bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher serum uric acid is associated with poorer cognitive performance in healthy middle-aged people: a cross-sectional study
Authors: Khaled Yousef , Abdelhamid Aya A. , Al-Mazroey Hissa , Almannai Abdulrahman K. , Fetais Sara , Al-Srami Aisha S. , Ahmed Shaima , Al-Hajri Noora , Mustafa Ayman , Chivese Tawanda , Djouhri Laiche
Published: June 2023

Age-related cognitive impairment can occur many years before the onset of the clinical symptoms of dementia. Uric acid (UA), a metabolite of purine-rich foods, has been shown to be positively associated with improved cognitive function, but such association remains controversial. Moreover, most of the previous studies investigating the association included elderly participants with memory-related diseases. Therefore, the present study aimed at investigating whether serum UA (sUA) is associated with cognitive performance in healthy middle-aged individuals. We conducted a cross-sectional study on a cohort of middle-aged individuals (40–60 years old) who participated in the Qatar Biobank. The participants had no memory-related diseases, schizophrenia, stroke, or brain damage. They were divided according to sUA level into a normal group (< 360 μmol/L) and a high group (≥ 360 μmol/L), and underwent an assessment of cognitive function using the Cambridge Neuropsychological Test Automated Battery. Two cognitive function domains were assessed: (a) speed of reaction/reaction time and (b) short-term visual memory. The median age of the 931 participants included in the study was 48.0 years (IQR: 44.0, 53.0), of which 47.6% were male. Adjusted multivariable linear regression analyses showed that higher sUA is associated with poorer performance on the visual memory domain of cognitive function (β = − 6.87, 95% CI − 11.65 to − 2.10, P = 0.005), but not on the speed of reaction domain (β = − 55.16, 95% CI − 190.63 to 80.30, P = 0.424). Our findings support previous studies suggesting an inverse association between high sUA levels and cognitive function in elderly and extend the evidence for such a role to middle-aged participants. Further prospective studies are warranted to investigate the relationship between UA and cognition.
One-step thoracotomy approach for atrial-esophageal fistula repair without cardiopulmonary bypass
Authors: Lee June , Yoon Jeashin , Hong Seok Beom , Kim Yong Han , Kim Hwan Wook , Kim Do Yeon
Published: June 2023

Atrial-esophageal fistula is an extremely rare disease and a life-threatening complication after catheter ablation for atrial fibrillation. There is no consensus on the management or repair for atrial-esophageal fistula which has a high mortality rate. Here, we describe a lateral thoracotomy approach focused on simplifying the repair procedure for atrial-esophageal fistula in two patients.
Pseudodifferential operators with completely periodic symbols
Authors: Garello Gianluca , Morando Alessandro
Published: June 2023

Motivated by the recent paper of Boggiatto–Garello (J Pseudo-Differ Oper Appl 11:93–117, 2020) where a Gabor operator is regarded as pseudodifferential operator with symbol $$p(x,\omega )$$

p
(
x
,
ω
)

periodic on both the variables, we study the continuity and invertibility, on general time frequency invariant spaces, of pseudodifferential operators with completely periodic symbol and general $$\tau $$
τ
quantization.
Hypothyroidism, lipids, and lipidomics
Authors: Jonklaas Jacqueline
Published: June 2023

Purpose

Hypothyroidism is a relatively common endocrine disorder and is well documented to be associated with lipid abnormalities.

Methods

A narrative review was conducted of studies describing the alterations in the lipid profile accompanying both subclinical and overt hypothyroidism.

Results

Lipid abnormalities are seen with TSH values in the upper end of the accepted reference range, as well as with subclinical and overt hypothyroidism. The degree of lipid derangement is generally proportional to the degree of TSH elevation. Other factors such as age, sex, and body mass index can also influence the pattern of the lipid abnormalities seen. The most robust finding with TSH elevation is increases in the low density lipoprotein cholesterol. Thyroid hormone treatment is efficacious in reversing the lipid abnormalities in both subclinical and overt hypothyroidism.

Conclusion

Given the association of lipid abnormalities with metabolic and cardiovascular disease, consideration of hypothyroidism as an important non-communicable disease may facilitate studies that test the hypothesis that thyroid hormone treatment to reverse hypothyroidism-associated lipid abnormalities may improve metabolic and cardiovascular outcomes.
Mann–Dotson’s algorithm for a countable family of non-self strict pseudo-contractive mappings
Authors: Patel Prashant , Shukla Rahul
Published: June 2023

The aim of this paper to present some weak and strong convergence results for countable family of non-self mappings. More precisely, we employ the Mann–Dotson’s algorithm to approximate common fixed points of a countable family of non-self k-strict Pseudocontractive mappings in q-uniformly smooth Banach spaces.
Tephrosia kindiana (Leguminosae: Papilionoideae), a new species from Guinea
Authors: Haba Pepe M. , Holt Beverley J. , van der Burgt Xander M.
Published: June 2023

