bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Speech Assessment in Ataxia—Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Markers
Authors: Vogel Adam P. , Sobanska Anna , Gupta Anoopum , Vasco Gessica , Grobe-Einsler Marcus , Summa Susanna , Borel Stephanie
Published: October 2023

Dysarthria is a common and debilitating symptom of many neurodegenerative diseases, including those resulting in ataxia. Changes to speech lead to significant reductions in quality of life, impacting the speaker in most daily activities. Recognition of its importance as an objective outcome measure in clinical trials for ataxia is growing. Its viability as an endpoint across the disease spectrum (i.e. pre-symptomatic onwards) means that trials can recruit ambulant individuals and later-stage individuals who are often excluded because of difficulty completing lower limb tasks. Here we discuss the key considerations for speech testing in clinical trials including hardware selection, suitability of tasks and their role in protocols for trials and propose a core set of tasks for speech testing in clinical trials. Test batteries could include forms suitable for remote short, sensitive and easy to use, with norms available in several languages. The use of artificial intelligence also could improve accuracy and automaticity of analytical pipelines in clinic and trials.
Coupling major ions and trace elements to turbidity dynamics for allogenic contribution assessment in a binary karst system (Sierra de Ubrique, S Spain)
Authors: Fernández-Ortega Jaime , Barberá Juan Antonio , Andreo Bartolomé
Published: October 2023

This investigation deals with the application of a multi-technique approach combining data from turbidity, major ions, and trace elements to characterize the implications of allogenic recharge in a binary karst system and assess the relative hydrochemical contribution to karst springs captured for drinking use. Hydrodynamic and hydrochemical responses of the outlets to storm events were continuously monitored during four selected flooding events, and water samples were collected at the main sinking stream in the recharge area and discharge points (Cornicabra and Algarrobal springs) for chemical analysis. The obtained hydrogeochemical dataset was analyzed through mean of time-series and statistical analysis and allowed to describe the fate and origin of trace elements. Despite that most of analyzed components present a natural origin, the existence of a Wastewater Treatment Plant in the recharge area was determined to be the main source of P (phosphorus) concentrations measured in the karst springs. Sediment (particulate) transport constitutes the most important factor in the mobilization of Al, Mn, Ni, and Ba in both surface and groundwater, whilst Li, Sr, and P are mainly controlled by solute migration. The hydrochemical signature of allogenic water component was constrained by identifying characteristic correlations between Ba and Ca/Sr ratio in water samples. The combination of specific hydrogeological processes as ion solution and sorption processes onto solids between solutes and particles as well as water mixing processes (allogenic vs diffuse) result more evident in Algarrobal spring, which receives a higher contribution of allogenic component due to a greater feeding catchment.
A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits
Authors: Zeng Wen , Xie Fangfang , Pan Yiyun , Chen Zhengcong , Chen Hailong , Liu Xiaomei , Tian Keqiang , Xu Dechang
Published: October 2023

Background

Head and neck squamous cancer (HNSCC) presents variable phenotype and progression features. Clinically applicable, high-accuracy multifactorial prognostic models for HNSCC survival outcomes are warranted and an active area of research. This study aimed to construct a comprehensive prognostic tool for HNSCC overall survival by integrating cancer driver genes with tumor clinical and phenotype information.

Methods

Key overall survival-related cancer driver genes were screened from among main effector and reciprocal gene pairs using TCGA data using univariate Cox proportional hazard regression analysis. Independent validation was performed using the GSE41613 dataset. The main effector genes among these were selected using LASSO regression and transcriptome score modeling was performed using multivariate Cox regression followed by validation analysis of the prognostic score. Next, multivariate Cox regression analysis was performed using the transcriptome score combined with age, grade, gender, and stage. An ‘Accurate Prediction Model of HNSCC Overall Survival Score’ (APMHO) was computed and validated. Enriched functional pathways, gene mutational landscape, immune cell infiltration, and immunotherapy sensitivity markers associated with high and low APMHO scores were analyzed.

Results

Screening 107 overall survival-related cancer genes and 402 interacting gene pairs, 6 genes: CRLF2, HSP90AA1, MAP2K1, PAFAH1B2, MYCL and SET genes, were identified and a transcriptional score was obtained. Age, stage and transcriptional score were found to be significant predictors in Cox regression analysis and used to construct a final APMHO model showing an AUC > 0.65 and validated. Transcriptional score, age, pathologic_N, pathologic_T, stage, and TCGA_subtype were significantly different in distribution between high and low APMHO groups. High APMHO samples showed significantly higher mutation rate, enriched tumor-related pathways including Hypoxia, unfold_protein_response, Glycolysis, and mTORC1 signaling, along with differences in immune cell infiltration and immune checkpoint, interferon-γ pathway and m6A regulator expression patterns.

