bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative study of accuracy in major adaptive filters for motion artifact removal in sleep apnea tests
Authors: Chen Yongrui , Zheng Yurui , Johnson Sam , Wiffen Richard , Yang Bin
Published: December 2023

Sleep apnea is probably the most common respiratory disorder; respiration and blood oxygen saturation (SpO2) are major concerns in sleep apnea and are also the two main parameters checked by polysomnography (PSG, the gold standard for diagnosing sleep apnea). In this study, we used a simple, non-invasive monitoring system based on photoplethysmography (PPG) to continuously monitor SpO2 and heart rate (HR) for individuals at home. Various breathing experiments were conducted to investigate the relationship between SpO2, HR, and apnea under different conditions, where two techniques (empirical formula and customized formula) for calculating SpO2 and two methods (resting HR and instantaneous HR) for assessing HR were compared. Various adaptive filters were implemented to compare the effectiveness in removing motion artifacts (MAs) during the tests. This study fills the gap in the literature by comparing the performance of different adaptive filters on estimating SpO2 and HR during apnea. The results showed that up-down finger motion introduced more MA than left-right motion, and the errors in SpO2 estimation were increased as the frequency of movement was increased; due to the low sampling frequency features of these tests, the insertion of adaptive filter increased the noise in the data instead of eliminating the MA for SpO2 estimation; the normal least mean squares (NLMS) filter is more effective in removing MA in HR estimation than other filters.

Graphical abstract
ASCO 2023: highlights in breast cancer
Authors: Bartsch Rupert
Published: December 2023

The 2023 annual meeting of the American Society of Clinical Oncology (ASCO) was again held in June 2023 in Chicago. While not immediately practice changing, results from several interesting studies in the field of breast cancer (BC) were reported. In the phase III NATALEE trial, the addition of 3 years of ribociclib to standard adjuvant endocrine therapy resulted in a significant improvement in invasive disease-free survival (iDFS), making this the second positive study of CDK4/6 inhibitors in the adjuvant setting. A subgroup analysis from the MONARCHe trial indicated sustained benefit of adjuvant abemaciclib in the subset of patients with low dose intensity. Long-term outcome of the neoadjuvant phase II PHERgain trial indicated excellent iDFS results in patients receiving neoadjuvant trastuzumab and pertuzumab without chemotherapy based upon PET metabolic response as a dynamic biomarker. In a biomarker analysis from the SOFT trial, more high-risk tumors were observed in the very young patient subset, while the PAM50 risk-of-recurrence score was not predictive for benefit of ovarian function suppression. A large retrospective analysis evaluated the role of adjuvant chemotherapy in small, node-negative triple-negative breast cancer. A clear benefit for chemotherapy was only seen in tumors > 10 mm of size. In metastatic HR-positive breast cancer, the PALMIRA trial with palbociclib beyond progression yielded negative results. An update from the PADA-1 trial again indicates the promising role of repeated liquid biopsies for treatment guidance in metastatic disease. Patritumab deruxtecan, a HER3-directed antibody–drug conjugate yielded promising response rates in HER2-negative metastatic breast cancer patients. In addition, several retrospective analyses focused on the important question of treatment sequencing.
State of the art of passenger redirection during incidents in public transport systems, considering capacity constraints
Authors: Bachmann Frederik R. , Tsakarestos Antonios , Busch Fritz , Bogenberger Klaus
Published: December 2023

This paper gives a comprehensive insight into the investigations done in passenger redirection during incidents in public transport systems. In public transport operations, incidents such as traffic accidents, deployment of emergency forces, or technical failures happen every day and disrupt the service. Most of the investigations done in the field of incident management focus on the readjustment of the supply towards the incident situation and are therefore referred to as supply-centric part of incident management. However, especially in recent years, more and more investigations have also been done on the passenger-centric part of incident management. These rather focus on the effects of incidents on passengers or even include them in the solution of the incident situation, either by informing them adequately about the given situation (passive redirection) or by providing them with concrete path advice (active redirection). The results show that adequate passenger information during incidents can reduce the average delay of affected passengers and support the recovery of the public transport system. This improves the reliability of a public transport system and boosts its attractiveness.
Clopidogrel-loaded vascular grafts prepared using digital light processing 3D printing
Authors: Adhami Masoud , Picco Camila J. , Detamornrat Usanee , Anjani Qonita K. , Cornelius Victoria A. , Robles-Martinez Pamela , Margariti Andriana , Donnelly Ryan F. , Domínguez-Robles Juan , Larrañeta Eneko
Published: December 2023

