bluuebunny/crossref_metadata_2025 huggingface dataset:
124 Immediate Salvage with Inflatable Penile Prosthesis in an Infected Field: A Contemporary Multi-institutional Cohort
Authors: Jiang D , Barnard J , Choi E , Furr J , Lentz A , van Renterghem K , Selph P , Yafi FA
Published: April 2022

Introduction

Contemporary management of inflatable penile prosthesis (IPP) infections involves removal and replacement to minimize corporal fibrosis and penile shortening. Many urologists prefer a malleable prosthesis (MP) followed by staged conversion to IPP, a technique thought to improve outcomes by allowing treatment of the infection while maintaining intracorporeal volume. A staged procedure involves additional surgery with associated risks. Previous studies suggest an 18% infection risk of placing a second device in a non-infected, revision setting, and that infection risk increases with each subsequent procedure.

Objective

Our study aims to delineate whether immediate IPP salvage in an infected field yields similar complication rates to the staged approach.

Methods

Retrospective review at 5 different institutions from February 2010 to October 2020 identified patients with IPP infection who underwent IPP salvage. Patient demographic, laboratory, operative, and microbiology data were collected. Emphasis was placed on the salvage operative technique, duration of antibiotics, and post-salvage complications.

Results

Overall, 19 patients underwent immediate salvage with IPP in the setting of a suspected infection. Average age at initial implantation was 59.9 years. Median time from initial implant to presentation with infectious symptoms was 2.4 months, and revision was performed a median of 1.5 days after presentation and initiation of antibiotics. Intraoperative complications were rare (5.3%), and post-salvage complications were 21.1%, including 1 cylinder herniation and 3 post salvage infections (15.8%). Only 1 post-salvage infection showed concordance with initial cultures while 1 was discordant and the third showed no growth (Table 1). Fisher's exact test showed diabetes, purulence in the operative field, use of drain, or washout type were not associated with infection post-salvage.

Conclusions

Immediate IPP salvage in the setting of an acutely infected field shows a complication profile not exceeding published data in the staged revision setting. Although staged MP-IPP salvage has been favored by many surgeons, the complication profile may be equivalent to immediate IPP salvage, and the risks of a subsequent operation should be considered.

Disclosure

No
140 COVID-19 is Associated with New Onset Erectile Dysfunction: Insights From a Multinational Registry
Authors: Nackeeran S , Chu K , Masterson T , Ramasamy R
Published: April 2022

Introduction

As the COVID-19 pandemic has been ongoing since 2019, we are just beginning to see some of the short and long-term effects of infection. Vascular integrity is necessary for erectile function, and endothelial damage associated with COVID-19 is likely to affect the penile vasculature. Recent studies have showed evidence of COVID-19 virus within penile tissue through electron microscopy. We hypothesized that the COVID-19 infection may be a contributing factor to subsequent development of erectile dysfunction (ED).

Objective

To determine if men with recent COVID-19 infection was associated with subsequent increased risk for development of erectile dysfunction.

Methods

We assessed the risk of ED in men with COVID-19 in the United States (US) using the TriNetX Research Network, a federated EMR network of over 42 healthcare organizations and 66 million patients from the US, from 2009-2020. We identified adult men (≥18 years) with a recorded COVID-19 infection (ICD-10-CM B34.2, U07.1, U07.2, J12.81, J12.82, B97.29) since January 1, 2020 and compared them to an equivalent number of adult men who had COVID-19. Men with prior history or diagnosis of ED were excluded. We accounted for confounding variables through propensity score matching for age, race, body mass index (BMI), and history of the following comorbid medical conditions: diabetes mellitus (ICD-10-CM E11), hypertension (ICD-10-CM I10), or hyperlipidemia (ICD-10-CM E78). We assessed the association between COVID-19 and ED (ICD-10-CM N52) as a primary outcome through regression analysis with statistical significance assessed at p<.05.

Results

Prior to propensity score matching, men with COVID-19 had an average age of 47.1 + 21.4 years, 13% had diabetes mellitus, and 27% had hypertension, while in men without COVID-19, average age was 42.4 + 24.3 years, 7% had diabetes, and 22% had hypertension. After propensity score matching, we compared 230, 517 men with COVID-19 to 232,645 men without COVID-19 and found that COVID-19 diagnosis was significantly associated with ED (OR 1.120, 95% CI 1.004-1.248, p=0.0416). Strengths include large sample size and adjustment for confounding variables. Limitations include lack of data regarding ED (mild vs moderate vs severe) or COVID-19 infection severity.

Conclusions

Our study showed that there is an increased risk of developing ED post-COVID infection, suggesting possible long-term effects due underlying endothelial dysfunction. The exact mechanism of how COVID-19 virus leads to erectile dysfunction remains to be elucidated.

Disclosure

No
143 User Characteristics of Unique Men's Health Website
Authors: Alom M , Collins S , Nelson K , Carlson S , Tentis E , Helo S , Ziegelmann M , Trost L , Kohler T
Published: April 2022

Introduction

Covid-19 has helped drive all forms of medicine away from traditional brick and mortar medical interactions. Given the availability of online services to obtain treatments for ED, we developed a website to facilitate patient education, triage and men's health appointment scheduling.

