bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated design and fabricate of high sensitivity built-in thin-film thermocouple temperature measurement tool
Authors: Chen Jinguo , Lin Ying , Zhao Dongxu , Gao Siyuan , Zheng Minli , Ma Weiping , Chen Baoliang
Published: January 2024

Cutting temperature is playing a key role in evaluating the cutting process, which significantly affects the tool wear and the quality of the workpiece. Aiming at the problems of low precision, low aging, and poor stability of cutting temperature measurement on the front tool face, an integrated design and production scheme of a high sensitivity built-in wireless temperature measurement tool was proposed. The temperature distribution position on the front tool face was analyzed with 3D finite element simulation software, and the thermal contact position of the main and secondary film thermocouples was determined. SiO2 insulated films and NiCr/NiSi film thermocouples were prepared on the front tool surface by femtosecond laser micromachining, electrolyte-plasma polishing, plasma enhanced chemical vapor deposition and magnetron sputtering, and a static calibration experiment system for sensitivity and accuracy of the temperature measuring tool for the film thermocouple was established, and Seebeck coefficient of the film thermocouple was obtained. According to the actual cutting conditions, the wireless temperature measuring system of the thin film thermocouple tool was built and the field cutting test was carried out to obtain the influence law of different cutting parameters on the cutting temperature, and further verify the feasibility of the thin film temperature measuring sensor. The research results show that: Seebeck coefficients of the two kinds of thermocouples prepared by the NiCr/NiSi thin film thermocouple temperature measuring tool are 34.97 μV/°C and 34.96 μV/°C, and the slope of the temperature data fitting curve is 1.00398 and 0.997475, respectively. The linear correlation coefficient R2 is close to 1, which is close to the standard K-type thermocouple, which shows good sensitivity and accuracy. At the same time, the temperature measurement results are close to the commercial standard K thermocouple, and the error is less than 5%, indicating that the developed film thermocouple has a high measurement accuracy and can meet the needs of temperature measurement. Actual cutting test is carried out with developed wireless temperature measuring device of thin film thermocouple, which shows this device can meet the requirements of tool temperature measurement, and the feasibility of thin film temperature measuring sensor is further verified. The research provide technical reference for industrial intelligent manufacturing in order to realize the wireless measurement of cutting area temperature of tool front.
Lexicon and Logic: A Corpus-Based Investigation Into a Connection Between Prepositional Senses and Quantifier Scope
Authors: Grudzińska Justyna , Siemieniuk Aleksandra , Leczkowski Aleksander
Published: January 2024

Previous research has indicated that abstract grammatical rules and forms fall short of predicting quantifier scope and that lexical/pragmatic knowledge plays a significant part in quantifier scope disambiguation (QSD). More recent works have argued that world knowledge in the form of relations among objects may be salient to QSD. This paper contributes to this line of research by providing support to the claim that there is a connection between our lexical knowledge about preposition meanings and quantifier scope. More specifically, we propose that certain prepositional senses encode dependency relations that have an effect on scope-taking preferences. For example, the preposition of expressing ‘part-whole sense’ contributes to our choice of the inverse scope reading for the construction a day of every month by introducing a dependency between wholes (months) and their respective parts (days). Quantifying over this dependency yields the inverse scope reading: for every month, there is a different day that belongs to it (every month > a day). Furthermore, universal quantification in locative and temporal prepositional phrases tends to support inverse scope. For example, the locative preposition on — as in a store on each side of the street — implies ‘disjointness’ (objects do not occupy more than one place at a time), and hence can be interpreted as a dependency between each side of the street and the respective stores located on them. Quantifying over this dependency yields the inverse scope reading: for each side of the street, there is a different store located on it (each side of the street > a store). For studying the connection between prepositional senses and quantifier scope in the wild, we use a scope-disambiguated corpus created by AnderBois et al. ( 2012), additionally annotated with prepositional senses using the Semantic Network of Adposition and Case Supersenses (SNACS) scheme proposed in Schneider et al. ( 2018, 2020). The results of the corpus study combined with psycholinguistic experiments support the claim made here that certain prepositional senses are strong predictors of quantifier scope.
Full-model estimation for non-parametric multivariate finite mixture models
Authors: Du Roy de Chaumaray Marie , Marbac Matthieu
Published: January 2024

This paper addresses the problem of full-model estimation for non-parametric finite mixture models. It presents an approach for selecting the number of components and the subset of discriminative variables (i.e. the subset of variables having different distributions among the mixture components) by considering an upper bound on the number of components (this number being allowed to increase with the sample size). The proposed approach considers a discretization of each variable into B bins and a penalization of the resulting log-likelihood. Considering that the number of bins tends to infinity as the sample size tends to infinity, we prove that our estimator of the model (number of components and subset of relevant variables for clustering) is consistent under a suitable choice of the penalty term. The relevance of our proposal is illustrated on simulated and benchmark data.
Striking energy deals in disputed seas: the case of the Gaza Marine gas field
Authors: Rettig Elai , Spanier Benny
Published: January 2024

