bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure-volume analysis of thermodynamic workload of voiding - an application in pelvic organ prolapse patients subjected to robotic-assisted sacrocolpopexy
Authors: Lau Hui-Hsuan , Lai Cheng-Yuan , Hsieh Ming-Chun , Peng Hsien-Yu , Chou Dylan , Su Tsung-Hsien , Lee Jie-Jen , Lin Tzer-Bin
Published: December 2024

Purpose

Given objective benefits of robotic-assisted sacrocolpopexy (RSCP) to the voiding function/deficit of patients with pelvic organ prolapse (POP) waits to be clarified, this study investigated if RSCP modifies voiding functions of POP patients by focusing on its impact on the outlet resistance-dependent voiding workload using pressure-volume analysis (PVA), a protocol thermodynamically assaying work expenditure by the bladder in voiding cycles.

Methods

Pre- and post-operative cystometry and PVA of 22 female patients, who underwent RSCP for POP (stage ≥ II), were reviewed. Mean voiding resistance (Rvod), mean voiding pressure (Pvod), mean voiding flow (Fvod), voided volume (Vvod), voiding time (Tvod), and the trajectory-enclosed area (Apv) were analyzed.

Results

The PVA, in which trajectory shaped an enclosed loop representing a voiding cycle, was established by adapting from the time-domain cystometry. Compared to the pre-operative control, RSCP decreased Rvod, Pvod, and Tvod (p = 0.003, 0.042, and 0.040, respectively. All N = 22) but increased Fvod (p = 0.036, N = 22) without markedly affecting Vvod (p = 0.580, N = 22). Apv was decreased after RSCP (p = 0.017, N = 22). The RSCP-decreased Rvod (ΔRvod) displayed a moderate correlation with both the decreased Pvod (ΔPvod, r = 0.551, p = 0.007, N = 22) and the increased Fvod (ΔFvod, r=-0.625, p = 0.001, N = 22). The ΔFvod moderately correlated with the decreased Tvod (ΔTvod, r=-0.620, p = 0.002, N = 22). Moreover, the RSCP-decreased Apv (ΔApv) displayed correlation with the ΔPvod (r = 0.385, p = 0.047, N = 22).

Conclusions

Through diminishing outlet resistance of POP patients, RSCP not only prompted urine emission thereby increased voiding efficacy but also decreased the pressure developed for driving urine flow that lessened voiding workload.

Clinical Trial Registration ClinicalTrials.gov (NCT05682989).
The relationship between respiratory symptoms and frailty: findings from observational and Mendelian randomization analyses
Authors: Ruan Zhishen , Li Dan , Cong Xiaodong , Yuan Shasha , Fan Yiling , Xu Bo , Miao Qing
Published: December 2024

Introduction

As ageing accelerates, frailty increasingly impacts public health. Cough, sputum, wheezing and dyspnea are common respiratory symptoms, and the relationship to frailty is unclear. We aimed to analyze the relationship between respiratory symptoms and frailty.

Methods

Cross-sectional and Mendelian randomization (MR) studies were used. Cross-sectional data involved 14,021 participants from the National Health and Nutrition Examination Survey (NHANES). Logistic and linear regression were used to analyze the relationship between respiratory symptoms (cough, sputum, wheezing, dyspnea) and frailty. We adjusted for multiple variables and used propensity score matching (PSM). Mediation analysis was used to explore the role of inflammatory markers and age in the relationship between the two. We analyzed the relationship using a two-sample MR approach with data from genome-wide association studies (GWAS) to enhance causal inference.

Results

Observational studies have shown that cough (OR 1.74, 95 CI% 1.44, 2.09), sputum (OR 1.87, 95 CI% 1.57, 2.22), wheezing (OR 2.01, 95 CI% 1.68, 2.40), and dyspnea (OR 2.60, 95 CI% 2.28, 2.97) are associated with an elevated risk of frailty. The PSM results were stable. Mediation analyses indicated that elevated inflammatory markers and advancing age were mediators between respiratory symptoms and frailty. The results of the MR study showed that sputum and wheezing were associated with an elevated frailty index; and in the study of FI on respiratory symptoms, all respiratory symptoms were elevated with elevated FI.

Conclusions

Our study identified a potential association between frailty and respiratory symptoms. Inflammation and ageing may be essential factors mediating this association.
Extend the ProFamy cohort-component method to conduct probabilistic households and living arrangement projections
Authors: Zeng Yi , Wang Zhenglian , Feng Qiushi , Gu Danan , Zhang Junni , Tang Wei , Land Kenneth
Published: December 2024

In this commentary, we first briefly review the significant utilities of household and living arrangement projections and the main types of methods for conducting household projections. In the second and third sections, we summarize basic ideas, data needed, assessments and applications of ProFamy extended cohort-component methods/software for households and living arrangement projections; and we emphasize the importance to extend the ProFamy methods and software from deterministic to probabilistic households and living arrangement projections. In section 4, we demonstrate that the ProFamy approach provides an adequate and highly feasible modelling framework to extend probabilistic households and living arrangement projections (PHPs), in which the population size/structure projection outcomes are in consistence with those of probabilistic population projections (PPPs) released by United Nations Population Division (UNPD). In the last Section, we discuss and recommend applying the user-friendly R package DemoRates of ProFamy software to estimate rural/urban (or race)-sex-age-specific standard schedules and the demographic summary measures, to conduct analyses and projections, such as single-parent households, caregivers, and care needs/costs for disabled older adults, age-friendly housing and households-based energy demands, etc. for healthy aging and sustainable development studies. Finally, we discuss the prospects of our ongoing international collaborative research project to substantially extend ProFamy cohort-component method from deterministic into probabilistic households and living arrangement projection (PHPs). As compared with ProFamy deterministic projection method, the PHPs produces a lot of additional outcomes of probabilistically projected households and living arrangements in 2021–2100 with uncertainty intervals that are crucial for healthy aging and sustainable development studies.
Balance between photoreduction efficiency, cofactor affinity, and allosteric coupling of halogenase flavoenzymes
Authors: Diepold Niklas , Reese Friederike , Prior Tina , Schnepel Christian , Sewald Norbert , Kottke Tilman
Published: December 2024