Objective

We sought to assess characteristics of men who utilized a novel website to treat their ED.

Methods

We report on 50 patients who ultimately booked and attended appointments (video or in person) for erectile dysfunction. Patients found our website through our institution's main informational ED pages or through youtube links from our men's health video playlist library. Patients create an institutional account and are then asked a series of MD created questions designed to streamline patient triage and complete the majority of chart documentation ahead of the appointment. Patients are then sent videos relevant to their condition and future appointment options.

Results

2300 users investigated the ED portion of the website with 1.8% of patients ultimately following through with an appointment. 13% of patients who explored the ED portion of the site created a user account that allows a questionnaire to be taken. 90% of men who began the ED questionnaire completed with a mean time of 11 minutes. 52% of men offered an appointment based on their responses completed the patient scheduling form. 71% of traffic was on mobile devices with 29% on desktop/tablet. Site use by time of day is shown in figure 1. Mean age of patients was 53. 92% of patients had ED that occurred > 6 months. Mean SHIM score was 8.2 (IQR 4-12). 80% of participants had both desire and opportunity for sexual activity, 20% did not meet both criteria and thus SHIM scores were less valid for these men. Of the users 28% had never tried pde5s, 32% had partial success with pde5s, 24% could not tolerate or afford pde5s and 42% had unsatisfactory results with pde5s. PDE5 naïve patients were seen by an internal medicine MD specializing in men's health, 10 were seen by surgeons as they requested IPPs and the rest were seen by a combination of men's health APPS and urology attendings for second line treatments and penile doppler. Interestingly, 66% of men were interested in undergoing penile doppler to better understand the etiology of their ED. Hypertension (40%) and diabetes (22%) were the most common medical comorbidities. 36% of the cohort had a strong family history of cardiac disease.

Conclusions

Men with ED can be effectively triaged through a website application. Most men with pde5 refractory ED wish to pursue penile doppler. The majority of patients seen had watched educational video material ahead of time, facilitating a more sophisticated and streamlined patient interaction.

Disclosure

No
Generic View of Gendered Slurs and the Subset Argument
Authors: VALTONEN PASI
Published: April 2022

The neutral counterpart assumption is widely accepted in the study of slurs. It provides a simple and effective explanation for the meaning of slurs. Slurring terms are coextensional with their neutral counterparts. However, Lauren Ashwell (2016) has questioned this assumption. She argues that gendered slurs refer to a subset of their neutral counterparts. Hence, slurs are not coextensional with their counterparts. She goes on to present a view that is not based on the counterpart assumption. Still, her view is a unifying view of slurs as it also applies to ethnic and racial slurs. In this paper, I defend the counterpart assumption with a generic view of slurs. While being a unifying view, it accommodates the subset argument with its eponymous feature that the meaning of slurs involves a generic component.
Heat transfer increase by convection in liquid-infused surfaces for laminar and turbulent flows
Authors: Sundin Johan , Ciri Umberto , Leonardi Stefano , Hultmark Marcus , Bagheri Shervin
Published: April 2022

Liquid-infused surfaces can reduce friction drag in both laminar and turbulent flows. However, the heat transfer properties of such multi-phase surfaces have still not been investigated to a large extent. We use numerical simulations to study conjugate heat transfer of liquid-filled grooves. It is shown that heat transfer can increase for both laminar and turbulent liquid flows due to recirculation in the surface texture. Laminar flow simulations show that for the increase to be substantial, the thermal conductivity of the solid must be similar to the thermal conductivity of the fluids, and the recirculation in the grooves must be sufficiently strong (Péclet number larger than 1). The ratio of the surface cavity to the system height is an upper limit of the direct contribution from the recirculation. While this ratio can be significant for laminar flows in microchannels, it is limited for turbulent flows, where the system scale (e.g. channel height) usually is much larger than the texture height. However, heat transfer enhancement of the order of$10\,\%$is observed (with a net drag reduction) in a turbulent channel flow at a friction Reynolds number${{Re}}_\tau \approx 180$. It is shown that the turbulent convection in the bulk can be enhanced indirectly from the recirculation in the grooves.
Resistance Movements:The Tempest,Resurgence, and Indigenous Performance on Turtle Island
Authors: Clark Glenn
Published: April 2022

Inspired by the reinvigorating theory of Wai-Chee Dimok and Rita Felski, I argue thatThe Tempestresonates with current theory and performance of Indigenous resurgence in North America. With reference to the work of Indigenous performance theorist Floyd Favel, political thinkers Leanne Simpson and Glen Sean Coulthard, and to plays and performances by Yvette Nolan, Monique Mojica, Kevin Loring, and Spiderwoman Theatre, I describe resurgence as culturally recuperative practices of movement on the land that make it feel more comfortable, establish an Indigenous sense of sovereignty, and diminish shame. I emphasize the ways in which the physical and imaginative mobilities of Shakespeare’s Boatswain and Gonzalo anticipate the comforting—and insurgent—land-oriented movements of Caliban. I argue that Caliban’s sense of natural sovereignty is understood better in terms of free and secure mobility than in terms of rule or possession.
COVID-19 and Support for Executive Aggrandizement
Authors: Gidengil Elisabeth , Stolle Dietlind , Bergeron-Boutin Olivier
Published: April 2022

