bluuebunny/crossref_metadata_2025 huggingface dataset:
PP170 Health Impact Assessment Of Teleradiology Programs In Disadvantaged Areas
Authors: Davini Ottavio , Digiacomo Giovanni , Perusia Matteo , Romano Valeria , Rivoiro Chiara , Servetto Rosario , Giacometti Marika , Glisoni Marco , Gualano Maria Rosaria , Siliquini Roberta , Grosso Marco
Published: January 2018

INTRODUCTION:

Within the Home Radiology service of the Piedmont Region - R@dhome (1) - it was decided to employ a mobile radiological service to allow minor radiological procedures to be conducted in rural areas. Cortemilia (average age of population 51.6 years, population over 65 years 33.6 percent) is situated in Piedmont (Langhe region) and it is about 40 kilometers, with bad roads, from the nearest hospital. For this reason it's important to optimize the potential offered by telemedicine. The purpose of R@dhome is to provide simple radiological services (ambulatory) to vulnerable patients in outpatient settings. The aim of this work was to implement an assessment, based on Health Impact Analysis (HIA) (2,3) criteria, of the health intervention provided by the R@dhome service.

METHODS:

From January 2016 to December 2016 the following were assessed:

•

number of patients examined in the local radiological ambulatory service

•

inhabitants opinions (using questionnaires)

•

General Practitioner, Pharmacist, Family nurse opinions (using semi-structured interviews)

•

stakeholder opinions (Mayor, local politicians, using semi-structured interviews)

•

number of cars and ambulances used for the transport of patients to the nearest hospital

•

number of patients who avoided transportation to the nearest hospital

•

pollutants PM10 (particle size 10) related to cars and ambulance traffic.

RESULTS:

Forty percent of people interviewed were more than 60 years old, 76 percent needed x-rays (in 2015), 96.8 percent considered it useful to have a closer x-ray service, only 42 percent had a driver's licence but preferred not to drive; GP's said that 50 percent of local patients had trouble reaching the hospital and that 30 percent of local patients need informal or formal care. From Januay to December 2016 we examined (mainly chest and bone x-rays) in 598 patients using as an alternative to private cars and ambulances the radiological mobile station, and the pollutant emissions were shown to be reduced by 85 percent.

CONCLUSIONS:

This study has provided a comprehensive HIA report which shows that the R@dhome intervention improves patient's QOL, reduces social costs, reduces the number of patients in the Hospital Radiology Department, reduces rate of hospitalization and pollution.
VP53 Cost-Utility Analysis: Adalimumab Verus Etanercept in Rheumatoid Arthritis – Brazil
Authors: Silva Grazielle , Alvares Juliana , Andrade Eli Iola , Cherchiglia Mariangela , Guerra Augusto , Almeida Alessandra , Godman Brian , Acurcio Francisco
Published: January 2018

INTRODUCTION:

Rheumatoid arthritis (RA) is an inflammatory, autoimmune disease of unknown etiology that usually results in joint lesions and physical incapacitation. RA treatment includes disease-modifying antirheumatic drugs (DMARD), synthetic (sDMARD) and/or biologics (bDMARD). In this study we carried out a cost-utility analysis comparing Adalimumab (ADA) versus Etanercept (ETA), with or without synthetic DMARDs (± sDMARD).

METHODS:

Effectiveness measures used were the Clinical Disease Activity Index (CDAI) and Quality-Adjusted Life Years (QALY) obtained from an open prospective cohort study with Brazilian RA patients. Costs were obtained from a historical cohort composed of every patient who was prescribed medicines to treat RA in the State of Minas Gerais, Brazil. A public sector perspective was adopted. The Markov model included six-month cycles, time horizon of 5 years and 5 percent discount rates. Sensitivity analyses were performed by varying costs and outcome values.

RESULTS:

There was no significant difference in effectiveness between the two bDMARDs. Treatment with ETA (± sDMARD) was more expensive after 5 years of follow-up: incremental cost of USD28,210.87. Overall, treatment with ADA (± sDMARD) was more cost-effective: incremental cost-effectiveness ratio for ETA (± sDMARD) was USD79,148.34/ QALY. Sensitivity analysis showed that this was sensitive to changes in the cost of ETA (± sDMARD).

CONCLUSIONS:

Currently two Anti-tumour Necrosis Factor Alpha (anti-TNF alpha) medicines – ADA and ETA are available within the Brazilian public health system in addition to infliximab. Treatment with ADA (±sDMARD) was more cost-effective with an incremental cost effectiveness ratio for ETA (±sDMARD) at USD79,148.34 per QALY. Sensitivity analysis showed that outcomes are sensitive to changes in the cost of ETA (± sDMARD) treatment. Overall, both therapeutic alternatives are valuable from the public sector perspective especially when the Clinical Protocol and Therapeutic Guidelines are properly applied in patients no longer responding to treatment. Alternatives are needed as some patients will respond differently to different anti-TNF alpha medicines.
VP87 Extrapolation From Progression Free Survival To Overall Survival In Oncology
Authors: Hernandez-Villafuerte Karla , Fischer Alastair , Latimer Nicholas , Henshall Chris
Published: January 2018