Flavin-dependent halogenases (FDHs) are promising candidates for the sustainable production of halogenated organic molecules by biocatalysis. FDHs require only oxygen, halide and a fully reduced flavin adenine dinucleotide (FADH−) cofactor to generate the reactive HOX that diffuses 10 Å to the substrate binding pocket and enables regioselective oxidative halogenation. A key challenge for the application of FDHs is the regeneration of the FADH−. In vitro, FADH− can be regenerated by photoreduction of the oxidized FAD inside the protein using blue light, turning the halogenase into an inefficient artificial photoenzyme. We aimed to improve the photochemical properties of the tryptophan 5-halogenase PyrH from Streptomyces rugosporus by structure-guided mutagenesis. W279 and W281 of the conserved WxWxIP-motif close to FAD were exchanged against phenylalanine. Time-resolved UV-vis spectroscopy showed that the W281F exchange indeed increased the quantum yield of the one- and two-electron reduction, respectively. The cofactor binding affinity decreased slightly with dissociation constants rising from 31 to 74 μM, as examined by fluorescence anisotropy. FTIR difference spectroscopy demonstrated that the allosteric coupling between the FAD and substrate binding sites was mostly preserved. In contrast, the double mutant did not improve the yield further, while negatively affecting binding affinity and structural coupling. The distal W279F exchange was less effective in all parameters. Photoreductions were additionally delayed by a reversible inactive conformation. We conclude that there is a delicate balance to be considered for screening of FDHs for biocatalysis. Variant PyrH-W281F was found to be the most promising candidate for the application as artificial photoenzyme.

Graphical abstract
Tectono‐Geomorphic Features Related to the 1606 Jianshui Earthquake in the Southernmost Segment of the Xiaojiang Fault System, SE Tibet
Authors: Dong Shaopeng , Han Zhujun , Guo Peng , Hu Nan , Tan Xibin , Xie Zhangdi , Ran Hongliu
Published: December 2024

The activity and seismicity of the southern segment of the Xianshuihe‐Xiaojiang fault system (XXFS) are both crucial for differentiating kinematic models along the southeastern margin of the Tibetan Plateau. Based on tectono‐geomorphic interpretations of optical imagery, digital elevation model (DEM)‐derived hillshades, contour maps, and field observations of geomorphic features, we document a surface rupture zone with a maximum length of ∼75 km and a maximum offset of ∼6.8 m along the Jianshui fault (JSF) in the southern segment of the XXFS. By correlating geologic, chronological, and historical data, we suggest that an Mw 7.1–7.9 earthquake occurred on 30 November 1606, along the JSF that was previously considered as a minimal active fault, and the magnitude of this earthquake was cited as M63/4. A large surface offset and relatively short rupture length are likely related to the immaturity of the JSF, and this also implies southeastward growth of the SE Tibetan Plateau during the late Quaternary.
Revisiting the 10th‐Century Eldgjá Eruption: Modeling the Climatic and Environmental Impacts
Authors: Fuglestvedt Herman F. , Gabriel Imogen , Sigl Michael , Thordarson Thorvaldur , Krüger Kirstin
Published: December 2024

The 10th‐century Eldgjá eruption in Iceland is the largest basaltic flood lava eruption of the Common Era. However, the extent of its impacts is unclear due to limited historical records. Combining volcanology and ice‐core analyses from both recent and earlier studies, we present a gas emissions scenario for the Eldgjá eruption spanning 937 to 940 CE, co‐injecting volcanic sulfur and halogens. The combined tropospheric and stratospheric sulfur emissions are 3–8 times higher than those adopted for Eldgjá in existing paleoclimate simulations. Earth system modeling of this scenario under pre‐industrial conditions reveals a compound event with maximum northern extratropics surface cooling of C in summer‐autumn of 939 and 940 CE, prolonged Arctic sea ice growth, and large‐scale precipitation changes, concurrent with stratospheric ozone depletion and elevated pollution. These results imply that the combined climatic and environmental effects of the Eldgjá eruption may have significantly impacted human populations at the time.
Antarctic Wide Subglacial Hydrology Modeling
Authors: Ehrenfeucht Shivani , Dow Christine , McArthur Koi , Morlighem Mathieu , McCormack Felicity S.
Published: December 2024

