bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin of magmatic and tectonic fabrics in the Remal granite-gneiss, Singhbhum Craton, India
Authors: Dobe Ritabrata , Vukmanovic Zoja , Bose Narayan , Panigrahi Mruganka Kumar , Gupta Saibal
Published: June 2022

In the Singhbhum Craton of the Indian shield, the Remal granite-gneiss preserves felsic magmatic fabrics onto which a low-temperature segregation layering has been superposed. Planar, sub-horizontal to gently dipping layers (Sign1) comprise K-feldspar megacrysts, plagioclase and quartz, with the base of each layer defined by segregations of biotite. Sign2 consists of trough cross-bedded layers composed of K-feldspar phenocrysts, plagioclase and quartz with biotite schlieren defining the base of each layer. Microstructural features such as concentrically arranged mineral inclusions in K-feldspar phenocrysts and graphic intergrowth textures testify to the magmatic origin of these fabrics, with insignificant subsequent metamorphic reconstitution. The tectonic fabric S1 has developed sub-parallel to localized greenschist-facies mylonite bands, and is defined by weakly aligned flakes of biotite. Crystallographic preferred orientations away from the mylonitized domains show a strong alignment of K-feldspar, quartz and biotite parallel to the magmatic fabric due to efficient segregation during magmatic flow. Quartz crystallographic preferred orientations within the mylonitized domains show a strong preferred orientation and dextral asymmetry. Temperature constraints from synkinematic chlorites along with estimates of deformation temperature from quartz crystallographic preferred orientations indicate that mylonitization occurred at the lower limits of quartz crystal plasticity. The results of combined thermodynamic and multiphysics modelling studies show that felsic magmas can undergo significant convective motion for a wide range of crystallinities and water contents before solidification. Additionally, segregation layering resembling a gneissosity can develop at low temperatures owing to localized mylonitization and concomitant dissolution–precipitation of biotite.
A systematic review on efficacy, safety and cost-effectiveness of office-based laryngeal biopsy
Authors: Swaminathan R , Rosa Opatha S , Mughal Z , Prasad S
Published: June 2022

Objective

Laryngeal cancer is the second most prevalent head and neck malignancy in the USA. With recent advances in technology, this procedure is increasingly performed under local anaesthesia. This study aimed to identify the efficacy, safety and cost-effectiveness of laryngeal biopsy in out-patients by conducting a systematic review.

Method

A literature search was conducted using PubMed, Medline, Google Scholar and Embase over a 20-year period. Inclusion criteria were: studies performed on out-patient diagnostic biopsy procedures of the larynx. Exclusion criteria included all therapeutic procedures. The outcome measures were sensitivity and specificity, complication rate and cost-savings.

Results

Thirty-five studies were included in the analysis. The sensitivity and specificity varied from 60 to 100 per cent with a low complication rate and cost savings.

Conclusion

Office-based laryngeal biopsies are increasingly used in the diagnosis of laryngeal cancers, resulting in earlier diagnosis and commencement of treatment. The barrier to undertaking this procedure is low sensitivity.
FLUCTUATIONS AND GROWTH IN RAGNAR FRISCH’S ROCKING HORSE MODEL
Authors: Carret Vincent
Published: June 2022

Ragnar Frisch’s famous “rocking horse” model has been the object of much praise and even controversy since its publication in 1933. This paper offers a new simulation of the model to show that there exist cyclical trajectories in the propagation mechanism. By building an analytical solution taking the same form as Frisch’s original solution, we can provide new insights into the ideas encapsulated in his model, in particular the fact that the author constructed a model combining cycles and growth. The exploration of Frisch’s formal construction of the model leads us to link his statistical work on the decomposition of time series with his economic insights on investment cycles, which both led to the 1933 model. We contrast Frisch’s approach to that of other econometricians who used similar equations, showing that their different mathematical solutions were the product of what they wanted to show with their models.
Can dialectic materialism produce beauty? The “Great Aesthetic Debates” (1956–1962) in the People's Republic of China
Authors: Laikwan Pang
Published: June 2022

This article focuses on a set of aesthetic debates that took place in China in the late 1950s. By exploring the main arguments presented by different thinkers, particularly the writings of Zhu Guanqian and Li Zehou, this article demonstrates how the aesthetics took part in the ideological formation of the new socialist state. From the debates, we observe the tensions between the complexity of the material-political and the reductionism of the state ideology. We also recognize why and how aesthetics could be such an important site of political contestation in this young socialist country, and how the interactions between human senses and the material world are essential to arts universally. The dominant materialist aesthetics presented in the debate was less a theory of things than a theory of the social. This historical materialist approach might be useful as a social critique; however, when handled dogmatically, it not only rejects the autonomy of things, but also disallows art works to reflect the complex human interactions with the material world beyond economic power relations. We can find more sophisticated analysis in Zhu's aesthetic theory, which tries to incorporate the interactions between the subjects and the objects into materialism.
Broadbanding and multi-frequency in dielectric resonator antennas: a comprehensive review
Authors: Bhattacharya (Mitra) Sriparna , Ray Sekhar Chandra
Published: June 2022

