bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Thermal Conductivity and Tensile Strength in Cast Irons
Authors: Fourlakidis Vasilios , Hernando Juan Carlos , Holmgren Daniel , Diószegi Attila
Published: February 2023

Improved mechanical and thermal properties are important characteristics for enhancing the performance of cast iron components that operate at elevated temperatures. Thermal conductivity defines the temperature distribution within the casting and influences the magnitude of the thermally induced tensile stresses. The microstructural features that increase the thermal conductivity have a negative impact on tensile strength. The results reported in this work show that there is a unique inverse relationship between thermal conductivity and tensile strength, valid for the whole range of cast iron alloys regardless of graphite form, solidification rates, carbon content and matrix constituents. The finding indicates the challenges for the simultaneous improvement of these properties, and it can be utilized as a guideline during the design of cast iron components for high temperature applications.
Entscheidungsfindung und Einfluss bei Fridays for Future – Zur Rolle von Basisdemokratie, Hierarchien und Expertise
Authors: Mucha Witold , Soßdorf Anna , Ferschinger Laura , Burgi Viktor , Krach Philipp
Published: February 2023

Im Unterschied zur bisherigen Forschung über Fridays for Future, die sich vornehmlich mit der Genese, Mobilisierung und dem Framing der sozialen Bewegung beschäftigt, stehen deren interne Entscheidungsprozesse im Mittelpunkt des Aufsatzes: Wie werden Entscheidungen in der dezentral organisierten Bewegung getroffen und welche Faktoren haben dabei besonderen Einfluss? Auf Basis eines Mehrmethodendesigns, das sich Beobachtungen, Interviews und einer Online-Umfrage bedient, kommt die Studie zu drei Ergebnissen. Erstens bewegen sich Entscheidungsdynamiken insbesondere auf Bundesebene im Spannungsfeld zwischen basisdemokratischen Grundprinzipien auf der einen und dem Primat effizienter Prozesse auf der anderen Seite. Zweitens herrschen informelle Hierarchien innerhalb der verschiedenen Ebenen vor, die sowohl positiv als auch negativ von den Mitgliedern bewertet werden. Drittens nimmt der Einfluss auf Entscheidungen zu je erfahrener, kompetenter und besser vernetzt Aktivist:innen sind. Die Implikationen der Ergebnisse für anknüpfende Forschung im Bereich der Theorien der Sozialen Bewegungen sind zweierlei. Zum einen wird deutlich, dass eine Organisation wie Fridays for Future unabhängig der dezentralen Autonomie ihrer über 500 Ortsgruppen auch nach über drei Jahren seit ihrer Gründung entscheidungs- und mobilisierungsfähig geblieben ist. Im Vergleich zu anderen sozialen Bewegungen beweist Fridays for Future hinsichtlich ihres Wirkungsradius und ihrer Mitgliederstärke somit eine erstaunliche Resilienz. Zum anderen zeigen die Ergebnisse, dass es trotz einer beachtlichen Formalisierung und Differenzierung auf Seiten der Basis durchaus Unmut über Machtasymmetrien gegenüber den Entscheidungen auf Bundesebene gibt. Die Ergebnisse fußen auf einem Citizen-Science-Projekt, das etablierte Aktivist:innen der Bewegung mit Wissenschaftler:innen zusammenbrachte. Die Kooperation ermöglichte den exklusiven Zugang zu den Entscheidungsforen der Kernmitglieder.
Long COVID – eine neue Herausforderung in der Medizin: Fokus auf Schwangerschaft und Stillzeit
Authors: Han Emilie , Gyöngyösi Mariann
Published: February 2023

Long COVID wurde als eine neue Multiorganerkrankung beschrieben, die bei Frauen häufiger auftritt als bei Männern. Schwangere und stillende Frauen sind eine spezielle Untergruppe von Patienten, die bei einer Long-COVID-Erkrankung zu berücksichtigen sind, da bisher die Datenlage nur gering ausfällt. Menstruationsveränderungen werden häufig während oder nach einer akuten Erkrankung mit dem Coronavirus-2019 (COVID-19) beobachtet. Einige Studien stellen zudem einen Zusammenhang zwischen geringen Veränderungen der Zykluslänge und einer COVID-Impfung dar. Schwangere Frauen, die eine symptomatische Infektion mit dem schweren-akuten-Atemwegssyndrom-Coronavirus Typ 2 (SARS-CoV‑2) hatten, können ein höheres Risiko für Komplikationen in der Schwangerschaft, wie Frühgeburt oder Präeklampsie, haben. Darüber hinaus sind mehr Studien notwendig, um die Auswirkungen einer vertikalen Übertragung zu beurteilen. Das wirksamste Mittel gegen die Pandemie sind die verfügbaren COVID-Impfstoffe, da sie eine Infektion verhindern, aber auch Long-COVID-Symptome lindern können. Impfstoffe haben sich sowohl bei schwangeren als auch bei stillenden Frauen als sicher und wirksam erwiesen. Ziel dieses Artikels ist es, die aktuell verfügbaren Daten zu Long COVID bei schwangeren und stillenden Frauen darzustellen und die Risikofaktoren und therapeutischen Möglichkeiten aufzuzeigen.
The impacts of land cover spatial combination on nighttime light intensity in 2010 and 2020: a case study of Fuzhou, China
Authors: Yuan Yongxin , Chen Zuoqi
Published: February 2023

