bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidimensional Dynamic Programming Algorithm for N‐Level Batching with Hierarchical Clustering Structure
Authors: Lim Seung-Kil , Bang June-Young , Kim Jae-Gon
Published: April 2017

This study focuses on the N‐level batching problem with a hierarchical clustering structure. Clustering is the task of grouping a set of item types in such a way that item types in the same cluster are more similar (in some sense or another) to each other than to those in other clusters. In hierarchical clustering structure, more and more different item types are clustered together as the level of the hierarchy increases. N‐level batching is the process by which items with different types are grouped into several batches passed from level 1 to level N sequentially for given hierarchical clustering structure such that batches in each level should satisfy the maximum and minimum batch size requirements of the level. We consider two types of processing costs of the batches: unit processing cost and batch processing cost. We formulate the N‐level batching problem with a hierarchical clustering structure as a nonlinear integer programming model with the objective of minimizing the total processing cost. To solve the problem optimally, we propose a multidimensional dynamic programming algorithm with an example.
Impact of an Intensive Perinatal Handwashing Promotion Intervention on Maternal Handwashing Behavior in the Neonatal Period: Findings from a Randomized Controlled Trial in Rural Bangladesh
Authors: Ram Pavani Kalluri , Nasreen Sharifa , Kamm Kelly , Allen Jelena , Kumar Swapna , Rahman Mohammad Anisur , Zaman K. , El Arifeen Shams , Luby Stephen P.
Published: April 2017

One-quarter of neonatal deaths are attributed to infections. Maternal handwashing with soap may prevent neonatal sepsis. We examined impact of intensive handwashing promotion on handwashing behavior of mothers of neonates. In Matlab, Bangladesh, we randomly allocated pregnant women at 28–32 weeks’ gestation to intensive handwashing promotion or control. Behavior change communicators used a participatory approach to motivate maternal handwashing with soap and provided soap and handwashing stations. In the neonatal period, we observed soap and water at handwashing places and, at the end of the neonatal period, we estimated impact on maternal handwashing by structured observation. Among 253 women enrolled, intervention households were between 5.7 and 15.2 times as likely as control households to have soap and water present at the handwashing station in the baby’s sleeping area. Intervention mothers washed hands with soap 4.1 times as frequently as controls (95% CI 2.55–6.59); handwashing with soap at recommended times was infrequent in both intervention (9%) and control (2%) groups. Intensively promoting handwashing with soap resulted in increased availability of soap and water at handwashing places, but only a modest increase in maternal handwashing with soap. Novel approaches to motivating handwashing behavior to protect newborns should be developed and evaluated.
Mathematical Modeling for Risk Averse Firm Facing Loss Averse Customer’s Stochastic Uncertainty
Authors: Kim Seungbeom , Lee Jinpyo , Park Minjae
Published: April 2017

To optimize the firm’s profit during a finite planning horizon, a dynamic programming model is used to make joint pricing and inventory replenishment decision assuming that customers are loss averse and the firm is risk averse. We model the loss averse customer’s demand using the multinomial choice model. In this choice model, we consider the acquisition and transition utilities widely used by a mental accounting theory which also incorporate the reference price and actual price. Then, we show that there is an optimal inventory policy which is base‐stock policy depending on the accumulated wealth in each period.
Establishment and Characterization of a Nude Mouse Model of Subcutaneously Implanted Tumors and Abdominal Metastasis in Gastric Cancer
Authors: Zhu Yin , Hu Yi , Cheng Ming , Zeng Chun-Yan , Yang Zhen , Zhou Xiao-Dong , Chen Jiang , Lu Nong-Hua
Published: April 2017

A mouse gastric cancer model is an important tool for studying the mechanisms of gastric cancer. To establish subcutaneously implanted tumors, MKN-45 cell suspensions and tumor tissues were implanted into the middle of the right armpit of nude mice. To generate an abdominal metastasis model, MKN-45 cell suspensions and tumor tissue homogenates were implanted into the middle of the lower abdomen. We measured the weights of the nude mice and the longest dimension, shortest dimension, thickness, and volume of the tumor. We also analyzed the rate of tumor formation, the time required for tumor formation, and the number and size of abdominal tumors in the mice. The rates of formation of the subcutaneously implanted tumors were 100%, 0%, and 100% in the nude mice inoculated with 2 × 107cells/mL or 1 × 107cells/mL of the MKN-45 cell suspension or the tumor tissue homogenate (2 × 107cells/mL), respectively. The rates of metastatic abdominal tumor formation were 100%, 50%, and 75% in mice inoculated with 5 × 107cells/mL or 1 × 107cells/mL of the tumor tissue homogenate or the MKN-45 cell suspension (5 × 107cells/mL), respectively. We derived tumor tissues and tumor tissue homogenates from nude mice prior to establishing the subcutaneous model of implanted tumors and the abdominal metastasis model of gastric cancer, respectively.
Clara Cell Protein Expression in Mechanically Ventilated Term and Preterm Infants with Respiratory Distress Syndrome and at Risk of Bronchopulmonary Dysplasia: A Pilot Study
Authors: Guzmán-Bárcenas José , Calderón-Moore Antonio , Baptista-González Héctor , Irles Claudine
Published: April 2017

