bluuebunny/crossref_metadata_2025 huggingface dataset:
Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms
Authors: Lee JongBok , Minden Mark D. , Chen Weihsu C. , Streck Elena , Chen Branson , Kang Hyeonjeong , Arruda Andrea , Ly Dalam , Der Sandy D. , Kang Sohyeong , Achita Paulina , D'Souza Cheryl , Li Yueyang , Childs Richard W. , Dick John E. , Zhang Li
Published: October 2017

Purpose: To explore the potential of ex vivo expanded healthy donor–derived allogeneic CD4 and CD8 double-negative cells (DNT) as a novel cellular immunotherapy for leukemia patients.

Experimental Design: Clinical-grade DNTs from peripheral blood of healthy donors were expanded and their antileukemic activity and safety were examined using flow cytometry–based in vitro killing assays and xenograft models against AML patient blasts and healthy donor–derived hematopoietic cells. Mechanism of action was investigated using antibody-mediated blocking assays and recombinant protein treatment assays.

Results: Expanded DNTs from healthy donors target a majority (36/46) of primary AML cells, including 9 chemotherapy-resistant patient samples in vitro, and significantly reduce the leukemia load in patient-derived xenograft models in a DNT donor–unrestricted manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or affect hematopoietic stem/progenitor cell engraftment and differentiation, or cause xenogeneic GVHD in recipients. Mechanistically, DNTs express high levels of NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML cells. Upon recognition of AML cells, DNTs rapidly release IFNγ, which further increases NKG2D and DNAM-1 ligands’ expression on AML cells. IFNγ pretreatment enhances the susceptibility of AML cells to DNT-mediated cytotoxicity, including primary AML samples that are otherwise resistant to DNTs, and the effect of IFNγ treatment is abrogated by NKG2D and DNAM-1–blocking antibodies.

Conclusions: This study supports healthy donor–derived allogeneic DNTs as a therapy to treat patients with chemotherapy-resistant AML and also reveals interrelated roles of NKG2D, DNAM-1, and IFNγ in selective targeting of AML by DNTs. Clin Cancer Res; 24(2); 370–82. ©2017 AACR.
Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model
Authors: Alizai Patrick Hamid , Bertram Lea , Kroy Daniela , Kummer Julia , Andert Anne , Neumann Ulf Peter , Ulmer Tom Florian , Fragoulis Athanassious
Published: October 2017

Background: Liver regeneration requires the formation of new blood vessels. Endothelial cell proliferation is stimulated by vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was to investigate VEGFR-2 expression in vivo during liver regeneration after partial hepatectomy (PHx). Methods: Transgenic VEGFR-2-luc mice were used in which the luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3 PHx, the mice underwent in vivo bioluminescence imaging until the 14th postoperative day. Additionally, liver tissue was analyzed by immunohistochemistry, in vitro luminescence assays, and quantitative RT-PCR. Results: In vivo bioluminescence imaging showed a significant increase in VEGFR-2 promoter activity after PHx. Maximum signal was recorded on the 3rd day; 8 days postoperatively the signal intensity decreased significantly. On the 14th day, bioluminescence signal reached almost baseline levels. Immunohistochemistry, quantitative RT-PCR, and in vitro luminescence confirmed a significant increase on the 3rd day following resection. The mRNA expression of VEGFR-2 was significantly higher on day 3 than preoperatively as well as on day 8. Conclusion: In vivo bioluminescence imaging with transgenic VEGFR-2-luc mice is feasible and provides a convenient model for noninvasively studying VEGFR-2 expression during liver regeneration. This may facilitate further experiments with modulation of angiogenesis by different substances.
Einnahme von Vitaminen und Phytotherapeutika
Authors: Witt Claudia
Published: October 2017

Einleitung: Umfragen zufolge ist die Anwendung von komplementären und alternativen Heilverfahren (complementary and alternative medicine, CAM) bei Patienten mit malignen Erkrankungen stark verbreitet. CAM-Verfahren stören möglicherweise die Metabolisierung der tumorspezifischen Therapie. Die Kommunikation über die Anwendung komplementärer und alternativer Heilverfahren bei hämatologischen/onkologischen Patienten zwischen Patienten, Anbietern von CAM und Onkologen ist jedoch gering. Patienten und Methoden: Alle Patienten der hämatologischen/onkologischen Tagesklinik des Universitätsklinikums Regensburg erhielten einen Fragebogen zum Ausfüllen. Anschließend erfolgte eine Durchsicht der Akten aller CAM-Anwender. Ergebnisse: Die Fragebögen von 1016 Patienten wurden ausgewertet. Von diesen verwendeten 30% CAM, hauptsächlich in Form von Vitaminen und Mikronährstoffen. Die wichtigsten Informationsquellen über CAM-Methoden waren Ärzte, Heilpraktiker sowie Freunde und Angehörige. CAM-Therapien wurden überwiegend von Ärzten (29%), gefolgt von Heilpraktikern (14%) und den Patienten selbst (13%) durchgeführt. Zwar waren 62% der CAM-Anwender der Ansicht, ihr Onkologe könne über ihre CAM-Therapie Bescheid wissen, doch fand sich nur in 41% der Fälle ein entsprechender Eintrag in der Patientenakte. Schlussfolgerung: Komplementäre und alternative Heilverfahren werden von hämatologischen/onkologischen Patienten häufig angewendet. Eine systematische Kommunikation über CAM ist unabdingbar, um etwaige Arzneimittelinteraktionen zu vermeiden.
Neoadjuvante Chemotherapie und adjuvante Radiochemotherapie in der Behandlung des resezierten Adenokarzinoms des Magens: Eine Fallserie
Authors: Jabbour Salma K. , Hadzitherodorou Christina , Moss Rebecca A. , Kennedy Timothy
Published: October 2017

