bluuebunny/crossref_metadata_2025 huggingface dataset:
LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma
Authors: Jiang Wenjin , Cheng Xueling , Wang Tao , Song Xuepeng , Zheng Yanbo , Wang Ligang
Published: October 2019

Background

Hepatocellular carcinoma (HCC) has been recognized as a member of the most common human malignant tumors globally. According to multiple studies, long noncoding RNAs (lncRNAs) have been defined as vital regulators in tumor progression. Although previous studies have indicated that lncRNA long intergenic non‐protein coding RNA 467 (LINC00467) exerts oncogenic effect in tumorigenesis and the development of cancers, the specific function that LINC00467 induces in HCC remains obscure.

Methods

LINC00467 expression was examined by a quantitative reverse transcriptase‐polymerase chain reaction. CCK‐8, EdU, transwell, western blotting and caspase‐3 activity analyses were utilized to testify the role of LINC00467 in HCC. The interaction between IGF2BP3 and LINC00467 (or TRAF5) was investigated by luciferase reporter, RIP and RNA pull‐down assays.

Results

LINC00467 upregulation in HCC tissues and cells was observed. LINC00467 silencing suppressed cell proliferation and metastasis, whereas it facilitated cell apoptosis in HCC. The gene for tumor necrosis factor receptor‐associated factor 5 (TRAF5) was a neighboring gene of that for LINC00467 and its expression was positively modulated by LINC00467 in HCC. TRAF5 knockdown inhibited HCC progression. LINC00467 deficiency could decrease the mRNA stability of TRAF5 in HCC. Insulin‐like growth factor‐2 messenger RNA‐binding protein 3 (IGF2BP3) could bind with LINC00467 and its depletion could lower TRAF5 mRNA stability in HCC. Final rescue assays further indicated that downregulation of IGF2BP3 or TRAF5 acted against LINC00467 upregulation‐mediated function on HCC progression.

Conclusions

LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in HCC.
THUMP domain containing 2 protein possibly induces resistance to cisplatin and 5‐fluorouracil in in vitro human esophageal squamous cell carcinoma cells as revealed by transposon activation mutagenesis
Authors: Hayashi Masato , Kawakubo Hirofumi , Fukuda Kazumasa , Mayanagi Shuhei , Nakamura Rieko , Suda Koichi , Hayashida Testu , Wada Norihito , Kitagawa Yuko
Published: October 2019

Background

Although chemotherapy is a core treatment for esophageal cancer, some patients develop drug resistance. Gene screening with transposons (i.e. mobile genetic elements) is a novel procedure for identifying chemotherapy‐resistant genes. Transposon insertion can randomly affect nearby gene expression. By identifying the affected genes, candidate genes can be found. The present study aimed to identify cisplatin (CDDP)/5‐fluorouracil (5‐FU)‐resistant genes in in vitro human esophageal squamous cell carcinoma with transposons.

Methods

After establishing transposon‐tagged cells, we obtained CDDP/5‐FU‐resistant colonies. A polymerase chain reaction and sequencing were used to identify the transposon inserted site and candidate CDDP/5‐FU resistant genes. Focusing on one candidate gene, we confirmed CDDP/5‐FU resistance by comparing the IC50 between drug‐resistant and wild‐type cells. Furthermore, we investigated gene expression by a real‐time polymerase chain reaction. Finally, we mediated the candidate gene level with small interfering RNA to confirm the resistance.

Results

Thirty‐nine candidate genes for CDDP/5‐FU resistance were identified. Nineteen were for CDDP resistance and 27 were for 5‐FU resistance. Seven genes, THUMP domain‐containing protein 2 (THUMPD2), nuclear factor interleukin‐3‐regulated protein (NFIL3), tyrosine‐protein kinase transmembrane receptor 2 (ROR2), C‐X‐C chemokine receptor type 4 (CXCR4), thrombospondin type‐1 domain‐containing protein 2 (THSD7B) alpha‐parvin (PARVA) and TEA domain transcription factor 1 (TEAD1), were detected as candidate genes in both colonies. Regarding THUMPD2, its expression was downregulated and knocking down THUMPD2 suggested drug resistance in both drugs.

Conclusions

Thirty‐nine candidate genes were identified with transposons. The downregulation of THUMPD2 was suggested to play a role in multidrug resistance in in vitro esophageal squamous cell carcinoma.
Obesity and tooth wear among American adults: the role of sugar-sweetened acidic drinks
Authors: Kamal Yousaf , O’Toole Saoirse , Bernabé Eduardo
Published: October 2019

Background

To explore the association between obesity and tooth wear among American adults and the role of sugar-sweetened acidic drinks consumption in explaining that association.

Methods

We analyzed data from 3541 adult participants in the National Health and Nutrition Examination Survey. Obesity was determined using the body mass index and tooth wear was assessed using the modified tooth wear index. Daily intake of four categories of drinks was estimated as the average (drinks/day) of two consecutive 24-h dietary recalls. The association between obesity and number of surfaces with moderate-to-severe tooth wear was assessed in hurdle models adjusting for sociodemographic factors, acid reflux medication, and dental insurance.

Results

Overweight and obese adults had more surfaces with moderate-to-severe tooth wear than those with normal body size, after adjusting for confounders. The consumption of sugar-sweetened acidic drinks explained part, but not all the above association. More specifically, the estimate for obesity was fully attenuated, whereas the estimate for overweight was slightly attenuated but remained significant.