INTRODUCTION:

The outcomes from clinical and other healthcare trials of most interest to patients and health systems are usually increases in the quality and length of life (overall survival (OS)). This poses a problem, because complete knowledge on the true increase in OS is not available until the last person in the trial dies. However, if OS is sufficiently correlated with a surrogate endpoint that is observable within the trial period or soon after the treatment has finished, this can be used to estimate OS, without much error. The most widely-used surrogate endpoint in oncology is progression-free survival (PFS). We aim at (i) analyzing the methods used to extrapolate from PFS to OS in the field of oncology; (ii) identifying whether a clear guidance exists in the literature about what is considered to be ‘best practice’ in extrapolation from PFS to OS; (iii) determining the key limitations, weaknesses and gaps in the current literature and method used to test PFS surrogacy.

METHODS:

We extend the literature review carried out previously (1), we interview experts from regulatory and reimbursement bodies, and we explore academic research into the methodology of surrogacy and the need for better reporting of surrogacy papers.

RESULTS:

A number of factors affect the relationship between PFS and OS. Therefore, there is no unique correct answer for the question of whether PFS is an appropriate surrogate for OS in oncology. Many of these factors are related to the length and characteristics of post-progression survival (PPS).

CONCLUSIONS:

Any consideration of evidence relating to PFS should consider both tumour type and other factors, particularly those related to PPS. Protocols of future follow-up of clinical trial patients should specify procedures for gathering information about the effect of post-progression management of the disease. This should allow stronger conclusions to be extracted from statistical analyses. Improved reporting standards will aid in achieving this goal. In addition, it is very likely that increasing the use of IPD will result in greater precision in estimating the benefits of worthwhile drugs.
VP182 Network Amongst The Health Technology Assessment Ecosystem
Authors: Cinaroglu Songul , Baser Onur
Published: January 2018

INTRODUCTION:

There has been a growing interest in international collaboration among Health Technology Assessment (HTA) organizations on macro, meso, and micro policy-making levels. Global member-driven professional HTA societies make contributions to scientific improvement and enhance interactions in the HTA ecosystem. However, little is known about collaboration between HTA organizations at the global level. This study intends to examine the main drivers of network relationships of HTA organizations.

METHODS:

Social network analysis was used to ascertain the relationships between HTA organizations and to visualize the main drivers of collaboration. The total number of memberships of the HTA organizations of the International Society For Pharmacoeconomics and Outcomes Research (ISPOR), Health Technology Assessment International (HTAi), International Netowork of Agencies for HTA (INAHTA), EuroScan, European Network for HTA (EUnetHTA), HTAsiaLink, Red de Evaluación de Tecnologías en Salud de las Américas (RedETSA) were considered to create the network. Ten different types of HTA organizations were considered in the analysis including the Ministry of Health (MoH), university, for-profit, and hospitals. The Fruchterman-Reingold algorithm was used to perform network analysis; average clustering coefficient and average path length were examined to measure collaborative performance.

RESULTS:

A network graph of the HTA ecosystem shows the highest collaborative frequency in terms of HTA organizations, occurred with members of the Ministry of Health, government agencies, universities, and non-profit organizations. The average path length was 2.21 and the average clustering coefficient was 36.576 which indicates an obvious clustering effect.

CONCLUSIONS:

These study results highlight that the network throughout the HTA ecosystem is driven by government organizations. Integrating the private sector into the system, creating common information and data sharing strategies, and improving the number of internationally experienced HTA professionals are essential strategies to foster collaboration in HTA organizations. As HTA is shaped by local dynamics and there is no gold standard for HTA implementation, encouragement of collaborative efforts is the only way to prevent duplication of effort and to make health technologies available for everyone.
VP196 Impact Of Trial Registry Search Features On Searches In CT.gov/ICTRP
Authors: Hausner Elke , Knelangen Marco , Waffenschmidt Siw
Published: January 2018

INTRODUCTION:

In contrast to bibliographic databases, trial registries do not offer the option of formulating complex search queries, thus making targeted searches more difficult. However, ClinicalTrials.gov (CT.gov) and the International Clinical Trials Registry Platform (ICTRP) offer different search features that may help compensate this limitation. Our aim was to determine the importance of search features (for example, searches using synonyms or, additionally in CT.gov, automatic inclusion of further search fields) for trial registry searches.

METHODS:

We conducted a project called “Trial registry searches for studies of newly approved drugs” (1). One analysis investigated the question as to whether searches for different health conditions and interventions (new drugs) directly identified registry entries with the search terms entered or whether certain search features were responsible for this. We searched CT.gov and ICTRP for different conditions and interventions using the advanced search interface. For each search, we documented the synonyms listed in the two registries. We imported the registry entries into EndNote and evaluated whether the search terms used were available in the corresponding search fields (condition; intervention).

RESULTS:

For CT.gov, 96 registry entries on 18 interventions and 190 entries on 12 conditions were analysed. Of these, twenty-three (24 percent) entries for interventions and thirty-eight (20 percent) for conditions were identified by search features, not by search terms. For ICTRP, 32 entries on 10 interventions and 100 entries on 9 conditions were analysed. Of these, five (16 percent) entries for interventions and eight (8 percent) for conditions were identified by search features.

