bluuebunny/crossref_metadata_2025 huggingface dataset:
“Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)—Part-1”
Authors: Bonomi M. , Cangiano B. , Cianfarani S. , Garolla A. , Gianfrilli D. , Lanfranco F. , Rastrelli G. , Sbardella E. , Corona G. , Isidori A. M. , Rochira V.
Published: August 2024

Purpose

Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available.

Methods

The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system.

Results

A literature search of articles in English for the term “varicoceles”, “gynecomastia”, “fertility preservation”, “macroorchidism”, “precocious puberty” and “pubertal delay” has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders.

Conclusions

These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.
Retailers’ social impact perspective–discrepancies between theory and practice
Authors: Stefańska Magdalena , Olejnik Iwona
Published: August 2024

In recent years, the issue of social impact and its associated measurement methodologies has attracted considerable scholarly attention. This paper makes a contribution to the ongoing debate surrounding the dissonance between the theoretical conceptualization of social impact and the practical understanding of it held by business managers and consumers. To elucidate the discrepancies between theory and practice, as well as among the knowledge, attitudes and behaviors of stakeholders targeted by social impact initiatives, a qualitative research approach was employed. This paper has two main objectives. The first is to elucidate the concept of social impact within the framework of Corporate Social Responsibility (CSR). The second is to examine the understanding of social impact as depicted in CSR reports of retailers and its reception by consumers, particularly in the context of social activities undertaken by retail chains. The findings highlight significant discrepancies in the perception of social impact. Among enterprises, social impact is often associated with engagement in various activities. However, the resulting outcomes of these endeavors are frequently not quantified. Despite this absence of empirical data, managers often draw inferences regarding the presence of such impact. Conversely, consumers predominantly interpret social impact through changes in their purchasing behavior, prioritizing this aspect over heightened product knowledge, brand perception or corporate image enhancement.
Segmentation-aware relational graph convolutional network with multi-layer CRF for nested named entity recognition
Authors: Han Daojun , Wang Zemin , Li Yunsong , ma Xiangbo , Zhang Juntao
Published: August 2024

Named Entity Recognition (NER) is fundamental in natural language processing, involving identifying entity spans and types within a sentence. Nested NER contains other entities, which pose a significant challenge, especially pronounced in the domain of medical-named entities due to intricate nesting patterns inherent in medical terminology. Existing studies can not capture interdependencies among different entity categories, resulting in inadequate performance in nested NER tasks. To address this problem, we propose a novel Layer-based architecture with Segmentation-aware Relational Graph Convolutional Network (LSRGCN) for Nested NER in the medical domain. LSRGCN comprises two key modules: a shared segmentation-aware encoder and a multi-layer conditional random field decoder. The former part provides token representation including boundary information from sentence segmentation. The latter part can learn the connections between different entity classes and improve recognition accuracy through secondary decoding. We conduct experiments on four datasets. Experimental results demonstrate the effectiveness of our model. Additionally, extensive studies are conducted to enhance our understanding of the model and its capabilities.
Generalized spatial–temporal regression graph convolutional transformer for traffic forecasting
Authors: Xiong Lang , Su Liyun , Zeng Shiyi , Li Xiangjing , Wang Tong , Zhao Feng
Published: August 2024

Spatial–temporal data is widely available in intelligent transportation systems, and accurately solving non-stationary of spatial–temporal regression is critical. In most traffic flow prediction research, the non-stationary solution of deep spatial–temporal regression tasks is typically formulated as a spatial–temporal graph modeling problem. However, there are several issues: (1) the coupled spatial–temporal regression approach renders it unfeasible to accurately learn the dependencies of diverse modalities; (2) the intricate stacking design of deep spatial–temporal network modules limits the interpretation and migration capability; (3) the ability to model dynamic spatial–temporal relationships is inadequate. To tackle the challenges mentioned above, we propose a novel unified spatial–temporal regression framework named Generalized Spatial–Temporal Regression Graph Convolutional Transformer (GSTRGCT) that extends panel model in spatial econometrics and combines it with deep neural networks to effectively model non-stationary relationships of spatial–temporal regression. Considering the coupling of existing deep spatial–temporal networks, we introduce the tensor decomposition to explicitly decompose the panel model into a tensor product of spatial regression on the spatial hyper-plane and temporal regression on the temporal hyper-plane. On the spatial hyper-plane, we present dynamic adaptive spatial weight network (DASWNN) to capture the global and local spatial correlations. Specifically, DASWNN adopts spatial weight neural network (SWNN) to learn the semantic global spatial correlation and dynamically adjusts the local changing spatial correlation by multiplying between spatial nodes embedding. On the temporal hyper-plane, we introduce the Auto-Correlation attention mechanism to capture the period-based temporal dependence. Extensive experiments on the two real-world traffic datasets show that GSTRGCT consistently outperforms other competitive methods with an average of 62% and 59% on predictive performance.
Towards the 3D printing of innovative hydrogel scaffolds through vat polymerization techniques using methacrylated carboxymethylcellulose aqueous formulations
Authors: Soullard Lénaïc , Schlepp Angélique , Buret Raphaël , Lancelon-Pin Christine , Nonglaton Guillaume , Texier Isabelle , Jean Bruno , Rolere Sébastien
Published: August 2024