Tephrosia kindiana, a new plant species from Guinea, is described and illustrated. It is a shrub 90 – 120 cm tall, multi-stemmed from the base. The leaves have 5 – 13 oblanceolate leaflets; the inflorescence consists of solitary flowers in the leaf axils, or 2 – 3-flowered fascicles; the flowers are orange and 24 – 26 mm long. The species occurs in wooded grassland on sandstone plateaus at 300 – 420 m elevation. Three localities are known, at up to 13 km apart. Tephrosia kindiana is provisionally assessed as Endangered.
Metastatic Triple-Negative Breast Cancer
Authors: Zhang Xiaojie , Yeung Kay T.
Published: June 2023

Purpose of Review

Triple-negative breast cancer
(TNBC) is a heterogeneous disease group with a known aggressive phenotype and poor prognosis. To date, it remains a challenging disease given its lack of oncogenic targets as seen in hormone receptor + or HER2 + breast cancers, and limited efficacy with traditional chemotherapy. This article is a review of the latest key literature in the management of metastatic TNBC and offers a glimpse of ongoing drug development.

Recent Findings

Recent paradigm-shifting trials led to the incorporation of immune checkpoint inhibitors with chemotherapy in the frontline setting for TNBC with positive PDL1-expression. Novel antibody–drug conjugates with new targets (Trop2, HER2) now offer additional treatment options for metastatic TNBC.

There have been significant strides in understanding the tumor-immune microenvironment and molecular vulnerabilities in TNBC. As the treatment of metastatic TNBC evolves rapidly, novel combination therapies and therapeutic strategies will continue to improve patient outcomes.
Picturing the coast: unravelling community perceptions of seascapes, Blue Growth and coastal change
Authors: Pafi Maria , Flannery Wesley , Murtagh Brendan
Published: June 2023

Blue Growth is gaining momentum, opening up new frontiers for economic development, with potentially negative impacts on coastal communities and seascapes. The impact of Blue Growth projects on communities and seascapes is generally understood through narrow technical or economic approaches that focus on the potential loss of coastal views or the depreciating impacts on property values, ignoring the complex relationships communities have with seascapes. These approaches often dislodge non-quantifiable community-seascape relationships from Blue Growth strategies, leading to community frustration and contestation. Understanding community-seascape relationships is key to developing more locally attuned Blue Growth strategies. We conceptualise seascapes as a triadic space incorporating perceived, conceived and lived dimensions. These dimensions have an impact on how communities experience and respond to contestation. We use a participatory photo-elicitation methodology with two community groups on the west coast of Ireland to understand how contestation occurs in places faced with multiple Blue Growth pressures and the mechanisms communities deploy in response. We find that although communities care deeply about changes taking place at the coast and sea and frame their ‘common’ landscapes as cultural assets that are worthy of defence, community practices remain impotently emotional or focused on ephemeral oppositions to specific Blue Growth developments. Such responses, however, are not strong enough for sufficiently mobilising a sustainable solution to dominant growth models. We suggest that if communities are properly supported to invest in knowledge, skills, networks and assets, they can mobilise more sustainable solutions to dominant growth models that threaten their coastal seascapes and cultural heritage. Finally, we highlight the transformative potential of the lived space of communities, not as a descriptor of a different typology of coastal landscape, but rather as a resource to understand how communities affected by multiple pressures can understand their options, capacity to resist and what their goal might be for the future of the coast.
Women Surgeons in the Military: Perspectives on Deployed Surgical Leadership
Authors: Choi Pamela M. , Streit Stephanie , Wrenn-Maresh Katherine , Stuever Mary , Holt Danielle B. , Tadlock Matthew D. , Gurney Jennifer M.
Published: June 2023

Purpose of Review

To review the history of women surgeons in the US military and juxtapose this history with five invited commentaries on deployed surgical leadership from women of various experiences, services, and ranks, to help prepare future trainees and those surgeons who have not yet deployed.

Recent Findings

Throughout American history, women have played a significant role in serving the Armed Forces in both informal and formal roles including the Civil War and World War I, and World War II. The 1943 Sparkman-Johnson Act formally granted female physicians full appointments as reservists in the Army and Navy Medical Corps. It was not until 1972 that women physicians could receive a direct commission in the medical corps of the Armed Forces when Congress established the Health Professional Scholarship Program and authorized the creation of the Uniformed Services University of the Health Sciences. Currently, women comprise approximately17% of the Armed Forces.

Despite numerous challenges, military service, particularly during times of war, has provided opportunities for women in medicine and surgery to demonstrate various leadership qualities while caring for those who go into harm’s way. For those surgeons (women and men) who have not yet deployed, these five invited commentaries from women surgeons representing 75 years of collective active duty service provide several modern points of view on deployed surgical leadership.
Effect of Mold Casting Parameters in Interface Properties of Iron/Copper Bimetallic Composites Based upon an Ancient Quranic Metal Matrix Composite (QMMC)
Authors: Bahgat A. , El-Meniawi M. A. H. , Khafagy S. M. , Sallam Hossam El-Din M. , Atta Mahmoud
Published: June 2023

