bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive Standardised Uptake Value for Verification of the Use of Previously Validated Reference Region for [18F]Flortaucipir and [18F]Florbetapir Brain PET Studies
Authors: de Vries Bart M. , Timmers Tessa , Wolters Emma E. , Ossenkoppele Rik , Verfaillie Sander C. J. , Schuit Robert C. , Scheltens Philip , van der Flier Wiesje M. , Windhorst Albert D. , van Berckel Bart N. M. , Boellaard Ronald , Golla Sandeep S. V.
Published: January 2021

Purpose

The simplified reference tissue model (SRTM) is commonly applied for the quantification of brain positron emission tomography (PET) studies, particularly because it avoids arterial cannulation. SRTM requires a validated reference region which is obtained by baseline-blocking or displacement studies. Once a reference region is validated, the use should be verified for each new subject. This verification normally requires volume of distribution (VT) of a reference region. However, performing dynamic scanning and arterial sampling is not always possible, specifically in elderly subjects and in advanced disease stages. The aim of this study was to investigate the use of non-invasive standardised uptake value (SUV) approaches, in comparison to VT, as a verification of the previously validated grey matter cerebellum reference region for [18F]flortaucipir and [18F]florbetapir PET imaging in Alzheimer’s disease (AD) patients and controls.

Procedures

Dynamic 130-min [18F]flortaucipir PET scans obtained from nineteen subjects (10 AD patients) and 90-min [18F]florbetapir dynamic scans obtained from fourteen subjects (8 AD patients) were included. Regional VT’s were estimated for both tracers and were considered the standard verification of the previously validated reference region. Non-invasive SUVs corrected for body weight (SUVBW), lean body mass (SUL), and body surface area (SUVBSA) were obtained by using later time intervals of the dynamic scans. Simulations were also performed to assess the effect of flow and specific binding (BPND) on the SUVs.

Results

A low SUV corresponded well with a low VT for both [18F]flortaucipir and [18F]florbetapir. Simulation confirmed that SUVs were only slightly affected by flow changes and that increases in SUV were predominantly determined by the presence of specific binding.

Conclusions

In situations where dynamic scanning and arterial sampling is not possible, a low SUV(80–100 min) for [18F]flortaucipir and a low SUV(50–70 min) for [18F]florbetapir may be used as indication for absence of specific binding in the grey matter cerebellum reference region.
Vorbild KITA
Authors: Wirth Robert
Published: January 2021

Für das Gelingen einer stationären Unterbringung ist deren Beginn entscheidend. Der Beitrag schlägt ein Konzept vor, das die Fachkräfte sowohl im ambulanten als auch im stationären Bereich der Kinder- und Jugendhilfe an einem Fall arbeiten lässt.
Meteorological and hydrological drought monitoring using several drought indices
Authors: Salimi Hana , Asadi Esmail , Darbandi Sabereh
Published: January 2021

With respect to the necessity of comprehensive studies on drought and also high damages that caused by drought, this research studied the meteorological and hydrological droughts. In this study, Lighvan, Navroud and Seqez basins with different climates were selected. We used monthly data of stream flow, precipitation and evaporation from 1992 to 2016 for the study of drought phenomena. The aim at this study is to analyze the SPI and SPEI for determination of dry and wet meteorological periods and use of the SSI for the exploration of hydrological drought. The analysis of drought characteristics such as intensity and duration in three areas with different climates shows that the climate change has a major impact on the characteristics of the droughts. The relations between the duration and severity of drought have been more accurate in the period of 9 months in the Navroud watershed basin. The most significant events are SPI-9 with the duration of 57 months and the severity of 34.7, SPEI-9 with the duration of 34 months and the severity of 28.09 and SSI-9 with the duration of 41 months and the severity of 30.2. According to the obtained equations in different time periods, it was resulted that the highest accuracy was observed in the relationship between the meteorological and hydrological drought characteristics in the watershed basin of Seqez for a period of 6 months. The results show that in all three basins, the correlation between the meteorological and hydrological drought is significant at the level of 99%. Results show that hydrological and meteorological droughts in Navroud and Lighvan basins have a significant correlation with 48-month periods and in the Seqez basin with 12- and 24-month periods, and the relations between hydrological droughts and meteorological droughts were obtained using the nonlinear linear models (polynomial, exponential and logarithmic). The good R2 between the duration and severity of SPI-9 and SSI-9 is 0.8 and 0.92, respectively, for polynomial equations. The maximum determination coefficient of duration and severity of SPEI-9 and SSI-9 is 0.72 and 0.82, respectively, using polynomial equation. The application of several indices indicating different components of the hydrological cycle integrates many factors that affect and trigger droughts, and thus can help in providing a wider realization of the characteristics of droughts on various water sections.
Utility of forward and inverse modeling in 2D electric tomography for Hydrogeologic studies
Authors: Melouah Oualid , Hichem Zerrouki
Published: January 2021