Conclusion

The APMHO score combining transcriptional and clinical variables showed good prognostic ability for HNSCC overall survival outcomes and was associated with different patterns of phenotypical features, immune and mutational landscape, and immunotherapy sensitivity marker expression. Future studies should validate this score in independent clinical cohorts.
Automatic detection of delamination on tunnel lining surfaces from laser 3D point cloud data by 3D features and a support vector machine
Authors: Mizutani Tsukasa , Yamaguchi Takahiro , Yamamoto Kazutomo , Ishida Tetsuya , Nagata Yoshifumi , Kawamura Hinari , Tokuno Tomoaki , Suzuki Kiyoshi , Yamaguchi Yuya
Published: October 2023

A completely automatic algorithm for accurately detecting delamination on tunnel concrete lining surfaces using laser 3D point cloud data is first proposed to facilitate tunnel lining inspection. A mobile mapping system (MMS), which mounts laser sensors and a positioning system, is utilized to measure the geometries of the surfaces at high speed. The algorithm consists of two steps: extraction of the 3D shapes of anomalies and discrimination of delamination from appendages by a support vector machine (SVM). The article focusses on the second step. On tunnel linings, there are many conspicuous appendages such as cables, lights, signs, and water guides which mask the features of delamination. In this study, straightness, a novel 3D feature, is introduced to realize accurate discrimination. An automatic algorithm based on the SVM is developed and validated using real tunnel data, showing an accurate delamination map.
Stepping up foot care: assessment over foot care knowledge and behavior among individuals with diabetes of risk levels
Authors: Li Mengwen , Wei Mengyao , Han Binru , Wu Hongjuan
Published: October 2023

Background

Diabetic foot is a global threat to public health, as it can lead to infections and amputations and cause significant pain and economic costs for patients. Diabetic foot patients in northern China have more severe local ulcers, worse prognosis, and longer disease duration.

Objective

This study assessed the foot risk levels and foot care knowledge and behavior status of people with diabetes with different foot risk levels, and investigated the factors that influence the occurrence of high-risk foot in diabetes.

Methods

This cross-sectional survey included 410 hospitalized people with diabetes. Demographic and disease-related data and foot risk stratification status were collected using investigator-designed questionnaires. Foot care knowledge and behavior questionnaires were also used.

Results

Among the 410 participants, a total of 367 cases were classified as high-risk feet, among which 135 cases were rated as grade 1, 202 cases grade 2, and 30 cases grade 3. Foot care knowledge surveys revealed low scores in the areas of shoe and sock selection, foot and footwear examination, and management of foot problems. Foot care behavior surveys showed low scores in the areas of foot and footwear examination, management of foot problems, and foot injury risk behavior. One-way ANOVA revealed significant differences in foot care behaviors among patients with different foot risk classifications (p < 0.05), while no significant differences were observed in foot care knowledge scores. Multivariate logistic regression analysis showed that age, history of cerebrovascular disease, and foot care behavior scores were factors influencing the occurrence of high-risk foot in people with diabetes.

Conclusion

The results of this study showed a high prevalence of high-risk foot in diabetics; The knowledge and behavior of foot care in diabetics with different foot risk levels were both at a moderately low level; There were differences in foot behavior scores among patients with different foot risk classes, but, counter-intuitively, no significant differences in foot care knowledge. The study found that advanced age, history of cerebrovascular disease, and low foot care behavior scores are risk factors for high-risk foot in diabetes. Therefore, it is necessary to screen patients with diabetes for high-risk feet and implement targeted interventions according to the results.
Familial focal segmental glomerulosclerosis with Alport-like glomerular basement changes caused by paired box protein 2 gene variant
Authors: Yamada Yuko , Yokoyama Hiroki , Kinoshita Ryo , Kitamoto Koichi , Kawaba Yasuo , Okada Shinichi , Horie Takashi , Nagano China , Nozu Kandai , Namba Noriyuki
Published: October 2023

Paired box protein 2 (PAX2) gene variant causes renal coloboma syndrome (MIM#120330). Further, they are associated with focal segmental glomerulosclerosis and characterized by basement membrane changes similar to Alport syndrome.

Herein, we report an 8-year-old boy who presented with proteinuria and decreased renal function. His paternal uncle has focal segmental glomerulosclerosis and renal failure, and his paternal grandmother has renal failure and is receiving peritoneal dialysis. Further, his father has stage 2 chronic kidney disease. At 3 years of age, his serum creatinine-estimated glomerular filtration rate was 40–50 mL/min/1.73 m2. At 8 years of age, his renal function further decreased and he had proteinuria (urinary protein/Cr 3.39 g/g Cr). Renal histopathology showed oligonephronia and focal segmental glomerulosclerosis. A partial basket-weave pattern, similar to Alport syndrome, was also observed on a transmission electron microscope, and low-vacuum scanning electron microscopy revealed coarse meshwork changes in the glomerular basement membrane. Genetic analysis revealed a PAX2 heterozygous variant (NM_003987.4:c.959C  >  G), a nonsense variant in which the serine at position 320 changes to a stop codon, in our patient and his father. PAX2 is a transcription factor that is important for the podocyte variant. However, podocytes with PAX2 gene variants may cause abnormal basement membrane production and repair, thereby resulting in Alport-like changes.
BioGeoChemical‐Argo Floats Reveal Stark Latitudinal Gradient in the Southern Ocean Deep Carbon Flux Driven by Phytoplankton Community Composition
Authors: Terrats Louis , Claustre Hervé , Briggs Nathan , Poteau Antoine , Briat Benjamin , Lacour Léo , Ricour Florian , Mangin Antoine , Neukermans Griet
Published: October 2023

