bluuebunny/crossref_metadata_2025 huggingface dataset:
Rigorous Regional Air Quality Standards for Substantial Health Benefits
Authors: Zhang Wenxiao , Xu Haoran , Yu Xinyuan , Li Jin , Zhang Yuanzheng , Dai Rong , Zheng Shuxiu , Meng Wenjun , Shen Huizhong , Chen Yilin , Shen Guofeng , Ma Jianmin , Li Bengang , Liu Junfeng , Wang Xuejun , Tao Shu
Published: December 2023

Following a series of actions in China, the annual mean fine particle (PM2.5) concentrations have considerably reduced since 2013. However, in some cities, the PM2.5 concentrations exceed the national ambient air quality standard of 35 μg/m3. Herein, we evaluated the historical trends of PM2.5 from 2014 to 2022 in mainland China and found continuously declining trends. However, the annual decline rates decreased despite increasing investments on pollution control, showing considerably diminishing marginal effects of these investments. Accumulative reduction in PM2.5 concentrations is linearly dependent on the log‐transformed accumulative investment in air pollution control. The standard of 35 μg/m3 can be achieved by 2035 if the current efforts continue at the same pace. However, the standard of 35 μg/m3 can weaken the momentum of future actions in cities where the standard has already been implemented. We proposed and tested two tiers with four or six levels of specific regional standards based on the regression model predictions from the historical data and demonstrated that more rigorous standards for regions where the current standard is already attained could provide more momentum for strengthening abatement efforts. The results show that both tiers are feasible if the level of abatement endeavor is maintained even with marginal effects. We also demonstrate that additional 135,000 or 384,000 deaths can be avoided by applying the regional standards. Health benefits are monetized and compared with the control costs, suggesting that compared to Tier‐2, Tier‐1 is more cost‐effective and balanced across the mainland China.
Multi‐Objective Ensemble‐Processing Strategies to Optimize the Simulation of the Western North Pacific Subtropical High in Boreal Summer
Authors: Sun Cenxiao , Jiang Zhihong , Tang Zhenfei , Li Laurent
Published: December 2023

The western North Pacific Subtropical High (WNPSH) in boreal summer is a major atmospheric player affecting East Asian climate, but its simulation in state‐of‐the‐art climate models is still largely biased. Here we use a multi‐objective optimization strategy, the Pareto optimality, to incorporate multiple physical constraints in processing multi‐model simulations provided by the Coupled Model Intercomparison Project Phase 6. We aim to improve the simulation of WNPSH by this practice. Sea surface temperatures from three tropical oceanic basins are found highly related to WNPSH, and thus used as constraints. We also present an ameliorated strategy, which takes a subset of the raw Pareto optimality by imposing conditions of smallest errors. Results show that the overestimate of WNPSH is effectively corrected. The two multi‐objective optimization schemes both perform better than the traditional approach, revealing the importance of implementing physically based links in processing multi‐model ensemble simulations.
A Numerical Investigation on the Formation of the Stalling of the Cross‐Polar Jet in Midnight Thermospheric Winds
Authors: Tan Yusha , Dang Tong , Lei Jiuhou , Wang Wenbin , Zhang Binzheng
Published: December 2023

Thermospheric winds usually flow from noon to the midnight inside the polar cap and spill further equatorward around midnight, due to the combined effects of solar radiation‐driven pressure gradient and ion drag. Recent observations from the Scanning Doppler Imager at Poker Flat indicated a distinct feature that the cross‐polar jet stalls over short horizontal distances around the magnetic midnight. However, the mechanisms responsible for the occurrence of stalling have not been well understood. In this study, we investigated the physical mechanisms of the stalling of the cross‐polar jet based on the Thermosphere Ionosphere Electrodynamics General Circulation Model simulations. The model reproduced the general stalling features at midnight over a short horizontal distance. The occurrence of stalling is mainly associated with Joule heating, which enhances the neutral temperature and then turns winds poleward by the pressure gradient force, and ion‐neutral coupling, which drags neutral winds westward in the pre magnetic local time midnight sector and contributes to the poleward turning of the meridional winds by the poleward Coriolis force. Meanwhile, the stalling region has a large latitudinal range and depends on the interplanetary magnetic field (IMF). Under southward IMF Bz, thermospheric winds are likely to stall at lower latitudes associated with strong ionospheric convection. The stalling of the cross‐polar jet in the midnight thermospheric winds has UT/longitude dependence, which could be associated with the orientation of the alignment of geomagnetic and geographic poles with respect to ionospheric convection.
Effective Radiative Forcing of the Internally Mixed Sulfate and Black Carbon Aerosol in the GFDL AM4 Model: The Role Played by Other Aerosol Species
Authors: Govardhan Gaurav , Paynter David , Ramaswamy Venkatachalam
Published: December 2023