Dielectric resonator antennas (DRAs) are developed antennas that are lightweight, wideband, small-sized and have high radiation efficiency. A DRA is an appropriate candidate for any radio communication including radar applications mainly because of its high efficiency and wideband performance. As the development of DRAs has been a continuous process for more than five decades the plethora of the same has become magnificent in all possible ways. Scientists have walked the technical path for more than centuries and tried to meet the various challenges in the most graceful ways. Reduction of loss, lightweight, and desired radiation patterns are some of the issues which are effectively met by DRAs. This paper presents a brief comprehensive review of the state of art techniques, giving an exhaustive idea of achieving broadband and multi-frequency operations in the areas of DRAs. The paper associates the references of the past and correlates with the current and future trends of research in DRAs that could be of immense help to the young upcoming researchers interested in this field.
Near-Peers zuerst, ärztliche Tutorierende am Schluss. Zwischenbericht einer Mixed-Method-Studie zum Timing im Ultraschallunterricht
Authors: Alt Leander , Walter Robin , Hari Roman , Harris Michael
Published: June 2022

Zusammenfassung. In der universitären Ultraschalllehre finden sich häufig Formate, welche Unterricht durch ärztliche und studentische Tutorinnen und Tutoren kombinieren. Bisher wurde die optimale Kombination dieser Tutorengruppen kaum erforscht. In dieser Studie erhielten vier Gruppen mit je 16 Teilnehmerinnen und Teilnehmern insgesamt zwölf studentische und vier ärztliche Lektionen im Rahmen eines Ultraschall-Grundkurses. Die ärztlichen Lektionen fanden für jede Gruppe in einem anderen Viertel der Kurszeit statt. Im Anschluss wurden quantitative und qualitative Daten über einen Online-Fragebogen erhoben und 15 Teilnehmende zusätzlich in einem persönlichen Interview befragt. Diese Interimsanalyse der noch laufenden Studie zeigt: Beim Aufbau eines kombinierten Ultraschalllernprogramms für Anfängerinnen und Anfänger sollten studentische Tutorierende eher am Anfang und ärztliche Tutorierende eher am Ende des Programms eingesetzt werden.
Alles über das Pankreas
Authors: Dietrich Christoph F. , Zander Tobias
Published: June 2022

Zusammenfassung. Der Ultraschall hat durch die Kontrastmittelanwendung und Elastografie insbesondere bei Kranken mit kleinen, soliden Pankreasläsionen (SPL) <20mm und zystischen Tumoren (ZPL) jeder Grösse enorme Fortschritte erzielt. Bei soliden und zystischen Pankreasläsionen muss nach der Detektion zunächst die Differenzialdiagnose evaluiert werden, um die Indikationen für eine radikale Operation, Strategien zur Erhaltung des Pankreasparenchyms oder einfach nur Kontrolluntersuchungen zu definieren. Kontrastverstärkter transkutaner (TUS, CEUS) und endoskopischer (EUS, CE-EUS) Ultraschall und Elastografie erleichtern die weitere Charakterisierung von SPL und ZPL. Duktale Adenokarzinome des Pankreas (PDAC) zeigen eine Minderanreicherung (Hypoenhancement) im kontrastverstärkten Ultraschall. Die meisten wichtigen Differenzialdiagnosen sind dagegen mehranreichernd. PDAC sind so gut wie immer härter als gesundes Pankreasparenchym. Im Kontrast hierzu sind elastografisch weiche SPL mit sehr wenigen Ausnahmen gutartig. Diese Übersicht gibt einen Überblick über die Anwendung moderner Ultraschalltechniken zur Erkennung und Charakterisierung solider und zystischer Pankreasläsionen.
Identifying Geographical Patterns of Transient Deformation in the Geological Sea Level Record
Authors: Simon K. M. , Riva R. E. M. , Broerse T.
Published: June 2022

In this study, we examine the effect of transient mantle creep on the prediction of glacial isostatic adjustment (GIA) signals. Specifically, we compare predictions of relative sea level (RSL) change from GIA from a set of Earth models in which transient creep parameters are varied in a simple Burgers model to a reference case with a Maxwell viscoelastic rheology. The model predictions are evaluated in two ways: first, relative to each other to quantify the effect of parameter variation, and second, for their ability to reproduce well‐constrained sea level records from selected locations. Both the resolution and geographic location of the RSL observations determine whether the data can distinguish between model cases. Model predictions are most sensitive to the inclusion of transient mantle deformation in regions that are near‐field and peripheral relative to former ice sheets. This sensitivity appears particularly true along the North American west coast in the region of the former Cordilleran Ice Sheet, which experienced rapid sea‐level fall following deglaciation between 14 and 12 kyr BP. Relative to the Maxwell case, Burgers models better reproduce this rapid phase of regional postglacial sea‐level fall. As well, computed goodness‐of‐fit values in this region show a clear preference for models where transient deformation is present in the whole or lower mantle, and for models where the rigidity of the Kelvin element is weakened relative to the rigidity of the Maxwell element. In contrast, model predictions of relative sea‐level change in the far‐field show weak sensitivity to the inclusion of transient deformation.
Role of Ocean and Atmosphere Variability in Scale‐Dependent Thermodynamic Air‐Sea Interactions
Authors: Laurindo Lucas C. , Small R. Justin , Thompson LuAnne , Siqueira Leo , Bryan Frank O. , Chang Ping , Danabasoglu Gokhan , Kamenkovich Igor V. , Kirtman Ben P. , Wang Hong , Zhang Shaoqing
Published: June 2022

