bluuebunny/crossref_metadata_2025 huggingface dataset:
The nature of property in cryptoassets
Authors: Chan Timothy
Published: January 2023

Disputes relating to cryptoassets have proliferated in recent years, along with the rise of the cryptoasset market. Some of these can be resolved using traditional principles of contract, tort or trust law, but proprietary issues raise particular conundrums. While cryptoassets have generally been accepted to be property, that is merely the starting point. To properly resolve proprietary disputes, it is necessary to provide a reasoned and robust explanation for why particular rules of title originally developed in the context of tangible property should apply. In turn, two foundational questions must be answered. First, what is the subject-matter of the property right in cryptoassets? And secondly, what is the proprietary effect of a blockchain transaction? These issues have received relatively little attention in the literature, which has focused on whether cryptoassets are property at all, and existing contributions (including the Law Commission's recent Consultation Paper on Digital Assets) which do engage these issues are far from reaching consensus. This paper critically examines those views and puts forward its own reasoned approach for the application of traditional rules of title to cryptoassets.
Factors influencing nodal yield in neck dissections for head and neck malignancies
Authors: Hintze J , Lang B , Subramaniam T , Kruseman N , O'Regan E , Brennan S , Lennon P
Published: January 2023

Objective

A standard lateral neck dissection should yield at least 18 lymph nodes. The goal of the present study was to examine what factors might influence the number of lymph nodes retrieved during a neck dissection.

Methods

This was a retrospective cohort study in a tertiary academic referral centre for head and neck oncology. Two hundred and nineteen consecutive neck dissections were examined. Age of the patient and primary site were recorded, along with tumour histology, previous radiotherapy and final nodal count.

Results

The mean age was 62.2 ± 13.0 years. The most common primary site was the oral cavity (38.8 per cent). The mean number of lymph nodes was 30.63 ± 13.9. In total, 17.8 per cent had undergone previous radiotherapy. The mean number of lymph nodes was 33.26 ± 13.27 in patients with no previous radiation exposure and 18.47 ± 9.46 in those with previous radiation treatment.

Conclusion

Lymph node yield from a neck dissection is likely multi-factorial in nature. Previous radiotherapy, the only significant contributor, led to a mean reduction of lymph node yield from 33.3 to 18.5.
Entanglements of Scale: The Beer Purity Law from Bavarian Oddity to German Icon, 1906–1975
Authors: Terrell Robert Shea
Published: January 2023

Today, the Beer Purity Law (Reinheitsgebot) is presented as a timeless touchstone of German commercial sentiments, but that was not always the case. Until the mid-twentieth century, the law was relatively unknown and unevenly applied across Germany. This began to change thanks to the market protectionism of Bavarian brewers in two conflicts of integration between the 1950s and 1970s. The first was sparked by West German market integration and pitted capital interest Old Bavaria (Altbayern) against consumer practices in Franconia. The second followed a parallel development but was initiated by Western European market integration and set Bavarian and West German brewers and regulators in opposition to Brussels. In both, brewers, fearful that integration threatened their market share, rallied around the Reinheitsgebot to win political allies, cudgel industry outliers and generate popular support through claims to culture and tradition. Analysing the transformation of the Reinheitsgebot, this article theorises the causal ‘entanglements of scale’ by which a little-known provincial law transformed into a German icon.
Introduction—Authority Migration: Defining an Emerging
Research Agenda
Authors: Gerber Elisabeth R. , Kollman Ken
Published: January 2023

In every modern political system, power is shared to a greater or
lesser extent between levels of government. These power sharing
arrangements are perhaps most explicit in formal federal systems
like the United States and Canada, where federal constitutions
define the relative powers of central and subnational governments.
They may be no less important, however, in unitary democracies and
even authoritarian regimes where central governments require local
actors to implement policy on the ground and often delegate
significant authority to them. Indeed, in any large and complex
modern society, effective governance requires some sharing of power
between higher levels of government, capable of coordinating many
disparate actors and interests, and lower levels of government,
capable of responding to local conditions.
Governance in a Global Economy: Political Authority in
Transition
Authors: Kahler Miles , Lake David A.
Published: January 2023

Contemporary debate over globalization casts its political effects as
both revolutionary and contradictory. Globalization, it is claimed,
drains political authority from nation-states, long the dominant
form of political organization in world politics. The state's
monopoly of familiar governance functions erodes as authority
migrates down to newly empowered regions, provinces, and
municipalities; up to supranational organizations; and laterally to
such private firms and transnational nongovernmental organizations
(NGOs) that acquire previously “public” responsibilities.
On the Migration of Fiscal Sovereignty
Authors: Rodden Jonathan
Published: January 2023