The gravitational sinking of particles in the mesopelagic layer (∼200–1,000 m) transfers to the deep ocean a part of atmospheric carbon fixed by phytoplankton. This process, called the gravitational pump, exerts an important control on atmospheric CO2 levels but remains poorly characterized given the limited spatio‐temporal coverage of ship‐based flux measurements. Here, we examined the gravitational pump with BioGeoChemical‐Argo floats in the Southern Ocean, a critically under‐sampled area. Using time‐series of bio‐optical measurements, we characterized the concentration of particles in the productive zone, their export and transfer efficiency in the underlying mesopelagic zone, and the magnitude of sinking flux at 1,000 m. We separated float observations into six environments delineated by latitudinal fronts, sea‐ice coverage, and natural iron fertilization. Results show a significant increase in the sinking‐particle flux at 1,000 m with increasing latitude, despite comparable particle concentrations in the productive layer. The variability in deep flux was driven by changes in the transfer efficiency of the flux, related to the composition of the phytoplanktonic community and the size of particles, with intense flux associated with the predominance of micro‐phytoplankton and large particles at the surface. We quantified the relationships between the nature of surface particles and the flux at 1,000 m and used these results to upscale our flux survey across the whole Southern Ocean using surface observations by floats and satellites. We then estimated the basin‐wide Spring‐Summer flux of sinking particles at 1,000 m over the Southern Ocean (0.054 ± 0.021 Pg C).
A New Multi‐Method Assessment of Stratospheric Sulfur Load From the Okmok II Caldera‐Forming Eruption of 43 BCE
Authors: Peccia Ally , Moussallam Yves , Plank Terry , DallaSanta Kevin , Polvani Lorenzo , Burgisser Alain , Larsen Jessica , Schaefer Janet
Published: October 2023

The 43 BCE eruption of Okmok Volcano has been proposed to have had a significant climate cooling impact in the Northern Hemisphere. In this study, we quantify the climate cooling potential of the Okmok II eruption by measuring sulfur concentration in melt inclusions (up to 1,606 ppm) and matrix glasses and estimate a total of 62 ± 16 Tg S released. The proportion reaching the stratosphere (2.5%–25%, i.e., 1.5–15.5 Tg S) was constrained by physical modeling of the caldera‐collapse eruption. Using the NASA Goddard Institute for Space Studies E2.2 climate model we found a linear response between cooling and stratospheric sulfur load (0.05–0.08°C/Tg S). Thus, the 1–2°C of cooling derived from proxy records would require 16–32 Tg sulfur injection. This study underscores the importance of combining approaches to estimate stratospheric S load. For Okmok II, we find all methods are consistent with a range of 15–16 Tg S.
Contrasting Central Equatorial Pacific Oxygen Isotopic Signatures of the 2014/2015 and 2015/2016 El Niño Events
Authors: Stevenson S. , Cobb K. M. , Merrifield M. , Powell B. , Sanchez S. , Nusbaumer J. , O’Connor G. , Atwood A.
Published: October 2023

Paleoclimate reconstructions of El Niño/Southern Oscillation (ENSO) behavior often rely on oxygen isotopic records from tropical corals (δ18O). However, few reef‐based observations of physical conditions during El Niño events exist, limiting our ability to interpret coral δ18O. Here we present physical and geochemical measurements from Palmyra Atoll (5.9°N, 162.1°W) from 2014–2017, along with a data assimilation product using the isotope‐enabled Regional Ocean Modeling System (isoROMS). Coral δ18O signals are comparably strong in 2014–2015 and 2015–2016; notably, over 50% of the signal is driven by seawater δ18O, not temperature. If a constant seawater δ18O:salinity relationship were present, this would imply a comparable salinity anomaly during both events. However, salinity changes are much larger during 2014–2015, indicating a highly nonstationary relationship. isoROMS then shows that advection strongly influences δ18O during both the 2014–2015 and 2015–2016 El Niño, driving differences in the salinity/seawater δ18O relationship. This demonstrates the need for considering ocean dynamics when interpreting coral δ18O.
Postdepositional Behavior of Molybdenum in Deep Sediments and Implications for Paleoredox Reconstruction
Authors: Nan Jingbo , Tsang Man‐Yin , Li Jie , Köster Male , Henkel Susann , Lin Fanyu , Yao Weiqi
Published: October 2023