The relation between iron/copper bimetallic composites has many challenges; one of the most important characteristics is their diffusion and its effect on the properties of the interface region. This paper studies the influence of casting parameters on the interface region of these bimetallic composites and compares it to observations on those of the Quranic metal matrix composites based on the Dhul-Qarnayn dam (Gog and Magog Wall). A different number of steel rods (one, two, and three) were placed in an alloy steel mold, then heated at different temperatures of 350, 450, 550, and 650 °C. After that, molten copper was poured over them into the mold, followed by different cooling rates (fast, medium, and slow). The properties of the interface region (microstructure, microhardness, and bonding strength) were investigated. The finite element model was carried out to obtain the temperature distribution through the specimen. The microhardness test results revealed that the high preheating temperature and high cooling rate give a high interface microhardness due to the formation of iron oxides and fine grains. The present experimental results show the highest bond strength between steel and copper, which was achieved when the temperature of the interface region reached the austenitic phase (γ-phase) and held it sufficiently to reach a successful substitutional diffusion mechanism. The bond strength between copper and steel in each casting parameter obtained experimentally was used to predict the tensile strength of the obtained bimetal composites numerically.
Geometric characterization of the persistence of 1D maps
Authors: Biswas Ranita , Cultrera di Montesano Sebastiano , Edelsbrunner Herbert , Saghafian Morteza
Published: June 2023

We characterize critical points of 1-dimensional maps paired in persistent homology geometrically and this way get elementary proofs of theorems about the symmetry of persistence diagrams and the variation of such maps. In particular, we identify branching points and endpoints of networks as the sole source of asymmetry and relate the cycle basis in persistent homology with a version of the stable marriage problem. Our analysis provides the foundations of fast algorithms for maintaining a collection of sorted lists together with its persistence diagram.
The role of depression in the association between physiotherapy frequency and duration and outcomes after hip fracture surgery: secondary analysis of the physiotherapy hip fracture sprint audit
Authors: Milton-Cole Rhian , O’Connell Matthew D. L. , Sheehan Katie Jane , Ayis Salma
Published: June 2023

Purpose

It is not known whether the association between the frequency and duration of physiotherapy and patient outcomes varies for those with and without depression. This study aims to evaluate whether the associations between the frequency and duration of physiotherapy after hip fracture surgery and discharge home, surviving at 30 days post-admission, and being readmitted 30 days post discharge vary by depression diagnosis.

Methods

Data were from 5005 adults aged 60 and over included in the UK Physiotherapy Hip Fracture Sprint Audit who had undergone surgery for a nonpathological first hip fracture. Logistic regression models were used to estimate the unadjusted and adjusted odds ratios and their 95% confidence intervals for the associations between physiotherapy frequency and duration and outcomes.

Results

Physiotherapy frequency and duration were comparable between patients with and without depression (42.1% and 44.6%). The average adjusted odds for a 30-min increase in physiotherapy duration for those with and without depression for discharge home were 1.05 (95% CI 0.85–1.29) vs 1.16 (95% CI 1.05–1.28, interaction p = 0.36), for 30-day survival were 1.26 (95% CI 1.06–1.50) vs 1.11 (95% CI 1.05–1.17, interaction p = 0.45) and for readmission were 0.89 (95% CI 0.81–0.98) vs 0.97 (95% CI 0.93–1.00, interaction p = 0.09). None of the interaction tests reached formal significance, but the readmission models were close (p = 0.09).

Conclusion

Results suggest physiotherapy duration may be negatively associated with readmission in those with depression but not those without depression, while no clear difference in the other outcomes was noted.
Assessment of pollution and metal toxicity in the bed sediment of El-Rayan Lakes, Fayoum, Egypt
Authors: Khedr Alaa I. , Goher Mohamed E. , Salem Salem G. , El Sayed Seliem M. , Farhat Hassan I.
Published: June 2023

Sediments are vital components of aquatic ecosystems, which trap and store various essential elements as well as harmful polluting substances. This is why sediment quality assessment is of great importance in measuring the quality, or pollution, of water bodies. In this study, the levels, ecological risk, and toxicity indices of 17 heavy metals (HMs) were evaluated in the sediments of the two lakes: Upper Wadi El-Rayan Lake (UWRL) and Lower Wadi El-Rayan Lake (LWRL). Both are important wetlands in Egypt used as agricultural drainage water reservoirs for Fayoum province. As revealed by the texture of the sediments, the sand represented the major sediment portion of the UWRL, while the mud was dominant in the LWRL. According to ecological risk assessment, the sediments of the two lakes suffer different degrees of metal pollution, mainly Cd, Pb, and Ni. Based on sediment quality guidelines, toxicity indices indicated different potential toxic effects of the studied HMs on benthic-dwelling organisms, but Ni and Ba had the highest potential biological risk. Results also revealed that the area facing the El-Wadi Drain is the most polluted due to its proximity to the water drainage entrance. However, LWRL is generally more polluted than UWRL. This is related to the shrinkage of water volume and lake area; it causes an increase in the concentration of metals in water, and thus an increase in the sedimentation rate of these metals into the bottom.
Trends of Anthropogenic Dissolved Inorganic Carbon in the Northwest Atlantic Ocean Estimated Using a State Space Model
Authors: Boteler Claire , Dowd Michael , Oliver Eric C. J. , Krainski Elias T. , Wallace Douglas W. R.
Published: June 2023