Die Behandlung von Magenkrebs erfordert einen multimodalen Ansatz, um das Risiko eines lokoregionalen Rezidivs und einer Fernmetastasierung zu verringern. Der optimale Zeitpunkt von Chemotherapie, Operation und Bestrahlung wird derzeit in laufenden Studien untersucht. In den USA erhalten die Patienten im Anschluss an die chirurgische Resektion häufig eine adjuvante Radiochemotherapie oder eine Kombination aus neoadjuvanter und adjuvanter Chemotherapie. Wir berichten hier über 4 Patientinnen mit reseziertem Adenokarzinom des Magens, die mit einer Kombination dieser beiden Therapieansätze behandelt wurden und eine neoadjuvante Chemotherapie gefolgt von einer adjuvanten Radiochemotherapie erhielten. Übersetzung aus Case Rep Oncol 2017;10: 308-315 (DOI:10.1159/000464280).
Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery
Authors: Brettner Florian , Chappell Daniel , Schwartz Lisa , Lukasz Alexander , Kümpers Philipp , Becker Bernhard F. , Reichart Bruno , Rehm Markus , Bruegger Dirk
Published: October 2017

Background: Cardiac surgery often causes ischemia and development of a systemic inflammatory response syndrome, which impairs vascular barrier function, normally maintained by the endothelial cell line and the endothelial glycocalyx (EG). The EG normally covers and protects healthy endothelial cells throughout the vasculature. The aim of the present study was to assess the disruption of the cellular part of the microvascular barrier by determining parameters of endothelial cell activation known to influence and reflect cell-cell junctional integrity. Particular attention was placed on angiopoietins and their important effects on endothelial gap junctions. Furthermore, comparative measurements were undertaken in patients undergoing on- and off-pump cardiac surgery, the latter group presumably experiencing less ischemic stress. Methods: 30 patients undergoing elective coronary artery bypass surgery were assigned to the conventional coronary artery bypass (CCAB) group (n = 15) or the off-pump coronary artery bypass grafting (OPCAB) group (n = 15). Blood samples were obtained for measuring angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial (VE)-cadherin, and endocan at various time points. Results: There were significant increases in all measured parameters in both study groups versus the respective basal values. Maximal increases were as follows: Ang-1: CCAB +220%, OPCAB +166%, p < 0.05 each; Ang-2: CCAB +150%, OPCAB +20%, p < 0.05 each; VE-cadherin: CCAB +87%, OPCAB +66%, p < 0.05 each; endocan: CCAB +323%, OPCAB +72%, p < 0.05 each. Conclusion: The present study demonstrates the activation of endothelial cells, shedding of cell-cell contacts and a potential intrinsic counterregulation by Ang-1 and endocan in patients undergoing major cardiac surgery. Quantitatively greater deviations of parameters in the CCAB than in the OPCAB group suggest a relation between the occurrence of ischemia/reperfusion and the extent of endothelial activation.
Chronic Retinal Necrosis Severely Complicated by Neovascular Glaucoma: A Case Report
Authors: Matsuoka Takanori , Asao Kazunobu , Hashida Noriyasu , Nishida Kohji
Published: October 2017

Background: Chronic retinal necrosis (CRN) is a rare chronic granular necrotizing retinitis that was first described in 2013. CRN is characterized by intraocular inflammation accompanied by occlusive vasculitis, granular retinitis, and slowly progressing necrosis around the retina in a host with partial immune dysfunction. Cytomegalovirus (CMV) is reported to be a causative agent. There are several ocular complications such as retinal detachment and neovascular glaucoma; however, there has been no description of a clinical manifestation of neovascular glaucoma in CRN. We herein present a case of severe neovascular glaucoma in association with CRN. Case Presentation: An 80-year-old man was referred to our hospital with poor control of inflammation and intraocular pressure (IOP). The IOP in his left eye was 29 mm Hg. Anterior chamber cells (2+) and keratic precipitates were observed. In the peripheral retina, vitreous opacities and granular necrotizing retinitis were noticed. Fluorescein angiography revealed extensive retinal nonperfusion area from the macula lesion to the periphery. PCR analysis of aqueous humor showed the presence of CMV. A diagnosis of CRN was made soon afterwards. Antiviral drug and systemic corticosteroid were administered. The treatment temporally resolved the symptom; however, panretinal photocoagulation and intravitreal injection of bevacizumab were performed to treat iris neovascularization. During the follow-up, trabeculectomy was performed because of poor IOP control. At the final visit, severe uncontrolled neovascular glaucoma caused hyphema, and his left eye lost light perception. Conclusion: The prognosis of CRN is poor because of severe neovascular glaucoma and careful observation and active treatments are necessary.
Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients
Authors: Schimrigk Sebastian , Marziniak Martin , Neubauer Christine , Kugler Eva Maria , Werner Gudrun , Abramov-Sommariva Dimitri
Published: October 2017

Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (p = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.
Isolated Cleft Lip and Palate: Maxillary Gap Sign and Palatino-Maxillary Diameter at 11–13 Weeks
Authors: Lachmann Robert , Schilling Uwe , Brückmann Detlef , Weichert Alexander , Brückmann Andreas
Published: October 2017

Objective: To evaluate the maxillary gap sign and describe markers for the first-trimester diagnosis of isolated cleft lip and palate (CLP) at 11–13 weeks. Methods: Firstly, this was a prospective assessment of 1,087 fetuses including 5 cases of isolated CLP in 2 centers which were referred for the 11–13 weeks scan. Secondly, intra- and interobserver variability of the maxillary gap sign was evaluated for observers R.L. and A.B. in 2 sessions (affected cases vs. 50 normal fetuses in each session) to reduce the bias of different ultrasound manufacturer visualizations (Philips, GE). Thirdly, the palatino-maxillary diameter (PMD) was examined in stored images, DICOM loops and volumes of the midsagittal and parasagittal view of the fetal head and brain at 11+0–13+6 weeks of gestation from 5 fetuses with isolated CLP and 302 consecutively assessed normal controls. The PMD values in fetuses with isolated CLP and normal controls were compared. Results: Firstly, 5 out of 6 referred pregnancies with isolated CLP were detected prospectively using the midsagittal view for measurement of nuchal translucency due to an abnormal appearance. One out of 6 patients with isolated CLP declined the 11–13 weeks scan. Secondly, intra- and interobserver variability showed no false positive cases; all cases with isolated CLP were identified by both sonographers; however, in 2 cases the maxillary gap sign was doubtful. Therefore, thirdly, we developed the PMD measurement which increased significantly with crown-rump length (CRL) from respective mean values at CRL of 45 mm to 4.66 mm and to 8.95 mm at CRL of 84 mm. In the CLP group, the PMD was below the 5th percentile of the control group in 4 out of 5 (80%) cases. Conclusions: The midsagittal view for measurement of nuchal translucency shows a high reproducibility regarding abnormal views for maxillary gap sign. In the midsagittal view of the fetal head, face, and brain at 11–13 weeks, the majority of fetuses with isolated CLP have a measurable abnormality in addition, the PMD.
Jean-Martin Charcot (1825–1893): A Treatment Approach Gone Astray?
Authors: Walusinski Olivier
Published: October 2017

Jean-Martin Charcot’s reputation remains that of a physician who took little interest in treatments for the neurological diseases he did much to identify. After reviewing the limited number of medicinal remedies of slight effectiveness at Charcot’s disposal, we analyze in this review the numerous therapeutic tests that he conducted: vibratory medicine for Parkinson’s disease, treatment of tabes by suspension technique, metallotherapy and moral ­treatment for hysteria. Understanding that he fully and completely adhered to the far-reaching heredity-based theories of his day makes it possible to perceive his natural and fundamental pessimism. By drawing on both ­ancestral traditions and innovative approaches, Charcot “combined genius with charlatanism” in a surprising way: he demonstrated genius in the area of nosology, and a sort of charlatanism in the area of treatments.
Neuropsychological Training of Attention Improves MS-Related Fatigue: Results of a Randomized, Placebo-Controlled, Double-Blind Pilot Study
Authors: Flachenecker Peter , Meissner Heike , Frey Rebecca , Guldin Wolfgang
Published: October 2017

Background: Attentional deficits may be pathophysiologically relevant in MS-associated fatigue. Patients and Methods: Thirty MS patients with fatigue and attentional deficits in neuropsychological testing participated in this randomized, placebo-controlled, double-blind trial. The intervention group (IG; n = 14) was treated with 10 h of computerized, specific neuropsychological training performing simple reaction time tasks, whereas the control group (CG; n = 16) also runs through computerized, but unspecific neuropsychological training using tasks without time components. The subjective feeling of fatigue was assessed with the Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) questionnaire, and testing of alertness was used as an objective measure at baseline and after the 2-week study period. Results: Reaction times of alertness were significantly decreased in IG but not CG after 2 weeks. The subjective feeling of fatigue was ameliorated in both groups but more pronounced in IG. Effect sizes were below 0.7 for alertness and WEIMuS scores in CG but large and clinically meaningful in IG for both measures. Conclusions: Our pilot study suggests that neuropsychological training of attention may improve both measures of fatigue. The parallel improvement of attentional deficits and subjective fatigue after specific neuropsychological training support previous findings that fatigue may be at least partially caused by impaired intensity of attention.
Allele Drop Out Conferred by a Frequent CYP2D6 Genetic Variation For Commonly Used CYP2D6*3 Genotyping Assays
Authors: Scantamburlo Giada , Tziolia Konstantina , Zopf Michaela , Bernardinelli Emanuele , Soyal Selma M. , Civello Davide Antonio , Vanoni Simone , Dossena Silvia , Patsch Wolfgang , Patrinos George P. , Paulmichl Markus , Nofziger Charity
Published: October 2017