As authority over public expenditures has shifted from central to
provincial and local governments in countries around the world over
the last two decades, prevailing approaches to the study of
decentralization in welfare economics and public choice from the
1970s and 1980s have given way to new political economy approaches.
The first generation of theories envisioned central and lower-level
governments as distinct sovereigns within their own spheres of
activity. Recognizing a more complex reality, the political economy
literature is rethinking the notion of sovereignty in multi-tiered
systems. Motivated by recent difficulties with fiscal
decentralization and fiscal discipline, this essay rethinks the
notion of fiscal sovereignty, viewing it as an evolving set of
beliefs in the context of a dynamic game of incomplete information
played between central and subnational governments.
Provincial or local governments, along with their creditors and
voters, attempt to assess the credibility of the central
government's commitment to abide by pre-specified intergovernmental
fiscal arrangements. When higher-level governments dominate the
field of taxation and take on heavy co-financing obligations—as
central governments do in virtually all newly decentralizing
countries—the central government's commitment not to bail out
subnational governments in the event of debt-servicing crises is not
credible. In other words, subnational governments without
significant tax autonomy will not be viewed as sovereign borrowers,
and this has important implications for their fiscal behavior.
Ahead of its Time: On Martha Derthick's
Policymaking for Social
Security
Authors: Pierson Paul
Published: January 2023

Martha Derthick's Policymaking for Social Security
is a great work of political analysis—one of the best studies of the
politics of public policy ever produced. Written a quarter-century
ago, the argument remains fresh and compelling today—fresher, in
fact, than most policy work produced more recently. Indeed, what is
striking in revisiting this wonderful book is how Derthick
beautifully explores some themes that are only now reasserting
themselves in the discipline and commanding the attention of
political scientists.
International Constraints and the U.S. Foreign Policy
Agenda: A Semester-Long Class Simulation using the Blackboard Web
Platform
Authors: Gibler Douglas M.
Published: January 2023

I recently began a classroom discussion on U.S. foreign policy toward
the Middle East by asking a question concerning the likely actions
of the administration toward Iraq. I was immediately greeted with
this response from most of the class: “Do you mean in the simulation
or in real-life?” This response only amplifies the reactions of
other students—“der Deutsche Weg” was constantly
advocated by the student representing Germany, the student
representing Argentina sought the commitment of “funds” from U.S.
officials before and after every class, and most students claimed
that the Iraqi representative had been co-opted by his role and
called him “Saddam.”
Internationalization of APSA: Why? How?
Authors: Varshney Ashu
Published: January 2023

In a meeting of APSA's international committee in September 2003,
APSA President Susanne Rudolph suggested the need for a “mutual
de-parochialization” in our knowledge practices. She meant a closer
interaction between American and non-American political scientists
and a greater cross-fertilization of their substantive and
methodological concerns. Margaret Levi, the President-elect of APSA,
also emphasized the need for a greater internationalization of
American political science, with special emphasis paid to the
so-called international public realm.
From Primary to General Election: A Forecast of the Presidential Vote
Authors: Norpoth Helmut
Published: January 2023

Yogi Berra might have said it: the best predictor of an election is, well, an election. Not a trial-heat conducted by opinion polls, but a real election of voters going to the polls. In the U.S., at least, what is known as a “general” election is preceded by a “primary” election, and that has been the case for presidential contests since 1912. So is the voting in presidential primaries a leading indicator of the vote in November? Remarkably so, as it turns out. How well presidential candidates do in primary elections foretells their prospects in the November election with great accuracy. What is more, the use of primaries as a vote predictor makes it possible to include in the forecast model both the candidate of the incumbent party and the candidate of the party out of the White House. The forecast for 2004 uses candidate vote shares in primaries, not just a win-lose dichotomy as done in the model used to predict the vote in 2000 (Norpoth 2001).
A Look to the Future: Forecasting the 2004 Presidential Election
Authors: Lockerbie Brad
Published: January 2023

Forecasting provides the opportunity to put one's self to the test. Are our models of voting behavior accurate? It is easy to retrofit an explanation for what has happened in the past. Taking a chance on a forecast that can go wrong does not afford us that luxury. Forecasting can also teach a lesson in humility. Over the last decade, political scientists have been willing to gamble on their models. We have had some success. Everyone on the forecasting panel at the 1996 APSA Annual Meeting correctly forecast a Clinton victory. The forecasting of the 2000 presidential election was clearly a lesson in humility (at least for this author). None of the authors of this symposium forecast a Bush victory. Moreover, many forecast a rather substantial victory for Al Gore.
Political Science and Its Audience
Authors: Prewitt Kenneth
Published: January 2023

I start a course on Politics and Policy by asking 100 or so students from several dozen countries to say what comes to mind when they hear the word “science.” Terms mentioned are objectivity, truth-seeking, hypothesis testing, experiments, data, logic, and the like. I write them on the blackboard. I then ask what comes to mind to mind when they hear the word “politics.” Here they mention power, manipulation, ambition, conflict, partisanship, spin, ideology, and, less often, vision and purpose. This list is put on the blackboard. Then, with two word lists before us, I comment that because they have just joined a school of public policy they must have a view of what goes into thinking up, arguing about, designing, and implementing policy. After a bit of discussion it gradually it sinks in. Policy is the meeting ground of science and politics. It is where the two word-lists on the blackboard come together and thrash it out, neither side ever quite vanishing the other.
The Nuclear Option for Stopping Filibusters
Authors: Klotz Robert
Published: January 2023