The northwest Atlantic Ocean is an important sink for carbon dioxide produced by anthropogenic activities. However the strong seasonal variability in the surface waters paired with the sparse and summer biased observations of ocean carbon makes it difficult to capture a full picture of its temporal variations throughout the water column. We aim to improve the estimation of temporal trends of dissolved inorganic carbon (DIC) due to anthropogenic sources using a new statistical approach: a time series generalization of the extended multiple linear regression (eMLR) method. Anthropogenic increase of northwest Atlantic DIC in the surface waters is hard to quantify due to the strong, natural seasonal variations of DIC. We address this by separating DIC into its seasonal, natural and anthropogenic components. Ocean carbon data is often collected in the summer, creating a summer bias, however using monthly averaged data made our results less susceptible to the strong summer bias in the available data. Variations in waters below 1000m have usually been analyzed on decadal time scales, but our monthly analysis showed the anthropogenic carbon component had a sudden change in 2000 from stationary to an increasing trend at the same rate as the waters above. All depths layers had similar rates of anthropogenic increase of ∼0.57µmol kg−1 year−1, and our uncertainty levels are smaller than with eMLR results. Integration throughout the water column (0–3,500 m) gives an anthropogenic carbon storage rate of 1.37 ± 0.57 mol m−2 year−1, which is consistent with other published estimates.
North American Hydroclimate During Past Warms States: A Proxy Compilation‐Model Comparison for the Last Interglacial and the Mid‐Holocene
Authors: de Wet C. B. , Ibarra D. E. , Belanger B. K. , Oster J. L.
Published: June 2023

During the mid‐Holocene (MH: ∼6,000 years Before Present) and Last Interglacial LIG (LIG: ∼129,000–116,000 years Before Present) differences in the seasonal and latitudinal distribution of insolation drove Northern Hemisphere high‐latitude warming comparable to that projected for the end of the 21st century in low emissions scenarios. Paleoclimate proxy records point to distinct but regionally variable hydroclimatic changes during these past warm intervals. However, model simulations have generally disagreed on North American regional moisture patterns during the MH and LIG. To investigate how closely the latest generation of models associated with the Paleoclimate Model Intercomparison Project (PMIP4) reproduces proxy‐inferred moisture patterns during recent warm periods, we compare hydroclimate output from 17 PMIP4 models with newly updated compilations of moisture‐sensitive North American proxy records during the MH and LIG. Agreement is lower for the MH, with models producing wet anomalies across the western United States (US) where most proxies indicate increased aridity relative to the preindustrial period. The models that agree most closely with the LIG proxy compilation display relative wetness in the eastern US and Alaska, and dryness in the northwest and central US. An assessment of atmospheric dynamics using an ensemble of the three LIG simulations that best agree with the proxies suggests that weaker winter North Pacific pressure gradients and steeper summer North Pacific and Atlantic gradients drive LIG precipitation patterns. Our updated compilations and proxy‐model comparisons offer a tool for benchmarking climate models and their performance in simulating climate states that are warmer than present.
Unrestricted Solar Energetic Particle Access to the Moon While Within the Terrestrial Magnetotail
Authors: Liuzzo Lucas , Poppe Andrew R. , Lee Christina O. , Xu Shaosui , Angelopoulos Vassilis
Published: June 2023

This study presents observations of Solar Energetic Particle (SEP) protons that have penetrated Earth's magnetotail to reach the lunar environment. We apply data from Wind as an upstream monitor and compare to observations from THEMIS‐ARTEMIS within the tail to show clear signatures of SEPs at the Moon during two events. Combining modeling and data analysis, we show that SEPs above energies of ∼25 keV gain access to the Moon's position deep within the magnetotail through field lines that are open on one end to the solar wind. These results contradict previous studies that have suggested that the magnetotail is effective in shielding the Moon from SEPs with energies up to 1 GeV. Instead, we highlight that Earth's magnetosphere provides poor protection to the Moon from SEPs, which irradiate the lunar surface even within the tail. Our results have important implications regarding the safety of astronauts during upcoming lunar missions.
Field‐Line Curvature Scattering at the Outer Boundary of the Proton Radiation Belt
Authors: Selesnick R. S. , Looper M. D.
Published: June 2023

A model balancing diffusive field‐line curvature (FLC) scattering loss with other local source, loss, and transport processes is used to compute the L‐shell location of the proton radiation belt outer boundary, where intensity falls below observable levels. The FLC scattering rate increases with increasing L and proton energy, decreasing equatorial pitch angle, and increasing geomagnetic activity, as determined with the Kp‐dependent T89 external magnetic field combined with a dipole internal field. Simulated proton intensity near the outer boundary is compared to measurements from both the low‐altitude SAMPEX satellite and the high‐altitude Van Allen Probes satellites, with correction for instrumental biases caused by field‐of‐view, energy range, and the east‐west effect. Good agreement between observations and simulations is obtained for average boundary locations, time‐dependent variations caused by magnetic storms, and average equatorial pitch‐angle distributions.
Depth‐Dependent Aftershock Trigger Potential Revealed by 3D‐ETAS Modeling
Authors: Asayesh Behnam M. , Hainzl Sebastian , Zöller Gert
Published: June 2023