Two vat polymerization techniques were evaluated to print innovative hydrogel scaffolds for tissue engineering, from aqueous photo-crosslinkable formulations based on methacrylated carboxymethylcellulose (mCMC). A first formulation containing 2 wt% mCMC with a methacrylation degree (DM) of 34% and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photoinitiator was specifically developed for digital light processing (DLP). Considering their viscoelastic properties measured by shear rheology, the DLP-printed hydrogels were proposed for soft-tissue repair. Interestingly, the swelling ratio and shape of the printed hydrogels were found to be preserved when immersed in a physiological environment. While DLP-printed hydrogels demonstrated impressive X- and Y-resolutions (85 µm), they were limited in producing hollow objects in the Z-direction. To address this limitation, the 3D printing of complex mCMC hydrogels through two-photon polymerization (TPP) was investigated for the first time, using a second formulation composed of 4 wt% mCMC (DM = 50%). 3D scaffolds with cavities of 30 µm were successfully printed with a resolution of 10 µm, paving the way for the design of scaffolds with controlled and precise structures, for soft-tissue engineering.

Graphical abstract
Correlating outgassing and smoke phenomenon in electron beam powder bed fusion of Ti6Al4V using a residual gas analyzer
Authors: Ye Jihui , Chen Tiejue , Körner Carolin
Published: August 2024

Electron beam powder bed fusion (PBF-EB) is an additive manufacturing technique that fabricates customized components using an electron beam in a controlled vacuum environment. Maintaining high vacuum quality is crucial to prevent feedstock contamination. However, the inherent nature of the PBF-EB process introduces a gas load into the system, potentially affecting process stability and product quality. This study utilizes a residual gas analyzer to investigate experimentally outgassing associated with various process activities, including electron beam radiation, rake movement, and powder outgassing. The findings indicate that hydrogen, water, nitrogen, oxygen, argon, and carbon dioxide are the predominant gases present during PBF-EB processes. Moreover, rapid outgassing is identified as a likely trigger for powder movement, marking the initial stage of the smoke phenomenon. These results contribute fundamental insights into the gas atmospheres in PBF-EB processes.
The Role of Talus Pile Mobility in Valley Widening Processes and the Development of Wide Bedrock Valleys, Buffalo River, AR
Authors: Groeber O. H. , Langston A. L.
Published: August 2024

Valley width is largely controlled by lithology and upstream drainage area, but little work has focused on identifying the processes through which valleys widen. Bedrock valleys widen by first laterally eroding bedrock valley walls, followed by the collapse of overlying bedrock material that must then be transported away from the valley wall before the valley can continue widening. We hypothesize that talus piles that cannot be transported by the river protect the valley wall and slow valley widening, while talus piles that are rapidly transported allow for uninterrupted valley widening. We used field measurements from 40 locations in both wide and narrow valleys along the Buffalo River, AR to test this hypothesis. Our data show that wide valleys tend to have fewer talus piles and smaller talus grain sizes, whereas talus in narrow valleys is larger in size and more continuous along valley walls. We calculated potential talus block entrainment at each site location and found that talus blocks in wide valleys are potentially entrained and moved away from valley walls during moderate and large flood events, whereas talus blocks in narrow valleys are very rarely moved. Our results show that the potential transport of talus piles protecting bedrock valley walls from widening is controlled by the block size of collapsed bedrock wall material relative to stream competency. Our results also suggest that persistence versus mobility of collapsed talus piles is an important process in the development of wide bedrock valleys.
A Model for Melt‐Preferred Orientation and Permeabilities in Deformed Partially Molten Peridotites
Authors: Liu Boda , Qi Chao , Mitchell Ross N. , Lee Cin‐Ty A. , Liu Chuan‐Zhou
Published: August 2024

