bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhodium-Catalyzed Cascade Annulative Coupling of 3,5-Diarylisoxazoles with Alkynes
Authors: Noguchi Teppei , Nishii Yuji , Miura Masahiro
Published: September 2018

A rhodium-catalyzed cascade annulative coupling of 3,5-di­arylisoxazoles with three equivalents of an alkyne proceeds smoothly in the presence of a Cu(II) oxidant, where the sequential construction of isoquinoline and naphtho[1,8-bc]pyran frameworks connected by a biaryl linkage is achieved by a single operation. Most of the obtained polycyclic compounds exhibit visible fluorescence in both the solution and the solid state. The hexaphenylated isoquinoline-naphthopyran conjugate (R = Ph) as a representative product shows a green emission which can be turned off by making an isoquinolinium salt with an acid. The emission is also reversibly turned on by treatment with a base.
[4-Iodo-3-(isopropylcarbamoyl)phenoxy]acetic Acid as a Highly Reactive and Easily Separable Catalyst for the Oxidative Cleavage of Tetrahydrofuran-2-methanols to γ-Lactones
Authors: Yakura Takayuki , Fujiwara Tomoya , Nishi Hideyuki , Nishimura Yushi , Nambu Hisanori
Published: September 2018

[4-Iodo-3-(isopropylcarbamoyl)phenoxy]acetic acid was developed as a highly reactive and easily separable catalyst for the oxidative cleavage of tetrahydrofuran-2-methanols to γ-lactones in the presence of Oxone® (2KHSO5·KHSO4·K2SO4) as the co-oxidant. The reactivity of this new catalyst was considerably greater than that of our previously reported catalyst, 2-iodo-N-isopropylbenzamide. The new catalyst and product were easily separated by only liquid–liquid separation without chromatography. In addition, using a mixture of nitromethane and N,N-dimethylformamide as the solvent and heating enabled a low catalyst loading, a short reaction time, and high product yield. Oxidative cleavage using the new catalyst can be used as a practical and efficient method for synthesizing γ-lactones.
Integrated Electronic Discharge Summaries—Experience of a Tertiary Pediatric Institution
Authors: Katz Merav L. , South Mike , Cheng Daryl R.
Published: September 2018

Objective Succinct and timely discharge summaries (DSs) facilitate ongoing care for patients discharged from acute care settings. Many institutions have introduced electronic DS (eDS) templates to improve quality and timeliness of clinical correspondence. However, significant intrahospital and intraunit variability and application exists. A review of the literature and guidelines revealed 13 key elements that should be included in a best practice DS. This was compared against our pediatric institution's eDS template—housed within an integrated electronic medical record (EMR) and used across most inpatient hospital units.

Methods Uptake and adherence to the suggested key elements was measured by comparing all DSs for long stay inpatients (> 21-day admission) during the first year of the EMR eDS template's usage (May 2016–April 2017).

Results A total of 472 DSs were evaluated. Six of 13 key elements were completed in > 98.0% of DSs. Conversely, only < 5.0% included allergies or adverse reaction data, and < 11.0% included ceased medications or pending laboratory results. Inclusion of procedure information and pending laboratory results significantly improved with time (p = 0.05 and p < 0.04, respectively), likely as doctors became more familiar with EMR and autopopulation functions. Inclusion of “discharge diagnosis” differed significantly between medical (n = 406/472; 99.0%) and surgical (n = 32/472; 51.6%) DSs.

Conclusion Uptake and adherence to an EMR eDS template designed to meet best practice guidelines in a pediatric institution was strong, although significant improvements in specific data elements are needed. Strategies can include a modification of existing eDS templates and junior medical staff education around best practice.
Philosophische Grundlagen der Psychiatrie und ihre Anwendung
Authors: Fuchs T.
Published: September 2018

Die Philosophie lässt sich nicht nur als eine Nachbardisziplin, sondern auch als eine Grundlagenwissenschaft für die Psychiatrie auffassen, deren Bedeutung in den letzten Jahren national und international stark zugenommen hat. Der vorliegende Beitrag stellt drei grundlegende Aufgaben dar, die die Philosophie in der Psychiatrie erfüllen kann: 1. Klärung der psychiatrischen Grundbegriffe; 2. Methoden- und Paradigmenreflexion; 3. Grundlegung psychiatrischer Konzeptionen. Schließlich werden die speziellen Themen des 1. Leib-Seele-Problems, 2. des Ursachenbegriffs, 3. des Krankheitsbegriffs und 4. der Subjektivität erörtert.
Inanspruchnahme psychosozialer Hilfsangebote durch Frauen mit türkischem Migrationshintergrund in psychischen Krisen
Authors: Heredia Montesinos A. , Yesil R. , Bromand Z. , Temur-Erman S. , Heinz A. , Rapp M. A. , Schouler-Ocak M. , Aichberger M. C.
Published: September 2018