Current earthquake catalogs provide high‐precision depth values that contain valuable information. Thus, we extend the spatiotemporal Epidemic Type Aftershock Sequence model to 3D by considering hypocentral instead of epicentral distances. To explore the most appropriate parametric form of the spatial kernel, we first examine different triggering functions for the depth difference of the aftershock‐mainshock pairs identified by the Nearest‐Neighbor method, showing that a magnitude‐dependent power‐law kernel fits best the earthquakes data in Southern California. Therefore, we incorporate the corresponding kernel into the 3D‐ETAS model with space‐dependent background activity, where we additionally allow for depth‐dependent aftershock productivity. The application to Southern California shows that the model fits the data well. We also find that the aftershock productivity strongly depends on depth, similar to the seismic moment released by the mainshocks, which may be related to depth‐dependent seismic coupling.
Effect of Asymmetric Topography on Rupture Propagation Along Fault Stepovers
Authors: Douilly Roby
Published: June 2023

Complex fault systems are often located in regions with asymmetric topography on one side of a fault, and these systems are very common in Southern California. Along these fault systems, geometrical complexities such as stepovers can impact fault rupture. Previous rupture dynamic studies have investigated the effect of stepover widths on throughgoing rupture, but these studies didn't examine the influence of topography on the rupture behavior. To investigate the effect of asymmetric topography on rupture dynamics at stepovers, I consider three cases: (a) a flat topography, (b) a positive (mountain), and (c) a negative (basin) topography on only one side of the fault system outside of the stepover. In each case, I use the 3D finite element method to compute the rupture dynamics of these fault systems. The results show a significant time dependent variation of the normal stress for the topography cases as opposed to the flat surface case, which can have an important impact on rupture propagation at the stepover. For a positive topography on the right of the rupture propagation, there is a clamping effect behind the rupture front that prevents the rupture to jump a wider extensional stepover. The opposite is observed for a negative topography or for a positive topography on the left side of the rupture propagation, where the rupture can jump over a wider compressional stepover. These results suggest that topography should be considered in dynamic studies with geometric complexities such as stepovers, and perhaps bends and branched fault systems.
Reconstructing the Oxygen Depth Profile in the Arabian Sea During the Last Glacial Period
Authors: Lu Wanyi , Costa Kassandra M. , Oppo Delia W.
Published: June 2023

Reconstructing the strength and depth boundary of oxygen minimum zones (OMZs) in the glacial ocean advances our understanding of how OMZs respond to climate changes. While many efforts have inferred better oxygenation of the glacial Arabian Sea OMZ from qualitative indices, oxygenation and vertical extent of the glacial OMZ is not well quantified. Here we present glacial‐Holocene oxygen reconstructions in a depth transect of Arabian Sea cores ranging from 600 to 3,650 m water depths. We estimate glacial oxygen concentrations using benthic foraminiferal surface porosity and benthic carbon isotope gradient reconstructions. Compared to the modern Arabian Sea, glacial oxygen concentrations were approximately 10–15 μmol/kg higher in the shallow OMZ (<1,000 m), and 5–80 μmol/kg lower at greater depths (1,500–3,650 m). Our results suggest that the OMZ in the glacial Arabian Sea was slightly better oxygenated but remained in the upper 1,000 m. We propose that the small increase in oxygenation of the Arabian Sea OMZ during the last glacial period was due to weaker upper ocean stratification induced by stronger winter monsoon winds coupled with an increase in oxygen solubility due to lower temperatures, counteracting the effects of more oxygen consumption resulting from higher primary productivity. Large‐scale changes in ocean circulation may have also contributed to better ventilation of the glacial Arabian Sea OMZ.
A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
Authors: Huang Xing-Yao , Chen Qi , Sun Meng-Xu , Zhou Hang-Yu , Ye Qing , Chen Wu , Peng Jin-Yu , Qi Yi-Ni , Zhai Jun-Qiong , Tian Ying , Liu Zi-Xin , Huang Yi-Jiao , Deng Yong-Qiang , Li Xiao-Feng , Wu Aiping , Yang Xiao , Yang Guan , Shen Yongyi , Qin Cheng-Feng
Published: June 2023

Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk.
Direct laser writing of 3D electrodes on flexible substrates
Authors: Brown Morgan A. , Zappitelli Kara M. , Singh Loveprit , Yuan Rachel C. , Bemrose Melissa , Brogden Valerie , Miller David J. , Smear Matthew C. , Cogan Stuart F. , Gardner Timothy J.
Published: June 2023

This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The fabrication process combines traditional silicon thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. Direct laser-writing of 3D-printed electrodes has been described before, but this report is the first to provide a method for producing high-aspect-ratio structures. One prototype, a 16-channel array with 300 µm pitch, demonstrates successful electrophysiological signal capture from bird and mouse brains. Additional devices include 90 µm pitch arrays, biomimetic mosquito needles that penetrate through the dura of birds, and porous electrodes with enhanced surface area. The rapid 3D printing and wafer-scale methods described here will enable efficient device fabrication and new studies examining the relationship between electrode geometry and electrode performance. Applications include small animal models, nerve interfaces, retinal implants, and other devices requiring compact, high-density 3D electrodes.
Structure and proposed DNA delivery mechanism of a marine roseophage
Authors: Huang Yang , Sun Hui , Wei Shuzhen , Cai Lanlan , Liu Liqin , Jiang Yanan , Xin Jiabao , Chen Zhenqin , Que Yuqiong , Kong Zhibo , Li Tingting , Yu Hai , Zhang Jun , Gu Ying , Zheng Qingbing , Li Shaowei , Zhang Rui , Xia Ningshao
Published: June 2023