CONCLUSIONS:

Trial registry search features have an important impact on the sensitivity of searches. Many studies are not identified by the search terms entered, but by searches using synonyms and, additionally in CT.gov, by automatic inclusion of further search fields. Moreover, search features in CT.gov are more effective than in ICTRP – even though the same search terms are used, they consistently yield higher sensitivities.
VP200 Untangling What Information Specialists Should Document and Report
Authors: Tjosvold Lisa , Chojecki Dagmara
Published: January 2018

INTRODUCTION:

Thorough documentation and clear reporting are essential when conducting a comprehensive literature search for a health technology assessment (HTA) or systematic review. The ultimate goal of this process is transparency and reproducibility with the added benefit of increasing the reader's confidence in the research. Thorough documentation of the search also allows for critical appraisal of the methodology used and facilitates future updating of a review (1,2).

It has been found that large numbers of systematic review searches are inadequately documented and there is little consensus on best practices for reporting standards (3).

As part of the SuRe Info Project, we conducted a review of all current reporting standards relevant to HTAs and systematic reviews in addition to looking at the published literature on this topic in order to synthesize the evidence in this area and create a standard set of agreed upon recommendations.

METHODS:

We conducted a comprehensive search of Medline, Embase, and LISA (Library & Info Studies Abstracts) databases. We also examined the Equator Network (http://www.equator-network.org/) website. Reference lists of included studies and reporting guidelines were also consulted. Eleven reporting guidelines and eight studies were included in the review by two independent reviewers. Anything published before 2006, that was not a research article (other than the guidelines), and/or that did not provide new recommendations (that is, a review of another set of recommendations) was excluded.

RESULTS:

After collecting data on the suggested reporting elements described in the literature, we pooled our results to create an overarching list of the most commonly recommended elements to describe and the most commonly recommended methods to use when documenting a comprehensive search. Not only did these elements pertain to documenting the search strategy for the final report, but they also pertained to the protocol and the abstract of a review.

CONCLUSIONS:

It is hoped that this overview of the literature and compilation of the evidence will clarify some of the confusion that seems to exist when documenting and reporting searches and perhaps it will even help to reduce the existence of poorly described strategies in the research literature.
VP203 Performance Evaluation Of Eye-Tracking Devices
Authors: Recalde Luciano , Núñez José , Yegros César , Villegas Carolina
Published: January 2018

INTRODUCTION:

There are different devices, systems and technologies for people with disabilities. It's necessary to provide information on the effectiveness of products in the market and competitiveness in terms of price-quality, and providing an endorsement in the acquisition of technologies that improve their quality of life. The use of eye tracking devices is growing and its implementation in different areas has attracted the attention of several developers. Therefore the need to generate a product that evaluates the functionality of such devices is necessary in order to avoid unnecessary expenses when acquiring or repairing one of these devices.

METHODS:

An interface was created with different functionalities such as the location of the coordinates in which the pointer is located, standardized graphic interface design to provide statistical data that allow an objective result for its subsequent analysis and an endless number of design possibilities.

The tests performed were of accuracy and precision where the subject was asked to follow the instructions given and observe a sequence of points, especially the points located at the ends of the monitor as these are the critical points in which there is less coincidence between the cursor and the gaze.

RESULTS:

The results obtained provided information on the performance of the tracking device. In this way it was possible to establish that the accuracy of the ocular tracker: it was ± 12.83 pixels on the horizontal axis and ± 10.66 pixels on the vertical axis. The precision was ± 9.8 pixels on the horizontal axis and ± 14.23 pixels on the vertical axis.

This shows the use phenomenon caused due to the limited mobility of the eyes in the vertical axis in comparison to the horizontal mobility. The precision data obtained indicate that, because the movement on the vertical axis is smaller, there is a less continuous spectrum of positions on the axis, which translates to less precision.

CONCLUSIONS:

The data obtained can be used to compare with the results of the test with other eye tracking devices and thus this could serve as a tool to select an eye tracking device according to the user's need and his economical capabilities.
Introspection in Psychology
Authors: Weger Ulrich , Wagemann Johannes , Meyer Andreas
Published: January 2018

Abstract. Memory is typically conceptualized as a mental space where information is stored until it is retrieved for current processing. This archive account has been undermined by a multitude of findings, however, calling for a theoretical and also a methodological reorientation. In particular, we consider it timely to include an introspective mode of research into the study of memory because such introspective enquiry can provide insights into the recall process that go beyond those of third-person research. The limitations often associated with introspection (e.g., its seemingly subjective quality and its post hoc nature) are well justified – but only as long as the more immature impromptu introspections are concerned. A more systematically developed form of introspection can overcome these limitations. Such a systematic approach is outlined and used here to develop a taxonomy of mental processes involved in recall. Our observations lend support to a reconstruction account and allow for a differentiation of mental activities involved in various types of recall.
Designable and dynamic single-walled stiff nanotubes assembled from sequence-defined peptoids
Authors: Jin Haibao , Ding Yan-Huai , Wang Mingming , Song Yang , Liao Zhihao , Newcomb Christina J. , Wu Xuepeng , Tang Xian-Qiong , Li Zheng , Lin Yuehe , Yan Feng , Jian Tengyue , Mu Peng , Chen Chun-Long
Published: January 2018

