bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET Targeting Human PD-1 Expression
Authors: Natarajan Arutselvan , Patel Chirag B. , Habte Frezghi , Gambhir Sanjiv S. 
Published: January 2018

AbstractThe immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry. The tracer was utilized to image hPD-1 levels in two subcutaneous mouse models: (a) 293 T/hPD-1 cells xenografted into NOD-scid IL-2Rγnull mice (NSG/293 T/hPD-1) and (b) human peripheral blood mononuclear cells engrafted into NSG bearing A375 human melanoma tumors (hNSG/A375). In each mouse model two cohorts were evaluated (hPD-1 blockade with pembrolizumab [blk] and non-blocked [nblk]), for a total of four groups (n = 3–5/group). The xenograft-to-muscle ratio in the NSG/293 T/hPD-1 model at 24 h was significantly increased in the nblk group (7.0 ± 0.5) compared to the blk group (3.4 ± 0.9), p = 0.01. The radiotracer dosimetry evaluation (PET/CT ROI-based and ex vivo) in the hNSG/A375 model revealed the highest radiation burden to the liver. In summary, we validated the 64Cu-pembrolizumab tracer’s specific hPD-1 receptor targeting and predicted human dosimetry.
Association of Homocysteine with Aysmptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients
Authors: Wang Yan , Zhang Jin , Qian Yuesheng , Tang Xiaofeng , Ling Huawei , Chen Kemin , Li Yan , Gao Pingjin , Zhu Dingliang 
Published: January 2018

AbstractElevated plasma homocysteine (Hcy) is suggested as an independent risk factor for stroke. We aimed to investigate the association of Hcy concentration with intracranial atherosclerosis (ICAS) and extracranial AS (ECAS) in hypertensive patients without stroke in Chinese population and to explore modified effect of methylenetetrahydrofolate reductase (MTHFR) C677T on their relationship. The stenosis of intracranial and extracranial arteries were evaluated in a total of 929 subjects through computerized tomographic angiography (CTA) from aortic arch to the skull base. Hcy concentration showed significantly association with both ICAS (OR: 1.105; 95% CI: 1.057–1.155) and ECAS (OR: 1.096; 95% CI: 1.047–1.146) for 1 µmol/L increment in Hcy. Meanwhile, hyperhomocysteinemia (≥15 µmol/L) was also displayed association with ICAS (OR: 1.587; 95% CI: 1.029–2.446) and ECAS (OR: 2.164; 95% CI: 1.392–3.364) after fully adjustment. Furthermore, in the subgroup analysis, such association remained significant only in the subjects that were younger, with normal renal function and with MTHFR 677 C allele. Our study showed the significant association of Hcy with ECAS and ICAS in asymptomatic hypertension patients. Hcy played a universal effect on the cervico-cerebral atherosclerosis. Such association was modified by the MTHFR C677T genotype.
Effects of larvae density and food concentration on Crown-of-Thorns seastar (Acanthaster cf. solaris) development in an automated flow-through system
Authors: Uthicke S. , Liddy M. , Patel F. , Logan M. , Johansson C. , Lamare M. 
Published: January 2018

AbstractCoral-eating Crown-of-Thorns Sea stars (Acanthaster spp.) are major contributors to coral reef loss in the Indo-Pacific region. A release from food limitation of their planktotrophic larvae through enhanced pelagic productivity is one of the main hypothesis explaining population outbreaks (‘nutrient limitation hypothesis’). To improve the understanding of these outbreaks we developed an automated flow- through larvae rearing system that maintained food (microalgae) at set levels over the course of four 15d experiments. This resulted in stable food concentrations in experimental tanks. Increased algae concentrations had a significant positive effect on larval development and size at 10 and 15 days post fertilization (dpf). Larvae densities had no effect at 10 dpf. At 15 dpf greater larvae densities were associated with declines in larvae size. Larval development was slowed under higher larvae densities. Thus, the effects of algae concentration and larvae density were additive at 15 dpf, with larvae under low densities at a given algae concentration being further developed than those under higher densities. The development of a flow-through system gives greater insight into the effect of algae and larvae concentrations on Acanthaster development, and the system can be applied to further test the nutrient-limitation hypothesis for present and future outbreaks.
Large unexplained suite of chemically reactive compounds present in ambient air due to biomass fires
Authors: Kumar V. , Chandra B. P. , Sinha V. 
Published: January 2018