In June 2023, Israel approved the development of Gaza Marine, a small offshore gas field near the Gaza Strip that has remained dormant since its discovery in 2000. The field can potentially benefit the Palestinian Authority (PA) in terms of export revenue and energy independence. However, the legal status of the field remains unclear, and the 2023 Israel–Hamas war further complicated this matter. On the one hand, although Israel has not made any legal claim to Gaza Marine, its approval to develop the field is still considered necessary by all parties involved. On the other hand, while the PA views itself as the rightful owner of the field, it has had no effective control over Gaza’s coastline or waters since 2007, weakening its claim. This article reviews the complex history and evolving legal status of the Gaza Marine gas field up until the 2023 war. It argues that there is still room for optimism regarding the future development of the field, especially when considering its similarities to the successful 2022 maritime agreement between Israel and Lebanon.
Microbiological profile of long COVID and associated clinical and radiological findings: a prospective cross-sectional study
Authors: Dey Monalisa , Mishra Baijayantimala , Mohapatra Prasanta Raghab , Mohakud Sudipta , Behera Bijayini
Published: January 2024

Objective

To study the frequency of microbiological etiology of respiratory infections in patients with long COVID and their associated clinical and radiological findings.

Methods

Nasopharyngeal swabs and sputum specimens were collected from 97 patients with respiratory illness stemming from long COVID. The specimens were assessed for their microbiological profile (bacteria and virus) and their association with the overall clinical and radiological picture.

Results

In total, 23 (24%) patients with long COVID had viral infection (n = 12), bacterial infection (n = 9), or coinfection (n = 2). Microorganisms were detected at significantly higher rates in hospitalized patients, patients with moderate COVID-19, and patients with asthma (P < .05). Tachycardia (65%) was the most common symptom at presentation. A statistically significant number of patients with long COVID who had viral infection presented with cough and myalgia; and a statistically significant number of patients with long COVID who had bacterial infection presented with productive coughing (P < .05). Post-COVID fibrotic changes were found in 61% of cohort patients (31/51).

Conclusion

A decreasing trend of respiratory pathogens (enveloped viruses and bacteria) was found in long COVID. An analysis including a larger group of viral- or bacterial-infected patients with long COVID is needed to obtain high-level evidence on the presenting symptoms (cough, myalgia) and their association with the underlying comorbidities and severity.
Disguised Among the Sea: The Implications of Artificial Islands on Casualty Care in the Indo-Pacific
Authors: Leone Ryan M , Remondelli Mason H , Brill Jason B , Baker Jay B
Published: January 2024

As reported in the 2022 Biden-Harris National Security Strategy, China is perceived as the primary U.S. competitor with the intent and means to become the world’s greatest superpower. China’s efforts, which are at odds with America’s ambition to maintain its global influence, are complemented by ostensibly harmless “gray zone tactics,” defined as coercive geopolitical, economic, military, and cyber activities below the use of kinetic military force. Such tactics may be utilized with seemingly innocuous intentions, but in reality, they can complicate U.S. combat casualty care in the event of an Indo-Pacific conflict. One tactic of particular impact is China’s development of artificial islands throughout the South China Sea. By creating these islands, China is expanding its reach beyond its continental borders. These islands, alongside China’s well-developed naval and missile capabilities, will cause disruptions to U.S. casualty care staging, medical resupply, and aeromedical evacuations. To mitigate those threats, the USA should implement a robust regional Combatant Command Trauma System, improve global health security cooperation with local partner nations, and implement irregular or guerilla trauma systems that meet medical needs in impromptu, clandestine settings. Operational recommendations based on these efforts could include pre-positioning tactical combat casualty care and damage control resuscitation supplies and developing with nearby host-nation evacuation platforms such as small boat operators. These solutions, among others, require years of training, relationship-building, and capability development to institute successfully. As a result, U.S. Military leaders should act now to incorporate these strategies into their irregular warfare, low-intensity conflict, and large-scale combat operation toolkits.
The role of environment and AGN feedback in quenching local galaxies: comparing cosmological hydrodynamical simulations to the SDSS
Authors: Goubert Paul H , Bluck Asa F L , Piotrowska Joanna M , Maiolino Roberto
Published: January 2024