Conclusion

Obesity was positively associated with tooth wear in American adults. This association was only partially accounted for by the consumption of sugar-sweetened acidic drinks, a common risk factor for both conditions.

Practical implications

Dentists must be aware of the health consequences of sugar-sweetened acidic drinks and advocate for reduction in consumption and/or substitution with healthier alternatives.
Bioethanol Production from UK Seaweeds: Investigating Variable Pre-treatment and Enzyme Hydrolysis Parameters
Authors: Kostas Emily T. , White Daniel A. , Cook David J.
Published: October 2019

This study describes the method development for bioethanol production from three species of seaweed.Laminaria digitata,Ulva lactucaand for the first timeDilsea carnosawere used as representatives of brown, green and red species of seaweed, respectively. Acid thermo-chemical and entirely aqueous (water) based pre-treatments were evaluated, using a range of sulphuric acid concentrations (0.125–2.5 M) and solids loading contents (5–25 % [w/v]; biomass: reactant) and different reaction times (5–30 min), with the aim of maximising the release of glucose following enzyme hydrolysis. A pre-treatment step for each of the three seaweeds was required and pre-treatment conditions were found to be specific to each seaweed species.Dilsea carnosaandU. lactucawere more suited with an aqueous (water-based) pre-treatment (yielding 125.0 and 360.0 mg of glucose/g of pre-treated seaweed, respectively), yet interestingly non pre-treatedD. carnosayielded 106.4 g g−1glucose.Laminaria digitatarequired a dilute acid thermo-chemical pre-treatment in order to liberate maximal glucose yields (218.9 mg glucose/g pre-treated seaweed). Fermentations withS. cerevisiaeNCYC2592 of the generated hydrolysates gave ethanol yields of 5.4 g L−1, 7.8 g L−1and 3.2 g L−1fromD. carnosa,U. lactucaandL. digitata, respectively. This study highlighted that entirely aqueous based pre-treatments are effective for seaweed biomass, yet bioethanol production alone may not make such bio-processes economically viable at large scale.
Mineral chemistry and formation conditions of calc-silicate minerals of Qozlou Fe skarn deposit, Zanjan Province, NW Iran
Authors: Mokhtari Mir Ali Asghar , Kouhestani Hossein , Gholizadeh Kazem
Published: October 2019

The Qozlou Fe skarn deposit is located at the Abhar–Mahneshan belt of the Central Iranian Zone. It is associated with Upper Eocene porphyritic granite that intruded into the Upper Cretaceous impure carbonaceous rocks. The Qozlou granite has high-K calc-alkaline affinity and is classified as subduction-related metaluminous I-type granitoids. Skarn aureole in the Qozlou is composed of endoskarn and exoskarn zones, with the exoskarn zone being the main skarn and mineralized zone. It includes garnet skarn, garnet-pyroxene skarn, pyroxene skarn, epidote skarn, and pyroxene-bearing marble sub-zones. The Qozlou Fe deposit is 300 m long and 5–30 m wide. Magnetite is the main ore mineral associated to pyrite, chalcopyrite, and pyrrhotite. Garnet, clinopyroxene, actinolite, epidote, calcite, and quartz occur as gangue minerals. Covellite, hematite, and goethite were formed during the supergene processes. The ore and gangue minerals have massive, banded, disseminated, brecciated, vein–veinlets, replacement, and relict textures. EPMA data indicate that garnets have andradite–grossularite compositions (Ad39.97–100–Gr0–49.62) and clinopyroxenes have diopsidic composition (En29.43–42.5–Fs14.31–20.99–Wo43.08–50.17). Based on mineralogical and textural criteria, skarnification processes in the Qozlou skarn can be categorized into three discrete stages: (1) isochemical (metamorphic–bimetasomatic), (2) metasomatic prograde, and (3) metasomatic retrograde. Anhydrous calc-silicate minerals (garnet and clinopyroxene) were formed during the prograde metasomatic stage, while ore minerals and hydrous calc-silicate minerals were formed during the retrograde ore-forming sub-stage. Temperature and ƒO2conditions range between 430 and 550 °C and 10−26and 10−23, respectively, for the metasomatic prograde stage. The retrograde metasomatizing fluids had likely ƒS2= 10−6.5and temperatures < 430 °C at the beginning of the ore-forming sub-stage.
Pneumatosis cystoides intestinalis – an incidental finding with unpredictable evolution
Authors: Santos Marisa D. , Silva Cláudio , Silva Ana Cristina , Salgado Marta , França Manuela
Published: October 2019

Pneumatosis cystoides intestinalis is an uncommon disease with unknown etiology characterized by the presence of multiple gas-filled cysts within the submucosa or subserosa of the intestinal wall. Pneumoperitoneum and/or intestinal perforation are complications that may be associated with pneumatosis cystoides intestinalis. The patients are often prone to misdiagnosis or mistreatment.

