bluuebunny/crossref_metadata_2025 huggingface dataset:
A Distant Reading of Legal Dissertations from German Universities in the Seventeenth Century
Authors: Scholz Luca
Published: June 2021

Scholars and students at early modern European universities wrote hundreds of thousands of dissertations. One reason why these sources have long been neglected is that they defy any individual's capacity for close reading. This article adopts a digital distant reading approach to uncover long-term trends in the titles of over 20,000 legal dissertations written at German universities during the seventeenth century. Providing a pathway into a forbidding archive, the article highlights the dissertations’ interest for the history of jurisprudence and its receptiveness to social change, the history of universities and academic publishing, baroque rhetoric, and cultural, political, and economic history. The titles reveal a markedly declining interest in civil law, with topical issues like debt and marriage eluding this trend. Initially, dissertations were often written in dialogic form, but these were gradually supplanted by more single-voiced and monographic texts. Jurists increasingly preferred sharply delineated, diverse, and often original subjects, writing about anything from somnambulism to pearl fishing. The way in which seventeenth-century jurists expanded the scope of their writing reflects broader revaluations of scholarly curiosity and baroque polyhistorism as well as the heightened stature of an epistemic community that interpreted ever more spheres of life through its own categories.
Manufacturing agricultural working knowledge: the scientific study of agricultural work in industrial Europe, 1920s–60s
Authors: Auderset Juri
Published: June 2021

After the First World War, agricultural work became a subject of intense interdisciplinary scientific inquiry. The shortage of agricultural labour, the nutritional and agricultural crises and the increasing significance of the movement for the rationalisation of work contributed to the creation of new scientific institutions that focused on the study and improvement of agricultural work. This contribution sketches the emergence and development of the science of agricultural work in Europe from the 1920s to the 1960s and explores the intellectual controversies sparked by the attempts to shape farm work along the model of industrial manufacturing. The frictions and tensions between industrial ideals and agricultural idiosyncrasies not only led to a new scientific treatment of agricultural work, but also created a field of contestation between different conceptual approaches to perceiving, analysing and transforming agricultural work in the age of industrial capitalism.
THE COPERNICAN MULTIVERSE OF SETS
Authors: GORBOW PAUL K. , LEIGH GRAHAM E.
Published: June 2021

We develop an untyped framework for the multiverse of set theory.
$\mathsf {ZF}$
is extended with semantically motivated axioms utilizing the new symbols
$\mathsf {Uni}(\mathcal {U})$
and
$\mathsf {Mod}(\mathcal {U, \sigma })$
, expressing that
$\mathcal {U}$
is a universe and that
$\sigma $
is true in the universe
$\mathcal {U}$
, respectively. Here
$\sigma $
ranges over the augmented language, leading to liar-style phenomena that are analyzed. The framework is both compatible with a broad range of multiverse conceptions and suggests its own philosophically and semantically motivated multiverse principles. In particular, the framework is closely linked with a deductive rule of Necessitation expressing that the multiverse theory can only prove statements that it also proves to hold in all universes. We argue that this may be philosophically thought of as a Copernican principle that the background theory does not hold a privileged position over the theories of its internal universes. Our main mathematical result is a lemma encapsulating a technique for locally interpreting a wide variety of extensions of our basic framework in more familiar theories. We apply this to show, for a range of such semantically motivated extensions, that their consistency strength is at most slightly above that of the base theory
$\mathsf {ZF}$
, and thus not seriously limiting to the diversity of the set-theoretic multiverse. We end with case studies applying the framework to two multiverse conceptions of set theory: arithmetic absoluteness and Joel D. Hamkins’ multiverse theory.
Permafrost Dynamics Observatory—Part I: Postprocessing and Calibration Methods of UAVSAR L‐Band InSAR Data for Seasonal Subsidence Estimation
Authors: Michaelides Roger J. , Chen Richard H. , Zhao Yuhuan , Schaefer Kevin , Parsekian Andrew D. , Sullivan Taylor , Moghaddam Mahta , Zebker Howard A. , Liu Lin , Xu Xingyu , Chen Jingyi
Published: June 2021

