bluuebunny/crossref_metadata_2025 huggingface dataset:
Stalking im Jugendalter
Authors: Kliem Sören , Krieg Yvonne , Baier Dirk
Published: September 2021

Zusammenfassung. Theoretischer Hintergrund: Die Folgen für Betroffene von Stalking reichen von der Beeinträchtigung des sozialen Wohlbefindens über negative wirtschaftliche Folgen bis hin zu gesundheitlichen und psychischen Problemen. Fragestellung: Diese Studie präsentiert erstmalig die Lebenszeitprävalenz für die Opferwerdung von Stalking unter deutschen Jugendlichen und berichtet Zusammenhänge mit der psychischen Befindlichkeit. Methode: Daten einer repräsentativen Schüler_innenbefragung in Niedersachsen werden mittels T-Tests und χ2-Test überprüft. Ergebnisse: Die Ergebnisse weisen auf eine Prävalenz von 22.6 % von Stalking hin, die bei Mädchen und Jugendlichen höher ausfällt als bei Jungen und Erwachsenen. Betroffene leiden häufiger unter psychischen Problemen und problematischem Substanzkonsum als Nicht-Betroffene. Diskussion und Schlussfolgerung: Folglich sollten Schüler_innen über Stalking sowie dessen strafrechtliche Konsequenzen und gezielte Unterstützung der Betroffenen aufgeklärt werden.
Längsschnittstudie zum Verlauf motorischer Fähigkeiten von Grundschulkindern in Abhängigkeit auffälliger motorischer Leistungen der Fein- und Grobmotorik
Authors: Speer Andreas , Wagner Petra , Streicher Heike , Ziegeldorf Alexandra , Benkert Ines , Wulff und Hagen
Published: September 2021

Zusammenfassung. Theoretischer Hintergrund: Die motorische Leistungsfähigkeit (MLF) spielt eine zentrale Rolle in der Kindesentwicklung. Über den Verlauf der MLF über die Grundschulzeit in Abhängigkeit auffälliger motorischer Leistungen im Vorschulalter liegen nur wenige Befunde vor. Fragestellung: Liegen unterschiedliche Entwicklungsverläufe der MLF bei Kindern mit motorisch auffälligen Leistungen in der Fein- und Grobmotorik vor? Methode: Innerhalb einer Längsschnittstudie wurden die motorischen Dimensionen Kraft, Ausdauer, Schnelligkeit, Koordination und Beweglichkeit von Grundschulkindern ( N = 424) jährlich untersucht und mittels Varianzanalyse mit Messwiederholung geprüft. Ergebnisse: Kinder, die vor Schuleintritt grob- oder feinmotorische Auffälligkeiten (9-15 %) aufwiesen, blieben in ihrer motorischen Entwicklung deutlich hinter motorisch unauffälligen Kindern zurück. Diskussion und Schlussfolgerung: In der Folge können sich erhebliche Einschränkungen für die Alltagsmotorik und das Erlernen komplexer Bewegungen ergeben. Um gleiche motorische Startbedingungen für die betroffenen Kinder herzustellen, stellt die Erweiterung der bewegungsbezogenen Förderung der MLF vor Schulbeginn einen notwendigen Ansatz dar.
Labeling Poststorm Coastal Imagery for Machine Learning: Measurement of Interrater Agreement
Authors: Goldstein Evan B. , Buscombe Daniel , Lazarus Eli D. , Mohanty Somya D. , Rafique Shah Nafis , Anarde Katherine A. , Ashton Andrew D. , Beuzen Tomas , Castagno Katherine A. , Cohn Nicholas , Conlin Matthew P. , Ellenson Ashley , Gillen Megan , Hovenga Paige A. , Over Jin‐Si R. , Palermo Rose V. , Ratliff Katherine M. , Reeves Ian R. B. , Sanborn Lily H. , Straub Jessamin A. , Taylor Luke A. , Wallace Elizabeth J. , Warrick Jonathan , Wernette Phillipe , Williams Hannah E.
Published: September 2021

Classifying images using supervised machine learning (ML) relies on labeled training data—classes or text descriptions, for example, associated with each image. Data‐driven models are only as good as the data used for training, and this points to the importance of high‐quality labeled data for developing a ML model that has predictive skill. Labeling data is typically a time‐consuming, manual process. Here, we investigate the process of labeling data, with a specific focus on coastal aerial imagery captured in the wake of hurricanes that affected the Atlantic and Gulf Coasts of the United States. The imagery data set is a rich observational record of storm impacts and coastal change, but the imagery requires labeling to render that information accessible. We created an online interface that served labelers a stream of images and a fixed set of questions. A total of 1,600 images were labeled by at least two or as many as seven coastal scientists. We used the resulting data set to investigate interrater agreement: the extent to which labelers labeled each image similarly. Interrater agreement scores, assessed with percent agreement and Krippendorff's alpha, are higher when the questions posed to labelers are relatively simple, when the labelers are provided with a user manual, and when images are smaller. Experiments in interrater agreement point toward the benefit of multiple labelers for understanding the uncertainty in labeling data for machine learning research.
An Observational Based Modeling of the Surface Layer Particulate Nitrate in the North China Plain During Summertime
Authors: Tan Zhaofeng , Wang Haichao , Lu Keding , Dong Huabin , Liu Yuhan , Zeng Limin , Hu Min , Zhang Yuanhang
Published: September 2021