We are presenting a case of pneumatosis cystoides intestinalis in a 42 year-old woman affected by peritoneal free air and numerous, diffuse, bubble-like intramural gas collections into the jejunum and ileum, showed in CT-enterography images. The woman had a carcinoid tumor located in jejunum two years ago, treated with enterectomy. Recent complaints of nonspecific symptoms of abdominal discomfort and diarrhea motivated the realization of CT scan, serum chromogranin and urine 5-hidroxindolacetic acid for hypothesis of tumor carcinoid recurrence withdraw. The only change found was the presence of pneumatosis cystoides intestinalis in CT-enterography images without intestinal necrosis, bleeding or evident obstruction. For that reason no surgical procedure was realized and the patient stayed on surveillance. Actually, the patient complaints are sporadic abdominal discomfort, without pneumatosis cystoides intestinalis clinical evidence.

Conclusion The treatment plan of patient with PCI depends on underlying cause and clinical condition severity. When conservative treatment is adopted the clinical evolution of pneumatosis cystoides intestinalis is unpredictable and can even disappear in an indeterminate number of patients.
Clinic-pathological aspect of gastro-intestinal stromal tumors at tertiary care Hospital India
Authors: Subramanian Sankar , Sandhu Amamndeep Sing , Balu Jagan , Suresh P
Published: October 2019

Background This study defines the disease profile in south Indian population and determine the clinic-pathological aspects of Gastro-Intestinal Stromal Tumors.

Method In this prospective study patients diagnosed of gastrointestinal stromal tumors were taken thorough clinical examination and a database of Anthropometric details and clinical details were analyzed. Pathological data included tumor size, presence or absence necrosis, mitotic counts, immunohistochemistry for CD-117, CD-34.

Results There were 44 patients with confirmed diagnosis of gastro-intestinal stromal tumor. The highest incidence was found in the 6th decade. The most common symptoms were abdominal pain and gastrointestinal bleed. Stomach was most frequent site for gastro-intestinal stromal tumors. Immunochemistry for CD-117 was positive in 93.18% cases. Majority of tumors (79.5%) had pure spindle cell morphology and mitotic activity showed that 34% of the GISTs were of the high risk group. Forty two patients were suggestive of surgery as the primary treatment after presentation.

Conclusion Abdominal pain was the most common presenting complaint. Majority of the tumors aroused from the stomach. The majority of the tumors had pure spindle cell morphology and 93% of the tumors were CD-117 positive. A significant relationship between tumor size, tumor necrosis and mitotic activity with large tumors having necrosis and high mitotic rate having high risk of malignancy, was observed. Surgical resection is considered mainstay of treatment of gastro-intestinal stromal tumor. Imatinib therapy should be given to patients in moderate to severe risk categories.
Observed and Modeled Seasonal Air Quality and Respiratory Health in Senegal During 2015 and 2016
Authors: Toure Nafissatou Oumar , Gueye Ndeye Ramatoulaye Diagne , Mbow‐Diokhane Aminata , Jenkins Gregory S. , Li Maggie , Drame Mamadou S. , Coker Karen Adjoa Ronke , Thiam Khady
Published: October 2019

In this work, we use existing particulate matter (PM) data from Dakar, Senegal, satellite aerosol optical depth (AOD) and the Weather Research and Forecasting (WRF) model to evaluate the role of dust transport from the Sahara and PM concentrations and exposure into other administrative districts of Senegal during 2015 and 2016. We also use data from the Ministry of Health to examine spatial and temporal patterns of acute respiratory infections, asthma, bronchitis, and tuberculosis across Senegal with an emphasis on Northern Hemisphere winter December–February, when air quality is poor, and June–August when there is an improvement in air quality. Measurements in Dakar, Senegal, suggest hazardous PM10 concentrations associated with Saharan dust storms but lower PM10 concentrations during the summer. The WRF dust simulations show a similar temporal pattern to the observations in Dakar, Senegal, with notable biases. However, the WRF model suggests that the highest dust concentrations are found across the northern half of Senegal during the winter season where there are no currently PM measurements. Health data during 2015–2016 show the highest prevalence of asthma and bronchitis in Dakar, Senegal, suggesting that other sources of air pollution are important. Acute respiratory infection is prevalent throughout the country with the high prevalence found in rural zones, for children between 12 and 59 months. All measures including real‐time monitoring, air quality forecast, and communication should be used to protect the public from potentially hazardous environmental conditions during the winter season.
Oil Spills and Human Health: Contributions of the Gulf of Mexico Research Initiative
Authors: Eklund Ruth L. , Knapp Landon C. , Sandifer Paul A. , Colwell Rita C.
Published: October 2019

The Gulf of Mexico Research Initiative (GoMRI) was established in 2010 with $500 million in funding provided by British Petroleum over a 10‐year period to support research on the impacts of the Deepwater Horizon oil spill and recovery. Contributions of the GoMRI program to date focused on human health are presented in more than 32 peer‐reviewed papers published between 2011 and May 2019. Primary findings from review of these papers are (i) the large quantity of dispersants used in the oil cleanup have been associated with human health concerns, including through obesogenicity, toxicity, and illnesses from aerosolization of the agents; (ii) oil contamination has been associated with potential for increases in harmful algal blooms and numbers of pathogenic Vibrio bacteria in oil‐impacted waters; and (iii) members of Gulf communities who are heavily reliant upon natural resources for their livelihoods were found to be vulnerable to high levels of life disruptions and institutional distrust. Positive correlations include a finding that a high level of community attachment was beneficial for recovery. Actions taken to improve disaster response and reduce stress‐associated health effects could lessen negative impacts of similar disasters in the future. Furthermore, GoMRI has supported annual conferences beginning in 2013 at which informative human health‐related presentations have been made. Based on this review, it is recommended that the Oil Pollution Act of 1990 be updated to include enhanced funding for oil spill impacts to human health.
Metabolites in visceral fat: useful signals of metabolic syndrome?
Authors: Galavotti Sara , Gescher Andreas J. , Rufini Alessandro
Published: October 2019