Interferometric synthetic aperture radar (InSAR) has been used to quantify a range of surface and near surface physical properties in permafrost landscapes. Most previous InSAR studies have utilized spaceborne InSAR platforms, but InSAR datasets over permafrost landscapes collected from airborne platforms have been steadily growing in recent years. Most existing algorithms dedicated toward retrieval of permafrost physical properties were originally developed for spaceborne InSAR platforms. In this study, which is the first in a two part series, we introduce a series of calibration techniques developed to apply a novel joint retrieval algorithm for permafrost active layer thickness retrieval to an airborne InSAR dataset acquired in 2017 by NASA's Uninhabited Aerial Vehicle Synthetic Aperture Radar over Alaska and Western Canada. We demonstrate how InSAR measurement uncertainties are mitigated by these calibration methods and quantify remaining measurement uncertainties with a novel method of modeling interferometric phase uncertainty using a Gaussian mixture model. Finally, we discuss the impact of native SAR resolution on InSAR measurements, the limitation of using few interferograms per retrieval, and the implications of our findings for cross‐comparison of airborne and spaceborne InSAR datasets acquired over Arctic regions underlain by permafrost.
Carbon Isotope Fractionation in Noelaerhabdaceae Algae in Culture and a Critical Evaluation of the Alkenone Paleobarometer
Authors: Phelps Samuel R. , Hennon Gwenn M. M. , Dyhrman Sonya T. , Hernández Limón María D. , Williamson Olivia M. , Polissar Pratigya J.
Published: June 2021

The carbon isotope fractionation in algal organic matter (εp), including the long‐chain alkenones produced by the coccolithophorid family Noelaerhabdaceae, is used to reconstruct past atmospheric CO2 levels. The conventional proxy linearly relates εp to changes in cellular carbon demand relative to diffusive CO2 supply, with larger εp values occurring at lower carbon demand relative to supply (i.e., abundant CO2). However, the response of Gephyrocapsa oceanica, one of the dominant alkenone producers of the last few million years, has not been studied closely. Here, we subject G. oceanica to various CO2 levels by increasing pCO2 in the culture headspace, as opposed to increasing dissolved inorganic carbon (DIC) and alkalinity concentrations at constant pH. We note no substantial change in physiology, but observe an increase in εp as carbon demand relative to supply decreases, consistent with DIC manipulations. We compile existing Noelaerhabdaceae εp data and show that the diffusive model poorly describes the data. A meta‐analysis of individual treatments (unique combinations of lab, strain, and light conditions) shows that the slope of the εp response depends on the light conditions and range of carbon demand relative to CO2 supply in the treatment, which is incompatible with the diffusive model. We model εp as a multilinear function of key physiological and environmental variables and find that both photoperiod duration and light intensity are critical parameters, in addition to CO2 and cell size. While alkenone carbon isotope ratios indeed record CO2 information, irradiance and other factors are also necessary to properly describe alkenone εp.
Total Surface Current Vector and Shear From a Sequence of Satellite Images: Effect of Waves in Opposite Directions
Authors: Ardhuin Fabrice , Alday Matias , Yurovskaya Maria
Published: June 2021

The total surface current velocity (TSCV)—the horizontal vector quantity that advects seawater—is an essential climate variable, with few observations available today. The TSCV can be derived from the phase speed of surface gravity waves, and the estimates of the phase speeds of different wavelengths could give a measure of the vertical shear. Here, we combine 10‐m resolution Level‐1C of the Sentinel‐2 Multispectral Instrument, acquired with time lags up to 1 s, and numerical simulation of these images. Retrieving the near‐surface shear requires a specific attention to waves in opposing directions when estimating a single‐phase speed from the phase difference in an image pair. Opposing waves lead to errors in phase speeds that are most frequent for shorter wavelengths. We propose an alternative method using a least squares fit of the current speed and amplitudes of waves in opposing directions to the observed complex amplitudes of a sequence of three images. When applied to Sentinel‐2, this method generally provides more noisy estimate of the current. A byproduct of this analysis is the “opposition spectrum” which is a key quantity in the sources of microseisms and microbaroms. For future possible sensors, the retrieval of TSCV and shear can benefit from increased time lags, resolution, and exposure time of acquisition. These findings should allow new investigations of near‐surface ocean processes including regions of freshwater influence or internal waves, using existing satellite missions such as Sentinel‐2, and provide a basis for the design of future optical instruments.
Efficacy of green jackfruit flour as a medical nutrition therapy replacing rice or wheat in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study
Authors: Rao A. Gopal , Naik K. Sunil , Unnikrishnan A. G. , Joseph James
Published: June 2021

Background/Objectives

Medical nutrition therapy along with pharmacological interventions as a multidisciplinary approach is required to treat type 2 diabetes mellitus (T2DM). This study evaluated the efficacy of Jackfruit365™ green jackfruit flour as an integral part of daily meal in patients with T2DM.

Subjects/Methods

This was a randomized, double-blind, placebo-controlled study conducted between May 2019 and February 2020. Patients of either sex aged ≥18 to ≤60 years with a diagnosis of T2DM for >1 year receiving oral antihyperglycemic agents were randomized (1:1) to receive either jackfruit flour 30 g/day (Group A) or placebo flour (Group B) (breakfast and dinner) daily for 12 weeks replacing an equal volume of rice or wheat flour. The primary endpoint was a mean change in glycosylated hemoglobin (HbA1c). Other endpoints were mean changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profile, and body weight. The independent t-test was used to compare changes between the groups.

