bluuebunny/crossref_metadata_2025 huggingface dataset:
Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing
Authors: Weeks Janis C. , Roberts William M. , Leasure Caitlyn , Suzuki Brian M. , Robinson Kristin J. , Currey Heather , Wangchuk Phurpa , Eichenberger Ramon M. , Saxton Aleen D. , Bird Thomas D. , Kraemer Brian C. , Loukas Alex , Hawdon John M. , Caffrey Conor R. , Liachko Nicole F.
Published: January 2018

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.
The neural correlates of the unified percept of alcohol-related craving: a fMRI and EEG study
Authors: Huang Yuefeng , Mohan Anusha , De Ridder Dirk , Sunaert Stefan , Vanneste Sven
Published: January 2018

Alcohol addiction is accompanied by aberrant neural activity. Previously, task-based fMRI and resting-state EEG studies have revealed that craving, a critical component of addiction, is linked to abnormal activity in cortical regions including the dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAcc), posterior cingulate cortex (PCC) and pregenual anterior cingulate cortex (pgACC), etc. In this study, we combine these two imaging techniques to investigate a group of alcohol-addicted patients and provide convergent evidence for the neural correlates of craving not only in alcohol but substance abuse in general. We observe abnormal BOLD signal levels in the dACC, NAcc, pgACC, PCC, amygdala, and parahippocampus (PHC) in a cue-reactivity fMRI experiment. These findings are consistent with increased beta-band activity in the dACC and pgACC in resting-state EEG. We further observe desynchronization characterized by decreased functional connectivity in cue-based fMRI and hypersynchronization characterized by increased functional connectivity between these regions in the theta frequency band. The results of our study show a consistent pattern of alcohol craving elicited by external cues and internal desires. Given the advantage of superior spatial and temporal resolution, we hypothesize a “central craving network” that integrates the different aspects of alcohol addiction into a unified percept.
A novel α-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity
Authors: Liu Zhuguo , Bartels Peter , Sadeghi Mahsa , Du Tianpeng , Dai Qing , Zhu Cui , Yu Shuo , Wang Shuo , Dong Mingxin , Sun Ting , Guo Jiabin , Peng Shuangqing , Jiang Ling , Adams David J. , Dai Qiuyun
Published: January 2018

We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type calcium channel currents in isolated mouse DRG neurons which was independent of GABAB receptor activation. In HEK293 cells expressing CaV2.2 channels alone, Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage- and state-dependent manner. Inhibition of CaV2.2 by Eu1.6 was concentration-dependent (IC50 ~1 nM). Significantly, systemic administration of Eu1.6 at doses of 2.5–5.0 μg/kg exhibited potent analgesic activities in rat partial sciatic nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had no significant side-effect on spontaneous locomotor activity, cardiac and respiratory function, and drug dependence in mice. These findings suggest α-conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and chronic pain and opens a novel option for future analgesic drug design.
Expression and subcellular localisation of AID and APOBEC3 in adenoid and palatine tonsils
Authors: Seishima Noriko , Kondo Satoru , Wakae Kousho , Wakisaka Naohiro , Kobayashi Eiji , Kano Makoto , Moriyama-Kita Makiko , Nakanishi Yosuke , Endo Kazuhira , Imoto Tomoko , Ishikawa Kazuya , Sugimoto Hisashi , Hatano Miyako , Ueno Takayoshi , Koura Miki , Kitamura Koichi , Muramatsu Masamichi , Yoshizaki Tomokazu
Published: January 2018

Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing catalytic polypeptide 3 (A3) family are cytidine deaminases that play critical roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are thought to have several physiological or pathological roles. However, the expression of AID or A3s in these organs has not been investigated. Therefore, we investigated the expression profiles of AID and A3s, using 67 samples of adenoids and palatine tonsils from patients, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analyses. AID and A3s expression levels in the adenoids and the palatine tonsils of the same individual significantly correlated with each other. Of note, AID expression level in the adenoids negatively correlated with the age (r = −0.373, P = 0.003). The younger group with adenoid vegetation and tonsillar hypertrophy showed more abundant AID expression than the older group with recurrent tonsillitis and peritonsillar abscesses (P = 0.026). Moreover, immunohistochemical analysis revealed the distribution of AID and A3s in the epithelial cells as well as germinal centres. The localisation of AID expression and its relation to age may contribute to adenoid vegetation and inflammation.
Multi-wavelength growth of nanosecond laser-induced surface damage on fused silica gratings
Authors: Chambonneau Maxime , Lamaignère Laurent
Published: January 2018

