bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the Envelope Glycoprotein of HIV-1 Clade B toward Higher Infectious Properties over the Course of the Epidemic
Authors: Bouvin-Pley Mélanie , Beretta Maxime , Moreau Alain , Roch Emmanuelle , Essat Asma , Goujard Cécile , Chaix Marie-Laure , Moiré Nathalie , Martin Loïc , Meyer Laurence , Barin Francis , Braibant Martine
Published: December 2018

Following primary infection by HIV-1, neutralizing antibodies (NAbs) exert selective pressure on the HIV-1 envelope glycoprotein (Env), driving the evolution of the viral population. Previous studies suggested that, as a consequence, Env has evolved at the HIV species level since the start of the epidemic so as to display greater resistance to NAbs. Here, we investigated whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. Our data provide evidence that the infectious properties of the HIV-1 Env increased during the course of the epidemic. These changes may have contributed to increasing virulence of HIV-1 and an optimization of transmission between individuals.
Positive Selection at Key Residues in the HIV Envelope Distinguishes Broad and Strain-Specific Plasma Neutralizing Antibodies
Authors: Mabvakure Batsirai M. , Scheepers Cathrine , Garrett Nigel , Abdool Karim Salim , Williamson Carolyn , Morris Lynn , Moore Penny L.
Published: December 2018

Millions of people are still being infected with HIV decades after the first recognition of the virus. Currently, no vaccine is able to elicit bNAbs that will prevent infection by global HIV strains. Several studies have implicated HIV Env diversity in the development of breadth. However, Env evolution in individuals who fail to develop breadth despite mounting potent strain-specific neutralizing responses has not been well defined. Using longitudinal neutralization, epitope mapping, and sequence data from 14 participants, we found that overall measures of viral diversity were similar in all donors. However, the number of positively selected sites within Env epitopes was higher in bNAb participants than in strain-specific donors. We further identified common sites that were positively selected as bNAbs developed. These data indicate that while viral diversity is required for breadth, this should be highly targeted to specific residues to shape the elicitation of bNAbs by vaccination.
Achromobacter xylosoxidansin idiopathic cystic bronchiectasis
Authors: Bates Anthony Simon , Natarajan Manjula , Reddy Raja Vongala
Published: December 2018

This is the first case in the English language describingAchromobacter xylosoxidansin a patient with idiopathic bronchiectasis. A 66-year-old man with bronchiectasis presented with shortness of breath to the emergency department of our institution, a district hospital in the UK. His medications included long-term supplemental oxygen therapy and prophylactic azithromycin. Following 2 days admission to the respiratory unit, his saturations significantly deteriorated, and the patient was admitted to intensive care with type II respiratory failure. Following a week of intubation and ventilation, multidrug resistantA. xylosoxidanswas isolated from the tracheal aspiration secretions. The patient recovered after receiving targeted intravenous antimicrobial therapy.
Drug-induced Creutzfeldt-Jakob disease-like syndrome: early CSF analysis as useful tool for differential diagnosis
Authors: Paolini Paoletti Federico , Di Gregorio Maria , Calabresi Paolo , Parnetti Lucilla
Published: December 2018

We report the case of a 78-year-old man who showed a subacute onset of severe cognitive impairment, ataxia, tremor, stimulus sensitive myoclonus and hypophonia. Since a few weeks, he received a treatment with a combination of tricyclic antidepressants for mood disorder. The clinical picture mimicked Creutzfeldt-Jakob disease (CJD), but we could rule out this diagnosis by means of cerebrospinal fluid (CSF) analysis, which showed normal level of tau protein and Aβ1-42, being also negative for CSF 14-3-3 protein. A complete clinical recovery was observed after the discontinuation of antidepressants. So far, some cases of drug-induced CJD-like syndrome have been described. In our experience, early CSF analysis shows high diagnostic usefulness in order to exclude CJD.
Rare clinical manifestation of community-acquired pneumonia
Authors: Brikman Shay , Levi Omri , Dori Guy
Published: December 2018

A 71-year-old patient was admitted due to fever and persistent (>48 hours) hiccups. History and physical examination were not instructive. Lab tests were not specific, showing an inflammatory response. Chest film did not demonstrate opacities. The patient was treated with chlorpromazine with no relief. Fever and hiccups persisted, and therefore neck and chest CT was performed revealing a right lower lobe infiltrate, a finding consistent with pneumonia. Antibiotics were initiated and within 48 hours fever and hiccups resolved and patient recovered. Although hiccups are rarely described as a clinical manifestation of community acquired pneumonia, one should consider this diagnosis in a patient with unexplained fever.
Previously unreported deletion of CDC73 involving exons 1–13 was detected in a patient with recurrent parathyroid carcinoma
Authors: Mahajan Geeti , Sacerdote Alan
Published: December 2018

Parathyroid carcinoma (PC) is a rare malignancy, presenting sporadically or as part of a genetic syndrome. Diagnosis of PC includes the histopathological diagnosis based on capsular, perineural, or vascular invasion or metastasis. High suspicion for malignancy includes hypercalcaemia greater than 14 mg/dL, extremely high serum parathyroid hormone (PTH) levels, as well as large masses. Given the rarity of PC, it is challenging to design clinical trials for newer therapy. Currently, complete initial surgical excision of the tumour in high-risk patients offers the best chance of cure and prolonged disease-free survival in PC. In the absence of definite data, non-surgical therapies such as radiation and chemotherapy are not routinely recommended. For early detection of recurrence; long-term clinical follow-up with interval measurements of serum calcium and PTH is recommended. Localising studies of PC are helpful. Early screening for CDC73 mutation and multidisciplinary treatment by an endocrine/ENT/surgical oncology team is recommended.
Use of liothyronine (L-T3) as an augmentation therapy for depression during pregnancy
Authors: Bhella Vishal S , Garg Divya
Published: December 2018