Results

A total of 40 patients were enrolled (n = 20 each). A significantly higher reduction in HbA1c was observed in Group A compared to Group B from baseline to week 12 [−2.73 mmol/mol (−0.25%) vs. 0.22 mmol/mol (0.02%), p = 0.006]. The mean change in FPG and PPG was significantly higher in Group A than that of Group B (p = 0.043 and p = 0.001). The continuous glucose monitoring showed decreasing mean blood glucose in 7 days of administration of jackfruit flour meal.

Conclusion

Patients from Group A had a significantly higher reduction in HbA1c, FPG, and PPG than Group B demonstrating the efficacy of jackfruit flour in glycemic control as medical nutrition therapy replacing an equal volume of rice or wheat flour in daily meal.

Clinical trial registry

CTRI/2019/05/019417.
Fungal phytopathogen modulates plant and insect responses to promote its dissemination
Authors: Franco Flávia P , Túler Amanda C , Gallan Diego Z , Gonçalves Felipe G , Favaris Arodí P , Peñaflor Maria Fernanda G V , Leal Walter S , Moura Daniel S , Bento José Maurício S , Silva-Filho Marcio C
Published: June 2021

Vector-borne plant pathogens often change host traits to manipulate vector behavior in a way that favors their spread. By contrast, infection by opportunistic fungi does not depend on vectors, although damage caused by an herbivore may facilitate infection. Manipulation of hosts and vectors, such as insect herbivores, has not been demonstrated in interactions with fungal pathogens. Herein, we establish a new paradigm for the plant-insect-fungus association in sugarcane. It has long been assumed that Fusarium verticillioides is an opportunistic fungus, where it takes advantage of the openings left by Diatraea saccharalis caterpillar attack to infect the plant. In this work, we show that volatile emissions from F. verticillioides attract D. saccharalis caterpillars. Once they become adults, the fungus is transmitted vertically to their offspring, which continues the cycle by inoculating the fungus into healthy plants. Females not carrying the fungus prefer to lay their eggs on fungus-infected plants than mock plants, while females carrying the fungus prefer to lay their eggs on mock plants than fungus-infected plants. Even though the fungus impacts D. saccharalis sex behavior, larval weight and reproduction rate, most individuals complete their development. Our data demonstrate that the fungus manipulates both the host plant and insect herbivore across life cycle to promote its infection and dissemination.
The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study
Authors: Johnson Philip J. , Dhanaraj Sofi , Berhane Sarah , Bonnett Laura , Ma Yuk Ting
Published: June 2021

Background

The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC).

Methods

In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis.

Results

On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage.

Conclusion

NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.
Cascade screening for beta-thalassemia in Pakistan: development, feasibility and acceptability of a decision support intervention for relatives
Authors: Ahmed Shenaz , Jafri Hussain , Rashid Yasmin , Ehsan Yasmin , Bashir Shabnam , Ahmed Mushtaq
Published: June 2021

The government-funded ‘Punjab Thalassaemia Prevention Project’ (PTPP) in Pakistan includes cascade screening for biological relatives of children with beta-Thalassaemia Major (β-TM). However, there is low uptake of cascade screening. This paper presents the (i) development of a paper-based ‘decision support intervention for relatives’ (DeSIRe) to enable PTPP Field Officers to facilitate informed decision making about carrier testing, and (ii) assessment of the feasibility and acceptability of the DeSIRe. The intervention was developed using the International Patient Decision Aids Standards quality criteria and Ottawa Decision Support Framework. Twelve focus groups were conducted (September and October 2020) to explore the views of healthcare professionals (HCPs) and relatives of children with β-TM, in six cities. The focus groups were attended by 117 participants (60 HCPs and 57 relatives). Thematic analysis showed that the DeSIRe was considered acceptable for supporting relatives to make informed decisions about cascade screening, and potentially feasible for use in clinical practice. Suggestions for changing some words, the structure and adding information about how carrier testing relates to consanguineous marriages will enable further development of the DeSIRe. Participants generally welcomed the DeSIRe; however, they highlighted the perceived need to use more directive language, hence showed a cultural preference for directive genetic counselling. The findings highlight challenges for researchers using western theories, frameworks, policies and clinical guidelines to develop decision support interventions for implementation more globally. Future research is needed to evaluate the use of the DeSIRe in routine practice and whether it enables relatives to make informed decisions.
Negative electroretinograms: genetic and acquired causes, diagnostic approaches and physiological insights
Authors: Jiang Xiaofan , Mahroo Omar A.
Published: June 2021