The leading cause of death worldwide and a significant factor in decreased quality of life are the cardiovascular diseases. Endovascular operations like angioplasty, stent placement, or atherectomy are often used in vascular surgery to either dilate a narrowed blood artery or remove a blockage. As an alternative, a vascular transplant may be utilised to replace or bypass a dysfunctional or blocked blood vessel. Despite the advancements in endovascular surgery and its popularisation over the past few decades, vascular bypass grafting remains prevalent and is considered the best option for patients in need of long-term revascularisation treatments. Consequently, the demand for synthetic vascular grafts composed of biocompatible materials persists. To address this need, biodegradable clopidogrel (CLOP)-loaded vascular grafts have been fabricated using the digital light processing (DLP) 3D printing technique. A mixture of polylactic acid-polyurethane acrylate (PLA-PUA), low molecular weight polycaprolactone (L-PCL), and CLOP was used to achieve the required mechanical and biological properties for vascular grafts. The 3D printing technology provides precise detail in terms of shape and size, which lead to the fabrication of customised vascular grafts. The fabricated vascular grafts were fully characterised using different techniques, and finally, the drug release was evaluated. Results suggested that the performed 3D-printed small-diameter vascular grafts containing the highest CLOP cargo (20% w/w) were able to provide a sustained drug release for up to 27 days. Furthermore, all the CLOP-loaded 3D-printed materials resulted in a substantial reduction of the platelet deposition across their surface compared to the blank materials containing no drug. Haemolysis percentage for all the 3D-printed samples was lower than 5%. Moreover, 3D-printed materials were able to provide a supportive environment for cellular attachment, viability, and growth. A substantial increase in cell growth was detected between the blank and drug-loaded grafts.

Graphical Abstract
Use of Additives in Composting Promotes Passivation and Reduction in Bioavailability of Heavy Metals (HMs) in Compost
Authors: Ejileugha Chisom , Onyegbule Uzoma Oluchi , Osuoha Justice Obinna
Published: December 2023

Composting influences heavy metal (HM) speciation by transforming the exchangeable and reducible forms of HMs to oxidisable and residual forms, promoting the redistribution of HMs to a more stable form thereby reducing their mobility, leachability, and bioavailability. This enhances HM passivation hence reducing environmental contamination and possible HM-related toxicity. In this review, we explored the impact of additives/ameliorants on HM passivation during composting and the reduction in HM bioavailability in compost. Using additives in composting improved the passivation of HMs and reduced the bioavailability through several mechanisms. Additives may not reduce total HM concentration but reduce the bioavailable concentration, which is of importance in risk assessment. However, vermicomposting is exceptional, as it reduces total HM concentration. Improving humification and microbial activity is at the heart of HM passivation in composting. Overall, conditions and substances that promote humification, thermophilic phase, and improve microbial community structure enhance HM passivation in compost. Combining suitable composting additives depending on HMs of interest and vermicomposting the final compost is most likely to yield the best result in reducing HM bioavailability cum total concentration to achieve a safe final product.
Achieving sustainable built-environment using bamboo composite frame system with cow-dung masonry infills
Authors: Bhalla Suresh , Singh Anuj , Bhagat Diwakar , West Roger
Published: December 2023