The COVID-19 pandemic offers a critical opportunity to assess the extent to which Canadians can be considered reliable defenders of democratic norms and institutions. In the face of such a serious threat to their physical and economic well-being, how willing are Canadians to condone the loosening of restraints on the power of the executive? This article addresses this question by drawing on the terror management and threat literatures. Combining a cross-sectional regression analysis with a vignette experiment and a candidate-choice conjoint experiment, it tests two hypotheses: that people experiencing debilitating anxiety about COVID-19 are more likely to favour weakening checks on the executive and that people will be willing to trade off legislative checks for the sake of their preferred lockdown policy. Both hypotheses are confirmed. In the face of an unprecedented health crisis, COVID-related anxiety and a desire for protective policies may trump respect for democratic norms.
How the International Slave Trades Underdeveloped Africa
Authors: Whatley Warren
Published: April 2022

I use newly-developed data on Africa to estimate the effects of the international slave trades (circa 1500–1850) on the institutional structures of African economies and societies (circa 1900). I find that: (1) societies in slave catchment zones adopted slavery to defend against further enslavement; (2) slave trades spread slavery and polygyny together; (3) politically centralized aristocratic slave regimes emerge in West Africa and family-based accumulations of slave wealth in East Africa. I discuss implications for literatures on long-term legacies in African political and economic development.
In-House Attending Trauma Surgeon Does Not Reduce Mortality in Patients Presented to a Level 1 Trauma Center
Authors: Hakkenbrak Nadia AG , Mikdad Sarah , van Embden Daphne , Giannakopoulos Georgios F. , Bloemers Frank W. , Schepers Tim , Halm Jens A.
Published: April 2022

Background:

Trauma is the leading cause of death in the Western world. Trauma systems have been paramount in opposing this problem. Commonly, Level 1 Trauma Centers are staffed by in-house (IH) attending trauma surgeons available 24/7, whereas other institutions function on an on-call (OC) basis with defined response times. There is on-going debate about the value of an IH attending trauma surgeon compared to OC trauma surgeons regarding clinical outcome.

Methods:

This study was performed at a tertiary care facility complying with all requirements to be a designated Level 1 Trauma Center as defined by the American College of Surgeons Committee on Trauma (ACSCOT). Inclusion occurred from January 1, 2012 through December 31, 2013. Patients were assigned an identifier for IH trauma surgeon attendance versus OC attendance. The primary outcome variable studied was overall mortality in relation to IH or OC attending trauma surgeons. Additionally, time to operating theater, hospital length-of-stay (HLOS), and intensive care unit (ICU) admittance were investigated.

Results:

A total of 1,287 unique trauma cases in 1,285 patients were presented to the trauma team. Of all cases, 712 (55.3%) occurred between 1700h and 0800h. These 712 cases were treated by an IH attending in 66.3% (n = 472) and an OC attending in 33.7% (n = 240). In the group of patients treated by an IH attending trauma surgeon, the overall mortality rate was 5.5% (n = 26); in the group treated by an OC attending, the overall mortality rate was 4.6% (n = 11; P = .599). Cause of death was traumatic brain injury (TBI) in 57.6%. No significant difference was found in the time between initial presentation at the trauma room and arrival in the operating theater.

Conclusion:

In terms of trauma-related mortality during non-office hours, no benefit was demonstrated through IH trauma surgeons compared to OC trauma surgeons.
Air quality in welfare accounting
Authors: Balleer Almut , Endrikat Morten
Published: April 2022

We measure how taking into account air quality affects relative welfare levels and welfare convergence across countries. We use the equivalent variation framework by Jones and Klenow [(2016)American Economic Review106(9), 2426–2457.] which takes into account consumption, life expectancy, inequality, and leisure and extend it with respect to environmental quality in form of air pollution. Our results show that omitting environmental aspects from welfare accounting might lead to both a substantial over- or understatement of actual relative welfare and welfare developments for different (groups of) countries.
Shear‐Wave Velocity Reveals Heterogeneous Geometry of the Main Himalayan Thrust System and Deep Structure Beneath the Nepal Himalayas
Authors: Zhao Lingfeng , Li Lun , Liao Jie , Dong Shixian , Liang Yanling , Gao Rui
Published: April 2022