The nanosecond laser-induced damage growth phenomenon on the exit surface of fused silica grating is investigated at 1064 nm and 355 nm separately and also simultaneously. Experiments are first carried out on damage sites on a plane fused silica sample showing two different morphologies, and a damage type is selected for ensuring the repeatability of the subsequent tests. Comparing the mono-wavelength growth results on a grating and a plane fused silica sample, the periodic surface structure is found to be an aggravating factor for damage growth. This is highly supported by calculations of the enhancement of the optical electric field intensity thanks to Finite-Difference Time-Domain simulations. Finally, the mono-wavelength results enable us to quantify a coupling occurring in the multi-wavelength configuration, which could originate from the heating of the plasma (more likely produced in the ultraviolet) preferentially by the infrared pulse. This study provides interesting results about the involvement of the surface topography in damage growth, and paves the way towards the comprehension of this phenomenon at high-energy nanosecond laser facilities where fused silica gratings are simultaneously irradiated at several wavelengths.
Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
Authors: Koh Hong , Park Gun-Seok , Shin Sun-Mi , Park Chang Eon , Kim Seung , Han Seok Joo , Pham Huy Quang , Shin Jae-Ho , Lee Dong-Woo
Published: January 2018

Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in protein-coding mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA) are associated with hepatocellular dysfunction. This observation led us to investigate whether hepatic dysfunctions in BA is genetically associated with mtDNA mutations. We sequenced the mtDNA protein-coding genes in 14 liver specimens from 14 patients with BA and 5 liver specimens from 5 patients with choledochal cyst using next-generation sequencing. We found 34 common non-synonymous variations in mtDNA protein-coding genes in all patients examined. A systematic 3D structural analysis revealed the presence of several single nucleotide polymorphism-like mutations in critical regions of complexes I to V, that are involved in subunit assembly, proton-pumping activity, and/or supercomplex formation. The parameters of chronic hepatic injury and liver dysfunction in BA patients were also significantly correlated with the extent of hepatic failure, suggesting that the mtDNA mutations may aggravate hepatopathy. Therefore, mitochondrial mutations may underlie the pathological mechanisms associated with BA.
Determinants of population responses to environmental fluctuations
Authors: Vilar Jose M. G. , Rubi J. Miguel
Published: January 2018

Environmental fluctuations, such as changing conditions and variable nutrient availability, are an unavoidable component of the dynamics of virtually all populations. They affect populations in ways that are often difficult to predict and sometimes lead to paradoxical outcomes. Here, we present a general analytical approach to examine how populations respond to fluctuations. We show that there exist general explicit conditions that determine to what extent fluctuations propagate to the variability of the responses and how they change the behavior of the system, including whether they promote proliferation or death and whether they facilitate coexistence or exclusion of competing species. These conditions depend on linear and nonlinear terms of the growth rate and on the characteristic times of the fluctuations. We validated our general approach through computational experiments for both stochastic and chaotic fluctuations and for multiple types of systems. From an applied point of view, our results provide an avenue for the precise control of the population behavior through fluctuations in addition to just through average properties.
Decoupled in-plane Dipole Resonance Modulated Colorimetric Assay-Based Optical Ruler for Ultra-Trace Gold (Au) Detection
Authors: Mandal Ajoy , Bhattacharya Maireyee , Kuznetsov Denis V. , Ghosh Tapas , Das Chakraborty Sudeshna , Satpati Biswarup , Mazov Vsevolod , Senapati Dulal
Published: January 2018

Decoupling of different plasmon resonance modes (in-plane, and out-of-plane dipole and quadrupole resonances) by tuning nanoparticle’s size and shape offers a new field of plasmonics as colorimetric assay-based optical-ruler for ultra-trace sensing. Driven by its low cost, easy to perform and efficient way to measure trace level (up to 30 ppt in presence of common mining elements in natural gold ore) abundance, this study develops a highly selective and ultrasensitive turn-on colorimetric sensor to detect gold-ion from environmental samples. Different level of gold-ion tracer makes size variable spherical- and disc-shaped silver nanoparticles when added to a ‘growth solution’ which results decoupling of in-plane dipole resonance from in-plane quadrupole and out-of-plane dipole resonances with a wide range of in-plane dipole plasmon tunability to generate different colors. This color-coded sensing of gold-ion shows high selectivity and ultrasensitivity over other metal ions in the ppt level with an impurity aberration limit of 1 ppm. A plausible explanation explains the possible role of catalytic gold-ion to initiate unfavorable silver ion (Ag+) reduction by ascorbic acid to generate silver nanoparticles. Proposed technology has been applied in real mining sample (Bugunda Gold Deposit, Tajikistan) to detect gold concentration from ores to find potential application in mining technology.
A patient-specific lumped-parameter model of coronary circulation
Authors: Duanmu Zheng , Yin Min , Fan Xueling , Yang Xilan , Luo Xiaoyu
Published: January 2018

A new lumped-parameter model for coronary hemodynamics is developed. This model is developed for the whole coronary network based on CT scans of a patient-specific geometry including the right coronary tree, which is absent in many previous mathematical models. The model adopts the structured tree model boundary conditions similar to the work of Olufsen et al., thus avoiding the necessity of invasive perfusion measurements. In addition, we also incorporated the effects of the head loss at the two inlets of the large coronary arteries for the first time. The head loss could explain the phenomenon of a sudden increase of the resistance at the inlet of coronary vessel. The estimated blood pressure and flow rate results from the model agree well with the clinical measurements. The computed impedances also match the experimental perfusion measurement. The effects of coronary arterial stenosis are considered and the fractional flow reserve and relative flow in the coronary vessels for a stenotic vessel computed in this model show good agreement with published experimental data. It is believed that the approach could be readily translated to clinical practice to facilitate real time clinical diagnosis.
Drug self-assembly for synthesis of highly-loaded antimicrobial drug-silica particles
Authors: Stewart Cameron A. , Finer Yoav , Hatton Benjamin D.
Published: January 2018

