bluuebunny/crossref_metadata_2025 huggingface dataset:
Unilateral interruption of pulmonary artery with pulmonary hypertension: a case for heart lung transplantation?
Authors: Singhal Roopesh
Published: April 2019

Unilateral interruption of pulmonary artery is a rare congenital anomaly which is usually associated with other congenital heart disease. Even more rarely it may occur in isolation. Most of the cases are incidentally detected in adulthood. Some cases develop pulmonary hypertension for yet unknown reasons; such cases usually present in infancy with right heart failure. Surgical correction in such cases is associated with adverse outcomes. Heart lung transplantation should be considered in such patients. We report a 3-year-old boy with interruption of right pulmonary artery with severe pulmonary hypertension and right heart failure who was considered for heart lung transplantation.
Recurrence of coronary artery lesions after complete regression in a peculiar case of Kawasaki disease
Authors: Sharma Shiv D. , Chaturvedi Kanupriya , Saini Avesh , Rathore Swatantra , Tayal Mohit
Published: April 2019

Kawasaki disease is a leading cause of acquired heart disease in children with serious repercussions of coronary artery lesions. Recurrences of the disease are relatively rare in clinical practice. We present a case of recurrent Kawasaki disease, wherein the coronary artery lesions which were documented during the initial illness demonstrated complete regression over the following months, but reappeared with recurrence of the disease.
Management of violent behaviour and rapid tranquillisation during acute psychotic episode: discrepancy between routine practice and evidence. The SIEP-DIRECT's Project
Authors: Lora Antonio , Morganti Carla , Erlicher Arcadio , Burti Lorenzo , Buscaglia Giacinto , Pegoraro Marco , Davide Jacchetti , Cristofalo Doriana , Ruggeri Mirella , Semisa Domenico
Published: April 2019

Aims– To evaluate the quality of acute psychiatric care concerning the management of violent behaviour and rapid tran-quilization.Methods– Data concerning 13 indicators, drawn from NICE recommendations, were collected in 19 Departments of Mental Health, in the frame of the SIEP-DIRECT's Project, to evaluate the implementation of NICE recommendations in Italian Mental Health Services.Results– In about two thirds of Departments of Mental Health (DMHs) professionals were trained in the management of violent behaviour, while written procedures existed only in one fourth of DMHs. About a half of the professionals working in Psychiatric Wards in General Hospital were trained in rapid tranquilization, while procedures on this topic are practically absent and specific care for monitoring intensively the heavily sedated patient was not frequent.Conclusions– Management of violent behaviour and rapid tranquilization are two critical areas in the care performed by Psychiatric Wards in General Hospital. Training on these topics is more frequent than implementation of procedures. NICE recommendations and SIEP indicators are useful tools for improving the quality of acute psychiatric care.

Declaration of Interest: None.
The relationship among Mental Health Status (GHQ-12), Health Related Quality of Life (EQ-5D) and Health-State Utilities in a general population
Authors: Serrano-Aguilar Pedro , Ramallo-Fariña Yolanda , Trujillo-Martín Maria Del Mar , Muñoz-Navarro Sergio Raul , Perestelo-Perez Lilisbeth , Cuevas-Castresana Carlos De Las
Published: April 2019

Aim– To assess the relationship between mental health and health-related quality of life (HRQL) in the general population, and to map GHQ-12 as a screening test for population psychological distress to a generic health state measure (EQ-5D) in order to estimate health state values and allow deriving quality-adjusted life years.Methods– Relationship between mental health and HRQL was examined from the 2004 Canary Islands’ Health Survey. Participants were classified as probable psychiatric cases according to GHQ-12. HRQL was measured by the EQ-5D index. Multivariate lineal regression analysis was used to examine the association between mental health and HRQL adjusting by socio-demographic variables and comorbidities. A multivariate regression model was built from EQ-5D to estimate health states values using GHQ-12 as exposure.Results– EQ-5D index scores decreased as the GHQ-12 scores increased. Clinical and socio-demographic factors influenced HRQL without changing the overall trend for this negative relationship. The regression equation explained 43% of the variance. For estimation of utility scores, the model showed a high predictive capacity, with a mean forecast errors of 16%.Conclusions– HRQL progressively decreased when the probability of being a psychiatric case increased. Findings enable health state values to be derived from GHQ-12 scores for populations where utilities has not or cannot be measured directly.

Declaration of Interest:Authors declare no conflicts of interest. This work was supported by the Quality Plan for the National Health Service (Spanish Ministry of Health and Social Policy).
Is the exposure to antidepressant drugs in early pregnancy a risk factor for spontaneous abortion? A review of available evidences
Authors: Santone Giovanni , Ricchi Gianmatteo , Rocchetti David , Tofani Stefania , Bellantuono Cesario
Published: April 2019

Aim– To review studies conducted to establish the risk of spontaneous abortion (SA) in women exposed to anti-depressant drugs (ADs) during early pregnancy.Methods– By using different search terms, PubMed, Toxline, EMBASE, PsychINFO, and the Cochrane library databases were searched from January 1980 to March 2008, to identify studies assessing the risk of SA in women exposed to different classes of ADs during the first trimester of pregnancy.Results– Ten studies over 21 identified were selected for the analysis. All were performed prospectively and included as control group unexposed women, or exposed to non-teratogenic drugs or to placebo. In seven studies a depressive episode was specified as the reason for which the drug was prescribed, while the time of exposure was in nine.Conclusions– Only three studies over ten selected reported a significant association between an increased rate of SAs and early pregnancy exposure to some ADs. Many methodological flaws in the study design were found in all studies considered. Given this background and a lack of strong evidence on this issue, further prospective and better designed studies are needed to assess the risk of SA in pregnant women exposed to ADs against the risk of an untreated maternal depression.