The Himalayas is currently rising due to the collision of the Indian and Asian plates and hosts frequent earthquakes, some of which are devastating, such as the 2015 Mw7.8 Gorkha earthquake. Despite the importance of deep dynamic processes to understand the uplift of the Himalayas and the occurrence of large earthquakes, it remains limitedly constrained due to the lack of a detailed three‐dimensional subsurface image under this region. Here, we construct new models of shear‐wave velocity and radial anisotropy down to the 150 km depth from Rayleigh‐ and Love‐wave tomography in the Nepal Himalayas. We find that the 2015 Gorkha earthquake and its main aftershock occurred in a velocity contrast that is presumably interpreted as Main Himalayan Thrust (MHT). A duplex structure, imaged as relatively high velocities, is inferred to exist above MHT under the Lesser Himalayas. This duplex shows heterogeneous features along the strike of the Himalayas that may control the rupture behavior during the occurrence of a large earthquake. Additionally, a low‐velocity anomaly is observed at depths from Moho to 100 km under the Lhasa Terrane and north of the Himalayan Terrane between 85° and 88°E. We interpret this low‐velocity anomaly to be likely caused by mantle upwelling resulting from either possible Indian slab tearing, or northward subduction of the Indian plate. If this is the case, the north‐south trending rifts that situate within the dispersal of the low‐velocity anomaly are probably associated with the mantle upwelling. This study provides a new independent constraint on the geometry of the MHT system and deep dynamic processes occurring in the Nepal Himalaya.
Wave‐Climate Asymmetry Influence on Delta Evolution and River Dynamics
Authors: Hu Ningjie , Murray A. Brad , Ratliff Katherine M. , Little Zachary , Hutton Eric W. H.
Published: April 2022

On wave‐influenced river deltas, wave‐driven sediment redistribution affects river progradation, and therefore avulsions, while avulsions change where sediment is delivered to the coastline, affecting coastline shape. Coastline shape, in turn, affects sediment redistribution rates and patterns. Here we use a numerical model to investigate how the asymmetry of wave climates affects delta avulsion behaviors, which are coupled with delta shape evolution. Increasing wave‐climate asymmetry tends to reduce (increase) the curvature of updrift (downdrift) delta flanks, by increasing (decreasing) local shoreline diffusivity. In our model experiments, reduced shoreline curvature restricts the possible updrift post‐avulsion river mouth locations, while increased curvature expands the possible downdrift locations, favoring “downdrift avulsions.” However, under some wave climates, local diffusivity on the downdrift flank can become negative, leading to convexity and shoreline accretion, inhibiting downdrift avulsions. Increasing wave heights and decreasing superelevation threshold for avulsions both tend to reduce delta morphologic asymmetry, and therefore avulsion tendency.
Lower‐Hybrid Wave Structures and Interactions With Electrons Observed in Magnetotail Reconnection Diffusion Regions
Authors: Wang Shan , Chen Li‐Jen , Bessho Naoki , Ng Jonathan , Hesse Michael , Graham Daniel B. , Le Contel Olivia , Gershman Daniel , Giles Barbara
Published: April 2022

We investigate waves close to the lower‐hybrid frequency in 12 magnetotail reconnection electron diffusion region (EDR) events with guide field levels of near‐zero to 30%. In about half of the events, the wave vector has a small component along the current sheet normal, consistent with known lower‐hybrid drift wave properties, but the perpendicular magnetic field fluctuations can be comparable or greater than the parallel component, a feature unique to the waves inside and adjacent to EDRs. Another new wave property is that the wave vector has a significant component along the current sheet normal in some events and completely along the normal for one event. In 1/4 of the events, the term has a significant contribution to the wave electric field, possibly a feature of lower‐hybrid waves more likely to exist in the diffusion region than further away from the X‐line. Electron temperature variations are correlated with the wave potential, due to wave electric field acceleration and crossings at the corrugated separatrix region with different amounts of mixing between reconnection inflowing and outflowing populations. The latter also leads to the anti‐correlation between parallel and perpendicular temperature components. Using four‐spacecraft measurements, the magnetic field line twisting is demonstrated by the correlated fluctuations in and . The lower‐hybrid wave in the EDR of weak guide field reconnection may be generated near separatrices and penetrate to the mid‐plane or locally generated, and the latter possibility is beyond the prediction of previous reconnection simulations.
Reduction of Equatorial Obduction by Atmospheric Intraseasonal Oscillations in the Western and Central Pacific Ocean
Authors: Liu Lingling , Li Yuanlong , Wang Fan
Published: April 2022

Obduction is the large‐scale, irreversible upward water transport from the permanent pycnocline to the surface mixed layer. Using Hybrid Coordinate Ocean Model (HYCOM), this study explores the impact of atmospheric intraseasonal oscillations (ISOs) on the Pacific equatorial obduction that plays a fundamental role in regulating the tropical Pacific climate. Parallel HYCOM experiments forced by atmospheric fields with and without ISO variability are compared to assess the effect of ISOs on the ocean. The results suggest that the ISOs can reduce the annual obduction rate of the western and central equatorial Pacific Ocean (WCEPO; 150°E−160°W, 5°S–5°N) by ∼12%, and their impact on the eastern Pacific is rather limited. The ISOs cause prominent intraseasonal variability of mixed layer depth (MLD) in the WCEPO primarily through surface wind forcing, which in turn affects the two key processes controlling the annual obduction rate. First, the intraseasonal MLD deepening events narrow down the total time windows for obduction by ∼30% and thereby give rise to the decrease in obduction rate; second, it leads to high‐frequency entrainment events and enhances the entrainment rate by ∼18%. The increased entrainment rate is overwhelmed by the reduced time windows for effective entrainment, and the net effect of ISOs is to reduce the obduction rate and modify its seasonal cycle. This work highlights the importance of atmospheric ISOs in the equatorial ocean dynamics, with implications for tropical surface temperature and climate variabilities and biogeochemical cycle.
Detection of Tracer Plumes Using Full‐Waveform Inversion of Time‐Lapse Ground Penetrating Radar Data: A Numerical Study in a High‐Resolution Aquifer Model
Authors: Haruzi P. , Schmäck J. , Zhou Z. , van der Kruk J. , Vereecken H. , Vanderborght J. , Klotzsche A.
Published: April 2022