In a deforming partially molten rock, melt concentrates into a grain‐scale melt pocket aligned at a preferred orientation (melt‐preferred orientation, or MPO). However, observing this texture alone provides limited information on the 3D orientation and geometry of these melt pockets, which are critical parameters for estimating permeability. Here, we modeled the MPO of experimentally deformed peridotites by simulating melt streaks arising from melt pockets of various shapes and 3D orientations. The model aims to identify 3D distribution and characteristics of melt pockets that could account for the observed length, thickness, and the probability of melt streaks. Results show that melt pockets at preferred orientation exhibit greater length, thickness, and number density compared to those perpendicular. These results can be incorporated into the simulation of melt flow through individual melt pockets, which allows us to estimate the permeability corresponding to the observed MPO. We found that the permeability of vertically compressed peridotites increases with increasing compressive strain and a more elongated and thickened shape for melt pocket aligned at preferred orientation. The vertical permeability in the sample with 30% compressive strain is at least 40 times larger than that of an undeformed sample. For peridotites deformed under simple shear, the permeability exhibits an anisotropy of at least three. Such anisotropic permeability, coupled with the formation of melt‐rich bands and other melt channels, is believed to cause lateral melt focusing beneath mid‐ocean ridges.
Climate Change and Health: Perspectives From Ghana
Authors: Akakpo Martin Gameli , Hagan Sylvia , Bokpin Hayford Alufar
Published: August 2024

Climate change is impacting many aspects of human life in many ways. In Ghana, climate change knowledge remains low and discussions linking climate change and health are scarce. In this paper, authors contribute to the shaping of discussions about climate and health with a focus on how climate change increases certain ailments. First, the paper addresses the need for research in Ghanaian communities to link climate change and health. Second, the paper suggests the development of policies to address the link. Third, public health educators are advised in this paper to educate the public.
Seasonal and Interhemispheric Variations of the Afternoon Auroral Responses to the Interplanetary Magnetic Field By Polarity
Authors: Zhu Shengting , Luan Xiaoli , Lei Jiuhou
Published: August 2024

This work investigates seasonal and interhemispheric variations of the afternoon auroral responses to the interplanetary magnetic field (IMF) By effects. The auroral observations are adopted from the global ultraviolet imager instrument on board the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite during 2002–2007. The results show that in both summer and winter solstices, the stronger afternoon auroral intensity is associated with negative IMF By (By < 0) in the northern hemisphere, and with By > 0 in the southern hemisphere. This suggests stronger contributions from the upward field‐aligned currents (FACs), which can be induced by the By‐associated north‐south oriented electric field and the By‐associated flow shear in the ionosphere. In addition, the strongest afternoon aurora occurs in summer in each hemisphere. In summer, the absolute difference between the auroral peak intensity under the two By polarities is greater and occurs earlier than in winter, which may be related to changes in FACs and conductivity from winter to summer. Differently, in equinoxes stronger auroral intensity favors By conditions associated with more frequent occurrence of southward IMF Bz, such as By < 0 and By > 0 conditions in March and in September, respectively. Therefore, in equinoxes the effects of the favorable By, which were seen in solstices, are masked. We suggest that these are caused by the Russell‐McPherron effect, which leads to more southward Bz conditions, resulting in more energy deposited and subsequent stronger aurora in polar ionosphere. These results contribute to our deeper understanding of the asymmetrical phenomena in the Earth's magnetosphere‐ionosphere induced by IMF By.
Longitude Structure of Wavenumber 4 of the Ionosphere After Midnight Based on the OI135.6 nm Night Airglow Using FY‐3D Ionospheric Photometer
Authors: Zhang Bin , Fu Liping , Mao Tian , Hu Xiuqing , Wang Yungang , Jiang Fang , Jia Nan , Wang Tianfang , Peng Ruyi , Wang Jinsong
Published: August 2024

In this study, based on the OI135.6 nm night airglow data of the FY‐3D Ionospheric Photometer (IPM) during the 2018–2021 geomagnetically quiet period, the global wavenumber 4 longitudinal structure of the equatorial ionization anomaly (EIA) at 2:00 local time was discovered, and the component of the wavenumber 4 was extracted from these structures. Compared with the OI135.6 nm night airglow data of the Special Sensor Ultraviolet Spectrographic Imager (SSUSI) F18 during 2011–2014, there were significant differences in the variation pattern of the relative amplitude of the two versus solar activity and the seasonal variation in the proportion of the component of the wavenumber 4. Based on the neutral wind speed observation results of the Michelson Interferometer for Global High‐Resolution Thermospheric Imaging on board the Ionospheric Connection Explorer (ICON) from 2020 to 2021, the longitudinal structures of the 4 ionospheric waves after midnight are related to the cross‐equatorial meridional wind. We believe that the wavenumber 4 longitudinal structures after midnight originate from the semidiurnal eastward‐propagating with zonal wavenumber 2 (SE2) nonmigrating tide in the cross‐equatorial neutral wind rather than the diurnal eastward‐propagating with zonal wavenumber 3 (DE3) nonmigrating tide in from the zonal wind, which modulates the daytime wavenumber 4 longitudinal structures.
Quantitative Evaluation of the Effect of Pore Fluids Distribution on Complex Conductivity Saturation Exponents
Authors: Qiang Siyuan , Shi Xiaoqing , Revil André , Kang Xueyuan , Song Yalin , Xing Kun
Published: August 2024

