bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties
Authors: Luo Cheng , Chen Song , Xu Na , Wang Chi , Sai Wen bo , Zhao Wei , Li Ying chun , Hu Xiao jing , Tian Hong , Gao Xiang dong , Yao Wen bing 
Published: April 2017

AbstractPertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the roles of fucose and sialic acid in the function of therapeutic antibodies still need further investigation, especially the role of sialic acid in nonfucosylated antibodies. This study focused on the pharmacokinetic and pharmacodynamic properties of pertuzumab after glycoengineering. Herein, nonfucosylated pertuzumab was produced in CHOFUT8−/− cells, and desialylated pertuzumab was generated by enzymatic hydrolysis. Present data indicated that fucose was critical for ADCC activity by influencing the interaction between pertuzumab and FcγRIIIa, nevertheless removal of sialic acid increased the ADCC and CDC activity of pertuzumab. Meanwhile, regarding to sialic acid, sialidase hydrolysis directly resulted in asialoglycoprotein receptors (ASGPRs) dependent clearance in hepatic cells in vitro. The pharmacokinetic assay revealed that co-injection of asialofetuin can protect desialylated pertuzumab against ASGPRs-mediated clearance. Taken together, the present study elucidated the importance of fucose and sialic acid for pertuzumab, and also provided further understanding of the relationship of glycosylation/pharmacokinetics/pharmacodynamics of therapeutic antibody.
Fine dissection of the tarsal tunnel in 60 cases
Authors: Yang Y. , Du M. L. , Fu Y. S. , Liu W. , Xu Q. , Chen X. , Hao Y. J. , Liu Z. , Gao M. J. 
Published: April 2017

AbstractThe fine dissection of nerves and blood vessels in the tarsal tunnel is necessary for clinical operations to provide anatomical information. A total of 60 feet from 30 cadavers were dissected. Two imaginary reference lines that passed through the tip of the medial malleolus were applied. A detailed description of the branch pattern and the corresponding position of the posterior tibial nerve, posterior tibial artery, medial calcaneal nerve and medial calcaneal artery was provided, and the measured data were analyzed. Our results can be summarized as follows. I. A total of 81.67% of the bifurcation points of the posterior tibial nerve, which was divided into the medial and lateral plantar nerves, were located within the tarsal tunnel, not distal to the tarsal tunnel. II. The bifurcation points of the posterior tibial artery were all located in the tarsal tunnel. Almost all of the bifurcation points of the posterior tibial artery were lower than those of the posterior tibial nerve. The bifurcation point of the posterior tibial artery situated distal to the tarsal tunnel was not found. III. The number and the origin of the medial calcaneal nerves and arteries were highly variable.
The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
Authors: Masini D , Lopes-Aguiar C , Bonito-Oliva A , Papadia D , Andersson R , Fisahn A , Fisone G 
Published: April 2017

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine the effect of thioperamide, a histamine H3 receptor antagonist, on circadian activity, recognition memory and anxiety. A partial, bilateral 6-OHDA lesion of the striatum reduces motor activity during the active phase of the 24 h cycle. In addition, the lesion disrupts the endogenous circadian rhythm observed when mice are maintained in constant darkness. Administration of thioperamide to 6-OHDA-lesion mice rescues the normal rest/activity cycle. Moreover, thioperamide counteracts the deficit of novel object recognition produced by 6-OHDA. Our experiments show that this memory impairment is accompanied by disrupted gamma oscillations in the hippocampus, which are also rescued by thioperamide. In contrast, we do not observe any modification of the anxiogenic effect of 6-OHDA in response to administration of thioperamide. Our results indicate that thioperamide may act as a multifunctional drug, able to counteract disruptions of circadian rhythm and cognitive deficits associated with PD.
The Interest of Performing “On-Demand Chest X-rays” after Lung Resection by Minimally Invasive Surgery
Authors: Bubenheim Michael , Bernard Alain , Melki Jean , Peillon Christophe , Baste Jean-Marc , Haddad Laura 
Published: April 2017