Imaging subsurface small‐scale features and monitoring transport of tracer plumes at a fine resolution is of interest to characterize transport processes in aquifers. Full‐waveform inversion (FWI) of crosshole ground penetrating radar (GPR) measurements enables aquifer characterization at decimeter‐scale resolution. The method produces images of both relative dielectric permittivity (εr) and bulk electrical conductivity (σb) that can be related to hydraulic aquifer properties and tracer distributions. To test the potential of time‐lapse GPR FWI for imaging tracer plumes, we conducted a numerical tracer experiment by injecting saline water, desalinated water, and ethanol in a heterogeneous aquifer. The saline and desalinated tracers only changed σb, whereas ethanol changed both εr and σb. Tracer concentrations were retrieved from the inverted εr and σb models using information about petrophysical parameters. GPR FWI εr and σb tracer images could recover preferential paths of ∼0.2 m width, while the derived σb structures are smoother. FWI of 50 time‐lapse data sets demonstrated the potential of the FWI to derive spatially resolved breakthrough curves of the saline and ethanol tracer in the image plane between the boreholes. Thus, high‐resolution imaging with GPR FWI of tracers that produce a high permittivity contrast against the background has a great potential for characterization of heterogeneous transport in aquifers.
Statistical Attribution of the Influence of Urban and Tree Cover Change on Streamflow: A Comparison of Large Sample Statistical Approaches
Authors: Anderson Bailey J. , Slater Louise J. , Dadson Simon J. , Blum Annalise G. , Prosdocimi Ilaria
Published: April 2022

The strengths and weaknesses of different statistical methodologies for attributing changes in streamflow to land cover are still poorly understood. We examine the relationships between high (Q99), mean (Qmean), and low (Q01) streamflow and urbanization or tree cover change in 729 catchments in the United States between 1992 and 2018. We apply two statistical modeling approaches and compare their performance. Panel regression models estimate the average effect of land cover changes on streamflow across all sites, and show that on average, a 1%‐point increase in catchment urban area results in a small (0.6%–0.7%), but highly significant increase in mean and high flows. Meanwhile, a 1%‐point increase in tree cover does not correspond to strongly significant changes in flow. We also fit a generalized linear model to each individual site, which results in highly varied model coefficients. The medians of the single‐site coefficients show no significant relationships between either urbanization or tree cover change and any streamflow quantile (although at individual sites, the coefficients may be statistically significant and positive or negative). On the other hand, the GLM coefficients may provide greater nuance in catchments with specific attributes. This variation is not well represented through the panel model estimates of average effect, unless moderators are carefully considered. We highlight the value of statistical approaches for large‐sample attribution of hydrological change, while cautioning that considerable variability exists.
Role of Poroelasticity During the Early Postseismic Deformation of the 2010 Maule Megathrust Earthquake
Authors: Peña Carlos , Metzger Sabrina , Heidbach Oliver , Bedford Jonathan , Bookhagen Bodo , Moreno Marcos , Oncken Onno , Cotton Fabrice
Published: April 2022

Megathrust earthquakes impose changes of differential stress and pore pressure in the lithosphere‐asthenosphere system that are transiently relaxed during the postseismic period primarily due to afterslip, viscoelastic and poroelastic processes. Especially during the early postseismic phase, however, the relative contribution of these processes to the observed surface deformation is unclear. To investigate this, we use geodetic data collected in the first 48 days following the 2010 Maule earthquake and a poro‐viscoelastic forward model combined with an afterslip inversion. This model approach fits the geodetic data 14% better than a pure elastic model. Particularly near the region of maximum coseismic slip, the predicted surface poroelastic uplift pattern explains well the observations. If poroelasticity is neglected, the spatial afterslip distribution is locally altered by up to ±40%. Moreover, we find that shallow crustal aftershocks mostly occur in regions of increased postseismic pore‐pressure changes, indicating that both processes might be mechanically coupled.
Role of the gut–brain axis in energy and glucose metabolism
Authors: Wachsmuth Hallie R. , Weninger Savanna N. , Duca Frank A.
Published: April 2022