The induced polarization (IP) method holds a strong potential to better characterize the critical zone of our planet especially in areas characterized by multi‐phase flow. Power‐law relationships between the bulk, surface, and quadrature conductivities versus the pore water saturation are potentially useable to map the subsurface water content distribution. However, the saturation exponents n and p in these power‐law relationships have been observed to vary with the texture of geomaterials and the wettabilities of pore fluids. Traditional experimental setups in the laboratory do not allow to independently visualize the pore fluid distribution. Therefore, the physical interpretations of the two saturation exponents have remained unclear. We developed a novel milli‐fluidic micromodel using clay‐coated glass beads that exhibit excellent visibility and high IP response. Through laboratory experiments, we simultaneously determined the micromodel complex conductivity and acquired the corresponding pore‐scale fluid distributions generated by drainage and imbibition through such class of porous materials. Finite‐element simulations of complex conductivity based on the upscaling of the complex surface conductance of grains were conducted to determine the saturation exponents under ideal pore fluid distributions. Results indicate that saturation exponents n and p vary depending on the ganglia size of the insulating fluids. The saturation exponents n and p exhibit power‐law relationships with the change rate of pore water connectivity with saturation, which is calculated through the computation of the derivative of Euler characteristics. These findings provide a new physical explanation to the relationships between the saturation exponents and the microscopic fluid distributions within the geomaterials.
Investigation on the Impact of Solar Flares on the Martian Atmospheric Emissions in the Dayside Near‐Terminator Region: Case Studies
Authors: Ram Lot , Sharma Ritika , Rout Diptiranjan , Rathi Rahul , Sarkhel Sumanta
Published: August 2024

Solar transient events like flares can cause sudden changes in planetary plasma and neutral environment. However, there is less understanding about their impact on the Martian emissions. Here, we present an investigation of the variability of the Martian atmospheric emissions, viz. OI 130.4 nm, 135.6 nm, CO2+ ultraviolet doublet (UVD), and CO Cameron band (CB) in the dayside near‐terminator region during solar flare events. The two X8.2 and M6 class flares during September 2017 on Mars have been selected from existing catalogs. Using data from the imaging ultraviolet spectrograph aboard the Mars Atmosphere and Volatile EvolutioN spacecraft, we examined limb radiance profiles. We observed a significant increase in peak radiance (∼130–140 km) for major emissions with a more pronounced impact beneath the emissions peak during flares compared to quiet time. During solar flares, for 130.4 and 135.6 nm emission, the maximum deviation in radiance beneath peak approaches ∼63% and ∼123%, respectively. Whereas, for CO2+ UVD and CO CB, it is ∼64% and ∼50%, respectively. Additionally, we have presented an average scenario of the dayside near‐terminator (solar zenith angle ∼ 70–90°) and observed a notable trend of higher percentage deviation for atomic emissions compared to molecular emissions during flares. Further, our analysis depicts a higher percentage deviation during X8.2 compared to the M6 class flare. This study underscores that during flares, higher irradiance flux and photoelectron impact drive the airglow production processes, leading to enhanced emissions. The case studies offer a novel insight into the significant influence of the varying solar flares intensities on planetary atmospheric emissions.
Ter‐Diurnal Atmospheric Tide on Mars
Authors: Leino Joonas , Harri Ari‐Matti , Wilson Robert John , Banfield Don , Lemmon Mark , Paton Mark , Rodriguez‐Manfredi Jose‐Antonio , Savijärvi Hannu
Published: August 2024

Cyclic absorption of solar radiation generates oscillations in atmospheric fields. These oscillations are called atmospheric or thermal tides, which are furthermore modified by topography and surface properties. This leads to a complex mix of sun‐synchronous and non‐sun‐synchronous tides that propagate around the planet eastward and westward. This study focuses on analyzing the ter‐diurnal component (period of 8 hr) from surface pressure observations by Mars Science Laboratory (MSL), InSight, Viking Lander (VL) 1, and VL2. General Circulation Model (GCM) results are used to provide a global context for interpreting the observed ter‐diurnal tide properties. MSL and InSight have a clear and similar seasonal cycle, with local amplitude peaks at around solar longitude (Ls) 60°, Ls 130°, and Ls 320°. The amplitude peak at Ls 320° is related to the annual dust storm, while the Ls 230° dust storm is not detected by either platforms. During global dust storms, MSL, VL1, and VL2 detect their highest amplitudes. The GCM predicts the weakest amplitudes at the equinoxes, while the strongest ones are predicted in summer for both hemispheres. GCM amplitudes tend to differ from the observations but match slightly better around the aphelion season. During this time, model results suggest that the two most prominent modes are the sun‐synchronous ter‐diurnal tide and an eastward propagating resonantly enhanced Kelvin wave. Simulations with and without the effect of radiative heating by water ice clouds indicate the clouds may play a significant role in forcing the ter‐diurnal tide during northern hemisphere summer season.
Rates of Evacuation of Bedload Sediment From an Alpine Glacier Control Proglacial Stream Morphodynamics
Authors: Mancini D. , Roncoroni M. , Dietze M. , Jenkin M. , Müller T. , Ouvry B. , Miesen F. , Pythoud Q. , Hofmann M. , Lardet F. , Nicholas A. P. , Lane S. N.
Published: August 2024