Antimicrobial drug release from biomaterials for orthopedic repair and dental restorations can prevent biofilm growth and caries formation. Carriers for drug incorporation would benefit from long-term drug storage, controlled release, and structural stability. Mesoporous silica, synthesized through a co-assembly of silica and surfactant template, is an ideal drug encapsulation scaffold that maintains structural integrity upon release. However, conventional loading of drug within meso-silica pores via concentration-gradient diffusion limits the overall payload, concentration uniformity, and drug release control. Herein we demonstrate the co-assembly of an antimicrobial drug (octenidine dihydrochloride, OCT), and silica, to form highly-loaded (35% wt.) OCT-silica nanocomposite spheres of 500 nm diameter. Drug release significantly outlasted conventional OCT-loaded mesoporous silica, closely fit Higuchi models of diffusive release, and was visualized via electron microscopy. Extension of this concept to the broad collection of self-assembling drugs grants biomedical community a powerful tool for synthesizing drug-loaded inorganic nanomaterials from the bottom-up.
Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements
Authors: Li Ian M. H. , Liu Ke , Neal Alice , Clegg Peter D. , De Val Sarah , Bou-Gharios George
Published: January 2018

The transcriptional mechanism through which chondrocytes control the spatial and temporal composition of the cartilage tissue has remained largely elusive. The central aim of this study was to identify whether transcriptional enhancers played a role in the organisation of the chondrocytes in cartilaginous tissue. We focused on the Aggrecan gene (Acan) as it is essential for the normal structure and function of cartilage and it is expressed developmentally in different stages of chondrocyte maturation. Using transgenic reporter studies in mice we identified four elements, two of which showed individual chondrocyte developmental stage specificity. In particular, one enhancer (−80) distinguishes itself from the others by being predominantly active in adult cartilage. Furthermore, the −62 element uniquely drove reporter activity in early chondrocytes. The remaining chondrocyte specific enhancers, +28 and −30, showed no preference to chondrocyte type. The transcription factor SOX9 interacted with all the enhancers in vitro and mutation of SOX9 binding sites in one of the enhancers (−30) resulted in a loss of its chondrocyte specificity and ectopic enhancer reporter activity. Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood.
Three-dimensional migration behavior of juvenile salmonids in reservoirs and near dams
Authors: Li Xinya , Deng Zhiqun D. , Fu Tao , Brown Richard S. , Martinez Jayson J. , McMichael Geoffrey A. , Trumbo Bradly A. , Ahmann Martin L. , Renholds Jon F. , Skalski John R. , Townsend Richard L.
Published: January 2018

To acquire 3-D tracking data on juvenile salmonids, Juvenile Salmon Acoustic Telemetry System (JSATS) cabled hydrophone arrays were deployed in the forebays of two dams on the Snake River and at a mid-reach reservoir between the dams. The depth distributions of fish were estimated by statistical analyses performed on large 3-D tracking data sets from ~33,500 individual acoustic tagged yearling and subyearling Chinook salmon and juvenile steelhead at the two dams in 2012 and subyearling Chinook salmon at the two dams and the mid-reach reservoir in 2013. This research investigated the correlation between vertical migration behavior and passage routes. The depth distributions of fish within the forebays of the dams were significantly different from fish passing the mid-reach reservoir. Fish residing deeper in the forebay tended to pass the dam using deeper powerhouse routes. This difference in depth distributions indicated that the depth distribution of fish at the mid-reach reservoir was not related to behaviors of fish passing through certain routes of the adjacent dams. For fish that were detected deeper than 17.5 m in the forebays, the probability of powerhouse passage (i.e., turbine) increased significantly. Another important finding was the variation in depth distributions during dam passage associated with the diel period, especially the crepuscular periods.
Stereotactic topography of the greater and third occipital nerves and its clinical implication
Authors: Kim Hong-San , Shin Kang-Jae , O Jehoon , Kwon Hyun-Jin , Lee Minho , Yang Hun-Mu
Published: January 2018

This study aimed to provide topographic information of the greater occipital (GON) and third occipital (3ON) nerves, with the three-dimensional locations of their emerging points on the back muscles (60 sides, 30 cadavers) and their spatial relationship with muscle layers, using a 3D digitizer (Microscribe G2X, Immersion Corp, San Jose CA, USA). With reference to the external occipital protuberance (EOP), GON pierced the trapezius at a point 22.6 ± 7.4 mm lateral and 16.3 ± 5.9 mm inferior and the semispinalis capitis (SSC) at a point 13.1 ± 6.0 mm lateral and 27.7 ± 9.9 mm inferior. With the same reference, 3ON pierced, the trapezius at a point 12.9 ± 9.3 mm lateral and 44.2 ± 21.4 mm inferior, the splenius capitis at a point 10.0 ± 5.3 mm lateral and 59.2 ± 19.8 mm inferior, and SSC at a point 11.5 ± 9.9 mm lateral and 61.4 ± 15.3 mm inferior. Additionally, GON arose, winding up the obliquus capitis inferior, with the winding point located 52.3 ± 11.7 mm inferior to EOP and 30.2 ± 8.9 mm lateral to the midsagittal line. Knowing the course of GON and 3ON, from their emergence between vertebrae to the subcutaneous layer, is necessary for reliable nerve detection and precise analgesic injections. Moreover, stereotactic measurement using the 3D digitizer seems useful and accurate for neurovascular structure study.
Analysis of mitochondrial function in human induced pluripotent stem cells from patients with mitochondrial diabetes due to the A3243G mutation
Authors: Matsubara Masaki , Kanda Hajime , Imamura Hiromi , Inoue Mayumi , Noguchi Michio , Hosoda Kiminori , Kakizuka Akira , Nakao Kazuwa
Published: January 2018