This study investigates the influence of oceanic and atmospheric processes in extratropical thermodynamic air‐sea interactions resolved by satellite observations (OBS) and by two climate model simulations run with eddy‐resolving high‐resolution (HR) and eddy‐parameterized low‐resolution (LR) ocean components. Here, spectral methods are used to characterize the sea surface temperature (SST) and turbulent heat flux (THF) variability and co‐variability over scales between 50 and 10,000 km and 60 days to 80 years in the Pacific Ocean. The relative roles of the ocean and atmosphere are interpreted using a stochastic upper‐ocean temperature evolution model forced by noise terms representing intrinsic variability in each medium, defined using climate model data to produce realistic rather than white spectral power density distributions. The analysis of all datasets shows that the atmosphere dominates the SST and THF variability over zonal wavelengths larger than ∼2,000–2,500 km. In HR and OBS, ocean processes dominate the variability of both quantities at scales smaller than the atmospheric first internal Rossby radius of deformation (R1, ∼600–2,000 km) due to a substantial ocean forcing coinciding with a weaker atmospheric modulation of THF (and consequently of SST) than at larger scales. The ocean forcing also induces oscillations in SST and THF with periods ranging from intraseasonal to multidecadal, reflecting a red spectrum response to ocean forcing similar to that driven by atmospheric forcing. Such features are virtually absent in LR due to a weaker ocean forcing relative to HR.
Structural, molecular, and functional insights into Schlafen proteins
Authors: Jo Ukhyun , Pommier Yves
Published: June 2022

Schlafen (SLFN) genes belong to a vertebrate gene family encoding proteins with high sequence homology. However, each SLFN is functionally divergent and differentially expressed in various tissues and species, showing a wide range of expression in cancer and normal cells. SLFNs are involved in various cellular and tissue-specific processes, including DNA replication, proliferation, immune and interferon responses, viral infections, and sensitivity to DNA-targeted anticancer agents. The fundamental molecular characteristics of SLFNs and their structures are beginning to be elucidated. Here, we review recent structural insights into the N-terminal, middle and C-terminal domains (N-, M-, and C-domains, respectively) of human SLFNs and discuss the current understanding of their biological roles. We review the distinct molecular activities of SLFN11, SLFN5, and SLFN12 and the relevance of SLFN11 as a predictive biomarker in oncology.
Insights to estimate exposure to regulated and non-regulated disinfection by-products in drinking water
Authors: Redondo-Hasselerharm Paula E. , Cserbik Dora , Flores Cintia , Farré Maria J. , Sanchís Josep , Alcolea Jose A. , Planas Carles , Caixach Josep , Villanueva Cristina M.
Published: June 2022

Background

Knowledge about human exposure and health effects associated with non-routinely monitored disinfection by-products (DBPs) in drinking water is sparse.

Objective

To provide insights to estimate exposure to regulated and non-regulated DBPs in drinking water.

Methods

We collected tap water from homes (N = 42), bottled water (N = 10), filtered tap water with domestic activated carbon jars (N = 6) and reverse osmosis (N = 5), and urine (N = 39) samples of participants from Barcelona, Spain. We analyzed 11 haloacetic acids (HAAs), 4 trihalomethanes (THMs), 4 haloacetonitriles (HANs), 2 haloketones, chlorate, chlorite, and trichloronitromethane in water and HAAs in urine samples. Personal information on water intake and socio-demographics was ascertained in the study population (N = 39) through questionnaires. Statistical models were developed based on THMs as explanatory variables using multivariate linear regression and machine learning techniques to predict non-regulated DBPs.

Results

Chlorate, THMs, HAAs, and HANs were quantified in 98–100% tap water samples with median concentration of 214, 42, 18, and 3.2 μg/L, respectively. Multivariate linear regression models had similar or higher goodness of fit (R2) compared to machine learning models. Multivariate linear models for dichloro-, trichloro-, and bromodichloroacetic acid, dichloroacetonitrile, bromochloroacetonitrile, dibromoacetonitrile, trichloropropnanone, and chlorite showed good predictive ability (R2 = 0.8–0.9) as 80–90% of total variance could be explained by THM concentrations. Activated carbon filters reduced DBP concentrations to a variable extent (27–80%), and reverse osmosis reduced DBP concentrations ≥98%. Only chlorate was detected in bottled water samples (N = 3), with median = 13.0 µg/L. Creatinine-adjusted trichloroacetic acid was the most frequently detected HAA in urine samples (69.2%), and moderately correlated with estimated drinking water intake (r = 0.48).

Significance

Findings provide valuable insights for DBP exposure assessment in epidemiological studies. Validation of predictive models in a larger number of samples and replication in different settings is warranted.