Proglacial forefields commonly include highly dynamic fluvial systems associated with the fundamental instability between topography, flow hydraulics and sediment transport. However, there is limited knowledge of how these systems respond to changing subglacial hydrology and sediment supply. We investigated this relationship using the first continuous field‐collected data sets for both suspended and bedload sediment export and proglacial river dynamics for an Alpine glacier forefield, the Glacier d’Otemma, Switzerland. The results show a strong sensitivity of fluvial morphodynamics to the balance between sediment transport capacity and supply. When subglacial bedload export rates exceeded fluvial transport capacity, we found bar construction leading to net forefield aggradation and surficial coarsening, especially on bar heads. This intensified braiding buffered the downstream transport of coarse sediment. When subglacial bedload export rates were lower than transport capacity, incision occurred, with reduced braiding intensity, net erosion and important amounts of bedload leaving the proglacial system. We found a net fining of surficial deposits except for very isolated coarsening patterns on bar heads. Thus, proglacial forefield morphodynamics are strongly conditioned by subglacial hydrology and sediment supply, but this conditioning is also influenced by the response of the forefield itself. Proglacial forefields have an important influence on the longitudinal connectivity of sediment flux in regions sensitive to climate change, such as recently deglaciated high mountain areas. The linkages we report between subglacial processes and river morphodynamics are critical for understanding the development of embryonic forefield ecosystems.
Slip Distribution Along the Chenghai Fault From Airborne LiDAR and Tectonic Implications for the 1515 Yongsheng Earthquake, China
Authors: Ji Haomin , Ren Zhikun , Zhu Xiaoxiao , Bai Mingkun , Bao Guodong , Liu Jinrui , Ha Guanghao , He Zhongtai
Published: August 2024

The tectonic deformation of the southeastern margin of the Tibetan Plateau underwent significant changes before and after the Miocene, which led to the change of the deformation characteristics of the Sichuan‐Yunnan block, and some local areas in the block also showed structural patterns inconsistent with the macroscopic clockwise rotation deformation. Moreover, the Chenghai fault (CF) in the Sichuan‐Yunnan block was the seismogenic fault of the M 73/4 Yongsheng earthquake in 1515. However, the dense vegetation impeded the acquisition of surface deformation characteristics and small‐scale horizontal offsets along the fault, resulting in its misty kinematic properties, roughly determined geometric distribution, and the highly controversial rupture parameters of the Yongsheng earthquake. Therefore, we used airborne light detection and ranging, which can penetrate vegetation to obtain high‐resolution surface topography, to map the CF within 120 km. Combined with satellite images and field investigations, we determined that the CF consists of a series of secondary faults with simple geometric structures. Continuous offset linear landforms were preserved along the fault. 102 offsets below 30 m were statistically analyzed and the result revealed that the CF has a characteristic displacement of ∼6 m and it may rupture as a united rupture segment in each large earthquake or its two rupture segments cascade rupture to generate large earthquakes. The magnitude of the Yongsheng earthquake in 1515 was estimated at 7.7. Finally, based on this study, the kinematic characteristics of the Dali terrane and Sichuan‐Yunnan block, where the CF is located are discussed.
Comparison of the rate of healthcare encounters for influenza from source-specific PM2.5 before and after tier 3 vehicle standards in New York state
Authors: Croft Daniel P. , Utell Mark J. , Hopke Philip K. , Liu Han , Lin Shao , Thurston Sally W. , Thandra Sathvik , Chen Yunle , Islam Md Rayhanul , Thevenet-Morrison Kelly , Johnston Carl J. , Zhao Tianming , Yount Catherine , Rich David Q.
Published: August 2024

Background

Influenza healthcare encounters in adults associated with specific sources of PM2.5 is an area of active research.

Objective

Following 2017 legislation requiring reductions in emissions from light-duty vehicles, we hypothesized a reduced rate of influenza healthcare encounters would be associated with concentrations of PM2.5 from traffic sources in the early implementation period of this regulation (2017–2019).