Metabolic syndrome comprises a series of health conditions, such as increased blood pressure, high blood sugar, excess abdominal fat, and altered circulating cholesterol or triglyceride levels. A fast growing number of affected individuals are at an increased risk of heart disease, stroke and type-2 diabetes. Obesity, especially build-up of visceral fat, is a recognized major risk factor for the development of metabolic syndrome. However, our understanding of the mechanistic links and biomarkers that associate visceral fat with the development of conditions underlying metabolic syndrome is still inadequate. In a recent paper published in the Biochemical Journal [Biochem. J. (2018) 475, 1019–1035], Candi et al. address this lack of knowledge, performing high-throughput metabolomics analysis of visceral fat isolated from obese individuals, with and without metabolic syndrome, and non-obese healthy controls. The authors identify alterations in metabolic pathways that distinguish pathologically from healthy obese subjects. They identify metabolic cues that point to oxidative and inflammatory burden as the leitmotifs of metabolic syndrome. Of particular interest is the identification of increased metabolism of γ-glutamyl amino acids and plasmalogens in pathological obesity. γ-glutamyl amino acids, generated through the transfer of a γ-glutamyl moiety from glutathione to an amino acid acceptor, are involved in glutathione metabolism and the response to oxidative stress, whereas plasmalogens, a poorly studied class of phospholipids, are known contributors to insulin resistance and hypertension. Both classes of metabolites are intriguing candidate biomarkers that warrant further investigation.
Deciphering channel networks from aeromagnetic potential field data: the case of the North Sea Quaternary tunnel valleys
Authors: Brahimi S , Le Maire P , Ghienne J F , Munschy M
Published: October 2019

High-resolution magnetic data and potential field methods have been used to perform a detailed analysis of networks of late Quaternary subglacially-cut tunnel valleys (central Viking Graben, Norwegian sector of the North Sea). High-frequency, ribbon-like, sinuous, paired magnetic anomalies interpreted to be the signature of tunnel valleys are identified. Such magnetic anomalies have 1 to 8 nT amplitudes and reflect a magnetic susceptibility contrast between valley infills and the host sediments. Fractional vertical derivative and horizontal gradient transforms provide the best control on the accurately delineation of tunnel valleys by plotting automatically the extrema. The 2D forward modelling is a very effective approach to determinating the geometric parameters and magnetic susceptibility of the modeled valleys. It allows to determine the finite-width flat horizontal thin geometry as the most appropriate simple geometry to simulate the magnetic anomaly linked to a channel structure. The application of Euler deconvolution using complex algebra allows to substantiate the structural index (n = 1.5) for simple palaeovalley geometries and to determine fair valley depth estimates.
Opening the ‘implementation black-box’ of the user fee exemption policy for caesarean section in Benin: a realist evaluation
Authors: Dossou Jean-Paul , De Brouwere Vincent , Van Belle Sara , Marchal Bruno
Published: October 2019

To improve access to maternal health services, Benin introduced in 2009 a user fee exemption policy for caesarean sections. Similar to other low- and middle-income countries, its implementation showed mixed results. Our study aimed at understanding why and in which circumstances the implementation of this policy in hospitals succeeded or failed. We adopted the realist evaluation approach and tested the initial programme theory through a multiple embedded case study design. We selected two hospitals with contrastive outcomes. We used data from 52 semi-structured interviews, a patient exit survey, a costing study of caesarean section and an analysis of financial flows. In the analysis, we used the intervention-context-actor-mechanism-outcome configuration heuristic. We identified two main causal pathways. First, in the state-owned hospital, which has a public-oriented but administrative management system, and where citizens demand accountability through various channels, the implementation process was effective. In the non-state-owned hospital, managers were guided by organizational financial interests more than by the inherent social value of the policy, there was a perceived lack of enforcement and the implementation was poor. We found that trust, perceived coercion, adherence to policy goals, perceived financial incentives and fairness in their allocation drive compliance, persuasion, positive responses to incentives and self-efficacy at the operational level to generate the policy implementation outcomes. Compliance with the policy depended on enforcement by hierarchical authority and bottom-up pressure. Persuasion depended on the alignment of the policy with personal and organizational values. Incentives may determine the adoption if they influence the local stakeholder’s revenue are trustworthy and perceived as fairly allocated. Failure to anticipate the differential responses of implementers will prevent the proper implementation of user fee exemption policies and similar universal health coverage reforms.
Food insecurity and the extremes of childhood weight: defining windows of vulnerability
Authors: Zhu Yeyi , Mangini Lauren D , Hayward Mark D , Forman Michele R
Published: October 2019

Background

Weight extremes and food insecurity (FIS) represent public-health challenges, yet their associations in childhood remain unclear. We aimed to investigate the longitudinal time-specific relationship between FIS and risk of overweight/obesity and underweight in kindergarten through 8th grade.