The gastrointestinal tract plays a role in the development and treatment of metabolic diseases. During a meal, the gut provides crucial information to the brain regarding incoming nutrients to allow proper maintenance of energy and glucose homeostasis. This gut–brain communication is regulated by various peptides or hormones that are secreted from the gut in response to nutrients; these signaling molecules can enter the circulation and act directly on the brain, or they can act indirectly via paracrine action on local vagal and spinal afferent neurons that innervate the gut. In addition, the enteric nervous system can act as a relay from the gut to the brain. The current review will outline the different gut–brain signaling mechanisms that contribute to metabolic homeostasis, highlighting the recent advances in understanding these complex hormonal and neural pathways. Furthermore, the impact of the gut microbiota on various components of the gut–brain axis that regulates energy and glucose homeostasis will be discussed. A better understanding of the gut–brain axis and its complex relationship with the gut microbiome is crucial for the development of successful pharmacological therapies to combat obesity and diabetes.
Tea consumption and risk of incident dementia: A prospective cohort study of 377 592 UK Biobank participants
Authors: Hu He-Ying , Wu Bang-Sheng , Ou Ya-Nan , Ma Ya-Hui , Huang Yu-Yuan , Cheng Wei , Tan Lan , Yu Jin-Tai
Published: April 2022

As a widely consumed beverage, tea boasts diverse health benefits. Herein, we aimed to investigate the association between tea consumption and dementia risk. We conducted a prospective cohort study with 377 592 UK Biobank participants during a 9-year follow-up. Cox regression models adjusted for age, sex, ethnicity, Townsend deprivation index, education, body mass index, lifestyle factors, dietary factors and apolipoprotein E4 status were used to examine the association of tea consumption with dementia risk. Subgroup analyses stratified by age, sex and forms of dementia (Alzheimer’s disease [AD] and vascular dementia [VD]) were performed. Moreover, the restricted cubic splines were used to calculate the nonlinear relationship between daily dosage of tea and dementia risk. After adjustment for all covariates, tea drinkers were 16% (95% confidence interval: 8–23) less likely to develop dementia compared with non-drinkers. Moderate consumption (1–6 cups/day) of tea exerted significant protective effects. Subgroup analyses showed that mid-aged participants or males benefited more from tea consumption. Moreover, moderate drinkers had a 16–19% lower hazard of AD and a 25–29% lower hazard of VD. Furthermore, a U-shaped association between tea consumption and dementia risk was shown (Pnon-linearity = 7E−04), and the consumption of around three cups per day showed the strongest protective effect. Within 3 cups/day, drinking one extra cup of tea per day brought a 6% reduction of incidence. In conclusion, moderate consumption of tea was significantly associated with a reduced risk of dementia, suggesting that tea consumption could be a modifiable lifestyle factor for dementia.
Targeting NAD+: is it a common strategy to delay heart aging?
Authors: Yuan Yang , Liang Bing , Liu Xin-Lin , Liu Wen-Jing , Huang Bing-Huan , Yang Shan-Bo , Gao Yuan-Zhen , Meng Jing-Sen , Li Meng-Jiao , Ye Ting , Wang Chuan-Zhi , Hu Xiao-Kun , Xing Dong-Ming
Published: April 2022

Heart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.
TLR2/caspase-5/Panx1 pathway mediates necrosis-induced NLRP3 inflammasome activation in macrophages during acute kidney injury
Authors: Liu Chongbin , Shen Yanting , Huang Liuwei , Wang Jun
Published: April 2022

Acute kidney injury (AKI) is characterized by necroinflammation formed by necrotic tubular epithelial cells (TECs) and interstitial inflammation. In necroinflammation, macrophages are key inflammatory cells and can be activated and polarized into proinflammatory macrophages. Membranous Toll-like receptors (TLRs) can cooperate with intracellular NOD-like receptor protein 3 (NLRP3) to recognize danger signals from necrotic TECs and activate proinflammatory macrophages by assembling NLRP3 inflammasome. However, the cooperation between TLRs and NLRP3 is still unclear. Using conditioned medium from necrotic TECs, we confirmed that necrotic TECs could release danger signals to activate NLRP3 inflammasome in macrophages. We further identified that necrotic TECs-induced NLRP3 inflammasome activation was dependent on ATP secretion via Pannexin-1 (Panx1) channel in macrophages. Next, we verified that TLR2 was required for the activation of Panx1 and NLRP3 in macrophages. Mechanistically, we indicated that caspase-5 mediated TLR2-induced Panx1 activation. In addition, we showed that necrotic TECs-induced activation of TLR2/caspase-5/Panx1 axis could be decreased in macrophages when TECs was protected by N-acetylcysteine (NAC). Overall, we demonstrate that danger signals from necrotic TECs could activate NLRP3 inflammasome in macrophages via TLR2/caspase-5/Panx1 axis during AKI.
Excitations in a superconducting Coulombic energy gap
Authors: Estrada Saldaña Juan Carlos , Vekris Alexandros , Pavešić Luka , Krogstrup Peter , Žitko Rok , Grove-Rasmussen Kasper , Nygård Jesper
Published: April 2022

Cooper pairing and Coulomb repulsion are antagonists, producing distinct energy gaps in superconductors and Mott insulators. When a superconductor exchanges unpaired electrons with a quantum dot, its gap is populated by a pair of electron–hole symmetric Yu-Shiba-Rusinov excitations between doublet and singlet many-body states. The fate of these excitations in the presence of a strong Coulomb repulsion in the superconductor is unknown, but of importance in applications such as topological superconducting qubits and multi-channel impurity models. Here we couple a quantum dot to a superconducting island with a tunable Coulomb repulsion. We show that a strong Coulomb repulsion changes the singlet many-body state into a two-body state. It also breaks the electron–hole energy symmetry of the excitations, which thereby lose their Yu-Shiba-Rusinov character.
T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling
Authors: Chin Shu Shien , Guillen Erik , Chorro Laurent , Achar Sooraj , Ng Karina , Oberle Susanne , Alfei Francesca , Zehn Dietmar , Altan-Bonnet Grégoire , Delahaye Fabien , Lauvau Grégoire
Published: April 2022