We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production. In the first patient, complex I activity, mitochondrial respiration, and mitochondrial ATP production were decreased in the mutation-high clones compared with the mutation-undetectable clones, and mitochondrial membrane potential was decreased in a mutation-high clone compared with a mutation-undetectable clone. In the second patient, complex I activity was decreased in one mutation-high clone compared with the other clones. The other parameters showed no differences in any clones. In addition, the complex I activity and mitochondrial respiration of the mutation-undetectable clones from both patients were located in the range of those of iPS cells from healthy subjects. The present study suggests that the mitochondrial function of the mutation-undetectable iPS cell clones obtained from two patients with the A3243G mutation is comparable to the control iPS cells.
Magnetoencephalographic Correlates of Perceptual State During Auditory Bistability
Authors: Sanders Robert D. , Winston Joel S. , Barnes Gareth R. , Rees Geraint
Published: January 2018

Bistability occurs when two alternative percepts can be derived from the same physical stimulus. To identify the neural correlates of specific subjective experiences we used a bistable auditory stimulus and determined whether the two perceptual states could be distinguished electrophysiologically. Fourteen participants underwent magnetoencephalography while reporting their perceptual experience while listening to a continuous bistable stream of auditory tones. Participants reported bistability with a similar overall proportion of the two alternative percepts (52% vs 48%). At the individual level, sensor space electrophysiological discrimination between the percepts was possible in 9/14 participants with canonical variate analysis (CVA) or linear support vector machine (SVM) analysis over space and time dimensions. Classification was possible in 14/14 subjects with non-linear SVM. Similar effects were noted in an unconstrained source space CVA analysis (classifying 10/14 participants), linear SVM (classifying 9/14 subjects) and non-linear SVM (classifiying 13/14 participants). Source space analysis restricted to a priori ROIs showed discrimination was possible in the right and left auditory cortex with each classification approach but in the right intraparietal sulcus this was only apparent with non-linear SVM and only in a minority of particpants. Magnetoencephalography can be used to objectively classify auditory experiences from individual subjects.
Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells
Authors: Nanayakkara Amila K. , Follit Courtney A. , Chen Gang , Williams Noelle S. , Vogel Pia D. , Wise John G.
Published: January 2018

Overexpression of ATP-binding cassette (ABC) transporters is often linked to multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one of the best studied drug transporters associated with MDR. There are currently no approved drugs available for clinical use in cancer chemotherapies to reverse MDR by inhibiting P-glycoprotein. Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains. Several of these compounds showed successful MDR reversal when tested on a drug resistant prostate cancer cell line. Using conventional two-dimensional cell culture of MDR ovarian and prostate cancer cells and three dimensional prostate cancer microtumor spheroids, we demonstrated here that co-administration with chemotherapeutics significantly decreased cell viability and survival as well as cell motility. The P-gp inhibitors were not observed to be toxic on their own. The inhibitors increased cellular retention of chemotherapeutics and reporter compounds known to be transport substrates of P-gp. We also showed that these compounds are not transport substrates of P-gp and that two of the three inhibit P-gp, but not the closely related ABC transporter, ABCG2/BCRP. The results presented suggest that these P-gp inhibitors may be promising leads for future drug development.
Newly discovered Late Triassic Baqing eclogite in central Tibet indicates an anticlockwise West–East Qiangtang collision
Authors: Zhang Yu-Xiu , Jin Xin , Zhang Kai-Jun , Sun Wei-Dong , Liu Jian-Ming , Zhou Xiao-Yao , Yan Li-Long
Published: January 2018

The Triassic eclogite-bearing central Qiangtang metamorphic belt (CQMB) in the northern Tibetan Plateau has been debated whether it is a metamorphic core complex underthrust from the Jinsha Paleo-Tethys or an in-situ Shuanghu suture. The CQMB is thus a key issue to elucidate the crustal architecture of the northern Tibetan Plateau, the tectonics of the eastern Tethys, and the petrogenesis of Cenozoic high-K magmatism. We here report the newly discovered Baqing eclogite along the eastern extension of the CQMB near the Baqing town, central Tibet. These eclogites are characterized by the garnet + omphacite + rutile + phengite + quartz assemblages. Primary eclogite-facies metamorphic pressure–temperature estimates yield consistent minimum pressure of 25 ± 1 kbar at 730 ± 60 °C. U–Pb dating on zircons that contain inclusions (garnet + omphacite + rutile + phengite) gave eclogite-facies metamorphic ages of 223 Ma. The geochemical continental crustal signature and the presence of Paleozoic cores in the zircons indicate that the Baqing eclogite formed by continental subduction and marks an eastward-younging anticlockwise West–East Qiangtang collision along the Shuanghu suture from the Middle to Late Triassic.
Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
Authors: Yuan Yao , Wu Jiewei , Li Bailin , Niu Jia , Tan Haibo , Qiu Shengxiang
Published: January 2018