As human activities highly depend on the land resources and changed the land cover (LC) condition, the relationship between LC and nighttime light (NTL) intensity has been widely analyzed to support the foundation of NTL applications and help explain the drivers of urban economic development. However, previous studies always paid attention to the effect of each LC type on NTL intensity, with limited consideration of the joint effects of any two LC types. To fill this gap, this study measured the land cover spatial combination (LCSC) by using a spatial adjacency matrix, and then analyzed its impacts on NTL intensity based on an extreme gradient boosting (XGBoost) regression model with the assistant of sharpley additive explanations (SHAP) method. Our results presented that the LCSC can better (R2 of 82.4% and 98.1% in 2010 and 2020) explain the relationship between LC and NTL intensity with the traditional LC metrics (e.g., area and patch count), since the LCSC is much more sensitive to the diverse land functions. It is noteworthy that the impacts, as well as their dynamics, of LCSC between any two LC types on NTL intensity are various. LCSC associated with artificial surface contributed more to NTL intensity. In detail, the LCSC of water/wetland and artificial surface can increasingly promote the NTL intensity while the LCSC of grassland/forest and artificial surface has a decreasing or inverse U-shaped contribution to NTL intensity. Whereas LCSC associated with non-artificial surface were not conducive to the increase in NTL intensity due to high vegetation density. We also provided three implications to help further urbanization process and discussed the applications of LCSC.
The Profit Motive
Authors: Bainbridge Stephen M.
Published: February 2023

What responsibility, if any, does a corporation have to society? How should corporations balance environmental, social, and governance factors? The Profit Motive addresses these questions of corporate purpose using historical, legal, and economic perspectives. Stephen M. Bainbridge enters the debate around corporate social responsibility to mount an unabashed defense of shareholder capitalism and maximizing shareholder value. The book offers context for the current questions about corporate purpose, and provides a reference going forward. Direct and corrective, The Profit Motive argues that shareholder value maximization is not only required by law, but what the law ought to require.
Storying Mental Illness and Personal Recovery
Authors: Thomsen Dorthe Kirkegaard , Holm Tine , Jensen Rikke , Lind Majse , Pedersen Anne Mai
Published: February 2023

This book contains excerpts of life stories from 118 individuals diagnosed with schizophrenia, bipolar disorder, borderline personality disorder, and major depressive disorder. This library of personal narratives, heavily reproduced and quoted throughout the text, presents a composite image of the ways in which narrative identity can be affected by mental illness while also being a resource for personal recovery. Those researching, studying or practicing in mental health professions will find a wealth of humanizing first-person perspectives on mental illness that foster perspective-taking and aid patient-centered treatment and study. Researchers of narrative psychology will find a unique set of life stories synthesized with existing literature on identity and recovery. Moving towards intervention, the authors include a 'guide for narrative repair' with the aim of healing narrative identity damage and fostering growth of adaptive narrative identity.
Effective characterization of quasi-abelian surfaces
Authors: Mendes Lopes Margarida , Pardini Rita , Tirabassi Sofia
Published: February 2023

Let V be a smooth quasi-projective complex surface such that the first three logarithmic plurigenera

$\overline P_1(V)$

,

$\overline P_2(V)$

and

$\overline P_3(V)$

are equal to 1 and the logarithmic irregularity

$\overline q(V)$

is equal to

$2$

. We prove that the quasi-Albanese morphism

$a_V\colon V\to A(V)$

is birational and there exists a finite set S such that

$a_V$

is proper over

$A(V)\setminus S$

, thus giving a sharp effective version of a classical result of Iitaka [12].
Liberty, Slavery, and Biography: The Hidden Shapes of Free Speech
Authors: Dabhoiwala Fara
Published: February 2023

The first substantive theory of free speech as a secular political right was concocted by two anonymous London journalists, Thomas Gordon and John Trenchard, in their best-selling, endlessly reprinted newspaper column, Cato's Letters (1720–1723). Though its ideals became hugely influential, especially in the American colonies, Trenchard and Gordon's motives and the peculiar biases of their theory remain unexplored. John Locke's theorizing of personal liberty while accepting patriarchy and slavery has been much studied; that of Cato's Letters, a comparably significant text, not at all. Drawing on a wealth of newly discovered materials in British, Caribbean, and American archives, the author explores the telling roles of gender and especially race in early Anglophone ideals of free speech, connecting them to the lived experiences of Gordon, Trenchard, and their shadowy publisher, Elizée Dobrée. The article thus reframes our understanding of one of the most important Anglo-American political works of the eighteenth century, and exemplifies how to approach free speech historically, as both a theory and a practice. Freedom of expression does not simply arise from the lessening of “censorship” and restraint, nor is it ever equally accessible to all. Visibly and invisibly, like every kind of liberty, it always has a particular shape.
RADIOCARBON DATING OF MANUSCRIPTS KEPT IN THE CENTRAL LIBRARY OF THE UNIVERSITY OF TEHRAN
Authors: Aghaei Ali , Bahrololoumi Faranak , Hajdas Irka , Jafarian Rasul , Kordavani Lili , Marx Michael
Published: February 2023