Molybdenum (Mo) is a trace element sensitive to oceanic redox conditions. The fidelity of sedimentary Mo as a paleoredox proxy of coeval seawater depends on the extent of Mo remobilization during postdepositional processes. Here we present the Mo content and isotope profiles for deep sediments from the Nankai Trough, Japan. The Mo signature suggests that these sediments have experienced extensive early diagenesis and hydrothermal alteration at depth. Iron (Fe)‐manganese (Mn) (oxyhydr)oxide alteration combined with Mo thiolation leads to a more than twenty‐fold enrichment of Mo within the sulfate reduction zone. Hydrothermal fluids and Mo adsorption onto Fe‐Mn (oxyhydr)oxides cause extremely negative Mo‐isotope values at the underthrust zone. These postdepositional Mo signals might be misinterpreted as expanded anoxia in the water column. Our findings highlight the importance of constraining postdepositional effects on Mo‐based proxies during paleoredox reconstruction.
Is There the Equatorial Water Mass in the Atlantic Ocean?
Authors: Zhurbas Victor , Lebedev Konstantin , Kuzmina Natalia
Published: October 2023

Using temperature and salinity profiles from the Argo data repository, a detailed volumetric temperature‐salinity diagram is compiled for the upper 2,000 m layer of the Atlantic Ocean. It is generally accepted that, unlike the Pacific and Indian Oceans where the Equatorial Water is present, there is no Equatorial Water in the Atlantic Ocean and its place is occupied by the South Atlantic Central Water (SACW). However, the detailed volumetric T‐S diagram shows that the main thermocline in the latitude range of 10°S–10°N is characterized by its own tight T‐S relationship which is relatively close to but clearly distinguishable from the tight T–S relationship of SACW in the latitude range of 10°S–40°S. We argue that the Atlantic Equatorial Water can be considered as a separate water mass which is probably formed by isopycnal mixing of SACW and the North Atlantic Central Water (NACW) in proportion approx. 3.5:1.
Potential Predictability of the Madden‐Julian Oscillation in a Superparameterized Model
Authors: Weidman Sarah , Kuang Zhiming
Published: October 2023

The Madden‐Julian Oscillation (MJO) is a promising target for improving sub‐seasonal weather forecasts. Current forecast models struggle to simulate the MJO due to imperfect convective parameterizations and mean state biases, degrading their forecast skill. Previous studies have estimated a potential MJO predictability 5–15 days higher than current forecast skill, but these estimates also use models with parameterized convection. We perform a perfect‐model predictability experiment using a superparameterized global model in which the convective parameterization is replaced by a cloud resolving model. We add a second “silent” cloud resolving component to the control simulation that independently calculates convective‐scale processes using the same large‐scale forcings. The second set of convective states are used to initialize forecasts, representing uncertainty on the convective scale. We find a potential predictability of the MJO of 35–40 days in boreal winter using a single‐member ensemble forecast.
Remote Versus Local Impacts of Energy Backscatter on the North Atlantic SST Biases in a Global Ocean Model
Authors: Chang Chiung‐Yin , Adcroft Alistair , Zanna Laure , Hallberg Robert , Griffies Stephen M.
Published: October 2023

The use of coarse resolution and strong grid‐scale dissipation has prevented global ocean models from simulating the correct kinetic energy level. Recently parameterizing energy backscatter has been proposed to energize the model simulations. Parameterizing backscatter reduces long‐standing North Atlantic sea surface temperature (SST) and associated surface current biases, but the underlying mechanism remains unclear. Here, we apply backscatter in different geographic regions to distinguish the different physical processes at play. We show that an improved Gulf Stream path is due to backscatter acting north of the Grand Banks to maintain a strong deep western boundary current. An improved North Atlantic Current path is due to backscatter acting around the Flemish Cap, with likely an improved nearby topography‐flow interactions. These results suggest that the SST improvement with backscatter is partly due to the resulted strengthening of resolved currents, whereas the role of improved eddy physics requires further research.
Active Dipping Interface of the Southern San Andreas Fault Revealed by Space Geodetic and Seismic Imaging
Authors: Vavra Ellis J. , Qiu Hongrui , Chi Benxin , Share Pieter‐Ewald , Allam Amir , Morzfeld Matthias , Vernon Frank , Ben‐Zion Yehuda , Fialko Yuri
Published: October 2023

The Southern San Andreas Fault (SSAF) in California is one of the most thoroughly studied faults in the world, but its configuration at seismogenic depths remains enigmatic in the Coachella Valley. We use a combination of space geodetic and seismic observations to demonstrate that the relatively straight southernmost section of the SSAF, between Thousand Palms and Bombay Beach, is dipping to the northeast at 60–80° throughout the upper crust (<10 km), including the shallow aseismic layer. We constrain the fault attitude in the top 2–3 km using inversions of surface displacements associated with shallow creep, and seismic data from a dense nodal array crossing the fault trace near Thousand Palms. The data inversions show that the shallow dipping structure connects with clusters of seismicity at depth, indicating a continuous throughgoing fault surface. The dipping fault geometry has important implications for the long‐term fault slip rate, the intensity of ground shaking during future large earthquakes, and the effective strength of the southern SAF.
Interbasin Differences in Interannual Variations of the Antarctic Circumpolar Current Transport
Authors: Yang Chengcheng , Cheng Xuhua , von Storch Jin‐Song , Qin Jianhuang , Qiu Bo
Published: October 2023

