardial Noncompaction, and Transmural Crypts. Clinical‐Pathologic Correlation
Authors: Frustaci Andrea , De Luca Alessandro , Guida Valentina , Biagini Tommaso , Mazza Tommaso , Gaudio Carlo , Letizia Claudio , Russo Matteo Antonio , Galea Nicola , Chimenti Cristina
Published: February 2018

Background

Mutations of α‐actin gene (
ACTC
1) have been phenotypically related to various cardiac anomalies, including hypertrophic cardiomyopathy and dilated cardiomyopathy and left ventricular (LV) myocardial noncompaction. A novel
ACTC
mutation is reported as cosegregating for familial hypertrophic cardiomyopathy and LV myocardial noncompaction with transmural crypts.

Methods and Results

In an Italian family of 7 subjects, 4 aged 10 (
II
‐1), 14 (
II
‐2), 43 (I‐4) and 46 years (I‐5), presenting abnormal
ECG
changes, dyspnea and palpitation (
II
‐2, I‐4, and I‐5), and recurrent cerebral ischemic attack (I‐5), underwent 2‐dimensional echo, cardiac magnetic resonance, Holter monitoring, and next‐generation sequencing gene analysis. Patients
II
‐2 and I‐5 with ventricular tachycardia underwent a cardiac invasive study, including coronary with LV angiography and endomyocardial biopsy. In all the affected members,
ECG
showed right bundle branch block and left anterior hemiblock with age‐related prolongation of
QRS
duration. Two‐dimensional echo and cardiac magnetic resonance documented LV myocardial noncompaction in all and in I‐4, I‐5, and
II
‐2 a progressive
LV
hypertrophy up to 22‐mm maximal wall thickness. Coronary arteries were normal.
LV
angiography showed transmural crypts progressing to spongeous myocardial transformation with
LV
dilatation and dysfunction in the oldest subject. At histology and electron microscopy detachment of myocardiocytes were associated with cell and myofibrillar disarray and degradation of intercalated discs causing disanchorage of myofilaments to cell membrane. Next‐generation sequencing showed in affected members an unreported p.(Ala21Val) mutation of
ACTC
.

Conclusions

Novel p.(Ala21Val) mutation of
ACTC
1 causes myofibrillar and intercalated disc alteration leading to familial hypertrophic cardiomyopathy and LV myocardial noncompaction with transmural crypts.
Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis
Authors: Wen Guanmei , An Weiwei , Chen Jiangyong , Maguire Eithne M. , Chen Qishan , Yang Feng , Pearce Stuart W. A. , Kyriakides Maria , Zhang Li , Ye Shu , Nourshargh Sussan , Xiao Qingzhong
Published: February 2018

Background

To investigate whether neutrophil elastase (
NE
) plays a causal role in atherosclerosis, and the molecular mechanisms involved.

Methods and Results

NE
genetic–deficient mice (Apolipoprotein E
−/−
/
NE
−/−
mice), bone marrow transplantation, and a specific
NE
inhibitor (
GW
311616A) were employed in this study to establish the causal role of
NE
in atherosclerosis. Aortic expression of
NE mRNA
and plasma
NE
activity was significantly increased in high‐fat diet (
HFD
)–fed wild‐type (
WT
) (Apolipoprotein E
−/−
) mice but, as expected, not in
NE
‐deficient mice. Selective
NE
knockout markedly reduced
HFD
‐induced atherosclerosis and significantly increased indicators of atherosclerotic plaque stability. While plasma lipid profiles were not affected by
NE
deficiency, decreased levels of circulating proinflammatory cytokines and inflammatory monocytes (Ly6C
hi
/
CD
11b
+
) were observed in
NE
‐deficient mice fed with an
HFD
for 12 weeks as compared with
WT
. Bone marrow reconstitution of
WT
mice with
NE
−/−
bone marrow cells significantly reduced
HFD
‐induced atherosclerosis, while bone marrow reconstitution of
NE
−/−
mice with
WT
bone marrow cells restored the pathological features of atherosclerotic plaques induced by
HFD
in
NE
‐deficient mice. In line with these findings, pharmacological inhibition of
NE
in
WT
mice through oral administration of
NE
inhibitor
GW
311616A also significantly reduced atherosclerosis. Mechanistically, we demonstrated that
NE
promotes foam cell formation by increasing
ATP
‐binding cassette transporter
ABCA
1 protein degradation and inhibiting macrophage cholesterol efflux.