This article discusses radiocarbon dating results of documents preserved at the Central Library of the University of Tehran (hereafter, CLUT) as part of the project “Irankoran.” The paper adds new evidence to an ongoing campaign of dating Qurʾāns and Oriental manuscripts by the Corpus Coranicum Project. The dated manuscripts include one kūfī fragment of the Qurʾān on parchment (no. 10950) and a selection of Islamic and Persian manuscripts, all from the second millennium: the Arabic dictionary Muǧmal al-Luġah (Meškāt no. 203), the medical encyclopedia Ḏaḫīrah-ye Khwārazmšāhī (no. 5156), the epic Panǧ Ganǧ of Neẓāmī (no. 5179), the book of wisdom Ādāb al-Falāsifah (no. 2165) attributed to Ḥunayn b. Isḥāq (d. 873 CE), and one of the oldest extant manuscripts of the Avesta Wīdēwdād (no. 11263). Although the authenticity of their colophons is disputed, radiocarbon dating supports the dates of the colophons; even in cases where they were suspected of being tampered with, they most likely present the accurate original dates of the corresponding manuscripts. Only in the case of Ādāb al-Falāsifah (no. 2165), radiocarbon dating of the parchment has identified the manuscript as non-authentic. Inconsistent carbon dating results of two samples taken from Ḏaḫīrah-ye Khwārazmšāhī (no. 5156) and Panǧ Ganǧ (no. 5179) provide evidence of later replaced/added leaves.
The Early Political Thought and Publishing Career of V. K. Krishna Menon, 1928–1938
Authors: Bowman Jack
Published: February 2023

This article assesses Indian activist V. K. Krishna Menon's early political thought, formed during his years in Britain prior to Indian independence. It argues that this was more nuanced than has been previously characterized, with a range of influences and foundations. To analyse the formation and evolution of Menon's political thought, it looks at his political actions from this period, which largely fall into three areas; the India League, his engagement with the British Left, and his publishing career. His editorial work is what often tied together these strands of political action and was where his political thought manifested and expressed itself. This article analyses Menon's publishing career from roughly 1928 to 1938, highlighting the engagement of the three strands of his political action, before undertaking a book history of the India League text Condition of India. The article is a continuation of the expansion of book histories of twentieth-century empire, and argues for a reassessment of anti-colonial texts and figures along these lines, whilst also contributing to the growing historiographical trend that seeks to recast modern Indian political thought, as well as the politics of internationalist activists in interwar Britain.
Child food portion sizes in the home environment: how do parents decide?
Authors: Acolatse Lena , Pourshahidi L. Kirsty , Logue Caomhan , McCann Mary T. , Kerr Maeve A.
Published: February 2023

The consumption of larger portion sizes (PS) of food has been implicated in the increased prevalence of childhood obesity. The home is usually the first place children learn about food, however, little is known about how parents determine child PS in the home environment. This narrative review aimed to explore parental beliefs, decisions, strategies and barriers to the provision of appropriate food PS for children in the home environment. Results indicate that parental decisions on child food PS are based on the amounts they serve themselves, personal intuition and knowledge of child appetite. Owing to the habitual nature of food provision, parental decisions on child PS may be taken without conscious thought and/or could be part of a complex decision-making process influenced by several interlinked factors, including parental childhood mealtime experiences, other family members and child weight status. Strategies to determine child-appropriate PS include modelling the desired PS behaviour, use of unit-based food packaging and PS estimation aids, and providing the child with a degree of autonomy to rely on their own appetite cues. A lack of knowledge/awareness of PS guidance is a key barrier identified by parents to the provision of age-appropriate PS, warranting the inclusion of salient child-appropriate PS guidance within national dietary recommendations. Further home-based interventions to improve the provision of appropriate child PS are required, leveraged on parental strategies already in use, as outlined in this review.
Graph transformation in engineering design: an overview of the last decade
Authors: Voss Christopher , Petzold Frank , Rudolph Stephan
Published: February 2023

In engineering and architecture, different approaches have been developed that share the use of graph transformation to automate design processes or to search for design solutions by means of computational design synthesis. In order to give an overview of these approaches, we provide a review of articles published in the last decade. Forty-eight articles were reviewed to determine similarities and differences of these approaches. Research fields in method development for the representation of design problems and the processing of graph transformations, as well as the application of graph transformations in engineering, architecture, and shape grammars were identified. Different approaches for the documentation of the vocabulary and the rules were examined. Finally, different approaches for rule applications were analyzed. Based on found limitations, future research directions are suggested.
The value /me/ of the sign  in Achaemenid Elamite
Authors: Fattori Marco
Published: February 2023

The aim of this article is to show that in Achaemenid Elamite the sign  had a secondary phonetic value /me/. The evidence collected in support of this claim consists mainly in Elamite transcriptions of Iranian words in the Achaemenid Royal Inscriptions and in the Persepolis administrative texts, which are impossible or very difficult to account for only contemplating the usual value /man/.
Psychometric properties of the Turkish version of the Stress Scale for Nurses Providing End-of-Life Care for Children
Authors: Ayran Gülsün , Çevik Özdemir Hamide Nur
Published: February 2023

Objectives

This study was carried out to evaluate the validity and reliability of the Stress Scale for Pediatric Nurses Performing End-of-Life Care for Children in Turkey.