Methods

We used the Statewide Planning and Research Cooperative System (SPARCS) to study adult patients hospitalized (N = 5328) or treated in the emergency department (N = 18,247) for influenza in New York State. Using a modified case-crossover design, we estimated the excess rate (ER) of influenza hospitalizations and emergency department visits associated with interquartile range increases in source-specific PM2.5 concentrations (e.g., spark-ignition emissions [GAS], biomass burning [BB], diesel [DIE]) in lag day(s) 0, 0–3 and 0–6. We then evaluated whether ERs differed after Tier 3 implementation (2017–2019) compared to the period prior to implementation (2014–2016).

Results

Each interquartile range increase in DIE in lag days 0–6 was associated with a 21.3% increased rate of influenza hospitalization (95% CI: 6.9, 37.6) in the 2014–2016 period, and a 6.3% decreased rate (95% CI: −12.7, 0.5) in the 2017–2019 period. The GAS/influenza excess rates were larger in the 2017–2019 period than the 2014–2016 period for emergency department visits. We also observed a larger ER associated with increased BB in the 2017–2019 period compared to the 2014–2016 period.

Impact statement

We present an accountability study on the impact of the early implementation period of the Tier 3 vehicle emission standards on the association between specific sources of PM2.5 air pollution on influenza healthcare encounters in New York State. We found that the association between gasoline emissions and influenza healthcare encounters did not lessen in magnitude between periods, possibly because the emissions standards were not yet fully implemented. The reduction in the rates of influenza healthcare encounters associated with diesel emissions may be reflective of past policies to reduce the toxicity of diesel emissions. Accountability studies can help policy makers and environmental scientists better understand the timing of pollution changes and associated health effects.
Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks
Authors: Pankratov Vasili , Mezzavilla Massimo , Aneli Serena , Kuznetsov Ivan A. , Fusco Daniela , Wilson James F. , Metspalu Mait , Provero Paolo , Pagani Luca , Marnetto Davide
Published: August 2024

The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.
Unpacking the notion of “serious” genetic conditions: towards implementation in reproductive decision-making?
Authors: Kleiderman Erika , Boardman Felicity , Newson Ainsley J. , Laberge Anne-Marie , Knoppers Bartha Maria , Ravitsky Vardit
Published: August 2024

The notion of a “serious” genetic condition is commonly used in clinical contexts, laws, and policies to define and delineate both the permissibility of and, access to, reproductive genomic technologies. Yet, the notion lacks conceptual and operational clarity, which can lead to its inconsistent appraisal and application. A common understanding of the relevant considerations of “serious” is lacking. This article addresses this conceptual gap. We begin by outlining existing distinctions around the notion of “serious” that will factor into its appraisal and need to be navigated, in the context of prenatal testing and the use of reproductive genomic technologies. These include tensions between clinical care and population health; the impact of categorizing a condition as “serious”; and the role of perception of quality of life. We then propose a set of four core dimensions and four procedural elements that can serve as a conceptual tool to prompt a mapping of the features of seriousness in any given context. Ultimately, consideration of these core dimensions and procedural elements may lead to improvements in the quality and consistency of decision-making where the seriousness of a genetic condition is a pivotal component at both a policy and practice level.
Acoustofluidic-based therapeutic apheresis system
Authors: Wu Mengxi , Ma Zhiteng , Xu Xianchen , Lu Brandon , Gu Yuyang , Yoon Janghoon , Xia Jianping , Ma Zhehan , Upreti Neil , Anwar Imran J. , Knechtle Stuart J. , T. Chambers Eileen , Kwun Jean , Lee Luke P. , Huang Tony Jun
Published: August 2024

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 μL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients.
Signaling by a bacterial phytochrome histidine kinase involves a conformational cascade reorganizing the dimeric photoreceptor
Authors: Burgie E. Sethe , Basore Katherine , Rau Michael J. , Summers Brock , Mickles Alayna J. , Grigura Vadim , Fitzpatrick James A. J. , Vierstra Richard D.
Published: August 2024