We compute the effective radiative forcing (ERF) of the internally mixed sulfate‐black carbon (SBC) aerosol species in the Geophysical Fluid Dynamics Laboratory's (GFDL) Atmospheric Model version 4 (AM4) model using five different formulations. The formulations differ in how they account for the presence of other aerosol species. The global mean ERF of SBC in the GFDL AM4 model ranges from −0.51 ± 0.1 to −1.06 ± 0.1 W m−2. The three most realistic configurations of the five, in which the emissions of other aerosol species vary between 1850 and 2010 states, depict a tighter distribution of ERF (−0.51, −0.55, and −0.57 ± 0.1). The two outlier configurations completely exclude one or more other aerosol species, which is slightly unrealistic but included for completeness. The former three configurations, however, result in substantially different ERFs over the regional hot spots of aerosols, e.g., over the land‐mass of East China; the choice of the emission conditions for organic carbon (i.e., present‐day or preindustrial) affects the ERF of SBC by ∼37%. The component of ERF related to aerosol‐cloud interactions (ACI) gets principally affected by the presence of other aerosol species. The higher the emissions of other aerosol species, the lesser is the ERF of SBC associated with ACI. This finding suggests that for ERF estimates, the choice of the emission level/concentrations of the other aerosol species significantly affects the estimates of SBC, especially over the aerosol hot spots.
Preface to Monitoring the Earth Radiation Budget and Its Implication to Climate Simulations: Recent Advances and Discussions
Authors: Montillet J.‐P. , Haberreiter M. , Rozanov E.
Published: December 2023

This article acts as an introduction to the JGR‐Atmospheres special section titled Monitoring the Earth Radiation Budget and its Implication to Climate Simulations: Recent Advances and Discussions. It outlines the key findings presented in the articles published in the special section. Additionally, it delves into some of the emerging trends in the ongoing research within this field of research.
The Effect of Sediment Transport Models on Simulating River Dune Dynamics
Authors: Lokin L. R. , Warmink J. J. , Hulscher S. J. M. H.
Published: December 2023

River dunes, dynamic bedforms in the river bed, limit navigable depths during low flows and increase bed roughness. To predict the navigable depth or where maintenance dredging is needed, a numerical dune development model can be a powerful tool. To study the effect of sediment transport on dune shape and propagation, four different sediment transport models were applied in an existing dune development model. Each sediment transport model was able to simulate dune propagation, while only sediment transport models based on the shear stress reshaped the river dunes. The tested sediment transport models can simulate dune celerity similar to observations and realistic, though different, dune shapes for low and median discharges. Implementation of a gravitational bed slope effect combined with a critical shear stress results in low angle dunes, which are representative for river dunes during low river flows. Sediment transport models with spatial relaxation, also result in low angle dunes. However, the relaxation parameters need to be redefined for low flow situation to prevent transition to upper stage plane bed at too low flow velocities. Further analysis of the resulting dune shapes shows that the sediment transport model determines the dune shape in terms of slope angles, while the dune height is related to the total transport capacity.
Quantifying the Impact of Spatiotemporal Resolution on the Interpretation of Fluvial Geomorphic Feature Dynamics From Sentinel 2 Imagery: An Application on a Braided River Reach in Northern Italy
Authors: Bozzolan Elisa , Brenna Andrea , Surian Nicola , Carbonneau Patrice , Bizzi Simone
Published: December 2023

Machine learning algorithms applied on the publicly available Sentinel 2 images (S2) are opening the opportunity to automatically classify and monitor fluvial geomorphic feature (such as sediment bars or water channels) dynamics across scales. However, there are few analyses on the relative importance of S2 spatial versus temporal resolution in the context of geomorphic research. In a dynamic, braided reach of the Sesia River (Northern Italy), we thus analyzed how the inherent uncertainty associated with S2's spatial resolution (10 m pixel size) can impact the significance of the active channel (a combination of sediment and water) delineation, and how the S2's weekly temporal resolution can influence the interpretation of its evolutionary trajectory. A comparison with manually classified images at higher spatial resolutions (Planet: 3 m and orthophoto: 0.3 m) shows that the automatically classified water is ∼20% underestimated whereas sediments are ∼30% overestimated. These classification errors are smaller than the geomorphic changes detected in the 5 years analyzed, so the derived active channel trajectory can be considered robust. The comparison across resolutions also highlights that the yearly Planet‐ and S2‐derived active channel trajectory are analogous and they are both more effective in capturing the river geomorphic response after major flood events than the trajectory derived from sequential multiannual orthophotos. More analyses of this type, across different types of river could give insights on the transferability of the spatial uncertainty boundaries found as well as on the spatial and temporal resolution trade‐off needed for supporting different geomorphic analyses.
Conversions between metabolically unhealthy and healthy obesity from midlife to late-life
Authors: Ler Peggy , Ojalehto Elsa , Zhan Yiqiang , Finkel Deborah , Dahl Aslan Anna K. , Karlsson Ida K.
Published: December 2023

Introduction

Metabolically healthy obesity may be a transient phenotype, but studies with long follow-up, especially covering late-life, are lacking. We describe conversions between cross-categories of body mass index (BMI) and metabolic health in 786 Swedish twins with up to 27 years of follow-up, from midlife to late-life.