Methods

In the prospective Early Childhood Longitudinal Study–Kindergarten Cohort (1998–2007) of 6368 children, household FIS was assessed by the validated US Household Food Security Survey Module in kindergarten, 3rd, 5th and 8th grades. Multivariable linear-regression and Poisson-regression models were computed.

Results

Compared with children experiencing food security (FS), children exposed to FIS in 5th grade had 0.19 [95% confidence interval (CI): 0.07–0.30] and 0.17 (0.06–0.27) higher body mass index z-score (BMIZ) in the 5th and 8th grades, respectively, whereas FIS in the 8th grade was associated with a 0.29 (0.19–0.40) higher BMIZ at the same wave, after adjusting for covariates and FIS at earlier waves. Children with FIS vs FS had 27% (relative risk: 1.27, 95% CI: 1.07–1.51), 21% (1.21, 1.08–1.35) and 28% (1.28, 1.07–1.53) higher risk of overweight/obesity in the 3rd, 5th and 8th grades, respectively, adjusting for covariates and FIS at prior wave(s). Children with FIS vs FS in kindergarten had a 2.76-fold (1.22–6.25) higher risk of underweight in the 8th grade.

Conclusions

Proximal exposure to household FIS was associated with a higher risk of overweight/obesity in the 3rd, 5th and 8th grades. FIS in kindergarten was associated with a risk of underweight in the 8th grade. Thus, FIS coexists in weight extremes during vulnerable early-life windows in the USA, similarly to the global burden of FIS.
On the Number of Products Which Form Perfect Powers and Discriminants of Multiquadratic Extensions
Authors: de la Bretèche Régis , Kurlberg Pär , Shparlinski Igor E
Published: October 2019

We study some counting questions concerning products of positive integers $u_1, \ldots , u_n$, which form a nonzero perfect square, or more generally, a perfect $k$-th power. We obtain an asymptotic formula for the number of such integers of bounded size and in particular improve and generalize a result of D. I. Tolev (2011). We also use similar ideas to count the discriminants of number fields that are multiquadratic extensions of ${\mathbb{Q}}$ and improve and generalize a result of N. Rome (2017).
Does High-Frequency Social Media Data Improve Forecasts of Low-Frequency Consumer Confidence Measures?
Authors: Lehrer Steven , Xie Tian , Zeng Tao
Published: October 2019

Social media data present challenges for forecasters since one must convert text into data and deal with issues related to these measures being collected at different frequencies and volumes than traditional financial data. In this article, we use a deep learning algorithm to measure sentiment within Twitter messages on an hourly basis and introduce a new method to undertake mixed data sampling (MIDAS) that allows for a weaker discounting of historical data that is well-suited for this new data source. To evaluate the performance of approach relative to alternative MIDAS strategies, we conduct an out of sample forecasting exercise for the consumer confidence index with both traditional econometric strategies and machine learning algorithms. Irrespective of the estimator used to conduct forecasts, our results show that (i) including consumer sentiment measures from Twitter greatly improves forecast accuracy and (ii) there are substantial gains from our proposed MIDAS procedure relative to common alternatives.
hypercalcaemia due to a calcitriol-producing neuroendocrine tumour
Authors: van Lierop Antoon H , Bisschop Peter H , Boelen Anita , van Eeden Susanne , Engelman Anton F , Nieveen van Dijkum Elisabeth J , Klümpen Heinz-Josef
Published: October 2019

In this case report, we describe a 40-year-old patient with a large grade 2 pancreatic neuroendocrine tumour (pNET) with spleen metastasis. Albeit radical resection, he developed liver metastasis after 2 years, for which he underwent radio frequency ablation and embolization, and was treated successfully with different subsequent lines of systemic therapy. Eight years after the initial diagnosis, he was admitted for symptomatic and refractory hypercalcaemia, due to calcitriol synthesis by the liver metastasis. After tumour load reduction by hemihepatectomy, there was an initial normalization of hypercalcaemia, until it recurred after 18 months. In this period, the liver metastasis had progressed despite chemo- and immunotherapy. Patient underwent an additional extend hemihepatectomy, from which he recovered well with normalization of calcium levels. This case illustrates the hormonal plasticity of pNETs and shows how prolonged survival can be achieved for metastatic pNET by multimodality approach.
Metal-enriched galaxies in the first ∼1 billion years: evidence of a smooth metallicity evolution at z ∼ 5
Authors: Poudel Suraj , Kulkarni Varsha P , Cashman Frances H , Frye Brenda , Péroux Céline , Rahmani Hadi , Quiret Samuel
Published: October 2019