Methods

This was a methodological study conducted with 222 pediatric nurses. Data were collected using the information form for pediatric nurses and the “stress scale for nurses performing end-of-life care for children.” Content and construct validity, item analysis, confirmatory factor analysis and internal consistency were used to evaluate the data. The Global Pharmaceutical Regulatory Affairs Summit checklist was followed in this study.

Results

The content validity index of the scale was 0.93. Item-total score correlation values ranged from 0.594 to 0.885. The 5-factor structure of the scale was confirmed as a result of confirmatory factor analysis. Factor loads were greater than 0.30, and fit indices were greater than 0.80. The Cronbach’s alpha coefficient of the Turkish version of the scale was 0.97.

Significance of results

The stress scale for nurses performing end-of-life care for children is a valid and reliable measurement tool for the Turkish sample. This scale facilitates the assessment of the stress levels of pediatric nurses who provide end-of-life care to children. Also, this scale can be used in interventional studies to improve the well-being of pediatric nurses.
Downward Drifting F‐Region Irregularity Observed Above an Eastward Drifting One Before Midnight on 4 March 2014
Authors: Chen Gang , Zhang Min , Yan Chunxiao , Zhang Qiang , Yang Guotao , Li Yaxian , Zhang Shaodong , Gong Wanlin , He Zhiqiu
Published: February 2023

On the night of 4 March 2014, the Hainan COherent Scatter Phased Array Radar (HCOPAR) observed two irregularities appearing simultaneously in the radar scope at different height ranges. The global positioning system total electron content receivers also recorded two groups of plasma bubbles connecting in the observation scope of the HCOPAR. The topside irregularity moved slowly downward with almost no zonal movement, while the bottomside irregularity drifted eastward. There was not much difference among the h’F, hmF, and foF variations recorded by the Hainan Digisonde on that day and the reference days, except for a rapid descent in hmF between 20:45 and 21:15 LT. The downward moving irregularity was also recorded during this period. The prompt penetration electric fields induced by turnings of the interplanetary magnetic field Bz during weak geomagnetic activities are suggested not to influence the whole F‐layer heights at low latitudes but only to change the drift direction of the topside irregularity.
Tracking NO2 Pollution Changes Over Texas: Synthesis of In Situ and Satellite Observations
Authors: Gyawali Madhu S. , Lamsal Lok N. , Sedai Jay R. , Gyawali Bimal , Bhattarai Keshav , Williams Quintaria , Neige Shannon , Sharma Shriram , Aryal Rudra
Published: February 2023

Nitrogen oxides (NOx) are major air pollutants that play a crucial role in atmospheric chemistry. We compare Ozone Measuring Instrument's (OMI) NO2 records with the in situ surface measurements from the Air Quality System of the US Environmental Protection Agency and the Texas Commission on Environmental Quality network in the state of Texas with the goal of understanding the correspondence of satellite and in situ surface observations and identifying the potential synergies between the two observing systems. Our analysis of over 40 in situ daily surface site observations, mostly from urban areas, and OMI daily observed data suggests a correlation (r) ranging between 0.2 and 0.8. The correlation improves considerably (r > 0.5) for monthly average data. Weekly variation of surface NO2 with a Sunday minimum is well captured by OMI tropospheric NO2 column observations with similar weekend reductions. NO2 trend in Texas during 2005–2019 is characterized by significant reductions of 20%–36% in highly populated cities and urban centers. However, a significant (up to 80%) increase was observed in oil and gas producing regions of the Permian and Eagle Ford Basins over the same period. In March–April of 2020, like the other US and global cities, Texas experienced up to 60% reduction in NO2 levels in major cities due to travel restrictions imposed at local and national levels to contain the spread of COVID‐19. Though such reduction is temporary, these reductions were significantly larger than those achieved in the past 16 years of OMI record suggesting that technological advancement can curtail NOx emissions.
Morphodynamic Characteristics of a Complex Anabranching System in the Qinghai‐Tibet Plateau and the Implications for Anabranching Stability
Authors: Guo Xiwei , Gao Peng , Li Zhiwei
Published: February 2023

The understanding of fluvial processes controlling morphological adjustments and stability of anabranching rivers remains incomplete. Focusing on a complex anabranching system in the Upper Yellow River, this study quantifies the morphological characteristics and lateral dynamics of islands and channels in four reaches over a 56‐km river course from 1986 to 2017. Using five heuristic anabranching structures derived from the studied anabranching system, we estimate sediment transport capacities and assess their implications for the morphodynamics of anabranching rivers. These results show that the system exhibited a highly complex pattern featuring high channel multiplicity and dominance of islands. Over the study periods, the system exhibited an accreting disequilibrium state, which was highlighted by spatiotemporally diverse and dynamic patterns of islands. Morphological changes in islands were dominated by expansion and shrinkage, which caused more areal changes than other modes of change, including coalescence, cleavage, new island formation, and elimination. These processes controlled the creation and elimination of small anabranches, whereas the size and morphology of large channels remained comparatively stable, which maintained the stability of this anabranching pattern. The stability of the anabranching pattern is further supported by estimations of transport capacity in that the main channels transport most sediments and in that excess development of small anabranches promotes sediment deposition within the system. Overall, this study provides new insight into the morphodynamic properties of anabranching rivers, demonstrating that, instead of channel numbers, island dynamics and interactions with channels are controls of the evolutionary processes and stability of anabranching rivers.
Time Domain Reflectometry Waveform Interpretation With Convolutional Neural Networks
Authors: Wang Zhuangji , Hua Shan , Timlin Dennis , Kojima Yuki , Lu Songtao , Sun Wenguang , Fleisher David , Horton Robert , Reddy Vangimalla R. , Tully Katherine
Published: February 2023