Background There is a lack of consensus in hospital centers regarding costly daily routine chest X-rays after lung resection by minimally invasive surgery. Indeed, there is no evidence that performing daily chest X-rays prevents postoperative complications. Our objective was to compare chest X-rays performed on demand when there was clinical suspicion of postoperative complications and chest X-rays performed systematically in daily routine practice.
Methods This prospective single-center study compared 55 patients who had on-demand chest X-rays and patients in the literature who had daily routine chest X-rays. Our primary evaluation criterion was length of hospitalization.
Results The length of hospitalization was 5.3 ± 3.3 days for patients who had on-demand X-rays, compared with 4 to 9.7 days for patients who had daily routine X-rays. Time to chest tube removal (4.34 days), overall complication rate (27.2%), reoperation rate (3.6%), and mortality rate (1.8%) were comparable to those in the literature. On average, our patients only had 1.22 ± 1.8 on-demand X-rays, compared with 3.3 X-rays if daily routine protocol had been applied. Patients with complications had more X-rays (3.4 ± 1.8) than patients without complications (0.4 ± 0.7).
Conclusion On-demand chest X-rays do not seem to delay the diagnosis of postoperative complications or increase morbidity–mortality rates. Performing on-demand chest X-rays could not only simplify surgical practice but also have a positive impact on health care expenses. However, a broader randomized study is warranted to validate this work and ultimately lead to national consensus.
Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism
Authors: Benetti-Pinto Cristina Laguna , Piccolo Vanessa Berini , Yela Daniela Angerame , Garmes Heraldo 
Published: April 2017

Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism.
Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included.
Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR.
Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 – 10 mIU/L.
Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.
Can the Pessary Use Modify the Vaginal Microbiological Flora? A Cross-sectional Study
Authors: Giraldo Paulo César , Florentino Juliana Oquendo , Castro Edilson Benedito de , Brito Luiz Gustavo Oliveira , Juliato Cássia Raquel Teatin , Coelho Suelene Costa de Albuquerque 
Published: April 2017

Introduction Vaginal pessary is used as a conservative treatment for pelvic organ prolapse (POP). Some studies have shown that common complaints of its use may include vaginal discomfort and increased vaginal discharge. Scant information is available about the microflora status after using this device.
Objective To determine if the usage of vaginal pessary can interfere with the vaginal environment.
Methods A cross-sectional study was performed from March of 2014 to July of 2015 including 90 women with POP. The study group was composed of 45 women users of vaginal pessary and 45 nom-users. All enrolled women answered a standardized questionnaire and were subjected to a gynecological exam to collect vaginal samples for microbiological evaluation under optic microscopy. Clinical and microbiological data were compared between study and control groups.
Results Vaginal discharge was confirmed in 84% of the study group versus 62.2% in the control group (p < 0.01); itching was reported in 20 and 2.2%, respectively (p < .05); genital ulcers were only found in the pessary group (20%). There was no difference with regard to the type of vaginal flora. Bacterial vaginosis was prevalent in the study group (31.1% study group versus 22.2% control group), (p =.34).
Conclusion Women using vaginal pessaries for POP treatment presented more vaginal discharge, itching and genital ulcers than non-users.
Transperineal Ultrasound for Perianal Fistulas and Abscesses – A Systematic Review and Meta-Analysis
Authors: Maconi Giovanni , Greco Maria , Asthana Anil 
Published: April 2017

