bluuebunny/crossref_metadata_2025 huggingface dataset:
Ash dieback assessments on intensive monitoring plots in Germany: influence of stand, site and time on disease progression
Authors: Fuchs Sebastian , Häuser Henriette , Peters Sandra , Knauf Luisa , Rentschler Felix , Kahlenberg Georgia , Kätzel Ralf , Evers Jan , Paar Uwe , Langer Gitta Jutta
Published: March 2024

Since 2002, ash dieback caused by the invasive fungus Hymenoscyphus fraxineus has been observed in Germany. The pathogen and its associated symptoms have fatal consequences for the vitality and survival of European ash (Fraxinus excelsior L.), an economically and ecologically important tree species. This study analyses the ash monitoring results of eleven intensive monitoring plots of the FraxForFuture research network distributed across Germany and focuses on within-stand differences of symptoms in dependence of small-scale site and tree properties. A cohort of 1365 ash trees was surveyed six times over three years, testing and applying a summer and a winter version of a nationally standardised ash dieback assessment key. The main disease symptoms (crown dieback and basal lesions) were more pronounced in areas with higher ash density, in edaphically moist areas (hydromorphic soils), on younger/smaller ash trees, and generally increased over time. However, the trend over time differed between single plots. In case of considering only the surviving part of the ash populations, crown condition even improved in 6/11 plots, indicating a selection process. Large basal lesions at the beginning of the observation period were a very good predictor for deadfall probability, especially on trees with lower stem diameter. Generally, ash dieback related symptoms at stem and crown were highly correlated. Silvicultural management practice in the past that actively pushed ash towards the moister end of its water demand spectrum has to be questioned in the light of ash dieback. Cost-intensive ash re-cultivation in the future—possibly with less dieback-susceptible progenies—should avoid pure ash stands and hydromorphic soil conditions.
Simulation test on shaft deformation induced by mining subsidence under similar gravity field in deep soil strata
Authors: Han Xu , Qin Zhe , Han Ji-huan , Yang Wei-hao , Liu Yong-de , Zhang Jian
Published: March 2024

Many shafts in China have experienced large deformations in the deep soil Strata, which has had a significant impact on mining safety. This study conducted a geotechnical model test called the seepage force model to address the deformation issues of shafts caused by mining solid mineral resources in regions with deep soil strata. This test simulated the impact of mining disturbance on shaft deformation within the soil section. The simulation utilized monitoring data from the model shaft, facilitating the determination of deflection displacements across different protection areas. The findings indicated a nearly linear relationship between the maximum horizontal displacement of the shaft and the mining coal seam thickness. The shaft protection areas within the soil section were reconfigured by modifying the movement angle from 45° to 37.6°. Consequently, the maximum horizontal displacements of the prototype shaft decreased to 73.8, 112.7, and 170.9 mm for mining coal thicknesses of 2.7, 5.3, and 8.0 m, respectively. These values represent 26%, 24.6%, and 26.7% reductions from the original design shaft displacements. When combined with the probability integral method, the simulation test results concerning the shaft protection rock pillars were exhaustively examined. This analysis paves the way for a more logical and reliable design approach for shaft protection rock pillars in areas characterized by deep soil and thin rock strata. The study findings hold immense significance in effectively mitigating and managing mining-induced subsidence disasters and ensuring the optimal design of shaft protection zones.
Automatic Liver Segmentation from Multiphase CT Using Modified SegNet and ASPP Module
Authors: Nayantara P. Vaidehi , Kamath Surekha , Kadavigere Rajagopal , Manjunath Kanabagatte Nanjundappa
Published: March 2024

Liver cancer is one of the dominant causes of cancer death worldwide. Computed Tomography (CT) is the commonly used imaging modality for diagnosing it. Computer-based liver cancer diagnosis systems can assist radiologists in image interpretation and improve diagnosis speed and accuracy. Since liver segmentation is crucial to such systems, researchers are relentlessly pursuing various segmentation approaches. A clinically viable computer-aided system requires examining multiphase CT images. However, most of the research focuses only on the portal venous phase. In this work, we developed an automatic and efficient Deep Learning (DL) method using SegNet, atrous spatial pyramid pooling module and leaky ReLU layers for liver segmentation from quadriphasic abdominal CT volumes. The proposed method was validated on two datasets, an internal institutional dataset consisting of multiphase CT and a public dataset of portal venous phase CT volumes. The Dice Coefficients (DC) obtained were greater than 96% for the latter dataset and the portal venous phase of the former. For arterial, delayed and plain CT phases of the former dataset, the DC achieved were 94.61%, 95.01% and 93.23%, respectively. Experiments showed that our model performed better than the other state-of-the-art DL models. Ablation studies have revealed that the proposed model leverages the strengths of all the three components that make it up. The promising performance of the proposed method suggests that it is appropriate for incorporation in hepatic cancer diagnosis systems.
Conditioned Galton–Watson Trees: The Shape Functional, and More on the Sum of Powers of Subtree Sizes and Its Mean
Authors: Fill James Allen , Janson Svante , Wagner Stephan
Published: March 2024