Hintergrund: Bisher ist wenig über den Einfluss der Migrationsgeneration auf die tatsächliche und potenzielle Inanspruchnahme in psychischen Krisen durch Migrantinnen mit türkischer Herkunft bekannt. Methode: Es wurden 101 Frauen mit türkischem Migrationshintergrund Interviewer gestützt und mit Hilfe verschiedener Fragebögen befragt. Ergebnisse: Frauen mit türkischem Migrationshintergrund der ersten und der zweiten Generation unterschieden sich nicht bezüglich der potenziellen Inanspruchnahme in psychischen Krisensituationen. Migrantinnen der ersten Generation und Migrantinnen mit einem segregierten Akkulturationsstil berichteten, sich weniger über bestehende psychologische Angebote informiert zu fühlen. Sie gaben an Informationen über psychosoziale Hilfsdienste in der Muttersprache hilfreich zu finden. Schlussfolgerungen: Für eine Verbesserung der Inanspruchnahme psychosozialer Versorgungseinrichtungen scheint es wesentlich, gezielte Subgruppen anzusprechen, um insbesondere Frauen mit geringen Deutschkenntnissen den Zugang zu erleichtern.
Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of Perinatal Outcomes
Authors: Wang Michelle , Kuper Spencer , Sims Brian , Paddock Cayce , Dantzler John , Muir Suzanne , Harper Lorie
Published: September 2018

Objective We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy.

Study Design We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT. We sought studies with outcomes data on maternal abstinence at the time of delivery, neonatal abstinence syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled relative risks (RRs) with a random-effects model, assessed heterogeneity using the chi-square test for heterogeneity, and quantified heterogeneity using the I
2 test. We assessed publication bias using funnel plots and the Harbord test.

Results Three cohort studies met the inclusion criteria; eligible studies included 235 women with opioid use disorder in pregnancy. Maternal detoxification was associated with increased risk of relapse (RR = 1.91; 95% confidence interval [CI] = 1.14–3.21); however, no treatment differences were observed for the rates of NAS (RR = 0.99; 95% CI = 0.38–2.53) or PTB (RR = 0.39; 95% CI = 0.10–1.60).

Conclusion Our findings suggest an increased risk of relapse with detoxification treatment compared with ORT; however, detoxification does not alter the risk of PTB or NAS. Further studies should confirm our findings and explore mechanisms to fight the current opioid epidemic.
Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and Atypical Paternal Phenotype with Mosaicism
Authors: Meira Joanna Goes Castro , Sarno Manoel Alfredo Curvelo , Faria Ágatha Cristhina Oliveira , Yamamoto Guilherme Lopes , Bertola Débora Romeo , Scheibler Gabriela Gayer , Tavares Dione Fernandes , Acosta Angelina Xavier
Published: September 2018

Atelosteogenesis type I (AOI) is an autosomal dominant skeletal dysplasia caused by mutations in the filamin B (FLNB) gene with classic and well-recognizable clinical findings. However, parents affected with a mild phenotype, probably with somatic mosaicism, can generate offspring with a much more severe phenotype of AOI. In the present report, we describe a female newborn with classic AOI leading to early neonatal death, whose diagnostic was based on prenatal radiological findings and on the physical examination of the father. Since her father had limb deformities and corporal asymmetry, suggesting somatic mosaicism, his biological samples were analyzed through a gene panel for skeletal dysplasias. A missense mutation not previously described in the literature was detected in the FLNB gene, affecting ∼ 20% of the evaluated cells and, therefore, confirming the diagnosis of mosaic AOI in the father. The molecular analysis of the father was crucial to suggest the diagnosis of AOI in the newborn, since she died early and there were no biological samples available.
Shared Oocyte Donation: Ideas and Expectations in a Bioethical Context Based on a Qualitative Survey of Brazilian Women
Authors: Oppenheimer Drauzio , Oppenheimer Agatha Ramos , Vilhena Sthefano Teixeira de , Von Atzingen Augusto Castelli
Published: September 2018

Objective Assisted reproduction combines innovative technologies and new forms of procreation through gamete donation; however, it also leads to moral and ethical issues and to the wide application of referential bioethics. The objective of the present study was to understand the bioethical context of shared oocyte donation.

Methods The present qualitative study used the Collective Subject Discourse methodology to interview donors and recipients in Brazil.

Results Donors suffer from infertility, and in vitro fertilization opens the possibility of having a child; however, the cost is high, and helping the recipient is more important than the financial cost. The recipients regret delaying motherhood; adopting a child is their last option, and they desire to feel the physical stages of pregnancy. The recipients find the rules unfair regarding the lack of an oocyte bank and the fact that the treatment must be performed in shared cycles; however, oocyte donation makes it possible to realize the common dream of motherhood.

Conclusion The obtained data showed that the patients are suffering and frustrated due to infertility, and they realize that in vitro fertilization may be the treatment they need. These women believe that children are essential in the constitution of the family, and scientific advances bring about innovative technologies and new forms of family constitution, with repercussions in the social, economic, political, and family contexts that lead to bioethical questions in Postmodernity.
Risk Assessment and Treatment Guide for Obstetric Thromboprophylaxis: Comprehensive Review of Current Guidelines
Authors: Deering Shad , Thiel Lisa , Eubanks Allison
Published: September 2018

Objective Currently, there are numerous recommendations and often conflicting guidance provided for venous thromboembolism (VTE) prophylaxis in pregnancy. Our objective was to create a one-page risk assessment and treatment guide based on a review of the most recent and evidence-based publications on this subject to simplify the approach and allow all obstetric patients to be properly assessed for risk of VTE and treated if indicated.