In today's rapidly urbanizing world, there is dire need for adopting the principles of green/ sustainable built-environment so as to mitigate the ill effects of environmental degradation and climate change. However, demand for housing is on rise in developing countries like India, where sizeable population, especially the low-income strata, still lacks decent quality structurally safe housing. Extensive use of concrete and steel in construction over more than a century has led to detrimental environmental effects such uncontrolled release of greenhouse gases/ pollutants, deforestation and erosion, leading to now visible outcomes of climate change. Bamboo, on other hand provides a sustainable alternative to concrete and steel as a building material since it absorbs the atmospheric carbon dioxide, produces more oxygen than timber producing trees and is a lightweight and renewable building material. Unlike timber, it matures in four to five years and being grass family, is replenishable in nature. However, from structural point of view, the main drawback of bamboo culm is its large slenderness ratio, which renders it weak in resisting bending and compressive loads. This paper presents an alternate structural system utilizing fibre reinforced bamboo composite (FRBC) to overcome the structural deficiency of a single shoot bamboo and build a prototype structure after detailed laboratory evaluation and structural analysis. Structural elements made from FRBC are utilized for fabricating a prototype 3D frame structure, measuring about 24 m2 in plan, representing a modular unit amenable to horizontal and vertical expansion. Eco-friendly materials like cow-dung based bricks and mortar, which offer net zero additional carbon dioxide emissions and circumvent reliance on cement and river sand, have been utilized as masonry infills after structural evaluation. The built structure provides a proof-of-concept demonstration of the feasibility of using bamboo and cow-dung, sustainable building materials, for achieving a structurally safe built-environment. The technology is especially suitable for countries like India which are endowed with tropical climatic conditions. By adopting such environmentally friendly alternatives, the construction industry can create a healthier environment while addressing housing and infrastructure needs in sustainable manner.
A Model of Ganymede's Magnetic and Plasma Environment During the Juno PJ34 Flyby
Authors: Stahl Aaron , Addison Peter , Simon Sven , Liuzzo Lucas
Published: December 2023

Using a hybrid model (kinetic ions, fluid electrons), we provide context for plasma and magnetic field observations from Juno's PJ34 flyby of Ganymede on 07 June 2021. We consider five model configurations that successively increase the complexity of Ganymede's atmosphere and ionosphere by including additional particle species and ionization mechanisms. We examine the density and flow patterns of pick‐up ions with small , intermediate (H2O+), and large masses in Ganymede's interaction region. The results are validated by comparing the modeled magnetic field and ion densities against time series from Juno's magnetometer and plasma instruments. Our major findings are: (a) Ganymede's internal dipole dominated the magnetic field signature observed inside the moon's magnetosphere, while plasma currents shaped the field perturbations within the “wake” region detected along the Jupiter‐averted magnetopause. (b) Ganymede's pick‐up tail leaves a subtle, but clearly discernible imprint in the magnetic field downstream of the moon. (c) Heavy pick‐up ions dominate ionospheric outflow and form a tail with steep outer boundaries. (d) During the flyby, the position of Ganymede's Jupiter‐facing magnetopause varied in time due to Kelvin‐Helmholtz waves traveling along the boundary layer. As such, the location of the Jupiter‐facing magnetopause observed by Juno represents only a single snapshot of this time‐dependent process. (e) Ionospheric hydrogen ions are partially generated outside of Ganymede's magnetopause, forming a dilute corona that surrounds the moon's magnetosphere. (f) Most H2O+ ions are produced at low latitudes where field lines are closed, resulting in a very dilute pick‐up tail for this species.
General deep learning framework for emissivity engineering
Authors: Yu Shilv , Zhou Peng , Xi Wang , Chen Zihe , Deng Yuheng , Luo Xiaobing , Li Wangnan , Shiomi Junichiro , Hu Run
Published: December 2023