The dark-adapted human electroretinogram (ERG) response to a standard bright flash includes a negative-going a-wave followed by a positive-going b-wave that crosses the baseline. An electronegative waveform (or negative ERG) results when the b-wave is selectively reduced such that the ERG fails to cross the baseline following the a-wave. In the context of a normally sized a-wave, it indicates a site of retinal dysfunction occurring after phototransduction (commonly at the photoreceptor to bipolar cell synapse). This is an important finding. In genetic disease, the pattern of ERG abnormality can point to variants in a small group of genes (frequently those associated with congenital stationary night blindness and X-linked retinoschisis, but negative ERGs can also be seen in other conditions including syndromic disease). In acquired disease, there are numerous causes, but specific features may point to melanoma-associated retinopathy (MAR). In some cases, the visual symptoms precede the diagnosis of the melanoma and so the ERG findings can initiate investigations facilitating early detection and treatment. Negative ERGs can occur in other paraneoplastic conditions, and in a range of other diseases. This review will outline the physiological basis for the negative ERG, report prevalences in the literature from different cohorts, discuss the range of causes, displaying examples of a number of ERG phenotypes, highlight features of a clinical approach to patients, and briefly discuss further insights relating to current flows shaping the a-wave trough and from single-cell transcriptome analysis.
Ultra-strong bio-glue from genetically engineered polypeptides
Authors: Ma Chao , Sun Jing , Li Bo , Feng Yang , Sun Yao , Xiang Li , Wu Baiheng , Xiao Lingling , Liu Baimei , Petrovskii Vladislav S. , Bin Liu  , Zhang Jinrui , Wang Zili , Li Hongyan , Zhang Lei , Li Jingjing , Wang Fan , Gӧstl Robert , Potemkin Igor I. , Chen Dong , Zeng Hongbo , Zhang Hongjie , Liu Kai , Herrmann Andreas
Published: June 2021

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.
Light-emitting metalenses and meta-axicons for focusing and beaming of spontaneous emission
Authors: Mohtashami Yahya , DeCrescent Ryan A. , Heki Larry K. , Iyer Prasad P. , Butakov Nikita A. , Wong Matthew S. , Alhassan Abdullah , Mitchell William J. , Nakamura Shuji , DenBaars Steven P. , Schuller Jon. A.
Published: June 2021

Phased-array metasurfaces have been extensively used for wavefront shaping of coherent incident light. Due to the incoherent nature of spontaneous emission, the ability to similarly tailor photoluminescence remains largely unexplored. Recently, unidirectional photoluminescence from InGaN/GaN quantum-well metasurfaces incorporating one-dimensional phase profiles has been shown. However, the possibility of generating arbitrary two-dimensional waveforms—such as focused beams—is not yet realized. Here, we demonstrate two-dimensional metasurface axicons and lenses that emit collimated and focused beams, respectively. First, we develop off-axis meta-axicon/metalens equations designed to redirect surface-guided waves that dominate the natural emission pattern of quantum wells. Next, we show that photoluminescence properties are well predicted by passive transmission results using suitably engineered incident light sources. Finally, we compare collimating and focusing performances across a variety of different light-emitting metasurface axicons and lenses. These generated two-dimensional phased-array photoluminescence waveforms facilitate future development of light sources with arbitrary functionalities.
Engineering the protein dynamics of an ancestral luciferase
Authors: Schenkmayerova Andrea , Pinto Gaspar P. , Toul Martin , Marek Martin , Hernychova Lenka , Planas-Iglesias Joan , Daniel Liskova Veronika , Pluskal Daniel , Vasina Michal , Emond Stephane , Dörr Mark , Chaloupkova Radka , Bednar David , Prokop Zbynek , Hollfelder Florian , Bornscheuer Uwe T. , Damborsky Jiri
Published: June 2021

Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein AncHLD-RLucwhich catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of AncHLD-RLucchallenged the scaffold dynamics. Screening for both activities reveals InDel mutations localized in three distinct regions that lead to altered protein dynamics (based on crystallographic B-factors, hydrogen exchange, and molecular dynamics simulations). An anisotropic network model highlights the importance of the conformational flexibility of a loop-helix fragment ofRenillaluciferases for ligand binding. Transplantation of this dynamic fragment leads to lower product inhibition and highly stable glow-type bioluminescence. The success of our approach suggests that a strategy comprising (i) constructing a stable and evolvable template, (ii) mapping functional regions by backbone mutagenesis, and (iii) transplantation of dynamic features, can lead to functionally innovative proteins.
Lattice quantum electrodynamics in (3+1)-dimensions at finite density with tensor networks
Authors: Magnifico Giuseppe , Felser Timo , Silvi Pietro , Montangero Simone
Published: June 2021