AbstractBiomass fires impact global atmospheric chemistry. The reactive compounds emitted and formed due to biomass fires drive ozone and organic aerosol formation, affecting both air quality and climate. Direct hydroxyl (OH) Reactivity measurements quantify total gaseous reactive pollutant loadings and comparison with measured compounds yields the fraction of unmeasured compounds. Here, we quantified the magnitude and composition of total OH reactivity in the north-west Indo-Gangetic Plain. More than 120% increase occurred in total OH reactivity (28 s−1 to 64 s−1) and from no missing OH reactivity in the normal summertime air, the missing OH reactivity fraction increased to ~40 % in the post-harvest summertime period influenced by large scale biomass fires highlighting presence of unmeasured compounds. Increased missing OH reactivity between the two summertime periods was associated with increased concentrations of compounds with strong photochemical source such as acetaldehyde, acetone, hydroxyacetone, nitromethane, amides, isocyanic acid and primary emissions of acetonitrile and aromatic compounds. Currently even the most detailed state-of-the art atmospheric chemistry models exclude formamide, acetamide, nitromethane and isocyanic acid and their highly reactive precursor alkylamines (e.g. methylamine, ethylamine, dimethylamine, trimethylamine). For improved understanding of atmospheric chemistry-air quality-climate feedbacks in biomass-fire impacted atmospheric environments, future studies should include these compounds.
A novel approach for correction of crosstalk effects in pathway analysis and its application in osteoporosis research
Authors: Zhou Yu , Gao Yunlong , Xu Chao , Shen Hui , Tian Qing , Deng Hong-Wen 
Published: January 2018

AbstractOsteoporosis is a prevalent bone metabolic disease and peripheral blood monocytes represent a major systemic cell type for bone metabolism. To identify the key dysfunctional pathways in osteoporosis, we performed pathway analyses on microarray data of monocytes from subjects with extremely high/low hip bone mineral density. We first performed a traditional pathway analysis for which different pathways were treated as independent. However, genes overlap among pathways will lead to “crosstalk” phenomenon, which may lead to false positive/negative results. Therefore, we applied correction techniques including a novel approach that considers the correlation among genes to adjust the crosstalk effects in the analysis. In traditional analysis, 10 pathways were found to be significantly associated with BMD variation. After correction for crosstalk effects, three of them remained significant. Moreover, the MAPK signaling pathway, which has been shown to be important for osteoclastogenesis, became significant only after the correction for crosstalk effects. We also identified a new module mainly consisting of genes present in mitochondria to be significant. In summary, we describe a novel method to correct the crosstalk effect in pathway analysis and found five key independent pathways involved in BMD regulation, which may provide a better understanding of biological functional networks in osteoporosis.
Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer
Authors: Seabra Mariana Ataydes Leite , Cândido Eduardo Batista , Vidigal Paula Vieira Teixeira , Lamaita Rivia Mara , Rodrigues Angélica Nogueira , Silva Filho Agnaldo Lopes da 
Published: January 2018

Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association.
Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies.
Results The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples.
Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.
Myasthenia Gravis – Exacerbation and Crisis
Authors: Schroeter Michael , Thayssen Günther , Kaiser Julia 
Published: January 2018

AbstractMyasthenic exacerbation and crisis are most critical incidences in myasthenia gravis. Even nowadays myasthenic crisis is a life-threatening condition, with a lethality of 2–3%. We review means of avoiding myasthenic exacerbation and crisis, elaborate on red flags and how to establish highly-active therapy in a timely manner. This includes the reasonable use of cholinesterase inhibitors, immunoadsorption or plasma exchange, as well as immunoglobulins and steroids. Immunosuppressive agents and monoclonal antibody therapy add to the therapeutic options.Intensive care of myasthenic patients includes the management of dysphagia and delirium. Importantly, the perioperative management of patients undergoing thymectomy and weaning are specific challenges in the treatment of myasthenic patients in the ICU.Establishing timely consequent immunosuppression and treatment of myasthenic patients in specialized outpatient centres help to avoid repetitive exacerbations and crises.
Juvenile Myasthenia Gravis
Authors: Marina Adela , Schara Ulrike 
Published: January 2018

AbstractJuvenile myasthenia gravis (JMG) is an autoimmune disorder of neuromuscular transmission caused by production of antibodies against the postsynaptic membrane of the neuromuscular junction. Clinical signs in young children and adolescents range from isolated ocular symptoms to general muscular weakness and respiratory insufficiency. Clinical presentation of JMG in young children and adolescents shows distinct features compared to adults. Young children may show generalized muscular weakness already during the first two years of life, and in this group specific antibodies can be only slightly increased. Because of existing therapeutic options, an early diagnosis is important. In case of negative specific antibodies and onset of the first symptoms during infancy or early childhood, the diagnosis of a congenital myasthenic syndrome (CMS) must be considered and is not always clear to differentiate. Clinical symptoms, diagnostic procedures and therapeutic strategies with consideration of specificities of this age group are discussed.
Effects and Quality of Stroke Rehabilitation of BAR Phase D
Authors: Bussmann Marie-Luise , Neunzig Hans-Peter , Gerber Joachim , Steinmetz Jochen , Jung Svenja , Deck Ruth 
Published: January 2018