The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol has shown anti-proliferative effects against the human non-small cell lung cancer A549 cell line. M22 showed significant anti-proliferative activity at 6.80 μM and increased accumulation of G1 cells and effectively suppressed expression of the G1 arrest-related genes cyclins D1 and E1, CDK2 and CDC25A. This was further confirmed by Western blotting demonstrating decreased cyclin D1 and CDC25A protein levels. Furthermore, M22 caused induction of apoptosis that downregulated the anti-apoptotic BCL-2 gene and increased expression of BAX, CASP3 and CASP9 as well as the APAF1 gene. The effect of caspase-induced apoptosis was confirmed by an increase in reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP). Taken together, our findings indicated that M22 possessed potent anti-proliferative and apoptotic activities.
Human Papillomavirus Prophylactic Vaccination improves reproductive outcome in infertile patients with HPV semen infection: a retrospective study
Authors: Garolla Andrea , De Toni Luca , Bottacin Alberto , Valente Umberto , De Rocco Ponce Maurizio , Di Nisio Andrea , Foresta Carlo
Published: January 2018

In this study we aimed to evaluate the effect on reproductive outcome of HPV vaccination in male subjects of infertile couples with HPV semen infection. In this single-center study, we retrospectively enrolled 151 infertile couples with detection of HPV in semen, attending our Hospital Unit of Andrology between January 2013 and June 2015, counseled to receive adjuvant HPV vaccination. Seventy-nine accepted vaccination (vaccine group) whilst 72 did not (control group). Our protocol of follow-up, aimed to evaluate HPV viral clearance, consisted in semen analysis, INNO-LiPA and FISH for HPV in semen cells after 6 and 12 months from basal evaluation. Spontaneous pregnancies, miscarriages and live births were recorded. Progressive sperm motility and anti-sperm antibodies were improved in the vaccine group at both time points (p < 0,05 vs control arm). Forty-one pregnancies, 11 in the control group and 30 in the vaccine group, were recorded (respectively 15% and 38,9%, p < 0,05) and resulted into 4 deliveries and 7 miscarriages (control group) and 29 deliveries and one miscarriage (vaccine group, p < 0,05 vs control group). HPV detection on sperms was predictive of negative pregnancy outcome. Adjuvant vaccination associated with enhanced HPV healing in semen cells and increased rate of natural pregnancies and live births.
Sclerotic bone lesions as a potential imaging biomarker for the diagnosis of tuberous sclerosis complex
Authors: Brakemeier Susanne , Vogt Lars , Adams Lisa C. , Zukunft Bianca , Diederichs Gerd , Hamm Bernd , Budde Klemens , Eckardt Kai-Uwe , Makowski Marcus R.
Published: January 2018

Tuberous-sclerosis-complex (TSC) is associated with a high lifetime risk of severe complications. Clinical manifestations are largely variable and diagnosis is often missed. Sclerotic-bone-lesions (SBL) could represent a potential imaging biomarker for the diagnosis of TSC. In this study, computed tomography (CT) data sets of 49 TSC patients (31 females) were included and compared to an age/sex matched control group. Imaging features of SBLs included frequency, size and location pattern. Sensitivities, specificities and cutoff values for the diagnosis of TSC were established for the skull, thorax, and abdomen/pelvis. In TSC patients, 3439 SBLs were detected, including 665 skull SBLs, 1426 thoracal SBLs and 1348 abdominal/pelvic SBLs. In the matched control-collective, 157 SBLs could be found. The frequency of SBLs enabled a reliable differentiation between TSC patients and the control collective with the following sensitivities and specificities. Skull: ≥5 SBLs, 0.783, 1; thorax: ≥4 SBLs, 0.967, 0.967; abdomen/pelvis: ≥5 SBLs: 0.938, 0.906. SBL size was significantly larger compared to controls (p < 0.05). Based on the frequency, size and location pattern of SBLs TSC can be suspected. SBLs may serve as a potential imaging biomarker in the workup of TSC patients.
Sudden sensory neural hearing loss is not predictive of myocardial infarction: A longitudinal follow-up study using a national sample cohort
Authors: Kim So Young , Sim Songyong , Kim Hyung-Jong , Choi Hyo Geun
Published: January 2018