Global sea levels are rising due, in large part, to the increase in the rate of melting of ice sheets as a direct result of climate change. A large fraction of uncertainty in future sea level rise comes from limited understanding of basal conditions under ice sheets. Specifically, subglacial hydrology, which describes the volume and movement of meltwater underneath glaciers and resulting basal water pressures. This system exerts a strong control on ice basal sliding and the rate of ice shelf melt, both of which can destabilize glaciers and lead to enhanced sea level rise. Here, we present subglacial hydrology model results of the full Antarctic Ice Sheet derived using the Glacier Drainage System model. We examine water pressures of the distributed drainage system, the distribution of the channelized system, and freshwater discharge across grounding lines of major drainage basins in the steady state subglacial system under present day conditions.
Sea Ice Modulates Air–Sea Methane Flux in the Southern Ocean
Authors: Zhang Gong , Yang Qinghua , Han Bo , Prytherch John , Thornton Brett F. , Chen Dake
Published: December 2024

The Southern Ocean (SO) is predicted to be a weak sink for atmospheric CH4, although the magnitude is uncertain due to a lack of observations of the marginal ice zone (MIZ). Using both eddy covariance and bulk formula flux measurements from the icebreaker R/V Xuelong2, we found that the eastern SO during an austral summer was a sink for CH4. The strongest downward CH4 fluxes occurred in areas of low sea ice concentration (10%–40%), where sea‐ice melting resulted in low temperature and salinity, increasing CH4 solubility. The CH4 fluxes are weak in regions of high sea ice concentration (>50%) due to the blocking effect of sea ice. We estimate that the uptake of CH4 during one summer month in the study region offsets 1.2%–2.6% of annual global oceanic CH4 emissions. Suggesting that the Antarctic MIZ is more important in the global CH4 budget than previously thought.
Slip Deficit Rate and Seismic Potential on Crustal Faults in Tibet
Authors: Li Yanchuan , Shan Xinjian , Qu Chunyan , Zhang Guohong , Wang Xuening , Xiong Haicheng
Published: December 2024

Quantifying slip deficit rates on active faults in Tibet is essential for understanding fault kinematics and assessing seismic hazards, but has not been fully characterized, particularly on secondary faults. In this study, we integrate an updated interseismic Global Navigation Satellite Systems velocity field from 4,458 stations across continental China and its surroundings to calculate surface strain rates in Tibet, which we then use to invert for slip deficit rates on 263 crustal faults (383 segments). Our results reveal that ∼73% of strain rates are due to elastic strain accumulation on fault planes, and only a portion of the remaining strain rates may originate from unmodeled fault deformation. Quantitative calculations of seismic moment budgets on these fault segments indicate that they can produce earthquakes ranging from Mw 5.8 to 8.6, with 43 segments capable of generating earthquakes of Mw ≥ 7.5. Our findings provide a foundation for probabilistic seismic hazard analysis in Tibet.
Saturation Characteristics of Multi‐Band EMIC Waves in the Inner Magnetosphere and Observational Evidence for the Second Saturation Process
Authors: Xue Zuxiang , Yuan Zhigang , Deng Dan , Yu Xiongdong
Published: December 2024

The wave amplitude is vital for quantifying the impact of electromagnetic ion cyclotron (EMIC) waves on inner magnetospheric dynamics. Previous numerical studies mainly focused on the evolution of total wave energy/amplitude, whose maximum is usually modeled as a function of initial conditions. Recent quasilinear theory analysis shows existence of a second saturation of multi‐band EMIC waves which exhibits a dip of the total amplitude, emphasizing the need for more precise band‐specific models. Through one‐dimensional hybrid simulations, we reproduce the second saturation phenomenon and separately model wave characteristics for H+‐ and He+‐bands waves, including the maximum amplitudes and the time to maximum as a function of the initial maximum growth rate. Moreover, new parameters for the anisotropy‐beta inverse correlation of hot protons are obtained at the second saturation stage. We further present an in situ observation that first demonstrates the existence of the second saturation.
Coupled Thermosphere‐Ionosphere Tongue‐Like Structure During the Recovery Phase of the Geomagnetic Storm on 12 May 2021
Authors: Yu Tingting , Ren Zhipeng , Zhao Biqiang , Pedatella Nicholas , Wei Yong , Li Shaoyang , Zhai Changzhi , Zhao Lingxin
Published: December 2024

A coupled thermosphere‐ionosphere tongue‐like structure was observed in the daytime at middle latitudes by ground‐based Global Navigation Satellite System (GNSS) and Global‐scale Observations of the Limb and Disk (GOLD) observations during the storm recovery phase on 12 May 2021. The storm‐induced variations in total electron content (TEC) and the column density ratio of O to N2 (∑O/N2) both showed a relatively narrow region of enhancement in latitude, originating from low latitudes and surrounded by depleted regions. The concurrent neutral temperature observations also showed a tongue‐like decrease surrounded by temperature enhancements. The Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model (TIEGCM) qualitatively reproduced the observed thermosphere‐ionosphere structure. The simulations indicate that the formation of the TEC tongue‐like structure was dominated by the enhanced ΣO/N2. Unlike the previously reported tongue of ionization (TOI) driven by E × B drifts, the tongue‐like structure occurred at relatively lower geomagnetic latitudes (∼30–∼65) and had a smaller magnitude of enhancement. This is the first time that the concurrent tongue‐like structures in thermospheric composition, temperature and electron density are observed, which advances the understanding of thermosphere‐ionosphere coupling.
The Geometrical Features of Magnetic Flux Entanglement Events Observed by MMS
Authors: Ahmad Nisar , Shen Chao , Ji Yong , E Peng , Rehman Umer , Yao Guang‐Rui , Li Xiao‐Jie , Zhao Ying‐Jie , Ji Yan‐Fang
Published: December 2024

