bluuebunny/crossref_metadata_2025 huggingface dataset:
Tabulés dinantiens du Sud-Ouest du Portugal [Tabulate corals from the Dinantian of South-Western Portugal]
Authors: TOURNEUR Francis
Published: April 2020

A small fauna of Tabulate corals, collected in the Visean of South-Western Portugal (Carrapateira-Bordeira area), is systematically described. The genera Sutherlandia Cocke & Bowsher 1968, Smythina Weyer 1970 and Cladochonus McCoy 1847 are for the first time reported from the Dinantian of Portugal. A similar association is known from the Culm facies of England and Germany. That confirms the close affinities between these regions and Portugal in the early Carboniferous. The growth habits of the corals suggest that the community was living on a soft muddy bottom. A comparison is proposed with the classical Tabulate coral fauna of Basleo, in the Permian of Timor.
Inductively coupled plasma-mass spectrometric (ICP-MS) analysis of silicate rocks and minerals
Authors: VANDER AUWERA Jacqueline , BOLOGNE Guy , ROELANDTS Iwan , DUCHESNE Jean-Clair
Published: April 2020

The accurate measurement of low levels of trace elements is now necessary in most petrological studies. In this paper, we present the methods used in our laboratory ("Collectif interinstitutionnel de géochimie instrumentale") to analyse simultaneously, with the ICP-MS instrument, 26 trace elements in silicate rocks and minerals. Whole-rocks are prepared using a lithium metaborate fusion in order to assure dissolution of resistant mineral phases, whereas mineral separates (plagioclases, pyroxenes, apatites) are prepared using an open acid digestion. Calibration of the ICP-MS is made with international reference materials for whole-rocks and with synthetic aqueous solutions for mineral separates. The accuracy of the data as well as limits of quantification (LOQ) vary among elements but are usually very good (accuracy better than 6%, LOQ usually below 1 microg/g in solids). Combination of XRF and ICP-MS capabilities enables us to determine 38 elements (major and trace) on a routine basis.
Preface
Authors: Bultynck Pierre , Dejonghe Léon
Published: April 2020

The lithostratigraphic guide of Belgium is subdivided into ten chapters dealing respectively with Cambriam-Ordovician-Silurian formations, Devonian formations, Lower Carboniferous formations, Upper Carboniferous formations, Permian formations, Triassic and Jurassic formations, Cretaceous formations, Paleogene and Neogene formations, Quaternary formations. The different chapters have been prepared by the respective national stratigraphic subcommissions set up by the Belgian National Committee for Geological Sciences.
EAST JAVA ONLINE TRANSACTIONS: DEMAND SIDE ANALYSIS
Authors: Astuti Riska Dwi , Fazira Nadia
Published: April 2020

Despite the study of rapid growth of online-based transactions in East Java over the past few years, little is focused on the demand side in which consumer characteristics are crucial in this event. This study aims to analyze the relationship of consumer characteristics on the expansion of online-based transactions in East Java. Panel data consisting of 38 districts/cities in East Java province in the period 2015-2017 is analyzed using the random effects method. The results show that the increase of tertiary education participation has a significant positive effect on digital transactions both for goods/service transaction and the use of banking facilities. In addition, mobile phones ownership also has a significant positive role in improving online transactions for the sale and purchase of goods services through the internet. Share of non-food expenditure has a positive effect on online transactions, especially for financial transactions. On the other hand, the productive age population has a negative significant effect on online buying and selling activities. Health variable insignificantly affects online transactions since the activities of transactions through the internet can be done both in healthy and unhealthy conditions. Likewise with computer ownership that does not significantly affect online transactions because people tend to use mobile phones as the transaction device. Level of expenditure does not affect online transactions because online transactions have become the lifestyle in this digital era. Thus, the internet-based transaction is no longer influenced by economic conditions. Keywords: Transactions, Online, Random Effects, Consumers. JEL: G230, G400, O330
A New Cationic Polymer System That Improves Acid Diversion in Heterogeneous Carbonate Reservoirs
Authors: Sarmah Abhishek , Ibrahim Ahmed Farid , Nasr-El-Din Hisham , Jackson Jennifer
Published: April 2020

In-situ gelled acids are used for acid diversion in heterogeneous carbonate reservoirs. However, most of the gelled systems are based on anionic polymers that are difficult to clean up after the acid treatments. Residual polymer deposition leads to formation damage by blocking pore throats in the matrix. This work evaluates a new cationic-polymer acid system with self-breaking ability for application as an acid diverter in carbonate reservoirs.