The aim of this pilot study was to determine Clara cell protein (CC16) concentration in bronchoalveolar lavages (BAL) fluid from full-term and preterm (<37 weeks’ gestational age) neonates requiring respiratory support, having symptoms of neonatal respiratory distress syndrome, and at risk of bronchopulmonary dysplasia (BPD). We hypothesized that CC16 may be predictive of BPD diagnosis regardless of gestational age. BAL fluid CC16 was measured by ELISA at birth and at day 7 of life. Both groups that developed BPD showed significantly decreased BAL fluid CC16 levels compared to those infants that did not develop the disease. CC16 positively correlated with diagnosis of BPD and negatively with the severity of the disease. These results suggest that BAL fluid CC16 levels may have a diagnostic value at day 7 for BPD in both term and preterm infants. This study demonstrates the potential utility of BAL fluid CC16 levels as a biomarker for BPD in term infants.
Fatigue Life Assessment of Orthotropic Steel Deck with UHPC Pavement
Authors: Jiang Xu , Yuan Yuan , Wu Chong , Luo Chengwei
Published: April 2017

In recent years, a number of large-span bridges with orthotropic steel decks were constructed in China. With increasing traffic volumes and higher wheel loads, many fatigue cracks developed at the welds and the edge of cut-out holes. This paper aims at presenting the numerical analysis on the fatigue performance of the orthotropic steel deck using ultrahigh performance concrete (UHPC) overlay as the deck pavement instead of the conventional asphalt concrete pavement. By using finite element method (FEM) model, stress distribution at fatigue sensitive locations under the action of wheel loads is characterized and the obtained stress ranges indicate that the UHPC pavement significantly reduces the magnitude of the stress peak valued. A suggested truck stream model based on the weigh-in-motion (WIM) data of four bridges in China is employed to calculate the stress variation at specific fatigue details. Furthermore, the fatigue damage accumulation at fatigue details under the UHPC and conventional asphalt concrete pavement is studied based on Miner’s linear cumulative damage rule and the rain-flow method. The results indicate that the UHPC pavement on the orthotropic steel deck can extend the service lives of the concerned regions over 100 years, but the fatigue lives will reduce significantly when the elastic modulus of UHPC decreases to 50% of the original value.
A Predictive Model for Guillain-Barré Syndrome Based on Single Learning Algorithms
Authors: Canul-Reich Juana , Frausto-Solís Juan , Hernández-Torruco José
Published: April 2017

Background. Guillain-Barré Syndrome (GBS) is a potentially fatal autoimmune neurological disorder. The severity varies among the four main subtypes, named as Acute Inflammatory Demyelinating Polyneuropathy (AIDP), Acute Motor Axonal Neuropathy (AMAN), Acute Motor Sensory Axonal Neuropathy (AMSAN), and Miller-Fisher Syndrome (MF). A proper subtype identification may help to promptly carry out adequate treatment in patients. Method. We perform experiments with 15 single classifiers in two scenarios: four subtypes’ classification and One versus All (OvA) classification. We used a dataset with the 16 relevant features identified in a previous phase. Performance evaluation is made by 10-fold cross validation (10-FCV). Typical classification performance measures are used. A statistical test is conducted in order to identify the top five classifiers for each case. Results. In four GBS subtypes’ classification, half of the classifiers investigated in this study obtained an average accuracy above 0.90. In OvA classification, the two subtypes with the largest number of instances resulted in the best classification results. Conclusions. This study represents a comprehensive effort on creating a predictive model for Guillain-Barré Syndrome subtypes. Also, the analysis performed in this work provides insight about the best single classifiers for each classification case.
The Observer’s Guide to the Gamma-Ray Burst Supernova Connection
Authors: Cano Zach , Wang Shan-Qin , Dai Zi-Gao , Wu Xue-Feng
Published: April 2017

We present a detailed report of the connection between long-duration gamma-ray bursts (GRBs) and their accompanying supernovae (SNe). The discussion presented here places emphasis on how observations, and the modelling of observations, have constrained what we know about GRB-SNe. We discuss their photometric and spectroscopic properties, their role as cosmological probes, including their measured luminosity–decline relationships, and how they can be used to measure the Hubble constant. We present a statistical summary of their bolometric properties and use this to determine the properties of the “average” GRB-SN. We discuss their geometry and consider the various physical processes that are thought to power the luminosity of GRB-SNe and whether differences exist between GRB-SNe and the SNe associated with ultra-long-duration GRBs. We discuss how observations of their environments further constrain the physical properties of their progenitor stars and give a brief overview of the current theoretical paradigms of their central engines. We then present an overview of the radioactively powered transients that have been photometrically associated with short-duration GRBs, and we conclude by discussing what additional research is needed to further our understanding of GRB-SNe, in particular the role of binary-formation channels and the connection of GRB-SNe with superluminous SNe.
Effects of Force Load, Muscle Fatigue, and Magnetic Stimulation on Surface Electromyography during Side Arm Lateral Raise Task: A Preliminary Study with Healthy Subjects
Authors: Cao Liu , Wang Ying , Hao Dongmei , Rong Yao , Yang Lin , Zhang Song , Zheng Dingchang
Published: April 2017