For a complex number $$\alpha $$
α
, we consider the sum of the $$\alpha $$
α
th powers of subtree sizes in Galton–Watson trees conditioned to be of size n. Limiting distributions of this functional $$X_n(\alpha )$$

X
n

(
α
)

have been determined for $${\text {Re}}\alpha \ne 0$$

Re
α
≠
0

, revealing a transition between a complex normal limiting distribution for $${\text {Re}}\alpha < 0$$

Re
α
<
0

and a non-normal limiting distribution for $${\text {Re}}\alpha > 0$$

Re
α
>
0

. In this paper, we complete the picture by proving a normal limiting distribution, along with moment convergence, in the missing case $${\text {Re}}\alpha = 0$$

Re
α
=
0

. The same results are also established in the case of the so-called shape functional $$X_n'(0)$$

X
n
′

(
0
)

, which is the sum of the logarithms of all subtree sizes; these results were obtained earlier in special cases. In addition, we prove convergence of all moments in the case $${\text {Re}}\alpha < 0$$

Re
α
<
0

, where this result was previously missing, and establish new results about the asymptotic mean for real $$\alpha < 1/2$$

α
<
1
/
2

.

A novel feature for $${\text {Re}}\alpha =0$$

Re
α
=
0

is that we find joint convergence for several $$\alpha $$
α
to independent limits, in contrast to the cases $${\text {Re}}\alpha \ne 0$$

Re
α
≠
0

, where the limit is known to be a continuous function of $$\alpha $$
α
. Another difference from the case $${\text {Re}}\alpha \ne 0$$

Re
α
≠
0

is that there is a logarithmic factor in the asymptotic variance when $${\text {Re}}\alpha =0$$

Re
α
=
0

; this holds also for the shape functional.

The proofs are largely based on singularity analysis of generating functions.
Assessment of crushed rock aggregates addition to granular lateritic materials in sub-Saharan extensive urbanization context (Yaoundé Cameroon) for road construction purposes
Authors: Ndzié Mvindi Aloys Thierry , Lobe Bille Jean Francis , Ngo’o Ze Arnaud , Enock Embom Christophe , Tsoyi À Koung Emmanuel , Ngono Mbenti Emvana Michèle Stella , Onana Vincent Laurent
Published: March 2024

Granular lateritic materials (GLM) suitability for road construction after the addition of crushed rock aggregates (CRA) in the sub-Saharan extensive urbanization context was evaluated. The urbanization rate was made by using Landsat7 and Landsat8 radar images. The studied materials were subject to petrographic description and geotechnical analysis. The urbanized surface in the Yaoundé area increased by 41.88% from 2004 to 2020. The studied rock are gneisses composed of quartz, garnet, biotite, pyroxene, and feldspars. The gneisses obtained CRA have fines content of less than 10%, maximum dry density value of more than 2.00 g/cm3, good bearing capacity (CBR = 88%), and excellent mechanical characteristics (Los Angeles < 40%). This recommend their use as base course for low to medium volume traffic pavements. Gneisses-derived GLM, less load-bearing (CBR = 39 to 42%) than CRA, have limited behaviour in road construction and can be used as sub-base for all volume traffics. Their use in base courses requires prior treatment. CRA addition to these GLM result in the plasticity index decrease and compaction parameters improvement. CBR values increase shows a perfect correlation (R2 > 0.90) with the addition of CRA. Litho-stabilised materials (CBR ≥ 60%) can be used as base course for low-volume trafficked pavements. The addition of a CRA percentage greater than or equal to 25% is efficient for the optimization of their use. By reducing the amount of quarry aggregates, the improved material could be an economical alternative for road projects. This reduces and controls the haulage of materials within crowded urban area.
Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis
Authors: Oliphant Elizabeth A. , Hanning Sara M. , McKinlay Christopher J. D. , Alsweiler Jane M.
Published: March 2024

This systematic review and meta-analysis evaluated the evidence for dose and effectiveness of caffeine in preterm infants. MEDLINE, EMBASE, CINHAL Plus, CENTRAL, and trial databases were searched to July 2022 for trials randomizing preterm infants to caffeine vs. placebo/no treatment, or low (≤10 mg·kg−1) vs. high dose (>10 mg·kg−1 caffeine citrate equivalent). Two researchers extracted data and assessed risk of bias using RoB; GRADE evaluation was completed by all authors. Meta-analysis of 15 studies (3530 infants) was performed in REVMAN across four epochs: neonatal/infant (birth-1 year), early childhood (1–5 years), middle childhood (6–11 years) and adolescence (12–19 years). Caffeine reduced apnea (RR 0.59; 95%CI 0.46,0.75; very low certainty) and bronchopulmonary dysplasia (0.77; 0.69,0.86; moderate certainty), with higher doses more effective. Caffeine had no effect on neurocognitive impairment in early childhood but possible benefit on motor function in middle childhood (0.72; 0.57,0.91; moderate certainty). The optimal dose remains unknown; further long-term studies, are needed.
A randomized controlled trial evaluating low-intensity shockwave therapy for treatment of persistent storage symptoms following transurethral surgery for benign prostatic obstruction
Authors: Hegazy Mohammed , Sheir Khaled Z. , Gaballah Mohamed A. , Elshal Ahmed M.
Published: March 2024