We present an analysis of the quenching of local observed and simulated galaxies, including an investigation of the dependence of quiescence on both intrinsic and environmental parameters. We apply an advanced machine learning technique utilizing random forest classification to predict when galaxies are star forming or quenched. We perform separate classification analyses for three groups of galaxies: (a) central galaxies, (b) high-mass satellites ($M_{*} \gt 10^{10.5}\,{\rm {\rm M}_{\odot }}$), and (c) low-mass satellites ($M_{*} \lt 10^{10}\,{\rm {\rm M}_{\odot }}$) for three cosmological hydrodynamical simulations (Evolution and Assembly of GaLaxies and their Environments, Illustris, and IllustrisTNG), and observational data from the Sloan Digital Sky Survey. The simulation results are unanimous and unambiguous: quiescence in centrals and high-mass satellites is best predicted by intrinsic parameters (specifically central black hole mass), while it is best predicted by environmental parameters (specifically halo mass) for low-mass satellites. In observations, we find black hole mass to best predict quiescence for centrals and high-mass satellites, exactly as predicted by the simulations. However, local galaxy overdensity is found to be most predictive parameter for low-mass satellites. None the less, both simulations and observations do agree that it is environment which quenches low-mass satellites. We provide evidence which suggests that the dominance of local overdensity in classifying low-mass systems may be due to the high uncertainty in halo mass estimation from abundance matching, rather than it being fundamentally a more predictive parameter. Finally, we establish that the qualitative trends with environment predicted in simulations are recoverable in the observation space. This has important implications for future wide-field galaxy surveys.
Dust–gas dynamics driven by the streaming instability with various pressure gradients
Authors: Baronett Stanley A , Yang Chao-Chin , Zhu Zhaohuan
Published: January 2024

The streaming instability, a promising mechanism to drive planetesimal formation in dusty protoplanetary discs, relies on aerodynamic drag naturally induced by the background radial pressure gradient. This gradient should vary in discs, but its effect on the streaming instability has not been sufficiently explored. For this purpose, we use numerical simulations of an unstratified disc to study the non-linear saturation of the streaming instability with mono-disperse dust particles and survey a wide range of gradients for two distinct combinations of the particle stopping time and the dust-to-gas mass ratio. As the gradient increases, we find most kinematic and morphological properties increase but not always in linear proportion. The density distributions of tightly coupled particles are insensitive to the gradient whereas marginally coupled particles tend to concentrate by more than an order of magnitude as the gradient decreases. Moreover, dust–gas vortices for tightly coupled particles shrink as the gradient decreases, and we note higher resolutions are required to trigger the instability in this case. In addition, we find various properties at saturation that depend on the gradient may be observable and may help reconstruct models of observed discs dominated by streaming turbulence. In general, increased dust diffusion from stronger gradients can lower the concentration of dust filaments and can explain the higher solid abundances needed to trigger strong particle clumping and the reduced planetesimal formation efficiency previously found in vertically stratified simulations.
Star formation efficiency across large-scale galactic environments
Authors: Ghodsi Laya , Man Allison W S , Donevski Darko , Davé Romeel , Lim Seunghwan , Lovell Christopher C , Narayanan Desika
Published: January 2024

Environmental effects on the formation and evolution of galaxies have been one of the leading questions in galaxy studies during the past few decades. In this work, we investigate the relationship between the star formation activity of galaxies and their environmental matter density using the cosmological hydrodynamic simulation Simba. The galactic star formation activity indicators that we explore include the star formation efficiency (SFE), specific star formation rate (sSFR), and molecular hydrogen mass fraction ($f^{*}_{\mathrm{H_2}}$), and the environment is considered as the large-scale environmental matter density, calculated based on the stellar mass of nearby galaxies on a 1 h−1 Mpc  grid using the cloud in cell method. Our sample includes galaxies with $9\lt \log \frac{M_*}{{\rm M}_{\odot }}$ at 0 < z < 4, divided into three stellar mass bins to disentangle the effects of stellar mass and environment on the star formation activity of galaxies. For low- to intermediate-mass galaxies at low redshifts (z < 1.5), we find that the star formation efficiency of those in high-density regions are ∼0.3 dex lower than those in low-density regions. However, there is no significant environmental dependence of the star formation efficiency for massive galaxies over all our redshift range, and low- to intermediate-mass galaxies at high redshifts (z > 1.5). We present a scaling relation for the depletion time of cold molecular hydrogen (tdepl = 1/SFE) as a function of galaxy parameters including environmental density. Our findings provide a framework for quantifying the environmental effects on the star formation activities of galaxies as a function of stellar mass and redshift. The most significant environmental dependence is seen at later cosmic times (z < 1.5) and towards lower stellar masses ($9\lt \log \frac{M_*}{{\rm M}_{\odot }}\lt 10$). Future large galaxy surveys can use this framework to look for the environmental dependence of the star formation activity and examine our predictions.
Assembling a high-precision abundance catalogue of solar twins in GALAH for phylogenetic studies
Authors: Walsen Kurt , Jofré Paula , Buder Sven , Yaxley Keaghan , Das Payel , Yates Robert M , Hua Xia , Signor Theosamuele , Eldridge Camilla , Rojas-Arriagada Alvaro , Tissera Patricia B , Johnston Evelyn , Aguilera-Gómez Claudia , Zoccali Manuela , Gilmore Gerry , Foley Robert
Published: January 2024