Flux transfer events are momentary occurrences of self‐adjusting, rope‐like magnetized plasma structures near Earth's magnetopause, typically associated with a southward interplanetary magnetic field direction. This study aims to investigate the magnetic structural characteristics during three phases (initial, intermediate and final) of magnetic flux entanglement events and explore magnetic field gradient properties. Using the Nonlinear Magnetic Field Gradient Algorithm (NMG), we computed magnetic field curvature, helix angle, and torsion. Our analysis revealed that the central current sheet consistently exhibits the highest magnetic field curvature throughout all phases, while the lowest curvature occurs elsewhere. Notably, a polarity reversal in the normal component of magnetic field curvature is observed during the intermediate phase. The helix angle exhibits its maximum variation on both sides of the central current sheet during the initial phase. In the intermediate phase, however, the variation of the helix angle around the current sheet is minimal. By the final phase, the magnitude of the helix angle behaves in a manner opposite to that of the initial phase. Torsion around the current sheet initially undergoes significant changes during the initial phase but remains close to zero afterward. Conversely, in the intermediate phase, the magnetic flux regime shows minimal torsion initially, followed by an abrupt variations afterward. Nonetheless, during final phase, the magnetic flux regimes display a consistent pattern of increasing and decreasing torsion similar to the initial phase. In summary, flux tubes precede the emergence of flux ropes in the initial phase, structures resembling flux ropes dominate the intermediate phase, and both coexist in the final phase. This investigation sheds light on the interconnected nature of these structures, critical for understanding particle and energy exchange between the magnetosphere and solar wind.
Constraints on the Seismogenic Stress Tensor in Northeastern South Island, New Zealand
Authors: Walbert Olivia Leigh , Hetland Eric Andreas
Published: December 2024

The seismogenic tensorial stresses in the crust beneath northeastern South Island, New Zealand that are responsible for the 2010 Darfield and 22 February 2011 Christchurch earthquakes of the Canterbury Plains, South Island, New Zealand are compatible with an Andersonian strike‐slip regime with a NW–SE trending most compressive stress. The stresses we infer from coseismic slip models of these two earthquakes are consistent with previous estimates of stress from earthquake focal mechanisms near the Alpine Fault. The strike‐slip stress regime of the Canterbury Plains differs from the thrust stress regime that we previously estimated from coseismic models of the 2016 Kaikōura earthquake. We demonstrate that loading due to thick sediment deposits overlying the crust of the Canterbury Plains is a sufficient mechanism to rotate the principal stresses from a background thrust regime to a strike‐slip regime, constraining the absolute tectonic stress in the northeast of South Island to most likely be 26 MPa, and no larger than 80 MPa.
Intermediate‐Volatility Organic Compounds (IVOCs) Emissions Based on Source‐Specific Emission Ratios Relative to NonMethane Volatile Organic Compounds (NMVOCs) Give Better Representation of the Spatial Distribution of IVOCs in China
Authors: Yang Ning , Wang Qiaoqiao , Xiong Qi , Fan Zeman , Liu Guangjin , Li Fan , Zhu Shaowen , Zhou Yaqing , Tao Jiangchuan , Hong Juan , Wang Hongli , Huang Cheng , Sun Yele , Cheng Yafang , Su Hang , Ma Nan
Published: December 2024

Intermediate‐volatility organic compounds (IVOCs) and their contribution to secondary organic aerosols (SOA) in China are simulated in GEOS‐Chem with seven newly constructed IVOCs emission inventories (IEIs). The IEIs based on different references and source‐specific emission ratios show a large range of emissions in China (4.8–14 Tg yr−1) and also significant differences in major sources and spatial distributions. Among them, the IEI relative to nonMethane volatile organic compounds (NMVOCs) with a total emission of 12 Tg yr−1, dominated by solvent use, better captures observed spatial distributions of IVOCs and SOA. In contrast, IEIs relative to primary organic aerosols (POA) misinterpret the major sources and tend to have a negative bias in megacities even when the total emission is scaled up to 14 Tg yr−1. The study indicates that previous studies have underestimated IVOCs emission and hence the contribution to SOA. It also demonstrates the importance of using an appropriate reference to better represent the major sources and the spatial distribution of IVOCs.
On the Quantification of Thermodynamic Phases of Raining Clouds: Insights From Multi‐Year CloudSat and Ground‐Based Radar Observations Over Longmen, Southern China
Authors: Li Qinghui , Li Haoran , Sun Xuejin , Ruan Zheng , Liu Liping , Gao Wenhua , Liao Chenxi , Ding Han
Published: December 2024

The thermodynamic phase of clouds is fundamental to rain initiation and development. Although it is well established that majority of rainfall from mid‐ to‐high latitudes originates from ice, there is a lack of consensus on the major thermodynamic phase of raining clouds over low latitudes. Previous CloudSat‐based studies have yet reached consistent results on the fraction of ice‐phase raining clouds over Southern China. In this work, we found that CloudSat‐based approaches are subject to metrics used for flagging rainfall events, which may lead to different estimates. Analysis of multi‐year surface radar observations suggests that has diurnal variation and increases with rain rate, while the surface rainfall originating from warm clouds does not exceed 50 . Using disdrometer observations to flag surface rainfall events, we found that about 71 and 95 of surface rainfall events and rainfall accumulation come from cold clouds, respectively. In addition, the observed rainfall accumulations over Longmen are consistent with the fifth generation atmospheric reanalysis (ERA5), whereas the frequency of warm rainfall over Longmen is significantly underestimated in ERA5.
Insight Into the Molecular Photooxidation Evolution Mechanism of Brown Carbon Released From Residential Solid Fuel Combustion
Authors: Wang Diwei , Shen Zhenxing , Bai Gezi , Zhang Leiming , Huang Shasha , Sun Jian , Xu Hongmei , Cao Junji
Published: December 2024