The aim of this study was to evaluate the risk of myocardial infarction (MI) in SSNHL subjects with differently matched control groups. The Korean Health Insurance Review and Assessment Service - National Sample Cohort recruited subjects from 2002 to 2013. We used two study designs. In study I, we matched 4,467 SSNHL participants with a control group (17,868 subjects with no history of SSNHL) based on demographic factors (age, sex, income, and region of residence) and medical history (diabetes, dyslipidemia, and hypertension). In study II, we matched 4,467 SSNHL participants with a control group based on only demographic factors. The crude (simple) and adjusted hazard ratios (HRs) of SSNHL with MI were analyzed using the Cox-proportional hazard model. In study I, SSNHL was not associated with increased risk of MI. However, in study II, SSNHL was associated with increased risk of MI (adjusted HR = 1.39 95% CI = 1.00–1.93, P = 0.048). The SSNHL group did not exhibit increased risk of MI when compared to the control group matched by both demographic factors and medical history. However, compared to the control group not matched by medical history, the relative risk of MI was increased in the SSNHL group.
Faecal shedding of rotavirus vaccine in Chinese children after vaccination with Lanzhou lamb rotavirus vaccine
Authors: Li Jin-song , Cao Bing , Gao Han-chun , Li Dan-di , Lin Lin , LI LI-li , Liu Na , Duan Zhao-Jun
Published: January 2018

Lanzhou lamb rotavirus vaccine (LLR) is an oral live attenuated vaccine first licensed in China in 2000. To date, > 60 million doses of LLR have been distributed to children. However, very little is known about faecal shedding of LLR in children. Therefore, faecal samples (n = 1,184) were collected from 114 children for 15 days post-vaccination in September–November 2011/2012. Faecal shedding and viral loads were determined by an enzyme immunoassay kit (EIA) and real-time RT-PCR. The complete genome was sequenced and the vaccine strain was isolated by culture in MA104 cells. Approximately 14.0% (16/114) of children had rotavirus-positive samples by EIA for at least 1 day post-vaccination. Viral loads in EIA-positive samples ranged from < 1.0 × 103 to 1.9 × 108 copies/g. Faecal shedding occurred as early as post-vaccination day 2 and as late as post-vaccination day 13 and peaked on post-vaccination day 5–10. One LLR strain was isolated by culture in MA104 cells. Sequence analysis showed 99% identity with LLR prototype strain. Faecal shedding of LLR in stool is common within 15 days of LLR vaccination, indicating vaccine strains can replicate in human enteric tissues.
Estimating the impact of body mass index on bladder cancer risk: Stratification by smoking status
Authors: Choi Jin Bong , Lee Eun Joo , Han Kyung-Do , Hong Sung-Hoo , Ha U-Syn
Published: January 2018

We estimated the impact of obesity on bladder cancer with stratification by smoking status using nationally representative data on the Korean population from the National Health Insurance System (NHIS). Of the 45,850,458 people who underwent at last one health examination from 2009 to 2012, 23,378,895 without bladder cancer were followed from the January 2009 to the December 2015. First, the HR for bladder cancer was lowest in people with a BMI < 18.5 (HR = 0.92) and highest for those with BMI ≥ 30 (HR = 1.17) in multiple Cox regression analyses. The positive association between bladder cancer and BMI showed an increasing trend beyond the reference BMI. Second, an analysis of HR for bladder cancer stratified by obesity across smoking status strata showed a significant trend of increasing HR for bladder cancer across obesity and smoking status in multivariate-adjusted models. Conclusively, this population-based study showed that increasing BMI was a risk factor for bladder cancer independent of confounding variables. When stratified by smoking status, there was still a positive association between bladder cancer and BMI (P for trend < 0.01).
Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis and tuberculin skin test conversion among prisoners
Authors: Maceda Elisangela B. , Gonçalves Crhistinne C. M. , Andrews Jason R. , Ko Albert I. , Yeckel Catherine W. , Croda Julio
Published: January 2018

Poor vitamin D status has been associated with tuberculosis (TB); whether poor status is cause or consequence of disease is uncertain. We conducted a case-control study and two nested case-control studies to determine whether vitamin D levels were associated with active TB, tuberculin skin test (TST) conversion, and risk of progression to the active TB in prisoners in Brazil. In multivariable conditional logistic regression, subnormal vitamin D levels (OR, 3.77; 95% CI, 1.04–13.64) were more likely in prisoners with active TB. In contrast, vitamin D was not found to be a risk factor for either TST conversion (OR, 2.49; 95% CI, 0.64–9.66) or progression to active disease (OR, 0.59; 95% CI, 0.13–2.62). Black race (OR, 11.52; 95% CI, 2.01–63.36), less than 4 years of schooling (OR, 2.70; 95% CI, 0.90–8.16), cigarette smoking (OR, 0.23; 95% CI, 0.06–0.79) were identified as risk factors for TST conversion. Risk of progression to active TB was found to be associated with cigarette smoking (OR, 7.42; 95% CI, 1.23–44.70). Our findings in the prison population show that poor vitamin D status is more common in individuals with active TB, but is not a risk factor for acquisition of latent TB or progression to active TB.
Monitoring dynamic spiculation in red blood cells with scanning ion conductance microscopy
Authors: Zhu Cheng , Shi Wenqing , Daleke David L. , Baker Lane A.
Published: January 2018