Despite the critical role of the Antarctic Circumpolar Current (ACC) in global convey belt, its temporal variability and spatial difference are poorly investigated due to the lack of full‐depth observations. This study quantitatively investigates the interannual variability of the ACC transport in different basins using Gravity Recovery and Climate Experiment (GRACE) ocean bottom pressure (OBP) data and In Situ Analysis System 17 (ISAS17) temperature and salinity fields. The results reveal that the interannual variation differs significantly in the Indian basin, the Pacific and Atlantic basins, and is likely caused by the meridional distribution of the wind stress curl, rather than the westerly winds. The interannual variation is correlated with the Southern Annular Mode (SAM) in the Indian basin, but also modulated by El Niño–Southern Oscillation (ENSO) in the Pacific and Atlantic basins. The results are further verified by a mass conservation ocean model with elaborating the important influence of both local and global atmospheric variability on the spatial‐temporal variability of the ACC. The difference of the ACC transports in the major basins might be ascribed to the respective meridional transport in each basin.
Simulating the 3D Distribution of Absorbed Shortwave Radiation in a Tree Crown: Comparison of Simplified and Monte Carlo Models
Authors: Oshio H. , Asawa T.
Published: October 2023

Urban trees are expected to alleviate severe thermal environments in summer. The absorbed shortwave radiation is a key variable to estimate the microclimatic effects of trees. In numerical simulation tools for the urban and built thermal environment, the difficulty lies in how to calculate the absorbed radiation in terms of accuracy and computational load. Here we investigated the difference between a radiative transfer model calculating scattering by the Monte Carlo method and a simpler model that accounts for scattering by modifying the optical depth. The calculations of absorbed radiation were performed under various conditions of leaf normal distribution and zenith angle of incident radiation, using tree models represented by voxels with different leaf area density values. For the photosynthetically active radiation, the relative difference between models was less than 10% for most cases. For the near‐infrared radiation, the difference was also small for a large canopy consisting of several trees. The difference was 30%–60% and 0%–20% for zenith angles of incident radiation of 0° and 60°, respectively, for small isolated trees with a crown height and width of less than 5 m, which was a significantly different condition from a uniform canopy. This large difference was related to the uniformity of the canopy and was explained by the transmittance from each voxel to the outside of the canopy. The present study enables us to evaluate the applicability of the simple model and correct the difference from the Monte Carlo model.
Oysters' Integration on Submerged Breakwaters Offers New Adaptive Shoreline Protection in Low‐Energy Environments in the Face of Sea Level Rise
Authors: Vona Iacopo , Nardin William
Published: October 2023

Sea level rise (SLR) and increasing storm frequency threaten coastal environments. Engineering solutions such as breakwaters will become ineffective for wave attenuation and erosion control due to SLR. As a natural alternative, oysters create three‐dimensional, complex reef structures that attenuate wave energy and increase sedimentation rates. If coupled with breakwaters, oysters may maintain breakwaters' efficiency over time as they are expected to grow with SLR. Here, we measured bathymetric changes over 3 years (via GPS) and wave dampening due to four‐made intertidal breakwaters within a small cove of the Choptank River (MD, USA). Then, we modeled the coupling of such gray structures with oysters through Delft3D‐SWAN to evaluate the performances of such hybrid solutions on coastal protection, under future scenarios of SLR and climate change. Modeling hydrodynamic results showed a gradual reduction in wave attenuation due to SLR. However, when oysters were included in the modeling, wave dampening in 100 years was 75% and 60% greater than gray breakwaters, at high and low tides, respectively. Morphodynamic results showed increasing net export of sediment from the coast due to SLR. Oyster addition also provided shoreline protection and sediment retention in 100 years compared with the use of breakwaters alone, thanks to oysters' capability to grow with SLR. The coupling between oysters and breakwaters may represent a valuable and effective methodology to protect our coast over a changing climate and a rising sea, where optimal conditions for oyster survivability occur and are maintained over time.
Peanut oil in vitamin A and D preparations: Reactions to skin test and manifestation of symptoms
Authors: Kull I. , Hallner E. , Lilja G. , Öhman‐Johansson A.‐C. , Öman H. , Wickman M..
Published: October 2023

The aim of this study was to establish whether there is a link between sensitisation to peanut and exposure to peanut oil in vitamin A and D preparations. Forty‐one children with a positive vivo or in vitro test towards peanut were included. Twenty‐one children had consumed vitamins A and D in oil solution, 14 in water solution, and 6 both types. Refined and unrefined peanut oils were obtained and skin prick test extracts were prepared. None of the children exhibited a positive SPT in response to the refined peanut extract. In contrast, 15 children exhibited a positive SPT to the unrefined extract. There was no significant difference in the number of children reacting clinically to peanut exposure who had received vitamins A and D in oil‐based or water‐based formulations. However, children with clinical allergy to peanut and who had exclusively consumed vitamin A and D in peanut oil, exhibited a greater number of different allergic symptoms upon consumption of peanut compared with clinical allergic children who had consumed the vitamins in water solution or both types (p<0.01). This study indicates that sensitisation to peanut during childhood through consumption of vitamins A and D in oil‐based solution seems unlikely, but its consumption may contribute to the development of a wider range of clinical symptoms due to peanut exposure.
A novel online survey approach designed to measure consumer sunscreen application thickness—implications for estimating environmental emissions
Authors: Carrao Andrea M. , Coleman James C. , Guo Jeff J. , Kumari Harshita
Published: October 2023

Background

The effects of ultraviolet (UV) filters in the aquatic environment have been well studied, but environmental exposures remain unclear and understudied. Consumer usage directly influences the amount of sunscreen products, and subsequently UV filters, potentially released into the environment.