Wavelength-selective thermal emitters (WS-TEs) have been frequently designed to achieve desired target emissivity spectra, as a typical emissivity engineering, for broad applications such as thermal camouflage, radiative cooling, and gas sensing, etc. However, previous designs require prior knowledge of materials or structures for different applications and the designed WS-TEs usually vary from applications to applications in terms of materials and structures, thus lacking of a general design framework for emissivity engineering across different applications. Moreover, previous designs fail to tackle the simultaneous design of both materials and structures, as they either fix materials to design structures or fix structures to select suitable materials. Herein, we employ the deep Q-learning network algorithm, a reinforcement learning method based on deep learning framework, to design multilayer WS-TEs. To demonstrate the general validity, three WS-TEs are designed for various applications, including thermal camouflage, radiative cooling and gas sensing, which are then fabricated and measured. The merits of the deep Q-learning algorithm include that it can (1) offer a general design framework for WS-TEs beyond one-dimensional multilayer structures; (2) autonomously select suitable materials from a self-built material library and (3) autonomously optimize structural parameters for the target emissivity spectra. The present framework is demonstrated to be feasible and efficient in designing WS-TEs across different applications, and the design parameters are highly scalable in materials, structures, dimensions, and the target functions, offering a general framework for emissivity engineering and paving the way for efficient design of nonlinear optimization problems beyond thermal metamaterials.
Sleep spindle architecture associated with distinct clinical phenotypes in older adults at risk for dementia
Authors: Orlando Isabella F. , O’Callaghan Claire , Lam Aaron , McKinnon Andrew C. , Tan Joshua B. C. , Michaelian Johannes C. , Kong Shawn D. X. , D’Rozario Angela L. , Naismith Sharon L.
Published: December 2023

Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders. Here, we use a data-driven approach to examine the sleep, memory and default mode network connectivity phenotypes associated with sleep spindle architecture in older adults (mean age = 66 years). Participants were recruited from a specialist clinic for early diagnosis and intervention for cognitive decline, with a proportion showing mild cognitive deficits on neuropsychological testing. In a sample of 88 people who underwent memory assessment, overnight polysomnography and resting-state fMRI, a k-means cluster analysis was applied to spindle measures of interest: fast spindle density, spindle duration and spindle amplitude. This resulted in three clusters, characterised by preserved spindle architecture with higher fast spindle density and longer spindle duration (Cluster 1), and alterations in spindle architecture (Clusters 2 and 3). These clusters were further characterised by reduced memory (Clusters 2 and 3) and nocturnal hypoxemia, associated with sleep apnea (Cluster 3). Resting-state fMRI analysis confirmed that default mode connectivity was related to spindle architecture, although directionality of this relationship differed across the cluster groups. Together, these results confirm a diversity in spindle architecture in older adults, associated with clinically meaningful phenotypes, including memory function and sleep apnea. They suggest that resting-state default mode connectivity during the awake state can be associated with sleep spindle architecture; however, this is highly dependent on clinical phenotype. Establishing relationships between clinical and neuroimaging features and sleep spindle alterations will advance our understanding of the bidirectional relationships between sleep changes and neurodegenerative diseases of ageing.
A synergistic impact of body mass index and gamma gap on heart failure and mortality rate among older patients with coronary artery disease: a prospective study with 10-year follow-up
Authors: Liu Xiaofei , Zheng Yangrui , Li Da , Zhao Yali , Lv Houchen , Guan Lixun , Fu Shihui
Published: December 2023

Purpose

This prospective study with 10-year follow-up aimed to analyze potential impact of body mass index (BMI) and gamma gap on heart failure and mortality rate in older patients with coronary artery disease (CAD).

Methods

There were 987 consecutive older patients with CAD included and divided into four groups according to BMI and gamma gap levels.

Results

Median age was 86 years. The highest proportion of heart failure (46.2%) and the highest mortality rate (84.4%) was observed in patients with low BMI and high gamma gap, whereas the lowest proportion of heart failure (18.9%) and the lowest mortality rate (62.9%) was observed in those with high BMI and low gamma gap. After full adjustment in multivariate Logistic regression analysis, heart failure was most common in patients with low BMI and high gamma gap compared with those with high BMI and low gamma gap (hazard ratio [HR]: 2.82, 95% confidence interval [CI]: 1.79–4.48, P < 0.05). Meanwhile, multivariate Cox regression analysis showed that mortality rate was the highest in those with low BMI and high gamma gap compared with patients with high BMI and low gamma gap (HR: 1.65, 95% CI: 1.32–2.07, P < 0.05).

