bluuebunny/crossref_metadata_2025 huggingface dataset:
Community detection and percolation of information in a geometric setting
Authors: Eldan Ronen , Mikulincer Dan , Pieters Hester
Published: May 2022

We make the first steps towards generalising the theory of stochastic block models, in the sparse regime, towards a model where the discrete community structure is replaced by an underlying geometry. We consider a geometric random graph over a homogeneous metric space where the probability of two vertices to be connected is an arbitrary function of the distance. We give sufficient conditions under which the locations can be recovered (up to an isomorphism of the space) in the sparse regime. Moreover, we define a geometric counterpart of the model of flow of information on trees, due to Mossel and Peres, in which one considers a branching random walk on a sphere and the goal is to recover the location of the root based on the locations of leaves. We give some sufficient conditions for percolation and for non-percolation of information in this model.
Continuity and the everyday in architecture: four British practices working in Flanders
Authors: Antonissen Lucas
Published: May 2022

Since 2000, when the Flemish Government Architect established the ‘Open Oproep’, an instrument for awarding large public building projects in Flanders, it has been relatively easy for foreign offices to compete for commissions that are more difficult to obtain in their own countries. Participating in a competition, however, is one thing, winning it is another. The prevailing building culture creates a certain pattern of expectations against which entries are measured; in a design competition, the architecture needs to connect to this culture to meet these (typically implicit) expectations. In terms of these cultural resonances, Dirk Somers has referred to the ‘brown banana’, a metaphor for an architecture of mutual interest stretching from London, via Flanders, Germany, and Switzerland to part of northern Italy. This is an architecture linked by a certain continuity, defined by both invention and convention. This article takes a closer look at the northwestern part of Somers’s brown banana: Flanders and Great Britain. It examines the work of four contemporary British firms that have featured prominently in the final selection since the ‘Open Oproep’ began; namely, Sergison Bates, Tony Fretton, Maccreanor Lavington, and Witherford Watson Mann. On the basis of publications and lectures about and by these firms, a comparison is made between Flemish architecture and building culture, on one hand, as it has been described in recent years and the theoretical position of the four British firms, on the other. Key concepts in this study are collective memory, accumulation, continuity, style, phenomenology, teaching, and writing.
Microbiome-Inspired Green Infrastructure: a bioscience roadmap for urban ecosystem health
Authors: Robinson Jake M. , Watkins Harry , Man Ioana , Liddicoat Craig , Cameron Ross , Parker Brenda , Cruz Marcos , Meagher Laura
Published: May 2022

Microbiome-Inspired Green Infrastructure (MIGI) was recently proposed as an integrative system to promote healthy urban ecosystems through multidisciplinary design. Specifically, MIGI is defined as nature-centric infrastructure restored, designed, and managed to enhance health-promoting interactions between humans and environmental microbiomes while sustaining microbially mediated ecosystem functionality and resilience. MIGI also aims to stimulate a research agenda that focuses on considerations for the importance of urban environmental microbiomes.

In this article, we provide details of what MIGI entails from a bioscience and biodesign perspective, highlighting the potential dual benefits for human and ecosystem health. We present ‘what is known’ about the relationship between urban microbiomes, green infrastructure, and environmental factors that may affect urban ecosystem health - taken here to mean ecosystem functionality and resilience, as well as human health. We discuss how to start operationalising the MIGI concept based on current available knowledge and present a horizon-scan of emerging and future considerations in research and practice.

We conclude by highlighting challenges to implementing MIGI and propose a series of workshops to discuss multi-stakeholder needs and opportunities. This research will enable urban landscape managers to incorporate initial considerations for the microbiome in their development projects to promote human and ecosystem health. However, overcoming the challenges to operationalising MIGI will be essential to furthering its practical development. Although the research is in its infancy, there is considerable potential for MIGI to help deliver sustainable urban development driven by considerations for reciprocal relations between humans and the foundations of our ecosystems – the microorganisms.
Introduction to Fourier Ptychography: Part I
Authors: Zhou Kevin C. , Aidukas Tomas , Loetgering Lars , Wechsler Felix , Horstmeyer Roarke
Published: May 2022

Fourier ptychography is an emerging computational microscopy technique that can generate gigapixel-scale images of biological samples. With only the addition of a low-cost LED array to a standard digital microscope and a reconstruction algorithm, Fourier ptychography overcomes the fundamental trade-off between a microscope's resolution and field-of-view without any moving parts. This article is the first in a three-part series that aims to introduce the fundamentals of the technology to the broader microscopy community and beyond, using intuitive explanations.
The Effects of Model Complexity on Model Output Uncertainty in Co‐Evolved Coupled Natural‐Human Systems
Authors: Lin Chung‐Yi , Yang Yi‐Chen Ethan
Published: May 2022