Objective

To conduct a literature review of previous research into sunscreen application thickness, develop a questionnaire protocol designed to semi-quantify sunscreen usage by US consumers, and conduct a large-scale survey to determine a sunscreen application thickness (to face and body) that is more refined than conservative defaults. The United States Food & Drug Administration (US FDA) recommends a sunscreen application rate of 2 mg/cm2. This value is typically used as a worst-case assumption in environmental exposure assessments of UV filters.

Methods

Designed a novel approach to estimate lotion sunscreen application thickness using an online questionnaire protocol employing visual references and self-reported height and weight of the respondents. A literature review was also conducted to collect historical sunscreen usage.

Results

Over 9000 people were surveyed in the US, and after the dataset was refined, their sunscreen application thickness was estimated based on calculated body surface area and reported sunscreen amounts. The mean and median values for survey respondents are 3.00 and 1.78 mg/cm2, respectively, for facial application thickness and 1.52 and 1.35 mg/cm2, respectively, for body application thickness. Earlier research from 1985–2020 reported 36 of the 38 values are below the US FDA’s recommended application thickness of 2 mg/cm2 (range 0.2–5 mg/cm2).

Impact statement

This web-based survey is the first of its kind, designed specifically to quantify sunscreen application in a large and diverse set of consumers. This method provides a greater reach to larger populations thus enabling more granular data analysis and understanding. Exposure assessments of sunscreen ingredients typically use conservative parameters. These data can refine those assessments and allow for more informed and science-based risk management decisions.
Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma
Authors: Muccioli Silvia , Brillo Valentina , Varanita Tatiana , Rossin Federica , Zaltron Elisabetta , Velle Angelo , Alessio Giorgia , Angi Beatrice , Severin Filippo , Tosi Anna , D’Eletto Manuela , Occhigrossi Luca , Falasca Laura , Checchetto Vanessa , Ciaccio Roberto , Fascì Amelia , Chieregato Leonardo , Rebelo Ana Paula , Giacomello Marta , Rosato Antonio , Szabò Ildikò , Romualdi Chiara , Piacentini Mauro , Leanza Luigi
Published: October 2023

Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon. Here, we discovered a key function of Transglutaminase Type-2 (TG2) in regulating melanogenesis by modulating MITF transcription factor expression and its transcriptional activity. Importantly, we demonstrated that TG2 expression affects melanoma invasiveness, highlighting its positive value in SKCM. These results suggest that TG2 may have implications in the regulation of the phenotype switching by promoting melanoma differentiation and impairing its metastatic potential. Our findings offer potential perspectives to unravel melanoma vulnerabilities via tuning intra-tumor heterogeneity.
Salicylate induces AMPK and inhibits c-MYC to activate a NRF2/ARE/miR-34a/b/c cascade resulting in suppression of colorectal cancer metastasis
Authors: Liu Chunfeng , Rokavec Matjaz , Huang Zekai , Hermeking Heiko
Published: October 2023

Aspirin and its active metabolite salicylate have emerged as promising agents for the chemoprevention of colorectal cancer (CRC). Moreover, aspirin suppresses the progression of established CRCs. However, the underlying molecular mechanisms are not completely understood. Here we found that salicylate induces the expression of the miR-34a and miR-34b/c genes, which encode tumor suppressive microRNAs, in a p53-independent manner. Salicylate activated AMPK, thereby activating NRF2, which directly induced miR-34a/b/c expression via ARE motifs. In addition, salicylate suppressed c-MYC, a known repressor of NRF2-mediated transactivation, via activating AMPK. The suppression of c-MYC by salicylate was necessary for NRF2-mediated activation of miR-34a/b/c. Inactivation of miR-34a/b/c largely abrogated the inhibitory effects of salicylate on migration, invasion and metastasis formation by CRC cells. In the future, aspirin and its derivates may be used therapeutically to activate miR-34a and miR-34b/c in tumors that have lost p53.
Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury
Authors: Tarban Nastaran , Papp Albert Bálint , Deák Dávid , Szentesi Péter , Halász Hajnalka , Patsalos Andreas , Csernoch László , Sarang Zsolt , Szondy Zsuzsa
Published: October 2023