Background/Aim: Accurate genotyping of CYP2D6 is challenging due to its inherent genetic variation, copy number variation (duplications and deletions) and hybrid formation with highly homologous pseudogenes. Because a relatively high percentage (∼25%) of clinically prescribed drugs are substrates for this enzyme, accurate determination of its genotype for phenotype prediction is essential. Methods: A cohort of 365 patient samples was genotyped for CYP2D6 using Sanger sequencing (as the gold standard), hydrolysis probe assays or pyrosequencing. Results: A discrepant result between the three genotyping methods for the loss of function CYP2D6*3 (g.2549delA, rs35742686) genetic variant was found in one of the samples. This sample also contained the CYP2D6 g.2470T>C (rs17002852) variation, which had an allele frequency of 2.47% in our cohort. Redesign of the CYP2D6*3 pyrosequencing and hydrolysis probe assays to avoid CYP2D6 g.2470 corrected the anomaly. Conclusion: To evidence allele drop out and increase the accuracy of genotyping, intra-patient validation of the same genetic variation with at least two separate methods should be considered.
The Relationship Between Pulse Pressure, the Estimated Glomerular Filtration Rate, and Urine Microalbumin/Creatinine Ratio in Korean Adults
Authors: Seong Jeong Min , Park Chang Eun , Gi Mi Young , Sun Kwang Soon , Kim Yu Jeong , Yoon Hyun
Published: October 2017

Background/Aims: Pulse pressure (PP) is a predictor of adverse outcomes in patients on haemodialysis. Thus, the present study was conducted to assess the relationship between PP, estimated glomerular filtration rate (eGFR), and urine microalbumin/creatinine ratio (uACR) in Korean adults. Methods: Data of 9,409 adults (4,206 men and 5,203 women) aged ≥ 20 years from the Sixth Korean National Health and Nutrition Examination Survey (2013–2014) were analyzed. Results: A multivariate analysis revealed that systolic blood pressure (SBP) (β = -0.170, 95% confidence interval [CI], -0.216 to -0.159), diastolic blood pressure (DBP) (β = 0.088, 95% CI 0.108–0.200; p < 0.001), and PP (β = -0.134, 95% CI -0.215 to -0.157) were significant factors determining eGFR. In contrast, SBP (β = 0.152, 95% CI, 0.985–1.456; p < 0.001), DBP (β = -0.062, 95% CI -1.141 to -0.442; p < 0.001), and PP (β = 0.118, 95% CI 0.965–1.436; p < 0.001) were the significant factors determining uACR. The odds ratios (ORs) of a high PP (PP ≥ 60 mmHg) with a normal group [eGFR ≥ 60 ml/min/1.73 m2 and uACR < 30 mg/g] as a reference were significant for decreased eGFR [eGFR < 60 ml/min/1.73 m2, 1.484 (95% CI, 1.003–2.196)], elevated uACR [uACR ≥ 30 mg/g, 2.592 (95% CI, 2.085–3.223)], and decreased eGFR plus elevated uACR [eGFR < 60 ml/min/1.73 m2 and uACR ≥ 30 mg/g, 3.889 (95% CI, 2.519–6.004)]. Conclusion: Enhanced PP was associated with a decreased eGFR and an increase in uACR in Korean adults. In addition, the PP increased greatly when a decrease in eGFR and an increase in uACR appeared simultaneously.
Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats
Authors: Gholami Hanieh , Jeddi Sajad , Zadeh-Vakili Azita , Farrokhfall Khadije , Rouhollah Fatemeh , Zarkesh Maryam , Ghanbari Mahboubeh , Ghasemi Asghar
Published: October 2017

Background/Aims: Transient congenital hypothyroidism (TCH) could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target tissues of aged offspring rats. Methods: The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group) were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19. Results: Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91 fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively) and higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and lower in aged rats (44% and 5%, respectively). Conclusion: Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism.
Treatment of Enterococcal Peritonitis in Peritoneal Dialysis Patients by Oral Amoxicillin or Intra-Peritoneal Vancomcyin: a Retrospective Study
Authors: Szeto Cheuk Chun , Ng Jack Kit-Chung , Chow Kai Ming , Kwan Bonnie Ching-Ha , Kwong Vickie Wai-Ki , Law Man-Ching , Leung Chi Bon , Li Philip Kam-To
Published: October 2017