Studies have recently focused on using coupled natural‐human systems (CNHS) to inform policymaking. However, model uncertainty can increase with model complexity and affect the variance of the model outcomes. Therefore, this study explores an uncertainty analysis of coupled hydrological and human decision models to better evaluate CNHS modeling properties. Five coupled models are proposed with different model complexities for human behavior settings (i.e., model structure and the number of calibrated parameters): one static, two adaptive, and two learning adaptive. Learning adaptive models (the most complex) have both a learning component (capturing long‐term trends) and an adaptive component (capturing short‐term variations), while adaptive models omit the learning component. The static model is the simplest, without learning or adaptive components. Applying the law of total variance, the model output uncertainty is decomposed into three sources: (a) climate change scenario uncertainty, (b) climate internal variability, and (c) different model configurations with parameter sets or model structures that are equally capable of producing similar outcomes. Our exploratory analysis demonstrated that model uncertainty would likely increase with model complexity given uncertain input data (e.g., climate forcing) and different model configurations; the inclusion of a learning mechanism in the human system can potentially offset the impact of the natural system on uncertainty through coupling natural and human systems. We also discuss other uncertainty sources, such as assumptions about model structure due to incomplete knowledge and metrics for calibration target selection for future studies.
Shrinking Habitats and Native Species Loss Under Climate Change: A Multifactorial Risk Assessment of China's Inland Wetlands
Authors: Zhong Yehui , Xue Zhenshan , Davis Charles C. , Moreno‐Mateos David , Jiang Ming , Liu Bo , Wang Guodong
Published: May 2022

Wetlands are highly productive ecosystems that host unique biota and provide vital ecosystem services. Despite their critical importance, we still lack a fundamental understanding of factors controlling species suitability and climate change impacts in wetlands essential to conserving these imperiled ecosystems in the face of anthropogenic threats. Here, we applied ecological niche models (ENMs) inferred from a massive nationwide data set including field surveys and herbarium specimens representing 101 dominant plant species of China's inland wetlands, to explore the potential climate‐driven shifts in these ecosystems. Our optimal models applying machine learning and integrating key aspects of climate, soil, topographic hydrology, and anthropogenic disturbance, identified that (a) species of different types (e.g., woody/nonwoody) showed significant differences in their sensitivity to extracted key environmental factors (e.g., isothermality, water table depth) in wetlands; (b) native wetland species likely face habitat shrinkage under climate change, especially in Northeast China, as well as potential encroachment of xeric and nonnative species; (c) only less than 20% of projected conservation hotspots are currently protected. We propose four protection gaps that need to be addressed urgently in China's current wetland protection framework. This study clarifies the conservation priorities of China's inland wetlands and provides practical guidelines for the improvement of wetland conservation efforts.
Advantage of 30‐s‐Updating Numerical Weather Prediction With a Phased‐Array Weather Radar Over Operational Nowcast for a Convective Precipitation System
Authors: Honda T. , Amemiya A. , Otsuka S. , Taylor J. , Maejima Y. , Nishizawa S. , Yamaura T. , Sueki K. , Tomita H. , Miyoshi T.
Published: May 2022

Convective precipitation systems in the summer often cause sudden heavy precipitation and largely affect various human activities, but the rapid evolution limits our predicting capability. Phased‐array weather radars (PAWRs) with a high spatiotemporal resolution are useful for observing such precipitation system. A recently developed numerical weather prediction (NWP) system assimilates PAWR observations with a 500‐m mesh NWP model. It initiates 30‐min extended forecasts every 30 s, much more frequently than the operational NWP and nowcasting systems. This study investigates the benefits of the 30‐s‐updating NWP system in a single but representative convective precipitation event in which a convective cloud developed within 10 min, and its evolution was not well predicted by operational precipitation nowcasting. The rapidly updating NWP system successfully predicts the evolution of the convective cloud. Assimilating the PAWR observations every 30 s continuously modifies the moisture and dynamical fields and improves the forecast accuracy consistently.
Aerial Observations and Numerical Simulations Confirm Density‐Driven Streamwise Vortices at a River Confluence
Authors: Duguay J. , Biron P. M. , Lacey J.
Published: May 2022

When rivers collide, complex three‐dimensional coherent flow structures are generated along the confluence's mixing interface. These structures mix streamborne pollutants and suspended sediment and have considerable bearing on the morphology and habitat quality of the postconfluent reach. A particular structure of interest—streamwise orientated vortices (SOVs)—were first detected in numerical simulations to form in pairs, one on each side of the mixing interface rotating in the opposite sense of the other. Since, it has proven difficult to detect SOVs in situ with conventional pointwise velocimetry instrumentation. Despite the lack of clear evidence to confirm their existence, SOVs are nevertheless considered important drivers of mixing and sediment transport processes at confluences. Additionally, their causal mechanisms are not fully known which hinders a complete conceptual understanding of these processes. To address these gaps, we analyze observations of strongly coherent SOVs filmed in aerial drone video of a mesoscale confluence with a stark turbidity contrast between its tributaries. Eddy‐resolved modeling demonstrates the SOVs' dynamics could only be accurately reproduced when a density difference (Δρ) was imposed between the tributaries (Δρ = 0.5 kg/m3)—providing compelling evidence the observed SOVs are indeed a novel density‐driven class of SOV. This work confirms that SOVs exist, expands understanding of their generative processes and highlights the important role of small density gradients (e.g., ≤0.5 kg/m3) on river confluence hydrodynamics.
Oxygen Propagation Fronts in Porous Media Under Evaporative Conditions at the Soil/Atmosphere Interface: Lab‐Scale Experiments and Model‐Based Interpretation
Authors: Ahmadi Navid , Acocella Michela , Fries Elisabeth , Mosthaf Klaus , Rolle Massimo
Published: May 2022