Background

Low-intensity shockwave therapy (Li-SWT) can improve bladder function through enhancement of angiogenesis and nerve regeneration and suppression of inflammation and overactivity. In this trial, we aimed to evaluate the efficacy of Li-SWT on persistent storage symptoms after transurethral surgery (TUS) for benign prostatic obstruction (BPO).

Methods

Between July 2020 and July 2022, 137 patients with persistent storage symptoms; urgency episodes/24 h ≥ 1 and daytime frequency ≥8, for at least three months after TUS for BPO were randomly allocated to Li-SWT versus sham versus solifenacin 10 mg/day in 3:1:1 ratio. The primary end point was the percent reduction from baseline in overactive bladder symptom score (OABSS) at 3-month follow-up. The changes in 3-day voiding diary parameters, quality of life (QoL) score, peak flow rate and residual urine at 3 and 6-month follow-up were compared. Treatment-related adverse effects were also evaluated.

Results

Baseline data were comparable between groups. The percent reduction from baseline in OABSS at 3-month follow-up was significantly higher in Li-SWT compared to sham (−55% versus −11%), and it was comparable between Li-SWT and solifenacin-10 (−55% versus −60%). Li-SWT achieved significant improvement like solifenacin-10 in 3-day voiding diary parameters and QoL score at 3-month follow-up. This improvement remained comparable between Li-SWT and solifenacin-10 at 6-month follow-up. No adverse effects related to Li-SWT were noted apart from tolerable pain during the procedure. Solifenacin-10 was associated with bothersome adverse effects in 73% of the patients with 11.5% discontinuation rate.

Conclusions

Li-SWT ameliorates persistent storage symptoms and promotes QoL after TUS for BPO, with comparable efficacy and better tolerance compared to solifenacin.
Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis
Authors: Jiang Lingli , Ye Yishan , Han Yingli , Wang Qiwei , Lu Huan , Li Jinxin , Qian Wenchang , Zeng Xin , Zhang Zhaoru , Zhao Yanmin , Shi Jimin , Luo Yi , Qiu Yunfei , Sun Jun , Sheng Jinghao , Huang He , Qian Pengxu
Published: March 2024

Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors’ feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.
Hairpin trimer transition state of amyloid fibril
Authors: Sari Levent , Bali Sofia , Joachimiak Lukasz A. , Lin Milo M.
Published: March 2024

Protein fibril self-assembly is a universal transition implicated in neurodegenerative diseases. Although fibril structure/growth are well characterized, fibril nucleation is poorly understood. Here, we use a computational-experimental approach to resolve fibril nucleation. We show that monomer hairpin content quantified from molecular dynamics simulations is predictive of experimental fibril formation kinetics across a tau motif mutant library. Hairpin trimers are predicted to be fibril transition states; one hairpin spontaneously converts into the cross-beta conformation, templating subsequent fibril growth. We designed a disulfide-linked dimer mimicking the transition state that catalyzes fibril formation, measured by ThT fluorescence and TEM, of wild-type motif - which does not normally fibrillize. A dimer compatible with extended conformations but not the transition-state fails to nucleate fibril at any concentration. Tau repeat domain simulations show how long-range interactions sequester this motif in a mutation-dependent manner. This work implies that different fibril morphologies could arise from disease-dependent hairpin seeding from different loci.
DELVE: feature selection for preserving biological trajectories in single-cell data
Authors: Ranek Jolene S. , Stallaert Wayne , Milner J. Justin , Redick Margaret , Wolff Samuel C. , Beltran Adriana S. , Stanley Natalie , Purvis Jeremy E.
Published: March 2024

Single-cell technologies can measure the expression of thousands of molecular features in individual cells undergoing dynamic biological processes. While examining cells along a computationally-ordered pseudotime trajectory can reveal how changes in gene or protein expression impact cell fate, identifying such dynamic features is challenging due to the inherent noise in single-cell data. Here, we present DELVE, an unsupervised feature selection method for identifying a representative subset of molecular features which robustly recapitulate cellular trajectories. In contrast to previous work, DELVE uses a bottom-up approach to mitigate the effects of confounding sources of variation, and instead models cell states from dynamic gene or protein modules based on core regulatory complexes. Using simulations, single-cell RNA sequencing, and iterative immunofluorescence imaging data in the context of cell cycle and cellular differentiation, we demonstrate how DELVE selects features that better define cell-types and cell-type transitions. DELVE is available as an open-source python package:https://github.com/jranek/delve.
Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue
Authors: Dhavale Dhruva D. , Barclay Alexander M. , Borcik Collin G. , Basore Katherine , Berthold Deborah A. , Gordon Isabelle R. , Liu Jialu , Milchberg Moses H. , O’Shea Jennifer Y. , Rau Michael J. , Smith Zachary , Sen Soumyo , Summers Brock , Smith John , Warmuth Owen A. , Perrin Richard J. , Perlmutter Joel S. , Chen Qian , Fitzpatrick James A. J. , Schwieters Charles D. , Tajkhorshid Emad , Rienstra Chad M. , Kotzbauer Paul T.
Published: March 2024