Stellar chemical abundances have proved themselves a key source of information for understanding the evolution of the Milky Way, and the scale of major stellar surveys such as GALAH have massively increased the amount of chemical data available. However, progress is hampered by the level of precision in chemical abundance data as well as the visualization methods for comparing the multidimensional outputs of chemical evolution models to stellar abundance data. Machine learning methods have greatly improved the former; while the application of tree-building or phylogenetic methods borrowed from biology are beginning to show promise with the latter. Here, we analyse a sample of GALAH solar twins to address these issues. We apply The Cannon algorithm to generate a catalogue of about 40 000 solar twins with 14 high precision abundances which we use to perform a phylogenetic analysis on a selection of stars that have two different ranges of eccentricities. From our analyses, we are able to find a group with mostly stars on circular orbits and some old stars with eccentric orbits whose age–[Y/Mg] relation agrees remarkably well with the chemical clocks published by previous high precision abundance studies. Our results show the power of combining survey data with machine learning and phylogenetics to reconstruct the history of the Milky Way.
Are odd radio circles virial shocks around massive galaxies? Implications for cosmic-ray diffusion in the circumgalactic medium
Authors: Yamasaki Shotaro , Sarkar Kartick C , Li Zhaozhou
Published: January 2024

Recently, a new population of circular radio (∼GHz) objects has been discovered at high Galactic latitudes, called the odd radio circles (ORCs). A fraction of the ORCs encircles massive galaxies in the sky with stellar mass ∼1011 M⊙ situated at z = 0.2–0.6, suggesting a possible physical connection. In this paper, we explore the possibility that these radio circles originate from the accretion shocks/virial shocks around massive (${\gtrsim} 10^{13}\, \ {\rm M}_\odot$) dark matter halo at z ∼ 0.5. We found that the radio flux density of the emitting shell is marginally consistent with the ORCs. We also find that pure advection of electrons from the shock results in a radio-emitting shell that is considerably narrower than the observed one due to strong inverse-Compton cooling of electrons. Instead, we show that the diffusion of cosmic-ray (CR) electrons plays a significant role in increasing the width of the shell. We infer a diffusion coefficient, $D_{\rm cr} \sim 10^{30}\ {\rm cm^2\, s^{-1}}$, consistent with the values expected for low-density circumgalactic medium (CGM). If ORCs indeed trace virial shocks, then our derived CR diffusion coefficient represents one of the few estimations available for the low-density CGM. Finally, we show that the apparent discrepancy between ORC and halo number density can be mitigated by considering an incomplete halo virialization and the limited radiation efficiency of shocks. This study therefore opens up new avenues to study such shocks and non-thermal particle acceleration within them. Furthermore, our results suggest that low-mass galaxies (≲1013 M⊙) may not show ORCs due to their significantly lower radio surface brightness.
MaNGA AGN dwarf galaxies (MAD) – I. A new sample of AGNs in dwarf galaxies with spatially-resolved spectroscopy
Authors: Mezcua M , Sánchez H Domínguez
Published: January 2024

The finding of active galactic nuclei (AGNs) in dwarf galaxies has important implications for galaxy evolution and supermassive black hole formation models. Yet, how AGNs in dwarf galaxies form is still debated, in part due to scant demographics. We use the MaNGA survey, comprising ∼10 000 galaxies at z < 0.15, to identify AGN dwarf galaxies using a spaxel-by-spaxel classification in three spatially-resolved emission-line diagnostic diagrams (the [N ii]-, [S ii]-, and [O i]-BPT) and the WHAN diagram. This yields a sample of 664 AGN dwarf galaxies, the largest to date, and an AGN fraction of $\sim 20~{{\ \rm per\ cent}}$ that is significantly larger than that of single-fibre-spectroscopy studies (i.e. $\sim 1~{{\ \rm per\ cent}}$). This can be explained by the lower bolometric luminosity (<1042 erg s−1) and accretion rate (sub-Eddington) of the MaNGA AGN dwarf galaxies. We additionally identify 1176 SF-AGNs (classified as star-forming in the [N ii]-BPT but as AGNs in the [S ii]- and [O i]-BPT), 122 Composite, and 173 LINER sources. The offset between the optical centre of the galaxy and the median position of the AGN spaxels is more than 3 arcsec for ∼62% of the AGNs, suggesting that some could be off-nuclear. We also identify seven new broad-line AGNs with log MBH  = 5.0–5.9 M⊙. Our results show how integral-field spectroscopy is a powerful tool for uncovering faint and low-accretion AGNs and better constraining the demographics of AGNs in dwarf galaxies.
A global survey of small RNA interactors identifies KhpA and KhpB as major RNA-binding proteins in Fusobacterium nucleatum
Authors: Zhu Yan , Ponath Falk , Cosi Valentina , Vogel Jörg
Published: January 2024