The interchange of gas components and volatile compounds between terrestrial and atmospheric compartments is critical for biogeochemical cycles and has important environmental and climate implications. In this study, we focus on oxygen and we explore the coupling between oxygen mass transfer and evaporation at the soil/atmosphere interface. We performed well‐controlled single‐phase and two‐phase laboratory experiments to determine the spatial and temporal evolution of oxygen fronts and to elucidate the coupling between mass and heat transfer in porous media with different grain sizes and under different evaporative conditions (i.e., no evaporation, natural, and enhanced evaporation). We also developed a non‐isothermal multiphase and multicomponent model to quantitatively interpret the experimental outcomes. The experiments and modeling allowed us to characterize the effects of external forcing (i.e., temperature gradients, humidity conditions) and internal factors (e.g., grain size) on the transport and distribution of oxygen in the different setups. Depth‐resolved spatial profiles and breakthrough curves of oxygen in the two‐phase experiments with evaporation are notably different from the single‐phase experiments due to the progressive gas invasion. The two‐phase experiments reveal a stepwise propagation pattern of oxygen that migrates considerably faster and penetrates deeper in the porous media in contrast to the relatively slow diffusion‐dominated transport regime in the absence of evaporation. The outcomes also show deeper and faster oxygen propagation in finer‐textured porous media under similar evaporative conditions, indicating the importance of internal factors for the distribution of the fluid phases and for the migration behavior of gas components in two‐phase systems.
The Impact of the Indian Ocean Basin Mode on Antarctic Sea Ice Concentration in Interannual Time Scales
Authors: Yu Lejiang , Zhong Shiyuan , Vihma Timo , Sui Cuijuan , Sun Bo
Published: May 2022

The Antarctic sea ice variability has been linked to tropical sea surface temperature. However, little is known as to whether and how the Indian Ocean Basin Mode (IOBM) influences Antarctic sea ice changes. We revealed the existence of a teleconnection between the IOMB and Antarctic sea ice anomalies, which is much stronger in austral spring and autumn than summer and winter. In particular, under the positive phase of the IOBM, significant positive sea ice anomalies occur in the Bellingshausen and northern Weddell Seas, in contrast to negative anomalies in the Amundsen Sea, the southern Atlantic Ocean, and the coastal seas off Dronning Maud Land. This teleconnection is established by planetary wavetrains excited over the tropical Indian Ocean and the tropical Pacific Ocean and is modulated by El Niño‐Southern Oscillation. The IOBM‐related Antarctic sea ice anomalies are largely consistent with those of the anomalous surface air temperature and wind fields associated with the IOBM.
Interplate Coupling and Seismic Potential in the Atacama Seismic Gap (Chile): Dismissing a Rigid Andean Sliver
Authors: Yáñez‐Cuadra V. , Ortega‐Culaciati F. , Moreno M. , Tassara A. , Krumm‐Nualart N. , Ruiz J. , Maksymowicz A. , Manea M. , Manea V. C. , Geng J. , Benavente R.
Published: May 2022

Geodetically constrained interseismic interplate coupling has been widely used to assess seismic potential in subduction zones. Modeling interseismic deformation is challenging, as it involves interplate coupling and often ignores continental internal deformation processes. We present a novel methodology to jointly estimate interplate coupling along with upper plate rigid motion and surface strain, constrained by GNSS‐derived velocities. We use a least squares inversion with a spatially variable Equal Posterior Information Condition Tikhonov regularization, accounting for observational and elastic structure uncertainties. Our modeling reveals three megathrust regions with high tsunamigenic earthquake potential located within the Atacama Seismic Gap (Chile). This study indicates the presence of a downdip segmentation located just above the 1995 (Mw8.0) Antofagasta earthquake rupture, raising concerns for the potential of tsunamigenic earthquake occurrence at shallower depths. Additionally, we show that surface motion is dominated by strain, with rather negligible rigid motion, dismissing the rigid Andean microplate model typically assumed in previous studies.
The Influence of Sub‐Footprint Cloudiness on Three‐Dimensional Horizontal Wind From Geostationary Hyperspectral Infrared Sounder Observations
Authors: Li Jun , Zhang Yurong , Di Di , Ma Zheng , Li Zhenglong , Schmit Timothy J. , Menzel W. Paul
Published: May 2022