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.
The initial stages of cement hydration at the molecular level
Authors: Xu Xinhang , Qi Chongchong , Aretxabaleta Xabier M. , Ma Chundi , Spagnoli Dino , Manzano Hegoi
Published: March 2024

Cement hydration is crucial for the strength development of cement-based materials; however, the mechanism that underlies this complex reaction remains poorly understood at the molecular level. An in-depth understanding of cement hydration is required for the development of environmentally friendly cement and consequently the reduction of carbon emissions in the cement industry. Here, we use molecular dynamics simulations with a reactive force field to investigate the initial hydration processes of tricalcium silicate (C3S) and dicalcium silicate (C2S) up to 40 ns. Our simulations provide theoretical support for the rapid initial hydration of C3S compared to C2S at the molecular level. The dissolution pathways of calcium ions in C3S and C2S are revealed, showing that, two dissolution processes are required for the complete dissolution of calcium ions in C3S. Our findings promote the understanding of the calcium dissolution stage and serve as a valuable reference for the investigation of the initial cement hydration.
Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms
Authors: Agostini Antonio , Piro Geny , Inzani Frediano , Quero Giuseppe , Esposito Annachiara , Caggiano Alessia , Priori Lorenzo , Larghi Alberto , Alfieri Sergio , Casolino Raffaella , Scaglione Giulia , Tondolo Vincenzo , Cammarota Giovanni , Ianiro Gianluca , Corbo Vincenzo , Biankin Andrew V. , Tortora Giampaolo , Carbone Carmine
Published: March 2024

The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression.
Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients
Authors: De Biasi Sara , Lo Tartaro Domenico , Neroni Anita , Rau Moritz , Paschalidis Nikolaos , Borella Rebecca , Santacroce Elena , Paolini Annamaria , Gibellini Lara , Ciobanu Alin Liviu , Cuccorese Michela , Trenti Tommaso , Rubio Ignacio , Vitetta Francesca , Cardi Martina , Argüello Rafael José , Ferraro Diana , Cossarizza Andrea
Published: March 2024

Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.
Cholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds
Authors: Zhang Bao-cun , Laursen Marlene F. , Hu Lili , Hazrati Hossein , Narita Ryo , Jensen Lea S. , Hansen Aida S. , Huang Jinrong , Zhang Yan , Ding Xiangning , Muyesier Maimaitili , Nilsson Emil , Banasik Agnieszka , Zeiler Christina , Mogensen Trine H. , Etzerodt Anders , Agger Ralf , Johannsen Mogens , Kofod-Olsen Emil , Paludan Søren R. , Jakobsen Martin R.
Published: March 2024

The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification. This facilitates ER membrane curvature and STING trafficking to Golgi. Notably, we identify two cholesterol-binding motifs in STING and confirm their contribution to ER-retention of STING. Consequently, depletion of intracellular cholesterol levels enhances STING pathway activation upon cGAMP stimulation. In a preclinical tumour model, intratumorally administered cholesterol depletion therapy potentiated STING-dependent anti-tumoral responses, which, in combination with anti-PD-1 antibodies, promoted tumour remission. Collectively, we demonstrate that ER cholesterol sets a threshold for STING signalling through cholesterol-binding motifs in STING and we propose that this could be exploited for cancer immunotherapy.
Machine-learning-assisted and real-time-feedback-controlled growth of InAs/GaAs quantum dots
Authors: Shen Chao , Zhan Wenkang , Xin Kaiyao , Li Manyang , Sun Zhenyu , Cong Hui , Xu Chi , Tang Jian , Wu Zhaofeng , Xu Bo , Wei Zhongming , Xue Chunlai , Zhao Chao , Wang Zhanguo
Published: March 2024