Tailed bacteriophages (order, Caudovirales) account for the majority of all phages. However, the long flexible tail of siphophages hinders comprehensive investigation of the mechanism of viral gene delivery. Here, we report the atomic capsid and in-situ structures of the tail machine of the marine siphophage, vB_DshS-R4C (R4C), which infects Roseobacter. The R4C virion, comprising 12 distinct structural protein components, has a unique five-fold vertex of the icosahedral capsid that allows genome delivery. The specific position and interaction pattern of the tail tube proteins determine the atypical long rigid tail of R4C, and further provide negative charge distribution within the tail tube. A ratchet mechanism assists in DNA transmission, which is initiated by an absorption device that structurally resembles the phage-like particle, RcGTA. Overall, these results provide in-depth knowledge into the intact structure and underlining DNA delivery mechanism for the ecologically important siphophages.
A pharmacoproteomic landscape of organotypic intervention responses in Gram-negative sepsis
Authors: Mohanty Tirthankar , Karlsson Christofer A. Q. , Chao Yashuan , Malmström Erik , Bratanis Eleni , Grentzmann Andrietta , Mørch Martina , Nizet Victor , Malmström Lars , Linder Adam , Shannon Oonagh , Malmström Johan
Published: June 2023

Sepsis is the major cause of mortality across intensive care units globally, yet details of accompanying pathological molecular events remain unclear. This knowledge gap has resulted in ineffective biomarker development and suboptimal treatment regimens to prevent and manage organ dysfunction/damage. Here, we used pharmacoproteomics to score time-dependent treatment impact in a murine Escherichia coli sepsis model after administering beta-lactam antibiotic meropenem (Mem) and/or the immunomodulatory glucocorticoid methylprednisolone (Gcc). Three distinct proteome response patterns were identified, which depended on the underlying proteotype for each organ. Gcc enhanced some positive proteome responses of Mem, including superior reduction of the inflammatory response in kidneys and partial restoration of sepsis-induced metabolic dysfunction. Mem introduced sepsis-independent perturbations in the mitochondrial proteome that Gcc counteracted. We provide a strategy for the quantitative and organotypic assessment of treatment effects of candidate therapies in relationship to dosing, timing, and potential synergistic intervention combinations during sepsis.
Spatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4+ T cell fate
Authors: Zhu Fangming , McMonigle Ryan J. , Schroeder Andrew R. , Xia Xianyou , Figge David , Greer Braxton D. , González-Avalos Edahí , Sialer Diego O. , Wang Yin-Hu , Chandler Kelly M. , Getzler Adam J. , Brown Emily R. , Xiao Changchun , Kutsch Olaf , Harada Yohsuke , Pipkin Matthew E. , Hu Hui
Published: June 2023

Follicular helper T (Tfh) cells are essential for germinal center (GC) B cell responses. However, it is not clear which PD-1+CXCR5+Bcl6+CD4+ T cells will differentiate into PD-1hiCXCR5hiBcl6hi GC-Tfh cells and how GC-Tfh cell differentiation is regulated. Here, we report that the sustained Tigit expression in PD-1+CXCR5+CD4+ T cells marks the precursor Tfh (pre-Tfh) to GC-Tfh transition, whereas Tigit–PD-1+CXCR5+CD4+ T cells upregulate IL-7Rα to become CXCR5+CD4+ T memory cells with or without CCR7. We demonstrate that pre-Tfh cells undergo substantial further differentiation at the transcriptome and chromatin accessibility levels to become GC-Tfh cells. The transcription factor c-Maf appears critical in governing the pre-Tfh to GC-Tfh transition, and we identify Plekho1 as a stage-specific downstream factor regulating the GC-Tfh competitive fitness. In summary, our work identifies an important marker and regulatory mechanism of PD-1+CXCR5+CD4+ T cells during their developmental choice between memory T cell fate and GC-Tfh cell differentiation.
Snowflake-inspired and blink-driven flexible piezoelectric contact lenses for effective corneal injury repair
Authors: Yao Guang , Mo Xiaoyi , Liu Shanshan , Wang Qian , Xie Maowen , Lou Wenhao , Chen Shiyan , Pan Taisong , Chen Ke , Yao Dezhong , Lin Yuan
Published: June 2023