Declaration of Interest:None.
Mental uneasiness, perceived stress and help-seeking in a non-resident university student sample (in Italian)
Authors: Armando Marco , Fagioli Francesca , Borra Simone , Carnevali Rossella , Righetti Valentino , Saba Riccardo , Tarsitani Lorenzo , Biondi Massimo , Nastro Paolo Fiori
Published: April 2019

Il passaggio dal liceo all'università rappresenta quella che altrove è stata definita una “rivoluzione copernicana” (Fiori Nastroet al., 2008). Questo passaggio avviene in una fascia d'età compresa tra i 18 e i 20 anni, periodo estremamente delicato per quanto attiene le patologie psichiatriche dal momento che è stato stimato che il 75° dei disturbi mentali gravi esordisce entro i 24 anni (Patelet al., 2007; Costelloet al., 2003).
Innovations in the Utilization of Health Information Technology in Psychiatric Services
Authors: Plovnick Robert M.
Published: April 2019

There is ever-increasing activity in applying information technology to various areas of healthcare, including mental health. Examples of innovations include applications in screening, treatment, clinical decision support, communication and coordination, telemedicine, Internet-based education and services, public health research, training and education, and bioinformatics. Issues and challenges include protection of privacy, managing narrative free text, assessing the reliability of information found online, and mitigating impact on clinical workflow. While many of the innovations described will not be fully realized until national information systems reach a larger scale, many are having a positive impact on mental healthcare today.
Employment status, aspirations and perceptions of support amongst psychiatric service users in Pavia, Italy
Authors: Cirillo Irene , Politi Pierluigi , Rampi Elisa , Secker Jenny , Brasia Franca , Severino Anna
Published: April 2019

Aims– To describe the employment status of people using mental health service in Pavia, Italy; to explore their employment aspirations and perceptions of support to achieve these; and to test the feasibility of working with service users as researchers.Method– Face to face interviews carried out by two service user researchers with a consecutive sample of 200 service users attending the local psychiatric outpatient department using a translated version of a questionnaire developed for previous UK surveys.Results– A higher proportion of survey participants (42.5%) were in paid work compared to the UK, but 62.4% of those in work were dissatisfied with their employment. Amongst unemployed participants, 65.2% were interested in gaining employment but only 29.3% were receiving support to do so. Support was mainly limited to referral on to a generic disability organisation. The service user researchers carried out the survey to a high standard and reported benefits from undertaking the work. Conclusions – The results indicate a need in Pavia for specialist employment support using the Individual Placement and Support approach. Further development of service user involvement in research is indicated.
Stigma and discrimination against people with mental illness: a critical appraisal
Authors: Lauber Christoph
Published: April 2019

This editorial gives an overview of the different roots and forms of discrimination and stigmatisation towards people with mental illness. It explains the differences between stereotype, prejudice and discrimination. It further highlights some research foci of stigma research in the last decade. The emphasis was mostly on investigating the attitudes of the general population, but barely addressed other groups that have probably more intensive and more crucial contact with people with mental illness. Furthermore, only very few intervention programs were evaluated. This editorial concludes that other groups than the general population, e.g., mental health professionals, should be investigated about their attitudes to people with mental illness. Moreover, intervention campaigns should be additionally evaluated after a given period as it is not well known whether effects of interventions are long-lasting. It might be that anti-stigma campaigns, as every public health campaign, must be repeated if sustainability is the goal. Furthermore, the message must be carefully chosen. One option is to replace the “traditional” messages by focussing, e.g., on symptoms of mental illness, for instance anxiety, affective symptoms or suicidal ideations. Finally, a plea for more stigma-related research is given as research in stigma-related issues is also stigmatised.
Rotating Item Banks versus Restriction of Maximum Exposure Rates in Computerized Adaptive Testing
Authors: Barrada Juan Ramón , Olea Julio , Abad Francisco José
Published: April 2019

If examinees were to know, beforehand, part of the content of a computerized adaptive test, their estimated trait levels would then have a marked positive bias. One of the strategies to avoid this consists of dividing a large item bank into several sub-banks and rotating the sub-bank employed (Ariel, Veldkamp & van der Linden, 2004). This strategy permits substantial improvements in exposure control at little cost to measurement accuracy. However, we do not know whether this option provides better results than using the master bank with greater restriction in the maximum exposure rates (Sympson & Hetter, 1985). In order to investigate this issue, we worked with several simulated banks of 2100 items, comparing them, for RMSE and overlap rate, with the same banks divided in two, three… up to seven sub-banks. By means of extensive manipulation of the maximum exposure rate in each bank, we found that the option of rotating banks slightly outperformed the option of restricting maximum exposure rate of the master bank by means of the Sympson-Hetter method.
Neuropsychological Profile of Children with Early and Continuously Treated Phenylketonuria: Systematic Review and Future Approaches
Authors: Canton Marie , Gall Didier Le , Feillet François , Bonnemains Chrystele , Roy Arnaud
Published: April 2019