Solid fuels were one of the important emission sources of brown carbon (BrC). This study investigates molecular composition of BrC derived from combustion of five types of residential solid fuels (i.e., firewood, corn cob, bituminous coal, anthracite, and biomass briquette) and their photooxidation evolution mechanisms using an oxidation flow reactor. Results show that nitrogen‐containing and sulfur‐containing organic compounds are the main components of molecular composition of methanol‐soluble organic compounds (MSOC) emitted from these fuels, with their intensity being 33%–43% and 23%–56%, respectively, depending on fuel type. The photooxidation processes mediated by NO3⋅ and ⋅ OH significantly altered the molecular composition and distribution of aged MSOC. The formation of typical nitrogen‐containing BrC chromophores (e.g., nitro‐aromatic compounds) also proves the role of NO3 ⋅ in the photooxidation reaction. However, the photo‐enhancement effect of NO3 ⋅ mediated photooxidation reaction could not offset the destruction of the molecular conjugation degree and aromaticity of BrC by ⋅ OH oxidation, resulting in a significant reduction in the light absorption capacity of BrC. The mass absorption coefficient at 365 nm of BrC aged for 12 days derived from the remaining fuels decreased by 47.0%–55.8% compared to that of fresh BrC, except for firewood, which only decreased by 5.3%. These findings on the molecular evolution and oxidation mechanism of BrC generated from solid fuels are useful in reducing uncertainties in climate change studies involving BrC aerosol.
Mechanisms for the Influence of the MJO on Precipitation in Southwestern South America
Authors: Matus F. , Rondanelli R. , Rutllant J. , Henderson S.
Published: December 2024

During austral winter under neutral ENSO conditions, positive precipitation anomalies in Southwestern South America from 30 to 45S coincide with strong real‐time multivariate MJO (RMM) Phase 1 events. Using ERA5 composites arranged according to active RMM phases, we found that a three‐part mechanism, traced approximately 10–15 days before MJO Phase 1 events, roughly corresponding to RMM phases 7 and 8, explains these precipitation anomalies. This mechanism is composed of three Rossby wave trains in response to convective perturbations: two cross equatorial teleconnections attributed to suppressed convection in the Indian Ocean and the Maritime Continent, and an interhemispheric Rossby wave linked to enhanced convection over the warm pool of the western hemisphere. Composite analyses of OLR and wave activity flux, complemented with Rossby wave ray tracing, support these findings. This research provides insights into the MJO's influence on additional large‐scale teleconnection patterns across the Southern Hemisphere besides the Pacific South American (PSA) teleconnection mode. The dispersion of the convective RMM phase at different lags and the interaction between multiple wave trains introduce uncertainty when associating a specific RMM phase with precipitation anomalies.
Intravenous sedation for adults with profound acquired brain injury undergoing dental treatment - a seven-year service evaluation
Authors: Doshi Mili , Kahatab Ahmed , Gallagher Louise , Prasad Ria , Fitzgerald Richard
Published: December 2024

Background

Dental treatment may not be possible for patients with a profound acquired brain injury without pharmacological support. Intravenous (IV) sedation with midazolam is a widely accepted, safe, and effective mode of treatment for people with a disability, but there is limited evidence in this patient cohort.

Aims

This evaluation aimed to review the IV sedation service for patients with profound acquired brain injury within the dental department at the Royal Hospital for Neuro-disability.

Method

This study was a retrospective service evaluation of IV sedation for dental treatment over seven years. Descriptive statistics are presented.

Results

In total, 303 episodes of sedation were undertaken at the Royal Hospital of Neurodisability over seven years. Ninety-two percent were graded with an American Society of Anaesthesiologists (ASA) grade 3, and one-third had a history of stroke. 91% had treatment completed successfully. Complications occurred in 7.9% of cases, but all were minor, with no resulting patient harm (e.g. a transient drop in oxygen saturation).

Conclusion

Dentist-led IV sedation with midazolam is safe and effective for dental treatment for patients with a profound acquired brain injury in a specialised setting with experienced clinicians.
Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling
Authors: Feetham Claire H. , Collabolletta Valeria , Worth Amy A. , Shoop Rosemary , Groom Sam , Harding Court , Boutagouga Boudjadja Mehdi , Coskun Tamer , Emmerson Paul J. , D’Agostino Giuseppe , Luckman Simon M.
Published: December 2024

Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius. Thus, BDNFmNTS neurons are required for the weight-reducing actions of both GDF15 and the GLP1RA, Exendin-4. Moreover, acute activation of BDNFmNTS neurons is sufficient to reduce food intake and drive fatty acid oxidation and might provide a route for longer-term weight loss.
A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth
Authors: Good Marina R. , Fernández-Quintero Monica L. , Ji Wei , Rodriguez Alesandra J. , Han Julianna , Ward Andrew B. , Guthmiller Jenna J.
Published: December 2024