Methods

Metabolic health was defined as the absence of metabolic syndrome (MetS). We first visualized conversions between BMI-metabolic health phenotypes in 100 individuals with measurements available at ages 50–64, 65–79, and ≥80. Next, we modeled conversion in metabolic health status by BMI category in the full sample using Cox proportional hazards regression.

Results

The proportion of individuals with MetS and with overweight or obesity increased with age. However, one-fifth maintained a metabolically healthy overweight or obesity across all three age categories. Among those metabolically healthy at baseline, 59% converted to MetS during follow-up. Conversions occurred 56% more often among individuals with metabolically healthy obesity, but not overweight, compared to normal weight. Among those with MetS at baseline, 60% regained metabolic health during follow-up, with no difference between BMI categories.

Conclusions

Conversions between metabolically healthy and unhealthy status occurred in both directions in all BMI categories. While conversions to MetS were more common among individuals with obesity, many individuals maintained or regained metabolic health during follow-up.
Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation – a registry study on behalf of the EBMT Acute Leukemia Working Party
Authors: Duque-Afonso Jesús , Finke Jürgen , Ngoya Maud , Galimard Jacques-Emmanuel , Craddock Charles , Raj Kavita , Bloor Adrian , Nicholson Emma , Eder Matthias , Kim Orchard , Valerius Thomas , Snowden John A. , Tholouli Eleni , Crawley Charles , Collin Matthew , Wilson Keith M. O. , Gadisseur Alain , Protheroe Rachel , Wagner-Drouet Eva Maria , Savani Bipin N. , Spyridonidis Alexandros , Ciceri Fabio , Nagler Arnon , Mohty Mohamad
Published: December 2023

Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT.
IGF2 prevents dopaminergic neuronal loss and decreases intracellular alpha-synuclein accumulation in Parkinson’s disease models
Authors: Arcos Javiera , Grunenwald Felipe , Sepulveda Denisse , Jerez Carolina , Urbina Valentina , Huerta Tomas , Troncoso-Escudero Paulina , Tirado Daniel , Perez Angela , Diaz-Espinoza Rodrigo , Nova Esteban , Kubitscheck Ulrich , Rodriguez-Gatica Juan Eduardo , Hetz Claudio , Toledo Jorge , Ahumada Pablo , Rojas-Rivera Diego , Martín-Montañez Elisa , Garcia-Fernandez María , Vidal René L.
Published: December 2023

Parkinson’s disease (PD) is the second most common late-onset neurodegenerative disease and the predominant cause of movement problems. PD is characterized by motor control impairment by extensive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). This selective dopaminergic neuronal loss is in part triggered by intracellular protein inclusions called Lewy bodies, which are composed mainly of misfolded alpha-synuclein (α-syn) protein. We previously reported insulin-like growth factor 2 (IGF2) as a key protein downregulated in PD patients. Here we demonstrated that IGF2 treatment or IGF2 overexpression reduced the α-syn aggregates and their toxicity by IGF2 receptor (IGF2R) activation in cellular PD models. Also, we observed IGF2 and its interaction with IGF2R enhance the α-syn secretion. To determine the possible IGF2 neuroprotective effect in vivo we used a gene therapy approach in an idiopathic PD model based on α-syn preformed fibrils intracerebral injection. IGF2 gene therapy revealed a significantly preventing of motor impairment in idiopathic PD model. Moreover, IGF2 expression prevents dopaminergic neuronal loss in the SN together with a decrease in α-syn accumulation (phospho-α-syn levels) in the striatum and SN brain region. Furthermore, the IGF2 neuroprotective effect was associated with the prevention of synaptic spines loss in dopaminergic neurons in vivo. The possible mechanism of IGF2 in cell survival effect could be associated with the decrease of the intracellular accumulation of α-syn and the improvement of dopaminergic synaptic function. Our results identify to IGF2 as a relevant factor for the prevention of α-syn toxicity in both in vitro and preclinical PD models.
Longitudinal development of category representations in ventral temporal cortex predicts word and face recognition
Authors: Nordt Marisa , Gomez Jesse , Natu Vaidehi S. , Rezai Alex A. , Finzi Dawn , Kular Holly , Grill-Spector Kalanit
Published: December 2023