Cognate antigen signal controls CD8+ T cell priming, expansion size and effector versus memory cell fates, but it is not known if and how it modulates the functional features of memory CD8+ T cells. Here we show that the strength of T cell receptor (TCR) signaling controls the requirement for interleukin-2 (IL-2) signals to form a pool of memory CD8+ T cells that competitively re-expand upon secondary antigen encounter. Combining strong TCR and intact IL-2 signaling during priming synergistically induces genome-wide chromatin accessibility in regions targeting a wide breadth of biological processes, consistent with greater T cell functional fitness. Chromatin accessibility in promoters of genes encoding for stem cell, cell cycle and calcium-related proteins correlates with faster intracellular calcium accumulation, initiation of cell cycle and more robust expansion. High-dimensional flow-cytometry analysis of these T cells also highlights higher diversity of T cell subsets and phenotypes with T cells primed with stronger TCR and IL-2 stimulation than those primed with weaker strengths of TCR and/or IL-2 signals. These results formally show that epitope selection in vaccine design impacts memory CD8+ T cell epigenetic programming and function.
Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes
Authors: Jahed Zeinab , Yang Yang , Tsai Ching-Ting , Foster Ethan P. , McGuire Allister F. , Yang Huaxiao , Liu Aofei , Forro Csaba , Yan Zen , Jiang Xin , Zhao Ming-Tao , Zhang Wei , Li Xiao , Li Thomas , Pawlosky Annalisa , Wu Joseph C. , Cui Bianxiao
Published: April 2022

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.
A computational theory of the subjective experience of flow
Authors: Melnikoff David E. , Carlson Ryan W. , Stillman Paul E.
Published: April 2022

Flow is a subjective state characterized by immersion and engagement in one’s current activity. The benefits of flow for productivity and health are well-documented, but a rigorous description of the flow-generating process remains elusive. Here we develop and empirically test a theory of flow’s computational substrates: the informational theory of flow. Our theory draws on the concept of mutual information, a fundamental quantity in information theory that quantifies the strength of association between two variables. We propose that the mutual information between desired end states and means of attaining them — $$I({M;E})$$
I

(

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;
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— gives rise to flow. We support our theory across five experiments (four preregistered) by showing, across multiple activities, that increasing $$I({M;E})$$
I

(

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increases flow and has important downstream benefits, including enhanced attention and enjoyment. We rule out alternative constructs including alternative metrics of associative strength, psychological constructs previously shown to predict flow, and various forms of instrumental value.
Mesoscopic landscape of cortical functions revealed by through-skull wide-field optical imaging in marmoset monkeys
Authors: Song Xindong , Guo Yueqi , Li Hongbo , Chen Chenggang , Lee Jong Hoon , Zhang Yang , Schmidt Zachary , Wang Xiaoqin
Published: April 2022

The primate cerebral cortex is organized into specialized areas representing different modalities and functions along a continuous surface. The functional maps across the cortex, however, are often investigated a single modality at a time (e.g., audition or vision). To advance our understanding of the complex landscape of primate cortical functions, here we develop a polarization-gated wide-field optical imaging method for measuring cortical functions through the un-thinned intact skull in awake marmoset monkeys (Callithrix jacchus), a primate species featuring a smooth cortex. Using this method, adjacent auditory, visual, and somatosensory cortices are noninvasively parcellated in individual subjects with detailed tonotopy, retinotopy, and somatotopy. An additional pure-tone-responsive tonotopic gradient is discovered in auditory cortex and a face-patch sensitive to motion in the lower-center visual field is localized near an auditory region representing frequencies of conspecific vocalizations. This through-skull landscape-mapping approach provides new opportunities for understanding how the primate cortex is organized and coordinated to enable real-world behaviors.
Chalcogenide optomemristors for multi-factor neuromorphic computation
Authors: Sarwat Syed Ghazi , Moraitis Timoleon , Wright C. David , Bhaskaran Harish
Published: April 2022

Neuromorphic hardware that emulates biological computations is a key driver of progress in AI. For example, memristive technologies, including chalcogenide-based in-memory computing concepts, have been employed to dramatically accelerate and increase the efficiency of basic neural operations. However, powerful mechanisms such as reinforcement learning and dendritic computation require more advanced device operations involving multiple interacting signals. Here we show that nano-scaled films of chalcogenide semiconductors can perform such multi-factor in-memory computation where their tunable electronic and optical properties are jointly exploited. We demonstrate that ultrathin photoactive cavities of Ge-doped Selenide can emulate synapses with three-factor neo-Hebbian plasticity and dendrites with shunting inhibition. We apply these properties to solve a maze game through on-device reinforcement learning, as well as to provide a single-neuron solution to linearly inseparable XOR implementation.
Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association
Authors: Zhu Lin , Gao Ting , Huang Yi , Jin Jing , Wang Di , Zhang Leike , Jin Yanwen , Li Ping , Hu Yong , Wu Yan , Liu Hainan , Dong Qincai , Wang Guangfei , Zheng Tong , Song Caiwei , Bai Yu , Zhang Xun , Liu Yaoning , Yang Weihong , Xu Ke , Zou Gang , Zhao Lei , Cao Ruiyuan , Zhong Wu , Xia Xianzhu , Xiao Gengfu , Liu Xuan , Cao Cheng
Published: April 2022