The thyroid hormone triiodothyronine (T3) can be used as an augmentation therapy for depression. This case involves a patient who had been initiated on liothyronine (L-T3) for this purpose and subsequently became pregnant. The exogenous T3 affected maternal thyroid hormone production, including suppression of her thyroxine (T4) levels. In pregnancy, maternal T4 is important for fetal neurodevelopment. Accordingly, use of exogenous T3 for adjunct treatment of depression in pregnant patients or those planning pregnancy requires careful laboratory monitoring of thyroid function tests. In this case, L-T3 was discontinued and the patient was eventually started on levothyroxine (L-T4) and went on to have an uneventful pregnancy.
Hypermucoviscous capsular 1 (K1) serotypeKlebsiella pneumoniaenecrotising fasciitis and metastatic endophthalmitis
Authors: Chiu Harold Henrison Chang , Francisco Christian Nadonga , Bruno Racquel , Jorge II Manuel , Salvaña Edsel Maurice
Published: December 2018

A 48-year-old man presented with a non-healing wound on his left foot after stepping on a nail. He self-medicated with amoxicillin, but the wound progressed prompting consult. On examination, his left foot was diffusely swollen with surrounding erythema, areas of gangrene, foul-smelling purulent discharge and subcutaneous emphysema. He was managed as a case of necrotising fasciitis and underwent emergent amputation. Three days after amputation, he developed a sudden and progressive blurring of vision, swelling and conjunctival erythema, with purulent discharge and the presence of hypopyon on the left eye. He was then managed as a case of endophthalmitis of the left eye and underwent pars plana vitrectomy. All cultures (blood, tissue and vitreous fluid) grew pan-susceptible hypermucoviscousKlebsiella pneumoniae, with positive string tests and confirmed by multilocus gene sequencing and sequence type analysis. He gradually improved with intravenous antibiotics, but only regained light perception in the left eye.
ConcomitantPlasmodium vivaxmalaria and murine typhus infection with pulmonary involvement
Authors: Mansanguan Chayasin , Phumratanaprapin Weerapong
Published: December 2018

We report a case ofPlasmodium vivaxand murine typhus coinfection in a 30-year-old woman who presented with intermittent, high-grade fever. Her peripheral blood smear showed ring-form trophozoites ofP. vivax, with an initial murine typhus serological test being negative. Althoughthe P. vivaxinfection was successfully treated, she still had intermittent, high-grade fever, developed dyspnoea and bilateral interstitial pneumonitis shown in the chest X-ray. Thus, coinfection was suspected, and empirical antibiotics were given. The second serological test confirmed the concomitant murine typhus infection, and antibiotics treatment were successful with the complete recovery. This case emphasises that an initial negative murine typhus serological test does not necessarily rule out the presence of the disease. A follow-up murine typhus serological or molecular test within 1–2 weeks is therefore recommended.
Subglottic acute lymphoblastic leukaemia
Authors: Ojha Shilpa , Gaskin Julian , Saunders Michael
Published: December 2018

Acute lymphoblastic leukaemia (ALL) is one of the the most common malignancies of childhood and can occasionally present as acute airway obstruction. We present the unusual case of a 1-year-old boy who was referred to our Paediatric Otolaryngology (ENT) clinic with a recurrent history of croup. This is the first reported case of localised ALL presenting as a subglottic mass in a paediatric patient. It highlights the need to have a broader differential diagnosis in children presenting with ‘recurrent croup’ including extramedullary presentation of leukaemia and to have a low threshold for performing endoscopy in such cases.
Miliary tuberculosis developing during adalimumab treatment for Behçet’s disease with uveitis
Authors: Kim Minji Jennifer , Jones Nicholas , Steeples Laura R
Published: December 2018

Tumour necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine in non-infective uveitis (NIU). Adalimumab, an anti-TNF-α monoclonal antibody, is approved for the treatment of severe NIU by the European Medicines Agency. There is a recognised risk of serious infections, including tuberculosis (TB), during anti-TNF-α therapy in systemic immune-mediated diseases. We describe miliary pulmonary TB during adalimumab therapy for severe NIU. To our knowledge, this is the first detailed report of this complication in a patient with uveitis. We present the challenges of managing vision-threatening uveitis during life-threatening infection necessitating withdrawal of adalimumab and oral immunosuppression therapy. Uveitis activity was controlled during anti-TB therapy with oral corticosteroid therapy.
Difficulty of acute hepatitis C diagnosis in a hospitalised patient
Authors: Takamizawa Shigemasa , Yamada Toru , Kitamura Koichi , Hiraoka Eiji
Published: December 2018