The choice of adequate techniques and arrays in electric tomography prospection is a difficult task; it depends generally on subsurface geology and the referred objective, this study is conducted in southern Algerian Sahara aquifer using 2D electric tomography techniques, the goal is testing different arrays configuration, using 2D model simulating the subsurface geology, the validated parameters from the theoretical study are applied to the real data, the results attest the usefulness of synthetic modeling choosing the correct parameters in geophysical prospection.
An innovative approach for high-performance road pavement monitoring using black box
Authors: Meocci Monica , Branzi Valentina , Sangiovanni Andrea
Published: January 2021

One of the criteria adopted by the Word Bank with the aim of defining the economic level of a country is represented by the condition of the road pavements. To ensure adequate road pavement quality, road authorities should be continuously monitoring and repair the detected anomalies. To fast solve problems associated with poor quality of road surface such as comfort or safety, the presence of distress must be detected quickly. The high-performance pavement distress detection, such as those base on the image processing or on the laser scanning, is very expensive and does not allow to the road administration to conduct the appropriate monitoring campaigns. To solve these problems, the paper describes the pave box methodology, an innovative and immediately operational distress detection approach based on the exploitation of data collected by the black boxes located inside the vehicles that routinely pass on the road network. Data processing and the algorithms used in the post-processing evaluation of the vertical acceleration were compared with existing visual surveys procedures such as PCI. Two different indices have been proposed to detect and classify both the local damages and the global condition of the entire road. Pave box provides a robust evaluation of the pavement condition that allows to detect all the severe distress and not less than 70% of the minor damages on the pavement surface. The proposal is characterized by low time and cost consumption and it represents an effective tool for road authorities.
Der Biomarker adrenokortikotropes Hormon (ACTH)
Authors: Oremek G. M. , Passek K. , Bendels M. H. , Ohlendorf D.
Published: January 2021

Die vorliegende Übersicht über den Biomarker adrenokortikotropes Hormon (ACTH) wird im Rahmen der Serie „Tumormarker“ des Zentralblatt für Arbeitsmedizin, Arbeitsschutz und Ergonomie publiziert, die sich mit dem immer häufigeren Gebrauch der Bestimmung von spezifischen Markern bei sog. Manager-Vorsorgen und Check-up-Untersuchungen beschäftigt. ACTH eignet sich grundsätzlich nicht für solch eine Vorsorgeuntersuchung, sondern ist ein Marker zur Therapie‑, Verlaufs- und Rezidivkontrolle von Störungen der kortikotropen Achse. Hier zeigt dieser eine hohe Sensitivität und Spezifität, wobei der Marker aber auf keinen Fall als Screening-Parameter zur Frühdiagnostik aufgrund der zirkadianen Rhythmik und Abhängigkeit von Stressoren eingesetzt werden soll.
Die Gestaltung des Übergangs zur Weiterführenden Schule – Welche Maßnahmen wurden und werden an Grundschulen in NRW praktiziert?
Authors: van Ophuysen Stefanie , Schürer Sina , Bloh Bea
Published: January 2021

Studien zum Übergang von der Grund- in die weiterführende Schule gibt es zu zahlreichen Themen. Wie Grundschulen den Übergang zur weiterführenden Schule gestalten, wurde bislang jedoch kaum erforscht. Auf Basis des Forschungsstands werden relevante Maßnahmen identifiziert. In einer online-Befragung an 106 Grundschulen in Nordrhein-Westfalen wurde erfasst, inwiefern diese Maßnahmen tatsächlich umgesetzt werden und als wie relevant bzw. schwierig ihre Umsetzung erachtet wird. Die Ergebnisse werden verglichen mit Daten einer Studie, die 2002 an 71 Grundschulen durchgeführt wurde. Es zeigt sich eine hohe Stabilität der Gestaltung in den letzten 15 Jahren. Maßnahmen, die auf stufenübergreifender Kooperation basieren, werden heute zwar häufiger praktiziert, stehen aber weiterhin am Ende der Rangreihe.
Morphology and mineralogy of ambient particulate matter over mid-Brahmaputra Valley: application of SEM–EDX, XRD, and FTIR techniques
Authors: Bora Jayanta , Deka Pratibha , Bhuyan Pranamika , Sarma Kali Prasad , Hoque Raza Rafiqul
Published: January 2021

Ambient particulate matter (PM), collected during a dust event over mid-Brahmaputra Valley of India, was characterized. The PM samples were analyzed using scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM–EDX), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) techniques. The SEM micrographs revealed varied shapes of the PM, viz. spherical, irregular, angular, cluster, flaky, rod-like, crystalline and agglomerate structures indicating the probable nature of their sources and formation as biogenic, geogenic, or anthropogenic. Some biogenic particles like plant materials, pollens, and diatoms were captured under SEM. The presence of diatom in PM samples was indicative of wind-blown dust from the dried bed of the Brahmaputra River. The honeycomb-like structures of brochosomes secreted by the leafhoppers of the Cicadellidae family were also captured. On the contrary, the background sample had mostly carbonaceous particles. The XRD and FTIR analyses indicated the presence of quartz, feldspar, kaolinite, illite, augite, and calcium aluminum silicate, cerussite, calcite, montmorllonite, and organic carbon. The airmass backward trajectory analysis explained the local contribution of the dust.
Synthesis of metal–organic frameworks (MOFs) MIL-100(Fe) functionalized with thioglycolic acid and ethylenediamine for removal of eosin B dye from aqueous solution
Authors: Tella Adedibu C. , Bamgbose Janet T. , Adimula Vincent O. , Omotoso Mary , Elaigwu Sunday E. , Olayemi Victoria T. , Odunola Olusegun A.
Published: January 2021