Impact statement

Our study focused on assessing and describing the occurrence of several classes of DBPs in drinking water and developing exposure models of good predictive ability for non-regulated DBPs.
Electrically driven single microwire-based single-mode microlaser
Authors: Zhou Xiangbo , Jiang Mingming , Xu Kai , Liu Maosheng , Sha Shulin , Cao Shuiyan , Kan Caixia , Shi Da Ning
Published: June 2022

Engineering the lasing-mode oscillations effectively within a laser cavity is a relatively updated attentive study and perplexing issue in the field of laser physics and applications. Herein, we report a realization of electrically driven single-mode microlaser, which is composed of gallium incorporated zinc oxide microwire (ZnO:Ga MW) with platinum nanoparticles (PtNPs, d ~ 130 nm) covering, a magnesium oxide (MgO) nanofilm, a Pt nanofilm, and a p-type GaN substrate. The laser cavity modes could resonate following the whispering-gallery mode (WGM) among the six side surfaces by total internal reflection, and the single-mode lasing wavelength is centered at 390.5 nm with a linewidth of about 0.18 nm. The cavity quality factor Q is evaluated to about 2169. In the laser structure, the usage of Pt and MgO buffer layers can be utilized to engineer the band alignment of ZnO:Ga/GaN heterojunction, optimize the p-n junction quality and increase the current injection. Thus, the well-designed device structure can seamlessly unite the electron-hole recombination region, the gain medium, and optical microresonator into the PtNPs@ZnO:Ga wire perfectly. Such a single MW microlaser is essentially single-mode regardless of the gain spectral bandwidth. To study the single-mode operation, PtNPs working as superabsorber can engineering the multimode lasing actions of ZnO:Ga MWs even if their dimensions are typically much larger than that of lasing wavelength. Our findings can provide a straightforward and effective scheme to develop single-mode microlaser devices based on one-dimensional wire semiconductors.
Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile
Authors: Grimm Oliver , Thomä Lara , Kranz Thorsten M. , Reif Andreas
Published: June 2022

Recent GWAS allow us to calculate polygenic risk scores for ADHD. At the imaging level, resting-state fMRI analyses have given us valuable insights into changes in connectivity patterns in ADHD patients. However, no study has yet attempted to combine these two different levels of investigation. For this endeavor, we used a dopaminergic challenge fMRI study (L-DOPA) in healthy participants who were genotyped for their ADHD, MDD, schizophrenia, and body height polygenic risk score (PRS) and compared results with a study comparing ADHD patients and healthy controls. Our objective was to evaluate how L-DOPA-induced changes of reward-system-related FC are dependent on the individual polygenic risk score. FMRI imaging was used to evaluate resting-state functional connectivity (FC) of targeted subcortical structures in 27 ADHD patients and matched controls. In a second study, we evaluated the effect of ADHD and non-ADHD PRS in a L-DOPA-based pharmaco-fMRI-challenge in 34 healthy volunteers. The functional connectivity between the putamen and parietal lobe was decreased in ADHD patients. In healthy volunteers, the FC between putamen and parietal lobe was lower in ADHD high genetic risk participants. This direction of connectivity was reversed during L-DOPA challenge. Further findings are described for other dopaminergic subcortical structures. The FC between the putamen and the attention network showed the most consistent change in patients as well as in high-risk participants. Our results suggest that FC of the dorsal attention network is altered in adult ADHD as well as in healthy controls with higher genetic risk.
In-situ study of the impact of temperature and architecture on the interfacial structure of microgels
Authors: Bochenek Steffen , Camerin Fabrizio , Zaccarelli Emanuela , Maestro Armando , Schmidt Maximilian M. , Richtering Walter , Scotti Andrea
Published: June 2022

The structural characterization of microgels at interfaces is fundamental to understand both their 2D phase behavior and their role as stabilizers that enable emulsions to be broken on demand. However, this characterization is usually limited by available experimental techniques, which do not allow a direct investigation at interfaces. To overcome this difficulty, here we employ neutron reflectometry, which allows us to probe the structure and responsiveness of the microgels in-situ at the air-water interface. We investigate two types of microgels with different cross-link density, thus having different softness and deformability, both below and above their volume phase transition temperature, by combining experiments with computer simulations of in silico synthesized microgels. We find that temperature only affects the portion of microgels in water, while the strongest effect of the microgels softness is observed in their ability to protrude into the air. In particular, standard microgels have an apparent contact angle of few degrees, while ultra-low cross-linked microgels form a flat polymeric layer with zero contact angle. Altogether, this study provides an in-depth microscopic description of how different microgel architectures affect their arrangements at interfaces, and will be the foundation for a better understanding of their phase behavior and assembly.
Unraveling the molecular mechanism of MIL-53(Al) crystallization
Authors: Salionov Daniil , Semivrazhskaya Olesya O. , Casati Nicola P. M. , Ranocchiari Marco , Bjelić Saša , Verel René , van Bokhoven Jeroen A. , Sushkevich Vitaly L.
Published: June 2022

The vast structural and chemical diversity of metal−organic frameworks (MOFs) provides the exciting possibility of material’s design with tailored properties for gas separation, storage and catalysis. However, after more than twenty years after first reports introducing MOFs, the discovery and control of their synthesis remains extremely challenging due to the lack of understanding of mechanisms of their nucleation and growth. Progress in deciphering crystallization pathways depends on the possibility to follow conversion of initial reagents to products at the molecular level, which is a particular challenge under solvothermal conditions. The present work introduces a detailed molecular-level mechanism of the formation of MIL-53(Al), unraveled by combining in situ time-resolved high-resolution mass-spectrometry, magic angle spinning nuclear magnetic resonance spectroscopy and X-ray diffraction. In contrast to the general belief, the crystallization of MIL-53 occurs via a solid-solid transformation mechanism, associated with the spontaneous release of monomeric aluminum. The role of DMF hydrolysis products, formate and dimethylamine, is established. Our study emphasizes the complexity of MOF crystallization chemistry, which requires case-by-case investigation using a combination of advanced in situ methods for following the induction period, the nucleation and growth across the time domain.
Host lung microbiota promotes malaria-associated acute respiratory distress syndrome
Authors: Mukherjee Debanjan , Chora Ângelo Ferreira , Lone Jean-Christophe , Ramiro Ricardo S. , Blankenhaus Birte , Serre Karine , Ramirez Mário , Gordo Isabel , Veldhoen Marc , Varga-Weisz Patrick , Mota Maria M.
Published: June 2022