Regions in ventral temporal cortex that are involved in visual recognition of categories like words and faces undergo differential development during childhood. However, categories are also represented in distributed responses across high-level visual cortex. How distributed category representations develop and if this development relates to behavioral changes in recognition remains largely unknown. Here, we used functional magnetic resonance imaging to longitudinally measure the development of distributed responses across ventral temporal cortex to 10 categories in school-age children over several years. Our results reveal both strengthening and weakening of category representations with age, which was mainly driven by changes across category-selective voxels. Representations became particularly more distinct for words in the left hemisphere and for faces bilaterally. Critically, distinctiveness for words and faces across category-selective voxels in left and right lateral ventral temporal cortex, respectively, predicted individual children’s word and face recognition performance. These results suggest that the development of distributed representations in ventral temporal cortex has behavioral ramifications and advance our understanding of prolonged cortical development during childhood.
JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer’s disease
Authors: Scopa Chiara , Barnada Samantha M. , Cicardi Maria E. , Singer Mo , Trotti Davide , Trizzino Marco
Published: December 2023

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer’s disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death in AD progenitors and neurons. Notably, inhibiting c-Jun effectively blocks all these downstream molecular processes and rescues neuronal death and the impaired neurogenesis phenotype in AD progenitors. Our findings open new avenues for identifying therapeutic strategies and biomarkers to counteract disease progression and diagnose AD in the early, pre-symptomatic stages.
Clonal heterogeneity in ER+ breast cancer reveals the proteasome and PKC as potential therapeutic targets
Authors: Beumers Lukas , Vlachavas Efstathios-Iason , Borgoni Simone , Schwarzmüller Luisa , Penso-Dolfin Luca , Michels Birgitta E. , Sofyali Emre , Burmester Sara , Heiss Daniela , Wilhelm Heike , Yarden Yosef , Helm Dominic , Will Rainer , Goncalves Angela , Wiemann Stefan
Published: December 2023

Intratumoral heterogeneity impacts the success or failure of anti-cancer therapies. Here, we investigated the evolution and mechanistic heterogeneity in clonal populations of cell models for estrogen receptor positive breast cancer. To this end, we established barcoded models of luminal breast cancer and rendered them resistant to commonly applied first line endocrine therapies. By isolating single clones from the resistant cell pools and characterizing replicates of individual clones we observed inter- (between cell lines) and intra-tumor (between different clones from the same cell line) heterogeneity. Molecular characterization at RNA and phospho-proteomic levels revealed private clonal activation of the unfolded protein response and respective sensitivity to inhibition of the proteasome, and potentially shared sensitivities for repression of protein kinase C. Our in vitro findings are consistent with tumor-heterogeneity that is observed in breast cancer patients thus highlighting the need to uncover heterogeneity at an individual patient level and to adjust therapies accordingly.
A meta-analysis identifies factors predicting the future development of freezing of gait in Parkinson’s disease
Authors: Herman Talia , Barer Yael , Bitan Michal , Sobol Shani , Giladi Nir , Hausdorff Jeffrey M.
Published: December 2023

Freezing of gait (FOG) is a debilitating problem that is common among many, but not all, people with Parkinson’s disease (PD). Numerous attempts have been made at treating FOG to reduce its negative impact on fall risk, functional independence, and health-related quality of life. However, optimal treatment remains elusive. Observational studies have recently investigated factors that differ among patients with PD who later develop FOG, compared to those who do not. With prediction and prevention in mind, we conducted a systematic review and meta-analysis of publications through 31.12.2022 to identify risk factors. Studies were included if they used a cohort design, included patients with PD without FOG at baseline, data on possible FOG predictors were measured at baseline, and incident FOG was assessed at follow-up. 1068 original papers were identified, 38 met a-priori criteria, and 35 studies were included in the meta-analysis (n = 8973; mean follow-up: 4.1 ± 2.7 years). Factors significantly associated with a risk of incident FOG included: higher age at onset of PD, greater severity of motor symptoms, depression, anxiety, poorer cognitive status, and use of levodopa and COMT inhibitors. Most results were robust in four subgroup analyses. These findings indicate that changes associated with FOG incidence can be detected in a subset of patients with PD, sometimes as long as 12 years before FOG manifests, supporting the possibility of predicting FOG incidence. Intriguingly, some of these factors may be modifiable, suggesting that steps can be taken to lower the risk and possibly even prevent the future development of FOG.
The relationship of school performance with self-control and grit is strongly genetic and weakly causal
Authors: Kevenaar Sofieke T. , van Bergen Elsje , Oldehinkel Albertine J. , Boomsma Dorret I. , Dolan Conor V.
Published: December 2023

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R2 = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance.
First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial
Authors: Fizazi Karim , Azad Arun A. , Matsubara Nobuaki , Carles Joan , Fay Andre P. , De Giorgi Ugo , Joung Jae Young , Fong Peter C. C. , Voog Eric , Jones Robert J. , Shore Neal D. , Dunshee Curtis , Zschäbitz Stefanie , Oldenburg Jan , Ye Dingwei , Lin Xun , Healy Cynthia G. , Di Santo Nicola , Laird A. Douglas , Zohren Fabian , Agarwal Neeraj
Published: December 2023

Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; N = 805 (169 were HRR-deficient)), followed by an HRR-deficient-only cohort (cohort 2; N = 230). We present results from the alpha-controlled primary analysis for the combined HRR-deficient population (N = 399). Patients were randomized in a 1:1 ratio to talazoparib or placebo, plus enzalutamide. The primary endpoint, radiographic progression-free survival, was met (median not reached at the time of the analysis for the talazoparib group versus 13.8 months for the placebo group; hazard ratio, 0.45; 95% confidence interval, 0.33 to 0.61; P < 0.0001). Data for overall survival, a key secondary endpoint, are immature but favor talazoparib (hazard ratio, 0.69; 95% confidence interval, 0.46 to 1.03; P = 0.07). Common adverse events in the talazoparib group were anemia, fatigue and neutropenia. Combining talazoparib with enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC harboring HRR gene alterations, supporting talazoparib plus enzalutamide as a potential first-line treatment for these patients. ClinicalTrials.gov Identifier: NCT03395197.
SEVtras delineates small extracellular vesicles at droplet resolution from single-cell transcriptomes
Authors: He Ruiqiao , Zhu Junjie , Ji Peifeng , Zhao Fangqing
Published: December 2023

Small extracellular vesicles (sEVs) are emerging as pivotal players in a wide range of physiological and pathological processes. However, a pressing challenge has been the lack of high-throughput techniques capable of unraveling the intricate heterogeneity of sEVs and decoding the underlying cellular behaviors governing sEV secretion. Here we leverage droplet-based single-cell RNA sequencing (scRNA-seq) and introduce an algorithm, SEVtras, to identify sEV-containing droplets and estimate the sEV secretion activity (ESAI) of individual cells. Through extensive validations on both simulated and real datasets, we demonstrate SEVtras’ efficacy in capturing sEV-containing droplets and characterizing the secretion activity of specific cell types. By applying SEVtras to four tumor scRNA-seq datasets, we further illustrate that the ESAI can serve as a potent indicator of tumor progression, particularly in the early stages. With the increasing importance and availability of scRNA-seq datasets, SEVtras holds promise in offering valuable extracellular insights into the cell heterogeneity.
Gut microbiomes of agropastoral children from the Adadle region of Ethiopia reflect their unique dietary habits
Authors: Yersin Simon , Garneau Julian R. , Schneeberger Pierre H. H. , Osman Kadra Ali , Cercamondi Colin Ivano , Muhummed Abdifatah Muktar , Tschopp Rea , Zinsstag Jakob , Vonaesch Pascale
Published: December 2023

The composition and function of the intestinal microbiota are major determinants of human health and are strongly influenced by diet, antibiotic treatment, lifestyle and geography. Nevertheless, we currently have only little data on microbiomes of non-westernized communities. We assess the stool microbiota composition in 59 children aged 2–5 years from the Adadle district of Ethiopia, Somali Regional State. Here, milk and starch-rich food are predominant components of the local diet, where the inhabitants live a remote, traditional agropastoral lifestyle. Microbiota composition, function and the resistome were characterized by both 16S rRNA gene amplicon and shotgun metagenomic sequencing and compared to 1471 publicly available datasets from children living in traditional, transitional, and industrial communities with different subsistence strategies. Samples from the Adadle district are low in Bacteroidaceae, and Prevotellaceae, the main bacterial representatives in the feces of children living in industrialized and non-industrialized communities, respectively. In contrast, they had a higher relative abundance in Streptococcaceae, Bifidobacteriaceae and Erysipelatoclostridiaceae. Further, genes involved in degradation pathways of lactose, d-galactose and simple carbohydrates were enriched. Overall, our study revealed a unique composition of the fecal microbiota of these agropastoral children, highlighting the need to further characterize the fecal bacterial composition of human populations living different lifestyles.
An image deblurring method using improved U-Net model based on multilayer fusion and attention mechanism
Authors: Lian Zuozheng , Wang Haizhen
Published: December 2023