Experimental studies have been conducted to examine the rheological properties of these polymer-based acid systems. The apparent viscosities of the live and the partially neutralized acids at pH from 0 to 5 were measured against the shear rate (0 to 1000 s−1). The effects of salinity and temperature (80 to 250°F) on the rheological properties of the acid system were also studied. The viscoelastic properties of the gelled acid system were evaluated using an oscillatory rheometer. Dynamic sweep tests were used to determine the elastic (G′) and viscous (G″) moduli of the system. Single-coreflood experiments were conducted on Indiana limestone cores to study the nature of diversion caused by the polymer-acid system. The effect of permeability contrast on the process of diversion was investigated by conducting dual-coreflood experiments on Indiana limestone cores that had permeability contrasts of 1.5 to 20. Computed tomography (CT) scans were conducted to study wormhole propagation after acid injection for both single and dual cores.

The live acid system displayed a non-Newtonian shear-thinning behavior with the viscosity declining as temperature increased. For 5 wt% hydrochloric acid (HCl) and 20 gal/t polymer content at 10 s−1, the viscosity decreased from 230 to 40 cp as the temperature increased from 88 to 250°F. Acid-spending tests demonstrated that the acid generated a gel with improved viscosity of 260 cp (at 250°F and 10 s−1) after it reached a pH of 2. The highly viscous gel plugged the wormhole and forced the acid that followed to the next higher-permeability zone. The viscosity of the gel continued to increase until it broke down to 69 cp (at 250°F and 10 s−1) at a pH of 4.8, which indicates a self-breaking system and more thorough cleanup potential. Coreflood studies indicated that the wormhole and the diversion process are dependent on the temperature and the flow rate. There was no indication of any damage caused by the system. The injected acid pore volume to breakthrough (PVBT) decreased from 2.2 to 1.4 when the temperature increased from 150 to 250°F.

The strong elastic nature of the gel (G′ = 3.976 Pa at 1 Hz) formed by the partially neutralized acid system proves its suitability as a candidate for use as a diverting agent. This new acid-polymer system has significant promise for use in acid diversion to improve stimulation of carbonate reservoirs.
Predicting the potential distribution of the parasitic Cuscuta chinensis under global warming
Authors: Ren Zichun , Zagorchev Lyuben , Ma Junxia , Yan Ming , Li Junmin
Published: April 2020

Background: The climate is the dominant factor that affects the distribution of plants. Cuscuta chinensis is a stem holoparasitic plant without leaves or roots, which develops a haustorium and sucks nutrients from host plants. The potential distribution of the parasitic plant C. chinensis has not been predicted to date. This study used Maxent modeling to predict the potential global distribution of C. chinensis, based on the following six main bioclimatic variables: annual mean temperature, isothermality, temperature seasonality, precipitation seasonality, precipitation of the warmest quarter, and precipitation of the coldest quarter.Results: The optimal annual average temperature and isothermality of C. chinensis ranged from 4 to 37°C and less than 45, respectively, while the optimal temperature seasonality and precipitation seasonality ranged from 4000 to 25000 and from 50 to 130, respectively. The optimal precipitation of the warmest season ranged from 300 to 1000 mm and from 2500 to 3500 mm, while that of the coldest season was less than 20000 mm. In Asia, C. chinensis is mainly distributed at latitudes ranging from 20° N to 50° N. During three specific historical periods (last glacial maximum, mid-Holocene, and 1960–1990) the habitats suitable for C. chinensis were concentrated in the central, northern, southern, and eastern parts of China. From the last glacial maximum to the mid-Holocene, the total area with suitability of 0.5-1 increased by 0.0875 million km2; however, from the mid-Holocene to 1960–1990, the total area with suitability of 0.5-1 decreased by 0.0759 million km2. The simulation results of habitat suitability in the two representative concentration pathways (RCP) 2.6 (i.e., the low greenhouse gas emissions pathway) and 8.5 (i.e., the high greenhouse gas emissions pathway) indicate that the habitat suitability of C. chinensis decreased in response to the warming climate. Compared with RCP2.6, areas with averaged suitability and high suitability for survival (RCP8.5) decreased by 0.18 million km2.Conclusion: Suitable habitats of C. chinensis are situated in central, northern, southern, and eastern China. The habitat suitability of C. chinensis decreased in response to the warming climate. These results provide a reference for the management and control of C. chinensis.
Screening of organic micropollutants in raw and drinking water in the Yangtze River Delta, China
Authors: Ren Hanwei , Tröger Rikard , Ahrens Lutz , Wiberg Karin , Yin Daqiang
Published: April 2020