The cornea is a tissue susceptible to various injuries and traumas with a complicated cascade repair process, in which conserving its integrity and clarity is critical to restoring visual function. Enhancing the endogenous electric field is recognized as an effective method of accelerating corneal injury repair. However, current equipment limitations and implementation complexities hinder its widespread adoption. Here, we propose a snowflake-inspired, blink-driven flexible piezoelectric contact lens that can convert mechanical blink motions into a unidirectional pulsed electric field for direct application to moderate corneal injury repair. The device is validated on mouse and rabbit models with different relative corneal alkali burn ratios to modulate the microenvironment, alleviate stromal fibrosis, promote orderly epithelial arrangement and differentiation, and restore corneal clarity. Within an 8-day intervention, the corneal clarity of mice and rabbits improves by more than 50%, and the repair rate of mouse and rabbit corneas increases by over 52%. Mechanistically, the device intervention is advantageous in blocking growth factors’ signaling pathways specifically involved in stromal fibrosis whilst preserving and harnessing the signaling pathways required for indispensable epithelial metabolism. This work put forward an efficient and orderly corneal therapeutic technology utilizing artificial endogenous-strengthened signals generated by spontaneous body activities.
Non disseminative nano-strategy against in vivo Staphylococcus aureus biofilms
Authors: Pinto Rita M. , Yazdani Saleh , Seabra Catarina Leal , De Jonge Martine , Izci Mukaddes , Cruz Rebeca , Casal Susana , Soenen Stefaan J. , Reis Salette , Nunes Cláudia , Van Dijck Patrick
Published: June 2023

Staphylococcus aureus is considered a high priority pathogen by the World Health Organization due to its high prevalence and the potential to form biofilms. Currently, the available treatments for S. aureus biofilm-associated infections do not target the extracellular polymeric substances (EPS) matrix. This matrix is a physical barrier to bactericidal agents, contributing to the increase of antimicrobial tolerance. The present work proposes the development of lipid nanoparticles encapsulating caspofungin (CAS) as a matrix-disruptive nanosystem. The nanoparticles were functionalized with D-amino acids to target the matrix. In a multi-target nano-strategy against S. aureus biofilms, CAS-loaded nanoparticles were combined with a moxifloxacin-loaded nanosystem, as an adjuvant to promote the EPS matrix disruption. In vitro and in vivo studies showed biofilm reduction after combining the two nanosystems. Besides, the combinatory therapy showed no signs of bacterial dissemination into vital organs of mice, while dissemination was observed for the treatment with the free compounds. Additionally, the in vivo biodistribution of the two nanosystems revealed their potential to reach and accumulate in the biofilm region, after intraperitoneal administration. Thus, this nano-strategy based on the encapsulation of matrix-disruptive and antibacterial agents is a promising approach to fight S. aureus biofilms.
Nitrate and a nitrate-reducing Rothia aeria strain as potential prebiotic or synbiotic treatments for periodontitis
Authors: Mazurel Danuta , Carda-Diéguez Miguel , Langenburg Thomas , Žiemytė Miglė , Johnston William , Martínez Carlos Palazón , Albalat Fernando , Llena Carmen , Al-Hebshi Nezar , Culshaw Shauna , Mira Alex , Rosier Bob T.
Published: June 2023

A few studies indicate that nitrate can reduce dysbiosis from a periodontitis point of view. However, these experiments were performed on samples from healthy individuals, and it is unknown if nitrate will be effective in periodontal patients, where the presence of nitrate-reducing bacteria is clearly reduced. The aim of this study was to test the effect of nitrate and a nitrate-reducing R. aeria (Ra9) on subgingival biofilms of patients with periodontitis. For this, subgingival plaque was incubated with 5 mM nitrate for 7 h (n = 20) or 50 mM nitrate for 12 h (n = 10), achieving a ~50% of nitrate reduction in each case. Additionally, Ra9 was combined with 5 mM nitrate (n = 11), increasing the nitrate reduced and nitrite produced (both p < 0.05). The addition of nitrate to periodontitis communities decreased biofilm mass (50 mM > 5 mM, both p < 0.05). Five millimolar nitrate, 50 mM nitrate and 5 mM nitrate + Ra9 led to 3, 28 and 20 significant changes in species abundance, respectively, which were mostly decreases in periodontitis-associated species. These changes led to a respective 15%, 63% (both p < 0.05) and 6% (not significant) decrease in the dysbiosis index. Using a 10-species biofilm model, decreases in periodontitis-associated species in the presence of nitrate were confirmed by qPCR (all p < 0.05). In conclusion, nitrate metabolism can reduce dysbiosis and biofilm growth of periodontitis communities. Five millimolar nitrate (which can be found in saliva after vegetable intake) was sufficient, while increasing this concentration to 50 mM (which could be achieved by topical applications such as a periodontal gel) increased the positive effects. Ra9 increased the nitrate metabolism of periodontitis communities and should be tested in vivo.
Machine learning molecular dynamics simulation identifying weakly negative effect of polyanion rotation on Li-ion migration
Authors: Xu Zhenming , Duan Huiyu , Dou Zhi , Zheng Mingbo , Lin Yixi , Xia Yinghui , Zhao Haitao , Xia Yongyao
Published: June 2023