The interaction of eosin B dye from aqueous solution with MIL-100(Fe) and functionalized MIL-100(Fe) metal–organic frameworks (MOFs) is reported in this study. MIL-100(Fe) was prepared and functionalized with thioglycolic acid (TH) and ethylenediammine (ED) separately by incorporating the thiol (–SH) and the amine (–NH2) group of the functionalizing agents into the open metal sites of the MIL-100(Fe) to obtain the acidic (TH-MIL-100) and basic (ED-MIL-100) forms of the MOF respectively. Characterization of the MOFs was done by melting point analysis, elemental analysis, spectroscopic techniques, scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) analysis. The adsorption experiments were carried out at different conditions such as pH, adsorbent dosage, contact time, temperature, and initial concentration of the dye to estimate the optimum conditions and the maximum adsorption capacities. Adsorption capacities were observed to increase in the order of ED-MIL-100 < MIL-100 < TH-MIL-100, while the TH-MIL-100 was the most effective in the removal process due to acid–base interaction between the acidic thiol group (–SH) and the alkaline medium of eosin B dye solution. The Langmuir Isotherm was seen to fit well to adsorption data obtained for all three adsorbent materials studied, and adsorption processes followed the pseudo-second order kinetics. This study, therefore, indicates the suitability of functionalization of MIL-100(Fe) towards improving its adsorption capacity.
Design aspects of (super)hydrophobic mesh based oil-collecting device with improved efficiency
Authors: Xu Weikang , Zhang Zhentao , Cai Xiaomei , Hong Yazhen , Lin Tianliang , Lei Tingping
Published: January 2021

Effective treatment of frequent oil spills and endless discharged oily wastewater is crucial for the ecosystem and human health. In the past two decades, the collection of oil from water surface has been widely studied through the simple fabrication of superhydrophobic meshes with various coating materials, but little attention is paid to the design aspects of the meshes based oil-collecting device and practical oil collection. Here, 3D-printing devices with different configurations of (super)hydrophobic meshes, circular truncated cone (CTC), cylinder and inverted CTC, and the same inverted cone-shaped structure (below the meshes for temporary oil storage) are investigated. Results demonstrate that the CTC meshes based device especially for an oblate one not only shows higher stability and discharge of the collected oils than previous reports, but also allows floating oils to enter the (super)hydrophobic mesh faster. We anticipate that future success in developing high-performance (super)hydrophobic meshes and the further optimization of the CTC mesh-based device parameters will make our proposed device more practical for the treatment of real-life oil spills.
After the Accord
Authors: Garbade Kenneth D.
Published: January 2021

In this book Garbade, a former analyst at a primary dealer and researcher at the Federal Reserve Bank of New York, traces the evolution of open market operations, Treasury debt management, and the microstructure of the US government securities markets following the 1951 Treasury-Federal Reserve. This volume examines how these operations evolved, responding both to external forces and to one another. Utilising a vast scope of primary material, the work provides insight into how officials fashioned the instruments, facilities, and procedures needed to advance their policy objectives in light of their novel freedoms and responsibilities. Students and scholars of macroeconomics, financial regulation, and the history of central banking and the Federal Reserve will find this volume a welcome addition to Garbade's earlier studies of Treasury debt operations during World War I, the 1920s, and the Great Depression and since 1983.
The Study of Speech Processes
Authors: Boucher Victor J.
Published: January 2021

There has been a longstanding bias in the study of spoken language towards using writing to analyse speech. This approach is problematic in that it assumes language to be derived from an autonomous mental capacity to assemble words into sentences, while failing to acknowledge culture-specific ideas linked to writing. Words and sentences are writing constructs that hardly capture the sound-making actions involved in spoken language. This book brings to light research that has long revealed structures present in all languages but which do not match the writing-induced concepts of traditional linguistic analysis. It demonstrates that language processes are not physiologically autonomous, and that speech structures are structures of spoken language. It then illustrates how speech acts can be studied using instrumental records, and how multisensory experiences in semantic memory couple to these acts, offering a biologically-grounded understanding of how spoken language conveys meaning and why it develops only in humans.
Medievalism
Authors: Utz Richard
Published: January 2021