Despite recent advances in the assembly of organic nanotubes, conferral of sequence-defined engineering and dynamic response characteristics to the tubules remains a challenge. Here we report a new family of highly designable and dynamic nanotubes assembled from sequence-defined peptoids through a unique “rolling-up and closure of nanosheet” mechanism. During the assembly process, amorphous spherical particles of amphiphilic peptoid oligomers crystallize to form well-defined nanosheets before folding to form single-walled nanotubes. These nanotubes undergo a pH-triggered, reversible contraction–expansion motion. By varying the number of hydrophobic residues of peptoids, we demonstrate tuning of nanotube wall thickness, diameter, and mechanical properties. Atomic force microscopy-based mechanical measurements show peptoid nanotubes are highly stiff (Young’s Modulus ~13–17 GPa). We further demonstrate the precise incorporation of functional groups within nanotubes and their applications in water decontamination and cellular adhesion and uptake. These nanotubes provide a robust platform for developing biomimetic materials tailored to specific applications.
Structural basis of trans-synaptic interactions between PTPδ and SALMs for inducing synapse formation
Authors: Goto-Ito Sakurako , Yamagata Atsushi , Sato Yusuke , Uemura Takeshi , Shiroshima Tomoko , Maeda Asami , Imai Ayako , Mori Hisashi , Yoshida Tomoyuki , Fukai Shuya
Published: January 2018

Synapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPδ, PTPσ and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding. Here, we report the crystal structures of apo-SALM5, and PTPδ–SALM2 and PTPδ–SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTPδ, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTPδ. Unexpectedly, the structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture assay using site-directed SALM5 mutants demonstrates that presynaptic differentiation induced by PTPδ–SALM5 requires the dimeric property of SALM5.
A biosensor-based framework to measure latent proteostasis capacity
Authors: Wood Rebecca J. , Ormsby Angelique R. , Radwan Mona , Cox Dezerae , Sharma Abhishek , Vöpel Tobias , Ebbinghaus Simon , Oliveberg Mikael , Reid Gavin E. , Dickson Alex , Hatters Danny M.
Published: January 2018

The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins. Conditions of proteostasis stimulation and stress alter QC holdase activity and aggregation rates. The method reveals the HSP70 chaperone cycle to be rate limited by HSP70 holdase activity under normal conditions, but this is overcome by increasing levels of the BAG1 nucleotide exchange factor to HSPA1A or activation of the heat shock gene cluster by HSF1 overexpression. This scheme opens new paths for biosensors of disease and proteostasis systems.
Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors regardless of gender
Authors: Wei Yi-Chao , Wang Shao-Ran , Jiao Zhuo-Lei , Zhang Wen , Lin Jun-Kai , Li Xing-Yu , Li Shuai-Shuai , Zhang Xin , Xu Xiao-Hong
Published: January 2018

The medial preoptic area (mPOA) differs between males and females in nearly all species examined to date, including humans. Here, using fiber photometry recordings of Ca2+ transients in freely behaving mice, we show ramping activities in the mPOA that precede and correlate with sexually dimorphic display of male-typical mounting and female-typical pup retrieval. Strikingly, optogenetic stimulation of the mPOA elicits similar display of mounting and pup retrieval in both males and females. Furthermore, by means of recording, ablation, optogenetic activation, and inhibition, we show mPOA neurons expressing estrogen receptor alpha (Esr1) are essential for the sexually biased display of these behaviors. Together, these results underscore the shared layout of the brain that can mediate sex-specific behaviors in both male and female mice and provide an important functional frame to decode neural mechanisms governing sexually dimorphic behaviors in the future.
Structured thermal surface for radiative camouflage
Authors: Li Ying , Bai Xue , Yang Tianzhi , Luo Hailu , Qiu Cheng-Wei
Published: January 2018

Thermal camouflage has been successful in the conductive regime, where thermal metamaterials embedded in a conductive system can manipulate heat conduction inside the bulk. Most reported approaches are background-dependent and not applicable to radiative heat emitted from the surface of the system. A coating with engineered emissivity is one option for radiative camouflage, but only when the background has uniform temperature. Here, we propose a strategy for radiative camouflage of external objects on a given background using a structured thermal surface. The device is non-invasive and restores arbitrary background temperature distributions on its top. For many practical candidates of the background material with similar emissivity as the device, the object can thereby be radiatively concealed without a priori knowledge of the host conductivity and temperature. We expect this strategy to meet the demands of anti-detection and thermal radiation manipulation in complex unknown environments and to inspire developments in phononic and photonic thermotronics.
DNA multi-bit non-volatile memory and bit-shifting operations using addressable electrode arrays and electric field-induced hybridization
Authors: Song Youngjun , Kim Sejung , Heller Michael J. , Huang Xiaohua
Published: January 2018