The applications of self-assembled InAs/GaAs quantum dots (QDs) for lasers and single photon sources strongly rely on their density and quality. Establishing the process parameters in molecular beam epitaxy (MBE) for a specific density of QDs is a multidimensional optimization challenge, usually addressed through time-consuming and iterative trial-and-error. Here, we report a real-time feedback control method to realize the growth of QDs with arbitrary density, which is fully automated and intelligent. We develop a machine learning (ML) model named 3D ResNet 50 trained using reflection high-energy electron diffraction (RHEED) videos as input instead of static images and providing real-time feedback on surface morphologies for process control. As a result, we demonstrate that ML from previous growth could predict the post-growth density of QDs, by successfully tuning the QD densities in near-real time from 1.5 × 1010 cm−2 down to 3.8 × 108 cm−2 or up to 1.4 × 1011 cm−2. Compared to traditional methods, our approach can dramatically expedite the optimization process and improve the reproducibility of MBE. The concepts and methodologies proved feasible in this work are promising to be applied to a variety of material growth processes, which will revolutionize semiconductor manufacturing for optoelectronic and microelectronic industries.
Correlating fluorescence microscopy, optical and magnetic tweezers to study single chiral biopolymers such as DNA
Authors: Shepherd Jack W. , Guilbaud Sebastien , Zhou Zhaokun , Howard Jamieson A. L. , Burman Matthew , Schaefer Charley , Kerrigan Adam , Steele-King Clare , Noy Agnes , Leake Mark C.
Published: March 2024

Biopolymer topology is critical for determining interactions inside cell environments, exemplified by DNA where its response to mechanical perturbation is as important as biochemical properties to its cellular roles. The dynamic structures of chiral biopolymers exhibit complex dependence with extension and torsion, however the physical mechanisms underpinning the emergence of structural motifs upon physiological twisting and stretching are poorly understood due to technological limitations in correlating force, torque and spatial localization information. We present COMBI-Tweez (Combined Optical and Magnetic BIomolecule TWEEZers), a transformative tool that overcomes these challenges by integrating optical trapping, time-resolved electromagnetic tweezers, and fluorescence microscopy, demonstrated on single DNA molecules, that can controllably form and visualise higher order structural motifs including plectonemes. This technology combined with cutting-edge MD simulations provides quantitative insight into complex dynamic structures relevant to DNA cellular processes and can be adapted to study a range of filamentous biopolymers.
Subslab ultra low velocity anomaly uncovered by and facilitating the largest deep earthquake
Authors: Chen Weiwen , Wei Shengji , Wang Weitao
Published: March 2024

It is enigmatic that M8+ earthquakes can take place at depth greater than 600 km inside the slab, where the P-T conditions generally do not favor seismic slip rate (~m/s) on faults. Here we provide fresh insights to the initial rupture and mechanism of the Mw 8.3 Sea of Okhotsk earthquake by analyzing high-frequency (up to 0.8 Hz) teleseismic array data. We determine the relative location and timing of two early subevents, and the geometry and velocity perturbation of a nearby structure anomaly. We found a small-scale (~30 × 60 × 60 km) ultralow (−18 ± 2%) P-wave velocity anomaly located beneath the Pacific slab around the 660 km discontinuity. The volatile-bearing highly melted nature of the anomaly provides significant buoyancy, stressing the slab dramatically closer to the critical condition for thermal runaway weakening that allows the rupture to propagate beyond the metastable olivine wedge, forming M8+ events. Enormous velocity reduction urges for further mineral physics and geodynamic investigations.
Lactobacillus plantarum L168 improves hyperoxia-induced pulmonary inflammation and hypoalveolarization in a rat model of bronchopulmonary dysplasia
Authors: Shen Xian , Yang Zhaocong , Wang Qiang , Chen Xu , Zhu Qihui , Liu Zhi , Patel Nishant , Liu Xingyin , Mo Xuming
Published: March 2024

Alteration of gut microbiota can affect chronic lung diseases, such as asthma and chronic obstructive pulmonary disease, through abnormal immune and inflammatory responses. Previous studies have shown a feasible connection between gut microbiota and bronchopulmonary dysplasia (BPD) in preterm infants. However, whether BPD can be ameliorated by restoring the gut microbiota remains unclear. In preterm infants with BPD, we found variance in the diversity and structure of gut microbiota. Similarly, BPD rats showed gut dysbiosis, characterized by a deficiency of Lactobacillus, which was abundant in normal rats. We therefore explored the effect and potential mechanism of action of a probiotic strain, Lactobacillus plantarum L168, in improving BPD. The BPD rats were treated with L. plantarum L168 by gavage for 2 weeks, and the effect was evaluated by lung histopathology, lung function, and serum inflammatory markers. Subsequently, we observed reduced lung injury and improved lung development in BPD rats exposed to L. plantarum L168. Further evaluation revealed that L. plantarum L168 improved intestinal permeability in BPD rats. Serum metabolomics showed altered inflammation-associated metabolites following L. plantarum L168 intervention, notably a marked increase in anti-inflammatory metabolites. In agreement with the metabolites analysis, RNA-seq analysis of the intestine and lung showed that inflammation and immune-related genes were down-regulated. Based on the information from RNA-seq, we validated that L. plantarum L168 might improve BPD relating to down-regulation of TLR4 /NF-κB /CCL4 pathway. Together, our findings suggest the potential of L. plantarum L168 to provide probiotic-based therapeutic strategies for BPD.
Effect of 60 days of head down tilt bed rest on amplitude and phase of rhythms in physiology and sleep in men
Authors: Bonmatí-Carrión María-Ángeles , Santhi Nayantara , Atzori Giuseppe , Mendis Jeewaka , Kaduk Sylwia , Dijk Derk-Jan , Archer Simon N.
Published: March 2024