We present seven new abundance measurements of the elements O, C, and Si at z > 4.5, doubling the existing sample of weakly depleted elements in gas-rich galaxies, in order to constrain the first ∼1 billion years of cosmic metal evolution. These measurements are based on quasar spectra of damped Lyman α absorbers (DLAs) and sub-DLAs obtained with the Magellan Inamori Kyocera Echelle (MIKE) and Magellan Echellette (MagE) spectrographs on Magellan-South, and the X-Shooter spectrograph on the Very Large Telescope. We combine these new measurements with those drawn from the literature to estimate the $N_{\rm H\, {\small I}}$-weighted binned mean metallicity of −1.51 ± 0.18 at z = 4.8. This metallicity value is in excellent agreement with the prediction from lower redshift DLAs, supporting the interpretation that the metallicity evolution is smooth at z ∼ 5, rather than showing a sudden decline at z > 4.7. Furthermore, the metallicity evolution trends for the DLAs and sub-DLAs are similar within our uncertainties. We also find that the [C/O] ratios for z ∼ 5 DLAs are consistent with those of the very metal-poor DLAs. Additionally, using [C/O] and [Si/O] to constrain the nucleosynthesis models, we estimate that the probability distributions of the progenitor star masses for three relatively metal-poor DLAs are centred around 12–17 M⊙. Finally, the z ∼ 5 absorbers show a different metallicity–velocity dispersion relation than lower redshift DLAs, suggesting that they may be tracing a different population of galaxies.
PPR20 Is Required for the cis-Splicing of Mitochondrial nad2 Intron 3 and Seed Development in Maize
Authors: Yang Yan-Zhuo , Ding Shuo , Wang Yong , Wang Hong-Chun , Liu Xin-Yuan , Sun Feng , Xu Chunhui , Liu Baohui , Tan Bao-Cai
Published: October 2019

Pentatricopeptide repeat (PPR) proteins are helical repeat RNA-binding proteins that function in RNA processing by conferring sequence-specific RNA-binding activity. Owing to the lethality of PPR mutants, functions of many PPR proteins remain obscure. In this study, we report the function of PPR20 in intron splicing in mitochondria and its role in maize seed development. PPR20 is a P-type PPR protein targeted to mitochondria. The ppr20 mutants display slow embryo and endosperm development. Null mutation of PPR20 severely reduces the cis-splicing of mitochondrial nad2 intron 3, resulting in reduction in the assembly and activity of mitochondrial complex I. The ppr20-35 allele with a Mu insertion in the N-terminal region shows a much weaker phenotype. Molecular analyses revealed that the mutant produces a truncated transcript, coding for PPR20ΔN120 lacking the N-terminal 120 amino acids. Subcellular localization revealed that PPR20ΔN120:GFP is able to target to mitochondria as well, suggesting the sequence diversity of the mitochondrial targeting peptides. Another mutant zm_mterf15 was also found to be impaired in the splicing of mitochondrial nad2 intron 3. Further analyses are required to identify the exact function of PPR20 and Zm_mTERF15 in the splicing of nad2 intron 3.
Trauma exposure, mental health and tobacco use among vulnerable Syrian refugee youth in Jordan
Authors: Kheirallah Khalid A , Cobb Caroline O , Alsulaiman Jomana W , Alzoubi Abdallah , Hoetger Cosima , Kliewer Wendy , Mzayek Fawaz
Published: October 2019

Background

Little is known about tobacco use among youth exposed to armed conflicts, or the influence of trauma on tobacco use in this context. This study examined patterns of smoking by tobacco product and gender among Syrian refugee youth living in host communities in Jordan and assessed the associations of post-traumatic stress disorder (PTSD) and depression symptoms, trauma exposure and social support with current smoking status in boys and girls.

Methods

Syrian refugee students (mean [standard deviation] age = 14.9 [1.33] years) were identified through the public school system. Data were collected using an online Arabic questionnaire that included questions about demographics, trauma exposure, current smoking (cigarette and waterpipe), PTSD, depression and perceived social support. Logistic regression was used to assess the adjusted effects of independent variables on current smoking status.

Results

One in 7 boys and one in 14 girls were current smokers, with boys reporting greater tobacco use than girls. Among boys, current smokers reported significantly higher family member loss and lower perceived family social support than nonsmokers; among girls, current smokers also reported significantly higher family member loss as well as greater PTSD symptoms and lower perceived significant other/special person social support.

Conclusions

Tobacco use is established among this vulnerable group. The findings highlight the potential role of psychosocial support for tobacco prevention and cessation strategies.
ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus
Authors: Parodis Ioannis , Gokaraju Sirisha , Zickert Agneta , Vanarsa Kamala , Zhang Ting , Habazi Deena , Botto João , Serdoura Alves Clara , Giannopoulos Panagiotis , Larsson Anders , Svenungsson Elisabet , Gunnarsson Iva , Mohan Chandra
Published: October 2019

Objectives

We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement.

Methods

Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine.

Results

U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A–C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A–D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome.

Conclusion

While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.
Management of rheumatic complications of immune checkpoint inhibitor therapy – an oncological perspective
Authors: Steven Neil M , Fisher Benjamin A
Published: October 2019

Immune checkpoint inhibitors (CPIs) are an effective treatment for many cancers but cause diverse immune-related adverse events (IrAEs). Rheumatological IrAEs include arthralgia, arthritis, tenosynovitis, myositis, polymyalgia rheumatica and sicca syndrome. CPI use can unmask RA as well as causing flares of prior autoimmune or connective tissue disease. Oncologists categorize and grade IrAEs using the Common Terminology Criteria for Adverse Events and manage them according to international guidelines. However, rheumatological events are unfamiliar territory: oncologists need to work with rheumatologists to elicit and assess symptoms, signs, results of imaging and autoantibody testing and to determine the use of steroids and DMARDs. Myositis may overlap with myasthenic crisis and myocarditis and can be life-threatening. Treatment should be offered on balance of risk and benefit, including whether to continue CPI treatment and recognizing the uncertainty over whether glucocorticoids and DMARDs might compromise cancer control.
Clinical and genetic features of Chinese adult patients with tumour necrosis factor receptor-associated periodic fever syndrome
Authors: Zhao Mengzhu , Luo Yi , Wu Di , Yang Yunjiao , Sun Yang , Wang Rongrong , Shen Min
Published: October 2019