The aim of this study was to quantitatively investigate the effects of force load, muscle fatigue, and extremely low-frequency (ELF) magnetic stimulation on surface electromyography (SEMG) signal features during side arm lateral raise task. SEMG signals were recorded from 18 healthy subjects on the anterior deltoid using a BIOSEMI ActiveTwo system during side lateral raise task (with the right arm 90 degrees away from the body) with three different loads on the forearm (0 kg, 1 kg, and 3 kg; their order was randomized between subjects). The arm maintained the loads until the subject felt exhausted. The first 10 s recording for each load was regarded as nonfatigue status and the last 10 s before the subject was exhausted was regarded as fatigue status. The subject was then given a five-minute resting between different loads. Two days later, the same experiment was repeated on every subject, and this time the ELF magnetic stimulation was applied to the subject’s deltoid muscle during the five-minute rest period. Three commonly used SEMG features, root mean square (RMS), median frequency (MDF), and sample entropy (SampEn), were analyzed and compared between different loads, nonfatigue/fatigue status, and ELF stimulation and no stimulation. Variance analysis results showed that the effect of force load on RMS was significant (p<0.001) but not for MDF and SampEn (bothp>0.05). In comparison with nonfatigue status, for all the different force loads with and without ELF stimulation, RMS was significantly larger at fatigue (allp<0.001) and MDF and SampEn were significantly smaller (allp<0.001).
Characterization of Focal Liver Lesions Indistinctive on B Mode Ultrasound: Benefits of Contrast-Enhanced Ultrasound
Authors: Dong Yi , Mao Feng , Cao Jiaying , Fan Peili , Wang Wen-Ping
Published: April 2017

Aim. The aim of this prospective study was to evaluate the additional value of contrast-enhanced ultrasound (CEUS) in identifying and characterizing of focal liver lesions (FLLs) that are indistinctive on B mode ultrasound (BMUS). Methods. The study focused on 70 consecutive patients (male 46, female 24; mean age, 53.1 years ± 10). All lesions were detected by MRI but could not be clearly visualized by BMUS. CEUS was performed by injected SonoVue® (Bracco Imaging Spa, Milan, Italy) as a quick bolus into the antecubital vein. All lesions were proved by pathologic and MRI findings as primary or metastatic hepatic malignancies. Results. On CEUS, 45 (64.2%) FLLs displayed arterial hyperenhancement and 55 (78.5%) lesions showed hypoenhancement in portal venous and late phase (PVLP). Homogeneous and complete hyperenhancement pattern during the arterial phase is highly suspicious for HCC in liver cirrhosis (96.8%). Arterial isoenhancement and early washout during PVLP are characteristic for metastasis (73.3%). For recurrence lesions, arterial hyperenhancement and isoenhancement during PVLP are more common (60%). Conclusion. CEUS may provide added diagnostic values in FLLs appearing indistinctive on BMUS. Presence of early arterial enhancement and washout during PVLP may be helpful for detection of those lesions.
Therapeutic Risk and Benefits of Concomitantly Using Herbal Medicines and Conventional Medicines: From the Perspectives of Evidence Based on Randomized Controlled Trials and Clinical Risk Management
Authors: Zhang Xiu-lai , Chen Meng , Zhu Ling-ling , Zhou Quan
Published: April 2017

Despite increased awareness of the potential of herb‐drug interactions (HDIs), the lack of rigorous clinical evidence regarding the significance provides a challenge for clinicians and consumers to make rational decisions about the safe combination of herbal and conventional medicines. This review addressed HDIs based on evidence from randomized controlled trials (RCTs). Literature was identified by performing a PubMed search till January 2017. Risk description and clinical risk management were described. Among 74 finally included RCTs, 17 RCTs (22.97%) simply addressed pharmacodynamic HDIs. Fifty‐seven RCTs (77.03%) investigated pharmacokinetic HDIs and twenty‐eight of them showed potential or actual clinical relevance. The extent of an HDI may be associated with the factors such as pharmacogenomics, dose of active ingredients in herbs, time course of interaction, characteristics of the object drugs (e.g., administration routes and pharmacokinetic profiles), modification of herbal prescription compositions, and coexistence of inducers and inhibitors. Clinical professionals should enhance risk management on HDIs such as increasing awareness of potential changes in therapeutic risk and benefits, inquiring patients about all currently used conventional medicines and herbal medicines and supplements, automatically detecting highly substantial significant HDI by computerized reminder system, selecting the alternatives, adjusting dose, reviewing the appropriateness of physician orders, educating patients to monitor for drug‐interaction symptoms, and paying attention to follow‐up visit and consultation.
Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice
Authors: Dhondup Yangchen , Sjaastad Ivar , Sandanger Øystein , Aronsen Jan Magnus , Ahmed Muhammad Shakil , Attramadal Håvard , Finsen Alexandra Vanessa , Zhang Lili , Ranheim Trine , Alfsnes Katrine , Aukrust Pål , Christensen Geir , Yndestad Arne , Vinge Leif Erik
Published: April 2017

Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision.Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced survival compared to SERC2a KO mice, with a median life expectancy of 58 days compared to 63 days. Both HF groups displayed increased left atrium size, lung weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis. However, there were no significant differences between the groups.Conclusion. In mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median life expectancy. The cause remains elusive, as all investigated HF parameters were unaltered. Still, these findings support a salutary role of TLR9 in some subsets of HF conditions and underline the importance for future studies on the mechanisms of TLR9 in diastolic HF.
Multifunctional Telodendrimer Nanocarriers Restore Synergy of Bortezomib and Doxorubicin in Ovarian Cancer Treatment
Authors: Wang Lili , Shi Changying , Wright Forrest A. , Guo Dandan , Wang Xu , Wang Dongliang , Wojcikiewicz Richard J.H. , Luo Juntao
Published: April 2017

We have developed multifunctional nanoparticles for codelivery of bortezomib and doxorubicin to synchronize their pharmacokinetic profiles and synergize their activities in solid tumor treatment, a need still unmet in the clinic. Micellar nanoparticles were formed by a spatially segregated, linear-dendritic telodendrimer containing three segments: a hydrophilic polyethylene glycol (PEG), a bortezomib-conjugating intermediate, and a dendritic doxorubicin-affinitive interior. Bortezomib-conjugated telodendrimers, together with doxorubicin, self-assembled into monodispersed micelles [NP(BTZ-DOX)] with small particle sizes (20–30 nm) for dual drug delivery. NP(BTZ-DOX) displayed excellent drug-loading capacity and stability, which minimized premature drug leakage and synchronized drug release profiles. Bortezomib release was accelerated significantly by acidic pH, facilitating drug availability in the acidic tumor microenvironment. Synergistic anticancer effects of combined bortezomib and doxorubicin were observed in vitro against both multiple myeloma and ovarian cancer cells. NP(BTZ-DOX) prolonged payload circulation and targeted tumors in vivo efficiently with superior signal ratios of tumor to normal organs. In vitro and in vivo proteasome inhibition analysis and biodistribution studies revealed decreased toxicity and efficient intratumoral bortezomib and doxorubicin delivery by nanoformulation. NP(BTZ-DOX) exhibited significantly improved ovarian cancer treatment in SKOV-3 xenograft mouse models in comparison with free drugs and their combinations, including bortezomib and Doxil. In summary, tumor-targeted and synchronized delivery system elicits enhanced anticancer effects and merits further development in the clinical setting. Cancer Res; 77(12); 3293–305. ©2017 AACR.
Blind SELEX Approach Identifies RNA Aptamers That Regulate EMT and Inhibit Metastasis
Authors: Yoon Sorah , Armstrong Brian , Habib Nagy , Rossi John J.
Published: April 2017

Identifying targets that are exposed on the plasma membrane of tumor cells, but expressed internally in normal cells, is a fundamental issue for improving the specificity and efficacy of anticancer therpeutics. Using blind cell Systemic Evolution of Ligands by EXponetial enrichment (SELEX), which is untargeted SELEX, we have identified an aptamer, P15, which specifically bound to the human pancreatic adenocarcinoma cells. To identify the aptamer binding plasma membrane protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used. The results of this unbiased proteomic mass spectrometry approach identified the target of P15 as the intermediate filament vimentin, biomarker of epithelial–mesenchymal transition (EMT), which is an intracellular protein but is specifically expressed on the plasma membrane of cancer cells. As EMT plays a pivotal role to transit cancer cells to invasive cells, tumor cell metastasis assays were performed in vitro. P15-treated pancreatic cancer cells showed the significant inhibition of tumor metastasis. To investigate the downstream effects of P15, EMT-related gene expression analysis was performed to identify differently expressed genes (DEG). Among five DEGs, P15-treated cells showed the downregulated expression of matrix metallopeptidase 3 (MMP3), which is involved in cancer invasion. These results, for the first time, demonstrate that P15 binding to cell surface vimentin inhibits the tumor cell invasion and is associated with reduced MMP3 expression. Thus, suggesting that P15 has potential as an anti-metastatic therapy in pancreatic cancer.

Implications: This study reveals that anti-vimentin RNA aptamers selected via blind-SELEX inhibit the tumor cell metastasis. Mol Cancer Res; 15(7); 811–20. ©2017 AACR.
Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention
Authors: Weinberg David S. , Lin Jieru E. , Foster Nathan R. , Della'Zanna Gary , Umar Asad , Seisler Drew , Kraft Walter K. , Kastenberg David M. , Katz Leo C. , Limburg Paul J. , Waldman Scott A.
Published: April 2017

Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of 0.87 mg of oral linaclotide daily for 7 days to healthy volunteers, after oral colon preparation with polyethylene glycol solution (MoviPrep), activates GUCY2C, resulting in accumulation of its product cyclic (c)GMP in epithelial cells of the cecum, transverse colon, and distal rectum. GUCY2C activation by oral linaclotide was associated with homeostatic signaling, including phosphorylation of vasodilator-stimulated phosphoprotein and inhibition of proliferation quantified by reduced Ki67-positive epithelial cells. In the absence of the complete oral colonoscopy preparation, linaclotide did not alter cGMP production in epithelial cells of the colorectum, demonstrating that there was an effect related to the laxative preparation. These data show that the current FDA-approved formulation of oral linaclotide developed for small-bowel delivery to treat chronic idiopathic constipation is inadequate for reliably regulating GUCY2C in the colorectum to prevent tumorigenesis. The study results highlight the importance of developing a novel GUCY2C agonist formulated for release and activity targeted to the large intestine for colorectal cancer prevention. Cancer Prev Res; 10(6); 345–54. ©2017 AACR.
Phonological Process Occurrence in Typically Developing Toddlers
Authors: Petinou Kakia , Armostis Spyros
Published: April 2017