DNA has been employed to either store digital information or to perform parallel molecular computing. Relatively unexplored is the ability to combine DNA-based memory and logical operations in a single platform. Here, we show a DNA tri-level cell non-volatile memory system capable of parallel random-access writing of memory and bit shifting operations. A microchip with an array of individually addressable electrodes was employed to enable random access of the memory cells using electric fields. Three segments on a DNA template molecule were used to encode three data bits. Rapid writing of data bits was enabled by electric field-induced hybridization of fluorescently labeled complementary probes and the data bits were read by fluorescence imaging. We demonstrated the rapid parallel writing and reading of 8 (23) combinations of 3-bit memory data and bit shifting operations by electric field-induced strand displacement. Our system may find potential applications in DNA-based memory and computations.
Superconducting gap anisotropy sensitive to nematic domains in FeSe
Authors: Hashimoto Takahiro , Ota Yuichi , Yamamoto Haruyoshi Q. , Suzuki Yuya , Shimojima Takahiro , Watanabe Shuntaro , Chen Chuangtian , Kasahara Shigeru , Matsuda Yuji , Shibauchi Takasada , Okazaki Kozo , Shin Shik
Published: January 2018

The structure of the superconducting gap in unconventional superconductors holds a key to understand the momentum-dependent pairing interactions. In superconducting FeSe, there have been controversial results reporting nodal and nodeless gap structures, raising a fundamental issue of pairing mechanisms of iron-based superconductivity. Here, by utilizing polarization-dependent laser-excited angle-resolved photoemission spectroscopy, we report a detailed momentum dependence of the gap in single- and multi-domain regions of orthorhombic FeSe crystals. We confirm that the superconducting gap has a twofold in-plane anisotropy, associated with the nematicity due to orbital ordering. In twinned regions, we clearly find finite gap minima near the vertices of the major axis of the elliptical zone-centered Fermi surface, indicating a nodeless state. In contrast, the single-domain gap drops steeply to zero in a narrow angle range, evidencing for nascent nodes. Such unusual node lifting in multi-domain regions can be explained by the nematicity-induced time-reversal symmetry breaking near the twin boundaries.
Novel Miniature Membrane Active Lipopeptidomimetics against Planktonic and Biofilm Embedded Methicillin-Resistant Staphylococcus aureus
Authors: Joshi Seema , Mumtaz Sana , Singh Jyotsna , Pasha Santosh , Mukhopadhyay Kasturi
Published: January 2018

Escalating multidrug resistance and highly evolved virulence mechanisms have aggravated the clinical menace of methicillin-resistant Staphylococcus aureus (MRSA) infections. Towards development of economically viable staphylocidal agents here we report eight structurally novel tryptophan-arginine template based peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S-7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and good to potent activity against clinically relevant pathogens MRSA, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (MIC: 1.4–22.7 μg/mL). Mechanistically, the active peptidomimetics dissipated membrane potential and caused massive permeabilization on MRSA concomitant with loss of viability. Against stationary phase MRSA under nutrient-depleted conditions, active peptidomimetics S-7 and S-8 achieved > 6 log reduction in viability upon 24 h incubation while both S-7 (at 226 μg/mL) and S-8 (at 28 μg/mL) also destroyed 48 h mature MRSA biofilm causing significant decrease in viability (p < 0.05). Encouragingly, most active peptidomimetic S-8 maintained efficacy against MRSA in presence of serum/plasma while exhibiting no increase in MIC over 17 serial passages at sub-MIC concentrations implying resistance development to be less likely. Therefore, we envisage that the current template warrants further optimization towards the development of cell selective peptidomimetics for the treatment of device associated MRSA infections.
Gender specific association of parathyroid hormone and vitamin D with metabolic syndrome in population with preserved renal function
Authors: Kim Min-Hee , Lee Jeongmin , Ha Jeonghoon , Jo Kwanhoon , Lim Dong-Jun , Lee Jung-Min , Chang Sang-Ah , Kang Moo-Il , Cha Bong Yun
Published: January 2018

The association of parathyroid hormone (PTH) and vitamin D with Metabolic syndrome (MetS) was evaluated using representative data from the Korean population. Data from 7004 subjects aged 50 or older with preserved renal function (excluding chronic kidney disease stage 3b to 5) who were included in the Korean National Health and Nutrition Examination Survey between 2008 and 2010 were analysed. Higher PTH levels (pg/ml) were observed in subjects with MetS than in those without MetS among both genders (60.1 (58.6–61.6) vs. 62.4 (60.7–64.2) in males p = 0.018, 60.7 (59.4–62.1) vs. 63.9 (62.4–65.6) in females, p < 0.001). For females, PTH levels were significantly higher in subjects with MetS than in those without MetS after adjustment for possible covariates. Lower 25(OH)D levels were significantly associated with MetS only in male subjects (p = 0.004). As the number of MetS components increased, a significant rise in PTH levels (p for trend 0.005 in males and 0.024 in females) and a decrease in 25(OH)D levels (p for trend < 0.001 in males and 0.053 in females) were observed. In conclusion, among subjects with preserved renal function, PTH levels were possibly associated with MetS in females, whereas vitamin D levels exhibited a possible link to MetS in males.
Comparative analyses of fecal microbiota in Chinese isolated Yao population, minority Zhuang and rural Han by 16sRNA sequencing
Authors: Liao Ming , Xie Yuanliang , Mao Yan , Lu Zheng , Tan Aihua , Wu Chunlei , Zhang Zhifu , Chen Yang , Li Tianyu , Ye Yu , Yao Ziting , Jiang Yonghua , Li Hongzhe , Li Xiaoming , Yang Xiaobo , Wang Qiuyan , Mo Zengnan
Published: January 2018