Clade 2.3.4.4b H5N1 is causing an unprecedented outbreak in dairy cows in the United States. To understand if recent H5N1 viruses are changing their receptor use, we screened recombinant hemagglutinin (HA) from historical and recent 2.3.4.4b H5N1 viruses for binding to distinct glycans bearing terminal sialic acids using a glycan microarray. We find that H5 from A/Texas/37/2024, an isolate from the dairy cow outbreak, has increased binding breadth to core glycans bearing terminal α2,3 sialic acids, the avian receptor, compared to historical and recent 2.3.4.4b H5N1 viruses. We do not observe any binding to α2,6 sialic acids, the receptor used by human seasonal influenza viruses. Using molecular dynamics and a cryo-EM structure of A/Texas/37/2024 H5, we show A/Texas/37/2024 H5 is more flexible within the receptor-binding site compared to a 2.3.4.4b H5 from 2022. We identify a single mutation outside of the receptor binding site, T199I, is responsible for increased binding breadth, as it increases receptor binding site flexibility. Together, these data show recent H5N1 viruses are evolving increased receptor binding breadth which could impact the host range and cell types infected with H5N1.
Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance
Authors: Ngwana-Joseph Gabrielle C. , Phelan Jody E. , Manko Emilia , Dombrowski Jamille G. , da Silva Santos Simone , Suarez-Mutis Martha , Vélez-Tobón Gabriel , Tobón Castaño Alberto , Machado Ricardo Luiz Dantas , Marinho Claudio R. F. , Nolder Debbie , Nosten François , Sutherland Colin J. , Campino Susana , Clark Taane G.
Published: December 2024

Increasing reports of chloroquine resistance (CQR) in Plasmodium vivax endemic regions have led to several countries, including Indonesia, to adopt dihydroarteminsin-piperaquine instead. However, the molecular drivers of CQR remain unclear. Using a genome-wide approach, we perform a genomic analysis of 1534 P. vivax isolates across 29 endemic countries, detailing population structure, patterns of relatedness, selection, and resistance profiling, providing insights into potential drivers of CQR. Selective sweeps in a locus proximal to pvmdr1, a putative marker for CQR, along with transcriptional regulation genes, distinguish isolates from Indonesia from those in regions where chloroquine remains highly effective. In 106 isolates from Indonesian Papua, the epicentre of CQR, we observe an increasing prevalence of novel SNPs in the candidate resistance gene pvmrp1 since the introduction of dihydroartemisinin-piperaquine. Overall, we provide novel markers for resistance surveillance, supported by evidence of regions under recent directional selection and temporal analysis in this continually evolving parasite.
Operando real-space imaging of a structural phase transformation in the high-voltage electrode LixNi0.5Mn1.5O4
Authors: Sun Yifei , Hy Sunny , Hua Nelson , Wingert James , Harder Ross , Meng Ying Shirley , Shpyrko Oleg , Singer Andrej
Published: December 2024

Discontinuous solid-solid phase transformations play a pivotal role in determining the properties of rechargeable battery electrodes. By leveraging operando Bragg Coherent Diffractive Imaging (BCDI), we investigate the discontinuous phase transformation in LixNi0.5Mn1.5O4 within an operational Li metal coin cell. Throughout Li-intercalation, we directly observe the nucleation and growth of the Li-rich phase within the initially charged Li-poor phase in a 500 nm particle. Supported by the microelasticity model, the operando imaging unveils an evolution from a curved coherent to a planar semi-coherent interface driven by dislocation dynamics. Our data indicates negligible kinetic limitations from interface propagation impacting the transformation kinetics, even at a discharge rate of C/2 (80 mA/g). This study highlights BCDI’s capability to decode complex operando diffraction data, offering exciting opportunities to study nanoscale phase transformations with various stimuli.
Grain engineering for efficient near-infrared perovskite light-emitting diodes
Authors: Baek Sung-Doo , Shao Wenhao , Feng Weijie , Tang Yuanhao , Lee Yoon Ho , Loy James , Gunnarsson William B. , Yang Hanjun , Zhang Yuchen , Faheem M. Bilal , Kaswekar Poojan Indrajeet , Atapattu Harindi R. , Qin Jiajun , Coffey Aidan H. , Park Jee Yung , Yang Seok Joo , Yang Yu-Ting , Zhu Chenhui , Wang Kang , Graham Kenneth R. , Gao Feng , Qiao Quinn , Guo L. Jay , Rand Barry P. , Dou Letian
Published: December 2024

Metal halide perovskites show promise for next-generation light-emitting diodes, particularly in the near-infrared range, where they outperform organic and quantum-dot counterparts. However, they still fall short of costly III-V semiconductor devices, which achieve external quantum efficiencies above 30% with high brightness. Among several factors, controlling grain growth and nanoscale morphology is crucial for further enhancing device performance. This study presents a grain engineering methodology that combines solvent engineering and heterostructure construction to improve light outcoupling efficiency and defect passivation. Solvent engineering enables precise control over grain size and distribution, increasing light outcoupling to ~40%. Constructing 2D/3D heterostructures with a conjugated cation reduces defect densities and accelerates radiative recombination. The resulting near-infrared perovskite light-emitting diodes achieve a peak external quantum efficiency of 31.4% and demonstrate a maximum brightness of 929 W sr−1 m−2. These findings indicate that perovskite light-emitting diodes have potential as cost-effective, high-performance near-infrared light sources for practical applications.
A coopetition-driven strategy of parallel/perpendicular aromatic stacking enabling metastable supramolecular polymerization
Authors: Gao Zhao , Xie Xuxu , Zhang Juan , Yuan Wei , Yan Hongxia , Tian Wei
Published: December 2024