Background/Aims: The study examined the phonological development in Cypriot Greek (CG)-speaking, typically developing (TD) toddlers for the purpose of observing occurrences of initial consonant deletion (ICD), regressive assimilation (RAS), and their interactive relationship as a function of time. Participants and Methods: Subjects were 8 CG-speaking TD toddlers assessed longitudinally at ages 24-28 and 32-36 months. Word targets from spontaneously produced utterances via language sample collection were analyzed for the percentage of occurrence of ICD and RAS. Results: Results revealed a significant change of phonological process occurrence as a function of time as well as an antagonistic relationship between ICD and correct onset production. Comparisons between measures showed that trisyllabic (three-syllable) words exhibited higher rates of ICD than disyllabic words. Conclusions: Early patterns of phonological development and phonological assessment should include a hierarchical account of phonological behavior in the form of word structure shapes and a possible interaction among phonological process occurrence.
Blunt Traumatic Extracranial Cerebrovascular Injury and Ischemic Stroke
Authors: Foreman Paul M. , Harrigan Mark R.
Published: April 2017

Background: Ischemic stroke occurs in a significant subset of patients with blunt traumatic cerebrovascular injury (TCVI). The patients are victims of motor vehicle crashes, assaults or other high-energy collisions, and suffer ischemic stroke due to injury to the extracranial carotid or vertebral arteries. Summary: An increasing number of patients with TCVI are being identified, largely because of the expanding use of computed tomography angiography for screening patients with blunt trauma. Patients with TCVI are particularly challenging to manage because they often suffer polytrauma, that is, numerous additional injuries including orthopedic, chest, abdominal, and head injuries. Presently, there is no consensus about optimal management. Key Messages: Most literature about TCVI and stroke has been published in trauma, general surgery, and neurosurgery journals; because of this, and because these patients are managed primarily by trauma surgeons, patients with stroke due to TCVI have been essentially hidden from view of neurologists. This review is intended to bring this clinical entity to the attention of clinicians and investigators with specific expertise in neurology and stroke.
Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Drug Induction: A Retrospective Single-Center Analysis
Authors: Thoennissen Gabriela B. , Görlich Dennis , Bacher Ulrike , Aufenberg Thomas , Hüsken Anne-Christin , Hansmeier Anna Antonia , Evers Georg , Mikesch Jan-Henrik , Fritz Fleur , Bokemeyer Carsten , Müller-Tidow Carsten , Stelljes Matthias , Mesters Rolf M. , Krug Utz , Kropff Martin H. , Thoennissen Nils H. , Berdel Wolfgang E.
Published: April 2017

Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0.03) and stage 3 according to the International Staging System (p = 0.006) as adverse risk factors regarding PFS. Median OS was significantly better in newly diagnosed MM patients receiving induction therapy with novel agents, e.g., bortezomib, thalidomide, or lenalidomide, compared with a traditional regimen (69 vs. 58 months; p = 0.01). More patients achieved at least a very good partial remission in the period from 2005 to 2012 than from 1996 to 2004 (65 vs. 30%; p < 0.001), with a longer median OS in the later period (71 vs. 52 months, p = 0.027). In conclusion, our analysis confirms HDCT-ASCT as an effective therapeutic strategy in an unselected large myeloma patient cohort with a low TRD rate and improved prognosis due to novel induction strategies.
Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence
Authors: Sousos Nikolaos , Adamidou Despoina , Klonizakis Philippos , Agapidou Alexandra , Theodoridou Stamatia , Spanos Georgios , Psarras Kyriakos , Vetsiou Evaggelia , Vyzantiadis Timoleon-Achilleas , Vlachaki Efthymia
Published: April 2017

Extramedullary hematopoiesis (EMH) results from the extension of hematopoietic tissue beyond the confines of the bones. Since the initiation of regular transfusion programs from an early age for all thalassemia major (ΤΜ) patients, EMH has not been considered a clinical issue anymore. The present study aims to record the prevalence of EMH in chronically transfused ΤΜ patients followed at our institution and to investigate possible risk factors associated with its occurrence. The project was designed as a retrospective, nonexperimental, descriptive, exploratory study. In total, the study enrolled 104 patients. EMH was revealed in 15/104 (14%) patients. The presence of intravening sequence (IVS)-I-6 was significantly related with the development of EMH (p < 0.05). No other demographic or biological factor studied was found to be related with the presence of EMH. The study stresses a profound incidence of asymptomatic EMH in a solid group of well-transfused ΤΜ patients. Given the high incidence of the IVS-I-6 allele in the Mediterranean and Middle Eastern region, high-quality, prospective, multicenter studies could confirm the association of EMH occurrence with the presence of the IVS-I-6 mutation and further evaluate the exact role of this mutation in the EMH process.
Sperm Sediment Cytology: A New Technique for Diagnosing Occult Urologic Infections
Authors: Sapozhkova Zhanna , Kasoyan Karina , Kovalchuk Elena , Shabalova Irina
Published: April 2017