Background: The vast occurrence of organic micropollutants in surface waters has raised concerns about drinking water safety and public health. The Tai Hu Basin region in China, a typical developing and populous area, is facing the challenge of water pollution. To ensure drinking water safety, the knowledge on how treatment techniques and raw water quality affect the quality of finished water must be improved. The aim of the current study was to evaluate drinking water quality with respect to organic micropollutants and how the purity of finished water depends on source water contamination and drinking water treatment strategies. Five drinking water treatment plants (DWTPs), using three different source waters in the Tai Hu River Basin, (i) Yangtze River, (ii) Wetland River Network, and (iii) Lake Tai Hu, were studied by analyzing 291 micropollutants in raw and finished water. Results: Major differences in concentrations and composition profiles of organic micropollutants were observed between the source waters. Among the studied micropollutants, the dominating group was pesticides in the wetland river network and flame retardants in Yangtze. The total concentration of poly- and perfluoroalkyl substances (PFASs) in Tai Hu water was far higher than in other samples. In total, 51 compounds were detected in finished water, with an overall average total concentration of 730 ± 160 ng L-1. The removal efficiency of the detected compounds in the DWTPs averaged 24 ± 150 %, which highlights the major challenge for the DWTPs to remove emerging organic micropollutants through current treatment processes. Conclusions: Our study showed that if the source water contains high levels of PFASs and organophosphorus flame retardants, even advanced treatment procedures are inefficient in removing the micropollutants, and the finished drinking water may contain cumulative levels of organic micropollutants in the mg L-1 range. On the other hand, if pesticides and pharmaceuticals dominate, high overall treatment efficiencies may be obtained if using advanced treatment techniques. DWTPs are advised to use advanced treatment techniques or alternative water sources to guarantee the safety of drinking water. As surface water systems are highly impacted by upstream activities, efforts should also be made in the water sector for improved surface water quality.
Emerging high-risk ST101 and ST307 carbapenem-resistant Klebsiella pneumoniae clones from bloodstream infections in Southern Italy
Authors: Loconsole Daniela , Accogli Marisa , Lisa De Robertis Anna , Loredana Capozzi , Angelica Bianco , Anna Morea , Rosanna Mallamaci , Michele Quarto , Antonio Parisi , Chironna Maria
Published: April 2020

Background: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is an urgent public health issue in Italy. This pattern of resistance is due mainly to dissemination of carbapenemase genes. Molecular characterization of carbapenem-resistant Klebsiella pneumoniae (CR-KP) strains was performed over a three-year period. In-depth analysis was performed on a subset of emerging CR-KP ST101 and ST307 clones.Methods: A prospective study was performed on 691 patients with CR-KP bloodstream infections hospitalized in 19 hospitals located in three large provinces in Southern Italy. Carbapenemase genes were identified via genotyping methods. Multi-locus sequence typing (MLST) and Whole Genome Sequencing (WGS) were carried out on ST101 and ST307 isolates.Results: Among the CR-KP isolates, blaKPC was found in 95.6%, blaVIM was found in 3.5%, blaNDM was found in 0.1% and blaOXA-48 was found in 0.1%. The blaKPC-3 variant was identified in all 104 characterized KPC-KP isolates. MLST of 231 representative isolates revealed ST512 in 45.5%, ST101 in 20.3% and ST307 in 18.2% of the isolates. cgMLST of ST307 and ST101 isolates revealed presence of more than one beta-lactam resistance gene. Amino acid substitution in the chromosomal colistin-resistance gene pmrB was found in two ST101 isolates.Conclusions: ST512 is widespread in Southern Italy, but ST101 and ST307 are emerging since they were found in a significant proportion of cases. Aggressive infection control measures and a continuous monitoring of these high-risk clones are necessary to avoid rapid spread of CR-KP, especially in hospital settings.
Spinal cord stimulation for chronic intractable trunk or limb pain: study protocol for a Chinese multicenter randomized withdrawal trial (CITRIP study)
Authors: Lu Yang , Mao Peng , Wang Guihuai , Tao Wei , Xiong Donglin , Ma Ke , Li Rongchun , Feng Dan , Duan Wanru , Li Shun , Fu Zhijian , Feng Zhiying , Jin Yi , Wan Li , Lu Yan , Fan Bifa , Wang James Jin , Li Luming
Published: April 2020