Study Design We identified studies by completing a PubMed and MEDLINE search from January of 1980 through March 2017 with articles utilizing a specific combination of the selected general keywords (thrombophilia, pregnancy, VTE, prophylaxis, hypercoagulability, antepartum, postpartum, risk, etc.). We completed the search at the saturation point, meaning that all combinations of the relevant words were directing us to the same articles. After collecting the relevant sources and reviewing them, a total of 10 articles/guidelines were selected for inclusion in the analysis.

Results We outlined every recommendation in the identified articles and guidelines and included any recommendation that was cited in at least three different sources in the final guide. We used American College of Obstetrics and Gynecology recommendations as the base for screening and dosing guidelines and utilized known and published absolute risk values and odds ratios to stratify risk factors. This stratification was used for both antepartum and postpartum recommendations and a single-page guideline was created.

Conclusion This compilation of guidelines integrates the complicated topic into a simple comprehensive guide where women can be identified early and accurately for appropriate VTE prophylaxis to protect them during and after pregnancy.
Sprache und ihre Störungen in der Psychiatrie
Authors: Heim S.
Published: September 2018

Sprache ist zentraler Bestandteil der therapeutischen Interaktion vom Erstkontakt über die Diagnostik bis hin zur Intervention. Trotz dieser Allgegenwart in Psychiatrie und Psychotherapie werden Sprache und Sprachstörungen häufig ausschließlich der Neurologie, Neuropsychologie und Logopädie zugeordnet. Der vorliegende Artikel widmet sich daher zunächst der Einordnung der Sprachfähigkeit in den therapeutischen Alltag. Der zweite Teil erläutert die neurobiologischen Grundlagen der Sprachverarbeitung, die auf der Basis funktioneller Magnetresonanztomografie und unter Verwendung des Jülich-Düsseldorfer zytoarchitektonischen Wahrscheinlichkeitsatlasses des Gehirns identifiziert wurden. Der Fokus liegt hier auf den Funktionen der Broca-Region im linken Frontalhirn und ihrer Einbindung in verteilte Netzwerke der Sprachverarbeitung.
Sport psychiatry – a new frontier in a challenging world
Authors: Morse E. , Reardon C. L. , Newmark T. , Glick I. D.
Published: September 2018

This paper provides an overview of the field of sport psychiatry, including what a psychiatrist does, data on psychiatric issues related to athletes, evolution of the field, how to break into the field, and needs and challenges. Further controlled research is greatly needed, but 2010 may be the moment in time that the field blossoms and grows into maturity.
Structural stability and electro-elastic property of YCOB crystal annealed in harsh environment
Authors: Tian Shiwei , Li Lili , Yu Fapeng , Li Yanlu , Chen Feifei , Duan Xiulan , Cheng Xiufeng , Wang Zhengping , Zhang Shujun , Zhao Xian
Published: September 2018

The YCa4O(BO3)3 (YCOB) piezoelectric crystal has been actively studied for high temperature sensor applications in the last few years. In this paper, the structure stability and electro-elastic properties of the YCOB crystal annealed in a harsh environment (high temperatures of 600–1100 °C and a low atmospheric pressure of 2 × 10−5 atm for 24 h) were studied. The chemical bonding energy of the annealed YCOB crystal was studied, with variations being less than 0.2 eV, showing the high stability of the electronic structure in the YCOB crystal. The energies of vacancy formation (EVF) for Y, Ca, O, and B atoms were analyzed via first principles calculation. The O atoms were found to possess the lowest EVF value, being easier to escape (annealing in critical conditions) and compensate (thermal treatment at elevated temperatures in air) when compared to other atoms, thus leading to oxygen vacancy defects and a decrease in the chemical bonding strength after the annealing process. This is deemed to be the main factor dominating the electro-elastic property changes and their recovery behaviours.
An actively shielded gradient coil design for use in planar MRI systems with limited space
Authors: Wang Yaohui , Wang Qiuliang , Guo Lei , Chen Zhifeng , Niu Chaoqun , Liu Feng
Published: September 2018

In planar magnetic resonance imaging (MRI) systems, gradient coils are usually placed within a very limited space owing to the physical constraints of the small gap size (pole-pole) distance of the permanent magnet. Typically, the unshielded or partially shielded design scheme is adopted to generate required magnetic fields with reduced system costs. However, non-fully shielded coils can induce large eddy currents on the surrounding metal structures, including magnet poles, that significantly impact the imaging performance. This paper elaborates a new design strategy to resolve the limited space problem. Using the peripheral sections of the MRI system, a set of actively shielded gradient coils are purposefully designed. Between the two magnet poles, the actively shielded gradient coils occupy merely four coil layers (six coil layers are usually required), which offers an excellent shielding effect, thus reducing the image distortions. The saved space can be used to integrate a high-efficient cooling system. Moreover, the design scheme does not significantly increase the fabricating complexity.
High-resolution fiber optic surface plasmon resonance sensor for biomedical applications
Authors: Tomyshev Kirill A. , Tazhetdinova Diana K. , Manuilovich Egor S. , Butov Oleg V.
Published: September 2018