Severe malaria can manifest itself with a variety of well-recognized clinical phenotypes that are highly predictive of death – severe anaemia, coma (cerebral malaria), multiple organ failure, and respiratory distress. The reasons why an infected individual develops one pathology rather than another remain poorly understood. Here we use distinct rodent models of infection to show that the host microbiota is a contributing factor for the development of respiratory distress syndrome and host mortality in the context of malaria infections (malaria-associated acute respiratory distress syndrome, MA-ARDS). We show that parasite sequestration in the lung results in sustained immune activation. Subsequent production of the anti-inflammatory cytokine IL-10 by T cells compromises microbial control, leading to severe lung disease. Notably, bacterial clearance with linezolid, an antibiotic commonly used in the clinical setting to control lung-associated bacterial infections, prevents MA-ARDS-associated lethality. Thus, we propose that the host’s anti-inflammatory response to limit tissue damage can result in loss of microbial control, which promotes MA-ARDS. This must be considered when intervening against life-threatening respiratory complications.
Limited effects of m6A modification on mRNA partitioning into stress granules
Authors: Khong Anthony , Matheny Tyler , Huynh Thao Ngoc , Babl Vincent , Parker Roy
Published: June 2022

The presence of the m6A modification in mammalian mRNAs is proposed to promote mRNA recruitment to stress granules through the interaction with YTHDF proteins. We test this possibility by examining the accumulation of mRNAs in stress granules in both WT and ∆METTL3 mES cells, which are deficient in m6A modification. A critical observation is that all m6A modified mRNAs partition similarly into stress granules in both wild-type and m6A-deficient cells by single-molecule FISH. Moreover, multiple linear regression analysis indicates m6A modification explains only 6% of the variance in stress granule localization when controlled for length. Finally, the artificial tethering of 25 YTHDF proteins on reporter mRNAs leads to only a modest increase in mRNA partitioning to stress granules. Since most mammalian mRNAs have 4 or fewer m6A sites, and those sites are not fully modified, this argues m6A modifications are unlikely to play a significant role in recruiting mRNAs to stress granules. Taken together, these observations argue that m6A modifications play a minimal, if any, role in mRNA partitioning into stress granules.
Boosting electrocatalytic CO2–to–ethanol production via asymmetric C–C coupling
Authors: Wang Pengtang , Yang Hao , Tang Cheng , Wu Yu , Zheng Yao , Cheng Tao , Davey Kenneth , Huang Xiaoqing , Qiao Shi-Zhang
Published: June 2022

Electroreduction of carbon dioxide (CO2) into multicarbon products provides possibility of large-scale chemicals production and is therefore of significant research and commercial interest. However, the production efficiency for ethanol (EtOH), a significant chemical feedstock, is impractically low because of limited selectivity, especially under high current operation. Here we report a new silver–modified copper–oxide catalyst (dCu2O/Ag2.3%) that exhibits a significant Faradaic efficiency of 40.8% and energy efficiency of 22.3% for boosted EtOH production. Importantly, it achieves CO2–to–ethanol conversion under high current operation with partial current density of 326.4 mA cm−2 at −0.87 V vs reversible hydrogen electrode to rank highly significantly amongst reported Cu–based catalysts. Based on in situ spectra studies we show that significantly boosted production results from tailored introduction of Ag to optimize the coordinated number and oxide state of surface Cu sites, in which the *CO adsorption is steered as both atop and bridge configuration to trigger asymmetric C–C coupling for stablization of EtOH intermediates.
The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma
Authors: Vo Josh N. , Wu Yi-Mi , Mishler Jeanmarie , Hall Sarah , Mannan Rahul , Wang Lisha , Ning Yu , Zhou Jin , Hopkins Alexander C. , Estill James C. , Chan Wallace K. B. , Yesil Jennifer , Cao Xuhong , Rao Arvind , Tsodikov Alexander , Talpaz Moshe , Cole Craig E. , Ye Jing C. ,   Multiple Myeloma Research Consortium, Ailawadhi Sikander , Berdeja Jesus G. , Hofmeister Craig C. , Jagannath Sundar , Jakubowiak Andrzej , Krishnan Amrita , Kumar Shaji , Levy Moshe Yair , Lonial Sagar , Orloff Gregory J. , Siegel David , Trudel Suzanne , Usmani Saad Z. , Vij Ravi , Wolf Jeffrey L. , Zonder Jeffrey A. , Bergsagel P. Leif , Auclair Daniel , Cho Hearn Jay , Robinson Dan R. , Chinnaiyan Arul M.
Published: June 2022