The investigation of image deblurring techniques in dynamic scenes represents a prominent area of research. Recently, deep learning technology has gained extensive traction within the field of image deblurring methodologies. However, such methods often suffer from limited inherent interconnections across various hierarchical levels, resulting in inadequate receptive fields and suboptimal deblurring outcomes. In U-Net, a more adaptable approach is employed, integrating diverse levels of features effectively. Such design not only significantly reduces the number of parameters but also maintains an acceptable accuracy range. Based on such advantages, an improved U-Net model for enhancing the image deblurring effect was proposed in the present study. Firstly, the model structure was designed, incorporating two key components: the MLFF (multilayer feature fusion) module and the DMRFAB (dense multi-receptive field attention block). The aim of these modules is to improve the feature extraction ability. The MLFF module facilitates the integration of feature information across various layers, while the DMRFAB module, enriched with an attention mechanism, extracts crucial and intricate image details, thereby enhancing the overall information extraction process. Finally, in combination with fast Fourier transform, the FRLF (Frequency Reconstruction Loss Function) was proposed. The FRLF obtains the frequency value of the image by reducing the frequency difference. The present experiment results reveal that the proposed method exhibited higher-quality visual effects. Specifically, for the GoPro dataset, the PSNR (peak signal-to-noise ratio) reached 31.53, while the SSIM (structural similarity index) attained a value of 0.948. Additionally, for the Real Blur dataset, the PSNR achieved 31.32, accompanied by an SSIM score of 0.934.
Effect of contact inhibition locomotion on confined cellular organization
Authors: Potdar Harshal , Pagonabarraga Ignacio , Muhuri Sudipto
Published: December 2023

Experiments performed using micro-patterned one dimensional collision assays have allowed a precise quantitative analysis of the collective manifestation of contact inhibition locomotion (CIL) wherein, individual migrating cells reorient their direction of motion when they come in contact with other cells. Inspired by these experiments, we present a discrete, minimal 1D Active spin model that mimics the CIL interaction between cells in one dimensional channels. We analyze the emergent collective behaviour of migrating cells in such confined geometries, as well as the sensitivity of the emergent patterns to driving forces that couple to cell motion. In the absence of vacancies, akin to dense cell packing, the translation dynamics is arrested and the model reduces to an equilibrium spin model which can be solved exactly. In the presence of vacancies, the interplay of activity-driven translation, cell polarity switching, and CIL results in an exponential steady cluster size distribution. We define a dimensionless Péclet number Q—the ratio of the translation rate and directional switching rate of particles in the absence of CIL. While the average cluster size increases monotonically as a function of Q, it exhibits a non-monotonic dependence on CIL strength, when the Q is sufficiently high. In the high Q limit, an analytical form of average cluster size can be obtained approximately by effectively mapping the system to an equivalent equilibrium process involving clusters of different sizes wherein the cluster size distribution is obtained by minimizing an effective Helmholtz free energy for the system. The resultant prediction of exponential dependence on CIL strength of the average cluster size and $$Q^{1/2}$$

Q

1
/
2

dependence of the average cluster size is borne out to reasonable accuracy as long as the CIL strength is not very large. The consequent prediction of a single scaling function of Q, particle density and CIL interaction strength, characterizing the distribution function of the cluster sizes and resultant data collapse is observed for a range of parameters.
Hypergraph reconstruction from uncertain pairwise observations
Authors: Lizotte Simon , Young Jean-Gabriel , Allard Antoine
Published: December 2023

The network reconstruction task aims to estimate a complex system’s structure from various data sources such as time series, snapshots, or interaction counts. Recent work has examined this problem in networks whose relationships involve precisely two entities—the pairwise case. Here, using Bayesian inference, we investigate the general problem of reconstructing a network in which higher-order interactions are also present. We study a minimal example of this problem, focusing on the case of hypergraphs with interactions between pairs and triplets of vertices, measured imperfectly and indirectly. We derive a Metropolis-Hastings-within-Gibbs algorithm for this model to highlight the unique challenges that come with estimating higher-order models. We show that this approach tends to reconstruct empirical and synthetic networks more accurately than an equivalent graph model without higher-order interactions.
Kinetic modelling of ultrasound-triggered chemotherapeutic drug release from the surface of gold nanoparticles
Authors: Hornsby Tyler K. , Kashkooli Farshad Moradi , Jakhmola Anshuman , Kolios Michael C. , Tavakkoli Jahangir
Published: December 2023

Therapeutic ultrasound can be used to trigger the on-demand release of chemotherapeutic drugs from gold nanoparticles (GNPs). In the previous work, our group achieved doxorubicin (DOX) release from the surface of GNPS under low-intensity pulsed ultrasound (LIPUS) exposure. However, the specific release kinetics of ultrasound-triggered DOX release from GNPs is not known. Here, we present a release kinetics study of DOX from GNPs under ultrasound exposure for the first time. A novel dialysis membrane setup was designed to quantify DOX release from LIPUS-activated GNPs at 37.0 °C and 43.4 °C (hyperthermia temperature range). Contributions of thermal and non-thermal mechanisms of LIPUS-triggered DOX release were also quantified. Non-thermal mechanisms accounted for 40 ± 7% and 34 ± 5% of DOX release for 37.0 °C and 43.4 °C trials, respectively. DOX release under LIPUS exposure was found to follow Korsmeyer–Peppas (K–P) kinetics, suggesting a shift from a Fickian (static) to a non-Fickian (dynamic) release profile with the addition of non-thermal interactions. DOX release was attributed to an anomalous diffusion release mechanism from the GNP surface. A finite element model was also developed to quantify the acoustic radiation force, believed to be the driving force of non-thermal DOX release inside the dialysis bag.
Making sense of chemical space network shows signs of criticality
Authors: Amoroso Nicola , Gambacorta Nicola , Mastrolorito Fabrizio , Togo Maria Vittoria , Trisciuzzi Daniela , Monaco Alfonso , Pantaleo Ester , Altomare Cosimo Damiano , Ciriaco Fulvio , Nicolotti Orazio
Published: December 2023