Gauge theories are of paramount importance in our understanding of fundamental constituents of matter and their interactions. However, the complete characterization of their phase diagrams and the full understanding of non-perturbative effects are still debated, especially at finite charge density, mostly due to the sign-problem affecting Monte Carlo numerical simulations. Here, we report the Tensor Network simulation of a three dimensional lattice gauge theory in the Hamiltonian formulation including dynamical matter: Using this sign-problem-free method, we simulate the ground states of a compact Quantum Electrodynamics at zero and finite charge densities, and address fundamental questions such as the characterization of collective phases of the model, the presence of a confining phase at large gauge coupling, and the study of charge-screening effects.
Strong interaction between interlayer excitons and correlated electrons in WSe2/WS2 moiré superlattice
Authors: Miao Shengnan , Wang Tianmeng , Huang Xiong , Chen Dongxue , Lian Zhen , Wang Chong , Blei Mark , Taniguchi Takashi , Watanabe Kenji , Tongay Sefaattin , Wang Zenghui , Xiao Di , Cui Yong-Tao , Shi Su-Fei
Published: June 2021

Heterobilayers of transition metal dichalcogenides (TMDCs) can form a moiré superlattice with flat minibands, which enables strong electron interaction and leads to various fascinating correlated states. These heterobilayers also host interlayer excitons in a type-II band alignment, in which optically excited electrons and holes reside on different layers but remain bound by the Coulomb interaction. Here we explore the unique setting of interlayer excitons interacting with strongly correlated electrons, and we show that the photoluminescence (PL) of interlayer excitons sensitively signals the onset of various correlated insulating states as the band filling is varied. When the system is in one of such states, the PL of interlayer excitons is relatively amplified at increased optical excitation power due to reduced mobility, and the valley polarization of interlayer excitons is enhanced. The moiré superlattice of the TMDC heterobilayer presents an exciting platform to engineer interlayer excitons through the periodic correlated electron states.
SARS-CoV-2 infection and transmission in the North American deer mouse
Authors: Griffin Bryan D. , Chan Mable , Tailor Nikesh , Mendoza Emelissa J. , Leung Anders , Warner Bryce M. , Duggan Ana T. , Moffat Estella , He Shihua , Garnett Lauren , Tran Kaylie N. , Banadyga Logan , Albietz Alixandra , Tierney Kevin , Audet Jonathan , Bello Alexander , Vendramelli Robert , Boese Amrit S. , Fernando Lisa , Lindsay L. Robbin , Jardine Claire M. , Wood Heidi , Poliquin Guillaume , Strong James E. , Drebot Michael , Safronetz David , Embury-Hyatt Carissa , Kobasa Darwyn
Published: June 2021

Widespread circulation of SARS-CoV-2 in humans raises the theoretical risk of reverse zoonosis events with wildlife, reintroductions of SARS-CoV-2 into permissive nondomesticated animals. Here we report that North American deer mice (Peromyscus maniculatus) are susceptible to SARS-CoV-2 infection following intranasal exposure to a human isolate, resulting in viral replication in the upper and lower respiratory tract with little or no signs of disease. Further, shed infectious virus is detectable in nasal washes, oropharyngeal and rectal swabs, and viral RNA is detectable in feces and occasionally urine. We further show that deer mice are capable of transmitting SARS-CoV-2 to naïve deer mice through direct contact. The extent to which these observations may translate to wild deer mouse populations remains unclear, and the risk of reverse zoonosis and/or the potential for the establishment ofPeromyscusrodents as a North American reservoir for SARS-CoV-2 remains unknown.
Population-scale peach genome analyses unravel selection patterns and biochemical basis underlying fruit flavor
Authors: Yu Yang , Guan Jiantao , Xu Yaoguang , Ren Fei , Zhang Zhengquan , Yan Juan , Fu Jun , Guo Jiying , Shen Zhijun , Zhao Jianbo , Jiang Quan , Wei Jianhua , Xie Hua
Published: June 2021

A narrow genetic basis in modern cultivars and strong linkage disequilibrium in peach (Prunus persica) has restricted resolution power for association studies in this model fruit species, thereby limiting our understanding of economically important quality traits including fruit flavor. Here, we present a high-quality genome assembly for a Chinese landrace, Longhua Shui Mi (LHSM), a representative of the Chinese Cling peaches that have been central in global peach genetic improvement. We also map the resequencing data for 564 peach accessions to this LHSM assembly at an average depth of 26.34× per accession. Population genomic analyses reveal a fascinating history of convergent selection for sweetness yet divergent selection for acidity in eastern vs. western modern cultivars. Molecular-genetics and biochemical analyses establish that PpALMT1 (aluminum-activated malate transporter 1) contributes to their difference of malate content and that increases fructose content accounts for the increased sweetness of modern peach fruits, as regulated by PpERDL16 (early response to dehydration 6-like 16). Our study illustrates the strong utility of the genomics resources for both basic and applied efforts to understand and exploit the genetic basis of fruit quality in peach.
Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities
Authors: Lee Changhon , Verma Ravi , Byun Seohyun , Jeun Eun-Ji , Kim Gi-Cheon , Lee Suyoung , Kang Hye-Ji , Kim Chan Johng , Sharma Garima , Lahiri Abhishake , Paul Sandip , Kim Kwang Soon , Hwang Dong Soo , Iwakura Yoichiro , Speciale Immacolata , Molinaro Antonio , De Castro Cristina , Rudra Dipayan , Im Sin-Hyeog
Published: June 2021