They did not seem to be in a position to help the other body. Yet, on October 10, 2002, members of the House Judiciary Committee listened to witnesses discuss how the Senate could be more efficient. In 2003, Senate committees heard similar testimony. During the hearings, eminent law professors suggested that the practice of allowing filibusters on judicial nominees could not be imposed by previous Senates on the current one. It, therefore, would be within the power of the 51 Republican Senators to uphold a point of order against the filibuster and proceed to govern by majority rule (Kmiec 2003). In Washington, this course of action is called the “nuclear option.” Although the informal use of the nuclear option has several variations, each variation has a common underlying feature that can be formally defined. The nuclear option is a dramatic refusal to recognize delaying tactics permitted under the rules that facilitates the institutionalization of majoritarian procedures in a legislative body. Occurring in legislatures such as the 1881 British House of Commons, the use of the nuclear option can be a watershed event wherever the majority lacks an unassailable way to end debate.
Assessment is Not a Four-Letter Word
Authors: Smoller Fred
Published: January 2023

The past two decades has seen a rising tide of criticism of American universities. This criticism is expressed in national reports, voter initiatives, legislative reports, and by employers and accrediting agencies who have concluded that there is “a crisis of educational quality in our nation's colleges and universities” (Gardiner 1998, 71–88) and that “a disturbing and dangerous mismatch exists between what American society needs from higher education and what it is receiving” (Wingspread Group on Higher Education 1993). From such criticisms, the assessment movement was born (see, for example, Diamond 1998; Palomba and Banta 1999; Allen 2004).
Fred Kort
Authors: Cole George F. , Davis I. Ridgway
Published: January 2023

Fred Kort, professor emeritus at the University of Connecticut, passed away at the age of 85 on July 17, 2004, after a long battle with cancer. Born in Vienna, Fred witnessed the rise of the Nazis and was a student of law at the University of Vienna until 1938 when Jewish students were expelled. As a result, Fred emigrated to the United States in 1939. In 1942 he volunteered for the U.S. Army and returned to Europe with the 11th Armored Division, fought in the Battle of the Bulge and other engagements, and eventually was stationed in Vienna. Upon his return to the United States, Fred enrolled at Northwestern University in 1946, earning his B.A., M.A., and Ph.D. in four years. He joined the department of political science at the University of Connecticut in 1950 and taught for 40 years, retiring in 1990.
Metin Tamkoc
Authors: Cochran Clarke E. , Ellis Kathleen A.
Published: January 2023

The world lost a true gentleman and a scholar–an aristocrat of the highest order—in early 2004 when Metin Tamkoc passed away in Istanbul, Turkey. One of his colleagues described him as having “possessed a rare combination of urbanity, seriousness of purpose, and good humor. He treated students and faculty alike with deep respect and pursued the highest standards of scholarship.”
Reflections on Political Science in Azerbaijan
Authors: Rizayev Elchin
Published: January 2023

My interest in the world of politics began when I was a high school student. However, in the authoritarian structure of Soviet society political science as an independent scientific discipline, was, for a long period, considered to be a “capitalist” science. When I was in Azerbaijan State Pedagogical University there was no major in political science so I chose history as my major because it was the closest.
APSA Teaching and Learning Conference: A Summary of Four
Tracks
Authors: Lamborn Alan , Martin Pamela
Published: January 2023

Combining the presentations on diversity and global perspectives
turned out to be very productive. We discovered a natural affinity
between the conference's goal of creating a collaborative teaching
and learning environment that bridges the cosmopolitan and local
knowledge teachers and students bring together in the classroom and
the substance of what we wanted students to learn about diversity
within and among countries in a period of accelerating
globalization. While the contexts and stakes could not be more
different, the challenges of combining a professor's “cosmopolitan
knowledge” with students' “local knowledge” are theoretically
analogous to the political challenges of honoring the local
knowledge that grows out of our diversity while simultaneously
nurturing a more shared, cosmopolitan knowledge that can connect us
in mutually acceptable ways. Put differently, when it comes to
understanding the politics of diversity and globalization, the
classroom can be used both as an example and as an application of
political theory. Working within this broad theme, we discussed a
variety of very specific ideas to promote collaborative and active
learning about diversity and world politics.
Observed Opposite Fall‐to‐Winter Variations in the Air‐Sea Latent Heat Flux Between the Western Boundary Currents and Coastal Seas
Authors: Song Xiangzhou
Published: January 2023