Background: Ill-defined chronic symptoms such as itching, burning, urethral discharge, and pelvic pain are not uncommon in male urologic patients. Often, microscopic urinalysis, bacterial cultures, and laboratory testing are non-contributory. We have developed a technique for sperm sedimentation and used the cytologic examination of the sediment routinely in more than 4,000 patients with urologic complaints over the last 5 years. Case: We present 3 exemplary cases, documenting the diagnostic power of sperm sediment cytology (SSC). In all 3 cases, conventional laboratory testing failed to reveal a causative agent. Case 1 is that of a 28-year-old male patient with a history of occasional swelling of the lymph nodes in the left inguinal region for 1 year. Case 2 is that of a 51-year-old male patient with a history of itching and burning of the urethra of 2 months' duration. Case 3 is that of a 22-year-old female patient with copious vaginal discharge after intercourse for 18 months, non-responsive to treatment. Conclusion: We were able to identify causative pathologic organisms in the sediment of all patients or their partner. Subsequent specific treatment did clear and alleviate the symptoms documenting the clinical relevance of this new technique. In our experience, SSC has proven to be a valuable technique for diagnosing occult urologic infections.
Downregulation of
Plzf
Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat
Authors: Liška František , Landa Vladimír , Zídek Václav , Mlejnek Petr , Šilhavý Jan , Šimáková Miroslava , Strnad Hynek , Trnovská Jaroslava , Škop Vojtěch , Kazdová Ludmila , Starker Colby G. , Voytas Daniel F. , Izsvák Zsuzsanna , Mancini Massimiliano , Šeda Ondřej , Křen Vladimír , Pravenec Michal
Published: April 2017

The spontaneously hypertensive rat (SHR), one of the most widely used model of essential hypertension, is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, quantitative trait loci influencing blood pressure, left ventricular mass, and heart interstitial fibrosis were genetically isolated within a minimal congenic subline that contains only 7 genes, including mutant
Plzf
(promyelocytic leukemia zinc finger) candidate gene. To identify
Plzf
as a quantitative trait gene, we targeted
Plzf
in the SHR using the transcription activator-like effector nuclease technique and obtained SHR line harboring targeted
Plzf
gene with a premature stop codon. Because the
Plzf
targeted allele is semilethal, morphologically normal heterozygous rats were used for metabolic and hemodynamic analyses. SHR-
Plzf
+/−
heterozygotes versus SHR wild-type controls exhibited reduced body weight and relative weight of epididymal fat, lower serum and liver triglycerides and cholesterol, and better glucose tolerance. In addition, SHR-
Plzf
+/−
rats exhibited significantly increased sensitivity of adipose and muscle tissue to insulin action when compared with wild-type controls. Blood pressure was comparable in SHR versus SHR-
Plzf
+/−
; however, there was significant amelioration of cardiomyocyte hypertrophy and cardiac fibrosis in SHR-
Plzf
+/−
rats. Gene expression profiles in the liver and expression of selected genes in the heart revealed differentially expressed genes that play a role in metabolic pathways, PPAR (peroxisome proliferator-activated receptor) signaling, and cell cycle regulation. These results provide evidence for an important role of
Plzf
in regulation of metabolic and cardiac traits in the rat and suggest a cross talk between cell cycle regulators, metabolism, cardiac hypertrophy, and fibrosis.
Joint Association of Low Vitamin D and Vitamin K Status With Blood Pressure and Hypertension
Authors: van Ballegooijen Adriana J. , Cepelis Aivaras , Visser Marjolein , Brouwer Ingeborg A. , van Schoor Natasja M. , Beulens Joline W.
Published: April 2017

Low vitamin D and K status are both associated with an increased cardiovascular risk. New evidence from experimental studies on bone health suggest an interaction between vitamin D and K; however, a joint association with vascular health outcomes is largely unknown. To prospectively investigate whether the combination of low vitamin D and K status is associated with higher systolic and diastolic blood pressure in 402 participants and with incident hypertension in 231 participants free of hypertension at baseline. We used data from a subsample of the Longitudinal Aging Study Amsterdam, a population-based cohort of Dutch participants aged 55 to 65 years. Vitamin D and K status were assessed by 25-hydroxyvitamin D and dp-ucMGP (dephosphorylated uncarboxylated matrix gla protein) concentrations (high dp-ucMGP is indicative for low vitamin K status) in stored samples from 2002 to 2003. Vitamin D and K status were categorized into 25-hydroxyvitamin D <50/≥50 mmol/L and median dp-ucMGP <323/≥323 pmol/L. During a median follow-up of 6.4 years, 62% of the participants (n=143) developed hypertension. The combination of low vitamin D and K status was associated with increased systolic 4.8 mm Hg (95% confidence interval, 0.1–9.5) and diastolic 3.1 mm Hg (95% confidence interval, 0.5–5.7) blood pressure compared with high vitamin D and K status (
P
for interaction =0.013 for systolic blood pressure and 0.068 for diastolic blood pressure). A similar trend was seen for incident hypertension: hazard ratio=1.62 (95% confidence interval, 0.96–2.73) for the low vitamin D and K group. The combination of low vitamin D and K status was associated with increased blood pressure and a trend for greater hypertension risk.
Longitudinal Study of Hypertensive Subjects With Type 2 Diabetes Mellitus
Authors: Safar Michel E. , Gnakaméné Jean-Barthélémy , Bahous Sola Aoun , Yannoutsos Alexandra , Thomas Frédérique
Published: April 2017