Skeletal muscle regeneration is a complex process orchestrated by multiple interacting steps. An increasing number of reports indicate that inflammatory responses play a central role in linking initial muscle injury responses to timely muscle regeneration following injury. The nucleoside adenosine has been known for a long time as an endogenously produced anti-inflammatory molecule that is generated in high amounts during tissue injury. It mediates its physiological effects via four types of adenosine receptors. From these, adenosine A3 receptors (A3Rs) are not expressed by the skeletal muscle but are present on the surface of various inflammatory cells. In the present paper, the effect of the loss of A3Rs was investigated on the regeneration of the tibialis anterior (TA) muscle in mice following cardiotoxin-induced injury. Here we report that regeneration of the skeletal muscle from A3R−/− mice is characterized by a stronger initial inflammatory response resulting in a larger number of transmigrating inflammatory cells to the injury site, faster clearance of cell debris, enhanced proliferation and faster differentiation of the satellite cells (the muscle stem cells), and increased fusion of the generated myoblasts. This leads to accelerated skeletal muscle tissue repair and the formation of larger myofibers. Though the infiltrating immune cells expressed A3Rs and showed an increased inflammatory profile in the injured A3R−/− muscles, bone marrow transplantation experiments revealed that the increased response of the tissue-resident cells to tissue injury is responsible for the observed phenomenon. Altogether our data indicate that A3Rs are negative regulators of injury-related regenerative inflammation and consequently also that of the muscle fiber growth in the TA muscle. Thus, inhibiting A3Rs might have a therapeutic value during skeletal muscle regeneration following injury.
The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance
Authors: Fitzgerald Marie-Claire , O’Halloran Philip J. , Kerrane Sean A. , Ní Chonghaile Triona , Connolly Niamh M. C. , Murphy Brona M.
Published: October 2023

Medulloblastoma is the most common malignant paediatric brain tumour, representing 20% of all paediatric intercranial tumours. Current aggressive treatment protocols and the use of radiation therapy in particular are associated with high levels of toxicity and significant adverse effects, and long-term sequelae can be severe. Therefore, improving chemotherapy efficacy could reduce the current reliance on radiation therapy. Here, we demonstrated that systems-level analysis of basal apoptosis protein expression and their signalling interactions can differentiate between medulloblastoma cell lines that undergo apoptosis in response to chemotherapy, and those that do not. Combining computational predictions with experimental BH3 profiling, we identified a therapeutically-exploitable dependence of medulloblastoma cells on BCL-XL, and experimentally validated that BCL-XL targeting, and not targeting of BCL-2 or MCL-1, can potentiate cisplatin-induced cytotoxicity in medulloblastoma cell lines with low sensitivity to cisplatin treatment. Finally, we identified MCL-1 as an anti-apoptotic mediator whose targeting is required for BCL-XL inhibitor-induced apoptosis. Collectively, our study identifies that BCL-XL and MCL-1 are the key anti-apoptotic proteins in medulloblastoma, which mediate distinct protective roles. While BCL-XL has a first-line role in protecting cells from apoptosis basally, MCL-1 represents a second line of defence that compensates for BCL-XL upon its inhibition. We provide rationale for the further evaluation of BCL-XL and MCL-1 inhibitors in the treatment of medulloblastoma, and together with current efforts to improve the cancer-specificity of BCL-2 family inhibitors, these novel treatment strategies have the potential to improve the future clinical management of medulloblastoma.
Wastewater sequencing reveals community and variant dynamics of the collective human virome
Authors: Tisza Michael , Javornik Cregeen Sara , Avadhanula Vasanthi , Zhang Ping , Ayvaz Tulin , Feliz Karen , Hoffman Kristi L. , Clark Justin R. , Terwilliger Austen , Ross Matthew C. , Cormier Juwan , Moreno Hannah , Wang Li , Payne Katelyn , Henke David , Troisi Catherine , Wu Fuqing , Rios Janelle , Deegan Jennifer , Hansen Blake , Balliew John , Gitter Anna , Zhang Kehe , Li Runze , Bauer Cici X. , Mena Kristina D. , Piedra Pedro A. , Petrosino Joseph F. , Boerwinkle Eric , Maresso Anthony W.
Published: October 2023

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.
A super liquid-repellent hierarchical porous membrane for enhanced membrane distillation
Authors: Hou Youmin , Shah Prexa , Constantoudis Vassilios , Gogolides Evangelos , Kappl Michael , Butt Hans-Jürgen
Published: October 2023

Membrane distillation (MD) is an emerging desalination technology that exploits phase change to separate water vapor from saline based on low-grade energy. As MD membranes come into contact with saline for days or weeks during desalination, membrane pores have to be sufficiently small (typically <0.2 µm) to avoid saline wetting into the membrane. However, in order to achieve high distillation flux, the pore size should be large enough to maximize transmembrane vapor transfer. These conflicting requirements of pore geometry pose a challenge to membrane design and currently hinder broader applications of MD. To address this fundamental challenge, we developed a super liquid-repellent membrane with hierarchical porous structures by coating a polysiloxane nanofilament network on a commercial micro-porous polyethersulfone membrane matrix. The fluorine-free nanofilament coating effectively prevents membrane wetting under high hydrostatic pressure (>11.5 bar) without compromising vapor transport. With large inner micro-porous structures, the nanofilament-coated membrane improves the distillation flux by up to 60% over the widely used commercially available membranes, while showing excellent salt rejection and operating stability. Our approach will allow the fabrication of high-performance composite membranes with multi-scale porous structures that have wide-ranging applications beyond desalination, such as in cleaning wastewater.
A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development
Authors: O’Keefe Ryan N. , Carli Annalisa L. E. , Baloyan David , Chisanga David , Shi Wei , Afshar-Sterle Shoukat , Eissmann Moritz F. , Poh Ashleigh R. , Pal Bhupinder , Seillet Cyril , Locksley Richard M. , Ernst Matthias , Buchert Michael
Published: October 2023