The hepatitis C virus (HCV) causes acute hepatitis C and is commonly detected via HCV antibody testing. However, delayed seroconversion of HCV antibodies and non-specific symptoms may hinder the diagnosis of this disease. A 71-year-old woman developed acute hepatitis while hospitalised for back pain. An HCV antibody test was negative, and she had no risk factors for hepatitis C. She was referred to our hospital for further evaluation. The HCV antibody test was repeated 16 days after the initial test; owing to a positive result, she was diagnosed with acute hepatitis C. Several months thereafter, the HCV spontaneously cleared. When diagnosing an HCV infection, the time at which the testing is performed needs to coincide with the time at which HCV antibody seroconversion occurs. Timely diagnosis of an HCV infection allows appropriate treatment during the acute phase which may prevent disease progression to the chronic phase.
Varicella zoster in sudden infant death
Authors: Dauger Stéphane , Le Goff Jerome , Deho Anna , Jones Peter
Published: December 2018

A 2-month-old girl with normal development and no previous physical illnesses was resuscitated having been found lifeless on her back at home. On admission to Paediatric Intensive Care, she had severe metabolic disturbance, associated with an extremely troubling neurological signs. She died 2 hours later. A full body CT scan did not reveal injury and her parents declined an autopsy. Peripheral blood and cerebrospinal fluid samples were sterile. However, a broad-range PCR coupled with electrospray-ionisation mass spectrometry onto the PLEX-ID automat of peripheral blood revealed the presence of varicella zoster virus. There was a specific viral load in whole blood of 20 542 copies/ml. It is presumed that Varicella myocarditis was the likely cause of death. Our case illustrates the potential usefulness of a broad range PCR strategy in determining infectious causes of death in sudden infant death. Varicella is a potential cause of sudden infant death.
Primary synovial osteochondromatosis of the shoulder: a rare cause of shoulder pain
Authors: Poyser Emma , Morris Rhys , Mehta Hemang
Published: December 2018

Synovial osteochondromatosis is a benign neoplastic condition which manifests as multiple cartilaginous or osteocartilaginous nodules within a joint, bursa and tendon sheath. It typically results in pain and stiffness of the affected joint, and is thought to arise as a result of synovial membrane proliferation and metaplasia.1We report the diagnosis and management of a 36-year-old man who presented with a long history of shoulder pain, which had been managed conservatively prior to referral to orthopaedics. Following investigation and subsequent diagnosis, he underwent successful surgical treatment of primary synovial osteochondromatosis, in the form of open synovial debridement and excision of nodules, with no recurrence demonstrated at 1-year follow-up. This case illustrates the diagnosis and management of primary synovial osteochondromatosis, and emphasises the importance of serial imaging and specialist referral for cases of diagnostic uncertainty or failure to respond to treatment as expected.
Brief behavioural intervention, delivered as standard care, to support physical activity engagement in men with prostate cancer: a pilot study protocol
Authors: Fox Louis , Wiseman Theresa , Cahill Declan , Fleure Louisa , Kinsella Janette , Van Hemelrijck Mieke
Published: December 2018

Introduction

Physical activity is beneficial to men with prostate cancer, but there remain barriers to fulfilling the potential of National Health Service trusts to support men with prostate cancer to be physically active. This article describes protocols for two pilot studies, each conducted in a different setting, designed to assess the potential of a behavioural intervention to affect patients’ motivation to exercise. The intervention is theory based and inspired by recent empirical observations.

Methods and analysis

The intervention consists of a 10 min talk, delivered to patients by a man with a history of prostate cancer treatment and a good experience of exercise, as part of their standard care. This talk either takes place in a preradical prostatectomy seminar (study one), or a post-treatment seminar designed to assist patients in adjusting to life after treatment (study two). Outcomes will be compared between patients attending the existing seminar format, and patients attending the novel seminar format. The two primary outcomes are: (1) differences in self-reported physical activity before and 90 days after the seminar and (2) the likelihood of the patient seeing an in-house exercise physiotherapist in those 90 days. Data on quality of life, fatigue and exercise behavioural regulations will also be captured at the same time points.

Ethics and dissemination

These two projects have been approved by internal clinical audit committees due to their focus on service improvement. Findings from these pilot studies will be presented at oncology meetings and submitted for publication in academic journals.
Face scale rating of perceived exertion during cardiopulmonary exercise test
Authors: Morishita Shinichiro , Tsubaki Atsuhiro , Nashimoto Satoshi , Fu Jack B , Onishi Hideaki
Published: December 2018

Objective

This study aimed to investigate the correlation between the face scale and heart rate (HR), exercise load and oxygen uptake (V̇O2) during cardiopulmonary exercise testing.

Methods

This was a prospective, observational study of face scale rating of perceived exertion (RPE) and HR, exercise load and V̇O2during cardiopulmonary exercise testing. A total of 30 healthy college men and 21 healthy college women were included. Subjects performed a cardiopulmonary exercise test with ramps and an increment increase in workload of 20 W/min. We recorded the responses of subjects using a face scale for RPE, HR, exercise load and V̇O2every minute during the cardiopulmonary exercise test.

Results

In men, there was a significant positive correlation between the face scale RPE and HR (ρ=0.856, p<0.01), exercise load (ρ=0.888, p<0.01) and V̇O2(ρ=0.878, p<0.01) during the cardiopulmonary exercise test. Similarly, in women, there was a significant positive correlation between the face scale RPE and HR (ρ=0.885, p<0.01), exercise load (ρ=0.908, p<0.01) and V̇O2(ρ=0.895, p<0.01) during the cardiopulmonary exercise tests.