Objectives

TNF receptor-associated periodic fever syndrome (TRAPS) is an autosomal dominant systemic autoinflammatory disease caused by mutations of TNF receptor superfamily member 1 A (TNFRSF1A) gene. TRAPS has hardly been reported in the Chinese population. We aimed to characterize the clinical and genetic features of Chinese adult patients with TRAPS.

Methods

Nine adult patients (≥16 years) were diagnosed during April 2015 to June 2019, at the Department of Rheumatology, Peking Union Medical College Hospital. Clinical and genetic features of these patients were evaluated and compared with those from Japan and Europe.

Results

The median age of disease onset was 3 (0.5–38.5) years old, and adult-onset was observed in two (22.2%) patients. The median time of diagnosis delay was 16.5 (1.5–50.5) years. One patient had a family history of TRAPS. The frequent symptoms were fever (nine, 100%), rash (seven, 77.8%), arthralgia/arthritis (five, 55.6%) and abdominal pain (five, 55.6%). Only two (22.2%) patients had periorbital oedema. Nine TNFRSF1A gene variants were detected, including C58R, G65E, F89L, C99G, V202G, V202D, c.769-23T>C, S290I and c.*64T>C. Rash was more frequently seen in Chinese than in Japanese and European patients, while chest pain and amyloidosis occurred less frequently.

Conclusion

This is the first and largest case series of TRAPS in Chinese adult patients. Two novel TNFRSF1A variants, S290I and V202G, have been identified. The different clinical manifestations of our patients compared with those from Japan and Europe might be related to their TNFRSF1A variants.
Identifying an accurate self‐reported screening tool for alcohol use disorder: evidence from a Swiss, male population‐based assessment
Authors: Baggio Stéphanie , Trächsel Bastien , Rousson Valentin , Rothen Stéphane , Studer Joseph , Marmet Simon , Heller Patrick , Sporkert Frank , Daeppen Jean‐Bernard , Gmel Gerhard , Iglesias Katia
Published: October 2019

Background and aims

Short screenings for alcohol use disorder (AUD) are crucial for public health purposes, but current self‐reported measures have several pitfalls and may be unreliable. The main aim of our study was to provide empirical evidence on the psychometric performance of self‐reports currently used. Our research questions were: compared with a gold standard clinical interview, how accurate are (1) self‐reported AUD, (2) self‐reported alcohol use over time and (3) biomarkers of alcohol use among Swiss men? Finally, we aimed to identify an alternative screening tool.

Design

A single‐center study with a cross‐sectional design and a stratified sample selection.

Setting

Lausanne University Hospital (Switzerland) from October 2017 to June 2018.

Participants

We selected participants from the French‐speaking participants of the ongoing Cohort Study on Substance Use and Risk Factors (n = 233). The sample included young men aged on average 27.0 years.

Measurements

We used the Diagnostic Interview for Genetic Studies as the gold standard for DSM‐5 AUD. The self‐reported measures included 11 criteria for AUD, nine alcohol‐related consequences, and previous 12 months’ alcohol use. We also assessed biomarkers of chronic excessive drinking (ethyl glucuronide and phosphatidylethanol).

Findings

None of the self‐reported measures/biomarkers taken alone displayed both sensitivity and specificity close to 100% with respect to the gold standard (e.g. self‐reported AUD: sensitivity = 92.3%, specificity = 45.8%). The best model combined eight self‐reported criteria of AUD and four alcohol‐related consequences. Using a cut‐off of three, this screening tool yielded acceptable sensitivity (83.3%) and specificity (78.7%).

Conclusions

Neither self‐reported alcohol use disorder nor heavy alcohol use appear to be adequate to screen for alcohol use disorder among young men from the Swiss population. The best screening alternative for alcohol use disorder among young Swiss men appears to be a combination of eight symptoms of alcohol use disorder and four alcohol‐related consequences.
Experimental manipulations of behavioral economic demand for addictive commodities: a meta‐analysis
Authors: Acuff Samuel F. , Amlung Michael , Dennhardt Ashley A. , MacKillop James , Murphy James G.
Published: October 2019

Background and Aims

Reinforcing value, an index of motivation for a drug, is commonly measured using behavioral economic purchase tasks. State‐oriented purchase tasks are sensitive to phasic manipulations, but with heterogeneous methods and findings. The aim of this meta‐analysis was to characterize the literature examining manipulations of reinforcing value, as measured by purchase tasks and multiple‐choice procedures, to inform etiological models and treatment approaches

Methods

A random‐effects meta‐analysis of published findings in peer‐reviewed articles. Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) protocol, studies were gathered through searches in PsycINFO and PubMed/MEDLINE (published 22 May 2018). Searches returned 34 unique studies (aggregate sample n = 2402; average sample size = 68.94) yielding 126 effect sizes. Measurements included change (i.e. Cohen's d) in six behavioral economic indices (intensity, breakpoint, Omax, Pmax, elasticity, cross‐over point) in relation to six experimental manipulations (cue exposure, stress/negative affect, reinforcer magnitude, pharmacotherapy, behavioral interventions, opportunity cost).