This paper presents a modified design of a high-resolution fiber optic sensor that operates on the surface plasmon resonance effect. The sensor is based on the well-known method of generating surface plasmons with the help of an inscribed tilted fiber Bragg grating that excites the cladding modes. Because the original design solution used a polarizing fiber, it was possible to significantly improve the stability of the sensor readings. The specialized mathematical apparatus was used to determine the surface plasmon resonance spectral position. It was experimentally shown that the limit of detection to the refractive index of such a sensor is 2 × 10−6 refractive index units. The sensor's response to the investigated medium temperature change is presented and analyzed. The high resolution of the sensor in detecting protein molecules was demonstrated. Such sensors open wide perspectives for their application in real high-sensitivity sensor systems as biosensors for immune analysis in medical diagnostics.
Patterning well-controlled cross section of ordered 3D architecture via capillary bridge route
Authors: Pi Yueyang , Zhang Bo , Wu Yuchen , Zhang Chi
Published: September 2018

Three-dimensional (3D) ordered nanoparticle microstructures possess multidimensional effects than 2D structures, which bring novel features for the application of biotechnology, magnetic device, catalysis and optoelectronic. However, complexity to manipulate ordered microstructures with additional dimensions triggered by long distance interactions between nanoparticles or external force from fluid, electric or magnetic field, thus leading to random and uncontrollable displacement of nanoparticle. In the present work, well-controlled cross-section of ordered 3D microstructures is proposed on assembly of nanoparticles, which achieved by manipulating capillary bridges. Experimental results reveal that the formation of various cross-sections dependents on concentration (C) and diameter of nanoparticle. Due to the building block and solvents has no special request, this technique can be extend to other materials. Owing to the controllable morphology, we can manipulate the waveguiding distance of 3D architectures. Thus, our research highlight the opportunity for creating cross section controlled 3D architectures with potential applications in optoelectronics.
Reference Correlations for the Thermal Conductivity of 13 Inorganic Molten Salts
Authors: Chliatzou Ch. D. , Assael M. J. , Antoniadis K. D. , Huber M. L. , Wakeham W. A.
Published: September 2018

The available experimental data for the thermal conductivity of 13 inorganic molten salts have been critically examined with the intention of establishing thermal conductivity reference correlations. All experimental data have been categorized into primary and secondary data according to the quality of measurement specified by a series of criteria. Standard reference correlations are proposed for the following molten salts (with estimated uncertainties at the 95% confidence level given in parentheses): LiNO3 (7%), NaNO3 (7%), KNO3 (15%), NaBr (15%), KBr (15%), RbBr (15%), LiCl (17%), NaCl (20%), KCl (17%), RbCl (17%), CsCl (10%), NaI (17%), and RbI (20%).
Contrasting altitudinal trends in leaf anatomy between three dominant species in an alpine meadow
Authors: Zhong Mengying , Shao Xinqing , Wu Ruixin , Wei Xiaoting , van Logtestijn Richard S. P. , Cornelissen Johannes H. C.
Published: September 2018

Variation in leaf anatomical traits underpins the adaptations and phenotypic responses of plant species to their different natural environments. Temperature is a primary driver of plant trait variation along altitudinal gradients. However, other environmental drivers may also play important roles, and the interactions between drivers may have different effects on leaf anatomy for different species of the same larger clade. Such interactions might be especially important along shorter altitudinal (i.e. temperature) gradients. We predicted, therefore, that different monocot species could show idiosyncratic responses of leaf anatomical traits to a short altitudinal gradient. Moreover, for a species in which vegetative growth and reproduction are separated in time, its anatomical responses to altitude may differ and trade-offs between leaf and flowering stem anatomy may occur. To test these hypotheses, we examined leaf anatomy and δ13C signature (a possible indicator of anatomy-related water use efficiency or indicator of response to a decrease in CO2 concentration with altitude) of three dominant and widely distributed monocot species (Scirpus distigmaticus, Elymus nutans, Carex moorcroftii) from seven elevations in an alpine meadow on the Qinghai-Tibetan Plateau. In addition, we examined the flowering stem anatomy of S. distigmaticus, across a short altitudinal gradient (four elevations) in the same region. Leaf anatomical traits (e.g. epidermal cell area, epidermal cell thickness, cuticular layer thickness, xylem transect area, phloem transect area) varied with altitude, but the patterns varied substantially among species and among anatomical traits within species. Additionally, for S. distigmaticus, (allometric) coordination between leaves and flowering stems was apparent for xylem transect area and phloem transect area. Trade-offs between leaf and flowering stem traits were also found for epidermal cell area, epidermal cell thickness and mesophyll cell area. Leaves were more responsive to altitude in their anatomical traits than flowering stems in S. distigmaticus, perhaps reflecting their relatively short period of stem development during a climatically relatively favourable season compared with that for leaves, which already start growing earlier in the year. Further research is needed on the interactive effects of environmental variables, as well as vegetative versus reproductive phenology both across and within suites of species to better understand and upscale plant anatomical responses to climate warming in alpine environments.
Soil erodibility affected by vegetation restoration on steep gully slopes on the Loess Plateau of China
Authors: Zhang Bao-jun , Zhang Guang-hui , Yang Han-yue , Wang Hao , Li Ning-ning
Published: September 2018