Conclusions

We outlined a pathogenic role for
NE
in foam cell formation and atherosclerosis development. Consequently, inhibition of
NE
may represent a potential therapeutic approach to treating cardiovascular disease.
Lejeunea streimannii (Lejeuneaceae, Marchantiophyta), a remarkable new species with robust stems and 5(or 6)-keeled perianths from Papua New Guinea
Authors: WEI YU-MEI , TANG QI-MING , ZHU RUI-LIANG
Published: February 2018

Lejeunea streimannii, a new species from Papua New Guinea, is described and illustrated. The new species is characterized by the dioicous plants, robust stem with 18‒21 rows of cortical cells and a ventral merophyte 4‒6 cells wide, ovate leaves with a rounded, strongly incurved leaf apex, small lobules with unicelluar first tooth and blunt second tooth, large underleaves with a cordate base, inflated perianths with 5(or 6) crenate, slightly winged keels.
WIVERN: A New Satellite Concept to Provide Global In-Cloud Winds, Precipitation, and Cloud Properties
Authors: Illingworth A. J. , Battaglia A. , Bradford J. , Forsythe M. , Joe P. , Kollias P. , Lean K. , Lori M. , Mahfouf J.-F. , Melo S. , Midthassel R , Munro Y. , Nicol J. , Potthast R. , Rennie M. , Stein T. H. M. , Tanelli S. , Tridon F. , Walden C. J. , Wolde M.
Published: February 2018

This paper presents a conically scanning spaceborne Dopplerized 94-GHz radar Earth science mission concept: Wind Velocity Radar Nephoscope (WIVERN). WIVERN aims to provide global measurements of in-cloud winds using the Doppler-shifted radar returns from hydrometeors. The conically scanning radar could provide wind data with daily revisits poleward of 50°, 50-km horizontal resolution, and approximately 1-km vertical resolution. The measured winds, when assimilated into weather forecasts and provided they are representative of the larger-scale mean flow, should lead to further improvements in the accuracy and effectiveness of forecasts of severe weather and better focusing of activities to limit damage and loss of life. It should also be possible to characterize the more variable winds associated with local convection. Polarization diversity would be used to enable high wind speeds to be unambiguously observed; analysis indicates that artifacts associated with polarization diversity are rare and can be identified. Winds should be measurable down to 1 km above the ocean surface and 2 km over land. The potential impact of the WIVERN winds on reducing forecast errors is estimated by comparison with the known positive impact of cloud motion and aircraft winds. The main thrust of WIVERN is observing in-cloud winds, but WIVERN should also provide global estimates of ice water content, cloud cover, and vertical distribution, continuing the data series started by CloudSat with the conical scan giving increased coverage. As with CloudSat, estimates of rainfall and snowfall rates should be possible. These nonwind products may also have a positive impact when assimilated into weather forecasts.
Numerical Simulations of Two-Layer Flow past Topography. Part I: The Leeside Hydraulic Jump
Authors: Rotunno Richard , Bryan George H.
Published: February 2018

Laboratory observations of the leeside hydraulic jump indicate it consists of a statistically stationary turbulent motion in an overturning wave. From the point of view of the shallow-water equations (SWE), the hydraulic jump is a discontinuity in fluid-layer depth and velocity at which kinetic energy is dissipated. To provide a deeper understanding of the leeside hydraulic jump, three-dimensional numerical solutions of the Navier–Stokes equations (NSE) are carried out alongside SWE solutions for nearly identical physical initial-value problems. Starting from a constant-height layer flowing over a two-dimensional obstacle at constant speed, it is demonstrated that the SWE solutions form a leeside discontinuity owing to the collision of upstream-moving characteristic curves launched from the obstacle. Consistent with the SWE solution, the NSE solution indicates the leeside hydraulic jump begins as a steepening of the initially horizontal density interface. Subsequently, the NSE solution indicates overturning of the density interface and a transition to turbulence. Analysis of the initial-value problem in these solutions shows that the tendency to form either the leeside height–velocity discontinuity in the SWE or the overturning density interface in the exact NSE is a feature of the inviscid, nonturbulent fluid dynamics. Dissipative turbulent processes associated with the leeside hydraulic jump are a consequence of the inviscid fluid dynamics that initiate and maintain the locally unstable conditions.
Updating Autonomous Underwater Vehicle Risk Based on the Effectiveness of Failure Prevention and Correction
Authors: Brito Mario P. , Griffiths Gwyn
Published: February 2018

Autonomous underwater vehicles (AUVs) have proven to be feasible platforms for marine observations. Risk and reliability studies on the performance of these vehicles by different groups show a significant difference in reliability, with the observation that the outcomes depend on whether the vehicles are operated by developers or nondevelopers. This paper shows that this difference in reliability is due to the failure prevention and correction procedures—risk mitigation—put in place by developers. However, no formalization has been developed for updating the risk profile based on the expected effectiveness of the failure prevention and correction process. A generic Bayesian approach for updating the risk profile is presented, based on the probability of failure prevention and correction and the number of subsequent deployments on which the failure does not occur. The approach, which applies whether the risk profile is captured in a parametric or nonparametric survival model, is applied to a real case study of the International Submarine Engineering Ltd. (ISE) Explorer AUV.