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease’s molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45–65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.
Deep learning to diagnose Hashimoto’s thyroiditis from sonographic images
Authors: Zhang Qiang , Zhang Sheng , Pan Yi , Sun Lin , Li Jianxin , Qiao Yu , Zhao Jing , Wang Xiaoqing , Feng Yixing , Zhao Yanhui , Zheng Zhiming , Yang Xiangming , Liu Lixia , Qin Chunxin , Zhao Ke , Liu Xiaonan , Li Caixia , Zhang Liuyang , Yang Chunrui , Zhuo Na , Zhang Hong , Liu Jie , Gao Jinglei , Di Xiaoling , Meng Fanbo , Zhang Linlei , Wang Yuxuan , Duan Yuansheng , Shen Hongru , Li Yang , Yang Meng , Yang Yichen , Xin Xiaojie , Wei Xi , Zhou Xuan , Jin Rui , Zhang Lun , Wang Xudong , Song Fengju , Zheng Xiangqian , Gao Ming , Chen Kexin , Li Xiangchun
Published: June 2022

Hashimoto’s thyroiditis (HT) is the main cause of hypothyroidism. We develop a deep learning model called HTNet for diagnosis of HT by training on 106,513 thyroid ultrasound images from 17,934 patients and test its performance on 5051 patients from 2 datasets of static images and 1 dataset of video data. HTNet achieves an area under the receiver operating curve (AUC) of 0.905 (95% CI: 0.894 to 0.915), 0.888 (0.836–0.939) and 0.895 (0.862–0.927). HTNet exceeds radiologists’ performance on accuracy (83.2% versus 79.8%; binomial test, p < 0.001) and sensitivity (82.6% versus 68.1%; p < 0.001). By integrating serologic markers with imaging data, the performance of HTNet was significantly and marginally improved on the video (AUC, 0.949 versus 0.888; DeLong’s test, p = 0.004) and static-image (AUC, 0.914 versus 0.901; p = 0.08) testing sets, respectively. HTNet may be helpful as a tool for the management of HT.
Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277
Authors: Willegems Katrien , Eldstrom Jodene , Kyriakis Efthimios , Ataei Fariba , Sahakyan Harutyun , Dou Ying , Russo Sophia , Van Petegem Filip , Fedida David
Published: June 2022

The KCNQ1 ion channel plays critical physiological roles in electrical excitability and K+recycling in organs including the heart, brain, and gut. Loss of function is relatively common and can cause sudden arrhythmic death, sudden infant death, epilepsy and deafness. Here, we report cryogenic electron microscopic (cryo-EM) structures ofXenopusKCNQ1 bound to Ca2+/Calmodulin, with and without the KCNQ1 channel activator, ML277. A single binding site for ML277 was identified, localized to a pocket lined by the S4-S5 linker, S5 and S6 helices of two separate subunits. Several pocket residues are not conserved in other KCNQ isoforms, explaining specificity. MD simulations and point mutations support this binding location for ML277 in open and closed channels and reveal that prevention of inactivation is an important component of the activator effect. Our work provides direction for therapeutic intervention targeting KCNQ1 loss of function pathologies including long QT interval syndrome and seizures.
Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor
Authors: Guo Xuanming , Asthana Pallavi , Gurung Susma , Zhang Shuo , Wong Sheung Kin Ken , Fallah Samane , Chow Chi Fung Willis , Che Sijia , Zhai Lixiang , Wang Zening , Ge Xin , Jiang Zhixin , Wu Jiayan , Zhang Yijing , Wu Xiaoyu , Xu Keyang , Lin Cheng Yuan , Kwan Hiu Yee , Lyu Aiping , Zhou Zhongjun , Bian Zhao-Xiang , Wong Hoi Leong Xavier
Published: June 2022

Insulin sensitivity progressively declines with age. Currently, the mechanism underlying age-associated insulin resistance remains unknown. Here, we identify membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) as a central regulator of insulin sensitivity during ageing. Ageing promotes MMP14 activation in insulin-sensitive tissues, which cleaves Insulin Receptor to suppress insulin signaling. MT1-MMP inhibition restores Insulin Receptor expression, improving insulin sensitivity in aged mice. The cleavage of Insulin Receptor by MT1-MMP also contributes to obesity-induced insulin resistance and inhibition of MT1-MMP activities normalizes metabolic dysfunctions in diabetic mouse models. Conversely, overexpression of MT1-MMP in the liver reduces the level of Insulin Receptor, impairing hepatic insulin sensitivity in young mice. The soluble Insulin Receptor and circulating MT1-MMP are positively correlated in plasma from aged human subjects and non-human primates. Our findings provide mechanistic insights into regulation of insulin sensitivity during physiological ageing and highlight MT1-MMP as a promising target for therapeutic avenue against diabetes.
Evaluating utility and feasibility of mismatch repair testing of colorectal cancer patients in a low-middle-income country
Authors: Elsayed Inas , Geraghty Robert , Mekki Salwa O. , Mohamedani Ahmed A. , Ahern Susan , Salim Omer E. H. , Khalil Balgis B. M. , Abdelrahim Sawsan , Suliman Suliman H. , Elhassan Moawia M. A. , Salah Salah O. , Salih Mohamed E. , Widatalla Abubakr H. , Abdelhamed Osman S. , Wang Xiaosheng , Ryan Éanna J. , Winter Des , Bakhiet Salih , Sheahan Kieran
Published: June 2022