This study presents observations of opposite fall‐to‐winter variations in the air‐sea latent heat fluxes (LHs) between the western boundary currents (WBCs) and coastal seas obtained using eight air–sea buoys in the Northern Hemisphere. Different from the WBCs, the wintertime LH along the coast is strangely reduced by approximately 60 Wm−2 compared to that in fall. The reduced sea–air humidity differences account for these opposite seasonal variations, although the sea–air temperature differences are enhanced, while the roles played by winds and the nonlinear effects are minor. The boundary layer stability also varies in terms of the air‐sea parameters from fall to winter. However, the conditions of the WBCs meet the traditional expectation: that is, the LH in winter is 60 Wm−2 higher than that in fall with near‐neutral/unstable boundary layer stability. Enhanced winds in winter determine the seasonal enhancement of the LH over the WBCs, indicating a specialized regional character.
Resonant Diurnal Internal Tides in the North Atlantic: 2. Modeling
Authors: Dushaw B. D. , Menemenlis D.
Published: January 2023

An unconstrained global ocean simulation for 2020 supports past observations of diurnal internal tides by acoustic tomography during the 1991–1992 Acoustic Mid‐Ocean Dynamics Experiment in the Western North Atlantic. Explicitly representing the tides, the simulation reproduces the functional form and resonant state of K1 and O1 internal‐tide standing waves, while providing a more realistic physical picture of them. The tomographic data were used to predict the tides in 2020. Not surprisingly, the characteristics of the barotropic and internal tides of the unconstrained simulation deviate from observations. The simulated barotropic tidal currents have excessive, irregular amplitude and lead the acoustic tidal predictions by about 2 hr. While internal‐tide phase coherence is apparent, the simulated internal‐tide variations were irregular in amplitude and phase, unlike the observations. The tomographic tidal measurements therefore provide a quantitative benchmark for improved model representation of tides, internal tides, and dissipation.
A Physics‐Based Empirical Model for the Seasonal Prediction of the Central China July Precipitation
Authors: Li Gen , Chen Lin , Lu Bo
Published: January 2023

July is the rainy peak month of central China, with a large interannual variation of local precipitation often causing serious droughts and floods. The seasonal prediction of the central China July precipitation (CCJP) is an important but still challenging task. Here, we suggest several robust seasonal predictors for the CCJP, including the preceding winter intensity of El Niño‐South Oscillation (ENSO), the winter‐to‐spring decaying rate of ENSO signals in the central Pacific, as well as the spring tropical and subpolar North Atlantic sea surface temperature anomalies. A physics‐based empirical model is then developed to predict the CCJP by using the principal component regression of the aforementioned seasonal predictors. In our statistical model, the seasonal prediction skill of the CCJP is high, with the cross‐validated reforecast skill at 0.81 during 1993–2021. This suggests a skillful seasonal prediction of the CCJP, with potentially enormous benefits for the local society and economy.
Multi‐Event Analysis of Magnetosphere‐Ionosphere Coupling of Nighttime Medium‐Scale Traveling Ionospheric Disturbances From the Ground and the Arase Satellite
Authors: Kawai K. , Shiokawa K. , Otsuka Y. , Oyama S. , Connors M. G. , Kasahara Y. , Kasaba Y. , Nakamura S. , Tsuchiya F. , Kumamoto A. , Shinbori A. , Matsuoka A. , Shinohara I. , Miyoshi Y.
Published: January 2023

Kawai et al. (2021) reported the first ground‐satellite conjugate observation of nighttime medium‐scale traveling ionospheric disturbances (MSTIDs), by analyzing measurements from an airglow imager at Gakona (geographic latitude: 62.39°N, geographic longitude: 214.78°E, magnetic latitude: 63.60°N) and the Arase satellite in the magnetosphere on 3 November 2018. The Arase satellite observed variations in both the polarization electric field and the electron density as the Arase footprint passed through the MSTID structures in the ionosphere. In this study, we investigated whether these electric field and density variations associated with MSTIDs at subauroral latitudes are always observed by Arase in the magnetosphere. We used three airglow imagers installed at Gakona, Athabasca (geographic latitude: 54.60°N, geographic longitude: 246.36°E, magnetic latitude: 61.10°N), and Kapuskasing (geographic latitude: 49.39°N, geographic longitude: 277.81°E, magnetic latitude: 58.70°N) and the Arase satellite. We found eight observations of MSTIDs conjugate with Arase. They indicate that electric field and density variations associated with MSTIDs are not always observed in the magnetosphere. These variations tend to be observed in the magnetosphere during geomagnetically quiet times and when the amplitude of the MSTID is large. We categorized the MSTIDs into those caused by plasma instabilities and gravity waves and found that the electric field and density variations can be observed in the magnetosphere for both types of MSTIDs.
Trend and Multi‐Frequency Analysis Through Empirical Mode Decomposition: An Application to a 20‐Year Record of Atmospheric Carbonyl Sulfide Measurements
Authors: Serio C. , Montzka S. A. , Masiello G. , Carbone V.
Published: January 2023