Phytochromes (Phys) are a divergent cohort of bili-proteins that detect light through reversible interconversion between dark-adapted Pr and photoactivated Pfr states. While our understandings of downstream events are emerging, it remains unclear how Phys translate light into an interpretable conformational signal. Here, we present models of both states for a dimeric Phy with histidine kinase (HK) activity from the proteobacterium Pseudomonas syringae, which were built from high-resolution cryo-EM maps (2.8–3.4-Å) of the photosensory module (PSM) and its following signaling (S) helix together with lower resolution maps for the downstream output region augmented by RoseTTAFold and AlphaFold structural predictions. The head-to-head models reveal the PSM and its photointerconversion mechanism with strong clarity, while the HK region is interpretable but relatively mobile. Pr/Pfr comparisons show that bilin phototransformation alters PSM architecture culminating in a scissoring motion of the paired S-helices linking the PSMs to the HK bidomains that ends in reorientation of the paired catalytic ATPase modules relative to the phosphoacceptor histidines. This action apparently primes autophosphorylation enroute to phosphotransfer to the cognate DNA-binding response regulator AlgB which drives quorum-sensing behavior through transient association with the photoreceptor. Collectively, these models illustrate how light absorption conformationally translates into accelerated signaling by Phy-type kinases.
Conditional RNA interference in mammalian cells via RNA transactivation
Authors: Zhou Yu , Sheng Peike , Li Jiayi , Li Yudan , Xie Mingyi , Green Alexander A.
Published: August 2024

RNA interference (RNAi) is a powerful tool for sequence-specific gene knockdown in therapeutic and research applications. However, spatiotemporal control of RNAi is required to decrease nonspecific targeting, potential toxicity, and allow targeting of essential genes. Herein we describe a class of de-novo-designed RNA switches that enable sequence-specific regulation of RNAi in mammalian cells. Using cis-repressing RNA elements, we engineer RNA devices that only initiate microRNA biogenesis when binding with cognate trigger RNAs. We demonstrate that this conditional RNAi system, termed Orthogonal RNA Interference induced by Trigger RNA (ORIENTR), provides up to 14-fold increases in artificial miRNA biogenesis upon activation in orthogonal libraries. We show that integration of ORIENTR triggers with dCas13d enhances dynamic range to up to 31-fold. We further demonstrate that ORIENTR can be applied to detect endogenous RNA signals and to conditionally knockdown endogenous genes, thus enabling regulatory possibilities including cell-type-specific RNAi and rewiring of transcriptional networks via RNA profile.
Physics-informed deep generative learning for quantitative assessment of the retina
Authors: Brown Emmeline E. , Guy Andrew A. , Holroyd Natalie A. , Sweeney Paul W. , Gourmet Lucie , Coleman Hannah , Walsh Claire , Markaki Athina E. , Shipley Rebecca , Rajendram Ranjan , Walker-Samuel Simon
Published: August 2024

Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels, based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks with no human input and which out-performs human labelling. Segmentation of DRIVE and STARE retina photograph datasets provided near state-of-the-art vessel segmentation, with training on only a small (n = 100) simulated dataset. Our findings highlight the potential of PI-GAN for accurate retinal vasculature characterization, with implications for improving early disease detection, monitoring disease progression, and improving patient care.
On the origin of low-valent uranium oxidation state
Authors: Silva C. L. , Amidani L. , Retegan M. , Weiss S. , Bazarkina E. F. , Graubner T. , Kraus F. , Kvashnina K. O.
Published: August 2024

The significant interest in actinide bonding has recently focused on novel compounds with exotic oxidation states. However, the difficulty in obtaining relevant high-quality experimental data, particularly for low-valent actinide compounds, prevents a deeper understanding of 5f systems. Here we show X-ray absorption near-edge structure (XANES) measurements in the high-energy resolution fluorescence detection (HERFD) mode at the uranium M4 edge for the UIII and UIV halides, namely UX3 and UX4 (X = F, Cl, Br, I). The spectral shapes of these two series exhibit clear differences, which we explain using electronic structure calculations of the 3d-4f resonant inelastic X-ray scattering (RIXS) process. To understand the changes observed, we implemented crystal field models with ab initio derived parameters and investigated the effect of reducing different contributions to the electron-electron interactions involved in the RIXS process. Our analysis shows that the electron-electron interactions weaken as the ligand changes from I to F, indicative of a decrease in ionicity both along and between the UX3 and UX4 halide series.
Symbolic metaprogram search improves learning efficiency and explains rule learning in humans
Authors: Rule Joshua S. , Piantadosi Steven T. , Cropper Andrew , Ellis Kevin , Nye Maxwell , Tenenbaum Joshua B.
Published: August 2024