Background: Although effective results of many studies support the use of spinal cord stimulation in the chronic pain patients, no randomized controlled trial has been undertaken in China to date. CITRIP is a multicenter, prospective, randomized, withdrawal study designed to evaluate the clinical effectiveness and safety of spinal cord stimulation plus remote programming management in patients with intractable trunk or limb pain.Method：Participants will be recruited in approximately 10 centers across China. Eligible participants with intractable trunk or limb and an average Visual Analog Scale (VAS) score ≥ 5 will undergo spinal cord stimulation test. Participants with VAS score reduction ≥ 50% could move forward to receive implantation of an implanted pulse generator. In the withdrawal period at 3-months follow-up visit, participants randomized to the experimental group (EG) will undergo continuous stimulation while ceasing the stimulation in the control group (CG). The outcome assessment will occur at baseline and at 1, 3 (pre and post randomization) and 6 months. The primary outcome is the difference of maximal visual analog scale (VAS) score between EG and CG in the withdrawal period compared with baseline before the withdrawal period. Additional outcomes include VAS score change at 1, 3 and 6-month follow-ups, responder rate (VAS score improving by 50%), achievement rate of a desirable pain state (VAS score ≤ 4), awake times during sleep, Beck Depression Inventory for depression evaluation, short-form 36 for quality of life evaluation, drug usage, satisfaction rating of the device. Adverse events will be collected. The primary analysis will follow the intention-to-treat principle. Discussion：The CITRIP study seeks to evaluate the effectiveness and safety of a randomized withdrawal trial of spinal cord stimulation for patients with intractable trunk or limb pain.Trial registration: NCT03858790, clinicaltrials.gov, registered on March 1st, 2019, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858790
Informal Support for People With Alzheimer’s Disease and Related Dementias in Rural Uganda: A Qualitative Study
Authors: Nankinga Pia Ngoma , Maling Samuel , Chemali Zeina , Wakida Edith , Obua Celestino , Okello Elialilia S
Published: April 2020

Background: The generation of people getting older has become a public health concern worldwide. People aged 65 and above are the most at risk for Alzheimer’s disease which is associated with physical and behavioral changes. This nurtures informal support needs for people living with dementia where their families together with other community members are the core providers of day to day care for them in the rural setting. Despite global concern around this issue, information is still lacking on informal support delivered to these people with dementia. Objective: Our study aimed at establishing the nature of informal support provided for people with dementia (PWDs) and its perceived usefulness in rural communities in South Western Uganda. Methods: This was a qualitative study that adopted a descriptive design and conducted among 22 caregivers and 8 opinion leaders in rural communities of Kabale, Mbarara and Ibanda districts in South Western Uganda. The study included dementia caregivers who had been in that role for a period of at least six months and opinion leaders in the community. We excluded trained health workers. Results: The study highlights important forms of informal support offered to PWDs such as support in activities of daily living, enabling access to medical attention, recovering misplaced items, provision of herbal remedy, informal counseling, and sourcing carers from other families to offer presence and support in the hope to impact positively on behavioral outbursts and the frustration of living with dementia.Conclusion: The study revealed various forms of informal support that are available for PWDs in South Western Uganda and stressed the role of caregivers and the perceived usefulness of the care provided.
Occurrence and multiple-level ecological risk assessment of pharmaceuticals and personal care products (PPCPs) in two shallow lakes of China
Authors: Liu Na , Jin Xiaowei , Yan Zheng , Luo Ying , Feng Chenglian , Fu Zhiyou , Tang Zhi , Wu Fengchang , Giesy John P.
Published: April 2020

Background: Management of pharmaceuticals and personal care products (PPCPs) in the environment has become a social issue. In the present study, concentrations of 140 PPCPs at 20 sites in Baiyangdian Lake and Tai Lake from 2016 to 2017 were analyzed by Ultra Performance Liquid Chromatography Mass Spectrometer (UPLC-MS). Risk quotients (RQ) were calculated for each detected chemical at all sites and prioritization indices (PI), based on maximum RQ, were calculated. To assess the risk of chemicals that identified high priority (PI>1), a more accurate method of joint probability curves (JPCs) was applied. Results: A total of 42 PPCPs were identified and quantified detected in the two lakes, with maximum concentrations ranged from 0.04 to 889 ng/L. Among these, seven PPCPs were identified as high or moderate risk pollutants for at least one site, 3 in Tai Lake and 5 in Baiyangdian Lake. Carbamazepine posed significant ecological risk at all 20 sites, such that more attention should be paid to that drug. Based on results of the JPCs, sulfamethoxazole, caffeine, diethyltoluamide, and carbamazepine were categorized as high or intermediate risks. Conclusion: Occurrences and distributions of PPCPs were different in the two lakes. Multiple-level risk assessment from simple to more complex was appropriate in chemical risk management.
Measuring Antibody Avidity to Plasmodium Falciparum Merozoite Antigens Using a Multiplex Immunoassay Approach
Authors: Taylor Diane Wallace , Bobbili Naveen , Kayatani Alexander K , Tassi-Yunga Samuel , Kidima Winifrida , Leke Rose FG
Published: April 2020