Although gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here, we report the pro-tumorigenic properties of the crosstalk between intestinal tuft cells and type 2 innate lymphoid cells (ILC2) that is evolutionarily optimized for epithelial remodeling in response to helminth infection. We demonstrate that tuft cell-derived interleukin 25 (IL25) drives ILC2 activation, inducing the release of IL13 and promoting epithelial tuft cell hyperplasia. While the resulting tuft cell - ILC2 feed-forward circuit promotes gastric metaplasia and tumor formation, genetic depletion of tuft cells or ILC2s, or therapeutic targeting of IL13 or IL25 alleviates these pathologies in mice. In gastric cancer patients, tuft cell and ILC2 gene signatures predict worsening survival in intestinal-type gastric cancer where ~40% of the corresponding cancers show enriched co-existence of tuft cells and ILC2s. Our findings suggest a role for ILC2 and tuft cells, along with their associated cytokine IL13 and IL25 as gatekeepers and enablers of metaplastic transformation and gastric tumorigenesis, thereby providing an opportunity to therapeutically inhibit early-stage gastric cancer through repurposing antibody-mediated therapies.
Mechanism of synergistic activation of Arp2/3 complex by cortactin and WASP-family proteins
Authors: Fregoso Fred E. , Boczkowska Malgorzata , Rebowski Grzegorz , Carman Peter J. , van Eeuwen Trevor , Dominguez Roberto
Published: October 2023

Cortactin coactivates Arp2/3 complex synergistically with WASP-family nucleation-promoting factors (NPFs) and stabilizes branched networks by linking Arp2/3 complex to F-actin. It is poorly understood how cortactin performs these functions. We describe the 2.89 Å resolution cryo-EM structure of cortactin’s N-terminal domain (Cort1-76) bound to Arp2/3 complex. Cortactin binds Arp2/3 complex through an inverted Acidic domain (D20-V29), which targets the same site on Arp3 as the Acidic domain of NPFs but with opposite polarity. Sequences N- and C-terminal to cortactin’s Acidic domain do not increase its affinity for Arp2/3 complex but contribute toward coactivation with NPFs. Coactivation further increases with NPF dimerization and for longer cortactin constructs with stronger binding to F-actin. The results suggest that cortactin contributes to Arp2/3 complex coactivation with NPFs in two ways, by helping recruit the complex to F-actin and by stabilizing the short-pitch (active) conformation, which are both byproducts of cortactin’s core function in branch stabilization.
The Lin28b/Wnt5a axis drives pancreas cancer through crosstalk between cancer associated fibroblasts and tumor epithelium
Authors: Shu Zhaoqi , Fan Minghe , Tu Bo , Tang Zhiheng , Wang Haojie , Li Haimeng , Li Hengchao , Yuan Meng , Bai Jingru , Huo Sihan , Wang Lina , Zhu Wei-Guo , Wang Wei , Liu Xiaoyun , Shu Shaokun , Zhao Ying
Published: October 2023

Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9’s production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-‍tumorigenic contexture.
Precise synthetic control of exclusive ligand effect boosts oxygen reduction catalysis
Authors: Tao Lu , Wang Kai , Lv Fan , Mi Hongtian , Lin Fangxu , Luo Heng , Guo Hongyu , Zhang Qinghua , Gu Lin , Luo Mingchuan , Guo Shaojun
Published: October 2023

Ligand effect, induced by charge transfer between catalytic surface and substrate in core/shell structure, was widely proved to benefit Pt-catalyzed oxygen reduction reaction by tuning the position of d-band center of Pt theoretically. However, ligand effect is always convoluted by strain effect in real core/shell nanostructure; therefore, it remains experimentally unknown whether and how much the ligand effect solely contributes electrocatalytic activity improvements. Herein, we report precise synthesis of a kind of Pd3Ru1/Pt core/shell nanoplates with exclusive ligand effect for oxygen reduction reaction. Layer-by-layer growth of Pt overlayers onto Pd3Ru1 nanoplates can guarantee no lattice mismatch between core and shell because the well-designed Pd3Ru1 has the same lattice parameters as Pt. Electron transfer, due to the exclusive ligand effect, from Pd3Ru1 to Pt leads to a downshift of d-band center of Pt. The optimal Pd3Ru1/Pt1-2L nanoplates achieve excellent activity and stability for oxygen reduction reaction in alkaline/acid electrolyte.