Objective:To provide a comprehensive systematic review of the literature by examining studies published on all cognitive aspects of children with early and continuously treated phenylketonuria (ECT-PKU) included in the databases Medline, PsycINFO, and PsycARTICLE.Method:In addition to a classical approach, we summarized methodology and results of each study in order to discuss current theoretical and methodological issues. We also examined recent advances in biochemical markers and treatments of PKU, with implications for future research on metabolic control and its role as a determinant of neuropsychological outcome.Results:Consistent with previous reviews, the hypothesis of a specific and central executive impairment in children with ECT-PKU was suggested. However, findings are inconclusive regarding the nature of executive impairments as well as their specificity, impact on everyday life, persistence over time, and etiology.Conclusion:Given the current state of the science, we suggest future directions for research that utilizes a developmental and integrative approach to examine the effects of recent advances in biochemical markers and treatment of PKU. (JINS, 2019,25, 624–643)
Lachenmann's Silent Voices (and the Speechless Echoes of Nono and Stockhausen)
Authors: LEIPERT TRENT
Published: April 2019

In order to assess Helmut Lachenmann's characterization of (his) music as an ‘existential experience’ this article focuses on a specific aspect of many of his compositions: stretches of near-silence and minimized musical activity such as reduced dynamics and gestures which contrasts the surrounding material. I argue that in the case of his early vocal compositions Consolation I and II (1967 and 1968) these ‘meta-musical fermatas’ relate to a key portion of each work's text in order to encourage self-reflection on the part of the listener. My analyses reveal the influence of Luigi Nono and Karlheinz Stockhausen, particularly in terms of word-setting and of the works’ spiritual and political messages. I further trace the changes undertaken in these compositions and in Lachenmann's commentaries for them over the following decade. I suggest these changes relate to political events in Germany occurring between 1968 and 1977 which also led to the conception of Lachenmann's ‘music with images’, Das Mädchen mit den Schwefelhölzern.
Should we use the criminal law to punish HIV transmission?
Authors: Schüklenk Udo
Published: April 2019

Legislators around the world are grappling with the question of whether or not the criminal law should be deployed in order to punish HIV transmission that is the result of voluntary sexual encounters between competent, consenting adults. A few years ago, when I was working in South Africa, that country’s Law Reform Commission proposed to declare HIV transmissions that are the result of voluntary sexual encounters among competent consenting adults a criminal offence that ought to fall under the category of rape (Schüklenk, 2003). Rape and voluntariness do not go too well together, so – not being a lawyer – I was surprised about the seemingly otherworldly machinations of legal minds in the context of HIV/AIDS. Matthew Weait points out in his book Intimacy and Responsibility: The Criminalisation of HIV Transmission that many liberal democracies have made HIV transmission a criminal offence, among these Canada, Sweden, Germany, Norway, Denmark, the Netherlands, the UK and many others. In most countries, HIV infected people who demonstrably knew about their infection have been successfully prosecuted for transmitting HIV to their sexual partners.
Germination ecology for Florida populations of carpetweed (Mollugo verticillata), Carolina geranium (Geranium carolinianum), eclipta (Eclipta prostrata), and goosegrass (Eleusine indica)
Authors: Sharpe Shaun M. , Boyd Nathan S.
Published: April 2019

Row-middle weed control in Florida vegetable production is challenging and often necessitates several PRE and POST herbicide applications. Coordinating POST spray applications with emergence timings should increase herbicide efficacy by targeting susceptible growth stages. Most published emergence models were developed in temperate climates, and adapting them to subtropical climates can be complex and requires reductionist insights into seed ecology, particularly germination and dormancy. The study objective was to examine the influence of temperature and osmotic potential on seed germination of carpetweed (Mollugo verticillata L.), Carolina geranium (Geranium carolinianum L.), eclipta [Eclipta prostrata (L.) L.], and goosegrass [Eleusine indica (L.) Gaertn.]. Mollugo verticillata seed germination was positively photoblastic, with increased germination at high temperatures (≥35 C), more so with high fluctuating temperatures (35/20 and 35/25 C), and occurred at osmotic potentials as low as −0.5 MPa. Geranium carolinianum seed germinated between 10 and 20 C in light or darkness and at osmotic potentials as low as −0.4 MPa. Eclipta prostrata seed germination was entirely positively photoblastic, occurring optimally between 15 and 25 C and at osmotic potentials as low as −1 MPa. Eleusine indica seed germination demonstrated some degree of positive photoblasticity, with greater germination in the light, peak germination at 35 C, and germination occurring at osmotic potentials as low as −0.5 MPa. Described germination ecology for selected species will provide insights for building ecology-based growing degree-day accounting restrictions for empirically derived emergence models.
In der Alltagsroutine angekommen: Die endovenöse, ambulante Therapie der Varikose
Authors: Proebstle Thomas M.
Published: April 2019