The common oral microbe Fusobacterium nucleatum has recently drawn attention after it was found to colonize tumors throughout the human body. Fusobacteria are also interesting study systems for bacterial RNA biology as these early-branching species encode many small noncoding RNAs (sRNAs) but lack homologs of the common RNA-binding proteins (RBPs) CsrA, Hfq and ProQ. To search for alternate sRNA-associated RBPs in F. nucleatum, we performed a systematic mass spectrometry analysis of proteins that co-purified with 19 different sRNAs. This approach revealed strong enrichment of the KH domain proteins KhpA and KhpB with nearly all tested sRNAs, including the σE-dependent sRNA FoxI, a regulator of several envelope proteins. KhpA/B act as a dimer to bind sRNAs with low micromolar affinity and influence the stability of several of their target transcripts. Transcriptome studies combined with biochemical and genetic analyses suggest that KhpA/B have several physiological functions, including being required for ethanolamine utilization. Our RBP search and the discovery of KhpA/B as major RBPs in F. nucleatum are important first steps in identifying key players of post-transcriptional control at the root of the bacterial phylogenetic tree.
H2A.Z is involved in premature aging and DSB repair initiation in muscle fibers
Authors: Belotti Edwige , Lacoste Nicolas , Iftikhar Arslan , Simonet Thomas , Papin Christophe , Osseni Alexis , Streichenberger Nathalie , Mari Pierre-Olivier , Girard Emmanuelle , Graies Mohamed , Giglia-Mari Giuseppina , Dimitrov Stefan , Hamiche Ali , Schaeffer Laurent
Published: January 2024

Histone variants are key epigenetic players, but their functional and physiological roles remain poorly understood. Here, we show that depletion of the histone variant H2A.Z in mouse skeletal muscle causes oxidative stress, oxidation of proteins, accumulation of DNA damages, and both neuromuscular junction and mitochondria lesions that consequently lead to premature muscle aging and reduced life span. Investigation of the molecular mechanisms involved shows that H2A.Z is required to initiate DNA double strand break repair by recruiting Ku80 at DNA lesions. This is achieved via specific interactions of Ku80 vWA domain with H2A.Z. Taken as a whole, our data reveal that H2A.Z containing nucleosomes act as a molecular platform to bring together the proteins required to initiate and process DNA double strand break repair.
Understanding intercalative modulation of G-rich sequence folding: solution structure of a TINA-conjugated antiparallel DNA triplex
Authors: Garavís Miguel , Edwards Patrick J B , Serrano-Chacón Israel , Doluca Osman , Filichev Vyacheslav V , González Carlos
Published: January 2024

We present here the high-resolution structure of an antiparallel DNA triplex in which a monomer of para-twisted intercalating nucleic acid (para-TINA: (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol) is covalently inserted as a bulge in the third strand of the triplex. TINA is a potent modulator of the hybridization properties of DNA sequences with extremely useful properties when conjugated in G-rich oligonucleotides. The insertion of para-TINA between two guanines of the triplex imparts a high thermal stabilization (ΔTM = 9ºC) to the structure and enhances the quality of NMR spectra by increasing the chemical shift dispersion of proton signals near the TINA location. The structural determination reveals that TINA intercalates between two consecutive triads, causing only local distortions in the structure. The two aromatic moieties of TINA are nearly coplanar, with the phenyl ring intercalating between the flanking guanine bases in the sequence, and the pyrene moiety situated between the Watson–Crick base pair of the two first strands. The precise position of TINA within the triplex structure reveals key TINA–DNA interactions, which explains the high stabilization observed and will aid in the design of new and more efficient binders to DNA.
Structural insights into the HDAC4–MEF2A–DNA complex and its implication in long-range transcriptional regulation
Authors: Dai Shuyan , Guo Liang , Dey Raja , Guo Ming , Zhang Xiangqian , Bates Darren , Cayford Justin , Jiang Longying , Wei Hudie , Chen Zhuchu , Zhang Ye , Chen Lin , Chen Yongheng
Published: January 2024