Molecular pathology services for colorectal cancer (CRC) in Sudan represent a significant unmet clinical need. In a retrospective cohort study involving 50 patients diagnosed with CRC at three major medical settings in Sudan, we aimed to outline the introduction of a molecular genetic service for CRC in Sudan, and to explore the CRC molecular features and their relationship to patient survival and clinicopathological characteristics. Mismatch repair (MMR) and BRAF (V600E) mutation status were determined by immunohistochemistry. A mismatch repair deficient (dMMR) subtype was demonstrated in 16% of cases, and a presumptive Lynch Syndrome (LS) diagnosis was made in up to 14% of patients. dMMR CRC in Sudan is characterized by younger age at diagnosis and a higher incidence of right-sided tumours. We report a high mortality in Sudanese CRC patients, which correlates with advanced disease stage, and MMR status. Routine MMR immunohistochemistry (with sequential BRAF mutation analysis) is a feasible CRC prognostic and predictive molecular biomarker, as well as a screening tool for LS in low-middle-income countries (LMICs).
Relationship between electroencephalographic data and comfort perception captured in a Virtual Reality design environment of an aircraft cabin
Authors: Ricci Giulia , De Crescenzio Francesca , Santhosh Sandhya , Magosso Elisa , Ursino Mauro
Published: June 2022

Successful aircraft cabin design depends on how the different stakeholders are involved since the first phases of product development. To predict passenger satisfaction prior to the manufacturing phase, human response was investigated in a Virtual Reality (VR) environment simulating a cabin aircraft. Subjective assessments of virtual designs have been collected via questionnaires, while the underlying neural mechanisms have been captured through electroencephalographic (EEG) data. In particular, we focused on the modulation of EEG alpha rhythm as a valuable marker of the brain’s internal state and investigated which changes in alpha power and connectivity can be related to a different visual comfort perception by comparing groups with higher and lower comfort rates. Results show that alpha-band power decreased in occipital regions during subjects’ immersion in the virtual cabin compared with the relaxation state, reflecting attention to the environment. Moreover, alpha-band power was modulated by comfort perception: lower comfort was associated with a lower alpha power compared to higher comfort. Further, alpha-band Granger connectivity shows top-down mechanisms in higher comfort participants, modulating attention and restoring partial relaxation. Present results contribute to understanding the role of alpha rhythm in visual comfort perception and demonstrate that VR and EEG represent promising tools to quantify human–environment interactions.
Increased sleep duration and delayed sleep timing during the COVID-19 pandemic
Authors: Yuan Robin K. , Zitting Kirsi-Marja , Maskati Liyaan , Huang Jeff
Published: June 2022

Many studies have examined how the 2019 Coronavirus Disease (COVID-19) has impacted sleep health. Early evidence suggests that lockdown policies worldwide have led to changes in sleep timing, duration, and quality; however, few studies have attempted to look at the longer-term effects across multiple countries in a large data set. This study uses self-reported data from 64,858 users of the Sleep As Android smartphone application from around the world over a 24-month period in 2019 to 2020. We found a significant but modest increase in time in bed (TIB), as well as a significant delay in sleep timing that was especially prominent on weekdays. While this effect persisted throughout the year, differences in sleep timing were more widespread and pronounced in the earlier months of the pandemic. We observed a small overall increase in TIB when comparing 2020 to 2019, but these changes depended on location and time of year, suggesting that sleep duration may have more closely tracked the progression of the pandemic in each country. Our findings suggest that pandemic-induced changes in lifestyle, such as remote work and lockdown policies, may have facilitated later sleep timing but that these changes may diminish as restrictions are lifted.
Magnesium stable isotope composition, but not concentration, responds to obesity and early insulin-resistant conditions in minipig
Authors: le Goff Samuel , Godin Jean-Philippe , Albalat Emmanuelle , Nieves José Manuel Ramos , Balter Vincent
Published: June 2022

Hypomagnesemia is frequently associated with type 2 diabetes and generally correlates with unfavorable disease progression, but the magnesium status in pre-diabetic conditions remains unclear. Here, the magnesium metabolism is scrutinized in a minipig model of obesity and insulin resistance by measuring variations of the metallome—the set of inorganic elements—and the magnesium stable isotope composition in six organs of lean and obese minipigs raised on normal and Western-type diet, respectively. We found that metallomic variations are most generally insensitive to lean or obese phenotypes. The magnesium stable isotope composition of plasma, liver, kidney, and heart in lean minipigs are significantly heavier than in obese minipigs. For both lean and obese minipigs, the magnesium isotope composition of plasma and liver were negatively correlated to clinical phenotypes and plasma lipoproteins concentration as well as positively correlated to hyperinsulinemic-euglycemic clamp output. Because the magnesium isotope composition was not associated to insulin secretion, our results suggest that it is rather sensitive to whole body insulin sensitivity, opening perspectives to better comprehend the onset of insulin-resistant diabetic conditions.
Guiding antiferromagnetic transitions in Ca$$_{2}$$RuO$$_{4}$$
Authors: Porter D. G. , Forte F. , Granata V. , Cannavacciuolo M. , Fittipaldi R. , Cuoco M. , Bombardi A. , Vecchione A.
Published: June 2022