The gut microbiome in humans is associated with geography, diet, lifestyles and so on, but its relationship with some isolated populations is not clear. We used the 16sRNA technique to sequence the fecal microbiome in the Chinese isolated Yao population and compared it with the major minority Zhuang and the major ethnic Han populations living in the same rural area. Information about diet frequency and health status and routine serum measurements were collected. The unweighted UniFrac principal coordinates analysis showed significant structural differences in fecal microbiota among the three ethnic groups. Statistically significant differences were observed in the community richness estimator (chaos) and the diversity estimator (Shannon) among the three groups. At the genus level, the fecal samples of the isolated Yao population presented the lowest relative abundance of the Megamonas genus, which was potentially related to the high frequency of bean consumption in the diet. Two enterotypes were identified in the overall fecal microbiota in the three populations. In the isolated Yao population, a higher Bacteroides abundance was observed, but the Prevotella abundance decreased with increased alcohol consumption.
Genome-wide association study of self-reported food reactions in Japanese identifies shrimp and peach specific loci in the HLA-DR/DQ gene region
Authors: Khor Seik-Soon , Morino Ryoko , Nakazono Kazuyuki , Kamitsuji Shigeo , Akita Masanori , Kawajiri Maiko , Yamasaki Tatsuya , Kami Azusa , Hoshi Yuria , Tada Asami , Ishikawa Kenichi , Hine Maaya , Kobayashi Miki , Kurume Nami , Kamatani Naoyuki , Tokunaga Katsushi , Johnson Todd A.
Published: January 2018

Food allergy is an increasingly important health problem in the world. Several genome-wide association studies (GWAS) focused on European ancestry samples have identified food allergy-specific loci in the HLA class II region. We conducted GWAS of self-reported reactivity with common foods using the data from 11011 Japanese women and identified shrimp and peach allergy-specific loci in theHLA-DR/DQgene region tagged by rs74995702 (P = 6.30 × 10−17,OR = 1.91) and rs28359884 (P = 2.3 × 10−12,OR = 1.80), respectively. After HLA imputation using a Japanese population-specific reference, the most strongly associated haplotype wasHLA-DRB1*04:05-HLA-DQB1*04:01for shrimp allergy (P = 3.92 × 10−19,OR = 1.99) andHLA-DRB1*09:01-HLA-DQB1*03:03for peach allergy (P = 1.15 × 10−7,OR = 1.68). Additionally, both allergies’ associated variants were eQTLs for several HLA genes, withHLA-DQA2 the single eQTL gene shared between the two traits. Our study suggests that allergy to certain foods may be related to genetic differences that tag both HLA alleles having particular epitope binding specificities as well as variants modulating expression of particular HLA genes. Investigating this further could increase our understanding of food allergy aetiology and potentially lead to better therapeutic strategies for allergen immunotherapies.
Specific cyclic ADP-ribose phosphohydrolase obtained by mutagenic engineering of Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase
Authors: Ribeiro João Meireles , Canales José , Cabezas Alicia , Rodrigues Joaquim Rui , Pinto Rosa María , López-Villamizar Iralis , Costas María Jesús , Cameselle José Carlos
Published: January 2018

Cyclic ADP-ribose (cADPR) is a messenger for Ca2+ mobilization. Its turnover is believed to occur by glycohydrolysis to ADP-ribose. However, ADP-ribose/CDP-alcohol diphosphatase (ADPRibase-Mn) acts as cADPR phosphohydrolase with much lower efficiency than on its major substrates. Recently, we showed that mutagenesis of human ADPRibase-Mn at Phe37, Leu196 and Cys253 alters its specificity: the best substrate of the mutant F37A + L196F + C253A is cADPR by a short difference, Cys253 mutation being essential for cADPR preference. Its proximity to the ‘northern’ ribose of cADPR in docking models indicates Cys253 is a steric constraint for cADPR positioning. Aiming to obtain a specific cADPR phosphohydrolase, new mutations were tested at Asp250, Val252, Cys253 and Thr279, all near the ‘northern’ ribose. First, the mutant F37A + L196F + C253G, with a smaller residue 253 (Ala > Gly), showed increased cADPR specificity. Then, the mutant F37A + L196F + V252A + C253G, with another residue made smaller (Val > Ala), displayed the desired specificity, with cADPR kcat/KM ≈20–200-fold larger than for any other substrate. When tested in nucleotide mixtures, cADPR was exhausted while others remained unaltered. We suggest that the specific cADPR phosphohydrolase, by cell or organism transgenesis, or the designed mutations, by genome editing, provide opportunities to study the effect of cADPR depletion on the many systems where it intervenes.
A vacuolar sorting receptor-independent sorting mechanism for storage vacuoles in soybean seeds
Authors: Maruyama Nobuyuki , Matsuoka Yuki , Yokoyama Kazunori , Takagi Kyoko , Yamada Tetsuya , Hasegawa Hisakazu , Terakawa Teruhiko , Ishimoto Masao
Published: January 2018