Radiance measurements from a geostationary hyperspectral infrared sounder (GeoHIS) with high temporal resolution not only provide a continuous weather cube of atmospheric temperature and moisture information at different pressure levels, but also enable derivation of three‐dimensional (3D) horizontal winds by tracking atmospheric water vapor features. However, GeoHIS radiances are influenced by sub‐footprint cloudiness, which needs to be considered in tracking the moisture features for deriving the atmospheric wind fields. By combining the collocated high spatial resolution cloud information from an imager onboard the same platform, the 3D horizontal wind retrievals can be improved, and the influence of sub‐footprint cloudiness on winds can be quantified for better applications. Using data from the Advanced Geostationary Radiation Imager (AGRI) and Geostationary Interferometric Infrared Sounder onboard the same experimental geostationary satellite Fengyun‐4A, it is found that 3D horizontal wind retrievals can be derived under both clear and partially clear skies with reasonable accuracy. Sub‐footprint cloud information provides noticeable improvement in wind retrievals; higher/lower clouds have more/less influence while thicker/thinner clouds have more/less influence, respectively, on the wind product. The sub‐footprint cloudiness (cloud‐top pressure and cloud coverage) provides a good indication of the quality flag for quantitative applications of the 3D horizontal wind product.
Complex Rupture and Triggered Aseismic Creep During the 14 August 2021 Haiti Earthquake From Satellite Geodesy
Authors: Maurer J. , Dutta R. , Vernon A. , Vajedian S.
Published: May 2022

The 2021 August 14 MW 7.2 Nippes, Haiti earthquake occurred 75 km west of the epicenter of the 2010 Leogane earthquake (Haiti) on the transpressive Caribbean ‐ North America plate boundary. We present an updated fault map for Hispaniola and model coseismic and early postseismic fault slip using Interferometric Synthetic Aperture Radar and pixel offsets. We find the earthquake ruptured multiple segments of the Enriquillo‐Plantain Garden Fault Zone. Slip occurred in two main sub‐events on either side of a restraining bend at Pic Macaya, with ∼2.7 m of peak reverse‐slip east of the bend. To the west, slip jumps the restraining bend and further ruptures with ∼1.2 m of left‐lateral slip. Afterslip in the 4 days following the event occurred at shallow depth and adjacent to the coseismic rupture areas and reached the surface east of Pic Macaya.
Effect of an interactive mobile health support system and daily weight measurements for pediatric obesity treatment, a 1-year pragmatical clinical trial
Authors: Hagman Emilia , Johansson Linnea , Kollin Claude , Marcus Erik , Drangel Andreas , Marcus Love , Marcus Claude , Danielsson Pernilla
Published: May 2022

Background

Pediatric obesity lifestyle treatment is not always successful. Frequent clinical visits are of major importance to certify sufficient effect but are difficult due to the associated costs and the great demands on families. We hypothesized that an interactive digital support may reduce the need for frequent physical visits. The aim of the study was to assess 1-year weight outcome for patients using a digital support system compared with standard care.

Methods

An obesity lifestyle treatment with a digital support system was implemented in one clinic in Stockholm, Sweden. Measurements from a custom-made body scale without digits for daily home measurement of weights were transferred via Bluetooth to a mobile application, where BMI Z-score was calculated and presented graphically with an individualized weight loss target curve. An automatic transfer of data to the web-based clinic interface enables a close monitoring of treatment progress, and frequent written communication between the clinical staff and families via the application. One-year outcome was compared with a randomly retrieved, age and sex matched control group from the Swedish childhood obesity treatment register (BORIS), which received standard treatment at other clinics. Main outcome was change in BMI Z-score and missing data was imputed.

Results

107 children were consecutively included to digi-physical treatment and 321 children to standard care. Age range 4.1–17.4 years (67% males). The attrition rate was 36% and 46% respectively, p = 0.08. After 1 year, the mean ± SD change in BMI Z-score in the treatment group was −0.30 ± 0.39 BMI Z-score units and in the standard care group −0.15 ± 0.28, p = 0.0002. The outcome was better for both sexes and all age groups in the digi-physical treated group.

Conclusion

A digital support system with a personalized weight-loss target curve and daily weight measurements shared by the family and the clinic is more effective than a standard care childhood obesity treatment.

Clinicaltrial.gov ID

NCT04323215
Machine learning for understanding and predicting neurodevelopmental outcomes in premature infants: a systematic review
Authors: Baker Stephanie , Kandasamy Yogavijayan
Published: May 2022

Background

Machine learning has been attracting increasing attention for use in healthcare applications, including neonatal medicine. One application for this tool is in understanding and predicting neurodevelopmental outcomes in preterm infants. In this study, we have carried out a systematic review to identify findings and challenges to date.

Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases were searched in February 2022, with articles then screened in a non-blinded manner by two authors.

Results

The literature search returned 278 studies, with 11 meeting the eligibility criteria for inclusion. Convolutional neural networks were the most common machine learning approach, with most studies seeking to predict neurodevelopmental outcomes from images and connectomes describing brain structure and function. Studies to date also sought to identify features predictive of outcomes; however, results varied greatly.

Conclusions

Initial studies in this field have achieved promising results; however, many machine learning techniques remain to be explored, and the consensus is yet to be reached on which clinical and brain features are most predictive of neurodevelopmental outcomes.

Impact

This systematic review looks at the question of whether machine learning can be used to predict and understand neurodevelopmental outcomes in preterm infants.

Our review finds that promising initial works have been conducted in this field, but many challenges and opportunities remain.

Quality assessment of relevant articles is conducted using the Newcastle–Ottawa Scale.

This work identifies challenges that remain and suggests several key directions for future research.