Vegetation restoration influences near soil-surface characteristics and thus likely affects soil erodibility. This study was performed to quantify the effects of vegetation restoration on soil erodibility on steep gully slopes, and to identify the potential influencing factors on the Loess Plateau. Three shrub and four grass types distributed on different gully slopes were selected, and six erodibility indicators and an integrated erodibility index (IEI) were applied to indirectly evaluate the effects of vegetation restoration on soil erodibility. The former included the soil erodibility K factor, aggregate stability (the mean weight diameter, MWD, and the mean number of drop impacts, MND), saturated hydraulic conductivity (Ks), cohesion (Coh), and penetration resistance (PR), and the latter was calculated using these indicators and a weighted integration method. The results showed that vegetation restoration on steep gully slopes was effective in reducing soil erodibility on the Loess Plateau, and grasses seemed more effective than shrubs. Compared with the control, the K of vegetation-restored gully slopes decreased by 4.1–24.0%, and MWD, MND, Ks, Coh, and PR increased by 64.0–284.3, 51.4–269.5, 100.5–417.4, 10.1–172.2, and 63.3–278.9% respectively. Consequently, the IEI of the vegetation-restored gully slopes declined by 33.1–81.9%, and the mean reduction percentage of the four grasses was 1.5 times that of the three shrubs. The variation in soil erodibility was closely related to the changes in the soil organic matter content and root mass density with vegetation restoration. The results will help in understanding the soil conservation mechanisms of vegetation restoration on steep gully slopes.
Phasic locus coeruleus activity regulates cortical encoding of salience information
Authors: Vazey Elena M. , Moorman David E. , Aston-Jones Gary
Published: September 2018

Significance

Locus coeruleus (LC) function has been associated with focused attention across species. LC neurons fire tonically or with short phasic bursts. We found that phasic, but not tonic, LC activity produced attentional signals across cortex, including the P300 event-related potential, and revealed distinct long-latency signals in sensory networks. These long-latency signals were seen in subpopulations normally activated by intense or salient stimuli, meaning that phasic LC activation produced salience in sensory neurons. Phasic LC-generated sensory salience signals were tightly temporally regulated, and precisely timed phasic LC activation was able to generate “false salience” in sensory processing networks, in the absence of intense stimuli. Importantly, LC-induced salience signals occurred without changes in arousal, demonstrating independent mechanisms of LC-mediated arousal and attention.
Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin
Authors: Taracanova Alexandra , Tsilioni Irene , Conti Pio , Norwitz Errol R. , Leeman Susan E. , Theoharides Theoharis C.
Published: September 2018

Significance

Mast cells are mandatory for allergic reactions and participate in inflammatory responses in which the peptide substance P (SP) and the cytokine IL-33 are involved. This report shows that SP administered together with IL-33 to cultured human mast cells causes a marked increase in the secretion and gene expression of IL-1β. These responses are mediated via the activation of the SP receptor NK-1 and the IL-33 receptor ST2 and can be inhibited by the natural flavonoid methoxyluteolin. These findings highlight the important role of SP and IL-33 in mast cell secretion of IL-1β and point to targets for the development of therapies for inflammatory diseases.
Enhancement of tensile properties by room-temperature quenching and partitioning of 0.2C–10Mn–2Al steel
Authors: Kim Dong Hwi , Kang Jee-Hyun , Ryu Joo Hyun , Kim Sung-Joon
Published: September 2018

Processing conditions better than those of conventional quenching and partitioning process are suggested for 0.2C–10Mn–2Al steel. The steel can retain 24% of austenite on quenching to room temperature and effectively partition carbon from martensite to austenite at 200°C. The resulting tensile properties were comparable to those produced by conventional quenching and partitioning. Moreover, the suggested processing condition resolves an issue of intercritically annealed medium Mn steels by improving the yield strength and eliminating yield point phenomenon as well as serrated flow.

This paper is part of a Thematic Issue on Medium Manganese Steels.
Emerging mechanisms of asymmetric stem cell division
Authors: Venkei Zsolt G. , Yamashita Yukiko M.
Published: September 2018

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.
Transient T-bet expression functionally specifies a distinct T follicular helper subset
Authors: Fang Difeng , Cui Kairong , Mao Kairui , Hu Gangqing , Li Rao , Zheng Mingzhu , Riteau Nicolas , Reiner Steven L. , Sher Alan , Zhao Keji , Zhu Jinfang
Published: September 2018

T follicular helper (Tfh) cells express transcription factor BCL-6 and cytokine IL-21. Mature Tfh cells are also capable of producing IFN-γ without expressing the Th1 transcription factor T-bet. Whether this IFN-γ–producing Tfh population represents a unique Tfh subset with a distinct differentiation pathway is poorly understood. By using T-bet fate–mapping mouse strains, we discovered that almost all the IFN-γ–producing Tfh cells have previously expressed T-bet and express high levels of NKG2D. DNase I hypersensitivity analysis indicated that the Ifng gene locus is partially accessible in this “ex–T-bet” population with a history of T-bet expression. Furthermore, multicolor tissue imaging revealed that the ex–T-bet Tfh cells found in germinal centers express IFN-γ in situ. Finally, we found that IFN-γ–expressing Tfh cells are absent in T-bet–deficient mice, but fully present in mice with T-bet deletion at late stages of T cell differentiation. Together, our findings demonstrate that transient expression of T-bet epigenetically imprints the Ifng locus for cytokine production in this Th1-like Tfh cell subset.
A smooth mixing flow on a surface with nondegenerate fixed points
Authors: Chaika Jon , Wright Alex
Published: September 2018