Metastable supramolecular polymerization under kinetic control has recently been recognized as a closer way to biosystem than thermodynamic process. While impressive works on metastable supramolecular systems have been reported, the library of available non-covalent driving modes is still small and a simple yet versatile solution is highly desirable to design for easily regulating the energy landscapes of metastable aggregation. Herein, we propose a coopetition-driven metastability strategy for parallel/perpendicular aromatic stacking to construct metastable supramolecular polymers derived from a class of simple monomers consisting of lateral indoles and aromatic core. By subtly increasing the stacking strength of aromatic cores from phenyl to anthryl, the parallel face-to-face stacked aggregates are competitively formed as metastable products, which spontaneously transform into thermodynamically favorable species through the cooperativity of perpendicular edge-to-face stacking and parallel offset stacking. The slow kinetic-to-thermodynamic transformation could be accelerated by adding seeds for realizing the desired living supramolecular polymerization. Besides, this transformation of parallel/perpendicular aromatic stacking accompanied by time-dependent emission change from red to yellow is employed to dynamic cell imaging, largely avoiding the background interferences. The coopetition relationship of different aromatic stacking for metastable supramolecular systems is expected to serve as an effective strategy towards pathway-controlled functional materials.
Atomically engineering interlayer symmetry operations of two-dimensional crystals
Authors: Han Ziyi , Wu Shengqiang , Huang Chun , Xuan Fengyuan , Han Xiaocang , Long Yinfeng , Zhang Qing , Li Junxian , Meng Yuan , Wang Lin , Zhou Jiahuan , Hu Wenping , Qiao Jingsi , Geng Dechao , Zhao Xiaoxu
Published: December 2024

Crystal symmetry, which governs the local atomic coordination and bonding environment, is one of the paramount constituents that intrinsically dictate materials’ functionalities. However, engineering crystal symmetry is not straightforward due to the isotropically strong covalent/ionic bonds in crystals. Layered two-dimensional materials offer an ideal platform for crystal engineering because of the ease of interlayer symmetry operations. However, controlling the crystal symmetry remains challenging due to the ease of gliding perpendicular to the Z direction. Herein, we proposed a substrate-guided growth mechanism to atomically fabricate AB′-stacked SnSe2 superlattices, containing alternating SnSe2 slabs with periodic interlayer mirror and gliding symmetry operations, by chemical vapor deposition. Some higher-order phases such as 6 R, 12 R, and 18 C can be accessed, exhibiting modulated nonlinear optical responses suggested by first-principle calculations. Charge transfer from mica substrates stabilizes the high-order SnSe2 phases. Our approach shows a promising strategy for realizing topological phases via stackingtronics.
Lactobacillus crispatus S-layer proteins modulate innate immune response and inflammation in the lower female reproductive tract
Authors: Decout Alexiane , Krasias Ioannis , Roberts Lauren , Gimeno Molina Belen , Charenton Chloé , Brown Romero Daniel , Tee Qiong Y. , Marchesi Julian R. , Ng Sherrianne , Sykes Lynne , Bennett Phillip R. , MacIntyre David A.
Published: December 2024

Lactobacillus species dominance of the vaginal microbiome is a hallmark of vaginal health. Pathogen displacement of vaginal lactobacilli drives innate immune activation and mucosal barrier disruption, increasing the risks of STI acquisition and, in pregnancy, of preterm birth. We describe differential TLR mediated activation of the proinflammatory transcription factor NF-κB by vaginal pathogens and commensals. Vaginal Lactobacillus strains associated with optimal health selectively interact with anti-inflammatory innate immune receptors whereas species associated with suboptimal health including L. iners and Gardnerella vaginalis interact with both pro- and anti-inflammatory receptors. Anti-inflammatory action of L. crispatus is regulated by surface layer protein (SLPs)-mediated shielding of TLR ligands and selective interaction with the anti-inflammatory receptor DC-SIGN. Detection of SLPs within cervicovaginal fluid samples is associated with decreased concentrations of pro-inflammatory cytokines in Lactobacillus crispatus-dominated samples. These data offer mechanistic insights into how vaginal microbiota modulate host immune response and thus reproductive health and disease states.
INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform
Authors: Yau Chun Ngo , Hung Jacky Tin Shing , Campbell Robert A. A. , Wong Thomas Chun Yip , Huang Bei , Wong Ben Tin Yan , Chow Nick King Ngai , Zhang Lichun , Tsoi Eldric Pui Lam , Tan Yuqi , Li Joshua Jing Xi , Wing Yun Kwok , Lai Hei Ming
Published: December 2024

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume. Diverse antigens, mRNAs, neurotransmitters, and post-translational modifications are well-preserved and simultaneously visualized. INSIHGT also allows multi-round, highly multiplexed 3D molecular probing and is compatible with downstream traditional histology and nucleic acid sequencing. With INSIHGT, we map undescribed podocyte-to-parietal epithelial cell microfilaments in mouse glomeruli and neurofilament-intensive inclusion bodies in the human cerebellum, and identify NPY-proximal cell types defined by spatial morpho-proteomics in mouse hypothalamus. We anticipate that INSIHGT can form the foundations for 3D spatial multi-omics technology development and holistic systems biology studies.
Evolutionary origins and functional diversification of Auxin Response Factors
Authors: Hernández-García Jorge , Carrillo-Carrasco Vanessa Polet , Rienstra Juriaan , Tanaka Keita , de Roij Martijn , Dipp-Álvarez Melissa , Freire-Ríos Alejandra , Crespo Isidro , Boer Roeland , van den Berg Willy A. M. , Lindhoud Simon , Weijers Dolf
Published: December 2024