Particulate nitrate (pNO3−) is an important component in atmospheric fine particulate matter. Here, we present a case study investigating the production and loss processes of pNO3− in surface‐layer based on the observation at a regional site Wangdu in North China Plain (NCP) during summer. The averaged diurnal of nitric acid (HNO3) production reached a maximum of 1.5 μg m−3 h−1 determined from the observed OH and NO2, indicating a fast HNO3 production in the surface layer during the daytime. The chemical processes affecting surface nitrate concentration and daily variation were simulated by a box model based on the Regional Atmospheric Chemical Mechanism version 2 and coupled with the ISORROPIA‐II thermodynamic equilibrium model. The chemical formation of total soluble nitrate (TNO3) at the surface layer cannot explain the fast increase of pNO3− in the morning and overshoot pNO3− in the afternoon, suggesting missing processes in the model. The pNO3− budget analysis suggests the importance of entrainment from residual layer air into the surface layer as an important process for surface pNO3− concentration enhancement in the early morning. In the afternoon, the partition to pNO3− was limited due to the high temperature near the ground. Nevertheless, the observed fast nitrate production still significantly overshot pNO3− in the afternoon. This difference indicates HNO3 production was less efficient throughout the boundary layer than what was observed in the surface layer. Our results highlight the importance of vertical measurements to understand the formation mechanism of nitrate pollution in summer.
Dual targeting of JAK2 and ERK interferes with the myeloproliferative neoplasm clone and enhances therapeutic efficacy
Authors: Brkic Sime , Stivala Simona , Santopolo Alice , Szybinski Jakub , Jungius Sarah , Passweg Jakob R. , Tsakiris Dimitrios , Dirnhofer Stefan , Hutter Gregor , Leonards Katharina , Lischer Heidi E. L. , Dettmer Matthias S. , Neel Benjamin G. , Levine Ross L. , Meyer Sara C.
Published: September 2021

Myeloproliferative neoplasms (MPN) show dysregulated JAK2 signaling. JAK2 inhibitors provide clinical benefits, but compensatory activation of MAPK pathway signaling impedes efficacy. We hypothesized that dual targeting of JAK2 and ERK1/2 could enhance clone control and therapeutic efficacy. We employed genetic and pharmacologic targeting of ERK1/2 in Jak2V617F MPN mice, cells and patient clinical isolates. Competitive transplantations of Jak2V617F vs. wild-type bone marrow (BM) showed that ERK1/2 deficiency in hematopoiesis mitigated MPN features and reduced the Jak2V617F clone in blood and hematopoietic progenitor compartments. ERK1/2 ablation combined with JAK2 inhibition suppressed MAPK transcriptional programs, normalized cytoses and promoted clone control suggesting dual JAK2/ERK1/2 targeting as enhanced corrective approach. Combined pharmacologic JAK2/ERK1/2 inhibition with ruxolitinib and ERK inhibitors reduced proliferation of Jak2V617F cells and corrected erythrocytosis and splenomegaly of Jak2V617F MPN mice. Longer-term treatment was able to induce clone reductions. BM fibrosis was significantly decreased in MPLW515L-driven MPN to an extent not seen with JAK2 inhibitor monotherapy. Colony formation from JAK2V617F patients’ CD34+ blood and BM was dose-dependently inhibited by combined JAK2/ERK1/2 inhibition in PV, ET, and MF subsets. Overall, we observed that dual targeting of JAK2 and ERK1/2 was able to enhance therapeutic efficacy suggesting a novel treatment approach for MPN.
High-resolution two-photon polymerization: the most versatile technique for the fabrication of microneedle arrays
Authors: Faraji Rad Zahra , Prewett Philip D. , Davies Graham J.
Published: September 2021

Microneedle patches have received much interest in the last two decades as drug/vaccine delivery or fluid sampling systems for diagnostic and monitoring purposes. Microneedles are manufactured using a variety of additive and subtractive micromanufacturing techniques. In the last decade, much attention has been paid to using additive manufacturing techniques in both research and industry, such as 3D printing, fused deposition modeling, inkjet printing, and two-photon polymerization (2PP), with 2PP being the most flexible method for the fabrication of microneedle arrays. 2PP is one of the most versatile and precise additive manufacturing processes, which enables the fabrication of arbitrary three-dimensional (3D) prototypes directly from computer-aided-design (CAD) models with a resolution down to 100 nm. Due to its unprecedented flexibility and high spatial resolution, the use of this technology has been widespread for the fabrication of bio-microdevices and bio-nanodevices such as microneedles and microfluidic devices. This is a pioneering transformative technology that facilitates the fabrication of complex miniaturized structures that cannot be fabricated with established multistep manufacturing methods such as injection molding, photolithography, and etching. Thus, microstructures are designed according to structural and fluid dynamics considerations rather than the manufacturing constraints imposed by methods such as machining or etching processes. This article presents the fundamentals of 2PP and the recent development of microneedle array fabrication through 2PP as a precise and unique method for the manufacture of microstructures, which may overcome the shortcomings of conventional manufacturing processes.
Nanomedicine and graphene-based materials: advanced technologies for potential treatments of diseases in the developing nervous system
Authors: Cellot Giada , Franceschi Biagioni Audrey , Ballerini Laura
Published: September 2021