Abstract
Purpose Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying perianal fistulae and abscesses.
Method The National Library of Medicine and Embase were searched for articles on TPUS for the assessment of idiopathic and Crohn’s perianal fistulae and abscesses. Two reviewers independently reviewed eligible studies and rated them for quality using the QUADAS tool. The primary outcome measure was the accuracy of TPUS as measured by its sensitivity and positive predictive value (PPV) in detecting and classifying perianal fistulae, internal openings and perianal abscesses.
Results We included 12 studies (565 patients). Overall, the methodological quality of the studies was suboptimal. 3 studies were retrospective and 4 showed significant risks of bias in the application of the reference standard. The sensitivity of TPUS in detecting perianal fistulae on a per-lesion basis was 98 % (95 % CI 96 – 100 %) and the PPV was 95 % (95 % CI 90 – 98 %). The detection of internal openings had a sensitivity of 91 % (95 % CI 84 – 97 %) with a PPV of 87 % (95 % CI 76 – 95 %). The classification of fistulae yielded a sensitivity of 92 % (95 % CI 85 – 97 %) and a PPV of 92 % (95 % CI 83 – 98 %). TPUS had a sensitivity of 86 % (95 % CI 67 – 99 %) and PPV of 90 % (95 % CI 76 – 99 %) in the detection of perianal abscesses.
Conclusion The current literature on TPUS illustrates good overall accuracy in the assessment of perianal fistulae and abscesses. However, many studies had methodological flaws suggesting that further research is required.
Adenoma detection with blue-water infusion colonoscopy: a randomized trial
Authors: Lesne Adriane , Rouquette Olivier , Touzet Sandrine , Petit-Laurent Fabien , Tourlonias Gwenaelle , Pasquion Audrey , Rivory Jérôme , Aguero Garcete Guillermo , Scanzi Julien , Chalumeau Sylvaine , Chambon-Augoyard Christine , Moussata Driffa , Leger-Nguyen Florence , Degeorges Stéphane , Chauvenet Marion , Fontanges Thierry , Baubet Sandrine , Brulet Philippe , Billioud Claire , Thimonier Elsa , Stroeymeyt-Martin Karine , Hamel Benjamin , Graillot Emmanuelle , Cruiziat Claire , Scalone Olivia , O’Brien Marc , Péré-Vergé Denis , Souquet Jean-Christophe , Phelip Jean-Marc , Poincloux Laurent , Poupon-Bourdy Stéphanie , Denis Angélique , Magaud Laurent , Ponchon Thierry , Pioche Mathieu 
Published: April 2017

Abstract
Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy.
Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded.
Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 – 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P < 0.001).
Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known.Clinical trials registration: EudraCT 2012-A00548 – 35; NCT01937429.
Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human
Authors: Li Yan , Zhou Yanyan , Si Nan , Han Lingyu , Ren Wei , Xin Shaokun , Wang Hongjie , Zuo Ran , Wei Xiaolu , Yang Jian , Zhao Haiyu , Bian Baolin 
Published: April 2017

AbstractProtoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids.
Discourse as virtue ethics: Muslim women in the American Southwest
Authors: C. Taha Maisa 
Published: April 2017

AbstractThis article examines naturally occurring speech among participants in a young women’s halaqa, or study circle, at a mosque in the southwest United States to detail how “tactics of linguistic objectification” provide anchor points for ethical negotiations of difference. By focusing on linguistic micro-practices, including codeswitching and mock “foreign” accents, this paper brings a linguistic anthropological approach to bear upon this inquiry into discourse as a mode of phronesis. It is argued that, during informal conversation, core members of this group of largely second-generation immigrant women highlighted features of non-native English speech to monitor, examine, and mediate their own and their families’ hypervisibility as U.S. Muslims. As policy and public opinion paint a picture of Muslims as an existential threat to the west, these women’s language use, narratives and laughter act as in-group responses to social scrutiny that makes acknowledgement and normalization of Muslim difference obligatory. This article is published as part of a collection on discourse studies.
Adaptation aftereffects reveal that tactile distance is a basic somatosensory feature
Authors: Calzolari Elena , Azañón Elena , Danvers Matthew , Vallar Giuseppe , Longo Matthew R. 
Published: April 2017