Zusammenfassung. In den vergangenen 20 Jahren wurden endovenöse Therapieverfahren entwickelt, die in vielen Ländern die Venenchirurgie abgelöst haben oder aber als gleichwertige Alternativen gelten. Mit den endothermischen Verfahren Laser und Radiofrequenz zur Stammvenenbehandlung stehen Verfahren zur Verfügung, die in der Regel ambulante Behandlungen in örtlicher Betäubung erlauben und eine umgehende Rückkehr in den Alltag ermöglichen. Prospektiv randomisierte Studien mit fünf Jahren Nachbeobachtungszeitraum belegen, dass Effizienz und Nebenwirkungsspektrum der modernen Varizen-Chirurgie gleichkommen. In den Guidelines verschiedener internationaler Fachgesellschaften werden die endovenösen Methoden deshalb vor der Chirurgie oder wenigstens als gleichwertig empfohlen. Die sogenannten Nicht-Thermischen-Nicht-Tumeszenz-Verfahren wie Arcrylatkleber und mechanochemische Ablation schlagen aktuell ein neues Kapitel in der Stammvenenbehandlung auf. Erste Resultate sind vielversprechend, vergleichende randomisierte Studien zu den etablierten Techniken sind aber vorerst noch Mangelware.
Zinc and Manganese of serum were negatively, but Copper positively influenced by Iron elevation in diet of male Wistar rats
Authors: Zolfaghari Ali , Reza Gheisari Hamid , Omidi Arash , Nazifi Saeed
Published: April 2019

Abstract. The purpose of the study was to determine the effect of dietary iron on distribution of zinc, manganese, copper, calcium and magnesium in the body of Wistar rats. Commercial Sangak, an Iranian traditional flat bread was used in this study. It was prepared by additionof yeast and sourdough. Different doses of iron (35, 70, 140, and 210 mg/kg per diet) were added to bread vehicle for 30 days with or without baking soda (250 mg/kg per diet). The concentrations of the above elements were determined by graphite furnace and flame atomic absorption spectroscopy. Serum zinc and manganese concentrations were significantly lower (P < 0.05) in rats that received higher concentrations of iron compared to the controls. Serum iron, and copper concentrations increased significantly (P < 0.05) with an increase in dietary iron compared to the controls. Increments of dietary concentrations of iron raised the concentration of iron, zinc and manganese in the feces, and lowered the concentration of copper and calcium in the feces (P < 0.05). Diets that contained baking soda showed a statistically significant increase in phytic acid (P < 0.05). Lower serum iron was seen in rats that received baking soda with diet of the control group. Conversely, feces iron and zinc were increased in this group. It is concluded that iron absorption might interfere with zinc and manganese because of similar physicochemical properties. Knowledge about these interactions is essential when supplementation of some elements is recommended in populations with a high risk of some deficiencies such as iron and zinc.
Effect of Vitamin D Supplementation in Prostate Cancer: A Systematic Review of Randomized Control Trials
Authors: Petrou Spyros , Mamais Ioannis , Lavranos Giagkos , P. Tzanetakou Irene , Chrysostomou Stavri
Published: April 2019

Abstract. Vitamin D is important in many cellular functions including cell cycling and proliferation, differentiation, and apoptosis. Via the induction of cell cycle arrest and/or apoptosis, vitamin D inhibits normal prostatic epithelial cells growth. Review the evidence of the effect of vitamin D supplementation on prostate cancer (PC) biomarkers and patient survival and assess optimal dosage, formulation and duration. Pubmed, Medline and Ebsco Host databases were systematically searched for relevant literature. 8 Randomized Controlled Trials were included in this review. All studies, besides one, were of high methodological quality. 4 studies used calcitriol (0,5-45 μg/weekly), 2 studies have used vitamin D3 (150-1000 μg/daily) and 2 other studies have used 1α-hydroxy Vitamin D2 (10 μg/ daily or weekly). Duration of supplementation varied between 28 days up to 18.3 months. Two studies had positive effects on prostate specific antigen (PSA) (p < .05), 1 study had a significant positive effect on median survival (p < .05) and 1 study showed a significant reduction of vitamin D receptor (VDR) expression (p < .05). The remaining studies showed negative or no effect on PC characteristics, clinical outcomes and/or survival. Current evidence suggests that vitamin D supplementation in conjunction with standard of care (e.g. chemotherapy, radiation therapy) may confer clinical benefits such as a decrease in serum PSA levels and VDR expression but further research is required to ascertain these results. Calcitriol supplementation in doses ranging from 250-1000 mg for 3–8 weeks or a lower dose of 45 mg for 18.3 months, appear most beneficial regarding outcomes of PC progression and survival.
On the Regional and Seasonal Ozone Depletion Potential of Chlorinated Very Short‐Lived Substances
Authors: Claxton Tom , Hossaini Ryan , Wild Oliver , Chipperfield Martyn P. , Wilson Chris
Published: April 2019