Conclusion

The face scale proposed in this study was related to physiological parameters, which suggests that it may be used to determine the intensity of exercise in healthy adults.
Sediment distribution pattern of the South Caspian Sea: possible hydroclimatic implications
Authors: Lahijani H.A.K. , Abbasian H. , Naderi Beni A. , Leroy S.A.G. , Haghani S. , Habibi P. , Hosseindust M. , Shahkarami S. , Yeganeh S. , Zandinasab Z. , Tavakoli V. , Vahabi-Asil F. , Azizpour J. , Sayed-Valizadeh M. , Pourkerman M. , Shah-Hosseini M.
Published: December 2018

The south Caspian subbasin extends from the foot of the Alborz Mountains to the deepest part of Caspian Sea. The lithological background and tectonic setting of the study area primarily control the deposition of thick sedimentary sequences of the basin, while hydroclimatic processes exert secondary impacts on the sediment distribution pattern. To evaluate past hydroclimatic changes, short sediment cores were retrieved from the continental shelf and upper slope of the south Caspian Sea and were treated for basic sedimentological properties and mineralogy. The results show that the sediments are composed of terrigenous, biogenic, and chemical components. The chemical component has a significant signature in the internal structure of the sediment, which reflects degradation of organic material due to a succession of aerobic and anaerobic conditions. Aerobic conditions reflect the extreme climatic conditions that lead to formation of well-oxygenated deep water in lowstands and extremely cold winters, when dense oxygenated water is allowed to touch the bottom sediments. The sediment distribution pattern demonstrates three distinctive areas in the southern continental margin with different organic matter and carbonate content. Fluvial inputs and wave hydrodynamics control the sediment properties and their distribution pattern in the upper shelf, while in deeper parts, the dynamics of water stratification and its temporal and long-term variations, relating to climate and water level changes, determine sediment composition. Overall, the sedimentary distribution pattern is a result of their sources in the catchment basin and the hydroclimate of the Caspian Sea.
Semantic Plug and Play — Self-Descriptive Modular Hardware for Robotic Applications
Authors: Eymüller Christian , Wanninger Constantin , Hoffmann Alwin , Reif Wolfgang
Published: December 2018

This paper describes the use of semantically annotated data for the expression of sensors and actuators with their properties and capabilities. For this purpose, a plug and play mechanism is presented in order to exchange self-descriptions between several hardware devices and then use the established information for the execution of capabilities. For the combination of different capabilities distributed on multiple hardware devices an architecture is presented to link abstract capabilities. These abstract capabilities are initialized through concrete capabilities of the discovered hardware devices by the plug and play mechanism.
ASYMMETRIC IMPACT OF EXCHANGE RATE CHANGES ON THE TRADE BALANCE: DOES GLOBAL FINANCIAL CRISIS MATTER?
Authors: CHANG BISHARAT HUSSAIN , RAJPUT SURESH KUMAR OAD , GHUMRO NIAZ HUSSAIN
Published: December 2018

Recent studies have been mainly focusing on whether exchange rate changes have a symmetric or asymmetric effect on the trade balance. We revisit this question in the context of US and further extend previous studies by determining whether the relationship between these underlying variables change as a result of the global financial crisis. We use both linear autoregressive distributed lag (ARDL) and non-linear ARDL models for the whole sample period as well as in the pre- and post-crisis periods. Findings suggest that exchange rate changes have an asymmetric effect on the trade balance; however, the asymmetric behavior of the underlying variables change as a result of the financial crisis. In the short run, exchange rate asymmetrically affects trade balance in the post-crisis period only. In the long run, there is an asymmetric effect for all sample periods, where only the devaluation of currency significantly affects the trade balance when the whole sample period is selected. On the other hand, in pre- and post-crisis periods, only appreciation of currency significantly affects the trade balance. This study indicates that determining the asymmetric relationship without considering the global financial crisis may lead to spurious results.
fMRI Evidence of Magnitude Manipulation during Numerical Order Processing in Congenitally Deaf Signers
Authors: Andin Josefine , Fransson Peter , Rönnberg Jerker , Rudner Mary
Published: December 2018

Congenital deafness is often compensated by early sign language use leading to typical language development with corresponding neural underpinnings. However, deaf individuals are frequently reported to have poorer numerical abilities than hearing individuals and it is not known whether the underlying neuronal networks differ between groups. In the present study, adult deaf signers and hearing nonsigners performed a digit and letter order tasks, during functional magnetic resonance imaging. We found the neuronal networks recruited in the two tasks to be generally similar across groups, with significant activation in the dorsal visual stream for the letter order task, suggesting letter identification and position encoding. For the digit order task, no significant activation was found for either of the two groups. Region of interest analyses on parietal numerical processing regions revealed different patterns of activation across groups. Importantly, deaf signers showed significant activation in the right horizontal portion of the intraparietal sulcus for the digit order task, suggesting engagement of magnitude manipulation during numerical order processing in this group.
Method for Analyzing the Molecular and Carbon Isotope Composition of Volatile Hydrocarbons (C1–C9) in Natural Gas
Authors: Cao Chunhui , Li Zhongping , Li Liwu , Du Li
Published: December 2018