This book is called a manifesto because it has an unapologetically political objective. Richard Utz wants to help reform the way we think about and practise our academic engagement with medieval culture, and he uses his own observations as a medievalist and medievalism-ist over the last twenty-five years to offer ways in which we might reconnect with the general public that has allowed us to become, since the late nineteenth century, a rather exclusive clan of specialists who communicate mostly with each other. The traditional academic study of the Middle Ages, after more than a century of growing and plateauing, is now on the decline. While, at least over the next five to ten years, we will still be basking in the reassuring proximity (at conferences) of thousands of others who are involved in what we do ourselves, there is a manifest discrepancy between the large number of students who request that we address their love of Harry Potter, Lord of the Rings, Game of Thrones, and medieval-themed video and computer games, and the decreasing number of actual medievalists hired to replace retiring colleagues. We should pursue more lasting partnerships with so-called amateurs and enthusiasts for the sake of a sustainable future engagement with medieval culture. Richard Utz suggests some ways we might do this, and looks forward to 'a more truly co-disciplinary, inclusive, democratic, and humanistic engagement with what we call, for better or worse, the Middle Ages'.
Looking for Loopholes
Authors: Leun Joanne van der
Published: January 2021

Looking for Loopholes is a detailed account of how illegal immigrants manage to integrate into Dutch society. Drawing on long-term research in the four largest cities in the Netherlands, van der Leun discusses illegal immigration's relationships with illegal employment and criminal involvement, as well as aspects of education, housing, health care and police surveillance. Throughout, she combines the perspectives of immigrants with that of those who implement policies to discourage them, revealing growing tensions between restrictive rules and day-to-day reality.
An Introduction to International Migration Studies
Authors: Martiniello Marco
Published: January 2021

Focusing mainly on the European experience including Eastern Europe, this important volume offers an advanced introduction to immigrant incorporation studies from a historical, empirical and theoretical perspective. Beyond incorporation theories, renowned scholars in the field explore incorporation in action in different fields, policy issues and normative dimensions.
Human or not? Political rhetoric and foreign policy attitudes
Authors: Utych Stephen M.
Published: January 2021

When the United States intervenes in foreign countries, the lives of both foreign combatants and foreign civilians are put at risk. I examine two rhetorical strategies, the use of sanitized and dehumanizing language that can influence the public's support of foreign intervention. In the context of foreign policy, sanitized language operates by obscuring casualties of war, while dehumanizing language operates by devaluing the lives of groups of individuals. Drawing on data from two experiments, I find that sanitized language operates through creating less of an emotional reaction toward casualties of war, which causes individuals to adopt more hawkish foreign policy attitudes. I find that dehumanizing language also leads to more hawkish foreign policy attitudes, but, contrary to expectations, does not lead to increased disgust or anger toward dehumanized groups.
BIASES IN INTEGER PARTITIONS
Authors: KIM BYUNGCHAN , KIM EUNMI
Published: January 2021

We show that there are biases in the number of appearances of the parts in two residue classes in the set of ordinary partitions. More precisely, let

$p_{j,k,m} (n)$
be the number of partitions of n such that there are more parts congruent to j modulo m than parts congruent to k modulo m for

$m \geq 2$
. We prove that

$p_{1,0,m} (n)$
is in general larger than

$p_{0,1,m} (n)$
. We also obtain asymptotic formulas for

$p_{1,0,m}(n)$
and

$p_{0,1,m}(n)$
for

$m \geq 2$
.
School-based obesity interventions in the metropolitan area of Rio De Janeiro, Brazil: pooled analysis from five randomised studies
Authors: Rodrigues Renata da R. M. , Hassan Bruna K. , Sgambato Michele R. , Souza Bárbara da S. N. , Cunha Diana B. , Pereira Rosangela A. , Yokoo Edna M. , Sichieri Rosely
Published: January 2021

School-based studies, despite the large number of studies conducted, have reported inconclusive results on obesity prevention. The sample size is a major constraint in such studies by requiring large samples. This pooled analysis overcomes this problem by analysing 5926 students (mean age 11·5 years) from five randomised school-based interventions. These studies focused on encouraging students to change their drinking and eating habits, and physical activities over the one school year, with monthly 1-h sessions in the classroom; culinary class aimed at developing cooking skills to increase healthy eating and attempts to family engagement. Pooled intention-to-treat analysis using linear mixed models accounted for school clusters. Control and intervention groups were balanced at baseline. The overall result was a non-significant change in BMI after one school year of positive changes in behaviours associated with obesity. Estimated mean BMI changed from 19·02 to 19·22 kg/m2 in the control group and from 19·08 to 19·32 kg/m2 in the intervention group (P value of change over time = 0·09). Subgroup analyses among those overweight or with obesity at baseline also did not show differences between intervention and control groups. The percentage of fat measured by bioimpedance indicated a small reduction in the control compared with intervention (P = 0·05). This large pooled analysis showed no effect on obesity measures, although promising results were observed about modifying behaviours associated with obesity.
Binge eating among young adults: association with sociodemographic factors, nutritional intake, dietary n-6:n-3 ratio and impulsivity
Authors: Khoury Maryse , Chamsine Santa , Merheb Camil , Arfoul Edouard , Rached Maria , Younes Farah , El Osta Nada , Laye Sophie , Aoun Carla , Papazian Tatiana , Rabbaa Khabbaz Lydia
Published: January 2021