The Empirical Mode Decomposition (EMD) is a fully non‐parametric analysis of frequency modes and trends in a given series that is based on the data alone. We have devised an improved strategy based on a series of best practices to use EMD successfully in the analysis of the monthly time series of carbonyl sulfide (OCS) atmospheric mole fractions measured at NOAA network stations (2000–2020). Long‐term trends and intra‐ and inter‐annual variability has been assessed. After a phase of generally increasing mole fractions up to 2015, with a temporary decline around 2009, we found that the OCS atmospheric mole fraction subsequently decreased at all stations, reflecting a recent imbalance in its total sources and losses. Our analysis has revealed a characteristic time scale for variation of 8–10 years. The variance associated with this long‐term behavior ranges from 15% to 40% of the total strength of the signal, depending on location. Apart from this complex long‐term behavior, the OCS time series show a strong annual cycle, which primarily results from the well‐known OCS uptake by vegetation. In addition, we have also found one more frequency of minor variance intensity in the measured mole fraction time‐history, which corresponds to periods in the range of 2–3 years. This inter‐annual variability of OCS may be linked to the Quasi‐Biennial Oscillation.
RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy
Authors: Tang Chao , Jin Meiyuan , Ma Bingbing , Cao Bin , Lin Chao , Xu Shouying , Li Jiayong , Xu Qiang
Published: January 2023

Production of estradiol (E2) by the placenta during human pregnancy ensures successful maintenance of placental development and fetal growth by stimulating trophoblast proliferation and the differentiation of cytotrophoblasts into syncytiotrophoblasts. Decreased levels of E2 are closely associated with obstetrical diseases such as preeclampsia (PE) in the clinic. However, the mechanisms underlying the inhibition of placental E2 biosynthesis remain poorly understood. Here, we report that regulator of G-protein signaling 2 (RGS2) affects E2 levels by regulating aromatase, a rate-limiting enzyme for E2 biosynthesis, by using human trophoblast-derived JEG-3 cells and human placental villus tissues. RGS2 enhanced the protein degradation of the transcription factor heart and neural crest derivatives expressed 1 (HAND1) by suppressing ubiquitin-specific protease 14 (USP14)-mediated deubiquitination of HAND1, resulting in the restoration of HAND1-induced trans-inactivation of the aromatase gene and subsequent increases in E2 levels. However, aromatase bound to RGS2 and repressed RGS2 GTPase activating protein (GAP) activity. Moreover, we observed a positive correlation between RGS2 and aromatase expression in clinical normal and preeclamptic placental tissues. Our results uncover a hitherto uncharacterized role of the RGS2-aromatase axis in the regulation of E2 production by human placental trophoblasts, which may pinpoint the molecular pathogenesis and highlight potential biomarkers for related obstetrical diseases.
Human lung carcinomas synthesize immunoregulatory glucocorticoids
Authors: Merk Verena M. , Grob Leonie , Fleischmann Achim , Brunner Thomas
Published: January 2023

The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are mainly known as a combination drug to attenuate side-effects of chemotherapies. However, endogenous extra-adrenal GC have been shown to substantially regulate local immune responses within various tissues, including the lung. In this study we investigated whether primary lung tumors have maintained the capacity to synthesize GC and may thereby regulate anti-tumor immune responses. We show that several non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) cell lines express key steroidogenic enzymes and synthesize bioactive GC under steady state conditions. We also show that tumor-derived GC can inhibit splenic T cell activation, thus demonstrating their immunoregulatory potential. Moreover, steroidogenic enzymes were detected by quantitative RT-PCR and immunohistochemistry in tissue sections of different human lung tumors, further strengthening the idea that human lung carcinomas regulate their microenvironment by releasing immunoregulatory GC, which potentially contributes to immune evasion and treatment resistance.
Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure
Authors: Rämö Joel T. , Kiiskinen Tuomo , Seist Richard , Krebs Kristi , Kanai Masahiro , Karjalainen Juha , Kurki Mitja , Hämäläinen Eija , Häppölä Paavo , Havulinna Aki S. , Hautakangas Heidi ,   FinnGen, Mägi Reedik , Palta Priit , Esko Tõnu , Metspalu Andres , Pirinen Matti , Karczewski Konrad J. , Ripatti Samuli , Milani Lili , Stankovic Konstantina M. , Mäkitie Antti , Daly Mark J. , Palotie Aarno
Published: January 2023

Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p < 5 × 10−8) and report an association in RELN and three previously reported candidate gene or linkage regions (TGFB1, MEPE, and OTSC7). We demonstrate developmental stage-dependent immunostaining patterns of MEPE and RUNX2 in mouse otic capsules. In most association loci, the nearest protein-coding genes are implicated in bone remodelling, mineralization or severe skeletal disorders. We highlight multiple genes involved in transforming growth factor beta signalling for follow-up studies.
Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation
Authors: Saarentaus Elmo C. , Karjalainen Juha , Rämö Joel T. , Kiiskinen Tuomo , Havulinna Aki S. , Mehtonen Juha , Hautakangas Heidi , Ruotsalainen Sanni , Tamlander Max , Mars Nina ,   FINNGEN, Toppila-Salmi Sanna , Pirinen Matti , Kurki Mitja , Ripatti Samuli , Daly Mark , Palotie Tuula , Mäkitie Antti , Palotie Aarno
Published: January 2023

Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.
Cleavage of non-polar C(sp2)‒C(sp2) bonds in cycloparaphenylenes via electric field-catalyzed electrophilic aromatic substitution
Authors: Lin Junfeng , Lv Yaxin , Song Kai , Song Xuwei , Zang Hongjun , Du Pingwu , Zang Yaping , Zhu Daoben
Published: January 2023

Electrophilic aromatic substitution (EAS) is one of the most fundamental reactions in organic chemistry. Using an oriented external electric field (OEEF) instead of traditional reagents to tune the EAS reactivity can offer an environmentally friendly method to synthesize aromatic compounds and hold the promise of broadening its scope. Despite these advantages, OEEF catalysis of EAS is difficult to realize, due to the challenge of microscopically orienting OEEF along the direction of electron reorganizations. In this work, we demonstrate OEEF-catalyzed EAS reactions in a series of cycloparaphenylenes (CPPs) using the scanning tunneling microscope break junction (STM-BJ) technique. Crucially, the unique radial π-conjugation of CPPs enables a desired alignment for the OEEF to catalyze the EAS with Au STM tip (or substrate) acting as an electrophile. Under mild conditions, the OEEF-catalyzed EAS reactions can cleave the inherently inert C(sp2)-C(sp2) bond, leading to high-yield (~97%) formation of linear oligophenylenes terminated with covalent Au-C bonds. These results not only demonstrate the feasibility of OEEF catalysis of EAS, but also offer a way of exploring new mechanistic principles of classic organic reactions aided by OEEF.
Isolated Fe-Co heteronuclear diatomic sites as efficient bifunctional catalysts for high-performance lithium-sulfur batteries
Authors: Sun Xun , Qiu Yue , Jiang Bo , Chen Zhaoyu , Zhao Chenghao , Zhou Hao , Yang Li , Fan Lishuang , Zhang Yu , Zhang Naiqing
Published: January 2023

The slow redox kinetics of polysulfides and the difficulties in decomposition of Li2S during the charge and discharge processes are two serious obstacles to the practical application of lithium-sulfur batteries. Herein, we construct the Fe-Co diatomic catalytic materials supported by hollow carbon spheres to achieve high-efficiency catalysis for the conversion of polysulfides and the decomposition of Li2S simultaneously. The Fe atom center is beneficial to accelerate the discharge reaction process, and the Co atom center is favorable for charging process. Theoretical calculations combined with experiments reveal that this excellent bifunctional catalytic activity originates from the diatomic synergy between Fe and Co atom. As a result, the assembled cells exhibit the high rate performance (the discharge specific capacity achieves 688 mAh g−1 at 5 C) and the excellent cycle stability (the capacity decay rate is 0.018% for 1000 cycles at 1 C).
Endosomal sorting results in a selective separation of the protein corona from nanoparticles
Authors: Han Shen , da Costa Marques Richard , Simon Johanna , Kaltbeitzel Anke , Koynov Kaloian , Landfester Katharina , Mailänder Volker , Lieberwirth Ingo
Published: January 2023

The formation of the protein corona is a well-known effect when nanoparticles (NP) are exposed to biological environments. The protein corona is the most important factor, which determines the rate and route of endocytosis, and decisively impacts cellular processes and even the release of the active pharmaceutical ingredient from the nanoparticles. While many studies concentrate on the effect of the protein corona formation extracellularly or the uptake consequences, little is known about the fate of the protein corona inside of cells. Here, we reconstruct for the first time the separation of the protein corona from the NPs by the cell and their further fate. Ultimately, the NPs and protein corona are separated from each other and end up in morphologically different cellular compartments. The cell directs the NPs towards recycling endosomes, whereas the protein corona gathers in multivesicular bodies. From this, we conclude that the NPs are prepared for subsequent exocytosis, while the protein corona remains in the cell and is finally metabolized there.
Electrolyte engineering via ether solvent fluorination for developing stable non-aqueous lithium metal batteries
Authors: Zhao Yan , Zhou Tianhong , Mensi Mounir , Choi Jang Wook , Coskun Ali
Published: January 2023

Fluorination of ether solvents is an effective strategy to improve the electrochemical stability of non-aqueous electrolyte solutions in lithium metal batteries. However, excessive fluorination detrimentally impacts the ionic conductivity of the electrolyte, thus limiting the battery performance. Here, to maximize the electrolyte ionic conductivity and electrochemical stability, we introduce the targeted trifluoromethylation of 1,2-dimethoxyethane to produce 1,1,1-trifluoro-2,3-dimethoxypropane (TFDMP). TFDMP is used as a solvent to prepare a 2 M non-aqueous electrolyte solution comprising bis(fluorosulfonyl)imide salt. This electrolyte solution shows an ionic conductivity of 7.4 mS cm–1 at 25 °C, an oxidation stability up to 4.8 V and an efficient suppression of Al corrosion. When tested in a coin cell configuration at 25 °C using a 20 μm Li metal negative electrode, a high mass loading LiNi0.8Co0.1Mn0.1O2-based positive electrode (20 mg cm–2) with a negative/positive (N/P) capacity ratio of 1, discharge capacity retentions (calculated excluding the initial formation cycles) of 81% after 200 cycles at 0.1 A g–1 and 88% after 142 cycles at 0.2 A g–1 are achieved.
Stem cell–nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy
Authors: Lai Yen-Ho , Su Chia-Yu , Cheng Hung-Wei , Chu Chao-Yi , Jeng Long-Bin , Chiang Chih-Sheng , Shyu Woei-Cherng , Chen San-Yuan
Published: January 2023