Solid-phase microextraction (SPME) coupled with gas chromatography-isotope ratio mass spectrometry (GC-IRMS) has already been applied to collect and identify volatile light hydrocarbons in oil and source rocks. However, this technology has not yet been used to analyze volatile light hydrocarbons in dry gas (natural gas with C1/C2+> 95%). In this study, we developed a method to measure the molecular and carbon isotope composition of natural gas using divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber. This fiber proved to be suitable for extracting C1–C9hydrocarbons from natural gas without inducing carbon isotopic fractionation. Notably, the extraction coefficients of the analytes were not the same but rather increased with the increasing carbon number of the hydrocarbons. Nevertheless, we successfully identified 24 hydrocarbons from the in-lab standard natural gas, while also obtaining the carbon isotope composition of C1to C9hydrocarbons with satisfying repeatability. The relative standard deviation (RSD) of the molecular composition data was in the range of 0.06–0.74%, with the RSDs of the carbon isotope composition data not exceeding 1‰. Finally, seven natural gas samples, collected from different sedimentary basins, were successfully analyzed and the stable carbon isotope compositions of C1–C9hydrocarbons present in these were determined through this method. Overall, the new approach provides a simple but useful technique to obtain more geochemical information about the source and evolution of natural gas.
Sensorimotor Robotic Measures of tDCS- and HD-tDCS-Enhanced Motor Learning in Children
Authors: Cole Lauran , Dukelow Sean P. , Giuffre Adrianna , Nettel-Aguirre Alberto , Metzler Megan J. , Kirton Adam
Published: December 2018

Transcranial direct-current stimulation (tDCS) enhances motor learning in adults. We have demonstrated that anodal tDCS and high-definition (HD) tDCS of the motor cortex can enhance motor skill acquisition in children, but behavioral mechanisms remain unknown. Robotics can objectively quantify complex sensorimotor functions to better understand mechanisms of motor learning. We aimed to characterize changes in sensorimotor function induced by tDCS and HD-tDCS paired motor learning in children within an interventional trial. Healthy, right-handed children (12–18 y) were randomized to anodal tDCS, HD-tDCS, or sham targeting the right primary motor cortex during left-hand Purdue pegboard test (PPT) training over five consecutive days. A KINARM robotic protocol quantifying proprioception, kinesthesia, visually guided reaching, and an object hit task was completed at baseline, posttraining, and six weeks later. Effects of the treatment group and training on changes in sensorimotor parameters were explored. Twenty-four children (median 15.5 years, 52% female) completed all measures. Compared to sham, both tDCS and HD-tDCS demonstrated enhanced motor learning with medium effect sizes. At baseline, multiple KINARM measures correlated with PPT performance. Following training, visually guided reaching in all groups was faster and required less corrective movements in the trained arm (H(2) = 9.250,p=0.010). Aspects of kinesthesia including initial direction error improved across groups with sustained effects at follow-up (H(2) = 9.000,p=0.011). No changes with training or stimulation were observed for position sense. For the object hit task, the HD-tDCS group moved more quickly with the right hand compared to sham at posttraining (χ2(2) = 6.255,p=0.044). Robotics can quantify complex sensorimotor function within neuromodulator motor learning trials in children. Correlations with PPT performance suggest that KINARM metrics can assess motor learning effects. Understanding how tDCS and HD-tDCS enhance motor learning may be improved with robotic outcomes though specific mechanisms remain to be defined. Exploring mechanisms of neuromodulation may advance therapeutic approaches in children with cerebral palsy and other disabilities.
Cascading Failure Model for Command and Control Networks Based on an m-Order Adjacency Matrix
Authors: Wang Yun-ming , Chen Bo , Chen Xiao-shuang , Gao Xiu-e
Published: December 2018

Cascading failure models for command and control networks (C2 networks) continue to be a challenging and important research area. Current solutions share a common limitation because the solutions focus only on the importance of each node in isolation using one index rather than considering the contribution degree of neighboring nodes, which makes the initial load definition inaccurate and affects the cascading invulnerability of the network. To address this limitation, a new cascading failure model for C2 networks is proposed. The new model CFMAdjM, which is based on an m-order adjacency matrix, proposes a method of initial load definition using the contribution degree of m-order neighboring nodes and defines the nonlinear load capacity model according to the nonlinear relationship between load and capacity. Finally, the influence of model parameters on the cascading failure of C2 networks is analyzed through simulation, and the results demonstrate that the new model effectively resists the cascading failure and enhances the survivability of the network by defining the initial load and adjusting the coefficient appropriately.
Tobacco and Substance Use among Psychiatric Inpatients in a Community Hospital: Cessation Counseling, Correlates, and Patterns of Use
Authors: Jegede Oluwole , Ojo Olawale , Ahmed Saad , Kodjo Kodjovi , Virk Inderpreet , Rimawi Dina , Mellon Cory , Jolayemi Ayodeji , Olupona Tolu
Published: December 2018

Background. Epidemiological and experimental models have been applied to describe the disproportionately high prevalence of tobacco use in patients with mental illness. This observed association has become a dire public health concern. The main objective of the present study was to examine the provision of tobacco treatment strategies in a community teaching hospital serving a predominantly underserved African American population. Methods. The study was designed as a retrospective review of eight hundred and thirty patients admitted to the inpatient psychiatric units. Results. 52.2% of the entire cohort described themselves as current smokers. Gender, primary psychiatric diagnosis, and urine toxicology showed significant differences in the tobacco smoking and nontobacco smoking groups (P<0.05). Almost all current tobacco smokers (91.9%) had tobacco cessation counseling during the course of their hospitalization, but only 64% were offered treatments for tobacco dependence. More than half (57.9%) of the 680 participants who had urine toxicology reports were positive for any illicit substance with cannabis and cocaine being the most frequently used (32.4% and 23.2%). Direct logistic regression revealed gender, psychiatric diagnosis, and substance use as the only significant predictors of tobacco smoking among our cohort (P= 0.021, 0.001, and 0.001, respectively). Conclusions. Tobacco screening, cessation counseling, and treatment continue to be a challenge in community psychiatric hospitals and need increased focus in the comprehensive management of patients with psychiatric disorders. The strong association between tobacco smoking and other substance use lends itself to the hypothesis that tobacco smoking debut prevention may be an effective public health strategy for addressing illicit drug use.
Scale Effect on the Anisotropy of Acoustic Emission in Coal
Authors: Song Honghua , Zhao Yixin , Jiang Yaodong , Wang Jiehao
Published: December 2018