Background: Antibodies (Ab) play a significant role in immunity to Plasmodium falciparum malaria. Usually, following repeated exposure to pathogens, affinity maturation and clonal selection take place, resulting in increased antibody avidity. However, some studies suggest affinity maturation may not occur to malaria antigens in endemic areas. Information on development of antibody avidity is confusing and conflicting, in part, because different techniques have been used to measure avidity. Today, bead-based multiplex immunoassays (MIA) are routinely used to simultaneously quantitate antibody levels to multiple antigens. This study evaluated the feasibility of developing an avidity MIA with 5 merozoite antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3) that uses a single chaotropic concentration.Methods: The most common ELISA protocols that used the chaotropic reagents guanidine HCl (GdHCl), urea, and ammonium thiocyanate (NH4SCN) were adapted to a multiplex MIA format. Then, different concentrations of chaotropes and incubation times were compared and results were expressed as an Avidity Index (AI), i.e., percentage of antibody remaining bound in the presence of chaotrope. Experiments were conducted to i) identify the assay with the widest range of AI (discriminatory power), ii) determine the amount of chaotrope needed to release 50% of bound Ab using plasma from adults and infants, and iii) evaluate assay repeatability. Results: Overall, 4M GdHCl and 8M urea were weaker chaotropes than 3M NH4SCN. For example, they failed to release significant amounts of Ab bound to MSP1-42 in adult plasma samples; whereas, a range of AI values was obtained with NH4SCN. Titration of NH4SCN revealed that 2M NH4SCN gave the widest range of AI for the 5 antigens. Binding studies using plasma from 40 adults and 57 one-year old infants in Cameroon showed that 2.1M ± 0.32 (mean ± SD) NH4SCN (adults) and 1.8M ± 0.23M (infants) released 50% of bound Ab from the merozoite antigens. Conclusions: An avidity MIA is feasible for the 5 merozoite antigens that uses a single concentration (2M) of NH4SCN. The assay provides a simple method to quickly obtain information about Ab quantity and quality in the acquisition of immunity to malaria in endemic populations.
NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways
Authors: Cao Lin , Wang Xin , Yang Juhong , Guo Jia , Li Xiang , Yang Xiaomin , Tan Zengqi , Guan Feng
Published: April 2020

Background Neural cell adhesion molecule (NCAM), a common mammalian cell surface glycoprotein, is the major substrate of polysialic acid (polySia). Polysialylated NCAM occurs in many types of cancer, but rarely in normal adult tissues. Epithelial-mesenchymal transition (EMT) is an important process contributing to tumor metastasis. The functional role of NCAM hypersialylation in EMT is unclear. Method Expression of NCAM and polysialylated NCAM in breast cancer progression were evaluated by western blot (WB), immunohistochemistry, semi-quantitative PCR and immunoprecipitation (IP). Overexpression of NCAM-140 and ST8SiaII were performed to assess the functional role of NCAM hypersialylation by liposome transfection. Cell proliferation ability was investigated with MTT assay. Transwell and wound closure assay were conducted to evaluate cell migratory ability. Phagokinetic gold sol assay and cell adhesion assay were performed to assess cell motility ability and cell adhesion ability, respectively. Furthermore, WB and IP were used to reveal the activated signaling pathway. Results The present study indicates that NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways, based on the following observations: (i) NCAM and polysialylated NCAM were aberrantly regulated in breast cancer cells; (ii) NCAM and polysialylated NCAM expression were upregulated in normal breast epithelial cells undergoing EMT; (iii) NCAM overexpression induced EMT in breast epithelial cells; (iv) NCAM promoted cell proliferation and migration through activation of a β-catenin/slug signaling pathway; (v) modification of polySia attached to NCAM inhibited cell adhesion and promoted cell motility through activation of an EGFR/STAT3 pathway.Conclusion This study demonstrates that NCAM and polysialylated NCAM facilitate different signaling pathway and affect different cell behaviors. Switching between the NCAM-mediated pathways appeared to depend on polySia decoration.
Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum
Authors: Lu Lingxue , Mao Yufeng , Kou Mengyun , Cui Zhenzhen , Jin Biao , Chang Zhishuai , Wang Zhiwen , Ma Hongwu , Chen Tao
Published: April 2020