Throughout their lives, humans seem to learn a variety of rules for things like applying category labels, following procedures, and explaining causal relationships. These rules are often algorithmically rich but are nonetheless acquired with minimal data and computation. Symbolic models based on program learning successfully explain rule-learning in many domains, but performance degrades quickly as program complexity increases. It remains unclear how to scale symbolic rule-learning methods to model human performance in challenging domains. Here we show that symbolic search over the space of metaprograms—programs that revise programs—dramatically improves learning efficiency. On a behavioral benchmark of 100 algorithmically rich rules, this approach fits human learning more accurately than alternative models while also using orders of magnitude less search. The computation required to match median human performance is consistent with conservative estimates of human thinking time. Our results suggest that metaprogram-like representations may help human learners to efficiently acquire rules.
Covalent penicillin-protein conjugates elicit anti-drug antibodies that are clonally and functionally restricted
Authors: Deimel Lachlan P. , Moynié Lucile , Sun Guoxuan , Lewis Viliyana , Turner Abigail , Buchanan Charles J. , Burnap Sean A. , Kutuzov Mikhail , Kobras Carolin M. , Demyanenko Yana , Mohammed Shabaz , Stracy Mathew , Struwe Weston B. , Baldwin Andrew J. , Naismith James , Davis Benjamin G. , Sattentau Quentin J.
Published: August 2024

Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates and their off-target side-conjugates have the potential to elicit antibodies, with implications for allergy and drug sequestration. Although β-lactam antibiotics are a drug class long associated with these immunological phenomena, the molecular underpinnings of off-target drug-protein conjugation and consequent drug-specific immune responses remain incomplete. Here, using the classical β-lactam penicillin G (PenG), we probe the B and T cell determinants of drug-specific IgG responses to such conjugates in mice. Deep B cell clonotyping reveals a dominant murine clonal antibody class encompassing phylogenetically-related IGHV1, IGHV5 and IGHV10 subgroup gene segments. Protein NMR and x-ray structural analyses reveal that these drive structurally convergent binding modes in adduct-specific antibody clones. Their common primary recognition mechanisms of the penicillin side-chain moiety (phenylacetamide in PenG)—regardless of CDRH3 length—limits cross-reactivity against other β-lactam antibiotics. This immunogenetics-guided discovery of the limited binding solutions available to antibodies against side products of an archetypal covalent inhibitor now suggests future potential strategies for the ‘germline-guided reverse engineering’ of such drugs away from unwanted immune responses.
Antibody gene features associated with binding and functional activity in malaria vaccine-derived human mAbs
Authors: Coelho Camila H. , Marquez Susanna , Nguemwo Tentokam Bergeline C. , Berhe Anne D. , Miura Kazutoyo , Rao Vishal N. , Long Carole A. , Doumbo Ogobara K. , Sagara Issaka , Healy Sara , Kleinstein Steven H. , Duffy Patrick E.
Published: August 2024

The impact of adjuvants on malaria vaccine-induced antibody repertoire is poorly understood. Here, we characterize the impact of two adjuvants, Alhydrogel® and AS01, on antibody clonotype diversity, binding and function, post malaria vaccination. We expressed 132 recombinant anti-Pfs230D1 human monoclonal antibodies (mAbs) from participants immunized with malaria transmission-blocking vaccine Pfs230D1, formulated with either Alhydrogel® or AS01. Anti-Pfs230D1 mAbs generated by Alhydrogel® formulation showed higher binding frequency to Pfs230D1 compared to AS01 formulation, although the frequency of functional mAbs was similar between adjuvant groups. Overall, the AS01 formulation induced anti-Pfs230D1 functional antibodies from a broader array of germline sequences versus the Alhydrogel® formulation. All mAbs using IGHV1-69 gene from the Alhydrogel® cohort bound to recombinant Pfs230D1, but did not block parasite transmission to mosquitoes, similar to the IGHV1-69 mAbs isolated from the AS01 cohort. These findings may help inform vaccine design and adjuvant selection for immunization with Plasmodium antigens.
Dynamic clade transitions and the influence of vaccination on the spatiotemporal circulation of SARS-CoV-2 variants
Authors: Banho Cecília Artico , de Carvalho Marques Beatriz , Sacchetto Lívia , Lima Ana Karoline Sepedro , Parra Maisa Carla Pereira , Lima Alex Ranieri Jeronimo , Ribeiro Gabriela , Martins Antonio Jorge , Barros Claudia Renata dos Santos , Elias Maria Carolina , Sampaio Sandra Coccuzzo , Slavov Svetoslav Nanev , Rodrigues Evandra Strazza , Santos Elaine Vieira , Covas Dimas Tadeu , Kashima Simone , Brassaloti Ricardo Augusto , Petry Bruna , Clemente Luan Gaspar , Coutinho Luiz Lehmann , Assato Patricia Akemi , da Silva da Costa Felipe Allan , Grotto Rejane Maria Tommasini , Poleti Mirele Daiana , Lesbon Jessika Cristina Chagas , Mattos Elisangela Chicaroni , Fukumasu Heidge , Giovanetti Marta , Alcantara Luiz Carlos Junior , Souza-Neto Jayme A. , Rahal Paula , Araújo João Pessoa , Spilki Fernando Rosado , Althouse Benjamin M. , Vasilakis Nikos , Nogueira Maurício Lacerda
Published: August 2024

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.