The interest in graphene-based nanomaterials (GBNs) application in nanomedicine, in particular in neurology, steadily increased in the last decades. GBNs peculiar physical–chemical properties allow the design of innovative therapeutic tools able to manipulate biological structures with subcellular resolution. In this review, we report GBNs applications to the central nervous system (CNS) when these nanomaterials are engineered as potential therapeutics to treat brain pathologies, with a focus on those of the pediatric age. We revise the state-of-the art studies addressing the impact of GBNs in the CNS, showing that the design of GBNs with different dimensions and chemical compositions or the use of specific administration routes and doses can limit unwanted side effects, exploiting GBNs efficacy in therapeutic approaches. These features favor the development of GBNs-based multifunctional devices that may find applications in the field of precision medicine for the treatment of disorders in the developing CNS. In this framework, we address the suitability of GBNs to become successful therapeutic tools, such as drug nano-delivery vectors when being chemically decorated with pharmaceutical agents and/or other molecules to obtain a high specific targeting of the diseased area and to achieve a controlled release of active molecules.

Impact

The translational potential of graphene-based nanomaterials (GBNs) can be used for the design of novel therapeutic approaches to treat pathologies affecting the brain with a focus on the pediatric age.

GBNs can be chemically decorated with pharmaceutical agents and molecules to obtain a highly specific targeting of the diseased site and a controlled drug release.

The type of GBNs, the selected functionalization, the dose, and the way of administration are factors that should be considered to potentiate the therapeutic efficacy of GBNs, limiting possible side effects.

GBNs-based multifunctional devices might find applications in the precision medicine and theranostics fields.
Consolidation/reconsolidation therapies for the prevention and treatment of PTSD and re-experiencing: a systematic review and meta-analysis
Authors: Astill Wright Laurence , Horstmann Louise , Holmes Emily A. , Bisson Jonathan I.
Published: September 2021

Translational research highlights the potential of novel 'memory consolidation/reconsolidation therapies' to treat re-experiencing symptoms and post-traumatic stress disorder (PTSD). This systematic review and meta-analysis assessed the efficacy of so-called memory consolidation/reconsolidation therapies in randomised controlled trials (RCTs) for prevention and treatment of PTSD and symptoms of re-experiencing in children and adults (PROSPERO: CRD42020171167). RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD/re-experiencing severity. Twenty-five RCTs met inclusion criteria (16 prevention and nine treatment trials). The methodology of most studies had a significant risk of bias. We found a large effect of reconsolidation interventions in the treatment of PTSD (11 studies, n = 372, SMD: −1.42 (−2.25 to −0.58), and a smaller positive effect of consolidation interventions in the prevention of PTSD (12 studies, n = 2821, RR: 0.67 (0.50 to 0.90). Only three protocols (hydrocortisone for PTSD prevention, Reconsolidation of Traumatic Memories (RTM) for treatment of PTSD symptoms and cognitive task memory interference procedure with memory reactivation (MR) for intrusive memories) were superior to control. There is some emerging evidence of consolidation and reconsolidation therapies in the prevention and treatment of PTSD and intrusive memories specifically. Translational research should strictly adhere to protocols/procedures describing precise reconsolidation conditions (e.g. MR) to both increase the likelihood of positive findings and more confidently interpret negative findings of putative reconsolidation agents.
Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions
Authors: Reus Lianne M. , Jansen Iris E. , Mol Merel O. , van Ruissen Fred , van Rooij Jeroen , van Schoor Natasja M. , Tesi Niccolò , Reinders Marcel J. T. , Huisman Martijn A. , Holstege Henne , Visser Pieter Jelle , de Boer Sterre C. M. , Hulsman Marc , Ahmad Shahzad , Amin Najaf , Uitterlinden Andre G. , Ikram Arfan , van Duijn Cornelia M. , Seelaar Harro , Ramakers Inez H. G. B. , Verhey Frans R. J. , van der Lugt Aad , Claassen Jurgen A. H. R. , Jan Biessels Geert , De Deyn Peter Paul , Scheltens Philip , van der Flier Wiesje M. , van Swieten John C. , Pijnenburg Yolande A. L. , van der Lee Sven J.
Published: September 2021

Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10−9, rs117204439: OR = 4.9, P = 6.0 × 10−9) and replication analysis (P < 1.1 × 10−3). These variants also significantly associated with amyotrophic lateral sclerosis in a publicly available dataset. Using haplotype analyses in 1200 individuals, we showed that these variants tag a sub-haplotype of the founder haplotype of the repeat expansion that was previously found to be present in virtually all pathological C9ORF72 G4C2 repeat lengths. This new risk haplotype was 10 times more likely to contain a C9ORF72 pathological repeat length compared to founder haplotypes without one of the two risk variants (~22% versus ~2%; P = 7.70 × 10−58). In haplotypes without a pathologic expansion, the founder risk haplotype had a higher number of repeats (median = 12 repeats) compared to the founder haplotype without the risk variants (median = 8 repeats) (P = 2.05 × 10−260). In conclusion, the identified risk haplotype, which is carried by ~4% of all individuals, is a major risk factor for pathological repeat lengths of C9ORF72 G4C2. These findings strongly indicate that longer C9ORF72 repeats are unstable and more likely to convert to germline pathological C9ORF72 repeat expansions.
Neural correlates of emotional reactivity and regulation in traumatized North Korean refugees
Authors: Lee Kyung Hwa , Lee Ha Young , Park Inkyung , Lee Yu Jin , Kim Nambeom , Jeon Sehyun , Kim Soohyun , Jeon Jeong Eun , Kim Seog Ju
Published: September 2021