Background: Acetoin, especially the optically pure (3S)- or (3R)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the production of optically pure acetoin enantiomers are rarely reported. Previously, we systematically engineered the GRAS microorganism Corynebacterium glutamicum to efficiently produce (3R)-acetoin from glucose. Nevertheless, its yield and average productivity were still unsatisfactory for industrial bioprocesses.Results: In this study, cellular carbon fluxes in the acetoin producer CGR6 were further redirected toward acetoin synthesis using several metabolic engineering strategies, including blocking anaplerotic pathways, attenuating key genes of the TCA cycle and integrating additional copies of the alsSD operon into the genome. Among them, the combination of attenuation of citrate synthase and inactivation of phosphoenolpyruvate carboxylase showed a significant synergistic effect on acetoin production. Finally, the optimal engineered strain CGS11 produced a titer of 102.45 g/L acetoin with a yield of 0.419 g/g glucose at a rate of 1.86 g/L/h in a 5 L fermenter. The optical purity of the resulting (3R)-acetoin surpassed 95%.Conclusion: To the best of our knowledge, this is the highest titer of highly enantiomerically enriched (3R)-acetoin, together with a competitive product yield and productivity, achieved in a simple, green processes without expensive additives or substrates. This process therefore opens the possibility to achieve easy, efficient, economical and environmentally-friendly production of (3R)-acetoin via microbial fermentation in the near future.
A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits
Authors: xie xiaohui , Zu Meidan , Zhang Long , Bai Tongjian , Wei Ling , Huang Wanling , JI Gong-Jun , Qiu Bensheng , Hu Panpan , Tian Yanghua , Wang Kai
Published: April 2020

Background: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Methods: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image（rs-fMRI）. The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). Results: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype.Conclusion: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.
Dynamic alterations of genome and transcriptome in KRAS G13D mutant CRC PDX model treated with cetuximab.
Authors: zhang hangyu , yuan liyun , liu lulu , yan cong , cheng jinming , fu qihan , tong zhou , jiang weiqin , zheng yi , zhao peng , zhang guoqing , fang weijia
Published: April 2020

Background: KRAS mutations have been characterized as the major predictive biomarkers for resistance to cetuximab treatment. However, studies indicate that not all KRAS mutations are associated with equivalent treatment outcomes. KRAS G13D mutations were observed to account for approximately 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients can benefit from cetuximab has not been determined.Methods: An established KRAS G13D mutant colorectal cancer (CRC) patient-derived xenograft (PDX) model was treated with cetuximab. After repeated use of cetuximab, treatment-resistant PDX models were established. Tissue samples were collected before and during treatment, and multiomics data were subsequently sequenced and processed, including whole-exome, mRNA and miRNA data, to explore potential dynamic changes.Results: Cetuximab treatment initially slowed tumor growth, but resistance developed not long after treatment. WES (whole-exome sequencing) and RNA sequencing found that 145 genes had low P values (< 0.01) when analyzed between the locus genotype and its related gene expression level. Among these genes, SWAP70 was believed to be a probable cause of acquired resistance. JAK2, PRKAA1, FGFR2 and RALBP1, as well as 10 filtered immune-related genes, also exhibited dynamic changes during the treatment.Conclusions: Cetuximab may be effective in KRAS G13D mutation patients. Dynamic changes in transcription, as determined by WES and RNA sequencing, occurred after repeated drug exposure, and these changes were believed to be the most likely cause of drug resistance.
A Geriatric Core Curriculum for Undergraduate Dental Students
Authors: Stuck Anna K. , Schimmel Martin
Published: April 2020

BackgroundIt is well-accepted that graduating dentists require geriatric competencies to ensure proper treatment of their elderly patients. Nevertheless, geriatric competencies in a curriculum for undergraduate dental students are often not adequately addressed. Thus, the purpose is to develop an efficient teaching model covering geriatric competencies in a dedicated geriatric core curriculum instructed by a geriatrician.MethodsTo design and develop a geriatric core curriculum, we selected domains based on clinical relevance for dental practice and specified learning objectives, aligning them to discrete competency levels. We used a case-based approach and developed real patient and/or clinical practice scenarios to elaborate the geriatric domains. In a pilot study, we implemented this geriatric core curriculum. Student satisfaction was evaluated using a feedback survey.ResultsOur geriatric core curriculum was successfully implemented for undergraduate dental students in this pilot study. Detailed learning objectives for each domain aligned to corresponding competency levels are described. Clinical practice scenarios for the case-based approach are matched to corresponding domains. Overall, the majority of students rated the domains of polypharmacy (93%), pain (71%), and decision-making capacity (57%) as highly relevant for their future clinical practice. Nevertheless, we encountered several challenges in this pilot study, namely low attendance and a suboptimal learning setting.ConclusionWe conclude that this pilot geriatric core curriculum proves to be largely feasible and serves as an educational template.
Inhibition of autophagy enhanced chemosensitivity in cisplatin resistant hypopharyngeal squamous carcinoma cells
Authors: dong pin , Zhang Jia , Mao Wei , Liu Yuying , Ding Jian , Wang Jie , Yu Ziwei , Huang Ruo fei , Yang Sen , Sun Ying
Published: April 2020