Despite adequate glycemic and blood pressure control, treated type 2 diabetic hypertensive subjects have a significantly elevated overall/cardiovascular risk. We studied 244 816 normotensive and 99 720 hypertensive subjects (including 7480 type 2 diabetics) attending medical checkups between 1992 and 2011. We sought to identify significant differences in overall/cardiovascular risk between hypertension with and without diabetes mellitus. Mean follow-up was 12.7 years; 14 050 all-cause deaths were reported. From normotensive to hypertensive populations, a significant progression in overall/cardiovascular mortality was observed. Mortality was significantly greater among diabetic than nondiabetic hypertensive subjects (all-cause mortality, 14.05% versus 7.43%; and cardiovascular mortality, 1.28% versus 0.7%). No interaction was observed between hemodynamic measurements and overall/cardiovascular risk, suggesting that blood pressure factors, even during drug therapy, could not explain the differences in mortality rates between diabetic and nondiabetic hypertensive patients. Using cross-sectional regression models, a significant association was observed between higher education levels, lower levels of anxiety and depression, and reduced overall mortality in diabetic hypertensive subjects, while impaired renal function, a history of stroke and myocardial infarction, and increased alcohol and tobacco consumption were significantly associated with increased mortality. Blood pressure and glycemic control alone cannot reverse overall/cardiovascular risk in diabetics with hypertension. Together with cardiovascular measures, overall prevention should include recommendations to reduce alcohol and tobacco consumption and improve stress, education levels, and physical activity.
Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology
Authors: Martini Alexandre G. , Xa Lucie K. , Lacombe Marie-Josée , Blanchet-Cohen Alexis , Mercure Chantal , Haibe-Kains Benjamin , Friesema Edith C.H. , van den Meiracker Anton H. , Gross Kenneth W. , Azizi Michel , Corvol Pierre , Nguyen Geneviève , Reudelhuber Timothy L. , Danser A.H. Jan
Published: April 2017

Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular cells of the kidney. Chronic stimulation of renin release results in a recruitment of new juxtaglomerular cells by the apparent conversion of adjacent smooth muscle cells along the afferent arterioles. Because juxtaglomerular cells rapidly dedifferentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain unclear. To overcome this limitation, we have performed RNA expression analysis on 4 human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in kidneys of 5-day-old mice, adult mice, and adult mice treated with captopril. From the top 100 genes, 10 encoding for ligands were selected for further analysis. Medium of human embryonic kidney 293 cells transfected with the mouse cDNA encoding these ligands was applied to (pro)renin-synthesizing As4.1 cells. Among the ligands, only platelet-derived growth factor B reduced the medium and cellular (pro)renin levels, as well as As4.1 renin gene expression. In addition, platelet-derived growth factor B–exposed As4.1 cells displayed a more elongated and aligned shape with no alteration in viability. This was accompanied by a downregulated expression of α-smooth muscle actin and an upregulated expression of interleukin-6, suggesting a phenotypic shift from myoendocrine to inflammatory. Our results add 36 new genes to the list that characterize renin-producing cells and reveal a novel role for platelet-derived growth factor B as a regulator of renin-synthesizing cells.
Tollip Deficiency Alters Atherosclerosis and Steatosis by Disrupting Lipophagy
Authors: Chen Keqiang , Yuan Ruoxi , Zhang Yao , Geng Shuo , Li Liwu
Published: April 2017

Background

Compromised lipophagy with unknown mechanisms may be critically involved in the intracellular accumulation of lipids, contributing to elevated atherosclerosis and liver steatosis. We hypothesize that toll‐interacting protein (Tollip), a key innate immune molecule involved in the fusion of autolysosome, may play a significant role in lipophagy and modulate lipid accumulation during the pathogenesis of atherosclerosis and liver steatosis.

Methods and Results

By comparing mice fed with either a Western high‐fat diet or a regular chow diet, we observed that both atherosclerosis and liver steatosis were aggravated in apolipoprotein E–deficient (ApoE
−/−
)/Tollip
−/−
mice as compared with ApoE
−/−
mice. Through electron microscopy analyses, we observed compromised fusion of lipid droplets with lysosomes within aortic macrophages as well as liver hepatocytes from ApoE
−/−
/Tollip
−/−
mice as compared with ApoE
−/−
mice. As a molecular indicator for disrupted lysosome fusion, the levels of p62 were significantly elevated in aortic and liver tissues from ApoE
−/−
/Tollip
−/−
mice. Molecules involved in facilitating lipophagy completion such as Ras‐related protein 7 and gamma‐aminobutyric acid receptor‐associated protein were reduced in ApoE
−/−
/Tollip
−/−
mice as compared with ApoE
−/−
mice. Intriguingly, ApoE
−/−
/Tollip
−/−
mice had reduced circulating levels of inflammatory cytokines such as tumor necrosis factor‐α and increased levels of transforming growth factor‐β. The reduced inflammation due to Tollip deficiency is consistent with a stable atherosclerotic plaque phenotype with increased levels of plaque collagen and smooth muscle cells in ApoE
−/−
/Tollip
−/−
mice.