Yeast is an integral part of mammalian microbiome, and like commensal bacteria, has the potential of being harnessed to influence immunity in clinical settings. However, functional specificities of yeast-derived immunoregulatory molecules remain elusive. Here we find that while under steady state, β-1,3-glucan-containing polysaccharides potentiate pro-inflammatory properties, a relatively less abundant class of cell surface polysaccharides, dubbed mannan/β-1,6-glucan-containing polysaccharides (MGCP), is capable of exerting potent anti-inflammatory effects to the immune system. MGCP, in contrast to previously identified microbial cell surface polysaccharides, through a Dectin1-Cox2 signaling axis in dendritic cells, facilitates regulatory T (Treg) cell induction from naïve T cells. Furthermore, through a TLR2-dependent mechanism, it restrains Th1 differentiation of effector T cells by suppressing IFN-γ expression. As a result, administration of MGCP display robust suppressive capacity towards experimental inflammatory disease models of colitis and experimental autoimmune encephalomyelitis (EAE) in mice, thereby highlighting its potential therapeutic utility against clinically relevant autoimmune diseases.
Dissecting the multi-omics atlas of the exosomes released by human lung adenocarcinoma stem-like cells
Authors: Luo Hai-Tao , Zheng Yuan-Yuan , Tang Jun , Shao Li-Juan , Mao Yi-Heng , Yang Wei , Yang Xiao-Fei , Li Yang , Tian Rui-Jun , Li Fu-Rong
Published: June 2021

Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.
The progression of disorder-specific brain pattern expression in schizophrenia over 9 years
Authors: Lieslehto Johannes , Jääskeläinen Erika , Kiviniemi Vesa , Haapea Marianne , Jones Peter B. , Murray Graham K. , Veijola Juha , Dannlowski Udo , Grotegerd Dominik , Meinert Susanne , Hahn Tim , Ruef Anne , Isohanni Matti , Falkai Peter , Miettunen Jouko , Dwyer Dominic B. , Koutsouleris Nikolaos
Published: June 2021

Age plays a crucial role in the performance of schizophrenia vs. controls (SZ-HC) neuroimaging-based machine learning (ML) models as the accuracy of identifying first-episode psychosis from controls is poor compared to chronic patients. Resolving whether this finding reflects longitudinal progression in a disorder-specific brain pattern or a systematic but non-disorder-specific deviation from a normal brain aging (BA) trajectory in schizophrenia would help the clinical translation of diagnostic ML models. We trained two ML models on structural MRI data: an SZ-HC model based on 70 schizophrenia patients and 74 controls and a BA model (based on 561 healthy individuals, age range = 66 years). We then investigated the two models’ predictions in the naturalistic longitudinal Northern Finland Birth Cohort 1966 (NFBC1966) following 29 schizophrenia and 61 controls for nine years. The SZ-HC model’s schizophrenia-specificity was further assessed by utilizing independent validation (62 schizophrenia, 95 controls) and depression samples (203 depression, 203 controls). We found better performance at the NFBC1966 follow-up (sensitivity = 75.9%, specificity = 83.6%) compared to the baseline (sensitivity = 58.6%, specificity = 86.9%). This finding resulted from progression in disorder-specific pattern expression in schizophrenia and was not explained by concomitant acceleration of brain aging. The disorder-specific pattern’s progression reflected longitudinal changes in cognition, outcomes, and local brain changes, while BA captured treatment-related and global brain alterations. The SZ-HC model was also generalizable to independent schizophrenia validation samples but classified depression as control subjects. Our research underlines the importance of taking account of longitudinal progression in a disorder-specific pattern in schizophrenia when developing ML classifiers for different age groups.
Author Correction: Interferometric measurements of refractive index and dispersion at high pressure
Authors: Kim Yong‑Jae , Celliers Peter M. , Eggert Jon H. , Lazicki Amy , Millot Marius
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Corticotropin-releasing factor neurons in the bed nucleus of the stria terminalis exhibit sex-specific pain encoding in mice
Authors: Yu Waylin , Caira Christina M. , del R. Rivera Sanchez Natalia , Moseley Garrett A. , Kash Thomas L.
Published: June 2021