Chloroform (CHCl3), dichloromethane (CH2Cl2), perchloroethylene (C2Cl4), and 1,2‐dichloroethane (C2H4Cl2) are chlorinated Very Short‐Lived Substances (Cl‐VSLS) with a range of commercial/industrial applications. Recent studies highlight the increasing influence of Cl‐VSLS on the stratospheric chlorine budget and therefore their possible role in ozone depletion. Here we evaluate the ozone depletion potential (ODP) of these Cl‐VSLS using a three‐dimensional chemical transport model and investigate sensitivity to emission location/season. The seasonal dependence of the ODPs is small, but ODPs vary by a factor of 2–3 depending on the continent of emission: 0.0143–0.0264 (CHCl3), 0.0097–0.0208 (CH2Cl2), 0.0057–0.0198 (C2Cl4), and 0.0029–0.0119 (C2H4Cl2). Asian emissions produce the largest ODPs owing to proximity to the tropics and efficient troposphere‐to‐stratosphere transport of air originating from industrialized East Asia. The Cl‐VSLS ODPs are generally small, but the upper ends of the CHCl3 and CH2Cl2 ranges are comparable to the mean ODP of methyl chloride (0.02), a longer‐lived ozone‐depleting substance.
Changing Moho Beneath the Tibetan Plateau Revealed by GRACE Observations
Authors: Jiao Jiashuang , Zhang Yongzhi , Yin Peng , Zhang Kainan , Wang Yipeng , Bilker‐Koivula Mirjam
Published: April 2019

A wide range of mass gain in the inland of the Tibetan Plateau (TP) has been observed by the Gravity Recovery and Climate Experiment (GRACE). But there are still controversies on how to understand this phenomenon. In this paper, satellite geodesy data and hydrological models are combined and applied for extracting signals caused by tectonic processes in the TP during the period from 2003 to 2009. We find that in the inland of the TP there are three regions with a significant signal that should be attributed to tectonic processes. The three prominent mass signals, each located in the western, central, and eastern TP, are estimated to be at the rate of 1.47 ± 0.43, −0.85 ± 0.53, and 1.51 ± 0.56 cm/year, respectively, in equivalent water height. However, the rate caused by Earth surface deformation constrained by GPS is 0.33 ± 0.15/0.30 ± 0.10/0.14 ± 0.24 cm/year in equivalent water height, which cannot explain the whole tectonic signals and indicates that a significant mass change occurs beneath the crust, that is, the deformation of the Moho interface. We estimate the Moho change rate in the inland of the TP and find that the Moho interface is suffering an uneven deformation. The Moho is uprising at a rate of 18.1 ± 7.2 mm/year in the west and 21.7 ± 9.7 mm/year in the east of the TP, while there is an obvious deepening rate of −18.3 ± 8.6 mm/year in the central TP.
Prediction Model for Solar Energetic Proton Events: Analysis and Verification
Authors: Zhong Qiuzhen , Wang Jingjing , Meng Xuejie , Liu Siqing , Gong Jiancun
Published: April 2019

Solar energetic protons (SEPs) can cause radiation damage to satellites. The Space Environment Prediction Center of China defines the start of a SEP event as the time when three consecutive instances of the 5‐min‐averaged integral flux of >10 MeV protons equal or exceed the 10 proton flux unit threshold. In this study, we analyzed the 5‐min‐averaged soft X‐ray flux and the differential and integral proton flux obtained by the Geostationary Operational Environmental Satellites for the period from January 1990 to September 2017 and developed SEP prediction models and their products. The statistical models take one or two data products and the given thresholds as the predictor and predict whether a SEP event will occur or not in the next 24 hr. The quality of the forecast models was measured by comparing the model results against certain verification metrics. Our model taking the products of 5‐min‐averaged integral flux of >10 MeV protons and long wavelength of soft X‐ray flux as predictors can provide a probability of detection of 0.80 (152/190), a false alarm ratio of 0.26 (53/205), and an average warning time of 2.6 hr for the correctly predicted events. In addition, the model can provide a critical success index of 0.63, a Gilbert skill score of 0.62, and a Heidke skill score of 0.76.
Understanding Stream Metabolism with Reactive Tracers
Authors: Sidder Aaron
Published: April 2019

When the blue dye resazurin encounters living microorganisms, it transforms into fluorescent pink resorufin and helps scientists understand ecosystem respiration, but it has its limitations.
California Heat Waves Triggered by Pacific Thunderstorms
Authors: Morton Mary
Published: April 2019

New link may offer 5-week lead time on predicting extreme heat in California’s fruit belt.
Temperature-induced amorphization in CaCO3 at high pressure and implications for recycled CaCO3 in subduction zones
Authors: Hou Mingqiang , Zhang Qian , Tao Renbiao , Liu Hong , Kono Yoshio , Mao Ho-kwang , Yang Wenge , Chen Bin , Fei Yingwei
Published: April 2019

Calcium carbonate (CaCO3) significantly affects the properties of upper mantle and plays a key role in deep carbon recycling. However, its phase relations above 3 GPa and 1000 K are controversial. Here we report a reversible temperature-induced aragonite-amorphization transition in CaCO3 at 3.9–7.5 GPa and temperature above 1000 K. Amorphous CaCO3 shares a similar structure as liquid CaCO3 but with much larger C-O and Ca-Ca bond lengths, indicating a lower density and a mechanism of lattice collapse for the temperature-induced amorphous phase. The less dense amorphous phase compared with the liquid provides an explanation for the observed CaCO3 melting curve overturn at about 6 GPa. Amorphous CaCO3 is stable at subduction zone conditions and could aid the recycling of carbon to the surface.
Macroscale cortical organization and a default-like apex transmodal network in the marmoset monkey
Authors: Buckner Randy L. , Margulies Daniel S.
Published: April 2019