Understanding the physical picture of Li ion transport in the current ionic conductors is quite essential to further develop lithium superionic conductors for solid-state batteries. The traditional practice of directly extrapolating room temperature ion diffusion properties from the high-temperature (>600 K) ab initio molecular dynamics simulations (AIMD) simulations by the Arrhenius assumption unavoidably cause some deviations. Fortunately, the ultralong-time molecular dynamics simulation based on the machine-learning interatomic potentials (MLMD) is a more suitable tool to probe into ion diffusion events at low temperatures and simultaneously keeps the accuracy at the density functional theory level. Herein, by the low-temperature MLMD simulations, the non-linear Arrhenius behavior of Li ion was found for Li3ErCl6, which is the main reason for the traditional AIMD simulation overestimating its ionic conductivity. The 1μs MLMD simulations capture polyanion rotation events in Li7P3S11 at room temperature, in which four [PS4]3− tetrahedra belonging to a part of the longer-chain [P2S7]4− group are noticed with remarkable rotational motions, while the isolated group [PS4]3− does not rotate. However, no polyanion rotation is observed in Li10GeP2S12, β-Li3PS4, Li3ErCl6, and Li3YBr6 at 300 K during 1μs simulation time. Additionally, the ultralong-time MLMD simulations demonstrate that not only there is no paddle-wheel effect in the crystalline Li7P3S11 at room temperature, but also the rotational [PS4]3− polyanion groups have weakly negative impacts on the overall Li ion diffusion. The ultralong-time MLMD simulations deepen our understanding of the relationship between the polyanion rotation and cation diffusion in ionic conductors at room environments.
Alteration of medieval stained glass windows in atmospheric medium: review and simplified alteration model
Authors: Verney-Carron Aurélie , Sessegolo Loryelle , Chabas Anne , Lombardo Tiziana , Rossano Stéphanie , Perez Anne , Valbi Valentina , Boutillez Chloé , Muller Camille , Vaulot Cyril , Trichereau Barbara , Loisel Claudine
Published: June 2023

Stained glass windows are a precious heritage to pass on to future generations. However, medieval stained glass windows are particularly altered due to their chemical composition and the effects of climatic (mainly water and temperature), environmental (pollution) and biological factors. In this review, we present the alteration patterns observed on ancient Si-K-Ca stained glass windows. To better understand their formation mechanisms and determine the alteration rates, different exposure campaigns to the current atmosphere in a position sheltered from rain or not and laboratory experiments in aqueous medium or in gaseous phase have been conducted. Either model glass or ancient stained glass windows were studied. Isotopic tracers (D,18O,29Si) have been used as they constitute a powerful tool to elucidate the involved processes and to measure their kinetics. Thanks to all of these data, an alteration scenario of medieval stained glass alteration is proposed. Besides, the extrapolation of kinetic data based on several hypotheses over seven centuries gives very consistent results compared to the ancient stained glass samples.
Probing resonating valence bonds on a programmable germanium quantum simulator
Authors: Wang Chien-An , Déprez Corentin , Tidjani Hanifa , Lawrie William I. L. , Hendrickx Nico W. , Sammak Amir , Scappucci Giordano , Veldhorst Menno
Published: June 2023

Simulations using highly tunable quantum systems may enable investigations of condensed matter systems beyond the capabilities of classical computers. Quantum dots and donors in semiconductor technology define a natural approach to implement quantum simulation. Several material platforms have been used to study interacting charge states, while gallium arsenide has also been used to investigate spin evolution. However, decoherence remains a key challenge in simulating coherent quantum dynamics. Here, we introduce quantum simulation using hole spins in germanium quantum dots. We demonstrate extensive and coherent control enabling the tuning of multi-spin states in isolated, paired, and fully coupled quantum dots. We then focus on the simulation of resonating valence bonds and measure the evolution between singlet product states which remains coherent over many periods. Finally, we realize four-spin states with s-wave and d-wave symmetry. These results provide means to perform non-trivial and coherent simulations of correlated electron systems.
A chromosome-level genome assembly of tomato pinworm, Tuta absoluta
Authors: Liu Ying , Chen Xi , Yin Yanqiong , Li Xiaowei , He Kang , Zhao Xueqing , Li Xiangyong , Luo Xiyan , Mei Yang , Wang Zuoqi , Shu Runguo , Cheng Ziqi , Gebretsadik Kifle Gebreegziabiher , Luo Chen , Wang Ran , Lv Yaobin , Chen Aidong , Li Fei
Published: June 2023

The tomato pinworm, Tuta absoluta, or Phthorimaea absouta, is native to South America, but quickly spread to other regions of world, including Europe, Africa, and Asia, devastating to global tomato production. However, a lack of high-quality genome resources makes it difficult to understand its high invasiveness and ecological adaptation. Here, we sequenced the genome of the tomato pinworm using Nanopore platforms, yielding a genome assembly of 564.5 Mb with contig N50 of 3.33 Mb. BUSCO analysis demonstrated that this genome assembly has a high-level completeness of 98.0% gene coverage. In total, 310 Mb are repeating sequences accounting for 54.8% of genome assembly, and 21,979 protein-coding genes are annotated. Next, we used the Hi-C technique to anchor 295 contigs to 29 chromosomes, yielding a chromosome-level genome assembly with a scaffold N50 of 20.7 Mb. In sum, the high-quality genome assembly of the tomato pinworm is a useful gene resource that contributes to a better understanding of the biological characteristics of its invasiveness and will help in developing an efficient control policy.
Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection
Authors: Eder Julian , Schumm Leonie , Armann Jakob P. , Puhan Milo A. , Beuschlein Felix , Kirschbaum Clemens , Berner Reinhard , Toepfner Nicole
Published: June 2023

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.