Results

Cue exposure (d range = 0.25–0.44, all Ps < 0.05) and reinforcer magnitude [d = 0.60; 95% confidence interval (CI) = 0.18, 1.01; P < 0.005] manipulations resulted in significant increases in behavioral economic demand across studies. Stress/negative affect manipulations also resulted in a small, significant increase in Omax (d = 0.18; 95% CI = 0.01, 0.34; P = 0.03); all other effect sizes for negative affect/stress were non‐significant, albeit similar in size (d range = 0.14–0.18). In contrast, pharmacotherapy (d range = −0.37 to −0.49; Ps < 0.04), behavioral intervention (d = −0.36 to −1.13) and external contingency (d = −1.42; CI = −2.30, −0.54; P = 0.002) manipulations resulted in a significant decrease in intensity. Moderators (substance type) explained some of the heterogeneity in findings across meta‐analyses.

Conclusions

In behavioral economic studies, purchase tasks and multiple‐choice procedures appear to provide indices that are sensitive to manipulations found to influence motivation to consume addictive substances in field experiments.
The association of the optimal bolus of dexmedetomidine with its favourable haemodynamic outcomes in adult surgical patients under general anaesthesia
Authors: Wang Cheng‐yu , Chen Fang , Wu Junzheng , Fu Shu‐ying , Xu Xi‐mou , Chen Jia , Jiang Yi‐fei , Lian Qingquan , Liu Hua‐cheng
Published: October 2019

Aims

Dexmedetomidine is highly specific α2‐adrenoceptor agonist. A single bolus of dexmedetomidine can achieve clinical therapeutic effect. Therefore, it is essential to know the safety margin between the clinical effectiveness dosages of dexmedetomidine and its side effect.

Methods

A total of 42 patients who underwent elective thyroidectomy were enrolled in this study. Dexmedetomidine was given as a single bolus injection 30 min towards the end of surgery. The up‐and‐down sequential schedule was used in this study. The starting dose of dexmedetomidine was set at 0.1 μg/kg in the first patient and the next patient would then receive a dose of dexmedetomidine decremented by 0.05 μg/kg if the prior patient's baseline heart rate (HR) had a decrease of ≥20% and/or mean arterial blood pressure (MAP) increase or decrease of ≥20%, otherwise, the following patient would receive an incremental 0.05 μg/kg dose of dexmedetomidine. The analytic techniques of linear, linear‐logarithmic, exponential regressions and centred isotonic regression were used to determine the ED50 of dexmedetomidine and the residual standard errors were calculated for the comparison of goodness of fit among the different models.

Results

The median (interquartile range [range]) lowest HR was 57 beats/min (53–63.3[46–76]) with an average HR decrease of 8.0 beats/min (5–13 [4 to 23]). The median (interquartile range [range]) highest MAP was 98 mmHg (91.8–105 [83–126]) with a MAP increase of 10.0 mmHg (6.8–18.0 [2–24]). The ED50 (95% confidence interval) from 4 different statistical approaches (linear, linear‐logarithmic, exponential regressions and centred isotonic regression) were 0.262 μg/kg (0.243, 0.306), 0.252 μg/kg (0.238, 0.307), 0.283 μg/kg (0.238, 0.307), and 0.278 μg/kg, respectively. Among the 4 models, the exponential regression had the least residual standard error (0.03618).

Conclusion

The ED50 derived from 4 statistical models for an intravenous bolus of dexmedetomidine without significant haemodynamic effects was distributed in a narrow range of 0.252–0.283 μg/kg, and the exponential regression was the model to best match the study data.
Using GRADE methodology to assess innovation of new medicinal products in Italy
Authors: Fortinguerra Filomena , Tafuri Giovanni , Trotta Francesco , Addis Antonio
Published: October 2019

Aim

In April 2017 the Italian Medicine Agency (AIFA) developed new criteria to grant any new medicinal product with an innovative designation. The aim of this study is to describe this new model and how it works.

Methods

A retrospective descriptive analysis was performed on the results of the assessment process of innovativeness of new medicinal products (or therapeutic indications) based on the AIFA's new innovation criteria (therapeutic need, added therapeutic value and quality of clinical evidence through GRADE methodology) carried out between April 2017 and February 2019 and made publicly available on the AIFA website starting from January 2018.

Results

A total of 37 full reports (22 for oncological indications) explaining the rationale for the AIFA's decision is made publicly available on the agency's website. A total of 12 therapeutic indications (5 oncological) were evaluated as fully innovative, 13 indications (11 oncological) were evaluated as conditionally innovative, while 12 indications (6 oncological) as non‐innovative.

Conclusion

The new AIFA innovation criteria resulted in a much more flexible and transparent model to define and assess what constitutes a therapeutic innovation. In particular, the choice of AIFA to use the GRADE methodology to evaluate the quality of clinical evidence within a process of drug innovativeness assessment is essential for the early identification of the discrepancy between the need for patients of a rapid access to innovative therapies and the available clinical data needed to make decisions on drug innovativeness.