We construct a smooth, area preserving, mixing flow with finitely many nondegenerate fixed points and no saddle connections on a closed surface of genus

5
5

. This resolves a problem that has been open for four decades.
Atrophy subtypes in prodromal Alzheimer’s disease are associated with cognitive decline
Authors: ten Kate Mara , Dicks Ellen , Visser Pieter Jelle , van der Flier Wiesje M , Teunissen Charlotte E , Barkhof Frederik , Scheltens Philip , Tijms Betty M ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2018

Alzheimer’s disease is a heterogeneous disorder. Understanding the biological basis for this heterogeneity is key for developing personalized medicine. We identified atrophy subtypes in Alzheimer’s disease dementia and tested whether these subtypes are already present in prodromal Alzheimer’s disease and could explain interindividual differences in cognitive decline. First we retrospectively identified atrophy subtypes from structural MRI with a data-driven cluster analysis in three datasets of patients with Alzheimer’s disease dementia: discovery data (dataset 1: n = 299, age = 67 ± 8, 50% female), and two independent external validation datasets (dataset 2: n = 181, age = 66 ± 7, 52% female; dataset 3: n = 227, age = 74 ± 8, 44% female). Subtypes were compared on clinical, cognitive and biological characteristics. Next, we classified prodromal Alzheimer’s disease participants (n = 603, age = 72 ± 8, 43% female) according to the best matching subtype to their atrophy pattern, and we tested whether subtypes showed cognitive decline in specific domains. In all Alzheimer’s disease dementia datasets we consistently identified four atrophy subtypes: (i) medial-temporal predominant atrophy with worst memory and language function, older age, lowest CSF tau levels and highest amount of vascular lesions; (ii) parieto-occipital atrophy with poor executive/attention and visuospatial functioning and high CSF tau; (iii) mild atrophy with best cognitive performance, young age, but highest CSF tau levels; and (iv) diffuse cortical atrophy with intermediate clinical, cognitive and biological features. Prodromal Alzheimer’s disease participants classified into one of these subtypes showed similar subtype characteristics at baseline as Alzheimer’s disease dementia subtypes. Compared across subtypes in prodromal Alzheimer’s disease, the medial-temporal subtype showed fastest decline in memory and language over time; the parieto-occipital subtype declined fastest on executive/attention domain; the diffuse subtype in visuospatial functioning; and the mild subtype showed intermediate decline in all domains. Robust atrophy subtypes exist in Alzheimer’s disease with distinct clinical and biological disease expression. Here we observe that these subtypes can already be detected in prodromal Alzheimer’s disease, and that these may inform on expected trajectories of cognitive decline.
Improvement in Hepatic Fibrosis Biomarkers Associated With Chemokine Receptor Inactivation Through Mutation or Therapeutic Blockade
Authors: Sherman Kenneth E , Abdel-Hameed Enass , Rouster Susan D , Shata Mohamed Tarek M , Blackard Jason T , Safaie Parham , Kroner Barbara , Preiss Liliana , Horn Paul S , Kottilil Shyam
Published: September 2018

Background

The C-C chemokine receptor Type 5 (CCR5) is a key receptor for human immunodeficiency virus type 1 (HIV-1) entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a role in the development of hepatic fibrosis and evaluated the longitudinal effect of natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 patients.

Methods

To accomplish this goal, we examined 2 distinct cohorts. First, we evaluated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MHCS), which included subjects with HIV and hepatitis C virus (HCV) coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1 infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc. The enhanced liver fibrosis (ELF) index was validated against liver histology obtained from HCV/HIV and HCV patients and demonstrated strong correlation with fibrosis stage.

Results

In both the MHCS patients and patients treated with cenicriviroc, CCR5 mutation or blockade was associated with a significant decrease in the ELF index. Among the patients with the delta-32 allele, the ELF index rate significantly decreased in sequential samples as compared to CCR5 wild-type patients (P = .043). This was not observed in control subjects treated with efavirenz nor with a lower dose of 100 mg cenicriviroc.

Conclusion

These findings suggest that hepatic fibrosis in HIV-1 infected patients can be modulated by the mutation of CCR5 and/or use of CCR5/CCR2 blockade agents.

Clinical Trials Registration

NCT01338883.
The fascinating world of non-coding RNA and how it may help to unravel the mysteries of tooth movement regulation
Authors: Proff Peter , Kirschneck Christian
Published: September 2018

The innovative study presented by Huang and co-workers in this issue of the European Journal of Orthodontics is one of the first giving insight into the mostly disregarded world of non-coding ribonucleic acids in orthodontics. In other fields of science non-coding ribonucleic acids have been shown to play a major role in the regulation of cell metabolism as well as the aetiology of diseases such as cancer, Alzheimer’s disease, and periodontitis. Their pilot study on the possible function of differentially expressed long non-coding ribonucleic acids during mechanical compression of periodontal ligament stem cells, as well as methodological approach of whole-transcriptome sequencing with bioinformatory analyses, provides ample possibilities for future basic orthodontic research, which will hopefully greatly expand our knowledge of tooth movement regulation. This field could provide new therapeutic opportunities and diagnostic and treatment aids for orthodontists as well as our patients. This commentary will discuss the implications and importance of the findings of Huang and co-workers in the context of current research in orthodontics and molecular biology.
Children’s motivation overcame parental hesitation: active school transportation in Sweden
Authors: Rutberg Stina , Lindqvist Anna-Karin
Published: September 2018