Binge eating behaviour (BE) is the major symptom of binge eating disorder (BED). This study aimed to compare the nutritional intake in the presence or absence of BE, with a particular focus on dietary n-6:n-3 ratio, to assess the association between BE and impulsivity and the mediating effect of BMI on this association. A total of 450 university students (age 18–28 years) participated. The self-administered questionnaires were a semi-quantitative FFQ and the UPPS-P Impulsive Behavior Scale and the binge eating scale. The average BE score was 11·6 (se 7·388), and 20 % of the total participants scored above the cut-off of 17, thus presenting BE with 95 % CI of 16·3, 23·7 %. Our study revealed that greater BMI, higher total energy intake, greater negative urgency and positive urgency scores were significantly associated with BE. Participants with high value of dietary n-6:n-3 ratio were 1·335 more at risk to present a BE compared with those with a lower value of this ratio (P = 0·017). The relationship between BE score and UPPS domains score was not mediated by the BMI. This is the first study reporting a link between high dietary n-6:n-3 ratio and BE as well as the fact that BE was linked to both, negative and positive urgencies, and that the association between BE and impulsivity was not mediated by BMI. These findings can help to deal more efficiently with people suffering from BE, a symptom that can precede the development of BED.
RATIONAL LOCAL SYSTEMS AND CONNECTED FINITE LOOP SPACES
Authors: HEARD DREW
Published: January 2021

Greenlees has conjectured that the rational stable equivariant homotopy category of a compact Lie group always has an algebraic model. Based on this idea, we show that the category of rational local systems on a connected finite loop space always has a simple algebraic model. When the loop space arises from a connected compact Lie group, this recovers a special case of a result of Pol and Williamson about rational cofree G-spectra. More generally, we show that if K is a closed subgroup of a compact Lie group G such that the Weyl group WGK is connected, then a certain category of rational G-spectra “at K” has an algebraic model. For example, when K is the trivial group, this is just the category of rational cofree G-spectra, and this recovers the aforementioned result. Throughout, we pay careful attention to the role of torsion and complete categories.
Depressive symptoms and allostatic load have a bidirectional association among Puerto Rican older adults
Authors: McClain Amanda C. , Xiao Rui S. , Tucker Katherine L. , Falcón Luis M. , Mattei Josiemer
Published: January 2021

Background

Depression is strongly associated with chronic disease; yet, the direction of this relationship is poorly understood. Allostatic load (AL) provides a framework for elucidating depression-disease pathways. We aimed to investigate bidirectional, longitudinal associations of baseline depressive symptoms or AL with 5-year AL or depressive symptoms, respectively.

Methods

Data were from baseline, 2-year, and 5-year visits of 620 adults (45–75 years) enrolled in the Boston Puerto Rican Health Study. The Center for Epidemiology Studies Depression (CES-D) scale (0–60) captured depressive symptoms, which were categorized at baseline as low (<8), subthreshold (8–15), or depression-likely (⩾16) symptoms. AL was calculated from 11 parameters of biological functioning, representing five physiological systems. Baseline AL scores were categorized by the number of dysregulated parameters: low (0–2), moderate (3–5), or high (⩾6) AL. Multivariable, multilevel random intercept and slope linear regression models were used to examine associations between 3-category baseline CES-D score and 5-year continuous AL score, and between baseline 3-category AL and 5-year continuous CES-D score.

Results

Baseline subthreshold depressive symptoms [(mean (95% CI)): 4.8 (4.5–5.2)], but not depression-likely symptoms [4.5 (4.2–4.9)], was significantly associated with higher 5-year AL scores, compared to low depressive symptoms [4.3 (3.9–4.7)]. Baseline high AL [19.4 (17.6–21.2)], but not low AL [18.5 (16.5–20.6)], was significantly associated with higher 5-year CES-D score, compared to baseline moderate AL [16.9 (15.3–18.5)].

Conclusions

Depressive symptoms and AL had a bi-directional relationship over time, indicating a nuanced pathway linking depression with chronic diseases among a minority population.
Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model
Authors: Fiksinski Ania M. , Heung Tracy , Corral Maria , Breetvelt Elemi J. , Costain Gregory , Marshall Christian R. , Kahn Rene S. , Vorstman Jacob A.S. , Bassett Anne S.
Published: January 2021

Background

Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders.

Methods

We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures.

Results

Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes −1.39 to −2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia.