Scanning ion conductance microscopy (SICM) is an ideal method to study dynamic phospholipid-induced morphological changes of RBCs in physiological conditions.
Quinoline-para-quinones and metals: coordination-assisted formation of quinoline-ortho-quinones
Authors: Kubanik Mario , Lam Nelson Y. S. , Holtkamp Hannah U. , Söhnel Tilo , Anderson Robert F. , Jamieson Stephen M. F. , Hartinger Christian G.
Published: January 2018

Attempts to obtain quinolinedione organometallics resulted in the metal-assisted formation of quinoline-ortho-quinones after reaction with protic solvents.
To the homogeneity range of tris(8-hydroxyquinoline)gallium
Authors: Avetissov I. Ch. , Akkuzina A. A. , Kozlova N. N. , Avetisov R. I.
Published: January 2018

The p8-Hq–T diagram of non-stoichiometrical tris(8-hydroxyquinoline)gallium was plotted in the 408–665 K temperature range using a newly developed technique.
Layered gadolinium hydroxides for simultaneous drug delivery and imaging
Authors: Xu Yadong , Goyanes Alvaro , Wang Yuwei , Weston Andrew J. , So Po-Wah , Geraldes Carlos F. G. C. , Fogg Andrew M. , Basit Abdul W. , Williams Gareth R.
Published: January 2018

Drug intercalates of a layered gadolinium hydroxide have been prepared, and their drug delivery and imaging properties explored.
Water-soluble transition metal complexes of ruthenium(ii), osmium(ii), rhodium(iii) and iridium(iii) with chelating N-heterocyclic carbene ligands in hydrogenation and transfer hydrogenation catalysis
Authors: Bayón Castañón Esther , Kaposi Marlene , Reich Robert M. , Kühn Fritz E.
Published: January 2018

The synthesis of novel Ru(ii), Os(ii), Rh(iii) and Ir(iii) mono-N-heterocyclic carbene (NHC) complexes and their application in hydrogenation catalysis is reported.
Rational construction of an ssa-type of MOF through pre-organizing the ligand's conformation and its exceptional gas adsorption properties
Authors: Wang Yao , He Minghui , Tian Zhi , Zhong Haoyan , Zhu Lisha , Zhang Yingying , Zhang Xiaoping , Chen De-Li , He Yabing
Published: January 2018

A ligand conformation-controlled assembly strategy has been successfully employed to construct a copper-based MOF with the desired ssa-type topology, which exhibits exceptional C2H2 and CO2 adsorption properties.
Impact of Ni content on the thermoelectric properties of half-Heusler TiNiSn
Authors: Tang Yinglu , Li Xiaoshuang , Martin Lukas H. J. , Cuervo Reyes Eduardo , Ivas Toni , Leinenbach Christian , Anand Shashwat , Peters Matthew , Snyder G. Jeffrey , Battaglia Corsin
Published: January 2018

Thermoelectric properties vary dramatically between two boundary compositions of Ni-rich and Ni-poor TiNiSn, up to 25% in zT.
Design and construction of Ni3−xCoxO4nanorods grown on Ni foam for tuning synthetic natural gas heating values
Authors: Sun Jiaqiang , Chen Zheng , Xue Yingying , Chen Jiangang
Published: January 2018

Ni3−xCoxO4nanorods with different Ni/Co ratios were fabricated on Ni foam, which show excellent catalytic activity and can tune synthetic natural gas heating values.
Synthesis and characterization of fused imidazole heterocyclic selenoesters and their application for chemical detoxification of HgCl2
Authors: Sharma Nidhi , Kumar Sanjeev , Kumar Sangit , Mehta S. K. , Bhasin K. K.
Published: January 2018

Selenoester derivatives of imidazo[1,2-a]pyridine/imidazo[1,2-a]pyrimidine has been synthesized by the reaction of sodium selenocarboxylates with 2-(chloromethyl)imidazo[1,2-a]pyridine/pyrimidine.
A catalyst-free intermolecular trans-iodoalkylation of alkynes
Authors: Liu Jie-Jie , Huang Hong-Yan , Cheng Liang , Liu Qi , Wang Dong , Liu Li
Published: January 2018

The first catalyst-free and trans-selective iodoalkylation reaction of alkynes with a series of α-carbonyl compounds was reported.
Mercury-free nitrogen-doped activated carbon catalyst: an efficient catalyst for the catalytic coupling reaction of acetylene and ethylene dichloride to synthesize the vinyl chloride monomer
Authors: Shen Zhaobing , Zhao Hong , Liu Yue , Kan Zeyuan , Xing Ping , Zhong Jinguang , Jiang Biao
Published: January 2018

The global “Minamata Convention on Mercury” came into effect in 2017 exerting huge environmental pressure on acetylene-based polyvinyl chloride (PVC) processes.
Determining the uncertainty in microstructural parameters extracted from tomographic data
Authors: Pietsch P. , Ebner M. , Marone F. , Stampanoni M. , Wood V.
Published: January 2018

The procedure for binarization of X-ray tomographic data affects the quantitative analysis of microstructural parameters in lithium ion battery electrodes.
Cyclotriphosphazene core-based dendrimers for biomedical applications: an update on recent advances
Authors: Wang Le , Yang Yun-Xia , Shi Xiangyang , Mignani Serge , Caminade Anne-Marie , Majoral Jean-Pierre
Published: January 2018