Acoustic emission (AE) in coal is anisotropic. In this paper, we investigate the microstructure‐related scale effect on the anisotropic AE feature in coal at unconfined loading process. A series of coal specimens were processed with diameters of 25 mm, 38 mm, 50 mm, and 75 mm (height to diameter ratio of 2) and anisotropic angles of 0°, 15°, 30°, 45°, 60°, and 90°. The cumulative AE counts and energy dissipation increase with the specimen size, while the energy dissipation per AE count behaves in the opposite way. This may result from the increasing amount of both preexisting discontinuities and cracks (volume/number) needed for specimen failure and the lower energy dissipation AE counts generated by them. The effect of microstructures on the anisotropies of AE weakens with the increasing specimen size. The TRFD and its anisotropy reduce as the specimen size increases, and the reduction of fractal dimension is most pronounced at the anisotropic angle of 45°. The correlation between TRFD and cumulative AE energy in the specimens with different sizes are separately consistent with the negative exponential equation proposed by Xie and Pariseau. With the specimen size gain, the reduction of the TRFD weakens with the increasing amount of cumulative absolute AE energy.
Zonisamide Enhances Motor Effects of Levodopa, Not of Apomorphine, in a Rat Model of Parkinson’s Disease
Authors: Nishijima Haruo , Miki Yasuo , Ueno Shinya , Tomiyama Masahiko
Published: December 2018

Zonisamide is a relatively recent drug for Parkinson’s disease. Multiple hypotheses have been proposed to explain the antiparkinsonian effects of zonisamide. However, it is still unclear whether the effect of zonisamide is mainly due to dopaminergic modification in the striatum, or if zonisamide works through nondopaminergic pathways. We conducted the present study to determine the mechanism that is mainly responsible for zonisamide’s effects in Parkinson’s disease. We examined the effects of zonisamide on motor symptoms in a hemiparkinsonian rat model when administered singly, coadministered with levodopa, a dopamine precursor, or apomorphine, a D1 and D2 dopamine receptor agonist. We used 6-hydroxydopamine-lesioned hemiparkinsonian rats, which were allocated to one of five groups: 14 rats received levodopa only (6 mg/kg), 12 rats received levodopa (6 mg/kg) plus zonisamide (50 mg/kg), six rats received apomorphine only (0.05 mg/kg), six rats received apomorphine (0.05 mg/kg) plus zonisamide (50 mg/kg), and six rats received zonisamide only (50 mg/kg). The drugs were administered once daily for 15 days. We evaluated abnormal involuntary movement every 20 min during a 3 h period following the injection of drugs on treatment Days 1, 8, and 15. Western blot analyses for dopamine decarboxylase and vesicular monoamine transferase-2 were performed using striatal tissues in the lesioned side of rats in the levodopa only group (n = 6) and levodopa plus zonisamide group (n = 4). Levodopa-induced abnormal involuntary movement was significantly enhanced by coadministration of zonisamide. In contrast, zonisamide had no effect on apomorphine-induced abnormal involuntary movement. Zonisamide monotherapy did not induce abnormal involuntary movement. Zonisamide did not affect striatal expression of dopamine decarboxylase or vesicular monoamine transferase-2. In conclusion, zonisamide appears to generate its antiparkinsonian effects by modulating levodopa-dopamine metabolism in the parkinsonian striatum.
Abundant Small Genetic Alterations after Upland Cotton Domestication
Authors: Bao Ying , Zhang Xia , Xu Xin
Published: December 2018

Domestication has long been recognized as the most direct and effective way to intentionally influence morphological and physiological phenotypes in plants and animals. Consequently, understanding how small genetic alterations contribute to domestication is of considerable importance. In this study, we resequenced the genome of the wild upland cotton variety Gossypium hirsutum var. yucatanense, the putative wild ancestor of cultivated upland cotton, and then compared single nucleotide polymorphism (SNP) and short insertion and deletion (InDel) variations of the genome with the cultivated accession (TM-1) of G. hirsutum. We found approximately 6.6 million SNPs and 0.7 million InDels between the two genomes. Most of the small genetic variations were anchored in the noncoding regions. With regard to potential coding genes, we found 24,035 genes with nonsynonymous SNPs. Interestingly, 2603 genes in domesticated cotton are found that have changed the positions of stop codons or shifted reading frames from that in G. hirsutum var. yucatanense. This suggests that domestication may have been selected for mutations that restored gene function or that wild cotton has undergone a number of gene inactivation events since its divergence from cultivated cotton. The former scenario seems most likely due to the intense selective pressure applied during the domestication process. These results demonstrate that, within a relatively short period of time, the cotton genome has been readjusted through small genetic changes. The current study provides useful clues for seeking interesting genes for cotton improvement.
Chemometric-Assisted Spectrophotometric Method for the Simultaneous Determination of Ciprofloxacin and Doxycycline Hyclate in Pharmaceutical Formulations
Authors: Eticha Tadele , Kahsay Getu , Asefa Fitsum , Hailu Teklebrhan , Gebretsadik Hailekiros , Gebretsadikan Tesfamichael , Thangabalan Boovizhikannan
Published: December 2018