To meet the recommendation of 60 min of daily physical activity, children can be encouraged to walk or bike to school, which is known as active school transportation (AST). The aim of this study was to describe parents’ attitudes to AST and to explore their experience when implementing interventions to promote it. To explore parent’s experiences, we collected pre- and post-intervention data via three questionnaires, using both closed and open questioning techniques. The pre-intervention questionnaire informed development of the intervention. Open-ended questions (pre- and post-) were analyzed with qualitative content analysis. In the intervention, there were 42 children, with 63 parents answering pre-intervention questionnaires and 44 answering a post-intervention questionnaire. The analysis resulted in one main theme: children’s motivation and active travel reduces parents’ perception of problems, along with three subthemes: parental concerns and suggestions for solutions, children’s motivation guides parental choice of transport mode, and trying it changes attitudes. In conclusion, it is beneficial to use the enthusiasm and motivation of children to overcome parental hesitation with AST. In addition, it is critical to acknowledge their concerns, as they are the gatekeepers to the children’s use of AST and it is valuable to empower parents when designing relevant interventions. Interventions to increase AST could preferably target changed behavior, and parents’ confidence in their children’s ability to use active transport in a safe and effective way, vs focusing on changing parental attitudes.
Loss of CRB2 in Müller glial cells modifies a CRB1-associated retinitis pigmentosa phenotype into a Leber congenital amaurosis phenotype
Authors: Quinn Peter M , Mulder Aat A , Henrique Alves C , Desrosiers Mélissa , de Vries Sharon I , Klooster Jan , Dalkara Deniz , Koster Abraham J , Jost Carolina R , Wijnholds Jan
Published: September 2018

Variations in the human Crumbs homolog-1 (CRB1) gene lead to an array of retinal dystrophies including early onset of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) in children. To investigate the physiological roles of CRB1 and CRB2 in retinal Müller glial cells (MGCs), we analysed mouse retinas lacking both proteins in MGC. The peripheral retina showed a faster progression of dystrophy than the central retina. The central retina showed retinal folds, disruptions at the outer limiting membrane, protrusion of photoreceptor nuclei into the inner and outer segment layers and ingression of photoreceptor nuclei into the photoreceptor synaptic layer. The peripheral retina showed a complete loss of the photoreceptor synapse layer, intermingling of photoreceptor nuclei within the inner nuclear layer and ectopic photoreceptor cells in the ganglion cell layer. Electroretinography showed severe attenuation of the scotopic a-wave at 1 month of age with responses below detection levels at 3 months of age. The double knockout mouse retinas mimicked a phenotype equivalent to a clinical LCA phenotype due to loss of CRB1. Localization of CRB1 and CRB2 in non-human primate (NHP) retinas was analyzed at the ultrastructural level. We found that NHP CRB1 and CRB2 proteins localized to the subapical region adjacent to adherens junctions at the outer limiting membrane in MGC and photoreceptors. Our data suggest that loss of CRB2 in MGC aggravates the CRB1-associated RP-like phenotype towards an LCA-like phenotype.
Extent of Resection and Residual Tumor Thresholds for Postoperative Total Seizure Freedom in Epileptic Adult Patients Harboring a Supratentorial Diffuse Low-Grade Glioma
Authors: Still Megan E H , Roux Alexandre , Huberfeld Gilles , Bauchet Luc , Baron Marie-Hélène , Fontaine Denys , Blonski Marie , Mandonnet Emmanuel , Guillevin Remy , Guyotat Jacques , Taillandier Luc , Capelle Laurent , Duffau Hugues , Pallud Johan
Published: September 2018

BACKGROUND

Epileptic seizures impair quality of life in diffuse low-grade glioma (DLGG) patients. Tumor resection significantly impacts postoperative seizure control, but the precise extent of resection (EOR) required for optimal seizure control is not clear yet.

OBJECTIVE

To identify the EOR and residual tumor volume that correlated to postoperative seizure control, defined as a total seizure freedom (Class 1A in reference to Engel classification system) with and without antiepileptic drugs in patients undergoing surgical resection of supratentorial DLGG.

METHODS

A retrospective review was conducted of all patients who underwent first-line surgical resection of supratentorial DLGG who presented with preoperative seizures without adjuvant oncological treatment. EOR and residual tumor volume were quantified from pre- and post-operative magnetic resonance imagings. Receiver operating characteristic curves were plotted to determine the EOR and residual tumor volume that corresponded to optimal postoperative seizure control.

RESULTS

Of the 346 included patients, 65.5% had controlled seizures postoperatively, with higher age at resection (adjusted OR per unit, 1.03 [95% confidence interval:1.01-1.06], P = .043) and higher percentage of resection (adjusted OR per unit, 1.02 [95% confidence interval:1.00-1.03], P < .001) found as independent predictors of postoperative seizure control. Optimal EOR was ≥91% and optimal residual tumor volume was ≤19 cc to improve postoperative seizure control.