Conclusions

This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups.
Stele for Magistrate Jing Yun 景雲: An Eastern Han memorial stele from the south-west with reference to the Chuci 楚辭
Authors: Elias Hajni
Published: January 2021

An Eastern Han stele with an unusual relief decoration and 367 character memorial inscription tells us much about the south-west of China in early imperial times. Unearthed in 2004 from the banks of the Yangtze River and dated to 173ce, the stele was dedicated to Quren county magistrate Jing Yun who died 70 years earlier in 103ce. The paper provides a full translation, annotation, and analysis of the stele's commemorative text, which borrows from the content and language of one of China's oldest anthologies of poems, theChuci, and places it in its historical context. It also examines the iconography at the head of the stele which reflects beliefs in transcendence and the pursuit of immortality prevalent at the time and demonstrates its close relation to the inscription. Overall, the paper suggests that the decoration and text together exhibit a regional heritage that is distinct to the south-west, its memorial culture, and poetic and religious traditions.
Crystal structure from laboratory X-ray powder diffraction data, DFT-D calculations, Hirshfeld surface analysis, and energy frameworks of a new polymorph of 1-benzothiophene-2-carboxylic acid
Authors: Dugarte-Dugarte Analio J. , van de Streek Jacco , Díaz de Delgado Graciela , Rafalska-Lasocha Alicja , Delgado José Miguel
Published: January 2021

Several benzothiophene-based compounds, including 1-benzothiophene-2-carboxylic acid, exhibit a wide variety of pharmacological activities. They have been extensively used to treat various types of diseases with high therapeutic effectiveness. In this contribution, the crystal structure of a new polymorph of 1-benzothiophene-2-carboxylic acid (BTCA) was determined from laboratory X-ray powder diffraction data with DASH, refined by the Rietveld method with TOPAS-Academic, and optimized using DFT-D calculations. The new form of 1-benzothiophene-2-carboxylic acid crystallizes in space group C2/c (No. 15) with a = 14.635(4), b = 5.8543(9), c = 19.347(3) Å, β = 103.95(1)°, V = 1608.8(6) Å3, and Z = 8. The structure is a complex 3D arrangement which can be described in terms of hydrogen-bonded dimers of BTCA molecules, joined by the acid–acid homosynthon, which interact through C–H⋯O hydrogen bonds to produce tapes further connected through head-to-tail π⋯π and edge-to-face C–H⋯π interactions. A comparison with a previously reported triclinic polymorph and with the related 1-benzofuran-2-carboxylic acid (BFCA) is also presented.
Appetite disinhibition rather than hunger explains genetic effects on adult BMI trajectory
Authors: Brunner Eric J. , Maruyama Koutatsu , Shipley Martin , Cable Noriko , Iso Hiroyasu , Hiyoshi Ayako , Stallone Daryth , Kumari Meena , Tabak Adam , Singh-Manoux Archana , Wilson John , Langenberg Claudia , Wareham Nick , Boniface David , Hingorani Aroon , Kivimäki Mika , Llewellyn Clare
Published: January 2021

Background/objectives

The mediating role of eating behaviors in genetic susceptibility to weight gain during mid-adult life is not fully understood. This longitudinal study aims to help us understand contributions of genetic susceptibility and appetite to weight gain.

Subjects/methods

We followed the body-mass index (BMI) trajectories of 2464 adults from 45 to 65 years of age by measuring weight and height on four occasions at 5-year intervals. Genetic risk of obesity (gene risk score: GRS) was ascertained, comprising 92 BMI-associated single-nucleotide polymorphisms and split at a median (=high and low risk). At the baseline, the Eating Inventory was used to assess appetite-related traits of ‘disinhibition’, indicative of opportunistic eating or overeating and ‘hunger’ which is susceptibility to/ability to cope with the sensation of hunger. Roles of the GRS and two appetite-related scores for BMI trajectories were examined using a mixed model adjusted for the cohort effect and sex.

Results

Disinhibition was associated with higher BMI (β = 2.96; 95% CI: 2.66–3.25 kg/m2), and accounted for 34% of the genetically-linked BMI difference at age 45. Hunger was also associated with higher BMI (β = 1.20; 0.82–1.59 kg/m2) during mid-life and slightly steeper weight gain, but did not attenuate the effect of disinhibition.

Conclusions

Appetite disinhibition is most likely to be a defining characteristic of genetic susceptibility to obesity. High levels of appetite disinhibition, rather than hunger, may underlie genetic vulnerability to obesogenic environments in two-thirds of the population of European ancestry.
Maternal cafeteria diet exposure primes depression-like behavior in the offspring evoking lower brain volume related to changes in synaptic terminals and gliosis
Authors: Trujillo-Villarreal Luis A. , Romero-Díaz Viktor J. , Marino-Martínez Iván Alberto , Fuentes-Mera Lizeth , Ponce-Camacho Marco Antonio , Devenyi Gabriel A. , Mallar Chakravarty M. , Camacho-Morales Alberto , Garza-Villarreal Eduardo E.
Published: January 2021