Conclusions

Tollip deficiency selectively leads to enlarged yet stable atherosclerotic plaques, increased circulating lipids, liver steatosis, and reduced inflammation. Compromised lipophagy and reduced expression of inflammatory mediators due to Tollip deficiency may be the underlying causes. Our data suggest that lipid accumulation and inflammation may be intertwined yet independent processes during the progression of atherosclerosis and steatosis.
Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
Authors: Shendre Aditi , Irvin Marguerite R. , Wiener Howard , Zhi Degui , Limdi Nita A. , Overton Edgar T. , Shrestha Sadeep
Published: April 2017

Background

Local ancestry in relation to clinical cardiovascular events (
CVEs
) among African Americans can provide insight into their genetic susceptibility to the disease.

Methods and Results

We examined local European ancestry (
LEA
) association with
CVEs
among 3000 African Americans from the Atherosclerosis Risk in Communities Study (
ARIC
). We estimated
LEA
using
L
ocal
A
ncestry Inference in ad
M
ixed
P
opulations using
L
inkage
D
isequilibrium (
LAMP
‐
LD
) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121
LEA
regions in relation to
myocardial infarction
and 2 in relation to the cardiovascular disease composite. The
LEA
region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (
P
=1.45×10
−6
). The
LEA
region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (
P
=7.34×10
−4
), whereas the
LEA
region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (
P=
3.45×10
−4
). Association of
LEA
with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (
P
=9.69×10
−4
). Likewise, the
LEA
region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (
P=
3.04×10
−4
). We also found 20 of the
LEA
regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with
CVE
in our study.

Conclusions

Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with
CVEs
.
Developmental changes in the resting strategies of killer whale mothers and their calves in managed care from birth to 36 months
Authors: Hill Heather M. , Guarino Sara , Geraci Caitlyn , Sigman Julie , Noonan Michael
Published: April 2017

The development of cetacean sleep has not been explored fully. Questions such as whether cetacean mothers regulate their offspring’s resting behaviour and do resting behaviours change over the course of cetacean development remain unanswered. To address these questions, an investigation of the resting strategies and activity levels for four killer whale (Orcinus orca) calves and their mothers in managed care during free-swim conditions was conducted during the first three years of life. A series of interrelated hypotheses were assessed using three independent sets of archived data (24 h behaviour records, video recordings, and instantaneous sampling) collected from two facilities. Together, the results indicated that mothers adjusted their activity levels based on their calves’ current level of development. Floating, often a preferred resting behaviour, was rarely observed during the first post-parturition month for any of the mother–calf pairs. Rather, the mother–calf pairs tended to display fast-moving mother–calf swims with frequent trajectory changes as the calf gained swimming proficiency. Although floating occurred more frequently over time for all pairs, all four killer whale mother–calf pairs displayed a preference for a slower-paced pattern swim (i.e., swim-rest). Calves preferred to rest with their mothers over resting with others or independently. The similarities in resting strategies displayed by the killer whale mother–calf pairs housed in independent facilities without temporal overlap emphasizes the conserved nature and development of these strategies in a precocial cetacean species with extended maternal care.
Notes on Plectranthus montanus (Lamiaceae)—a poorly known species in India and reduction of Coleus subbaraoi as one of its synonyms
Authors: SMITHA KOKKARANIYIL , SUNOJKUMAR PURAYIDATHKANDY
Published: April 2017

Taxonomic identity of Plectranthus montanus, a poorly known species from India is discussed by providing a detailed description, photographs and notes on its distribution. The specific status of Coleus subbaraoi is also discussed here. Critical study reveals that Coleus subbaraoi is conspecific with Plectranthus montanus and it is thus synonymized.
Rohdea fargesii, the correct name for Rohdea chinensis (Asparagaceae)
Authors: DENG YUNFEI
Published: April 2017

The genus Rohdea Roth (1821: 196) (Asparagaceae) was established with a sole species R. japonica (Thunb. in Murray 1784: 340) Roth (1821: 196). It was recognized as a monospecific genus for long time (Wang & Tang 1978, Liang & Tamura 2000). The evidence from molecular analyses revealed that Campylandra Backer (1875: 582) might be merged with Rohdea (Yamashita & Tamura 2000, 2004). Tanaka (2003) and Yamashita & Tamura (2004) formally merged Campylandra with Rohdea and led the latter a genus including 17 species distributed in East Asia.
Erratum: Wu, L., Hareesh, V.-S. & Yu, X.-L. (2017) The taxonomic identity of Ophiorrhiza rarior and O. mycetiifolia (Rubiaceae). Phytotaxa 299 (2): 261–266.
Authors: WU LEI , HAREESH VADAKKOOT-SANKARAN , YU YUN-LIN
Published: April 2017

N/A
A new species of Hohenbergia (Bromeliaceae) from the Atlantic Forest of Northeast Brazil
Authors: GONÇALVES-OLIVEIRA RODRIGO CÉSAR , WANDERLEY MARIA DAS GRAÇAS LAPA
Published: April 2017

Hohenbergia isepponae (Bromeliaceae), a new species from the Atlantic Forest of Pernambuco, Brazil is described and illustrated herewith. We also compared it with the morphologically similar species.