Refugees often report heightened emotional reactivity and emotion regulation difficulties and are at high risk for mental health problems. Given that refugees are repeatedly exposed to traumatic events that may cause changes in the brain, the present study examined neural correlates of emotional reactivity and regulation and their associations with refugee features (e.g., cumulative trauma) and the severity of psychiatric symptoms (e.g., post-traumatic stress disorder [PTSD]) in North Korean (NK) refugees. Forty NK refugees with trauma exposure and varying levels of psychopathology and 41 healthy South Korean (SK) controls without trauma exposure participated in this study. They performed an emotion regulation task during a functional magnetic resonance imaging (fMRI) assessment. Region of interest (ROI), whole brain, and generalized psychophysiological interaction (gPPI) analyses were conducted. NK refugees with trauma exposure and varying levels of psychopathology showed increased activation in response to negative socio-affective pictures in regions involved in affective processing, including the amygdala and hippocampus, relative to healthy SK controls without trauma exposure. They also exhibited greater prefrontal cortex (PFC) activation, amygdala–PFC functional connectivity (FC), and hippocampal–PFC FC during emotion regulation. More severe PTSD symptoms were associated with greater hippocampal response to negative pictures (vs. neutral pictures) in NK refugees. This study provides neuroscientific evidence for neural alterations in association with emotional reactivity and regulation in traumatized refugees. These findings may contribute to a better mechanistic understanding of emotional reactivity and regulation in refugees and suggest potential ways to address the emotional and mental problems of traumatized refugees.
Predictive values of tumor necrosis factor-α for depression treatment outcomes: effect modification by hazardous alcohol consumption
Authors: Choi Wonsuk , Kang Hee-Ju , Kim Ju-Wan , Kim Hee Kyung , Kang Ho-Cheol , Lee Ju-Yeon , Kim Sung-Wan , Stewart Robert , Kim Jae-Min
Published: September 2021

Inflammation is potentially associated with poor antidepressant treatment outcomes. Pro-inflammatory cytokines are influenced by hazardous alcohol consumption. The aim of the present study was to investigate the effects of the serum tumor necrosis factor-α (sTNF-α) level on antidepressant treatment outcomes in terms of the 12-week and 12-month remission rates and 24-month relapse rate, and to investigate the potential modifying effects of alcohol consumption on these associations in patients with depressive disorders. At baseline, sTNF-α was measured and alcohol-related data from the Alcohol Use Disorders Identification Test (AUDIT) and consumption history were collected from 1094 patients. Patients received stepwise antidepressant treatment. Remission at 12 weeks and 12 months was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7. Relapse (HAMD score ≥ 14) was identified until 24 months for those who had initially responded (HAMD score <14) at 12 weeks. Higher sTNF-α levels were found to have significant effects on the 12-week and 12-month non-remission and 24-month relapse rates. These effects were more prominent in those with low levels of alcohol consumption (AUDIT score ≤ 8 or no current alcohol consumption); the effects were not significant in those exhibiting hazardous alcohol consumption (AUDIT score > 8 or current drinking). Significant interactions were found for the 12-month non-remission and relapse rates, although the interaction was not statistically significant for 12-week remission. In conclusion, baseline sTNF-α levels may be a useful predictor for both short- and long-term antidepressant treatment outcomes, and the consideration of alcohol consumption status may increase predictability, in particular for long-term outcomes.
LncRNA ZNFTR functions as an inhibitor in pancreatic cancer by modulating ATF3/ZNF24/VEGFA pathway
Authors: Li Wei , Han Shengbo , Hu Ping , Chen Ding , Zeng Zhu , Hu Yuhang , Xu Fengyu , Tang Jiang , Wang Fan , Zhao Yong , Huang Mengqi , Zhao Gang
Published: September 2021

The majority of long non-coding RNAs (lncRNAs) have been discovered to be overexpressed in pancreatic cancer (PC) and served as promoters in the tumorigenesis of PC, while the inhibitory functions of lncRNAs in the development of PC have not been fully elucidated yet. LncRNA microarray was adopted to analyze the differential expression of lncRNAs in PC tissues and that in normal peritumoral (NP) tissues. Functional role of lncRNA BM466146.1 on PC was evaluated by gain- and loss-of-function experiments in vivo and in vitro. RNA pull-down, RNA immunoprecipitation, luciferase reporter, and Chromatin-immunoprecipitation assays were performed to assess the mechanism of ZNFTR, respectively. The correlation between the expression of ZNFTR and various clinicopathological characteristics was accessed in PC specimens. This study displayed lncRNA BM466146.1 was downregulated in PC tissues and functioned as a suppressor through regulating the expression of adjacent gene Zinc finger protein 24 (ZNF24), which was assigned as ZNFTR. Mechanistically, ZNFTR interacted with activating transcription factor 3 (ATF3) and sequestered ATF3 away from the ZNF24 promoter, which consequently increased the expression of ZNF24. Further, ZNF24 inhibited the proliferative, metastatic, and pro-angiogenic abilities of PC cells by suppressing transcription of vascular endothelial growth factor A (VEGFA). Therefore, the downregulation of ZNFTR in PC led to the decreased expression of ZNF24, which further resulted in the upregulation of VEGFA to facilitate the development of PC. Meanwhile, ZNFTR was transcriptionally inhibited by the HIF-1α/HDAC1 complex-mediated deacetylation. Clinical results further demonstrated that the low expression of ZNFTR was associated with poor overall survival time. Taken together, our results implicated that ZNFTR was a hypoxia-responsive lncRNA, and functioned as an inhibitor by modulating ATF3/ZNF24/VEGFA pathway in PC.
Association of APOE4 genotype and treatment with cognitive outcomes in breast cancer survivors over time
Authors: Van Dyk Kathleen , Crespi Catherine M. , Bower Julienne E. , Carroll Judith E. , Petersen Laura , Ganz Patricia A.
Published: September 2021