Networks of widely distributed regions populate human association cortex. One network, often called the default network, is positioned at the apex of a gradient of sequential networks that radiate outward from primary cortex. Here, extensive anatomical data made available through the Marmoset Brain Architecture Project are explored to show a homologue exists in marmoset. Results reveal that a gradient of networks extend outward from primary cortex to progressively higher-order transmodal association cortex in both frontal and temporal cortex. The apex transmodal network comprises frontopolar and rostral temporal association cortex, parahippocampal areas TH / TF, the ventral posterior midline, and lateral parietal association cortex. The positioning of this network in the gradient and its composition of areas make it a candidate homologue to the human default network. That the marmoset, a physiologically- and genetically-accessible primate, might possess a default-network-like candidate creates opportunities for study of higher cognitive and social functions.
Regioselective radical α-borylation of α,β-unsaturated carbonyl compounds for direct synthesis of α-borylcarbonyl molecules
Authors: Ren Shi-Chao , Zhang Feng-Lian , Xu Ai-Qing , Yang Yinuo , Zheng Min , Zhou Xiaoguo , Fu Yao , Wang Yi-Feng
Published: April 2019

Organoboron compounds are highly valuable in synthetic chemistry. In particular, α-borylcarbonyl compounds have shown versatile synthetic applications, owing to fruitful chemistries of both the boryl and carbonyl moieties. However, the synthesis of these molecules still remains tedious and time-consuming. Here we report a straightforward and practical route to synthesize α-borylcarbonyl molecules based on a regioselective radical α-borylation of α,β-unsaturated carbonyl compounds. The reaction features unusual α-regioselectivity and high functional-group compatibility. Further synthetic applications of new α-borylated products were also demonstrated. DFT and kinetic studies implicated that the α-regioselectivity of β-aryl-α,β-unsaturated carbonyl compounds was determined by the thermodynamically more favorable radical α-addition step, whereas the formation of α-addition products from β-alkyl-α,β-unsaturated carbonyl compounds was driven by an energetically favored hydrogen atom transfer step. Given that α,β-unsaturated carbonyl compounds can be easily obtained in abundance and variety, this method enjoys great advantages in diverse and economical synthesis of valuable α-borylcarbonyl molecules.
Liquid-like behaviours of metallic glassy nanoparticles at room temperature
Authors: Cao C. R. , Huang K. Q. , Shi J. A. , Zheng D. N. , Wang W. H. , Gu L. , Bai H. Y.
Published: April 2019

Direct atomic-scale observations and measurements on dynamics of amorphous metallic nanoparticles (a-NPs) are challenging owing to the insufficient consciousness to their striking characterizations and the difficulties in technological approaches. In this study, we observe coalescence process of the a-NPs at atomic scale. We measure the viscosity of the a-NPs through the particles coalescence by in situ method. We find that the a-NPs have fast dynamics, and the viscosity of the a-NPs exhibits a power law relationship with size of the a-NPs. The a-NPs with sizes smaller than 3 nm are in a supercooled liquid state and exhibit liquid-like behaviours with a decreased viscosity by four orders of magnitude lower than that of bulk glasses. These results reveal the intrinsic flow characteristics of glasses in low demension, and pave a way to understand the liquid-like behaviours of low dimension glass, and are also of key interest to develop size-controlled nanodevices.
Crystal structure of the Lin28-interacting module of human terminal uridylyltransferase that regulates let-7 expression
Authors: Yamashita Seisuke , Nagaike Takashi , Tomita Kozo
Published: April 2019

Lin28-dependent oligo-uridylylation of precursor let-7 (pre-let-7) by terminal uridylyltransferase 4/7 (TUT4/7) represses let-7 expression by blocking Dicer processing, and regulates cell differentiation and proliferation. The interaction between the Lin28:pre-let-7 complex and the N-terminal Lin28-interacting module (LIM) of TUT4/7 is required for pre-let-7 oligo-uridylylation by the C-terminal catalytic module (CM) of TUT4/7. Here, we report crystallographic and biochemical analyses of the LIM of human TUT4. The LIM consists of the N-terminal Cys2His2-type zinc finger (ZF) and the non-catalytic nucleotidyltransferase domain (nc-NTD). The ZF of LIM adopts a distinct structural domain, and its structure is homologous to those of double-stranded RNA binding zinc fingers. The interaction between the ZF and pre-let-7 stabilizes the Lin28:pre-let-7:TUT4 ternary complex, and enhances the oligo-uridylylation reaction by the CM. Thus, the ZF in LIM and the zinc-knuckle in the CM, which interacts with the oligo-uridylylated tail, together facilitate Lin28-dependent pre-let-7 oligo-uridylylation.
CUT&Tag for efficient epigenomic profiling of small samples and single cells
Authors: Kaya-Okur Hatice S. , Wu Steven J. , Codomo Christine A. , Pledger Erica S. , Bryson Terri D. , Henikoff Jorja G. , Ahmad Kami , Henikoff Steven
Published: April 2019