Twenty-four-hour rhythms in physiology and behaviour are shaped by circadian clocks, environmental rhythms, and feedback of behavioural rhythms onto physiology. In space, 24 h signals such as those associated with the light-dark cycle and changes in posture, are weaker, potentially reducing the robustness of rhythms. Head down tilt (HDT) bed rest is commonly used to simulate effects of microgravity but how HDT affects rhythms in physiology has not been extensively investigated. Here we report effects of −6° HDT during a 90-day protocol on 24 h rhythmicity in 20 men. During HDT, amplitude of light, motor activity, and wrist-temperature rhythms were reduced, evening melatonin was elevated, while cortisol was not affected during HDT, but was higher in the morning during recovery when compared to last session of HDT. During recovery from HDT, time in Slow-Wave Sleep increased. EEG activity in alpha and beta frequencies increased during NREM and REM sleep. These results highlight the profound effects of head-down-tilt-bed-rest on 24 h rhythmicity.
Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach
Authors: Williams Bevelynn , Paterson Jamie , Rawsthorne-Manning Helena J. , Jeffrey Polly-Anne , Gillard Joseph J. , Lythe Grant , Laws Thomas R. , López-García Martín
Published: March 2024

Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is the strain used in the manufacture of the UK anthrax vaccine. Then, for the first time, we quantify PA production and degradation via mathematical modelling and Bayesian statistical techniques, making use of this new experimental data as well as two other independent published data sets. We propose a single mathematical model, in terms of delay differential equations (DDEs), which can explain the in vitro dynamics of all three data sets. Since we did not heat activate the B. anthracis spores prior to inoculation, germination occurred much slower in our experiments, allowing us to calibrate two additional parameters with respect to the other data sets. Our model is able to distinguish between natural PA decay and that triggered by bacteria via proteases. There is promising consistency between the different independent data sets for most of the parameter estimates. The quantitative characterisation of B. anthracis PA production and degradation obtained here will contribute towards the ambition to include a realistic description of toxin dynamics, the host immune response, and anti-toxin treatments in future mechanistic models of anthrax infection.
A unified dataset for the city-scale traffic assignment model in 20 U.S. cities
Authors: Xu Xiaotong , Zheng Zhenjie , Hu Zijian , Feng Kairui , Ma Wei
Published: March 2024

City-scale traffic data, such as traffic flow, speed, and density on every road segment, are the foundation of modern urban research. However, accessing such data on a city scale is challenging due to the limited number of sensors and privacy concerns. Consequently, most of the existing traffic datasets are typically limited to small, specific urban areas with incomplete data types, hindering the research in urban studies, such as transportation, environment, and energy fields. It still lacks a city-scale traffic dataset with comprehensive data types and satisfactory quality that can be publicly available across cities. To address this issue, we propose a unified approach for producing city-scale traffic data using the classic traffic assignment model in transportation studies. Specifically, the inputs of our approach are sourced from open public databases, including road networks, traffic demand, and travel time. Then the approach outputs comprehensive and validated citywide traffic data on the entire road network. In this study, we apply the proposed approach to 20 cities in the United States, achieving an average correlation coefficient of 0.79 in average travel time and an average relative error of 5.16% and 10.47% in average travel speed when compared with the real-world data.
Effects of light perception on visual function recovery in patients with traumatic optic neuropathy
Authors: Wang Jiancun , Xue Qiang , Tan Xuewen , Huang Jie , Zhu Yibai , Li Wen
Published: March 2024

This study aimed to assess the impact of light perception presence or absence on visual function recovery in patients with traumatic optic neuropathy (TON). A retrospective analysis was conducted on the clinical data of 206 TON patients. Based on the presence or absence of light perception after injury, patients were categorized into a light perception group and a non-light perception group. A comparison was made between the two groups regarding visual acuity recovery before and after treatment. The non-light perception group comprised 63 patients, with a treatment effectiveness rate of 39.68%. The light perception group consisted of 143 patients, with a treatment effectiveness rate of 74.83%. The difference between the two groups was statistically significant (χ2 = 23.464, P < 0.01). Subgroup analysis indicated that surgical treatment appeared to be more effective than steroid hormone therapy for patients with light perception. Conversely, for patients without light perception, there was no significant difference in the effectiveness of the two methods. The total effectiveness rate of the light perception group was significantly higher than that of the non-light perception group, suggesting that patients with light perception before treatment experience better outcomes compared to those without light perception. Treatment choices should be individualized to ensure optimal results.
Risk factors for suboptimal glycemic control in pediatrics with type 1 diabetes mellitus: a cross-sectional study
Authors: Ghazaiean Mobin , Najafi Behnam , Zamanfar Daniel , Alipour Mohammad Javad
Published: March 2024