Chemical space modelling has great importance in unveiling and visualising latent information, which is critical in predictive toxicology related to drug discovery process. While the use of traditional molecular descriptors and fingerprints may suffer from the so-called curse of dimensionality, complex networks are devoid of the typical drawbacks of coordinate-based representations. Herein, we use chemical space networks (CSNs) to analyse the case of the developmental toxicity (Dev Tox), which remains a challenging endpoint for the difficulty of gathering enough reliable data despite very important for the protection of the maternal and child health. Our study proved that the Dev Tox CSN has a complex non-random organisation and can thus provide a wealth of meaningful information also for predictive purposes. At a phase transition, chemical similarities highlight well-established toxicophores, such as aryl derivatives, mostly neurotoxic hydantoins, barbiturates and amino alcohols, steroids, and volatile organic compounds ether-like chemicals, which are strongly suspected of the Dev Tox onset and can thus be employed as effective alerts for prioritising chemicals before testing.
The new method of ZnIn2S4 synthesis on the titania nanotubes substrate with enhanced stability and photoelectrochemical performance
Authors: Roda D. , Trzciński K. , Łapiński M. , Gazda M. , Sawczak M. , Nowak A. P. , Szkoda M.
Published: December 2023

In this work, ZnIn2S4 layers were obtained on fluorine doped tin oxide (FTO) glass and TiO2 nanotubes (TiO2NT) using a hydrothermal process as photoanodes for photoelectrochemical (PEC) water splitting. Then, samples were annealed and the effect of the annealing temperature was investigated. Optimization of the deposition process and annealing of ZnIn2S4 layers made it possible to obtain an FTO-based material generating a photocurrent of 1.2 mA cm−2 at 1.62 V vs. RHE in a neutral medium. In contrast, the highest photocurrent in the neutral electrolyte obtained for the TiO2NT-based photoanode reached 0.5 mA cm−2 at 1.62 V vs. RHE. In addition, the use of a strongly acidic electrolyte allowed the generated photocurrent by the TiO2NT-based photoanode to increase to 3.02 mA cm−2 at 0.31 V vs. RHE. Despite a weaker photoresponse in neutral electrolyte than the optimized FTO-based photoanode, the use of TiO2NT as a substrate allowed for a significant increase in the photoanode's operating time. After 2 h of illumination, the photocurrent response of the TiO2NT-based photoanode was 0.21 mA cm−2, which was 42% of the initial value. In contrast, the FTO-based photoanode after the same time generated a photocurrent of 0.02 mA cm−2 which was only 1% of the initial value. The results indicated that the use of TiO2 nanotubes as a substrate for ZnIn2S4 deposition increases the photoanode's long-term stability in photoelectrochemical water splitting. The proposed charge transfer mechanism suggested that the heterojunction between ZnIn2S4 and TiO2 played an important role in improving the stability of the material by supporting charge separation.
Oral micro-electronic platform for temperature and humidity monitoring
Authors: Popović Željko V. , Thiha Aung , Ibrahim Fatimah , Petrović Bojan B. , Dahlan Nuraina Anisa , Milić Lazar , Kojić Sanja , Stojanović Goran M.
Published: December 2023

Intraoral theranostics, the integration of diagnostics and therapeutics within the oral cavity, is gaining significant traction. This pioneering approach primarily addresses issues like xerostomia (dry mouth), commonly resulting from cancer treatment, with a specific focus on monitoring temperature and humidity. This paper introduces the innovative Intra-Oral Portable Micro-Electronic (IOPM) fluidic theranostic device platform. It leverages conventional dental spoons by incorporating advanced sensors for precise measurements of oral temperature and humidity. Personalization options include a microfluidic chip and a tooth model, enabling targeted delivery of therapeutic agents to optimize treatment outcomes. The electronic control system simplifies the administration of fluid dosages, intelligently adjusted based on real-time oral cavity temperature and humidity readings. Rigorous experimental evaluations validate the platform’s precision in delivering fluid volumes at predefined intervals. This platform represents a transformative advancement for individuals contending with oral health challenges such as xerostomia (dry mouth). Furthermore, it has the potential to elevate oral healthcare standards by providing advanced diagnostics and tailored therapeutic solutions, benefiting both patients and dental professionals alike.
Applying a zero-corrected, gravity model estimator reduces bias due to heterogeneity in healthcare utilization in community-scale, passive surveillance datasets of endemic diseases
Authors: Evans Michelle V. , Ihantamalala Felana A. , Randriamihaja Mauricianot , Aina Andritiana Tsirinomen’ny , Bonds Matthew H. , Finnegan Karen E. , Rakotonanahary Rado J. L. , Raza-Fanomezanjanahary Mbolatiana , Razafinjato Bénédicte , Raobela Oméga , Raholiarimanana Sahondraritera Herimamy , Randrianavalona Tiana Harimisa , Garchitorena Andres
Published: December 2023