This prospective longitudinal study of breast cancer survivors (n = 167) examined the association of apolipoprotein ε4 (APOE ε4) genotype with cognition and interactions with chemotherapy or endocrine therapy up to 6 years after treatment. In general, we found no effects of ε4 across timepoints and treatment exposures; post hoc analysis at 3–6 years suggested a trend towards worse cognition in the domains of attention and learning among ε4 carriers exposed to endocrine therapy. Further study is needed.
Matrilin3/TGFβ3 gelatin microparticles promote chondrogenesis, prevent hypertrophy, and induce paracrine release in MSC spheroid for disc regeneration
Authors: Bello Alvin Bacero , Kim Yunkyung , Park Sunghyun , Muttigi Manjunatha S. , Kim Jiseong , Park Hansoo , Lee Soohong
Published: September 2021

Degenerative disc disease (DDD) is the leading cause of excruciating lower back pain and disability in adults worldwide. Among the current treatments for DDD, cell-based therapies such as the injection of both disc- and non-disc-derived chondrocytes have shown significant improvements in the patients’ condition. However, further advancement of these therapies is required to not only ensure a supply of healthy chondrocytes but also to promote regeneration of the defective cells in the injury site. Here, we report that the incorporation of gelatin microparticles coloaded with transforming growth factor beta 3 and matrilin 3 promoted chondrogenic differentiation of adipose-derived mesenchymal stem cell spheroids while preventing hypertrophy and terminal differentiation of cells. Moreover, these composite spheroids induced the release of chondrogenic cytokines that, in turn, promoted regeneration of degenerative chondrocytes in vitro. Finally, injections of these composite spheroids in a rat model of intervertebral disc disease promoted restoration of the chondrogenic properties of the cells, thereby allowing regeneration of the chondrogenic tissue in vivo.
Fractionated deep-inspiration breath-hold ZTE Compared with Free-breathing four-dimensional ZTE for detecting pulmonary nodules in oncological patients underwent PET/MRI
Authors: Chang Chih-Yung , Lee Tse-Hao , Liu Ren-Shyan , Li Chien-Ying , Yang Bang-Hung , Chang Wen-Yi , Lin Tzu-Ping , Chang Chi-Wei , Yao Shan-Fan , Wei Tzu-Chun , Lin Chien-Yuan , Shieh Charng-Chyi , Lu Chia-Feng
Published: September 2021

The zero echo time (ZTE) technique has improved the detection of lung nodules in PET/MRI but respiratory motion remains a challenge in lung scan. We investigated the feasibility and performance of fractionated deep-inspiration breath-hold (FDIBH) three-dimensional (3D) ZTE FDG PET/MRI for assessing lung nodules in patients with proved malignancy. Sixty patients who had undergone ZTE FDG PET/MRI and chest CT within a three-day interval were retrospectively included. Lung nodules less than 2 mm were excluded for analysis. Two physicians checked the adequacy of FDIBH ZTE and compared the lung nodule detection rates of FDIBH 3D ZTE and free-breathing (FB) four-dimensional (4D) ZTE, with chest CT as the reference standard. FDIBH resolved the effect of respiratory motion in 49 patients. The mean number and size of the pulmonary nodules identified in CT were 15 ± 31.3 per patient and 5.9 ± 4.6 mm in diameter. The overall nodule detection rate was 71% for FDIBH 3D ZTE and 70% for FB 4D ZTE (p = 0.73). FDIBH 3D ZTE significantly outperformed FB 4DZTE in detecting lung base nodules (72% and 68%; p = 0.03), especially for detecting those less than 6 mm (61% and 55%; p = 0.03). High inter-rater reliability for FDIBH 3D ZTE and FB 4D ZTE (k = 0.9 and 0.92) was noted. In conclusion, the capability of FDIBH 3D ZTE in respiratory motion resolution was limited with a technical failure rate of 18%. However, it could provide full expansion of the lung in a shorter scan time which enabled better detection of nodules (< 6 mm) in basal lungs, compared to FB 4D ZTE.
The relation between parietal GABA concentration and numerical skills
Authors: Zacharopoulos George , Sella Francesco , Emir Uzay , Cohen Kadosh Roi
Published: September 2021