Ebola virus (EBOV), one of the deadliest viruses, is the cause of fatal Ebola virus disease (EVD). The underlying mechanism of viral replication and EBOV-related hemorrhage is not fully understood. Here, we show that EBOV VP35, a cofactor of viral RNA-dependent RNA polymerase, binds human A kinase interacting protein (AKIP1), which consequently activates protein kinase A (PKA) and the PKA-downstream transcription factor CREB1. During EBOV infection, CREB1 is recruited into EBOV ribonucleoprotein complexes in viral inclusion bodies (VIBs) and employed for viral replication. AKIP1 depletion or PKA-CREB1 inhibition dramatically impairs EBOV replication. Meanwhile, the transcription of several coagulation-related genes, including THBD and SERPINB2, is substantially upregulated by VP35-dependent CREB1 activation, which may contribute to EBOV-related hemorrhage. The finding that EBOV VP35 hijacks the host PKA-CREB1 signal axis for viral replication and pathogenesis provides novel potential therapeutic approaches against EVD.
Engineering artificial photosynthetic life-forms through endosymbiosis
Authors: Cournoyer Jay , Altman Sarah D. , Gao Yang-le , Wallace Catherine L. , Zhang Dianwen , Lo Guo-Hsuen , Haskin Noah T. , Mehta Angad P.
Published: April 2022

The evolutionary origin of the photosynthetic eukaryotes drastically altered the evolution of complex lifeforms and impacted global ecology. The endosymbiotic theory suggests that photosynthetic eukaryotes evolved due to endosymbiosis between non-photosynthetic eukaryotic host cells and photosynthetic cyanobacterial or algal endosymbionts. The photosynthetic endosymbionts, propagating within the cytoplasm of the host cells, evolved, and eventually transformed into chloroplasts. Despite the fundamental importance of this evolutionary event, we have minimal understanding of this remarkable evolutionary transformation. Here, we design and engineer artificial, genetically tractable, photosynthetic endosymbiosis between photosynthetic cyanobacteria and budding yeasts. We engineer various mutants of model photosynthetic cyanobacteria as endosymbionts within yeast cells where, the engineered cyanobacteria perform bioenergetic functions to support the growth of yeast cells under defined photosynthetic conditions. We anticipate that these genetically tractable endosymbiotic platforms can be used for evolutionary studies, particularly related to organelle evolution, and also for synthetic biology applications.
Sign-problem free quantum stochastic series expansion algorithm on a quantum computer
Authors: Tan Kok Chuan , Bhowmick Dhiman , Sengupta Pinaki
Published: April 2022

A quantum implementation of the Stochastic Series Expansion (SSE) Monte Carlo method is proposed, and is shown to offer significant advantages over classical implementations of SSE. In particular, for problems where classical SSE encounters the sign problem, the cost of implementing a Monte Carlo iteration scales only linearly with system size in quantum SSE, while it may scale exponentially with system size in classical SSE. In cases where classical SSE can be efficiently implemented, quantum SSE still offers an advantage by allowing for more general observables to be measured.
Improved virtual extensometer measurement method in complex multi-fracture situation
Authors: Chai Jing , Ouyang Yibo , Liu Jinxuan , Zhang Dingding , Du Wengang , Yang Jianfeng , Liu Yongliang , Ma Zhe
Published: April 2022

To overcome the limitation of the virtual extensometer method in measuring the crack opening displacement (COD) in the process of complex multi-crack propagation of rock, the measurement error of Digital Image Correlation (DIC) local deformation is theoretically analyzed. An improved virtual extensometer method for measuring the COD is proposed, which considers the temporal and spatial characteristics of crack development in the process of complex crack propagation. The accuracy of the proposed method is verified by the strain localization band numerical simulation test and indoor single crack simulation test. Furthermore, the method is applied to the two-dimensional similarity simulation test of simulating complex multi-fractures in rock stratum. The COD obtained by the traditional and improved methods is compared with the measured COD. The results show that in the case of multiple complex cracks, to obtain the COD accurately, the relative distance between the virtual extensometer measuring point and the crack should be greater than half of the sum of the width of the crack strain localization zone and the subset size. With the development of the crack, the relative distance between the virtual extensometer measuring point and the crack should increase with the increase of the width of the crack strain localization zone. The error of the COD measured by the traditional method increases with fracture development, and the maximum is 21.20%. The maximum relative error between the COD measured by the improved method and the measured crack opening is 3.61%. The research results improve the accuracy of the virtual extensometer in measuring the COD under complex multi-crack conditions.