Understanding and controlling the transition between antiferromagnetic states having different symmetry content with respect to time-inversion and space-group operations are fundamental challenges for the design of magnetic phases with topologically nontrivial character. Here, we consider a paradigmatic antiferromagnetic oxide insulator, Ca$$_{2}$$

2

RuO$$_{4}$$

4

, with symmetrically distinct magnetic ground states and unveil a novel path to guide the transition between them. The magnetic changeover results from structural and orbital reconstruction at the transition metal site that in turn arise as a consequence of substitutional doping. By means of resonant X-ray diffraction we track the evolution of the structural, magnetic, and orbital degrees of freedom for Mn doped Ca$$_{2}$$

2

RuO$$_{4}$$

4

to demonstrate the mechanisms which drive the antiferromagnetic transition. While our analysis focuses on a specific case of substitution, we show that any perturbation that can impact in a similar way on the crystal structure, by reconstructing the induced spin–orbital exchange, is able to drive the antiferromagnetic reorganization.
Experimental and simulation study on aluminium alloy piston based on thermal barrier coating
Authors: Liu Yang , Lei Jilin , Niu Xiaoqiang , Deng Xiwen , Wen Jun , Wen Zhigao
Published: June 2022

Thermal barrier coatings (TBCs) have low thermal conductivity, effectively reducing the temperature of the metal matrix and improving thermal performance, knock resistance, and combustion performance of the piston. In this study, an off-road high-pressure common-rail diesel engine was chosen as the research object. Combined with the test results of the piston temperature field under the rated power and maximum torque conditions, a finite element simulation model of the thermal barrier coating piston was established. This model enabled the distribution characteristics and variation laws of the temperature field, stress, and deformation of the thermal barrier coating on the piston matrix to be analysed. The results show that the maximum temperature of the TBC piston is 12.2% and 13.73% lower than that of the aluminium alloy piston under the rated power and maximum torque conditions, respectively. The thermal stresses of the TBC piston at the top of the cavity were 25.9% and 26.8% lower than those of the aluminium piston, while the thermo-mechanical coupling stress of the TBC piston was slightly higher than that of the aluminium piston—1.2 MPa and 3.7 MPa in the bottom of the combustion chamber with geometric mutation, respectively. The radial thermal deformation of the TBC piston was 0.067 mm and 0.073 mm lower than that of the aluminium piston, with the radial thermo-mechanical coupling deformation also decreasing by 0.069 mm and 0.075 mm, respectively. The radial thermal deformation of the piston in the direction parallel to the pinhole axis was greater than that in the direction perpendicular to the pinhole axis; the difference in the magnitude of the change results in uneven thermal deformation of the piston.
Zinc nutritional status, mood states and quality of life in diarrhea-predominant irritable bowel syndrome: a case–control study
Authors: Rezazadegan Mahsa , Shahdadian Farnaz , Soheilipour Maryam , Tarrahi Mohammad Javad , Amani Reza
Published: June 2022

Zinc is an important trace element for structure, and regulation in the central nervous system, as well as the gut homeostasis. There are several mental disorders associated with zinc deficiency. The relationship between zinc nutritional status with mood states and quality of life (QoL) in diarrhea-predominant irritable bowel syndrome (IBS-D) has not been studied yet. This case–control study aimed to investigate the association between zinc nutritional status with mood states and QoL in IBS-D patients. Sixty-one newly diagnosed patients with IBS-D and 61 matched healthy controls were enrolled. Dietary zinc intakes and serum zinc levels were measured. Mood states and QoL were evaluated by validated questionnaires. Logistic regression was used to estimate the odds of IBS-D in relation to zinc deficiency. Decreased serum zinc levels were observed in the IBS-D group than in the controls (p = 0.001). There were higher scores of depression (p = 0.014), anxiety (p = 0.005), and stress (p = 0.001) among IBS-D patients. Moreover, overall QoL, physical and psychological health were lower in IBS-D patients compared to the controls (p < 0.001). “Food avoidance” had the lowest, while the “relationship” had the highest score among the patients (51.09 ± 26.80 and 78.14 ± 23.30, respectively). Dietary zinc intake was positively correlated with psychological health in the controls (r = 0.295, p = 0.022) and with body image in the patients (r = 0.266, p = 0.044). According to the logistic regression, zinc deficiency was not significantly associated with odds of IBS-D. Findings show that zinc deficiency may be associated with some parameters of IBS-D. Further clinical studies are needed to explore the causal relationship between zinc status and IBS pathogenesis.
Single-qubit reaped quantum state tomography
Authors: Choi Mahn-Soo
Published: June 2022

Quantum state tomography is the experimental procedure of determining an unknown state. It is not only essential for the verification of resources and processors of quantum information but is also important in its own right with regard to the foundation of quantum mechanics. Standard methods have been elusive for large systems because of the enormous number of observables to be measured and the exponential complexity of data post-processing. Here, we propose a new scheme of quantum state tomography that requires the measurement of only three observables (acting jointly on the system and pointer) regardless of the size of the system. The system is coupled to a “pointer” of single qubit, and the wavefunction of the system is “reaped” onto the pointer upon the measurement of the system. Subsequently, standard two-state tomography on the pointer and classical post-processing are used to reconstruct the quantum state of the system. We also developed an efficient and scalable iterative maximum likelihood algorithm to estimate states from statistically incomplete data.