Abstract
Background Stroke is a major public health problem of enormous epidemiological significance. Each year, approximately 200.000 people in Germany suffer a stroke. Stroke is the third leading cause of death and the most common cause of acquired disabilities in adults. About one fourth of stroke survivors report severe limitations in activities of daily living three months after acute stroke. The most common post-stroke conditions are motor and cognitive dysfunctions as well as affective problems. Stroke rehabilitation plays a crucial role in coping with stroke sequelae. The large number of strokes and the often debilitating consequences raise the question to what extent participation can be increased by medical rehabilitation.
Methods A prospective, multicenter survey study was conducted in six neurological inpatient rehabilitation centers. Recruitment focused on patients with recent acute stroke and disease severity corresponding to BAR phase D. Patients completed questionnaires at three points of measurement: at the beginning and at the end of the inpatient rehabilitation and after four months. Primary outcome was participation, secondary outcomes included several parameters of subjective well-being. Furthermore, utilization of aftercare and satisfaction with the rehabilitation program were measured.
Results At the beginning of the rehabilitation, patients experienced severe limitations in participation and reduced subjective well-being. At the end of inpatient rehabilitation, significant improvements of small effect sizes for subjective well-being and medium effect sizes for participation were achieved. After four months, effects had decreased, yet improvements compared to baseline were still noticeable. Patient ratings of the rehabilitation program and the outcomes achieved were consistently positive. Two thirds of the patients were advised to make use of aftercare offerings and most patients (83%) participated in an aftercare program of any kind.
Conclusions The results of this study support the notion that stroke rehabilitation has significant and sustainable effects. Participation in particular seems to improve through medical rehabilitation. Partly decreased effects after four months raise the question of adequate aftercare.
Kolaviron and Garcinia kola Seed Extract Protect Against Ischaemia/Reperfusion Injury on Isolated Rat Heart
Authors: Oyagbemi Ademola , Bester Dirk , Esterhuyse Johan , Farombi Ebenezer 
Published: January 2018

Abstract
Background The incidence of cardiovascular diseases and its associated complications have increased greatly in the past three decades. The purpose of this study was to evaluate the acute cardioprotective effects of Garcinia kola (GK) seed extract and Kolaviron (KV) and determine mechanisms of action involving RISK signalling pathways.
Methods Male Wistar rats were used in this study. Hearts were excised and mounted on the Langendorff perfusion system. The control, group 1 was perfused with dimethyl sulfoxide (DMSO), group II with KV and group III with GK respectively. Western blot analyses were performed on frozen heart tissues.
Results Isolated rat hearts perfused with KV and GK attenuated apoptotic pathways with significant reduction in p38 MAPK protein phosphorylation, as well as reduction in total caspase 3, cleaved caspase 3 (Asp 175) and PARP cleavage. KV and GK also down-regulated p-JNK1 (Tyr 185) and p-JNK 2 (Thr 183) protein expression at the 10 min reperfusion time ponit. Cardioprotection was achieved in part, by enhancement of the reperfusion injury signalling kinase (RISK) pathway; as evidenced by significant increases in protein expresion of Akt/PKB and p-Akt/PKB (Ser 473) in KV and GK respectively.
Conclusions KV and GK supplementation led to significant increases in the expressions of survival proteins. It is noteworthy that both KV and GK supplementation offered cardioprotection in ischaemic/reperfusion injury rat heart model. In all, GK showed better cardioprotective effect that KV.
A 9-Week Nordic and Free Walking Improve Postural Balance in Parkinson’s Disease
Authors: Franzoni Leandro , Monteiro Elren , Oliveira Henrique , da Rosa Rodrigo , Costa Rochelle , Rieder Carlos , Martinez Flávia , Peyré-Tartaruga Leonardo 
Published: January 2018

AbstractAerobic training has a neuroprotective effect in people with Parkinson’s disease. Recent evidence indicates that Nordic walking seems a promising alternative due to positive outcomes in functional mobility. However, the effects of Nordic walking compared to free walking on static and functional balance parameters are still unknown. The aim of this study was to evaluate the effects of nine weeks of Nordic and free walking training on static and functional balance. The sample size was 33 individuals with eight dropouts, leaving 25 individuals in the final sample (Nordic Walking, n=14, Free Walking, n=11). The participants underwent two evaluations in the present randomized clinical trial, pre- and post-training, to determine average velocity and root-mean-square values from center of pressure with eyes open and eyes closed. The functional balance showed approximately 5% improvement for the two groups (p=0.04). The results indicate that nine weeks of Nordic and free walking training were enough to induce improvements in the proprioceptive system and functional balance.
Unified description of H-atom–induced chemicurrents and inelastic scattering
Authors: Kandratsenka Alexander , Jiang Hongyan , Dorenkamp Yvonne , Janke Svenja M. , Kammler Marvin , Wodtke Alec M. , Bünermann Oliver 
Published: January 2018