To the best of the authors’ knowledge, this is the first systematic review to explore this topic.
Threat reversal learning and avoidance habits in generalised anxiety disorder
Authors: Roberts Clark , Apergis-Schoute Annemieke M. , Bruhl Annette , Nowak Magda , Baldwin David S. , Sahakian Barbara J. , Robbins Trevor W.
Published: May 2022

Avoidance and heightened responses to perceived threats are key features of anxiety disorders. These disorders are characterised by inflexibility in dynamically updating behavioural and physiological responses to aversively conditioned cues or environmental contexts which are no longer objectively threatening, often manifesting in perseverative avoidance. However, less is known about how anxiety disorders might differ in adjusting to threat and safety shifts in the environment or how idiosyncratic avoidance responses are learned and persist. Twenty-eight patients with generalised anxiety disorder (GAD), without DSM co-morbidities, and 27 matched healthy controls were administered two previously established paradigms: Pavlovian threat reversal and shock avoidance habits through overtraining (assessed following devaluation with measures of perseverative responding). For both tasks we used subjective report scales and skin conductance responses (SCR). In the Pavlovian threat reversal task, patients with GAD showed a significantly overall higher SCR as well as a reduced differential SCR response compared to controls in the early but not late reversal phase. During the test of habitual avoidance responding, GAD patients did not differ from controls in task performance, habitual active avoidance responses during devaluation, or corresponding SCR during trials, but showed a trend toward more abstract confirmatory subjective justifications for continued avoidance following the task. GAD patients exhibited significantly greater skin conductance responses to signals of threat than controls, but did not exhibit the major deficits in reversal and safety signal learning shown previously by patients with OCD. Moreover, this patient group, again unlike OCD patients, did not show evidence of altered active avoidance learning or enhanced instrumental avoidance habits. Overall, these findings indicate no deficits in instrumental active avoidance or persistent avoidance habits, despite enhanced responses to Pavlovian threat cues in GAD. They suggest that GAD is characterised by passive, and not excessively rigid, avoidance styles.
Immune checkpoint inhibitors alone vs immune checkpoint inhibitors—combined chemotherapy for NSCLC patients with high PD-L1 expression: a network meta-analysis
Authors: Wang Yimin , Han Hedong , Zhang Fang , Lv Tangfeng , Zhan Ping , Ye Mingxiang , Song Yong , Liu Hongbing
Published: May 2022

Background

We indirectly compared the effects of immune checkpoint inhibitors alone (ICI) and ICI-combined chemotherapy (chemo-ICI) in patients with non-small cell lung cancer who had high programmed death-ligand 1 (PD-L1) expression (defined as tumour proportion score ≥50% or TC3/IC3) through network meta-analyses.

Methods

Through literature searches, we shortlisted 22 randomised controlled trials encompassing 4289 patients, with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) set as the primary outcomes. The dichotomous data for ORR and hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS were extracted.

Results

We found that chemo-ICI had significantly improved ORR (OR 1.7, 95% CI 1.1–2.5) and PFS (HR 0.59, 95% CI: 0.48–0.74) relative to ICI. Although no significant difference in OS was observed, the analyses revealed that the chemo-ICI patients tended to undergo fewer progression events than ICI patients (HR 0.82, 95% CI 0.6–1.1). In subgroup analysis, the non-squamous, PD-1 inhibitor and first-line treatment cohorts exhibited significant differences in ORR and PFS, but not in OS. However, in the squamous, PD-L1 inhibitor, and previously treated cohorts, PFS, OS and ORR were not different between chemo-ICI and ICI patients.

Conclusions

In conclusion, for non-squamous NSCLC patients, accepting PD-1 as the first-line treatment may be a relatively better option.
Blocking connexin 43 and its promotion of ATP release from renal tubular epithelial cells ameliorates renal fibrosis
Authors: Xu Huzi , Wang Meng , Li Yinzheng , Shi Mengxia , Wang Zheng , Cao Chujin , Hong Yu , Hu Bin , Zhu Han , Zhao Zhi , Chu Xiaoxin , Zhu Fan , Deng Xuan , Wu Jianliang , Zhao Fenfei , Guo Jing , Wang Yuxi , Pei Guangchang , Zhu Fengming , Wang Xiaoyan , Yang Juan , Yao Ying , Zeng Rui
Published: May 2022

Whether metabolites derived from injured renal tubular epithelial cells (TECs) participate in renal fibrosis is poorly explored. After TEC injury, various metabolites are released and among the most potent is adenosine triphosphate (ATP), which is released via ATP-permeable channels. In these hemichannels, connexin 43 (Cx43) is the most common member. However, its role in renal interstitial fibrosis (RIF) has not been fully examined. We analyzed renal samples from patients with obstructive nephropathy and mice with unilateral ureteral obstruction (UUO). Cx43-KSP mice were generated to deplete Cx43 in TECs. Through transcriptomics, metabolomics, and single-cell sequencing multi-omics analysis, the relationship among tubular Cx43, ATP, and macrophages in renal fibrosis was explored. The expression of Cx43 in TECs was upregulated in both patients and mice with obstructive nephropathy. Knockdown of Cx43 in TECs or using Cx43-specific inhibitors reduced UUO-induced inflammation and fibrosis in mice. Single-cell RNA sequencing showed that ATP specific receptors, including P2rx4 and P2rx7, were distributed mainly on macrophages. We found that P2rx4- or P2rx7-positive macrophages underwent pyroptosis after UUO, and in vitro ATP directly induced pyroptosis by macrophages. The administration of P2 receptor or P2X7 receptor blockers to UUO mice inhibited macrophage pyroptosis and demonstrated a similar degree of renoprotection as Cx43 genetic depletion. Further, we found that GAP 26 (a Cx43 hemichannel inhibitor) and A-839977 (an inhibitor of the pyroptosis receptor) alleviated UUO-induced fibrosis, while BzATP (the agonist of pyroptosis receptor) exacerbated fibrosis. Single-cell sequencing demonstrated that the pyroptotic macrophages upregulated the release of CXCL10, which activated intrarenal fibroblasts. Cx43 mediates the release of ATP from TECs during renal injury, inducing peritubular macrophage pyroptosis, which subsequently leads to the release of CXCL10 and activation of intrarenal fibroblasts and acceleration of renal fibrosis.
Non-penetrating deep sclerectomy with the sub flap (Ahmed’s) suture: a 12-month comparative study
Authors: Abdelrahman Ahmed Mostafa , Hassan Lameece Moustafa , Habib Mina Maged
Published: May 2022