Class IIa Histone deacetylases (HDACs), including HDAC4, 5, 7 and 9, play key roles in multiple important developmental and differentiation processes. Recent studies have shown that class IIa HDACs exert their transcriptional repressive function by interacting with tissue-specific transcription factors, such as members of the myocyte enhancer factor 2 (MEF2) family of transcription factors. However, the molecular mechanism is not well understood. In this study, we determined the crystal structure of an HDAC4–MEF2A–DNA complex. This complex adopts a dumbbell-shaped overall architecture, with a 2:4:2 stoichiometry of HDAC4, MEF2A and DNA molecules. In the complex, two HDAC4 molecules form a dimer through the interaction of their glutamine-rich domain (GRD) to form the stem of the ‘dumbbell’; while two MEF2A dimers and their cognate DNA molecules are bridged by the HDAC4 dimer. Our structural observations were then validated using biochemical and mutagenesis assays. Further cell-based luciferase reporter gene assays revealed that the dimerization of HDAC4 is crucial in its ability to repress the transcriptional activities of MEF2 proteins. Taken together, our findings not only provide the structural basis for the assembly of the HDAC4–MEF2A–DNA complex but also shed light on the molecular mechanism of HDAC4-mediated long-range gene regulation.
Flexible structural arrangement and DNA-binding properties of protein p6 from Bacillus subtillis phage φ29
Authors: Alcorlo Martín , Luque-Ortega Juan Román , Gago Federico , Ortega Alvaro , Castellanos Milagros , Chacón Pablo , de Vega Miguel , Blanco Luis , Hermoso José M , Serrano Manuel , Rivas Germán , Hermoso Juan A
Published: January 2024

The genome-organizing protein p6 of Bacillus subtilis bacteriophage φ29 plays an essential role in viral development by activating the initiation of DNA replication and participating in the early-to-late transcriptional switch. These activities require the formation of a nucleoprotein complex in which the DNA adopts a right-handed superhelix wrapping around a multimeric p6 scaffold, restraining positive supercoiling and compacting the viral genome. Due to the absence of homologous structures, prior attempts to unveil p6’s structural architecture failed. Here, we employed AlphaFold2 to engineer rational p6 constructs yielding crystals for three-dimensional structure determination. Our findings reveal a novel fold adopted by p6 that sheds light on its self-association mechanism and its interaction with DNA. By means of protein–DNA docking and molecular dynamic simulations, we have generated a comprehensive structural model for the nucleoprotein complex that consistently aligns with its established biochemical and thermodynamic parameters. Besides, through analytical ultracentrifugation, we have confirmed the hydrodynamic properties of the nucleocomplex, further validating in solution our proposed model. Importantly, the disclosed structure not only provides a highly accurate explanation for previously experimental data accumulated over decades, but also enhances our holistic understanding of the structural and functional attributes of protein p6 during φ29 infection.
Porcine endogenous retroviruses in xenotransplantation
Authors: Denner Joachim
Published: January 2024

Xenotransplantation using pig cells, tissues or organs is under development to alleviate the shortage of human donor organs. Meanwhile, remarkably long survival times of pig organs in non-human primates have been reported, as well as the functionality of pig kidneys and hearts in brain-dead humans. Most importantly, two transplantations of pig hearts in patients were performed with survival times of the patients of 8 and 6 weeks. Xenotransplantation may be associated with the transmission of porcine microorganisms including viruses to the recipient. Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs and cannot be eliminated like other viruses can. PERVs are able to infect certain human cells and therefore pose a risk for xenotransplantation. It is well known that retroviruses are able to induce tumors and immunodeficiencies. However, until now, PERVs were not transmitted in all infection experiments using small animals and non-human primates, in all preclinical xenotransplantation trials in non-human primates and in all clinical trials in humans. In addition, several strategies including antiretrovirals, PERV-specific small interfering RNA, vaccines and genome editing using CRISPR/Cas have been developed to prevent PERV transmission.
Abundance models of endemic birds of the Sierra Nevada de Santa Marta, northern South America, suggest small population sizes and dependence on montane elevations
Authors: Botero-Delgadillo Esteban , Meza-Angulo Enrick , Bayly Nicholas J
Published: January 2024

Abundance measures are almost non-existent for several bird species threatened with extinction, particularly range-restricted Neotropical taxa, for which estimating population sizes can be challenging. Here we use data collected over 9 years to explore the abundance of 11 endemic birds from the Sierra Nevada de Santa Marta (SNSM), one of Earth’s most irreplaceable ecosystems. We established 99 transects in the “Cuchilla de San Lorenzo” Important Bird Area within native forest, early successional vegetation, and areas of transformed vegetation by human activities. A total of 763 bird counts were carried out covering the entire elevation range in the study area (~175–2,650 m). We applied hierarchical distance-sampling models to assess elevation- and habitat-related variation in local abundance and obtain values of population density and total and effective population size. Most species were more abundant in the montane elevational range (1,800–2,650 m). Habitat-related differences in abundance were only detected for 5 species, which were more numerous in either early succession, secondary forest, or transformed areas. Inferences of effective population size indicated that at least 4 endemics likely maintain populations no larger than 15,000–20,000 mature individuals. Inferences of species’ area of occupancy and effective population size were lower than most values previously described, a possible consequence of increasing anthropogenic threats. At least 4 of the endemics exceeded criteria for threatened species listing and a thorough evaluation of their extinction risk should be conducted. Population strongholds for most of the study species were located on the northern and western slopes of the SNSM between 1,500 and 2,700 m. We highlight the urgent need for facilitating effective protection of native vegetation in premontane and montane ecosystems to safeguard critical habitats for the SNSM’s endemic avifauna. Follow-up studies collecting abundance data across the SNSM are needed to obtain precise range-wide density estimations for all species.
Heavy Ion Injection of Fixed-Field Alternating Gradient Accelerator
Authors: Yonemura Yujiro , Arima Hidehiko , Nishibata Hiroki , Teranishi Takashi , Wakasa Tomotsugu , Ikeda Nobuo , Watanabe Kenichi , Shigyo Nobuhiro , Iwamura Tatsunori , Adachi Kyosuke , Takamatsu Koki , Kotani Motoki , Tanaka Hisato , Matsunaga Rintaro , Matsumoto Taichi , Takenaka Kyohei , Kajihara Takafumi , Matsunaga Sotaro , Shinohara Yusuke , Mori Yoshiharu
Published: January 2024