Significance
Catalytic reactions at surfaces are exceptionally complex, as they require a multitude of elementary steps. It is therefore very difficult to predict which chemical compounds are catalytically effective. In inelastic scattering experiments in ultrahigh vacuum, the first step of most surface reactions, which is the adsorption, can be studied on model systems in great detail. Based on such experiments new theoretical models can be developed that accurately describe the delicate interplay between electronic and nuclear motion in prototypical chemical reactions, a capability that is needed to make accurate predictions of reaction rates in heterogeneous catalysis, to design useful energy-conversion devices based on chemicurrents, and to understand photocatalysis.
Dynamics of charged excitons in electronically and morphologically homogeneous single-walled carbon nanotubes
Authors: Bai Yusong , Olivier Jean-Hubert , Bullard George , Liu Chaoren , Therien Michael J. 
Published: January 2018

Significance
Formation of quasiparticles, such as excitons, polarons, and trions in semiconductors are the foundation for modern optoelectronics. Unlike the widely investigated exciton and polaron, the trion, a three-body charge-exciton bound state, is less familiar due to its small binding energy in conventional inorganic semiconductors. Here, employing ultrafast spectroscopy and rigorously controlled charge-doping levels, we characterize trion creation and decay in single-walled carbon nanotubes (SWNTs), wherein trions are stable at room temperature. We show that SWNT trions derive exclusively from a precursor exciton state, and importantly, that exciton-to-trion conversion can approach unity under appropriate conditions. Because trions simultaneously carry excitation energy, charge, and spin, our findings may guide design of new SWNT-based optoelectronic devices, including photovoltaics, photodetectors, and spintronics.
Fenofibrate prevents skeletal muscle loss in mice with lung cancer
Authors: Goncalves Marcus D. , Hwang Seo-Kyoung , Pauli Chantal , Murphy Charles J. , Cheng Zhe , Hopkins Benjamin D. , Wu David , Loughran Ryan M. , Emerling Brooke M. , Zhang Guoan , Fearon Douglas T. , Cantley Lewis C. 
Published: January 2018

Significance
The cancer anorexia cachexia syndrome (CACS) is a condition characterized by skeletal muscle degradation with no effective treatment. CACS is particularly prevalent in patients with nonsmall cell lung cancer, where it reduces quality of life and increases mortality. Using an inducible lung cancer model, we characterize the changes in intermediary metabolism that occur during CACS in mice. We identify a unique serum metabolite profile consisting of low ketones and increased glucocorticoid levels. Hypoketonemia is associated with reduced expression of hepatic peroxisome proliferator-activated receptor-α (PPARα) targets that regulate fatty acid oxidation and ketogenesis. Replacing ketone production using the PPARα agonist, fenofibrate, reduced glucocorticoid levels, prevented skeletal muscle wasting, and minimized weight loss. These exciting results provide important preclinical data toward a therapeutic strategy.
Pyruvate induces torpor in obese mice
Authors: Soto Marion , Orliaguet Lucie , Reyzer Michelle L. , Manier M. Lisa , Caprioli Richard M. , Kahn C. Ronald 
Published: January 2018

Significance
Mice can reduce their body temperature and metabolic rate and enter torpor when they are subjected to cold, calorie deprivation, or administration of some metabolic inhibitors. Here we show that administration of pyruvate, a key metabolic intermediate and substrate for gluconeogenesis, induces torpor in obese mice, resulting in marked hypothermia, decreased activity, and decreased metabolic rate. This is dependent on adenosine signaling and on changes in key brain metabolites, including GABA. Lean mice are protected from pyruvate-induced torpor by activating their brown adipose tissue. Understanding this pathway can help provide new approaches for inducing a hypometabolic state in mammals, which could be beneficial in states of food deprivation or ischemia–reperfusion injury and for organ preservation in surgical situations.
Influence of anterior midcingulate cortex on drinking behavior during thirst and following satiation
Authors: Saker Pascal , Farrell Michael J. , Egan Gary F. , McKinley Michael J. , Denton Derek A. 
Published: January 2018

SignificanceThis study provides important insight into how the human brain regulates fluid intake in response to changes in hydration status. The findings presented here reveal that activity in the anterior midcingulate cortex (aMCC) is associated with drinking responses during a state of thirst, and that this region is likely to contribute to the facilitation of drinking during this state. These results are consistent with a reduction in the influence of the aMCC contributing to the conclusion of drinking during a state of satiation. Because drinking stops before changes in blood volume and chemistry signal the restoration of fluid balance, these results implicate the aMCC in the regulation of drinking behavior before these changes manifest within the circulatory system.