CONCLUSION

Postoperative seizure control is more likely when EOR is ≥91% and/or when residual tumor volume is ≤19 cc in supratentorial DLGG gliomas who present with seizures. Resected peritumoral cortex should, however, be taken into account in future studies.
Longitudinal Cognitive Performance in Individuals at Ultrahigh Risk for Psychosis: A 10-year Follow-up
Authors: Allott Kelly , Wood Stephen J , Yuen Hok Pan , Yung Alison R , Nelson Barnaby , Brewer Warrick J , Spiliotacopoulos Daniela , Bruxner Annie , Simmons Magenta , Broussard Christina , Mallawaarachchi Sumudu , Pantelis Christos , McGorry Patrick D , Lin Ashleigh
Published: September 2018

It remains unclear whether the onset of psychosis is associated with deterioration in cognitive performance. The aim of this study was to examine the course of cognitive performance in an ultrahigh risk (UHR) cohort, and whether change in cognition is associated with transition to psychosis and change in functioning. Consecutive admissions to Personal Assessment and Crisis Evaluation (PACE) Clinic between May 1994 and July 2000 who had completed a comprehensive cognitive assessment at baseline and follow-up were eligible (N = 80). Follow-up ranged from 7.3 to 13.4 years (M = 10.4 years; SD = 1.5). In the whole sample, significant improvements were observed on the Similarities (P = .03), Information (P < .01), Digit Symbol Coding (P < .01), and Trail Making Test-B (P = .01) tasks, whereas performance on the Rey Auditory Verbal Learning Test (Trials 1–3) declined significantly (P < .01) over the follow-up period. Change in performance on cognitive measures was not significantly associated with transition status. Taking time to transition into account, those who transitioned after 1 year showed significant decline on Digit Symbol Coding, whereas those who did not transition improved on this measure (P = .01; effect size [ES] = 0.85). Small positive correlations were observed between improvements in functioning and improvements in performance on Digit Symbol Coding and Arithmetic (0.24, P = .03 and 0.28, P = .01, respectively). In summary, the onset of psychosis was not associated with deterioration in cognitive ability. However, specific findings suggest that immediate verbal learning and memory, and processing speed may be relevant domains for future risk models and early intervention research in UHR individuals.
Orderliness predicts academic performance: behavioural analysis on campus lifestyle
Authors: Cao Yi , Gao Jian , Lian Defu , Rong Zhihai , Shi Jiatu , Wang Qing , Wu Yifan , Yao Huaxiu , Zhou Tao
Published: September 2018

Quantitative understanding of relationships between students' behavioural patterns and academic performances is a significant step towards personalized education. In contrast to previous studies that were mainly based on questionnaire surveys, recent literature suggests that unobtrusive digital data bring us unprecedented opportunities to study students' lifestyles in the campus. In this paper, we collect behavioural records from undergraduate students' (
N
= 18 960) smart cards and propose two high-level behavioural characters, orderliness and diligence. The former is a novel entropy-based metric that measures the regularity of campus daily life, which is estimated here based on temporal records of taking showers and having meals. Empirical analyses on such large-scale unobtrusive behavioural data demonstrate that academic performance (GPA) is significantly correlated with orderliness. Furthermore, we show that orderliness is an important feature to predict academic performance, which improves the prediction accuracy even in the presence of students' diligence. Based on these analyses, education administrators could quantitatively understand the major factors leading to excellent or poor performance, detect undesirable abnormal behaviours in time and thus implement effective interventions to better guide students' campus lives at an early stage when necessary.
The atypically high modulus of pollen exine
Authors: Qu Zihao , Meredith J. Carson
Published: September 2018

Sporopollenin, the polymer comprising the exine (outer solid shell) of pollen, is recognized as one of the most chemically and mechanically stable naturally occurring organic substances. The elastic modulus of sporopollenin is of great importance to understanding the adhesion, transport and protective functions of pollen grains. In addition, this fundamental mechanical property is of significant interest in using pollen exine as a material for drug delivery, reinforcing fillers, sensors and adhesives. Yet, the literature reports of the elastic modulus of sporopollenin are very limited. We provide the first report of the elastic modulus of sporopollenin from direct indentation of pollen particles of three plant species: ragweed (
Ambrosia artemisiifolia
), pecan (
Carya illinoinensis
) and Kentucky bluegrass (
Poa pratensis
). The modulus was determined with atomic force microscopy by using direct nanomechanical mapping of the pollen shell surface. The moduli were atypically high for non-crystalline organic biomaterials, with average values of 16 ± 2.5 GPa (ragweed), 9.5 ± 2.3 GPa (pecan) and 16 ± 4.0 GPa (Kentucky bluegrass). The amorphous pollen exine has a modulus exceeding known non-crystalline biomaterials, such as lignin (6.7 GPa) and actin (1.8 GPa). In addition to native pollen, we have investigated the effects of exposure to a common preparative base–acid chemical treatment and elevated humidity on the modulus. Base–acid treatment reduced the ragweed modulus by up to 58% and water vapour exposure at 90% relative humidity reduced the modulus by 54% (pecan) and 72% (Kentucky bluegrass). These results are in agreement with recently published estimates of the modulus of base–acid-treated ragweed pollen of 8 GPa from fitting to mechanical properties of ragweed pollen–epoxy composites.