Two chemometrics methods—principal component regression and partial least squares—were developed for simultaneous spectrophotometric estimation of ciprofloxacin and doxycycline hyclate in pharmaceutical dosage forms without any pretreatment. The UV spectra of both drugs were recorded at concentrations within their linear ranges between 200 and 400 nm with the intervalsλ= 2 nm at 100 wavelengths in distilled water. Beer’s law was obeyed for both drugs in the concentration ranges of 1–10 μg/mL for ciprofloxacin and 5–25 μg/mL for doxycycline hyclate. Two sets of standard mixtures, 25 as a calibration set and 9 as a validation set, were prepared. The calibration models were evaluated by cross-validation and external validation over synthetic mixtures. The optimized models were successfully applied for chemometric analysis of ciprofloxacin and doxycycline hyclate in synthetic and pharmaceutical mixtures with satisfactory accuracy (recovery values from 97.50% to 101.87%) and precision (RSD < 2%).
Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers
Authors: Lowery Maeve A. , Bradley Mikaela , Chou Joanne F. , Capanu Marinela , Gerst Scott , Harding James J. , Dika Imane El , Berger Michael , Zehir Ahmet , Ptashkin Ryan , Wong Philip , Rasalan-Ho Teresa , Yu Kenneth H. , Cercek Andrea , Morgono Ezra , Salehi Erica , Valentino Emily , Hollywood Ellen , O'Reilly Eileen M. , Abou-Alfa Ghassan K.
Published: December 2018

Purpose:

Mutations in the RAS/RAF/MEK/ERK signaling pathway are commonly found in biliary tract cancer (BTC). Binimetinib, a selective inhibitor of MEK1/2, has single-agent activity. Preclinical data support binimetinib combination with chemotherapy, when given in an interrupted dosing schedule.

Patients and Methods: A phase I/II trial evaluated binimetinib in combination with gemcitabine and cisplatin in patients with untreated advanced BTC. The primary endpoints were to determine the MTD (phase I), and PFS 6 and RR (phase II). Tumor tissue for targeted gene sequencing and blood samples for peripheral blood pERK expression were evaluated. Patients received oral binimetinib twice daily with gemcitabine and cisplatin on day 8 and 15 of a 21-day cycle. Binimetinib was held for 2 days prior to and on day of each chemotherapy treatment.

Results:

Twelve patients enrolled in the phase I showed the MTD of binimetinib at 45 mg orally twice daily with gemcitabine 800 and cisplatin 20 mg/m2. Twenty-nine patients were treated in the phase II. Six patients treated at MTD in phase I were evaluable as part of phase II. PFS 6 months was 54% and RR was 36%. Median overall survival was 13.3 months (95% CI, 9.8–16.5). MSK-IMPACT 410-gene panel showed aberrations in the RAS–RAF–MEK–ERK pathway and mutations in PIK3CA, AKT2, PIK3CG, BRAF, and MAP3K1 in responding patients.

Conclusions:

Binimetinib with gemcitabine and cisplatin did not show an improvement in PFS 6 and RR. Molecular profiling may help select patients who may benefit from this triplet therapy, which is not planned at this time.
A Mechanism of Resistance to Antibody-Targeted Immune Attack
Authors: Aldeghaither Dalal S. , Zahavi David J. , Murray Joseph C. , Fertig Elana J. , Graham Garrett T. , Zhang Yong-Wei , O'Connell Allison , Ma Junfeng , Jablonski Sandra A. , Weiner Louis M.
Published: December 2018

Targeted monoclonal antibody therapy is a promising therapeutic strategy for cancer, and antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial mechanism underlying these approaches. The majority of patients have limited responses to monoclonal antibody therapy due to the development of resistance. Models of ADCC provide a system for uncovering immune-resistance mechanisms. We continuously exposed epidermal growth factor receptor (EGFR+) A431 cells to KIR-deficient NK92-CD16V effector cells and the anti-EGFR cetuximab. Persistent ADCC exposure yielded ADCC-resistant cells (ADCCR1) that, compared with control ADCC-sensitive cells (ADCCS1), exhibited reduced EGFR expression, overexpression of histone- and interferon-related genes, and a failure to activate NK cells, without evidence of epithelial-to-mesenchymal transition. These properties gradually reversed following withdrawal of ADCC selection pressure. The development of resistance was associated with lower expression of multiple cell-surface molecules that contribute to cell–cell interactions and immune synapse formation. Classic immune checkpoints did not modulate ADCC in this unique model system of immune resistance. We showed that the induction of ADCC resistance involves genetic and epigenetic changes that lead to a general loss of target cell adhesion properties that are required for the establishment of an immune synapse, killer cell activation, and target cell cytotoxicity.
Inhibition of Cyclin D1 Expression in Human Glioblastoma Cells is Associated with Increased Temozolomide Chemosensitivity
Authors: Zhang Danfeng , Dai Dawei , Zhou Mengxia , Li Zhenxing , Wang Chunhui , Lu Yicheng , Li Yiming , Wang Junyu
Published: December 2018