Much research in recent years has focused on circular accelerators that accelerate and store secondary particles with a large momentum spread, such as muons, unstable nuclei, and heavy ions with different charge states. A fixed-field alternating gradient (FFAG) accelerator with large transverse and momentum acceptance has obvious advantages for such requirements. A versatile beam injection method is required to accelerate secondary particles with a large momentum spread and different charge states with an FFAG accelerator. In the present study, a method for charge exchange injection of positive heavy ions using the large momentum acceptance of an FFAG accelerator is proposed. A charge injection system, which converts a He1+ beam to a He2+ beam, is developed for a 150 MeV FFAG accelerator at the Center for Accelerator and Beam Applied Science (CABAS) of Kyushu University. As the first step to verify the injection method, an orbit shift from one charge state to the other is demonstrated. This is the first demonstration of heavy ion injection using an FFAG accelerator.
Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S)
Authors: Singh Ajay , Rastogi Ashu , Puri Goverdhan Dutt , Ganesh Venkata , Naik Naveen Bal , Kajal Kamal , Kahlon Shubhkarman , Soni Shiv Lal , Kaloria Narender , Saini Kulbhushan , Hazarika Amarjyoti , Mahajan Varun , Singla Karan , Bhadada Sanjay , Soni Vaishali
Published: January 2024

Background

efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied.

Objective

effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19.

Methods

participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo.

Outcomes

primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality.

Results

in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10–16) and 13 (12–18) ng/ml (P = 0.06) at baseline; and 60 (55–65) ng/ml and 4 (1–7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2–5) versus 5 (95% CI, 3–7), P = 0.01, intergroup difference − 2 (95% CI, −4 to −0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D.

Conclusions

single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19.

ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021.

What is already known on this topic—vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs.

What this study adds—high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19.

How this study might affect research, practice or policy—vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.
Identifying high cholesterol in the ambulance setting: a mixed-methods cohort study to tackle health inequality
Authors: Charlton Karl , Rees Jon , Burrow Emma
Published: January 2024

Background

Individuals with low socio-economic status (SES) have disproportionate rates of cardio- vascular disease (CVD) but poorer engagement with preventative health. This study aimed to compare characteristics of individuals with and without hyperlipidaemia and describe their health behaviours.

Methods

A mixed-methods study between January and December 2022. Patients aged ≥40 years using the ambulance service with blood pressure of ≥140/90 had their total cholesterol measured using a point of care device. Data including blood pressure, smoking status, National Early Warning Score 2 and clinical frailty scale (CFS) were analysed.

Results

Of 203 patients (59% female, mean age 65.7 years), 115 (56.7%) had total cholesterol ≥5.1 mmol/L. Thirty patients (14.8%) sought treatment and received either statins (n = 9; 4.4%), dietary modification (n = 7; 3.4%) or no further intervention (n = 14; 6.9%), whilst 85 patients (41.9%) took no further action. Lower CFS (OR 0.53 [0.31–0.93]) and higher total cholesterol (OR 2.07 [1.03–2.76]) predicted seeking further management. SES was not associated with hyperlipidaemia or likelihood of seeking further management, rather this was dictated by competing co-morbidity, poor health literacy and digital divide.

Conclusions

Undiagnosed hyperlipidaemia exists in patients using the ambulance service, irrespective of SES. Individual and healthcare system factors prevent engagement in cholesterol lowering behaviours.
A rare form of calcinosis in patients with systemic sclerosis–myositis overlap: report of four cases
Authors: Achieng Sheilla , Harris Jonathan , Samaranayaka Muditha , Herrick Ariane L
Published: January 2024

Objectives

Calcinosis is a well-described entity that occurs in patients with systemic sclerosis (SSc) and dermatomyositis (DM). Calcinosis in SSc typically occurs over pressure points and is usually nodular. We present a case series of four patients with SSc with a much rarer, diffuse form of calcinosis to illustrate this poorly recognized pattern of extensive and debilitating disease.