The objective of this research is to analyze the influence of various factors on glycemic control in pediatrics with type 1 diabetes mellitus (T1DM). The study, a cross-sectional analysis, involved 221 T1DM patients below 18 years old who visited our clinic between 2011 and 2020, predating the COVID-19 outbreak. Out of the initial pool, 204 participants were chosen based on specific criteria. By computing odds ratios and 95% confidence intervals, we determined the correlation between these factors and achieving optimal glycemic control (HbA1c < 7.5%). Of the 204 individuals, 55.9% (113 patients) were female. The average age at diagnosis was 6.93 ± 3.9 years. Mean HbA1c (A1C) level of optimal and suboptimal groups were 6.97, 95% CI 6.84 to 7.1 and 8.86, 95% CI 8.68 to 9.03, respectively (p-value < 0.001). Fifty patients had optimal glycemic control and 154 people experienced suboptimal glycemic control during the follow-up that the prevalence of each of them was 24.51, 95% CI 18.7 to 31 and 75.49, 95% CI 68.99 to 81.22, respectively. In the assessment of risk factors associated with suboptimal glycemic control, patients aged 10–14 years had the highest likelihood of experiencing suboptimal glycemic control (crude odds ratio [COR] 3.12, 95% CI 1.04 to 9.3), followed by duration of diabetes (COR 2.85, 95% CI 1.2 to 6.8), which both were significant. By utilizing multivariable logistic regression analysis, a noteworthy finding emerged. It was revealed that patients aged 10–14 years exhibited a significant association with suboptimal glycemic control, [adjusted odds ratio (AOR) 4.85, 95% CI 1.32 to 17.7]. Additionally, a statistically significant correlation was identified between individuals with a body mass index (BMI) falling within the ≥ 95th percentile category and suboptimal glycemic control, Cramer’s V = 0.21, p-value = 0.01. Our research has revealed a significant correlation between patients aged 10–14 years and obese individuals (BMI ≥ 95th) with suboptimal glycemic control. It is crucial to consider these factors as they can offer valuable insights during diagnosis, highlighting the increased risk of long-term suboptimal glycemic control.
Response of the metabolic activity and taxonomic composition of bacterial communities to mosaically varying soil salinity and alkalinity
Authors: Mucsi Márton , Borsodi Andrea K. , Megyes Melinda , Szili-Kovács Tibor
Published: March 2024

Soil salinity and sodicity is a worldwide problem that affects the composition and activity of bacterial communities and results from elevated salt and sodium contents. Depending on the degree of environmental pressure and the combined effect of other factors, haloalkalitolerant and haloalkaliphilic bacterial communities will be selected. These bacteria play a potential role in the maintenance and restoration of salt-affected soils; however, until recently, only a limited number of studies have simultaneously studied the bacterial diversity and activity of saline–sodic soils. Soil samples were collected to analyse and compare the taxonomic composition and metabolic activity of bacteria from four distinct natural plant communities at three soil depths corresponding to a salinity‒sodicity gradient. Bacterial diversity was detected using 16S rRNA gene Illumina MiSeq amplicon sequencing. Community-level physiological profiles (CLPPs) were analysed using the MicroResp™ method. The genus-level bacterial composition and CLPPs differed significantly in soils with different alkaline vegetation. The surface soil samples also significantly differed from the intermediate and deep soil samples. The results showed that the pH, salt content, and Na+ content of the soils were the main edaphic factors influencing both bacterial diversity and activity. With salinity and pH, the proportion of the phylum Gemmatimonadota increased, while the proportions of Actinobacteriota and Acidobacteriota decreased.
Long-term cardiovascular outcome in women with preeclampsia in Korea: a large population-based cohort study and meta-analysis
Authors: Choi Eun-Saem , Jung Young Mi , Kim Dayoung , Cho Su Eun , Park Eun Sun , Park Chan-Wook , Park Joong Shin , Jun Jong Kwan , Lee Seung Mi
Published: March 2024

Recent studies reported the long-term cardiovascular risk of preeclampsia. However, only a few studies have investigated the association between preeclampsia and long-term cardiovascular disease in Asian populations, although there could be racial/ethnic differences in the risk of cardiovascular diseases. Therefore, we aimed to evaluate the long-term effects of preeclampsia on cardiovascular disease in an Asian population. This study included 68,658 parous women in the Health Examinees Study (HEXA) cohort of South Korea and compared the risk of long-term cardiovascular disease, including ischemic heart disease and stroke, according to the history of preeclampsia. We also performed a meta-analysis combining current study data with data from existing literature in the Asian population. Among the study population, 3413 (5.23%) women had a history of preeclampsia, and 767 (1.12%) and 404 (0.59%) women developed ischemic heart disease and stroke for 22 years. Women with a history of preeclampsia were at a higher risk for both ischemic heart disease (adjusted hazard ratio 1.66 [1.19–2.04]) and stroke (adjusted hazard ratio 1.48 [1.02–2.16]) than those without. In the meta-analysis, the pooled hazard ratio of ischemic heart disease and stroke were also increased in women with a history of preeclampsia (ischemic heart disease 1.65 [1.51–1.82]; stroke 1.78 [1.52–2.10]).
Unveiling the antibacterial and antifungal potential of biosynthesized silver nanoparticles from Chromolaena odorata leaves
Authors: Bishoyi Ajit Kumar , Sahoo Chita Ranjan , Samal Priyanka , Mishra Nilima Priyadarsini , Jali Bigyan Ranjan , Khan Mohd Shahnawaz , Padhy Rabindra Nath
Published: March 2024