Conclusion

The combination of low BMI and high gamma gap could further promote heart failure and increase mortality rate in older patients with CAD. Future studies should explore the underlying mechanisms linking low BMI, high gamma gap, and mortality rate, as well as the potential benefits of nutritional and immunological interventions to improve health prognosis in older patients with CAD.
Associations between human milk oligosaccharides and infant growth in a Bangladeshi mother–infant cohort
Authors: Loutet Miranda G. , Narimani Arash , Qamar Huma , Yonemitsu Chloe , Pell Lisa G. , Mahmud Abdullah Al , Ahmed Tahmeed , Bode Lars , Bassani Diego G. , Roth Daniel E.
Published: December 2023

Background

We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age.

Methods

In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders.

Results

The concentrations of 6’sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months.

Conclusions

Since HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes.

Impact

6’sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants.

Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months.

Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.
Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study
Authors: Lee Yan Hiu Athena , Hui Jeremy Man Ho , Leung Chi Ho , Tsang Christopher Tze Wei , Hui Kyle , Tang Pias , Chan Jeffrey Shi Kai , Dee Edward Christopher , Ng Kenrick , McBride Sean , Nguyen Paul L. , Tse Gary , Ng Chi Fai
Published: December 2023

Background

While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients.

Methods

Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups.

Results

In total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3–21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59–0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42–0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33–0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59–0.85], p < 0.001).

Conclusion

Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.
Phosphorylation of MIF by PIP4K2a is necessary for cilia biogenesis
Authors: Zhang Lu , Zhang Hongbing , Agborbesong Ewud , Zhou Julie Xia , Li Xiaogang
Published: December 2023

Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Macrophage migration inhibitory factor (MIF) has long been recognized as a secreted cytokine in the pathogenesis of various human diseases, including cancer and autosomal dominant polycystic kidney disease (ADPKD). Unlike other cytokines, unique functional characteristics of intracellular MIF have emerged. In this study, we show that MIF is localized and formed a ring like structure at the proximal end of centrioles, where it regulates cilia biogenesis through affecting 1) the recruitment of TTBK2 to basal body and the removal of CP110 from mother centriole, 2) the accumulation of CEP290 at centriolar satellites, and 3) the trafficking of intraflagellar transport (IFT) related proteins. We also show that MIF functions as a novel transcriptional factor to regulate the expression of genes related to ciliogenesis via binding on the promotors of those genes. MIF also binds chromatin and regulates transcription of genes involved in diverse homeostatic signaling pathways. We identify phosphatidylinositol-5-phosphate 4-kinase type 2 alpha (PIP4K2a) as an upstream regulator of MIF, which interacts with and phosphorylates MIF at S91 to increase its interaction with 14-3-3ζ, resulting in its nuclear translocation and transcription regulation. This study suggests that MIF is a key player in cilia biogenesis and a novel transcriptional regulator in homeostasis, which forward our understanding of how MIF is able to carry out several nonoverlapping functions.
Surveillance of multiple congenital anomalies; searching for new associations
Authors: Morris Joan K. , Bergman Jorieke E. H. , Barisic Ingeborg , Wellesley Diana , Tucker David , Limb Elizabeth , Addor Marie-Claude , Cavero-Carbonell Clara , Matias Dias Carlos , Draper Elisabeth S. , Echevarría-González-de-Garibay Luis Javier , Gatt Miriam , Klungsøyr Kari , Lelong Nathalie , Luyt Karen , Materna-Kiryluk Anna , Nelen Vera , Neville Amanda , Perthus Isabelle , Pierini Anna , Randrianaivo-Ranjatoelina Hanitra , Rankin Judith , Rissmann Anke , Rouget Florence , Sayers Geraldine , Wertelecki Wladimir , Kinsner-Ovaskainen Agnieszka , Garne Ester
Published: December 2023

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008–2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher’s exact test. The Benjamini–Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation.
The alignment of companies' sustainability behavior and emissions with global climate targets
Authors: Cenci Simone , Burato Matteo , Rei Marek , Zollo Maurizio
Published: December 2023