Methods

Four patients with SSc and extensive calcinosis were identified from patients attending a tertiary rheumatology centre in the preceding 3 years. Their electronic case notes, radiographic images and medical photographs were reviewed.

Results

All four patients had the diffuse cutaneous subtype of SSc (dcSSc) and additionally a myositis overlap. This was in the context of 102 of 461 (22%) patients with SSc whose clinical details had been recorded in the preceding 3 years having dcSSc. Their ages at diagnosis ranged from 27 to 65 years. Three were female, two were anti-Scl70 antibody positive, and two were anti-PMScl antibody positive. Development of calcinosis occurred between 1 and 6 years after onset of SSc. Plain radiography showed very extensive calcinosis in various sites, distributed in a pattern akin to sheets of calcium-containing deposits in the skin and subcutaneous tissue.

Conclusions

Although calcinosis is common in SSc, extensive sheet-like calcinosis is very rare. Our experience suggests that when this form of calcinosis does occur, this is in the context of the diffuse cutaneous subtype of disease and with myositis overlap. The four cases described should raise awareness of this unusual and extensive pattern of disease.
Vasculitic neuropathy-related disability, pain, quality of life, and autonomic symptoms: a survey of 312 patients
Authors: Collins Michael P , Hadden Robert D M , Luqmani Raashid A
Published: January 2024

Objectives

To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis.

Methods

Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey.

Results

Three hundred and twelve patients (71% female) responded. Median age was 61–70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [s.d. 17.3] vs 75.2 [16.7]; P < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1–4] vs 0.5 [0–2]; P < 0.0001) and modified Rankin scale (median 2 [interquartile range 1–3] vs 2 [1–2)]; P = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [s.d. 2.6] vs 3.5 [2.8]; P = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [s.d. 0.29] vs 0.69 [0.28]; P < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy).

Conclusion

Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis.
Multimorbidity in psoriasis as a risk factor for psoriatic arthritis: a population-based study
Authors: Karmacharya Paras , Chakradhar Rikesh , Hulshizer Cassondra A , Gunderson Tina M , Ogdie Alexis , Davis III John M , Wright Kerry , Tollefson Megha M , Duarte-García Alí , Bekele Delamo , Maradit-Kremers Hilal , Crowson Cynthia S
Published: January 2024

Objectives

To examine multimorbidity in psoriasis and its association with the development of psoriatic arthritis (PsA).

Methods

A retrospective cohort study was performed using the Rochester Epidemiology Project. Population-based incidence (2000–09) and prevalence (1 January 2010) cohorts of psoriasis were identified by manual chart review. A cohort of individuals without psoriasis (comparators) were identified (1:1 matched on age, sex and county). Morbidities were defined using two or more Clinical Classification Software codes ≥30 days apart within prior 5 years. PsA was defined using ClASsification of Psoriatic ARthritis (CASPAR) criteria. χ2 and rank-sum tests were used to compare morbidities, and age-, sex- and race-adjusted Cox models to examine the association of baseline morbidities in psoriasis with development of PsA.

Results

Among 817 incident psoriasis patients, the mean age was 45.2 years with 52.0% females, and 82.0% moderate/severe psoriasis. No multimorbidity differences were found between incident psoriasis patients and comparators. However, in the 1088 prevalent psoriasis patients, multimorbidity was significantly more common compared with 1086 comparators (odds ratio 1.35 and 1.48 for two or more and five or more morbidities, respectively). Over a median 13.3-year follow-up, 23 patients (cumulative incidence: 2.9% by 15 years) developed PsA. Multimorbidity (two or more morbidities) was associated with a 3-fold higher risk of developing PsA.

Conclusion

Multimorbidity was more common in the prevalent but not incident cohort of psoriasis compared with the general population, suggesting that patients with psoriasis may experience accelerated development of multimorbidity. Moreover, multimorbidity at psoriasis onset significantly increased the risk of developing PsA, highlighting the importance of monitoring multimorbid psoriasis patients for the development of PsA.
A path to Glucocorticoid Stewardship: a critical review of clinical recommendations for the treatment of systemic lupus erythematosus
Authors: Bertsias George , Askanase Anca , Doria Andrea , Saxena Amit , Vital Edward M
Published: January 2024

Glucocorticoids (GCs) have revolutionized the management of SLE, providing patients with rapid symptomatic relief and preventing flares when maintained at low dosages. However, there are increasing concerns over GC-associated adverse effects and organ damage, which decrease patients’ quality of life (QOL) and increase healthcare costs. This highlights the need to balance effective GC use and minimize toxicity in patients with SLE. Herein, we provide an overview of the theoretical considerations and clinical evidence, in addition to the variations and similarities across nine national and eight international recommendations regarding the use of GCs across SLE manifestations and how these compare with real-world usage. In line with this, we propose possible actions toward the goal of GC Stewardship to improve the QOL for patients with lupus while managing the disease burden.