Background: Hypopharyngeal carcinoma is characterized by high degree of malignancy. The most common pathological type is squamous cell carcinoma (HSCC). It has been confirmed that high autophagy level promotes the development of hypopharyngeal cancer in recent years. Clinical researches have reported that high autophagy level often caused insensitivity to chemotherapy, a common phenomenon that greatly reduces therapeutic effect in cisplatin-resistant tumor cell lines. Therefore, exploring internal mechanisms of autophagy on cisplatin resistant HSCC is necessary for founding theoretical basis for synergistic antitumor drugs by interfering with autophagy.Methods: Part I: Cisplatin-resistant FaDu cell line was established and cultured. Cell counting kit-8 was used to detect drug resistance. Inverted microscope was used to observe the morphological changes at different concentrations, then the survival rate was calculated. After MDC staining, the autophagic vacuoles were observed by fluorescence microscopy. The expression of Beclin1 from each group was confirmed by RT-PCR and Western blot method. Part II: Beclin1 was knocked down by plasmid transfection, autophagy inhibitor 3-MA was applied for cisplatin-resistant cells intervention. Cell cycle was detected using flow cytometry assay, apoptosis with necrosis was detected by staining with propidium iodide (PI). CCK-8 was used to observe the cell survival rate in each group. The expression of autophagy-related gene Beclin1,LC3I,LC3II,Atg-5 and P62 in each group was verified by Western blot analysis.Results: Cisplatin-resistant FaDu cell line can be stably constructed by cisplatin intervention. Compared with normal group, autophagy and its related protein Beclin1 expression was enhanced in cisplatin resistant FaDu cells. Autophagy inhibition group showed significant cell cycle changes, mainly manifested by G1 arrest, increased apoptosis rate and significantly decreased survival rate at 24h level. Furthermore, Western blot showed that expression of Beclin1, lc3i, lc3ii, atg-5 protein decreased significantly after the inhibitor used, while the expression of p62 up-regulated, which also confirmed autophagy flow was blocked.Conclusion: Our work confirmed high autophagy level is important for the cisplatin-resistance of HSCC and insensitivity to chemotherapy. The use of 3-MA and Beclin 1 inhibition can significantly reduce autophagy level of cisplatin-resistant FaDu cells, arresting its cell cycle, promote apoptosis and reverse the multidrug resistance condition. These results provide the experimental basis for overcoming multidrug resistance through combination chemotherapy.#These authors contributed equally to this work.
Influence of automated visual field testing on intraocular pressure
Authors: Bertaud Samuel , Borowski Elisabeth Skarbek , Abbas Rachid , Baudouin Christophe , Labbé Antoine
Published: April 2020

Background
To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma.
Methods
We conducted a prospective observational study from October 2015 to July 2016 at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT with reliable standard automated perimetry (SAP) were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 minutes before and after VF testing. Subanalyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations.
Results
There was no significant change in IOP after VF testing, with IOP’s 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R²=0.12), whether based on duration of the VF test (P = 0.18) or the MD (P = 0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (p = 0.36), chronic angle closure glaucoma (P = 0.85) and OHT (P = 0.42). The subgroup of patients with an IOP elevation > 2 mmHg had a significantly higher SAP test duration (P = 0.002).
Conclusion
VF testing by SAP does not influence IOP as measured with a non-contact tonometer.
Antibiotics Prescription for Febrile Outpatients: A Health Facility-Based Secondary Data Analysis for the Greater Accra region of Ghana
Authors: Opoku Michael Mireku , Bonful Harriet Affran , Koram Kwadwo A.
Published: April 2020