Significance
Visual adaptation aftereffects have been termed “the psychologist’s microelectrode” for the insight they provide into the neural bases of human vision. Less research has explored such aftereffects in touch. We exploit the distinction in vision between “low-level” aftereffects, showing location- and orientation-specificity characteristics of the early retinotopic cortex, and “high-level” aftereffects, showing high generality to these characteristics, and presumably arising from higher processing stages. We demonstrate that distance aftereffects in passive touch share numerous characteristics with low-level visual aftereffects, including orientation and region specificity, lack of transfer contralaterally or across palm and dorsum, and encoding in skin-based space. These results provide experimental evidence that tactile distance is a basic somatosensory feature, computed at relatively early somatosensory processing stages.
Altering the allosteric pathway in IGPS suppresses millisecond motions and catalytic activity
Authors: Lisi George P. , East Kyle W. , Batista Victor S. , Loria J. Patrick 
Published: April 2017

SignificanceThe enzyme imidazole glycerol phosphate synthase (IGPS) fromThermotoga maritimais a potential therapeutic target absent in mammals but present in bacteria, plants, and fungi. The reported findings on how to affect allosteric pathways and suppress catalytic activity are particularly relevant to establish and alter allosteric mechanisms that could represent targets for drug discovery. In particular, many plant and human pathogens that infect the immunocompromised patient have an IGPS that is highly homologous to theSaccharomyces cerevisiaeandT. maritimaenzymes. It has also been demonstrated that gene knockouts of IGPS subunit HisF can increase the susceptibility of bacteria to β-lactam antibiotics and lessen their infectivity.
Complex fluid flow and heat transfer analysis inside a calandria based reactor using CFD technique
Authors: Kulkarni P. S. 
Published: April 2017

Abstract
Series of numerical experiments have been carried out on a calandria based reactor for optimizing the design to increase the overall heat transfer efficiency by using Computational Fluid Dynamic (CFD) technique. Fluid flow and heat transfer inside the calandria is governed by many geometric and flow parameters like orientation of inlet, inlet mass flow rate, fuel channel configuration (in-line, staggered, etc.,), location of inlet and outlet, etc.,. It was well established that heat transfer is more wherever forced convection dominates but for geometries like calandria it is very difficult to achieve forced convection flow everywhere, intern it strongly depends on the direction of inlet jet. In the present paper the initial design was optimized with respect to inlet jet angle, the optimized design has been numerically tested for different heat load mass flow conditions. To further increase the heat removal capacity of a calandria, further numerical studies has been carried out for different inlet geometry. In all the analysis same overall geometry size and same number of tubes has been considered. The work gives good insight into the fluid flow and heat transfer inside the calandria and offer a guideline for optimizing the design and/or capacity enhancement of a present design.
Fast radio bursts as pulsar lightning
Authors: Katz J. I. 
Published: April 2017

Abstract
There are striking phenomenological similarities between fast radio bursts (FRBs) and lightning in the Earth's and planetary atmospheres. Both have very low duty factors, ≲10−8–10−5 for FRBs and (very roughly) ∼10−4 for the main return strokes in an active thundercloud. Lightning occurs in an electrified insulating atmosphere when a conducting path is created by and permits current flow. FRBs may occur in neutron star magnetospheres whose plasma is believed to be divided by vacuum gaps. Vacuum is a perfect insulator unless electric fields are sufficient for electron–positron pair production by curvature radiation, a high-energy analogue of electrostatic breakdown in an insulating gas. FRB may be ‘electrars’ powered by the release of stored electrostatic energy, counterparts to soft gamma repeaters powered by the release of stored magnetostatic energy (magnetars). This frees pulsar FRB models from the constraint that their power not exceeds the instantaneous spin-down power. Energetic constraints imply that the sources of more energetic FRBs have shorter spin-down lifetimes, perhaps even less than the 3 yr over which FRB 121102 has been observed to repeat.