The potential clinical application of gadolinium-neutron capture therapy (Gd-NCT) for glioblastoma multiforme (GBM) treatment has been compromised by the fast clearance and nonspecific biodistribution of gadolinium-based agents. We have developed a stem cell–nanoparticle system (SNS) to actively target GBM for advanced Gd-NCT by magnetizing umbilical cord mesenchymal stem cells (UMSCs) using gadodiamide-concealed magnetic nanoparticles (Gd-FPFNP). Nanoformulated gadodiamide shielded by a dense surface composed of fucoidan and polyvinyl alcohol demonstrates enhanced cellular association and biocompatibility in UMSCs. The SNS preserves the ability of UMSCs to actively penetrate the blood brain barrier and home to GBM and, when magnetically navigates by an external magnetic field, an 8-fold increase in tumor-to-blood ratio is achieved compared with clinical data. In an orthotopic GBM-bearing rat model, using a single dose of irradiation and an ultra-low gadolinium dose (200 μg kg−1), SNS significantly attenuates GBM progression without inducing safety issues, prolonging median survival 2.5-fold compared to free gadodiamide. The SNS is a cell-based delivery system that integrates the strengths of cell therapy and nanotechnology, which provides an alternative strategy for the treatment of brain diseases.
Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST
Authors: Liu Wei , Liao Xu , Luo Ziye , Yang Yi , Lau Mai Chan , Jiao Yuling , Shi Xingjie , Zhai Weiwei , Ji Hongkai , Yeong Joe , Liu Jin
Published: January 2023

Spatially resolved transcriptomics involves a set of emerging technologies that enable the transcriptomic profiling of tissues with the physical location of expressions. Although a variety of methods have been developed for data integration, most of them are for single-cell RNA-seq datasets without consideration of spatial information. Thus, methods that can integrate spatial transcriptomics data from multiple tissue slides, possibly from multiple individuals, are needed. Here, we present PRECAST, a data integration method for multiple spatial transcriptomics datasets with complex batch effects and/or biological effects between slides. PRECAST unifies spatial factor analysis simultaneously with spatial clustering and embedding alignment, while requiring only partially shared cell/domain clusters across datasets. Using both simulated and four real datasets, we show improved cell/domain detection with outstanding visualization, and the estimated aligned embeddings and cell/domain labels facilitate many downstream analyses. We demonstrate that PRECAST is computationally scalable and applicable to spatial transcriptomics datasets from different platforms.
DNA methylation analysis explores the molecular basis of plasma cell-free DNA fragmentation
Authors: An Yunyun , Zhao Xin , Zhang Ziteng , Xia Zhaohua , Yang Mengqi , Ma Li , Zhao Yu , Xu Gang , Du Shunda , Wu Xiang’an , Zhang Shuowen , Hong Xin , Jin Xin , Sun Kun
Published: January 2023

Plasma cell-free DNA (cfDNA) are small molecules generated through a non-random fragmentation procedure. Despite commendable translational values in cancer liquid biopsy, however, the biology of cfDNA, especially the principles of cfDNA fragmentation, remains largely elusive. Through orientation-aware analyses of cfDNA fragmentation patterns against the nucleosome structure and integration with multidimensional functional genomics data, here we report a DNA methylation – nuclease preference – cutting end – size distribution axis, demonstrating the role of DNA methylation as a functional molecular regulator of cfDNA fragmentation. Hence, low-level DNA methylation could increase nucleosome accessibility and alter the cutting activities of nucleases during DNA fragmentation, which further leads to variation in cutting sites and size distribution of cfDNA. We further develop a cfDNA ending preference-based metric for cancer diagnosis, whose performance has been validated by multiple pan-cancer datasets. Our work sheds light on the molecular basis of cfDNA fragmentation towards broader applications in cancer liquid biopsy.
Effect of surface termination on the balance between friction and failure of Ti3C2Tx MXenes
Authors: Yang Quanpeng , Eder Stefan J. , Martini Ashlie , Grützmacher Philipp G.
Published: January 2023