Purpose

To assess the IOP-lowering effect of adding a mattress suture (Ahmed’s suture) to non-penetrating deep sclerectomy (NPDS), in patients with open angle glaucoma over a 12-month follow-up period.

Methods

This is a randomized controlled study comparing 52 eyes with a sub-flap Ahmed’s suture modified NPDS (group A) and 51 with a conventional NPDS (group B). Success of surgery was categorized as complete success if the IOP remained between 6 and 18 mmHg without medications and as qualified if topical medications were required.

Results

The post-operative IOP at the 1st week, 3rd, 6th, 9th & 12th months follow ups in group A were significantly lower (7.3 ± 2.1, 12.0 ± 2.3, 12.6 ± 2.7, 13.6 ± 3.4 & 13.8 ± 3.8 mmHg) than in B (9.2 ± 1.9, 14.0 ± 3.1, 14.8 ± 2.9, 15.4 ± 2.6 & 15.7 ± 2.7 mmHg) (p = 0.001, p = 0.001, p = 0.002, p = 0.027 & p = 0.029 respectively). The percentage of IOP reduction after 1 year was significantly higher in group A than in group B (49% vs. 36.5%). At the end of the 12-month follow-up, 81% of group A and 69% of group B were considered as complete success. Multivariate regression analysis showed lower 1st week post-operative IOP was associated with better outcome.

Conclusion

In conclusion, the Ahmed’s suture, a simple, novel and economic modification, maintains lower IOP levels and has a higher success rate over conventional DS, as it is 30% more effective in reducing the IOP.
Trophic position of Otodus megalodon and great white sharks through time revealed by zinc isotopes
Authors: McCormack Jeremy , Griffiths Michael L. , Kim Sora L. , Shimada Kenshu , Karnes Molly , Maisch Harry , Pederzani Sarah , Bourgon Nicolas , Jaouen Klervia , Becker Martin A. , Jöns Niels , Sisma-Ventura Guy , Straube Nicolas , Pollerspöck Jürgen , Hublin Jean-Jacques , Eagle Robert A. , Tütken Thomas
Published: May 2022

Diet is a crucial trait of an animal’s lifestyle and ecology. The trophic level of an organism indicates its functional position within an ecosystem and holds significance for its ecology and evolution. Here, we demonstrate the use of zinc isotopes (δ66Zn) to geochemically assess the trophic level in diverse extant and extinct sharks, including the Neogene megatooth shark (Otodus megalodon) and the great white shark (Carcharodon carcharias). We reveal that dietary δ66Zn signatures are preserved in fossil shark tooth enameloid over deep geologic time and are robust recorders of each species’ trophic level. We observe significant δ66Zn differences among the Otodus and Carcharodon populations implying dietary shifts throughout the Neogene in both genera. Notably, Early Pliocene sympatric C. carcharias and O. megalodon appear to have occupied a similar mean trophic level, a finding that may hold clues to the extinction of the gigantic Neogene megatooth shark.
Computationally designed hyperactive Cas9 enzymes
Authors: Vos Pascal D. , Rossetti Giulia , Mantegna Jessica L. , Siira Stefan J. , Gandadireja Andrianto P. , Bruce Mitchell , Raven Samuel A. , Khersonsky Olga , Fleishman Sarel J. , Filipovska Aleksandra , Rackham Oliver
Published: May 2022

The ability to alter the genomes of living cells is key to understanding how genes influence the functions of organisms and will be critical to modify living systems for useful purposes. However, this promise has long been limited by the technical challenges involved in genetic engineering. Recent advances in gene editing have bypassed some of these challenges but they are still far from ideal. Here we use FuncLib to computationally design Cas9 enzymes with substantially higher donor-independent editing activities. We use genetic circuits linked to cell survival in yeast to quantify Cas9 activity and discover synergistic interactions between engineered regions. These hyperactive Cas9 variants function efficiently in mammalian cells and introduce larger and more diverse pools of insertions and deletions into targeted genomic regions, providing tools to enhance and expand the possible applications of CRISPR-based gene editing.
Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen
Authors: Gorrie Claire L. , Mirčeta Mirjana , Wick Ryan R. , Judd Louise M. , Lam Margaret M. C. , Gomi Ryota , Abbott Iain J. , Thomson Nicholas R. , Strugnell Richard A. , Pratt Nigel F. , Garlick Jill S. , Watson Kerrie M. , Hunter Peter C. , Pilcher David V. , McGloughlin Steve A. , Spelman Denis W. , Wyres Kelly L. , Jenney Adam W. J. , Holt Kathryn E.
Published: May 2022