Background Misguided prescription of antibiotics is an important facilitator of the emergence and spread of antibiotic resistance. In the absence of the implementation of effective interventions to control antibiotic use, its consumption may increase out of proportion to requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the proper use of antibiotics. The objective of this study was to determine the factors associated with antibiotics prescription to febrile outpatients who seek care in health facilities within the Greater Accra region of Ghana.Methods Secondary data obtained from a review of medical records of 2,519 febrile patients at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2016 were used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations (blood film microscopy, malaria rapid diagnostic test, full blood count, urine and stool routine examinations), diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotics prescription.Results The prevalence of antibiotics prescription was 70.1% (95% CI: 67.7–72.4). Prescribers with more years of practice (> 5 years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (p < 0.001). Integrated Management of Neonatal and Childhood Illnesses (IMNCI) training was associated with a 2.3 (95% CI: 1.54, 3.53, p < 0.001) times higher odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to be prescribed antibiotics compared with those under 5 years (AOR = 0.40, 95% CI: 0.32, 0.51; p < 0.001). Patients referred for laboratory investigations were 29% less likely to be prescribed with antibiotics than those not referred. Presenting to the outpatient clinic with cough was associated with a 3.5 (95% CI: 2.54, 4.92) times higher odds of antibiotics prescribing.Conclusion Prescription of antibiotics to febrile outpatients was high. Promoting laboratory testing can potentially reduce irrational antibiotics prescribing. Prescribing antibiotics for children under five and the prescribing practices of prescribers with longer years of practice should be targeted with interventions to reduce high use of antibiotics.
Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections
Authors: Álvarez-Izquierdo María , Esteban J. Guillermo , Muñoz-Antoli Carla , Toledo Rafael
Published: April 2020

Background: Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been extensively used to investigate the factors that determine the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is critical for the development of resistance against E. caproni in mice. In fact, treatment of mice with recombinant IL-25 generates resistance against primary E. caproni infection. However, the mechanisms by which IL-25 induces resistance remain unknown.Methods: To study the mechanisms responsible for resistance elicited by IL-25, we analyze the ileal proteomic changes induced by IL-25 in mice and their potential role in resistance. To this purpose, we compare the protein expression profiles in the ileum of four experimental groups of mice: naïve controls; E. caproni-infected mice; rIL-25-treated mice; and rIL-25-treated mice exposed to E. caproni metacercariae.Results: Quantitative comparison by 2D-DIGE showed significant changes in a total of 41 spots. Forty of those spots validated protein spots were identified by mass spectrometry corresponding to 24 proteins.Conclusions: The analysis of our results indicates that resistance to infectiuon is associated with the maintenance of the intestinal epithelial homeostasis and the regulation of proliferation and cell death. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection and its transcendence in resistance.
NAMPT/SIRT2–mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells
Authors: Xu Yun , Nasri Masoud , Dannenmann Benjamin , Mir Perihan , Zahabi Azadeh , Welte Karl , Morishima Tatsuya , Skokowa Julia
Published: April 2020

Background: Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRTs pathway in the regulation of maintenance and differentiation of human induced pluripotent stem (iPS) cells is not fully elucidated. Methods: We evaluated the effects of specific inhibitors of NAMPT-, or SIRT2 on the pluripotency, proliferation, survival and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells. Results: We demonstrated that NAMPT is indispensable for the maintenance, survival and hematopoietic differentiation of induced pluripotent stem (iPS) cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affects hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system. Conclusions: Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.
Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis
Authors: Gäckler Anja , Schönermarck Ulf , Dobronravov Vladimir , Manna Gaetano La , Denker Andrew , Liu Peng , Vinogradova Maria , Yoon Sung-Soo , Praga Manuel
Published: April 2020

Background: Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum.Methods: This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 x 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. Results: Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1–45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred.Conclusions: Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. Clinical trial identifier: NCT02949128
Comparison of Body Mass Index (BMI) and fat percentage criteria classification of 7-13 year old rural boys in the Eastern Cape, South Africa
Authors: Gent Maya van , Pienaar Anita , Noorbhai Habib
Published: April 2020

Background:

The aim of this paper is to investigate whether BMI and fat percentage classification criteria, would classify a sample in similar criteria’s.
Methods:

A cross-sectional study with a stratified random sampling included 602 rural boys (7–13 years old). Fat percentage criteria classification and BMI was measured Maturity, age and peak height velocity (PHV) were indirectly determined. Statistical techniques included descriptive, Pearson product correlation, the Kappa agreement test and the McNemar’s test. The level of statistical significance was set at p ≤ 0.05.
Results:

All age groups presented statistically significant high correlations between BMI and fat percentage, and low to medium correlations between fat percentage and maturity age (MA). Measurement of agreement between BMI and fat percentage classifications showed poor to fair agreements for all age groups, with the exception of the eight-year old group which presented a moderate agreement.
Conclusion:

Classifications according to BMI and fat percentage, results in different classifications for the same population. Classifications for categorizing purpose should make use of adiposity rather than BMI, as it includes fat free mass within the assessment protocol.