Interpreting time domain reflectometry (TDR) waveforms obtained in soils with non‐uniform water content is an open question. We design a new TDR waveform interpretation model based on convolutional neural networks (CNNs) that can reveal the spatial variations of soil relative permittivity and water content along a TDR sensor. The proposed model, namely TDR‐CNN, is constructed with three modules. First, the geometrical features of the TDR waveforms are extracted with a simplified version of VGG16 network. Second, the reflection positions in a TDR waveform are traced using a 1D version of the region proposal network. Finally, the soil relative permittivity values are estimated via a CNN regression network. The three modules are developed in Python using Google TensorFlow and Keras API, and then stacked together to formulate the TDR‐CNN architecture. Each module is trained separately, and data transfer among the modules can be facilitated automatically. TDR‐CNN is evaluated using simulated TDR waveforms with varying relative permittivity but under a relatively stable soil electrical conductivity, and the accuracy and stability of the TDR‐CNN are shown. TDR measurements from a water infiltration study provide an application for TDR‐CNN and a comparison between TDR‐CNN and an inverse model. The proposed TDR‐CNN model is simple to implement, and modules in TDR‐CNN can be updated or fine‐tuned individually with new data sets. In conclusion, TDR‐CNN presents a model architecture that can be used to interpret TDR waveforms obtained in soil with a heterogeneous water content distribution.
Baked Contacts Focus a Lens on Ancient Lava Flows
Authors: Pivarunas Anthony , Avery Margaret , Biasi Joseph , Karlstrom Leif
Published: February 2023

Two studies, conducted 40 years apart, show how combining field observations and thermal modeling can reconstruct the history of massive lava flows and how they altered the surrounding landscape.
Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening
Authors: Deng Ling , Yang Li , Zhu Shuhan , Li Man , Wang Yu , Cao Xiaolong , Wang Qiongyao , Guo Linlang
Published: February 2023

There is currently a lack of efficacious treatments for patients with chemo-resistant small-cell lung cancer (SCLC), leading to poor prognoses. We examined a chemo-resistant SCLC cell line using genome-wide CRISPR/Cas9 screening and identified serine/threonine kinase cell division cycle 7 (CDC7) as a potential synergistic target. Silencing CDC7 in chemo-resistant SCLC cells decreased the IC50 and improved the efficacy of chemotherapy. Based on the highest single agent model, the CDC7 inhibitor XL413 had a synergistic effect with both cisplatin and etoposide in chemo-resistant SCLC cells, but had no such effect in chemo-sensitive SCLC cells; the combination of XL413 and chemotherapy significantly inhibited cell growth. Western blot and flow cytometry showed that the combined treatments increased apoptosis, whereas XL413 alone had little effect on apoptosis. An analysis of cell cycle and cyclin protein levels indicated that the combination of XL413 and chemotherapy-induced G1/S phase arrest and DNA damage in chemo-resistant SCLC cells. Xenografted tumor and histoculture drug response assays using patient-derived xenografts showed that XL413 improved the efficacy of chemotherapy in vivo and with SCLC tissues. These results suggest that XL413 exerts a synergistic effect with chemotherapy on chemo-resistant SCLC.
Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson’s disease
Authors: Soto Marta , Fernández Manel , Bravo Paloma , Lahoz Sara , Garrido Alicia , Sánchez-Rodríguez Antonio , Rivera-Sánchez María , Sierra María , Melón Paula , Roig-García Ana , Naito Anna , Casey Bradford , Camps Jordi , Tolosa Eduardo , Martí María-José , Infante Jon , Ezquerra Mario , Fernández-Santiago Rubén
Published: February 2023

The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson’s disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers (L2NMC) are at PD high risk but predicting pheno-conversion is challenging given the lack of progression biomarkers. To investigate novel biomarkers for PD premotor stages, we performed a longitudinal microRNA (miRNA) assessment of serum samples from G2019S L2NMC followed-up over 8 years. Our cohort consisted of G2019S L2NMC stratified by dopamine transporter single-photon emission computed tomography (DaT-SPECT) into DaT-negative (n = 20) and DaT-positive L2NMC (n = 20), pheno-converted G2019S L2PD patients (n = 20), idiopathic PD (iPD) (n = 19), and controls (n = 40). We also screened a second cohort of L2PD patients (n = 19) and controls (n = 20) (Total n = 158). Compared to healthy controls, we identified eight deregulated miRNAs in DaT-negative L2NMC, six in DaT-positive L2NMC, and one in L2PD. Between groups, the highest miRNA differences, 24 candidate miRNAs, occurred between DaT-positive L2NMC and L2PD. Longitudinally, we found 11 common miRNAs with sustained variation in DaT-negative and DaT-positive L2NMCs compared to their baselines. Our study identifies novel miRNA alterations in premotor stages of PD co-occurring with progressive DaT-SPECT decline before motor manifestation, whose deregulation seems to attenuate after the diagnosis of L2PD. Moreover, we identified four miRNAs with relatively high discriminative ability (AUC = 0.82) between non-pheno-converted DaT-positive G2019S carriers and pheno-converted L2PD patients (miR-4505, miR-8069, miR-6125, and miR-451a), which hold potential as early progression biomarkers for PD.
Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
Authors: Schaffrath Anja , Schleyken Sophia , Seger Aline , Jergas Hannah , Özdüzenciler Pelin , Pils Marlene , Blömeke Lara , Cousin Anneliese , Willbold Johannes , Bujnicki Tuyen , Bannach Oliver , Fink Gereon R. , Willbold Dieter , Sommerauer Michael , Barbe Michael T. , Tamgüney Gültekin
Published: February 2023

Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson’s disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that α-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies.
Immunological correlates of protection following vaccination with glucan particles containing Cryptococcus neoformans chitin deacetylases
Authors: Wang Ruiying , Oliveira Lorena V. N. , Lourenco Diana , Gomez Christina L. , Lee Chrono K. , Hester Maureen M. , Mou Zhongming , Ostroff Gary R. , Specht Charles A. , Levitz Stuart M.
Published: February 2023

Vaccination with glucan particles (GP) containing the Cryptococcus neoformans chitin deacetylases Cda1 and Cda2 protect mice against experimental cryptococcosis. Here, immunological correlates of vaccine-mediated protection were explored. Studies comparing knockout and wild-type mice demonstrated CD4+ T cells are crucial, while B cells and CD8+ T cells are dispensable. Protection was abolished following CD4+ T cell depletion during either vaccination or infection but was retained if CD4+ T cells were only partially depleted. Vaccination elicited systemic and durable antigen-specific immune responses in peripheral blood mononuclear cells (PBMCs), spleens, and lungs. Following vaccination and fungal challenge, robust T-helper (Th) 1 and Th17 responses were observed in the lungs. Protection was abrogated in mice congenitally deficient in interferon (IFN) γ, IFNγ receptor, interleukin (IL)-1β, IL-6, or IL-23. Thus, CD4+ T cells and specific proinflammatory cytokines are required for GP-vaccine-mediated protection. Importantly, retention of protection in the setting of partial CD4+ T depletion suggests a pathway for vaccinating at-risk immunocompromised individuals.
Stem stiffness functionality in a submerged canopy patch under oscillatory flow
Authors: Barcelona Aina , Colomer Jordi , Serra Teresa
Published: February 2023

Seagrass canopies are coastal ecosystems that are able to modify the abiotic environment through their architectural structure. They have different structural parameters, such as plant stem stiffness, patch length and canopy density, all of which determine their overall functionality in modifying the seafloor hydrodynamics within coastal areas. To determine the interaction between hydrodynamics and the canopy structure, a set of laboratory experiments were carried out with both rigid and flexible stems for different canopy densities, patch lengths and wave frequencies. In the upper part of the canopy, flexible plants move with the flow without generating drag or producing turbulent kinetic energy, while rigid plants generate drag and produce turbulent kinetic energy. In the inner canopy layer, both types of plants behave like rigid stems and produce turbulent kinetic energy. A non-dimensional model based on the turbulent kinetic energy, the wave velocity and the plant characteristics is presented to describe the behaviour of flexible and rigid plants under an oscillating flow. Flexible plants behave in a stiffer manner under high wave frequencies than under low wave frequencies, thus making their behaviour closer to that of rigid plant stems. This difference between both canopy structures can explain their distribution in the environment, with rigid canopies being more extended in more sheltered regions while flexible plants are characteristic of more exposed regions with high flow energy.
Effects of time-restricted feeding on letrozole-induced mouse model of polycystic ovary syndrome
Authors: Ryu Ki-Jin , Park Hyuntae , Han Young In , Lee Hee Jung , Nam Seunghyun , Jeong Hye Gyeong , Kim Tak
Published: February 2023

The present study aimed to investigate whether time-restricted feeding (TRF) ameliorates metabolic and reproductive phenotypes in a letrozole-induced mouse model of polycystic ovary syndrome (PCOS). Sixty female C57BL/6 N mice were randomly divided into two groups according to the type of food received: either a chow or a 60% high-fat diet. Those mice were subcutaneously implanted with letrozole or placebo pellets at four weeks of age. Then, letrozole-treated mice were randomly assigned to different feeding regimens: (1) TRF for 4 h (ZT12–ZT16) or (2) ad libitum diet. After 4 weeks of dietary intervention, estrous cycles were determined with daily vaginal smear examination, and serial tail-tip blood sampling was performed at 5-min intervals for 2 h to measure the luteinizing hormone (LH) pulse frequency, amplitude, and mean LH levels in the diestrus cycle stage. Letrozole-treated mice in the ad libitum group demonstrated multiple PCOS-like phenotypes including ovulatory dysfunction, polycystic ovaries, and increased body weight, parametrial fat weight, adipocyte size and inflammation, and higher expression of Cyp17, Cyp19, and Fshr in the ovary, and Kiss1r and Gnrh in the hypothalamus, elevated serum testosterone levels, and more rapid and elevated LH pulsatility, with increased pulse frequency, amplitude, and mean levels in the diestrus stage, compared with the controls. After TRF for 4 weeks, those phenotypes reverted to normal levels in letrozole-treated mice, except the percentage of diestrus cycles indicating the arrest of estrous cycling which did not differ between the TRF and ad libitum groups. Our results demonstrate that TRF has therapeutic effects on the reproductive and metabolic phenotypes of a letrozole-induced mouse model of PCOS.
Comparing event-related potentials of retrospective and prospective metacognitive judgments during episodic and semantic memory
Authors: Irak Metehan , Soylu Can , Yavuz Mustafa
Published: February 2023