Background/Aims: Enterococcal peritonitis in peritoneal dialysis (PD) patients is associated with a high complication rate. The optimal treatment regimen of PD-related enterococcal peritonitis is controversial. The latest international guideline recommends intra-peritoneal (IP) vancomycin. Although ampicillin is often effective for systemic enterococcal infections, they have little in vitro activity when added to common PD solutions. Since oral amoxicillin achieves therapeutic drug level in the peritoneal cavity, we explore the efficacy of oral amoxicillin for enterococcal peritonitis. Methods: We studied 105 episodes of enterococcal peritonitis over 20 years in our unit; 43 (41.0%) were treated with oral amoxicillin, and 62 (59.0%) with IP vancomycin. Their clinical outcome was reviewed. Result: The overall primary response rate to oral amoxicillin and IP vancomycin was 76.4% and 85.5%, respectively (p = 0.3). The complete cure rate of oral amoxicillin and IP vancomycin was 55.8% and 54.8%, respectively (p = 0.8). When the 5 episodes of ampicillin-resistant Enterococcus episodes were excluded, the primary response rate and complete cure rate of oral amoxicillin were 86.8% and 63.2%, respectively. Conclusion: Oral amoxicillin has an excellent primary response rate and complete cure rate for PD-related peritonitis episodes caused by Enterococcus species, indicating that oral amoxicillin is a valid and convenient therapeutic option for enterococcal peritonitis episodes.
A note on the population status and threats on two endemic and Endangered species of Garcinia of Agasthyamalai Biosphere Reserve, Tamil Nadu, India
Authors: Manikandan G. , Ramasubbu R.
Published: October 2017

The genus Garcinia comprises c. 35 species in India many of which are endemic and economically important with immense medicinal properties.  The two species viz., Garcinia imberti and G. travancorica are lesser-known endemic medium-sized straight-stemmed trees with horizontal branches.  The trees are distributed in the restricted forest areas (700–1,500 m) of Agasthyamalai Biosphere Reserve.  Both the species are dioecious trees and have male and female flowers in two different individuals, sometimes at a distance of a few kilometers from each other.  A large number of mature individuals of these species have been over-exploited from Agasthyamalai Biosphere Reserve and therefore a few mature individuals and seedlings alone exist.  The populations were severely fragmented and exist in a few locations of natural forest areas.  The number of mature individuals recorded in G. imbertI and G. travancorica was 127±14 and 112±14 respectively in the entire distributional areas.  There was an extreme fluctuation observed every year in the case of flowering and fruiting and also in the number of individuals due to the disturbance in the forest ecosystem.  Both species have been included under IUCN threatened category and therefore they need effective conservation measures.
Impact of CD14 Polymorphisms on Anti-Apolipoprotein A-1 IgG-Related Coronary Artery Disease Prediction in the General Population
Authors: Antiochos Panagiotis , Marques-Vidal Pedro , Virzi Julien , Pagano Sabrina , Satta Nathalie , Hartley Oliver , Montecucco Fabrizio , Mach François , Kutalik Zoltan , Waeber Gerard , Vollenweider Peter , Vuilleumier Nicolas
Published: October 2017

Objective—

We aimed to determine whether autoantibodies against apoA-1 (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease (CAD), defined as adjudicated incident myocardial infarction, angina, percutaneous coronary revascularization, or bypass grafting, in the general population. We further investigated whether this association is modulated by a functional CD14 receptor single nucleotide polymorphism.

Approach and Results—

In a prospectively studied, population-based cohort of 5220 subjects (mean age 52.6±10.7 years, 47.4% males), followed over a median period of 5.6 years, subjects positive versus negative for anti-apoA-1 IgG presented a total CAD rate of 3.9% versus 2.8% (
P
=0.077) and a nonfatal CAD rate of 3.6% versus 2.3% (
P
=0.018), respectively. After multivariate adjustment for established cardiovascular risk factors, the hazard ratios of anti-apoA-1 IgG for total and nonfatal CAD were: hazard ratio=1.36 (95% confidence interval, 0.94–1.97;
P
=0.105) and hazard ratio=1.53 (95% confidence interval, 1.03–2.26;
P
=0.034), respectively. In subjects with available genetic data for the C260T
rs2569190
single nucleotide polymorphism in the CD14 receptor gene (n=4247), we observed a significant interaction between anti-apoA-1 IgG and
rs2569190
allele status with regards to CAD risk, with anti-apoA-1 IgG conferring the highest risk for total and nonfatal CAD in non-TT carriers, whereas being associated with the lowest risk for total and nonfatal CAD in TT homozygotes (
P
for interaction =0.011 and
P
for interaction =0.033, respectively).

Conclusions—

Anti-apoA-1 IgG are independent predictors of nonfatal incident CAD in the general population. The strength of this association is dependent on a functional polymorphism of the CD14 receptor gene, a finding suggesting a gene–autoantibody interaction for the development of CAD.
Aphanius kruppi, a new killifish from Oman with comments on the A. dispar species group (Cyprinodontiformes: Aphaniidae)
Authors: FREYHOF JÖRG , WEISSENBACHER ANTON , GEIGER MATTHIAS
Published: October 2017