Many chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is bound in situ by a specific antibody, which then tethers a protein A-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline, and the entire procedure can be performed in one day. We demonstrate the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.
Changes in the Anterior Lamina Cribrosa Morphology with Glaucoma Severity
Authors: Tan Nicholas Y. Q. , Tham Yih-Chung , Thakku Sri Gowtham , Wang Xiaofei , Baskaran Mani , Tan Marcus C. L. , Mari Jean-Martial , Strouthidis Nicholas G. , Aung Tin , Girard Michaël J. A. , Cheng Ching-Yu
Published: April 2019

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = −0.34 [0.05]), followed by the mild-moderate POAG group (−0.31 [0.02]) and then controls (−0.23 [0.02], PTrend = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma (PTrend = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT.
A library of Neo Open Reading Frame peptides (NOPs) as a sustainable resource of common neoantigens in up to 50% of cancer patients
Authors: Koster Jan , Plasterk Ronald H. A.
Published: April 2019

Somatic mutations in cancer can result in neoantigens against which patients can be vaccinated. The quest for tumor specific neoantigens has yielded no targets that are common to all tumors, yet foreign to healthy cells. Single base pair substitutions (SNVs) at best can alter 1 amino acid which can result in a neoantigen; with the exception of rare site-specific oncogenic driver mutations (such as RAS) such mutations are private. Here, we describe a source of common neoantigens induced by frame shift mutations, based on analysis of 10,186 TCGA tumor samples. We find that these frame shift mutations can produce long neoantigens. These are completely new to the body, and indeed recent evidence suggests that frame shifts can be highly immunogenic. We report that many different frame shift mutations converge to the same small set of 3′ neo open reading frame peptides (NOPs), all encoded by the Neo-ORFeome. We find that a fixed set of only 1,244 neo-peptides in as much as 30% of all TCGA cancer patients. For some tumor classes this is higher; e.g. for colon and cervical cancer, peptides derived from only ten genes (saturated at 90 peptides) can be applied to 39% of all patients. 50% of all TCGA patients can be achieved at saturation (using all those peptides in the library found more than once). A pre-fabricated library of vaccines (peptide, RNA or DNA) based on this set can provide off the shelf, quality certified, ‘personalized’ vaccines within hours, saving months of vaccine preparation. This is crucial for critically ill cancer patients with short average survival expectancy after diagnosis.
Characterization of the Phosphorylation Site of GRTH/DDX25 and Protein Kinase A Binding Interface Provides Structural Basis for the Design of a Non-Hormonal Male Contraceptive
Authors: Raju Murugananthkumar , Hassan Sergio A. , Kavarthapu Raghuveer , Anbazhagan Rajakumar , Dufau Maria L.
Published: April 2019

Gonadotropin Regulated Testicular Helicase (GRTH/DDX25), expressed in the male gonad, is essential for the completion of spermatogenesis. Our early studies revealed a missense mutation (R242H) of GRTH in 5.8% of Japanese patient population with azoospermia. Transfection of the mutant GRTH construct in COS-1 cells leads to loss of the 61 kDa cytoplasmic phospho-species. Mice with knock-in of the human GRTH mutation are sterile and lack sperm with normal androgen and mating behavior. These findings provide an avenue for the development of a non-hormonal male contraceptive. Using site directed mutagenesis and a site-specific phospho-antibody, we have identified T239, structurally adjacent to the patient’s mutant site as the GRTH phospho-site. Molecular modelling provided structural basis for the role of R242 and other critical solvent-exposed residues at the GRTH/PKA interface (E165/K240/D237), on the control of GRTH phosphorylation at T239. Single or double mutations of these residues caused marked reduction or abolition of the phospho-form. These effects can be ascribed to critical disruptions of intramolecular H-bonds at the GRTH/PKA interface, which leads to modest but consequential structural changes that can affect PKA catalytic efficiency. Inhibition of phosphorylation may be achieved by small, drug-like molecules that bind to GRTH and reconfigure the GRTH/PKA interface.
SPARK-MSNA: Efficient algorithm on Apache Spark for aligning multiple similar DNA/RNA sequences with supervised learning
Authors: Vineetha V. , Biji C. L. , Nair Achuthsankar S.
Published: April 2019