This research investigates the biogenic synthesis of silver nanoparticles (AgNPs) using the leaf extract of Chromolaena odorata (Asteraceae) and their potential as antibacterial and antifungal agents. Characterization techniques like ultraviolet–visible, Fourier transform infrared (FTIR), Dynamic light scattering and zeta potential (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and field emission scanning electron microscopy and energy-dispersive X-ray spectroscopy (FESEM-EDX) confirmed the formation of spherical (AgNPs). UV–vis spectroscopy reaffirms AgNP formation with a peak at 429 nm. DLS and zeta potential measurements revealed an average size of 30.77 nm and a negative surface charge (− 0.532 mV). Further, XRD analysis established the crystalline structure of the AgNPs. Moreover, the TEM descriptions indicate that the AgNPs are spherical shapes, and their sizes ranged from 9 to 22 nm with an average length of 15.27 nm. The X-ray photoelectron spectroscopy (XPS) analysis validated the formation of metallic silver and elucidated the surface state composition of AgNPs. Biologically, CO-AgNPs showed moderate antibacterial activity but excellent antifungal activity against Candida tropicalis (MCC 1559) and Trichophyton rubrum (MCC 1598). Low MIC values (0.195 and 0.390 mg/mL) respectively, suggest their potential as effective antifungal agents. This suggests potential applications in controlling fungal infections, which are often more challenging to treat than bacterial infections. Molecular docking results validated that bioactive compounds in C. odorata contribute to antifungal activity by interacting with its specific domain. Further research could pave the way for the development of novel and safe antifungal therapies based on biogenic nanoparticles.
Precise analysis of single small extracellular vesicles using flow cytometry
Authors: Kobayashi Hisano , Shiba Takayuki , Yoshida Takeshi , Bolidong Dilireba , Kato Koroku , Sato Yoshiki , Mochizuki Mao , Seto Takafumi , Kawashiri Shuichi , Hanayama Rikinari
Published: March 2024

Methods that enable specific and sensitive quantification of small extracellular vesicles (sEVs) using flow cytometry are still under development. Aggregation or adsorption of antibodies causes sub-nano sized particles or non-specific binding and largely affects the results of flow cytometric analysis of single sEVs. Comparison of control IgG and target-specific IgG is inappropriate because they have different characters. Here, we evaluate four preparation methods for flow cytometry, including ultracentrifugation, density gradient centrifugation, size exclusion chromatography (SEC), and the TIM4-affinity method by using tetraspanin-deficient sEVs. The ultracentrifugation or density gradient centrifugation preparation method has large false-positive rates for tetraspanin staining. Conversely, preparation methods using SEC or the TIM4-affinity method show specific detection of single sEVs, which elucidate the roles of sEV biogenesis regulators in the generation of sEV subpopulations. The methods are also useful for the detection of rare disease-related markers, such as PD-L1. Flow cytometric analysis using SEC or the TIM4-affinity method could accelerate research into sEV biogenesis and the development of sEV-based diagnostics and therapies.
Extreme drought along the tropic of cancer (Yunnan section) and its impact on vegetation
Authors: Zhang Yanke , Gu Tengfei , He Suling , Cheng Feng , Wang Jinliang , Ye Hui , Zhang Yunfeng , Su Huai , Li Qinglei
Published: March 2024

The frequent occurrence of extreme weather events is one of the future prospects of climate change, and how ecosystems respond to extreme drought is crucial for response to climate change. Taking the extreme drought event in the Tropic of Cancer (Yunnan section) during 2009–2010 as a case study, used the standardized precipitation evapotranspiration index to analyse the impact of extreme drought on enhanced vegetation index (EVI), leaf area index (LAI) and gross primary productivity (GPP), and to analyzed the post extreme drought vegetation recovery status. The results indicate the following: (1) Due to the cumulative effects of drought and vegetation phenology, vegetation growth in the months of March to May in 2010 was more severely affected. (2) Compared to EVI and LAI, GPP is more sensitive to drought and can accurately indicate areas where drought has impacted vegetation. (3) Following an extreme drought event, 70% of the vegetation can recover within 3 months, while 2.87–6.57% of the vegetation will remain unrecovered after 6 months. (4) Cropland and grassland show the strongest response, with longer recovery times, while woodland and shrubland exhibit weaker responses and shorter recovery times. This study provides a reference for the effects of extreme drought on vegetation.