Several scientific, engineering, and medical advancements are based on breakthroughs made by people who excel in mathematics. Our current understanding of the underlying brain networks stems primarily from anatomical and functional investigations, but our knowledge of how neurotransmitters subserve numerical skills, the building block of mathematics, is scarce. Using 1H magnetic resonance spectroscopy (N = 54, 3T, semi-LASER sequence, TE = 32 ms, TR = 3.5 s), the study examined the relation between numerical skills and the brain’s major inhibitory (GABA) and excitatory (glutamate) neurotransmitters. A negative association was found between the performance in a number sequences task and the resting concentration of GABA within the left intraparietal sulcus (IPS), a key region supporting numeracy. The relation between GABA in the IPS and number sequences was specific to (1) parietal but not frontal regions and to (2) GABA but not glutamate. It was additionally found that the resting functional connectivity of the left IPS and the left superior frontal gyrus was positively associated with number sequences performance. However, resting GABA concentration within the IPS explained number sequences performance above and beyond the resting frontoparietal connectivity measure. Our findings further motivate the study of inhibition mechanisms in the human brain and significantly contribute to our current understanding of numerical cognition's biological bases.
Three-dimensional computational fluid dynamics analysis of an electric submerged arc furnace
Authors: Karalis K. , Karalis N. , Karkalos N. , Ntallis Ν. , Antipas G. S. E. , Xenidis A.
Published: September 2021

A computational fluid dynamics (CFD) method is proposed to analyze the operation of a submerged electric arc furnace (SAF) used in ferronickel production. A three-dimensional mathematical model was used for the time-dependent solution of the fluid flow, heat transfer and electromagnetic phenomena. The slag's physical properties, which play a crucial role in the SAF operation, were previously determined using classical molecular dynamics simulations and empirical relationships. The analysis revealed that the main slag properties affecting SAF operation are density, viscosity and electrical conductivity—the latter two being mutually dependent. The high electrical conductivity values of the slag favor melting via the high Joule heat produced within the slag region. Calculation of the dimensionless Péclet and Reynolds numbers revealed that the slag velocities play a decisive role in heat transfer and further indicate that the slag flow is laminar. The average slag velocity calculated 0.0001 m/s with maxima in the vicinity of the electrodes.
Characterization of a novel multidomain CE15-GH8 enzyme encoded by a polysaccharide utilization locus in the human gut bacterium Bacteroides eggerthii
Authors: Kmezik Cathleen , Krska Daniel , Mazurkewich Scott , Larsbrink Johan
Published: September 2021

Bacteroidetes are efficient degraders of complex carbohydrates, much thanks to their use of polysaccharide utilization loci (PULs). An integral part of PULs are highly specialized carbohydrate-active enzymes, sometimes composed of multiple linked domains with discrete functions—multicatalytic enzymes. We present the biochemical characterization of a multicatalytic enzyme from a large PUL encoded by the gut bacterium Bacteroides eggerthii. The enzyme, BeCE15A-Rex8A, has a rare and novel architecture, with an N-terminal carbohydrate esterase family 15 (CE15) domain and a C-terminal glycoside hydrolase family 8 (GH8) domain. The CE15 domain was identified as a glucuronoyl esterase (GE), though with relatively poor activity on GE model substrates, attributed to key amino acid substitutions in the active site compared to previously studied GEs. The GH8 domain was shown to be a reducing-end xylose-releasing exo-oligoxylanase (Rex), based on having activity on xylooligosaccharides but not on longer xylan chains. The full-length BeCE15A-Rex8A enzyme and the Rex domain were capable of boosting the activity of a commercially available GH11 xylanase on corn cob biomass. Our research adds to the understanding of multicatalytic enzyme architectures and showcases the potential of discovering novel and atypical carbohydrate-active enzymes from mining PULs.
LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
Authors: Rodriguiz Ramona M. , Nadkarni Vineet , Means Christopher R. , Pogorelov Vladimir M. , Chiu Yi-Ting , Roth Bryan L. , Wetsel William C.
Published: September 2021

Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2Aserotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin- (βArr) mediated signaling. To separate these signaling modalities, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, without effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and βArr1-KO animals. By contrast, in βArr2-KO mice head twitch responses are low with LSD and this psychedelic is without effects on other surrogates. The 5-HT2AR antagonist MDL100907 (MDL) blocks the LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and βArr1-KOs, but not in βArr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in βArr1-KOs. Collectively, these results reveal that LSD’s psychedelic drug-like actions appear to require βArr2.
Controlled diabetes amends oxidative stress as mechanism related to severity of diabetic retinopathy
Authors: Fahmy Rania , Almutairi Nouf M. , Al-Muammar May N. , Bhat Ramesa Shafi , Moubayed Nadine , El-Ansary Afaf
Published: September 2021

Oxidative stress is a well-accepted etiological mechanism that contributes to neuronal dysfunction. Role of oxidative stress as a mechanism of retinopathy in controlled type 2 diabetic patients was evaluated. Participants were divided into three groups: Group 1 as 30 normal eyes of 15 subjects, Group 2 comprised 24 eyes of 12 diabetic patients without retinopathy and Group 3 comprised 23 eyes of 12 diabetic patients with different grades of retinopathy (8 eyes with maculopathy). A complete ophthalmological examination was performed. Oxidative stress markers were measured in blood. Macular thickness was different in all quadrants among all groups and showed a tendency to increase in Group 3 due to diabetic retinopathy with insignificant changes in parapapillary retinal nerve fiber layer thickness although thinning was noted also with retinopathy. Non-significant differences in GST and lipid peroxide levels were observed between the three studied groups, whereas vitamin C and GSH levels were higher in diabetic patients when compared to those in controls. As oxidative stress, hyperglycemia and local inflammation are involved in the pathogenesis of DR, the present study proved that the progressive damage can be retarded in controlled type 2 diabetic patients using different treatment modalities that abated oxidative stress.
Quasi-homogenous photocatalysis of quantum-sized Fe-doped TiO2 in optically transparent aqueous dispersions
Authors: Einert Marcus , Hartmann Pascal , Smarsly Bernd , Brezesinski Torsten
Published: September 2021