It is unclear whether metacognitive judgments are made on the basis of domain-generality or domain-specificity. In the current study, we compared both behavioral and event-related potential (ERP) correlates of retrospective (retrospective confidence judgments: RCJs), and prospective (feeling of knowing: FOK) metacognitive judgments during episodic and semantic memory tasks in 82 participants. Behavioral results indicated that FOK judgments reflect a domain-specific process, while RCJ reflect a domain-general process. RCJ and FOK judgments produced similar ERP waveforms within the memory tasks, but with different temporal dynamics; thus supporting the hypothesis that retrospective and prospective metacognitive judgments are distinct processes. Our ERP results also suggest that metacognitive judgments are linked to distributed neural substrates, rather than purely frontal lobe functioning. Furthermore, the role of intra-subject and inter-subject differences in metacognitive judgments across and within the memory tasks are highlighted.
Adverse events are not increased by controlled delay in surgery of acute upper extremity fractures
Authors: Matias Torkki , Axel Somersalo , Hannu Kautiainen , Maarit Ax , Ilkka Kiviranta , Juha Paloneva
Published: February 2023

Management of the operative treatment of fractures is challenged by daily variation in patient flow. For upper limb fractures there has recently been an increasing tendency to temporarily discharge the patient to wait for a daytime operation to be performed during the next few days. The objective of this study was to study the safety of controlled delay in surgery. Upper limb fractures (N = 1 944) treated in a level 2 trauma center from 2010 to 2016 were identified and included in this retrospective cohort study with 5-year follow-up. Delay in surgery, inpatient time, readmissions, ED revisits and mortality were analyzed. Depending on the nature of the injury, controlled delay to surgery was implemented. Urgency of surgery was coded as green (2 days to 2 weeks) yellow (8–48 h) or red (less than 8 h). Harms and benefits to the groups were compared. Controlled delay of surgery (median delay of 5 days 7 h) was applied in 1 074 out of 1 944 fractures. The number of revisits to the emergency department (11.1% vs. 17.9–24.1%, p < 0.001) or hospital readmissions for any reason (0.99 per 100 person years in the delayed group vs. 3.74 and 4.35 in the non-delayed groups, p < 0.001) was no higher in patients with delayed (green) compared to those with non-delayed (yellow and red) operations. Inpatient time was significantly lower in the delayed group than other groups (IRR 2.31–3.36, (p < 0.001)). The standardized mortality ratio was 0.83 (CI 0.57–1.22) in the delayed group vs. 1.49 (CI 1.17–1.90) and 1.61 (CI 1.16–2.23) in the non-delayed groups. Controlled delay in upper limb trauma surgery did not lead to increased readmissions or mortality and was associated with reduced inpatient time.
Determination of the characteristic curves of a nonlinear first order system from Fourier analysis
Authors: Gonzalez Federico J.
Published: February 2023

Based on Fourier analysis, we develop an expression for modeling and simulating nonlinear first order systems. This expression is associated to a nonlinear first order differential equation $$y=f(x)+g(x)x'$$

y
=
f

(
x
)

+
g

(
x
)

x
′

, where $$x=x(t)$$

x
=
x
(
t
)

is the dynamical variable, $$y=y(t)$$

y
=
y
(
t
)

is the driving force, and the f and g functions are the characteristic curves which are associated to dissipative and memory elements, respectively. The model is obtained from the sinusoidal response, specifically by calculating the Fourier analysis of y(t) for $$x(t)=A_1\sin (\omega t)+A_0$$

x

(
t
)

=

A
1

sin

(
ω
t
)

+

A
0

, where the model parameters are the Fourier coefficients of the response, and the values of $$A_0$$

A
0

, $$A_1$$

A
1

and $$A_1'=A_1\omega$$

A
1
′

=

A
1

ω

. The same expression is used for two kinds of time-domain simulations: to calculate other driving force $$\hat{y}$$

y
^

based on a dynamical variable $$\hat{x}$$

x
^

; and, to calculate the dynamical variable $$\hat{x}$$

x
^

based on a driving force $$\hat{y}$$

y
^

. In both cases, the dynamical variable must remain in the range $$\hat{x}\in [A_0-A_1,A_0+A_1]$$

x
^

∈

[

A
0

-

A
1

,

A
0

+

A
1

]

. By analyzing this expression, we found an equivalence between the Fourier coefficients and the polynomial regressions of the characteristic curves of f and g. This result allows us to obtain the system modeling and simulation based on the amplitude and phase Fourier spectrum obtained from the Fast Fourier Transform (FFT) of the sampled $$y_n$$

y
n

version of y(t). It is shown that this technique has a low computational complexity, and it is expected to be suitable for real-time applications for system modeling, simulation and control, in particular when the explicit expressions of the characteristic curves are unknown. Fourier analysis is a fundamental tool in electronics, mathematics and physics, but to the best of the author’s knowledge, no work has found this clear evidence of the connection between the Fourier analysis and a first order differential equation. The aim of this work is to initiate a systematic study on this topic.
FMRP, FXR1 protein and Dlg4 mRNA, which are associated with fragile X syndrome, are involved in the ubiquitin–proteasome system
Authors: Shimizu Hideo , Hohjoh Hirohiko
Published: February 2023