Background/Aims: Cyclin D1 (CCND1) is frequently overexpressed in malignant gliomas. We have previously shown ectopic overexpression of CCND1 in human malignant gliomas cell lines. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blot (WB) was performed to investigate the expression of CCND1 in glioma tissues and cell lines. The biological function of CCND1 was also investigated through knockdown and overexpression of BCYRN1 in vitro. Results: Here we reported that CCND1 expression was positively associated with the pathological grade and proliferative activity of astrocytomas, as the lowest expression was found in normal brain tissue (N = 3) whereas the highest expression was in high-grade glioma tissue (N = 25). Additionally, we found that the expression level of CCND1 was associated with IC50 values in malignant glioma cell lines. Forced inhibition of CCND1 increased temozolomide efficacy in U251 and SHG-44 cells. After CCND1 overexpression, the temozolomide efficacy decreased in U251 and SHG-44 cells. Colony survival assay and apoptosis analysis confirmed that CCND1 inhibition renders cells more sensitive to temozolomide treatment and temozolomide-induced apoptosis in U251 and SHG-44 cells. Inhibition of P-gp (MDR1) by Tariquidar overcomes the effects of CCND1 overexpression on inhibiting temozolomide-induced apoptosis. Inhibition of CCND1 inhibited cell growth in vitro and in vivo significantly more effectively after temozolomide treatments than single temozolomide treatments. Finally, inhibition of CCND1 in glioma cells reduced tumor volume in a murine model. Conclusion: Taken together, these data indicate that CCND1 overexpression upregulate P-gp and induces chemoresistance in human malignant gliomas cells and that inhibition of CCND1 may be an effective means of overcoming CCND1 associated chemoresistance in human malignant glioma cells.
Coccomyxa Gloeobotrydiformis Polysaccharide Inhibits Lipopolysaccharide-Induced Inflammation in RAW 264.7 Macrophages
Authors: Dai Bo , Wei Dan , Zheng Ning-ning , Chi Zhi-hong , Xin Na , Ma Ting-xian , Zheng Lan-yan , Sumi Ryo , Sun Luning
Published: December 2018

Background/Aims: Inflammation plays a vital role in the etiology and pathogenesis of chronic noncommunicable diseases (NCDs), which are the leading health issues throughout the world. Our previous studies verified the satisfactory therapeutic effects of Coccomyxa gloeobotrydiformis (CGD) polysaccharide on several NCDs. In this study, we aimed to investigate the anti-inflammatory effects of CGD polysaccharide, and the corresponding molecular mechanisms, on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Methods: A viability assay and a lactate dehydrogenase (LDH) assay were used to measure the cytotoxic effects of CGD polysaccharide on LPS-stimulated RAW264.7 cells. To investigate the potential anti-inflammatory mechanisms of CGD polysaccharide in LPS-stimulated RAW264.7 cells, nitric oxide (NO) production was determined using a NO assay and the expression of inflammatory mediators (PGE2, iNOS and COX-2), inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and inflammation-related signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1pathways) were observed by western blotting. The translocation of NF-κB p65 was also observed using an immunofluorescent assay. Results: CGD polysaccharide significantly inhibited LPS-induced NO production and PGE2 expression by reducing the expression of iNOS and COX-2. It also suppressed the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β, and up-regulated the expression of the anti-inflammatory cytokine IL-10. Further experiments demonstrated that CGD polysaccharide could inhibit inflammatory signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK and JAK/STAT pathways). At the same time, it enhanced the anti-inflammatory pathway Nrf2/HO-1. In addition, CGD polysaccharide did not display any cytotoxic effects, even at a high concentration. Conclusion: Taken together, the results suggest that CGD polysaccharide significantly inhibits LPS-induced inflammation in RAW264.7 cells. This effect lies in its regulatory effects on the signaling pathways MAPK/ NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1.Our findings reveal that CGD polysaccharide has the potential to be used as a relatively safe and effective drug as part of the treatment of NCDs.
MACROD1/LRP16 Enhances LPS-Stimulated Inflammatory Responses by Up-Regulating a Rac1-Dependent Pathway in Adipocytes
Authors: Zang Li , Hong Quan , Yang Guoqing , Gu Weijun , Wang Anping , Dou Jingtao , Mu Yiming , Wu Di , Lyu Zhaohui 
Published: December 2018

Background/Aims: Chronic inflammation contributes to the development of type 2 diabetes mellitus by targeting the insulin receptor substrate protein-1 (IRS-1) signaling pathway. Previous studies showed that Leukemia related protein 16 (LRP16) reduced insulin stimulated glucose uptake in adipocytes by impairing the IRS-1 signaling pathway. We explored the mechanism by which LRP16 promotes the inflammatory response. Methods: We screened LRP16 induced proteins in the lipopolysaccharide (LPS)-stimulated inflammatory response using liquid chromatography-mass spectrometry (LC-MS) and analyzed the potential biological functions of these proteins using online bioinformatics tools. mRNA expression and protein expression of target genes were measured by real time PCR and Western blot, respectively. Results: A total of 390 differentially expressed proteins were identified. The mitogen-activated protein kinase (MAPK) signaling pathway was the primary activated pathway in LRP16-expressing cells. Overexpression of LRP16 activated ERK1/2 and Rac1, which are two key players related to the MAPK signaling pathway. Furthermore, knock down of endogenous LRP16 by RNA interference (RNAi) reduced Rac1 expression, ERK activation, and inflammatory cytokine expression in human adipocytes stimulated by LPS. The stimulatory effect of LRP16 was diminished by suppressing Rac1 expression and treating the cells with the ERK specific inhibitor, PD98059. Conclusion: These findings revealed the functions of LRP16 in promoting the inflammatory response through activating the Rac1-MAPK1/ERK pathway in human adipocytes.