In this study, the preparation of anatase TiO2 nanocrystals via a facile non-aqueous sol–gel route and their characterization are reported. The 3–4 nm particles are readily dispersable in aqueous media and show excellent photoreactivity in terms of rhodamine B degradation. The catalytic performance can be further increased considerably by doping with iron and UV-light irradiation as a pre-treatment. The effect of surface ligands (blocked adsorption sites, surface defects etc.) on the photoreactivity was thoroughly probed using thermogravimetric analysis combined with mass spectrometry. Photoelectrochemical characterization of thin-film electrodes made from the same TiO2 nanocrystals showed the opposite trend to the catalytic experiments, that is, a strong decrease in photocurrent and quantum efficiency upon doping due to introduction of shallow defect states.
Aberrant activation of the Hedgehog signalling pathway in squamous cell carcinoma of the vulva as a potential target for cancer therapy
Authors: Yap Jason K. W. , Uddin Khalil , Pounds Rachel , O’Neill Danielle , Kehoe Sean , Ganesan Raji , Dawson Christopher W.
Published: September 2021

In a previous study, we showed that the Hedgehog (Hh) signalling pathway is aberrantly activated in vulval squamous cell carcinoma (VSCC). In this study, we further validated our findings on a prospective cohort of primary VSCC cases, where immunohistochemical staining confirmed that key Hh pathway components were overexpressed in VSCC compared to normal vulval epithelium. We also undertook a series of in vitro studies to determine the extent of Hh pathway activation in VSCC-derived cell lines, and examine the consequences of pathway inhibition on the growth of these cells. We found that of six cell lines tested, four displayed elevated baseline Hh pathway activity that was dependent on SHH ligand, or in one case, a PTCH1 gene mutation. Hh signalling appeared necessary to sustain cell growth, as SHH ligand depletion with Robotikinin or SMO inhibition, either with chemical inhibitors (Itraconazole or LDE-225) or SMO-specific siRNA, attenuated GLI1 activity and cell proliferation in both monolayer and organotypic raft culture. Furthermore, treatment of Hh-dependent cell lines with SMO inhibitors sensitised cells to Cisplatin. Findings from our study offer us the opportunity to explore further the development of targeted chemotherapy for women with VSCC driven by aberrant Hh activation.
Microparticles and PD1 interplay added a prognostic impact in treatment outcomes of patients with multiple myeloma
Authors: Zahran Asmaa M. , Zahran Zeinab Albadry M. , Rayan Amal
Published: September 2021

Although multiple myeloma (MM) is still considered as an incurable disease by current standards, the development of several combination therapies, and immunotherapy approaches has raised the hope towards transforming MM into an indolent, chronic disease, and possibly achieving a cure. We tried to shed light on the expression of PD1 and different Microparticles (MPs) in MM and their interplay as a mechanism of resistance to standardized treatments, in addition, find their associations with prognostic factors of symptomatic MM. Thirty patients with newly diagnosed and chemotherapy naïve active MM, along with 19 healthy participants of comparable age and sex were recruited, after diagnosis of MM; blood samples were collected from both patients and controls for flow cytometric detection of CD4+, CD8+, CD4+PD1+, and CD8+PD1+T cells, total MPs, CD138+ MPs, and platelet MPs. MM patients had statistically significant higher levels of TMPs, CD138+ MPs compared to their controls, while PMPs exhibited no significant difference between both groups. Statistically significant higher percentages of CD8+, PD1CD8+, PD1CD4+T cells were detected in patients compared to controls, while the latter group had a significantly higher percentage of CD4+T cells than MM patients, patients who did not achieve complete response, had significantly higher percentages of PMPs, CD138+MPs, PD1+CD8+, PD1+CD4+, and CD8+T cells (cutoff values = 61, 10.6, 13.5, 11.3 and 20.1 respectively), (p-values = 0.002, 0.003, 0.017, 0.001 and 0.008 respectively). Microparticles and PD1 expressions were associated with proliferative potential and resistance to Bortezomib-based treatments, our results suggested that they played a crucial role in myeloma progression.
Magnetism and topology in Tb-based icosahedral quasicrystal
Authors: Watanabe Shinji
Published: September 2021

Quasicrystal (QC) possesses a unique lattice structure with rotational symmetry forbidden in conventional crystals. The electric property is far from complete understanding and it has been a long-standing issue whether the magnetic long-range order is realized in the QC. The main difficulty was lack of microscopic theory to analyze the effect of the crystalline electric field (CEF) at the rare-earth atom in QCs. Here we show the full microscopic analysis of the CEF in Tb-based QCs. We find that magnetic anisotropy arising from the CEF plays a key role in realizing unique magnetic textures on the icosahedron whose vertices Tb atoms are located at. Our analysis of the minimal model based on the magnetic anisotropy suggests that the long-range order of the hedgehog characterized by the topological charge of one is stabilized in the Tb-based QC. We also find that the whirling-moment state is characterized by unusually large topological charge of three. The magnetic textures as well as the topological states are shown to be switched by controlling compositions of the non-rare-earth elements in the ternary compounds. Our model is useful to understand the magnetism as well as the topological property in the rare-earth-based QCs and approximant crystals.
The effect of trichlormethiazide in autosomal dominant polycystic kidney disease patients receiving tolvaptan: a randomized crossover controlled trial
Authors: Uchiyama Kiyotaka , Kitayama Chigusa , Yanai Akane , Ishibashi Yoshitaka
Published: September 2021