Climate actions by the private sector are crucial to cutting global emissions and meeting the climate targets set by the Paris Agreement. However, despite an increasing number of climate pledges, the emissions pathways of most companies are still misaligned with the Paris targets. To identify the causes of this discrepancy between effort and outcome, we developed a systematic approach, based on extensive analyses of textual data, to track the actions implemented by major public corporations to reduce their emissions. Our findings suggest that the misalignment between companies’ climate goals, actions, and outcomes is due to a widespread over-investment in risk mitigation actions as opposed to innovation and cooperation activities to foster energy goals. Overall, we provide a systematic framework to track companies’ climate actions. Our approach can be used by investors and policymakers to redirect capital towards its most sustainable use and to design behaviourally founded climate policy interventions.
Ecological forecasts for marine resource management during climate extremes
Authors: Brodie Stephanie , Pozo Buil Mercedes , Welch Heather , Bograd Steven J. , Hazen Elliott L. , Santora Jarrod A. , Seary Rachel , Schroeder Isaac D. , Jacox Michael G.
Published: December 2023

Forecasting weather has become commonplace, but as society faces novel and uncertain environmental conditions there is a critical need to forecast ecology. Forewarning of ecosystem conditions during climate extremes can support proactive decision-making, yet applications of ecological forecasts are still limited. We showcase the capacity for existing marine management tools to transition to a forecasting configuration and provide skilful ecological forecasts up to 12 months in advance. The management tools use ocean temperature anomalies to help mitigate whale entanglements and sea turtle bycatch, and we show that forecasts can forewarn of human-wildlife interactions caused by unprecedented climate extremes. We further show that regionally downscaled forecasts are not a necessity for ecological forecasting and can be less skilful than global forecasts if they have fewer ensemble members. Our results highlight capacity for ecological forecasts to be explored for regions without the infrastructure or capacity to regionally downscale, ultimately helping to improve marine resource management and climate adaptation globally.
Plasmon mediated coherent population oscillations in molecular aggregates
Authors: Timmer Daniel , Gittinger Moritz , Quenzel Thomas , Stephan Sven , Zhang Yu , Schumacher Marvin F. , Lützen Arne , Silies Martin , Tretiak Sergei , Zhong Jin-Hui , De Sio Antonietta , Lienau Christoph
Published: December 2023

The strong coherent coupling of quantum emitters to vacuum fluctuations of the light field offers opportunities for manipulating the optical and transport properties of nanomaterials, with potential applications ranging from ultrasensitive all-optical switching to creating polariton condensates. Often, ubiquitous decoherence processes at ambient conditions limit these couplings to such short time scales that the quantum dynamics of the interacting system remains elusive. Prominent examples are strongly coupled exciton-plasmon systems, which, so far, have mostly been investigated by linear optical spectroscopy. Here, we use ultrafast two-dimensional electronic spectroscopy to probe the quantum dynamics of J-aggregate excitons collectively coupled to the spatially structured plasmonic fields of a gold nanoslit array. We observe rich coherent Rabi oscillation dynamics reflecting a plasmon-driven coherent exciton population transfer over mesoscopic distances at room temperature. This opens up new opportunities to manipulate the coherent transport of matter excitations by coupling to vacuum fields.
Wood-based superblack
Authors: Zhao Bin , Shi Xuetong , Khakalo Sergei , Meng Yang , Miettinen Arttu , Turpeinen Tuomas , Mi Shuyi , Sun Zhipei , Khakalo Alexey , Rojas Orlando J. , Mattos Bruno D.
Published: December 2023

Light is a powerful and sustainable resource, but it can be detrimental to the performance and longevity of optical devices. Materials with near-zero light reflectance, i.e. superblack materials, are sought to improve the performance of several light-centered technologies. Here we report a simple top-down strategy, guided by computational methods, to develop robust superblack materials following metal-free wood delignification and carbonization (1500 °C). Subwavelength severed cells evolve under shrinkage stresses, yielding vertically aligned carbon microfiber arrays with a thickness of ~100 µm and light reflectance as low as 0.36% and independent of the incidence angle. The formation of such structures is rationalized based on delignification method, lignin content, carbonization temperature and wood density. Moreover, our measurements indicate a laser beam reflectivity lower than commercial light stoppers in current use. Overall, the wood-based superblack material is introduced as a mechanically robust surrogate for microfabricated carbon nanotube arrays.
Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways
Authors: Denolly Solène , Stukalov Alexey , Barayeu Uladzimir , Rosinski Alina N. , Kritsiligkou Paraskevi , Joecks Sebastian , Dick Tobias P. , Pichlmair Andreas , Bartenschlager Ralf
Published: December 2023

Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their proteome. Forty-six host cell factors are enriched in ZIKV remodeled membranes, several of these having a role in redox and methylation pathways. Four proteins are characterized in detail: thioredoxin reductase 1 (TXNRD1) contributing to folding of disulfide bond containing proteins and modulating ZIKV secretion; aldo-keto reductase family 1 member C3 (AKR1C3), regulating capsid protein abundance and thus, ZIKV assembly; biliverdin reductase B (BLVRB) involved in ZIKV induced lipid peroxidation and increasing stability of viral transmembrane proteins; adenosylhomocysteinase (AHCY) indirectly promoting m6A methylation of ZIKV RNA by decreasing the level of S- adenosyl homocysteine and thus, immune evasion. These results highlight the involvement of redox and methylation enzymes in the ZIKV life cycle and their accumulation at virally remodeled ER membranes.
The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells
Authors: Claude-Taupin Aurore , Isnard Pierre , Bagattin Alessia , Kuperwasser Nicolas , Roccio Federica , Ruscica Biagina , Goudin Nicolas , Garfa-Traoré Meriem , Regnier Alice , Turinsky Lisa , Burtin Martine , Foretz Marc , Pontoglio Marco , Morel Etienne , Viollet Benoit , Terzi Fabiola , Codogno Patrice , Dupont Nicolas
Published: December 2023

Shear stress generated by urinary fluid flow is an important regulator of renal function. Its dysregulation is observed in various chronic and acute kidney diseases. Previously, we demonstrated that primary cilium-dependent autophagy allows kidney epithelial cells to adapt their metabolism in response to fluid flow. Here, we show that nuclear YAP/TAZ negatively regulates autophagy flux in kidney epithelial cells subjected to fluid flow. This crosstalk is supported by a primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway. We confirm the relevance of the YAP/TAZ-autophagy molecular dialog in vivo using a zebrafish model of kidney development and a unilateral ureteral obstruction mouse model. In addition, an in vitro assay simulating pathological accelerated flow observed at early stages of chronic kidney disease (CKD) activates YAP, leading to a primary cilium-dependent inhibition of autophagic flux. We confirm this YAP/autophagy relationship in renal biopsies from patients suffering from diabetic kidney disease (DKD), the leading cause of CKD. Our findings demonstrate the importance of YAP/TAZ and autophagy in the translation of fluid flow into cellular and physiological responses. Dysregulation of this pathway is associated with the early onset of CKD.
A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection
Authors: Tai Wanbo , Yang Kai , Liu Yubin , Li Ruofan , Feng Shengyong , Chai Benjie , Zhuang Xinyu , Qi Shaolong , Shi Huicheng , Liu Zhida , Lei Jiaqi , Ma Enhao , Wang Weixiao , Tian Chongyu , Le Ting , Wang Jinyong , Chen Yunfeng , Tian Mingyao , Xiang Ye , Yu Guocan , Cheng Gong
Published: December 2023

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.
Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine
Authors: Thwaites Ryan S. , Uruchurtu Ashley S. S. , Negri Victor Augusti , Cole Megan E. , Singh Nehmat , Poshai Nelisa , Jackson David , Hoschler Katja , Baker Tina , Scott Ian C. , Ros Xavier Romero , Cohen Emma Suzanne , Zambon Maria , Pollock Katrina M. , Hansel Trevor T. , Openshaw Peter J. M.
Published: December 2023

Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.
Large off-diagonal magnetoelectricity in a triangular Co2+-based collinear antiferromagnet
Authors: Xu Xianghan , Hao Yiqing , Peng Shiyu , Zhang Qiang , Ni Danrui , Yang Chen , Dai Xi , Cao Huibo , Cava R. J.
Published: December 2023