Maternal nutritional programming by caloric exposure during pregnancy and lactation results in long-term behavioral modification in the offspring. Here, we characterized the effect of maternal caloric exposure on synaptic and brain morphological organization and its effects on depression-like behavior susceptibility in rats’ offspring. Female Wistar rats were exposed to chow or cafeteria (CAF) diet for 9 weeks (pre-pregnancy, pregnancy, and lactation) and then switched to chow diet after weaning. By postnatal day 60, the male Wistar rat offspring were tested for depressive-like behavior using operational conditioning, novelty suppressed feeding, sucrose preference, and open-field test. Brain macro and microstructural morphology were analyzed using magnetic resonance imaging deformation-based morphometry (DBM) and western blot, immunohistochemistry for NMDA and AMPA receptor, synaptophysin and myelin, respectively. We found that the offspring of mothers exposed to CAF diet displayed deficient motivation showing decrease in the operant conditioning, sucrose preference, and suppressed feeding test. Macrostructural DBM analysis showed reduction in the frontomesocorticolimbic circuit volume including the nucleus accumbens (NAc), hippocampus, and prefrontal cortex. Microstructural analysis revealed reduced synaptic terminals in hippocampus and NAc, whereas increased glial fibrillary acidic protein in hippocampus and lateral hypothalamus, as well as a decrease in the hippocampal cell number and myelin reduction in the dentate gyrus and hilus, respectively. Also, offspring exhibited increase of the GluR1 and GLUR2 subunits of AMPA receptor, whereas a decrease in the mGluR2 expression in hippocampus. Our findings reveal that maternal programming might prime depression-like behavior in the offspring by modulating macro and micro brain organization of the frontomesocorticolimbic circuit.
Probing the clinical and brain structural boundaries of bipolar and major depressive disorder
Authors: Yang Tao , Frangou Sophia , Lam Raymond W. , Huang Jia , Su Yousong , Zhao Guoqing , Mao Ruizhi , Zhu Na , Zhou Rubai , Lin Xiao , Xia Weiping , Wang Xing , Wang Yun , Peng Daihui , Wang Zuowei , Yatham Lakshmi N. , Chen Jun , Fang Yiru
Published: January 2021

Bipolar disorder (BD) and major depressive disorder (MDD) have both common and distinct clinical features, that pose both conceptual challenges in terms of their diagnostic boundaries and practical difficulties in optimizing treatment. Multivariate machine learning techniques offer new avenues for exploring these boundaries based on clinical neuroanatomical features. Brain structural data were obtained at 3 T from a sample of 90 patients with BD, 189 patients with MDD, and 162 healthy individuals. We applied sparse partial least squares discriminant analysis (s-PLS-DA) to identify clinical and brain structural features that may discriminate between the two clinical groups, and heterogeneity through discriminative analysis (HYDRA) to detect patient subgroups with reference to healthy individuals. Two clinical dimensions differentiated BD from MDD (area under the curve: 0.76, P < 0.001); one dimension emphasized disease severity as well as irritability, agitation, anxiety and flight of ideas and the other emphasized mostly elevated mood. Brain structural features could not distinguish between the two disorders. HYDRA classified patients in two clusters that differed in global and regional cortical thickness, the distribution proportion of BD and MDD and positive family history of psychiatric disorders. Clinical features remain the most reliable discriminant attributed of BD and MDD depression. The brain structural findings suggests that biological partitions of patients with mood disorders are likely to lead to the identification of subgroups, that transcend current diagnostic divisions into BD and MDD and are more likely to be aligned with underlying genetic variation. These results set the foundation for future studies to enhance our understanding of brain–behavior relationships in mood disorders.
Structural diverseness of neurons between brain areas and between cases
Authors: Mizutani Ryuta , Saiga Rino , Yamamoto Yoshiro , Uesugi Masayuki , Takeuchi Akihisa , Uesugi Kentaro , Terada Yasuko , Suzuki Yoshio , De Andrade Vincent , De Carlo Francesco , Takekoshi Susumu , Inomoto Chie , Nakamura Naoya , Torii Youta , Kushima Itaru , Iritani Shuji , Ozaki Norio , Oshima Kenichi , Itokawa Masanari , Arai Makoto
Published: January 2021

The cerebral cortex is composed of multiple cortical areas that exert a wide variety of brain functions. Although human brain neurons are genetically and areally mosaic, the three-dimensional structural differences between neurons in different brain areas or between the neurons of different individuals have not been delineated. Here we report a nanometer-scale geometric analysis of brain tissues of the superior temporal gyrus of schizophrenia and control cases. The results of the analysis and a comparison with results for the anterior cingulate cortex indicated that (1) neuron structures are significantly dissimilar between brain areas and that (2) the dissimilarity varies from case to case. The structural diverseness was mainly observed in terms of the neurite curvature that inversely correlates with the diameters of the neurites and spines. The analysis also revealed the geometric differences between the neurons of the schizophrenia and control cases. The schizophrenia cases showed a thin and tortuous neuronal network compared with the controls, suggesting that the neuron structure is associated with the disorder. The area dependency of the neuron structure and its diverseness between individuals should represent the individuality of brain functions.
Effect of 5-HT2A receptor antagonism on levels of D2/3 receptor occupancy and adverse behavioral side-effects induced by haloperidol: a SPECT imaging study in the rat
Authors: Tsartsalis Stergios , Tournier Benjamin B. , Gloria Yesica , Millet Philippe , Ginovart Nathalie
Published: January 2021