Reactive molecular dynamics simulations of Ti3C2Tx with three different surface terminations were used to understand friction and failure of MXenes during sliding at normal pressures from 2–20 GPa and temperatures from 300–1100 K. The O-terminated MXene had the smallest shear stress at low pressures and temperatures, but failed at more severe conditions due to interlayer bonding and the formation of Ti–O–Ti bridges between MXene layers. Failure was not observed for the OH-terminated MXene or a heterostructure combining O- and OH-terminations. For these, at less severe operating conditions, shear stress was smaller for the OH-terminated MXene, while the opposite was observed at higher temperatures and pressures. These trends were explained in terms of adhesion and the complex effect of hydrogen atoms that can either facilitate or hinder sliding, depending on the termination and conditions. Results show that friction and failure are affected by and potentially tunable via MXene surface termination.
Artificial intelligence-based iliofemoral deep venous thrombosis detection using a clinical approach
Authors: Seo Jae Won , Park Suyoung , Kim Young Jae , Hwang Jung Han , Yu Sung Hyun , Kim Jeong Ho , Kim Kwang Gi
Published: January 2023

Early diagnosis of deep venous thrombosis is essential for reducing complications, such as recurrent pulmonary embolism and venous thromboembolism. There are numerous studies on enhancing efficiency of computer-aided diagnosis, but clinical diagnostic approaches have never been considered. In this study, we evaluated the performance of an artificial intelligence (AI) algorithm in the detection of iliofemoral deep venous thrombosis on computed tomography angiography of the lower extremities to investigate the effectiveness of using the clinical approach during the feature extraction process of the AI algorithm. To investigate the effectiveness of the proposed method, we created synthesized images to consider practical diagnostic procedures and applied them to the convolutional neural network-based RetinaNet model. We compared and analyzed the performances based on the model’s backbone and data. The performance of the model was as follows: ResNet50: sensitivity = 0.843 (± 0.037), false positives per image = 0.608 (± 0.139); ResNet152 backbone: sensitivity = 0.839 (± 0.031), false positives per image = 0.503 (± 0.079). The results demonstrated the effectiveness of the suggested method in using computed tomography angiography of the lower extremities, and improving the reporting efficiency of the critical iliofemoral deep venous thrombosis cases.
Micro-structure and morphology of tailings sand under different oxidation and acidification degree
Authors: Wang Gang , Liu Xiqi , Song Leibo , Ma Xiaoming , Chen Wenzhao , Qiao Jiaxing
Published: January 2023

The tailings pond is a dangerous source of man-made debris flow with high potential energy. The oxidative acidification of tailings may cause the instability of the pond and induce serious safety accidents. The influence of oxidation and acidification degree on macro mechanical properties of tailings is discussed from the aspects of mineral composition and microstructure. The results show that as the degree of oxidation and acidification of tailings sand increases, the overall structural performance and load-bearing capacity decrease, and its cohesion (c) and internal friction angle (φ) show a decreasing trend. In fact, the engineering properties of tailings with different oxidation and acidification degrees are dominated by the physicochemical composition and structural characteristics. On the one hand, as the degree of oxidation increases, acidic substance will neutralize with CaCO3 and CaMg(CO3)2, resulting in the loss of cemented substance and the decrease of cementation force between tailing sand particles as well as the gradual destruction of the integrity of tailing sand. On the other hand, the increase of oxidation and acidification degree of tailing sand leads to a gradual reduction of outline (2D) fractal dimension and gray surface (3D) fractal dimension of surface laminated structure as well as the obvious reduction of laminated structure and its roughness of tailings sand.
Artificial intelligence-based locoregional markers of brain peritumoral microenvironment
Authors: Riahi Samani Zahra , Parker Drew , Akbari Hamed , Wolf Ronald L. , Brem Steven , Bakas Spyridon , Verma Ragini
Published: January 2023

In malignant primary brain tumors, cancer cells infiltrate into the peritumoral brain structures which results in inevitable recurrence. Quantitative assessment of infiltrative heterogeneity in the peritumoral region, the area where biopsy or resection can be hazardous, is important for clinical decision making. Here, we derive a novel set of Artificial intelligence (AI)-based markers capturing the heterogeneity of tumor infiltration, by characterizing free water movement restriction in the peritumoral region using Diffusion Tensor Imaging (DTI)-based free water volume fraction maps. We leverage the differences in the peritumoral region of metastasis and glioblastomas, the former consisting of vasogenic versus the latter containing infiltrative edema, to extract a voxel-wise deep learning-based peritumoral microenvironment index (PMI). Descriptive characteristics of locoregional hubs of uniformly high PMI values are then extracted as AI-based markers to capture distinct aspects of infiltrative heterogeneity. The proposed markers are utilized to stratify patients’ survival and IDH1 mutation status on a population of 275 adult-type diffuse gliomas (CNS WHO grade 4). Our results show significant differences in the proposed markers between patients with different overall survival and IDH1 mutation status (t test, Wilcoxon rank sum test, linear regression; p < 0.01). Clustering of patients using the proposed markers reveals distinct survival groups (logrank; p < 10−5, Cox hazard ratio = 1.82; p < 0.005). Our findings provide a panel of markers as surrogates of infiltration that might capture novel insight about underlying biology of peritumoral microstructural heterogeneity, providing potential biomarkers of prognosis pertaining to survival and molecular stratification, with applicability in clinical decision making.