The seed storage proteins of soybean (Glycine max) are composed mainly of glycinin (11S globulin) and β-conglycinin (7S globulin). The subunits of glycinin (A1aB1b, A1bB2, A2B1a, A3B4, and A5A4B3) are synthesized as a single polypeptide precursor. These precursors are assembled into trimers with a random combination of subunits in the endoplasmic reticulum, and are sorted to the protein storage vacuoles. Proteins destined for transport to protein storage vacuoles possess a vacuolar sorting determinant, and in this regard, the A1aB1b subunit contains a C-terminal peptide that is sufficient for its sorting to protein storage vacuoles. The A3B4 subunit, however, lacks a corresponding C-terminal sorting determinant. In this study, we found that, unlike the A1aB1b subunit, the A3B4 subunit does not bind to previously reported vacuolar sorting receptors. Despite this difference, we observed that the A3B4 subunit is sorted to protein storage vacuoles in a transgenic soybean line expressing the A3B4 subunit of glycinin. These results indicate that a protein storage vacuolar sorting mechanism that functions independently of the known vacuolar sorting receptors in seeds might be present in soybean seeds.
Effects of CO2 enrichment on benthic primary production and inorganic nitrogen fluxes in two coastal sediments
Authors: Vopel Kay , Del-Río Cintya , Pilditch Conrad A.
Published: January 2018

Ocean acidification may alter the cycling of nitrogen in coastal sediment and so the sediment–seawater nitrogen flux, an important driver of pelagic productivity. To investigate how this perturbation affects the fluxes of NOX− (nitrite/nitrate), NH4+ and O2, we incubated estuarine sand and subtidal silt in recirculating seawater with a CO2-adjusted pH of 8.1 and 7.9. During a 41-day incubation, the seawater kept at pH 8.1 lost 97% of its NOX− content but the seawater kept at pH 7.9 lost only 18%. Excess CO2 increased benthic photosynthesis. In the silt, this was accompanied by a reversal of the initial NOX− efflux into influx. The estuarine sand sustained its initial NOX− influx but, by the end of the incubation, released more NH4+ at pH 7.9 than at pH 8.1. We hypothesise that these effects share a common cause; excess CO2 increased the growth of benthic microalgae and so nutrient competition with ammonia oxidising bacteria (AOB). In the silt, diatoms likely outcompeted AOB for NH4+ and photosynthesis increased the dark/light fluctuations in the pore water oxygenation inhibiting nitrification and coupled nitrification/denitrification. If this is correct, then excess CO2 may lead to retention of inorganic nitrogen adding to the pressures of increasing coastal eutrophication.
The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection
Authors: Wong Martin C. S. , Fung Franklin D. H. , Leung Colette , Cheung Wilson W. L. , Goggins William B. , Ng C. F.
Published: January 2018

We tested the hypotheses that the global incidence of bladder cancer was increasing but its mortality was reducing and its incidence was positively correlated with country-specific socioeconomic development. We retrieved data on age-standardized incidence and mortality rates/100,000 from the GLOBOCAN database in 2012. Temporal patterns were examined for 39 countries from the Cancer Incidence in Five Continents volumes I-X and other national registries. We evaluated the correlation between the incidence/mortality rates and Human Development Index (HDI)/ logarithmic values of Gross Domestic Product per capita (GDP). The average annual percent change of the incidence and mortality rates in the most recent 10 years was examined by joinpoint regression analysis. The highest incidence rates were observed in Southern Europe, Western Europe and North America. The mortality rates were the highest in Western Asia and Northern Africa. The incidence was positively correlated with HDI (r = 0.66 [men]; r = 0.50 [women]) and to a lesser extent logarithmic values of GDP per capita (r = 0.60 [men]; r = 0.50 [women], all p < 0.01). Many European countries experienced incidence rise. A substantial mortality reduction was observed in most countries, yet increases in mortality rates were observed in the Philippines and Iceland. These findings identified countries where more preventive actions are required.
Artificial selection for improved energy efficiency is reaching its limits in broiler chickens
Authors: Tallentire C. W. , Leinonen I. , Kyriazakis I.
Published: January 2018

Modern broiler chickens are a major animal husbandry success story, both in terms of efficient resource utilisation and environmental sustainability. However, continuing artificial selection for both efficiency and rapid growth will be subject to both biological limits and animal welfare concerns. Using a novel analytical energy flow modelling approach, we predict how far such selection can go, given the biological limits of bird energy intake and partitioning of energy. We find that the biological potential for further improvements in efficiency, and hence environmental impact reduction, is minimal relative to past progress already made via artificial selection. An alternative breeding strategy to produce slower-growing birds to meet new welfare standards increases environmental burdens, compared to current birds. This unique analytic approach provides biologically sound guidelines for strategic planning of sustainable broiler production.
The suppressive role of calcium sensing receptor in endometrial cancer
Authors: Xin Xiaoyan , Zeng Xianqin , Feng Dilu , Hua Teng , Liu Shuangge , Chi Shuqi , Hu Qinghua , Wang Hongbo
Published: January 2018