Eight species are recognised in the Aphanius dispar group. Aphanius dispar from the Red and Mediterranean Sea basins, A. stoliczkanus from coastal areas of the Arabian/Persian Gulf, the northern Arabian Sea east to Gujarat in India, the Gulf of Oman and some endorheic basins in Iran and Pakistan, A. richardsoni from springs in the Dead Sea basin in Jordan and Israel, A. sirhani from the Azraq Oasis in Jordan, A. ginaonis from one spring in Iran, A. furcatus from few streams and springs in Iran and A. stiassnyae from one lake in Ethiopia. Aphanius kruppi, new species, from the Wadi al Batha drainage in northern Oman, is distinguished from adjacent A. stoliczkanus by having 9–14 brown or grey lateral bars on the flank in the male, a roundish, diamond-shaped or somewhat vertically-elongate blotch centred on the caudal-fin base in the female and 2–3 scale rows on the caudal-fin base. The available molecular genetic data for A. dispar reject the hypothesis of the presence of a single widespread coastal species in the Middle East and make it likely that two additional unidentified species occur in the Red Sea basin.
New species and new records of Calycomyza Hendel (Diptera: Agromyzidae) in Brazil
Authors: MONTEIRO NILTON JUVENCIO SANTIAGO , ESPOSITO MARIA CRISTINA
Published: October 2017

Two new species and a new record of Calycomyza Hendel are described for the Brazilian Amazon: Calycomyza rolandrae sp. nov. and Calycomyza dryas sp. nov. This is the first time we recorded Calycomyza hyptisicola Spencer and Calycomyza richardsi (Spencer) in Brazil. These species can be distinguished by the structure of the male terminalia, but the female terminalia can be an important taxonomic character, especially the ninth abdominal sternite, ninth abdominal tergite and the marginal seta.
A novel symbiotic relationship between mites and recluse spiders (Sicariidae: Loxosceles), with a description of a new Callidosoma species (Trombidiformes: Erythraeidae)
Authors: BERNARDI LEOPOLDO FERREIRA DE OLIVEIRA , WOHLTMANN ANDREAS , LORENZON ISABELA M , FERREIRA RODRIGO LOPES
Published: October 2017

This study reports a symbiotic association between an unknown species of Loxosceles (Araneae: Sicariidae) and the adults of a new species of parasitengone mite that lives on their web in Brazilian caves. This mite is described as Callidosoma cassiculophylla sp. nov. (Parasitengona: Erythraeidae). The symbiotic association is clearly beneficial for the mite, which lives with the spider, and feeds on prey captured by their webs, without any aggressive behavior or expulsion of the mites by the spiders.
Checklist and new species of caddisfly (Insecta: Trichoptera) from Roraima state, Brazil
Authors: NETO JAIME DE LIEGE GAMA , PES ANA MARIA , HAMADA NEUSA
Published: October 2017

We conducted an inventory of the Trichoptera fauna of Serra do Tepequém, Amajari municipality (county), Roraima state, Brazil. Adult caddisflies were collected with Pennsylvania and Malaise traps operated beside three 2nd-order streams near the summit of Serra do Tepequém. We identified 27 Trichoptera species (including two new species), all representing new records for the state of Roraima, five of these species are recorded for the first time in Brazil. In this study, two new species are described: Marilia mahedae sp. nov. differs from all other species of the genus by the following combination of characters: Segment X subquadrate in dorsal view, bipartite, membranous mesally, with short apical V-shaped incision; preanal appendages wide at base in lateral view; endotheca with an acute subapicoventral projection, directed anterad in lateral view; phallotheca very short. Polyplectropus tepequemensis sp. nov. differs from all other species of the genus by the following combination of characters: Posterior margin of sternum IX nearly straight; slightly sclerotized intermediate appendages broad in the basal 2/3 and abruptly slender apically; two phallic ducts, each with an endothecal spine. With this inventory the number of Trichoptera species for Roraima state increased from 37 to 65.
Two new species of Suberitida (Porifera, Heteroscleromorpha) from the Bering Sea
Authors: LEHNERT HELMUT
Published: October 2017

Two new species, Plicatellopsis borealis and Spongosorites beringensis, from the Bering Sea are described; both belong to genera previously not reported from the area. The genus Plicatellopsis, Burton, 1932 (Porifera, Suberitida, Suberitidae) contains five valid species, all recorded from the southern hemisphere. The record of P. borealis n. sp. from the Bering Sea is consequently the first record of the genus from the northern hemisphere. The genus Spongosorites Topsent, 1896 (Porifera, Suberitida, Halichondriidae) contains 22 valid species but none reported from the North Pacific Ocean, Bering Sea or the Arctic Ocean. The geographically closest records are six species occurring in the North Atlantic Ocean. So the description of Spongosorites beringensis n.sp. is the first record of the genus in the region.
Avian Sensor Packages for Meteorological Measurements
Authors: Thomas Rick M. , MacKenzie A. Rob , Reynolds S. James , Sadler Jonathan P. , Cropley Ford , Bell Simon , Dugdale Stephen J. , Chapman Lee , Quinn Andrew , Cai Xiaoming
Published: October 2017