The bed nucleus of the stria terminalis (BNST) plays an emerging role in pain regulation. Pharmacological studies have found that inhibiting corticotropin-releasing factor (CRF) signaling in the BNST can selectively mitigate the sensory and affective-motivational components of pain. However, mechanistic insight on the source of CRF that drives BNST responses to these harmful experiences remains unknown. In the present study, we used a series of genetic approaches to show that CRF in the BNST is engaged in the processing and modulation of pain. We conducted cell-type specific in vivo calcium imaging in CRF-Cre mice and found robust and synchronized recruitment of BNSTCRF neurons during acute exposures to noxious heat. Distinct patterns of recruitment were observed by sex, as the magnitude and timing of heat responsive activity in BNSTCRF neurons differed for male and female mice. We then used a viral approach in Floxed-CRF mice to selectively reduce CRF expression in the BNST and found it decreased nociceptive sensitivity for both sexes and increased paw attending for females. Together, these findings reveal that CRF in the BNST influences multiple facets of the pain experience to impact the sex-specific expression of pain-related behaviors.
Cross sectional study of the clinical characteristics of French primary care patients with COVID-19
Authors: Sebo Paul , Tudrej Benoit , Lourdaux Julie , Cuzin Clara , Floquet Martin , Haller Dagmar M. , Maisonneuve Hubert
Published: June 2021

The early identification of patients suffering from SARS-CoV-2 infection in primary care is of outmost importance in the current pandemic. The objective of this study was to describe the clinical characteristics of primary care patients who tested positive for SARS-CoV-2. We conducted a cross-sectional study between March 24 and May 7, 2020, involving consecutive patients undergoing RT-PCR testing in two community-based laboratories in Lyon (France) for a suspicion of COVID-19. We examined the association between symptoms and a positive test using univariable and multivariable logistic regression, adjusted for clustering within laboratories, and calculated the diagnostic performance of these symptoms. Of the 1561 patients tested, 1543 patients (99%) agreed to participate. Among them, 253 were positive for SARS-CoV-2 (16%). The three most frequently reported ‘ear-nose-throat’ and non-‘ear-nose-throat’ symptoms in patients who tested positive were dry throat (42%), loss of smell (36%) and loss of taste (31%), respectively fever (58%), cough (52%) and headache (45%). In multivariable analyses, loss of taste (OR 3.8 [95% CI 3.3–4.4], p-value < 0.001), loss of smell (OR 3.0 [95% CI 1.9–4.8], p < 0.001), muscle pain (OR 1.6 [95% CI 1.2–2.0], p = 0.001) and dry nose (OR 1.3 [95% CI 1.1–1.6], p = 0.01) were significantly associated with a positive result. In contrast, sore throat (OR 0.6 [95% CI 0.4–0.8], p = 0.003), stuffy nose (OR 0.6 [95% CI 0.6–0.7], p < 0.001), diarrhea (OR 0.6 [95% CI 0.5–0.6], p < 0.001) and dyspnea (OR 0.5 [95% CI 0.3–0.7], p < 0.001) were inversely associated with a positive test. The combination of loss of taste or smell had the highest diagnostic performance (OR 6.7 [95% CI 5.9–7.5], sensitivity 44.7% [95% CI 38.4–51.0], specificity 90.8% [95% CI 89.1–92.3]). No other combination of symptoms had a higher performance. Our data could contribute to the triage and early identification of new clusters of cases.
Increases in adipose tissue and muscle function are longitudinally associated with better quality of life in colorectal cancer survivors
Authors: Kenkhuis Marlou-Floor , van Roekel Eline H. , Koole Janna L. , Breedveld-Peters José J. L. , Breukink Stéphanie O. , Janssen-Heijnen Maryska L. G. , Keulen Eric T. P. , van Duijnhoven Fränzel J. B. , Mols Floortje , Weijenberg Matty P. , Bours Martijn J. L.
Published: June 2021

Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). In a prospective cohort among stage I–III CRC survivors (n = 459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations. Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition. With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment.

Trial registration: NTR7099.
Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
Authors: Yamakaze Jayden , Lu Zhe
Published: June 2021

Strongly oxidative H2O2 is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H2O2 to H2O while oxidizing thiocyanate (SCN−) to relatively tissue-innocuous hypothiocyanite (OSCN−). SCN− is the only known natural, effective reducing-substrate of LPO; humans normally derive SCN− solely from food. While its enzymatic mechanism is understood, the actual biological role of the LPO-SCN− system in mammals remains unestablished. Our group previously showed that this system protected cultured human cells from H2O2-caused injuries, a basis for the hypothesis that general deficiency of such an antioxidative mechanism would lead to multisystem inflammation and tumors. To test this hypothesis, we globally deleted the Lpo gene in mice. The mutant mice exhibited inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence. Thus, this understudied LPO-SCN− system is an essential protective mechanism in vivo.
Time-domain based evaluation of detection efficiency in liquid scintillation counting
Authors: Mitev Krasimir , Dutsov Chavdar , Cassette Philippe , Sabot Benoît
Published: June 2021