Klebsiella pneumoniaeis a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study ofK. pneumoniaeclinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within theK. pneumoniaespecies complex (18%). Several infections were caused byK. variicola/K. pneumoniaehybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (mediann = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34,p = 0.015) and rhamnose-positive capsules (OR 3.12,p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21,p < 1 × 10−11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate thatK. pneumoniaeinfections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains.
Development and validation of a multivariable mortality risk prediction model for COPD in primary care
Authors: Shah Syed A. , Nwaru Bright I. , Sheikh Aziz , Simpson Colin R. , Kotz Daniel
Published: May 2022

Risk stratification of chronic obstructive pulmonary disease (COPD) patients is important to enable targeted management. Existing disease severity classification systems, such as GOLD staging, do not take co-morbidities into account despite their high prevalence in COPD patients. We sought to develop and validate a prognostic model to predict 10-year mortality in patients with diagnosed COPD. We constructed a longitudinal cohort of 37,485 COPD patients (149,196 person-years) from a UK-wide primary care database. The risk factors included in the model pertained to demographic and behavioural characteristics, co-morbidities, and COPD severity. The outcome of interest was all-cause mortality. We fitted an extended Cox-regression model to estimate hazard ratios (HR) with 95% confidence intervals (CI), used machine learning-based data modelling approaches including k-fold cross-validation to validate the prognostic model, and assessed model fitting and discrimination. The inter-quartile ranges of the three metrics on the validation set suggested good performance: 0.90–1.06 for model fit, 0.80–0.83 for Harrel’s c-index, and 0.40–0.46 for Royston and Saurebrei’s $$R_D^2$$

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with a strong overlap of these metrics on the training dataset. According to the validated prognostic model, the two most important risk factors of mortality were heart failure (HR 1.92; 95% CI 1.87–1.96) and current smoking (HR 1.68; 95% CI 1.66–1.71). We have developed and validated a national, population-based prognostic model to predict 10-year mortality of patients diagnosed with COPD. This model could be used to detect high-risk patients and modify risk factors such as optimising heart failure management and offering effective smoking cessation interventions.
Integrated usage of historical geospatial data and modern satellite images reveal long-term land use/cover changes in Bursa/Turkey, 1858–2020
Authors: Ettehadi Osgouei Paria , Sertel Elif , Kabadayı M. Erdem
Published: May 2022

Land surface of the Earth has been changing as a result of human induced activities and natural processes. Accurate representation of landscape characteristics and precise determination of spatio-temporal changes provide valuable inputs for environmental models, landscape and urban planning, and historical land cover change analysis. This study aims to determine historical land use and land cover (LULC) changes using multi-modal geospatial data, which are the cadastral maps produced in 1858, monochrome aerial photographs obtained in 1955, and multi-spectral WorldView-3 satellite images of 2020. We investigated two pilot regions, Aksu and Kestel towns in Bursa/Turkey, to analyze the long-term LULC changes quantitatively and to understand the driving forces that caused the changes. We propose methods to facilitate the preparation of historical datasets for the LULC change detection and present an object-oriented joint classification scheme for multi-source datasets to accurately map the spatio-temporal changes. Our approach minimized the amount of manual digitizing required for the boundary delineation of LULC classes from historical geospatial data. Also, our quantitative analysis of LULC maps indicates diverging developments for the selected locations in the long period of 162 years. We observed rural depopulation and gradual afforestation in Aksu; whereas, agricultural land abandonment and deforestation in Kestel.
Past 200 kyr hydroclimate variability in the western Mediterranean and its connection to the African Humid Periods
Authors: Camuera Jon , Ramos-Román María J. , Jiménez-Moreno Gonzalo , García-Alix Antonio , Ilvonen Liisa , Ruha Leena , Gil-Romera Graciela , González-Sampériz Penélope , Seppä Heikki
Published: May 2022