Studies have shown that calcium sensing receptor (CaSR) is involved in the progressions of several human cancers. However, the role of CaSR in endometrial cancer remains unknown. This study provides a preliminary analysis of the CaSR effect on endometrial cancer development. Ectopic CaSR expression by lentiviral transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular calcium ([Ca2+]i) levels and cell apoptosis. E-cadherin and β-catenin expression and complex formation at the membrane were increased in CaSR-OV Ishikawa cells relative to control Ishikawa cells (vector). Furthermore, CaSR-OV Ishikawa cells showed a reduced invasive potential, which was attributed to E-cadherin/β-catenin complex formation. Moreover, a reduction in CaSR expression in endometrial cancer relative to normal specimens was evident by immunohistochemistry and was positively associated with E-cadherin, but not β-catenin, expression. Furthermore, VEGFR3 was significantly down-regulated in CaSR-OV Ishikawa cells. Additionally, an immunohistochemical analysis showed that VEGFR3 was significantly increased in endometrial cancer compared with the normal endometrium and was inversely correlated with CaSR expression. However, the CaSR knockdown produced the opposite effects. These findings suggest an inhibitory role for CaSR in endometrial cancer. Therefore, reduced CaSR expression may be a suitable explanation and valuable predictor for endometrial cancer progression.
Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation
Authors: Lambers Christopher , Roth Michael , Jaksch Peter , Muraközy Gabriella , Tamm Michael , Klepetko Walter , Ghanim Bahil , Zhao Feng
Published: January 2018

Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-β1, or the combination. Cells were pre-incubated (30 min) with either Treprostinil, forskolin, di-deoxyadenosine (DDA), or vehicle. Treprostinil time dependently activated cAMP thereby preventing PDGF-BB induced proliferation and TGF-β1 secretion. Cell counts indicated proliferation; α-smooth muscle actin (α-SMA) indicted differentiation, and collagen type-1 or fibronectin deposition remodeling. Myo-fibroblast indicating α-SMA expression was significantly reduced and its formation was altered by Treprostinil. Collagen type-I and fibronectin deposition were also reduced by Treprostinil. The effect of Treprostinil on collagen type-I deposition was cAMP sensitive as it was counteracted by DDA, while the effect on fibronectin was not cAMP mediated. Treprostinil antagonized the pro-fibrotic effects of both PDGF-BB and TGF-β1 in primary human lung fibroblasts. The data presented propose a therapeutic relevant anti-fibrotic effect of Treprostinil in IPF.
In vivo Microscopic Photoacoustic Spectroscopy for Non-Invasive Glucose Monitoring Invulnerable to Skin Secretion Products
Authors: Sim Joo Yong , Ahn Chang-Geun , Jeong Eun-Ju , Kim Bong Kyu
Published: January 2018

Photoacoustic spectroscopy has been shown to be a promising tool for non-invasive blood glucose monitoring. However, the repeatability of such a method is susceptible to changes in skin condition, which is dependent on hand washing and drying due to the high absorption of infrared excitation light to the skin secretion products or water. In this paper, we present a method to meet the challenges of mid-infrared photoacoustic spectroscopy for non-invasive glucose monitoring. By obtaining the microscopic spatial information of skin during the spectroscopy measurement, the skin region where the infrared spectra is insensitive to skin condition can be locally selected, which enables reliable prediction of the blood glucose level from the photoacoustic spectroscopy signals. Our raster-scan imaging showed that the skin condition for in vivo spectroscopic glucose monitoring had significant inhomogeneities and large variability in the probing area where the signal was acquired. However, the selective localization of the probing led to a reduction in the effects of variability due to the skin secretion product. Looking forward, this technology has broader applications not only in continuous glucose monitoring for diabetic patient care, but in forensic science, the diagnosis of malfunctioning sweat pores, and the discrimination of tumors extracted via biopsy.
3D Imaging through Scatterers with Interferenceless Optical System
Authors: Mukherjee Saswata , Vijayakumar A. , Kumar Manoj , Rosen Joseph
Published: January 2018

Imaging through a scattering medium is a challenging task. We propose and demonstrate an interferenceless incoherent opto-digital technique for 3D imaging through a scatterer with a single lens and a digital camera. The light diffracted from a point object is modulated by a scattering mask. The modulated wavefront is projected on an image sensor using a spherical lens and the impulse response is recorded. An object is placed at the same axial location as the point object and another intensity pattern is recorded with identical experimental conditions and with the same scattering mask. The image of the object is reconstructed by a cross-correlation between a reconstructing function and the object hologram. For 3D imaging, a library of reconstructing functions are created corresponding to different axial locations. The different planes of the object are reconstructed by a cross-correlation of the object hologram with the corresponding reconstructing functions.