Several studies suggested that 5-HT2A receptor (5-HT2AR) blockade may provide a more favorable efficacy and side-effect profile to antipsychotic treatment. We hypothesized that a combined haloperidol (a D2/3 receptor (D2/3R) antagonist) and MDL-100,907 (a 5-HT2AR antagonist) treatment would reverse the side effects and the neurochemical alterations induced by haloperidol alone and would potentialize its efficacy. We thus chronically treated male Mdr1a knock-out rats with several doses of haloperidol alone or in combination with a saturating dose of a MDL-100,907. Receptor occupancy at clinically relevant levels was validated with a dual-radiotracer in-vivo SPECT imaging of D2/3R and 5-HT2AR occupancy. Experimental tests of efficacy (dizocilpine-disrupted prepulse inhibition (PPI) of the startle reflex) and side effects (catalepsy, vacuous chewing movements) were performed. Finally, a second dual-radiotracer in-vivo SPECT scan assessed the neurochemical changes induced by the chronic treatments. Chronic haloperidol failed to reverse PPI disruption induced by dizocilpine, whilst administration of MDL-100,907 along with haloperidol was associated with a reversal of the effect of dizocilpine. Haloperidol at 0.5 mg/kg/day and at 1 mg/kg/day induced catalepsy that was significantly alleviated (by ~50%) by co-treatment with MDL-100,907 but only at 0.5 mg/kg/day dose of haloperidol. Chronic haloperidol treatment, event at doses as low as 0.1 mg/kg/day induced a significant upregulation of the D2/3R in the striatum (by over 40% in the nucleus accumbens and over 20% in the caudate-putamen nuclei), that was not reversed by MDL-100,907. Finally, an upregulation of 5-HT2AR after chronic haloperidol treatment at a moderate dose only (0.25 mg/kg/day) was demonstrated in frontal cortical regions and the ventral tegmental area. Overall, a partial contribution of a 5-HT2AR antagonism to the efficacy and side-effect profile of antipsychotic agents is suggested.
Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation
Authors: Li Xiang-Rong , Cheng Xiaju , Sun Jia , Xu Yan S. , Chen Nannan , Hao Yimei , Huang Chao , Chin Y. Eugene
Published: January 2021

Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit β-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both β-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2–β-arrestin1/2–STAT3 signalosome is critical for glutamate-induced cell proliferation.
Omega 3 fatty acids stimulate thermogenesis during torpor in the Arctic Ground Squirrel
Authors: Rice S. A. , Mikes M. , Bibus D. , Berdyshev E. , Reisz J. A. , Gehrke S. , Bronova I. , D’Alessandro A. , Drew K. L.
Published: January 2021

Omega 3 polyunsaturated fatty acids (PUFAs) influence metabolism and thermogenesis in non-hibernators. How omega 3 PUFAs influence Arctic Ground Squirrels (AGS) during hibernation is unknown. Prior to hibernation we fed AGS chow composed of an omega 6:3 ratio approximately 1:1 (high in omega 3 PUFA, termed Balanced Diet), or an omega 6:3 ratio of 5:1 (Standard Rodent Chow), and measured the influence of diet on core body temperature (Tb), brown adipose tissue (BAT) mass, fatty acid profiles of BAT, white adipose tissue (WAT) and plasma as well as hypothalamic endocannabinoid and endocannabinoid-like bioactive fatty acid amides during hibernation. Results show feeding a diet high in omega 3 PUFAs, with a more balanced omega 6:3 ratio, increases AGS Tb in torpor. We found the diet-induced increase in Tb during torpor is most easily explained by an increase in the mass of BAT deposits of Balanced Diet AGS. The increase in BAT mass is associated with elevated levels of metabolites DHA and EPA in tissue and plasma suggesting that these omega 3 PUFAs may play a role in thermogenesis during torpor. While we did not observe diet-induced change in endocannabinoids, we do report altered hypothalamic levels of some endocannabinoids, and endocannabinoid-like compounds, during hibernation.
A mathematical model of tumor regression and recurrence after therapeutic oncogene inactivation
Authors: Hori Sharon S. , Tong Ling , Swaminathan Srividya , Liebersbach Mariola , Wang Jingjing , Gambhir Sanjiv S. , Felsher Dean W.
Published: January 2021

The targeted inactivation of individual oncogenes can elicit regression of cancers through a phenomenon called oncogene addiction. Oncogene addiction is mediated by cell-autonomous and immune-dependent mechanisms. Therapeutic resistance to oncogene inactivation leads to recurrence but can be counteracted by immune surveillance. Predicting the timing of resistance will provide valuable insights in developing effective cancer treatments. To provide a quantitative understanding of cancer response to oncogene inactivation, we developed a new 3-compartment mathematical model of oncogene-driven tumor growth, regression and recurrence, and validated the model using a MYC-driven transgenic mouse model of T-cell acute lymphoblastic leukemia. Our mathematical model uses imaging-based measurements of tumor burden to predict the relative number of drug-sensitive and drug-resistant cancer cells in MYC-dependent states. We show natural killer (NK) cell adoptive therapy can delay cancer recurrence by reducing the net-growth rate of drug-resistant cells. Our studies provide a novel way to evaluate combination therapy for personalized cancer treatment.