This work explores the distribution of time intervals between signals from the photomultiplier tubes (PMTs) of a liquid scintillation counting (LSC) system when a scintillation burst caused by an ionizing particle is detected. This distribution is termed the cross-correlation distribution and it is shown that it contains information about the probability to detect a scintillation event. A theoretical model that describes the cross-correlation distribution is derived. The model can be used to estimate the mean number of detected photons in a LSC measurement, which allows the calculation of the detection efficiency. The theoretical findings are validated by Monte Carlo simulations and by experiments with low-energy beta-emitting and electron-capture radionuclides ($$^3\hbox {H}$$

3

H

, $$^{14}\hbox {C}$$

14

C

, $$^{63}\hbox {Ni}$$

63

Ni

and $$^{55}\hbox {Fe}$$

55

Fe

), with dedicated LSC systems and several commercial LSC cocktails. The results show that some of the parameters of the cross-correlation distribution such as the peak height or the kurtosis can be used as detection efficiency estimators or quenching indicators in LSC. Thus, although the time domain and the cross-correlation distribution have received little to no attention in the practice of LSC, they have the capacity to bring significant improvements in almost all LSC applications related to activity determination of low-energy beta-emitting and electron-capture radionuclides. The results also suggest concepts for the development of innovative LSC systems.
Critical assessment of coiled-coil predictions based on protein structure data
Authors: Simm Dominic , Hatje Klas , Waack Stephan , Kollmar Martin
Published: June 2021

Coiled-coil regions were among the first protein motifs described structurally and theoretically. The simplicity of the motif promises that coiled-coil regions can be detected with reasonable accuracy and precision in any protein sequence. Here, we re-evaluated the most commonly used coiled-coil prediction tools with respect to the most comprehensive reference data set available, the entire Protein Data Bank, down to each amino acid and its secondary structure. Apart from the 30-fold difference in minimum and maximum number of coiled coils predicted the tools strongly vary in where they predict coiled-coil regions. Accordingly, there is a high number of false predictions and missed, true coiled-coil regions. The evaluation of the binary classification metrics in comparison with naïve coin-flip models and the calculation of the Matthews correlation coefficient, the most reliable performance metric for imbalanced data sets, suggests that the tested tools’ performance is close to random. This implicates that the tools’ predictions have only limited informative value. Coiled-coil predictions are often used to interpret biochemical data and are part of in-silico functional genome annotation. Our results indicate that these predictions should be treated very cautiously and need to be supported and validated by experimental evidence.
Characteristics of left atrial remodeling in patients with atrial fibrillation and hypertrophic cardiomyopathy in comparison to patients without hypertrophy
Authors: Nedios Sotirios , Dinov Borislav , Seewöster Timm , Lindemann Frank , Richter Sergio , Arya Arash , Dagres Nikolaos , Husser Daniela , Bollmann Andreas , Hindricks Gerhard , Müssigbrodt Andreas
Published: June 2021

Atrial fibrillation (AF) leads to remodeling characterized by changes in both size and shape of the left atrium (LA). Here we aimed to study the effect of hypertrophic cardiomyopathy (HCM) on the pattern of LA remodeling in AF-patients. HCM-patients (n = 23) undergoing AF ablation (2009–2012) were matched and compared with 125 Non-HCM patients from our prospective registry. Pre-procedural CT data were analyzed (EnSite Verismo, SJM, MN) to determine the maximal sagittal (anterior–posterior, AP), coronal (superior-inferior, SI and transversal, TV) dimensions and the sphericity index (LAS). Volume (LAV) was rendered after appendage (LAA) and pulmonary vein (PV) exclusion. A cutting plane, between PV ostia/LAA and parallel to the posterior wall, divided LAV into anterior- (LA­A) and posterior-LA (LA­P) parts. The ratio LA-A/LAV was defined as asymmetry index (ASI). HCM patients had a wider inter-ventricular septum and a smaller LV than Non-HCM patients. LA volume (LAV 166 ± 72 vs. 130 ± 36 ml, p = 0.03) and LA diameters were significantly larger in HCM patients. Anterior volume (LA-A: 112 ± 48 vs. 83 ± 26 ml, p < 0.001) differed significantly between groups, whereas the posterior volume LA-P (55 ± 28 vs. 47 ± 13 ml, p = 0.23) and LAS (75% vs. 78%, p = 0.089) was similar in both groups. As a result, ASI was significantly higher (67 ± 6 vs. 63 ± 6%, p = 0.01) in HCM than in Non-HCM patients. In conclusion, LA remodeling in patients with AF and HCM is characterized by asymmetric dilatation, driven by an anterior rather than a posterior dilatation. This can be characterized by three-dimensional imaging and could be used as surrogate of advanced atrial remodeling.