Multiple sequence alignment (MSA) is an integral part of molecular biology. But handling massive number of large sequences is still a bottleneck for most of the state-of-the-art software tools. Knowledge driven algorithms utilizing features of input sequences, such as high similarity in case of DNA sequences, can help in improving the efficiency of DNA MSA to assist in phylogenetic tree construction, comparative genomics etc. This article showcases the benefit of utilizing similarity features while performing the alignment. The algorithm uses suffix tree for identifying common substrings and uses a modified Needleman-Wunsch algorithm for pairwise alignments. In order to improve the efficiency of pairwise alignments, a knowledge base is created and a supervised learning with nearest neighbor algorithm is used to guide the alignment. The algorithm provided linear complexityO(m)compared toO(m2). Comparing with state-of-the-art algorithms (e.g., HAlign II), SPARK-MSNA provided 50% improvement in memory utilization in processing human mitochondrial genome (mt. genomes, 100x, 1.1. GB) with a better alignment accuracy in terms of average SP score and comparable execution time. The algorithm is implemented on big data framework Apache Spark in order to improve the scalability. The source code & test data are available at:https://sourceforge.net/projects/spark-msna/.
The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: A multicenter prospective registry-based observational study
Authors: Ryoo Seung Mok , Han Kap Su , Ahn Shin , Shin Tae Gun , Hwang Sung Yeon , Chung Sung Phil , Hwang Yoon Jung , Park Yoo Seok , Jo You Hwan , Chang Hyung Lan , Suh Gil Joon , You Kyoung Min , Kang Gu Hyun , Choi Sung-Hyuk , Lim Tae Ho , Kim Won Young ,   Korean Shock Society (KoSS) Investigators, Kim Youn-Jung , Lee Sung Woo , Jo Ik Joon , Kim Min Joung , Kwon Woon Yong , Lee Hui Jai , Shin Jong Hwan , Ko Byuk Sung
Published: April 2019

The objective of this study was to evaluate the prognostic value of C-reactive protein (CRP), procalcitonin (PCT), and their combination for mortality in patients with septic shock. This multicenter, prospective, observational study was conducted between November 2015 and December 2017. A total of 1,772 septic shock patients were included, and the overall 28-day mortality was 20.7%. Although both CRP and PCT were elevated in the non-survivor group, only CRP had statistical significance (11.9 mg/dL vs. 14.7 mg/dL, p = 0.003, 6.4 ng/mL vs. 8.2 ng/mL, p = 0.508). Multivariate analysis showed that CRP and PCT were not independent prognostic markers. In the subgroup analysis of the CRP and PCT combination matrix using their optimal cut-off values (CRP 14.0 mg/dL, PCT 17.0 ng/dL), both CRP and PCT elevated showed significantly higher mortality (Odds ratio 1.552 [95% Confidence intervals 1.184–2.035]) than both CRP and PCT not elevated (p = 0.001) and only PCT elevated (p = 0.007). However, both CRP and PCT elevated was also not an independent predictor in multivariate analysis. Initial levels of CRP and PCT alone and their combinations in septic shock patients had a limitation to predict 28-day mortality. Future research is needed to determine new biomarkers for early prognostication in patients with septic shock.
Linkage-based genome assembly improvement of oil palm (Elaeis guineensis)
Authors: Ong Ai-Ling , Teh Chee-Keng , Kwong Qi-Bin , Tangaya Praveena , Appleton David Ross , Massawe Festo , Mayes Sean
Published: April 2019

Meiotic crossovers in outbred species, such as oil palm (Elaeis guineensis Jacq., 2n = 32) contribute to allelic re-assortment in the genome. Such genetic variation is usually exploited in breeding to combine positive alleles for trait superiority. A good quality reference genome is essential for identifying the genetic factors underlying traits of interest through linkage or association studies. At the moment, an AVROS pisifera genome is publicly available for oil palm. Distribution and frequency of crossovers throughout chromosomes in different origins of oil palm are still unclear. Hence, an ultrahigh-density genomic linkage map of a commercial Deli dura x AVROS pisifera family was constructed using the OP200K SNP array, to evaluate the genetic alignment with the genome assembly. A total of 27,890 linked SNP markers generated a total map length of 1,151.7 cM and an average mapping interval of 0.04 cM. Nineteen linkage groups represented 16 pseudo-chromosomes of oil palm, with 61.7% of the mapped SNPs present in the published genome. Meanwhile, the physical map was also successfully extended from 658 Mb to 969 Mb by assigning unplaced scaffolds to the pseudo-chromosomes. A genic linkage map with major representation of sugar and lipid biosynthesis pathways was subsequently built for future studies on oil related quantitative trait loci (QTL). This study improves the current physical genome of the commercial oil palm, and provides important insights into its recombination landscape, eventually unlocking the full potential genome sequence-enabled biology for oil palm.
The interactome of a family of potential methyltransferases in HeLa cells
Authors: Ignatova Valentina V. , Jansen Pascal W. T. C. , Baltissen Marijke P. , Vermeulen Michiel , Schneider Robert
Published: April 2019

Human methytransferase like proteins (METTL) are part of a large protein family characterized by the presence of binding domains for S-adenosyl methionine, a co-substrate for methylation reactions. Despite the fact that members of this protein family were shown or predicted to be DNA, RNA or protein methyltransferases, most METTL proteins are still poorly characterized. Identification of complexes in which these potential enzymes act could help to understand their function(s) and substrate specificities. Here we systematically studied interacting partners of METTL protein family members in HeLa cells using label-free quantitative mass spectrometry. We found that, surprisingly, many of the METTL proteins appear to function outside of stable complexes whereas others including METTL7B, METTL8 and METTL9 have high-confidence interaction partners. Our study is the first systematic and comprehensive overview of the interactome of METTL protein family that can provide a crucial resource for further studies of these potential novel methyltransferases.