The Auxin Response Factors (ARFs) family of transcription factors are the central mediators of auxin-triggered transcriptional regulation. Functionally different classes of extant ARFs operate as antagonistic auxin-dependent and -independent regulators. While part of the evolutionary trajectory to the present auxin response functions has been reconstructed, it is unclear how ARFs emerged, and how early diversification led to functionally different proteins. Here, we use in silico and in vivo analyses to revisit the molecular events that led to the origin and subsequent evolution of the ARFs. We reveal the shared origin of ARFs from preexisting domains, uncovering a protein fold homologous to the ARF DNA-binding fold in a conserved eukaryotic chromatin regulator. Building on this, we reconstruct the complete evolutionary history of ARFs, including the divergence events leading to the appearance of the ARF classes and defining the main molecular targets for their functional diversification. We derive a complete evolutionary trajectory that led to the emergence of the nuclear auxin signalling pathway.
Electronic ferroelectricity in monolayer graphene moiré superlattices
Authors: Zhang Le , Ding Jing , Xiang Hanxiao , Liu Naitian , Zhou Wenqiang , Wu Linfeng , Xin Na , Watanabe Kenji , Taniguchi Takashi , Xu Shuigang
Published: December 2024

Extending ferroelectric materials to two-dimensional limit provides versatile applications for the development of next-generation nonvolatile devices. Conventional ferroelectricity requires materials consisting of at least two constituent elements associated with polar crystalline structures. Monolayer graphene as an elementary two-dimensional material unlikely exhibits ferroelectric order due to its highly centrosymmetric hexagonal lattices. Here, we report the observations of electronic ferroelectricity in monolayer graphene by introducing asymmetric moiré superlattice at the graphene/h-BN interface, in which the electric polarization stems from electron-hole dipoles. The polarization switching is probed through the measurements of itinerant Hall carrier density up to room temperature, manifesting as standard polarization-electric field hysteresis loops. We find ferroelectricity in graphene moiré systems exhibits generally similar characteristics in monolayer, bilayer, and trilayer graphene, which indicates layer polarization is not essential to observe the ferroelectricity. Furthermore, we demonstrate the applications of this ferroelectric moiré structures in multi-state nonvolatile data storage with high retention and the emulation of versatile synaptic behaviors. Our work not only provides insights into the fundamental understanding of ferroelectricity, but also demonstrates the potential of graphene for high-speed and multi-state nonvolatile memory applications.
Heat stable and intrinsically sterile liquid protein formulations
Authors: Lawanprasert Atip , Singh Harminder , Pimcharoen Sopida , Vargas Mariangely González , Dewan Arshiya , Kirimanjeswara Girish S. , Medina Scott H.
Published: December 2024

Over 80% of biologic drugs, and 90% of vaccines, require temperature-controlled conditions throughout the supply chain to minimize thermal inactivation and contamination. This cold chain is costly, requires stringent oversight, and is impractical in remote environments. Here, we report chemical dispersants that non-covalently solvate proteins within fluorous liquids to alter their thermodynamic equilibrium and reduce conformational flexibility. This generates non-aqueous, fluorine-based liquid protein formulations that biochemically rigidify protein structure to yield thermally stable biologics at extreme temperatures (up to 90 °C). These non-aqueous formulations are impervious to contamination by microorganismal pathogens, degradative enzymes, and environmental impurities, and display comparable pre-clinical pharmacokinetics and safety profiles to standard saline protein samples. As a result, we deliver a fluorochemical formulation paradigm that may limit the need for cold chain logistics of protein reagents and biopharmaceuticals.
Enhanced mechanical properties of alkali-activated dolomite dust emulsified asphalt composites
Authors: Liu Qun , Lin Weiqing , Xi Lei
Published: December 2024

The dolomite dust-emulsified asphalt composite (DAC) with excellent mechanical properties was successfully prepared using alkali activation. The effects of different alkali concentrations and emulsified asphalt contents on the mechanical properties of the materials were studied. And the micro-mechanisms of its mechanical performance changes were analyzed through SEM and XRD characterization. The experimental results show that the specimens have excellent mechanical properties: the 7-day compressive strength can reach 76.67 MPa, and the bending and compressive strength ratio is about twice that of silicate-based geopolymer-emulsified asphalt composite (SAC). With an increase in emulsified asphalt content, the compressive strength of the samples decreases, while the bending strength increases first and then decreases. When the emulsified asphalt content is 1%, the bending strength of the sample is up to 28.81 MPa, which is 25% higher than that of the sample without emulsified asphalt. The in-situ formation of calcium carbonate crystal clusters within the DAC was suggested that may support this performance. This crystalline structuring contributes to an expanded interfacial contact area between the asphalt and skeleton particles, thereby enhancing the demulsification and bonding properties of the emulsified asphalt. This indicates that an appropriate emulsified asphalt content can play a toughening role in the system, providing a new idea for designing high-toughness alkali-activated materials.