The increasing miniaturization of accurate, reliable meteorological sensors and logging systems allows the deployment of sensor packages on lightweight airborne platforms. Here, we demonstrate the safe and humane use of avian species (white-tailed and Spanish imperial eagles) to carry a prototype miniature sensor package to measure temperature with a 5-Hz response and ±0.2°C resolution. This technique could allow sensor deployment above complex urban terrain, where such data are urgently required. Recent meteorological work has been facilitated by using unmanned aerial vehicles (UAVs), but their use within, and adjacent to, urban areas is heavily controlled. The package contains a wind speed sensor, a GPS, a pressure altimeter, and accelerometers. Four flight tests were conducted in a steep valley (glen) at a remote Scottish location that provided contrasting vertical temperature profiles. The glen was instrumented with additional meteorological equipment at the bird launch and landing sites. Vertical temperature profile data from the raptors indicated the success of this approach with absolute temperatures and lapse rates consistent with those measured by the weather stations. Movement and airspeed data aided the interpretation of finescale temperature profiles in complex terrain. As well as the potential for meteorological sensing, this work is of interest to the avian ecology and behavior communities and to aerodynamicists interested in developing airborne robotics to mimic aspects of bird flight. These sensors are being miniaturized further for deployment on other bird species in urban areas for rapid, repeatable, and reliable measurements, with the potential to fulfill a measurement niche above the urban canopy.
A 65-yr Climatology of Unusual Tracks of Tropical Cyclones in the Vicinity of China’s Coastal Waters during 1949–2013
Authors: Zhang Xuerong , Li Ying , Zhang Da-Lin , Chen Lianshou
Published: October 2017

Despite steady improvements in tropical cyclone (TC) track forecasts, it still remains challenging to predict unusual TC tracks (UNTKs), such as the tracks of sharp turning or looping TCs, especially after they move close to coastal waters. In this study 1059 UNTK events associated with 564 TCs are identified from a total of 1320 TCs, occurring in the vicinity of China’s coastal waters, during the 65-yr period of 1949–2013, using the best-track data archived at the China Meteorological Administration’s Shanghai Typhoon Institute. These UNTK events are then categorized into seven types of tracks—sharp westward turning (169), sharp eastward turning (86), sharp northward turning (223), sharp southward turning (46), looping (153), rotating (199), and zigzagging (183)—on the basis of an improved UNTK classification scheme. Results show significant annual variability of unusual tracking TCs, ranging between 2 and 18 per year, many of which experience more than one UNTK event in the same or different UNTK types during their life spans. The monthly distribution of the UNTK events resembles that of TCs, with more occurring in June–November. An analysis of their spatial distributions reveals that all of the UNTK events tend to take place in the areas to the south of 30°N, most frequently in the South China Sea and to the east of the Philippines. The results suggest that more attention be paid to the improved understanding and prediction of UNTK events so that the current positive trend in TC track forecast accuracy can continue for many years to come.
FTY720 Story. Its Discovery and the following Accelerated Development of Sphingosine 1-Phosphate Receptor Agonists as Immunomodulators Based on Reverse Pharmacology
Authors: Adachi Kunitomo , Chiba Kenji
Published: October 2017

Fingolimod (FTY720) is the first of a novel class: sphingosine 1-phosphate (S1P) receptor modulator and is currently in phase 3 clinical trials for multiple sclerosis (MS). FTY720 was first synthesized in 1992 by chemical modification of an immunosuppressive natural product, ISP-I (myriocin). ISP-I was isolated from the culture broth of Isaria sinclairii, a type of vegetative wasp that was an ‘eternal youth’ nostrum in traditional Chinese medicine. ISP-I is an amino acid having three successive asymmetric centers and some functionalities. We simplified the structure drastically to find a nonchiral symmetric 2-substitued-2-aminopropane-1,3-diol framework for an in vivo immunosuppressive activity (inhibition of rat skin allograft rejection test or prolonging effect on rat skin allograft survival) and finally discovered FTY720. During the course of the lead optimization process, we encountered an unexpected dramatic change of the mechanism of action with an in vivo output unchanged. Since it proved that FTY720 did not inhibit serine palmitoyltransferase that is the target enzyme of ISP-I, reverse pharmacological approaches have been preformed to elucidate that FTY720 is mainly phosphorylated by sphingosine kinease 2 in vivo and the phosphorylated drug acts as a potent agonist of four of the five G protein coupled receptors for S1P: S1P1, S1P3, S1P4 and S1P5. Evidence has accumulated that immunomodulation by FTY720-P is based on agonism at the S1P1 receptor. Medicinal chemistry targeting S1P1 receptor agonists is currently in progress. The FTY720 story provides a methodology where in vivo screens rather than in vitro screens play important roles in the lead optimization. Unlike recent drug discovery methodologies, such a strategy as adopted by the FTY720 program would more likely meet serendipity.
Bioactive and Structural Metabolites of Pseudomonas and Burkholderia Species Causal Agents of Cultivated Mushrooms Diseases
Authors: Andolfi Anna , Cimmino Alessio , Cantore Pietro Lo , Iacobellis Nicola Sante , Evidente Antonio
Published: October 2017