The ubiquitin–proteasome system (UPS) is a proteolytic pathway that is essential for life maintenance and vital functions, and its disruption causes serious impairments, e.g., disease development. Thus, the UPS is properly regulated. Here we show novel UPS-related factors: the fragile X mental retardation 1 (FMR1) and Fmr1 autosomal homolog 1 (FXR1) proteins and discs large MAGUK scaffold protein 4 (Dlg4) mRNA, which are associated with Fragile X syndrome, are involved in UPS activity. Fmr1-, Fxr1- and Dlg4-knockdown and Fmr1- and Fxr1-knockdown resulted in increased ubiquitination and proteasome activity, respectively. FXR1 protein was further confirmed to be associated with proteasomes, and Dlg4 mRNA itself was found to be involved in the UPS. Knockdown of these genes also affected neurite outgrowth. These findings provide new insights into the regulatory mechanism of the UPS and into the interpretation of the pathogenesis of diseases in which these genes are involved as UPS-related factors.
Multimodal deep learning of fundus abnormalities and traditional risk factors for cardiovascular risk prediction
Authors: Lee Yeong Chan , Cha Jiho , Shim Injeong , Park Woong-Yang , Kang Se Woong , Lim Dong Hui , Won Hong-Hee
Published: February 2023

Cardiovascular disease (CVD), the leading cause of death globally, is associated with complicated underlying risk factors. We develop an artificial intelligence model to identify CVD using multimodal data, including clinical risk factors and fundus photographs from the Samsung Medical Center (SMC) for development and internal validation and from the UK Biobank for external validation. The multimodal model achieves an area under the receiver operating characteristic curve (AUROC) of 0.781 (95% confidence interval [CI] 0.766–0.798) in the SMC and 0.872 (95% CI 0.857–0.886) in the UK Biobank. We further observe a significant association between the incidence of CVD and the predicted risk from at-risk patients in the UK Biobank (hazard ratio [HR] 6.28, 95% CI 4.72–8.34). We visualize the importance of individual features in photography and traditional risk factors. The results highlight that non-invasive fundus photography can be a possible predictive marker for CVD.
A value-based deep reinforcement learning model with human expertise in optimal treatment of sepsis
Authors: Wu XiaoDan , Li RuiChang , He Zhen , Yu TianZhi , Cheng ChangQing
Published: February 2023

Deep Reinforcement Learning (DRL) has been increasingly attempted in assisting clinicians for real-time treatment of sepsis. While a value function quantifies the performance of policies in such decision-making processes, most value-based DRL algorithms cannot evaluate the target value function precisely and are not as safe as clinical experts. In this study, we propose a Weighted Dueling Double Deep Q-Network with embedded human Expertise (WD3QNE). A target Q value function with adaptive dynamic weight is designed to improve the estimate accuracy and human expertise in decision-making is leveraged. In addition, the random forest algorithm is employed for feature selection to improve model interpretability. We test our algorithm against state-of-the-art value function methods in terms of expected return, survival rate, action distribution and external validation. The results demonstrate that WD3QNE obtains the highest survival rate of 97.81% in MIMIC-III dataset. Our proposed method is capable of providing reliable treatment decisions with embedded clinician expertise.
Multi-modality data-driven analysis of diagnosis and treatment of psoriatic arthritis
Authors: Xu Jing , Ou Jiarui , Li Chen , Zhu Zheng , Li Jian , Zhang Hailun , Chen Junchen , Yi Bin , Zhu Wu , Zhang Weiru , Zhang Guanxiong , Gao Qian , Kuang Yehong , Song Jiangning , Chen Xiang , Liu Hong
Published: February 2023

Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients’ clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan–Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.
Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis
Authors: Wang Jing , Zhang Xinxin , Long Min , Yuan Mengqin , Yin Juan , Luo Wei , Wang Sha , Cai Yu , Jiang Wei , Chao Jie
Published: February 2023

Pulmonary fibrosis (PF) is a form of progressive lung disease characterized by chronic inflammation and excessive extracellular matrix (ECM) deposition. However, the protein changes in fibrotic ECM during PF and their contribution to fibrosis progression are unclear. Here we show that changes in expression of ECM components and ECM remodeling had occurred in silica-instilled mice. The macrophage-derived glycoprotein nonmetastatic melanoma protein B (GPNMB) captured by fibrotic ECM may activate resident normal fibroblasts around the fibrotic foci. Functional experiments demonstrated the activation of fibroblasts in fibrotic ECM, which was alleviated by GPNMB-neutralizing antibodies or macrophage deletion in the ECM of silica-instilled mice. Moreover, the Serpinb2 expression level was increased in fibroblasts in fibrotic ECM, and the expression of CD44 was increased in silica-instilled mice. In conclusion, macrophage-derived GPNMB is trapped by fibrotic ECM during transport and may activate fibroblasts via the CD44/Serpinb2 pathway, thus leading to the further development of fibrosis.