The Iberian Peninsula is located at the intersection between the subtropical and temperate climate zones and the paleoclimate records from this region are key to elucidate the varying humidity and changing dominance of atmospheric circulation patterns in the Mediterranean-North African region in the past. Here we present a quantitative hydroclimate reconstruction for the last ca. 200 kyr from southern Iberian Peninsula based on pollen data from the Padul lake sediment record. We use the newly developed Scale-normalized Significant Zero crossing (SnSiZer) method to detect not only the statistically significant precipitation changes but also to estimate the relative magnitude of these oscillations in our reconstruction. We identify six statistically significant main humid phases, termed West Mediterranean Humid Periods (WMHP 1–6). These humid periods correlate with other West/Central Mediterranean paleohydrological records, suggesting that similar climatic factors affected different areas of the Mediterranean. In addition, the WMPHs are roughly coeval with the African Humid Periods (AHPs) during high seasonality, suggesting the same North Atlantic ocean-atmospheric dynamics and orbital forcing as main drivers of both areas. In contrast, during low seasonality periods, the West Mediterranean still appears to be affected by the westerlies and the local Mediterranean rainfall systems with moderate-to-high precipitation, whereas West Africa was characterized by droughts.
The new preparation method for paraffin-embedded samples applying scanning electron microscopy revealed characteristic features in asthma-induced mice
Authors: Wakai Ken , Azuma Kazuhiko , Iwamura Chiaki , Maimaiti Maihulan , Mikami Kosuke , Yoneda Kei , Sakamoto Shinichi , Ikehara Sanae , Yamaguchi Takashi , Hirahara Kiyoshi , Ichikawa Tomohiko , Nakayama Toshinori , Ikehara Yuzuru
Published: May 2022

In bronchial asthma patients, mucous cell metaplasia (MCM) and fibrosis occur in the bronchial epithelium and interstitium, respectively. The mucus and collagen fibers are identified by Periodic acid-Schiff stain (PAS) or Sirius red stain on optical microscopy. On a scanning electron microscope (SEM) observation, formalin-fixed-paraffin-embedded specimens have high insulation, thereby attenuating the scattered electron signals leading to insufficient contrast. Moreover, there were no staining methods for SEM observation, which characterizes the changes in epithelium and interstitium by enhancing the scattered electrons. In this study, we established a method of coating osmium thin film on pathological tissue specimens using plasma chemical vapor deposition technology. This method ensured the intensity of scattered electron signals and enabled SEM observation. Furthermore, we found that morphological changes in MCM and interstitial fibrosis could be characterized by Grocott stain, which we optimized to evaluate pathological remodeling in bronchial asthma. Using these techniques, we compared asthma-induced mice with Amphiregulin (Areg) knockout mice, and found that Areg induce MCM, but the production of Grocott-stain-positive substrate in the interstitium is Areg-independent. The method developed in this study provides an understanding of the pathological spatial information linked to the ultrastructural changes in cells and interstitium due to disease-related signaling abnormalities.
Semiconducting hematite facilitates microbial and abiotic reduction of chromium
Authors: Chen Michael A. , Mehta Neha , Kocar Benjamin D.
Published: May 2022

Semi-conducting Fe oxide minerals, such as hematite, are well known to influence the fate of contaminants and nutrients in many environmental settings through sorption and release of Fe(II) resulting from microbial or abiotic reduction. Studies of Fe oxide reduction by adsorbed Fe(II) have demonstrated that reduction of Fe(III) at one mineral surface can result in the release of Fe(II) on a different one. This process is termed “Fe(II) catalyzed recrystallization” and is believed to be the result of electron transfer through semi-conducting Fe (hydr)oxides. While it is well understood that Fe(II) plays a central role in redox cycling of elements, the environmental implications of Fe(II) catalyzed recrystallization require further exploration. Here, we demonstrate that hematite links physically separated redox reactions by conducting the electrons involved in those reactions. This is shown using an electrochemical setup where Cr reduction is coupled with a potentiostat or Shewanella putrefaciens, a metal reducing microbe, where electrons donated to hematite produce Fe(II) that ultimately reduces Cr. This work demonstrates that mineral semi-conductivity may provide an additional avenue for redox chemistry to occur in natural soils and sediments, because these minerals can link redox active reactants that could not otherwise react due to physical separation.
Determinants of blood sugar level among type I diabetic patients in Debre Tabor General Hospital, Ethiopia: a longitudinal study
Authors: Gobena Molalign Gualu , Kassie Maru Zewdu
Published: May 2022

In 2019 among all populous countries in Africa, Ethiopia has the fourth-highest number of people with diabetes (1.7 million). This aggravated prevalence figure implies that diabetes mellitus is a major public health problem in Ethiopia. Due to urbanization, this problem is very critical in the Amhara region, Ethiopia. The study aimed to identify factors that affect the longitudinal fasting blood sugar among T1DM (Type I diabetes mellitus) patients in Debre Tabor General Hospital (DTGH); North-west Ethiopia. A retrospective study design was conducted from 210 randomly selected T1DM patients in the clinic (Outpatient Department) at Debre Tabor General Hospital under the follow-up period from September 2019 to August 2021. To fit these retrospective data records, we used Random intercept and slope models. In this study, the unstructured variance–covariance structure was the appropriate structure for the random intercept and slope model. At a 5% level of significance, family history of diabetes mellitus, age, comorbidity, hemoglobin, and visit time in months were significant factors. Also, all the random effect parameters were statistically significant. It implies that the variability within and between T1DM patients in FBS over time was statistically significant. The mean fasting blood sugar level at baseline was 5.4944 mg/dl and decreased to 5.0679 mg/dl at the final follow-up time. Major contributors for the increment of fasting blood sugar level were increasing age, decreasing haemoglobin, having comorbidity, and belonging from a family with diabetes history. The overall within and between variability in fasting blood sugar level among T1DM patients in DTGH were high. Intervention measures at DTGH level should be undertaken using health education and other measures by providing an emphasis on the prevention, early detection, and treatment of diabetes mellitus.