The vasopressin V2 receptor antagonist tolvaptan delays the progression of autosomal dominant polycystic kidney disease (ADPKD). However, some patients discontinue tolvaptan because of severe adverse aquaretic events. This open-label, randomized, controlled, counterbalanced, crossover trial investigated the effects of trichlormethiazide, a thiazide diuretic, in patients with ADPKD receiving tolvaptan (n = 10) who randomly received antihypertensive therapy with or without trichlormethiazide for 12 weeks. The primary and secondary outcomes included amount and osmolarity of 24-h urine and health-related quality-of-life (HRQOL) parameters assessed by the Kidney Disease Quality of Life-Short Form questionnaire, renal function slope, and plasma/urinary biomarkers associated with disease progression. There was a significant reduction in urine volume (3348 ± 584 vs. 4255 ± 739 mL; P < 0.001) and a significant increase in urinary osmolarity (182.5 ± 38.1 vs. 141.5 ± 38.1 mOsm; P = 0.001) in patients treated with trichlormethiazide. Moreover, trichlormethiazide improved the following HRQOL subscales: effects of kidney disease, sleep, emotional role functioning, social functioning, and role/social component summary. No significant differences were noted in renal function slope or plasma/urinary biomarkers between patients treated with and without trichlormethiazide. In patients with ADPKD treated with tolvaptan, trichlormethiazide may improve tolvaptan tolerability and HRQOL parameters.
Co-occurrence networks reveal the central role of temperature in structuring the plankton community of the Thau Lagoon
Authors: Trombetta Thomas , Vidussi Francesca , Roques Cécile , Mas Sébastien , Scotti Marco , Mostajir Behzad
Published: September 2021

To identify the environmental factors that drive plankton community composition and structure in coastal waters, a shallow northwestern Mediterranean lagoon was monitored from winter to spring in two contrasting years. The campaign was based on high-frequency recordings of hydrological and meteorological parameters and weekly samplings of nutrients and the plankton community. The collected data allowed the construction of correlation networks, which revealed that water temperature was the most important factor governing community composition, structure and succession at different trophic levels, suggesting its ubiquitous food web control. Temperature favoured phytoplanktonic flagellates (Cryptophyceae, Chrysophyceae, and Chlorophyceae) and ciliates during winter and early spring. In contrast, it favoured Bacillariophyceae, dinoflagellates, phytoplankton < 6 µm and aloricate Choreotrichida during spring. The secondary factors were light, which influenced phytoplankton, and wind, which may regulate turbidity and the nutrient supply from land or sediment, thus affecting benthic species such as Nitzschia sp. and Uronema sp. or salinity-tolerant species such as Prorocentrum sp. The central role of temperature in structuring the co-occurrence network suggests that future global warming could deeply modify plankton communities in shallow coastal zones, affecting whole-food web functioning.
Quantum interference effects in multi-channel correlated tunneling structures
Authors: Maslova N. S. , Mantsevich V. N. , Luchkin V. N. , Palyulin V. V. , Arseyev P. I. , Sokolov I. M.
Published: September 2021

In multi-channel tunneling systems quantum interference effects modify tunneling conductance spectra due to Fano effect. We investigated the impact of Hubbard type Coulomb interaction on tunneling conductance spectra for the system formed by several interacting impurity atoms or quantum dots localised between the contact leads. It was shown that the Fano shape of tunneling conductance spectra strongly changes in the presence of on-site Coulomb interaction between localised electrons in the intermediate system. The main effect which determines the shape of the tunneling peaks could be not Fano interference but mostly nonequilibrium dependence of the occupation numbers on bias voltage.
Simple linear ionic polysiloxane showing unexpected nanostructure and mechanical properties
Authors: Hara Mitsuo , Iijima Yuta , Nagano Shusaku , Seki Takahiro
Published: September 2021

Polysiloxanes are ubiquitous materials in industry and daily life derived from silicates, an abundant resource. They exhibit various properties, which depend on the main-chain network structure. Linear (1D backbone) polysiloxanes provide amorphous materials. They are recognized as fluid materials in the form of grease or oil with a low glass transition temperature. Herein we report that a simple linear polysiloxane, poly(3-aminopropylmethylsiloxane) hydrochloride, shows an elastic modulus comparable to that of stiff resins such as poly(tetrafluoroethylene). By introducing an ammonium salt at all the units of this polysiloxane, inter- and intramolecular ionic aggregates form, immensely enhancing the elastic modulus. This polysiloxane is highly hygroscopic, and its modulus can be altered reversibly 100 million times between moist and dry atmospheres. In addition, it works as a good adhesive for glass substrates with a shear strength of more than 1 MPa in the dry state. Despite its simple structure with a flexible backbone, this polymer unexpectedly self-assembles to form an ordered lamellar nanostructure in dry conditions. Consequently, this work reveals new functions and possibilities for polysiloxanes materials by densely introducing ionic groups.