Data on population health are vital to evidence-based decision making but are rarely adequately localized or updated in continuous time. They also suffer from low ascertainment rates, particularly in rural areas where barriers to healthcare can cause infrequent touch points with the health system. Here, we demonstrate a novel statistical method to estimate the incidence of endemic diseases at the community level from passive surveillance data collected at primary health centers. The zero-corrected, gravity-model (ZERO-G) estimator explicitly models sampling intensity as a function of health facility characteristics and statistically accounts for extremely low rates of ascertainment. The result is a standardized, real-time estimate of disease incidence at a spatial resolution nearly ten times finer than typically reported by facility-based passive surveillance systems. We assessed the robustness of this method by applying it to a case study of field-collected malaria incidence rates from a rural health district in southeastern Madagascar. The ZERO-G estimator decreased geographic and financial bias in the dataset by over 90% and doubled the agreement rate between spatial patterns in malaria incidence and incidence estimates derived from prevalence surveys. The ZERO-G estimator is a promising method for adjusting passive surveillance data of common, endemic diseases, increasing the availability of continuously updated, high quality surveillance datasets at the community scale.
Establishing the interpretability and utility of the 4-item BriefPCS
Authors: You Dokyoung S. , Cook Karon F. , Lannon Edward W. , Ziadni Maisa S. , Darnall Beth D. , Mackey Sean C.
Published: December 2023

To reduce the patient burden associated with completing the 13-item Pain Catastrophizing Scale (PCS), the 4-item “BriefPCS” was developed. To date, no crosswalk has been developed that associates scores on the BriefPCS with PCS scores. Further, no study has compared the use of BriefPCS and PCS scores in a randomized clinical trial (RCT). We aimed to: (1) establish the interpretability of BriefPCS scores in reference to PCS scores, (2) compare the concurrent validity between the BriefPCS and PCS, and (3) asssess the use of BriefPCS in an RCT. First, we conducted equipercentile linking, created a crosswalk that associated scores of BriefPCS with PCS, and calculated differences between PCS and crosswalked PCS scores. Secondly, we compared Bootstrap correlation coefficients between PCS and self-reported measures of other domains. Lastly, we compared results from an RCT using BriefPCS scores versus PCS scores. Findings indicated that the correlation coefficient estimates with the BriefPCS and PCS scores were not significantly different. BriefPCS and PCS scores had similar ability to detect treatment-related changes. The BriefPCS scores validly, reliably, and accurately distinguish levels of pain catastrophizing. Additionally, the BriefPCS scores are sensitive to changes after behavioral interventions, with less respondent burden compared to the PCS scores.
Facile synthesis of ZnO/Hal nanocomposite for arsenite (As(III)) removal from aqueous media
Authors: Khoddam Mohammad Ali , Norouzbeigi Reza , Velayi Elmira , Cavallaro Giuseppe
Published: December 2023

Arsenite (As(III)) is the most toxic form of arsenic that is a serious concern for water contamination worldwide. Herein a ZnO/Halloysite (Hal) nanocomposite was prepared by the chemical bath deposition method (CBD) through seed-mediated ZnO growth on the halloysite for eliminating As(III) from the aqueous solution. The growth of ZnO on seeded halloysite was investigated based on the HMTA: Zn2+ molar ratio in the solution. An optimum molar ratio of HMTA:Zn for nucleation and growth of ZnO upon halloysite was obtained 1:2 based on morphological analysis. The TGA results confirmed that thermal stability of HNT was enhanced by ZnO decoration. The prepared ZnO/Hal nanocomposite at optimal conditions was employed for arsenite (As(III)) removal from aqueous solutions. Experimental data were evaluated with different isothermal, thermodynamic, and kinetic models. Based on the zeta potential results, Hal nanocomposites had a greater negative value than pure Hal. Therefore, the ZnO/Hal nanocomposite exhibited efficient As(III) adsorption with a removal efficiency of 76% compared to pure Hal with a removal efficiency of 5%. Adsorption isotherm was well correlated by both non-linear Langmuir and Sips models, exhibiting maximum adsorption capacity of As(III) at 42.07 mg/g, and 42.5 mg/g, respectively. As a result of the study, it was found that the fabricated Hal nanocomposite with low toxicity can be used effectively in water treatment.