Pseudomonas tolaasii, P. reactans and Burkholderia gladioli pv. agaricicola, are responsible of diseases on some species of cultivated mushrooms. The main bioactive metabolites produced by both Pseudomonas strains are the lipodepsipeptides (LDPs) tolaasin I and II and the so called White Line Inducing Principle (WLIP), respectively, LDPs which have been extensively studied for their role in the disease process and for their biological properties. In particular, their antimicrobial activity and the alteration of biological and model membranes (red blood cell and liposomes) was established. In the case of tolaasin I interaction with membranes was also related to the tridimensional structure in solution as determined by NMR combined with molecular dynamic calculation techniques. Recently, five news minor tolaasins, tolaasins A-E, were isolated from the culture filtrates of P. tolaasii and their chemical structure was determined by extensive use of NMR and MS spectroscopy. Furthermore, their antimicrobial activity was evaluated on target micro-organisms (fungi–-including the cultivated mushrooms Agaricus bisporus, Lentinus edodes, and Pleurotus spp.–-chromista, yeast and bacteria). The Gram positive bacteria resulted the most sensible and a significant structure-activity relationships was apparent. The isolation and structure determination of bioactive metabolites produced by B. gladioli pv. agaricicola are still in progress but preliminary results indicate their peptide nature. Furthermore, the exopolysaccharide (EPS) from the culture filtrates of B. gladioli pv. agaricicola, as well as the O-chain and lipid A, from the lipo-polysaccharide (LPS) of the three bacteria, were isolated and the structures determined.
Sulforaphane from Broccoli Reduces Symptoms of Autism: A Follow-up Case Series from a Randomized Double-blind Study
Authors: Lynch Rhoda , Diggins Eileen L , Connors Susan L , Zimmerman Andrew W , Singh Kanwaljit , Liu Hua , Talalay Paul , Fahey Jed W
Published: October 2017

Introduction

Autism spectrum disorder (ASD) affects 1 in 68 children, is characterized by impaired social interaction and communication as well as restricted or repetitive behaviors, and varies widely with respect to its causes and presentations. There are no validated pharmacologic treatments for the core symptoms of ASD. The social, medical, and economic burdens of ASD on families and caregivers are profound. We recently showed in a small clinical trial that sulforaphane (SF) from broccoli sprouts could significantly reduce the behavioral symptoms of ASD.

Methods

After we completed the intervention phase of the original trial (2011–2013), many caregivers used over-the-counter dietary SF supplements in order to attempt to maintain improvements similar to those noted during the intervention. We periodically followed the progress of study participants through the summer of 2016.

Results

Families of 16 of the 26 subjects who received SF as part of the original study responded to requests for further information. Of these subjects, 6 did not continue taking SF supplements after the study. Nine of the 16 subjects are still taking an SF supplement and a 10th planned to. We present the edited testimonials of their caregivers in this case series.

Conclusions

Many parents and caregivers articulated the positive effects of SF, both during the intervention phase and in the ensuing 3 years reported herein. These observations may contribute to understanding ASD and to treatments that may alleviate some of its symptoms. Diet- and supplement-based therapies deserve careful consideration for their potential to provide vital clinical as well as biochemical information about ASD.
Geometric spreading in orthorhombic media
Authors: Stovas Alexey
Published: October 2017

Geometric spreading is an important factor that needs to be taken into account in the analysis of seismic amplitudes. In particular, when using any modification of amplitude variation with offset or amplitude versus azimuth methods, the effect of geometric spreading is crucial to isolate the effect of reflection from a particular interface. The relative geometric spreading controls the amplitude of seismic waves passing through a velocity model. In the case of an anisotropic medium, geometric spreading becomes very complicated. Usually, geometric spreading is computed from ray tracing. I have derived simple analytical formulas to compute the relative geometric spreading of P-waves in a stack of acoustic orthorhombic layers with azimuthal variations in symmetry planes. I also analyzed the kinematic properties of the derived equations and performed sensitivity analysis with respect to three anelliptic parameters. A simple and accurate approximation for the relative geometric spreading is derived and tested against well-known approximation. My approximations give insight into the role that anelliptic parameters play into the azimuthal distribution of amplitudes and can be used for amplitude analysis in multilayered orthorhombic models.
Shearlets and sparse representation for microresistivity borehole image inpainting
Authors: Assous Said , Elkington Peter
Published: October 2017

Microresistivity image logs from wireline tools commonly include nonmeasured gaps corresponding to the spaces between electrode-carrying pads in contact with the borehole wall. The missing data impede the development of automated processes that seek to provide objective and reproducible geologic analysis. Geologic features often manifest themselves as curvilinear objects representing a variety of discontinuities, such as layer boundaries and fractures, which lend themselves to sparse representation. Missing data may be inpainted by thresholding or minimizing the norm of their representation in a fitting dictionary. Curvelets have been found to provide good sparse approximation for these features, but shearlets are shown to be more computationally efficient. Results from a mix of synthetic and field image logs indicate more accurate reconstruction of sharp high-contrast edges.
Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2
Authors: Ganz Patricia A. , Romond Edward H. , Cecchini Reena S. , Rastogi Priya , Geyer Charles E. , Swain Sandra M. , Jeong Jong-Hyeon , Fehrenbacher Louis , Gross Howard M. , Brufsky Adam M. , Flynn Patrick J. , Wahl Tanya A. , Seay Thomas E. , Wade James L. , Biggs David D. , Atkins James N. , Polikoff Jonathan , Zapas John L. , Mamounas Eleftherios P. , Wolmark Norman
Published: October 2017

Purpose

Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment.

Patients and Methods

Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions.

Results

At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab.

Conclusion

In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.