This review highlights the recent advances of the synthesis of cyclotriphosphazene-based dendrimers for different biomedical applications.
Systematic investigation of self-organization behavior in supramolecular π-conjugated polymer for multi-color electroluminescence
Authors: Lin Jin-Yi , Liu Bin , Yu Meng-Na , Wang Xu-Hua , Bai Lu-Bing , Han Ya-Min , Ou Chang-Jin , Xie Ling-Hai , Liu Feng , Zhu Wen-Sai , Zhang Xin-Wen , Ling Hai-Feng , Stavrinou Paul N. , Wang Jian-Pu , Bradley Donal D. C. , Huang Wei
Published: January 2018

Understanding the chain behavior and conformational/aggregation behavior of supramolecular π-conjugated polymer for multi-color electroluminescence.
Selecting Treatments and Monitoring Outcomes: The Circle of Evidence-Based Practice and Client-Centered Care in Treating a Preschool Child Who Stutters
Authors: Bernstein Ratner Nan
Published: January 2018

Purpose

The purpose of the present clinical forum is to compare how 2 clinicians might select among therapy options for a preschool-aged child who presents with stuttering close to onset.

Method

I discuss approaches to full evaluation of the child's profile, advisement of evidence-based practice options open to the family, the need for monitoring of the child's response, and selection of other approaches, if the child appears nonresponsive to the 1st-line approach.

Results

Although some researchers and clinicians appear to favor endorsement of a single recommended treatment for early stuttering, I do not find this approach helpful or consistent with newer mandates for patient-centered care. I am also most comfortable recommending RESTART demands and capacities model as the 1st treatment approach, with parent consent, because its mechanism of action appears transparent and well-documented.

Conclusions

There are numerous well-supported intervention options for treating preschool children who stutter. No single therapy can possibly work for all clients. I discuss available options that I feel have sufficient evidence-based support for use with young children who stutter. I emphasize the need to consider more, not fewer, acceptable therapy options for children who do not respond positively to a selected treatment approach within a reasonable time frame.
Stuttering in Preschool Children: Direct Versus Indirect Treatment
Authors: Nippold Marilyn A.
Published: January 2018

Purpose

The purpose of this article is to discuss the controversial topic of stuttering in preschool children and how to evaluate the options for treatment, emphasizing the role of external research evidence.

Method

A hypothetical but realistic case study of a 3-year-old boy who stutters is described. Two contrasting approaches to treatment are presented, the Lidcombe Program (LP) and the demands and capacities model (DCM). Studies published in peer-reviewed research journals that have examined the effectiveness of each approach are summarized and critiqued.

Results

The review indicates that the LP is the preferred treatment approach for stuttering in preschool children and that it offers the best opportunity for rapid success.

Conclusion

The LP should be carried out by knowledgeable, experienced, and flexible speech-language pathologists who are able to accommodate the individual needs and differences of every child and family.
Best Practice for Developmental Stuttering: Balancing Evidence and Expertise
Authors: Byrd Courtney T. , Donaher Joseph
Published: January 2018

Purpose

Best practice for developmental stuttering remains a topic of debate. In the clinical forum following this introduction, four fluency experts balance the evidence and expertise to describe their approach to assessment and treatment.
Resonantly enhanced all‐optical switching in microfibre Mach–Zehnder interferometers
Authors: Kowsari A. , Saghaei H.
Published: January 2018

We propose an all‐optical switch based on a microfibre Mach–Zehnder interferometer (MMZI) in which the MMZI is considered with a microfibre loop resonator (MLR) in one arm of it. The authors numerically demonstrate that the enhanced phase shift of the MLR near its resonance wavelengths can be used for constructive/destructive interference and switching functionality of the MMZI. The calculated switching threshold power of the switch is about 2 mW, which can be further reduced by the use of an MLR with more finesse, and the rising and falling times are computed with 21 and 91 ps, respectively. Natural connection to silica single mode fibres, easy configuration and high speed make it as a suitable choice for all‐optical signal processing and communications applications.
Design of very simple frequency and polarisation reconfigurable antenna with finite ground structure
Authors: Liu Jie , Li Jianying , Xu Rui
Published: January 2018

A frequency and polarisation reconfigurable printed monopole antenna using switching PIN diodes is presented. This antenna is made up of a printed monopole, two switching circuits and a reflector. By controlling the on‐off states of these two switching circuits on the finite ground plane, a frequency and polarisation reconfigurable antenna is achieved. To verify this design, this antenna is fabricated and measured. The measured results show that this antenna has four states. These states are: state 1, 2.02–2.56 GHz (23.6%); state 2, 2.32–2.95 GHz (23.9%); state 3, 1.92–2.70 GHz (33.8%); state 4, 1.88–2.67 GHz (34.7%). In states 1 and 2, this antenna radiates linearly polarised wave as a traditional printed monopole. In states 3 and 4, this antenna radiates left‐hand circularly polarised wave and right‐hand circularly polarised wave, respectively.