Magnetic toroidicity is an uncommon type of magnetic structure in solid-state materials. Here, we experimentally demonstrate that collinear spins in a material with R-3 lattice symmetry can host a significant magnetic toroidicity, even parallel to the ordered spins. Taking advantage of a single crystal sample of CoTe6O13 with an R-3 space group and a Co2+ triangular sublattice, temperature-dependent magnetic, thermodynamic, and neutron diffraction results reveal A-type antiferromagnetic order below 19.5 K, with magnetic point group -3′ and k = (0,0,0). Our symmetry analysis suggests that the missing mirror symmetry in the lattice could lead to the local spin canting for a toroidal moment along the c axis. Experimentally, we observe a large off-diagonal magnetoelectric coefficient of 41.2 ps/m that evidences the magnetic toroidicity. In addition, the paramagnetic state exhibits a large effective moment per Co2+, indicating that the magnetic moment in CoTe6O13 has a significant orbital contribution. CoTe6O13 embodies an excellent opportunity for the study of next-generation functional magnetoelectric materials.
Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo
Authors: Kulhankova Katarina , Traore Soumba , Cheng Xue , Benk-Fortin Hadrien , Hallée Stéphanie , Harvey Mario , Roberge Joannie , Couture Frédéric , Kohli Sajeev , Gross Thomas J. , Meyerholz David K. , Rettig Garrett R. , Thommandru Bernice , Kurgan Gavin , Wohlford-Lenane Christine , Hartigan-O’Connor Dennis J. , Yates Bradley P. , Newby Gregory A. , Liu David R. , Tarantal Alice F. , Guay David , McCray Paul B.
Published: December 2023

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP. Following intratracheal aerosol delivery of Cy5-labeled peptide in rhesus macaques, we confirm delivery throughout the respiratory tract. Subsequently, we target CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieve editing efficiencies of up-to 5.3% in rhesus airway epithelia. Moreover, we document persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restores anion channel function in cultured human airway epithelia. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.
Strong temperature gradients in the ice age North Atlantic Ocean revealed by plankton biogeography
Authors: Jonkers Lukas , Laepple Thomas , Rillo Marina C. , Shi Xiaoxu , Dolman Andrew M. , Lohmann Gerrit , Paul André , Mix Alan , Kucera Michal
Published: December 2023

The cold Last Glacial Maximum, around 20,000 years ago, provides a useful test case for evaluating whether climate models can simulate climate states distinct from the present. However, because of the indirect and uncertain nature of reconstructions of past environmental variables such as sea surface temperature, such evaluation remains ambiguous. Instead, here we evaluate simulations of Last Glacial Maximum climate by relying on the fundamental macroecological principle of decreasing community similarity with increasing thermal distance. Our analysis of planktonic foraminifera species assemblages from 647 sites reveals that the similarity-decay pattern that we obtain when the simulated ice age seawater temperatures are confronted with species assemblages from that time differs from the modern. This inconsistency between the modern temperature dependence of plankton species turnover and the simulations arises because the simulations show globally rather uniform cooling for the Last Glacial Maximum, whereas the species assemblages indicate stronger cooling in the subpolar North Atlantic. The implied steeper thermal gradient in the North Atlantic is more consistent with climate model simulations with a reduced Atlantic meridional overturning circulation. Our approach demonstrates that macroecology can be used to robustly diagnose simulations of past climate and highlights the challenge of correctly resolving the spatial imprint of global change in climate models.
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Authors: Desai Jayesh , Alonso Guzman , Kim Se Hyun , Cervantes Andres , Karasic Thomas , Medina Laura , Shacham-Shmueli Einat , Cosman Rasha , Falcon Alejandro , Gort Eelke , Guren Tormod , Massarelli Erminia , Miller Wilson H. , Paz-Ares Luis , Prenen Hans , Amatu Alessio , Cremolini Chiara , Kim Tae Won , Moreno Victor , Ou Sai-Hong I. , Passardi Alessandro , Sacher Adrian , Santoro Armando , Stec Rafal , Ulahannan Susanna , Arbour Kathryn , Lorusso Patricia , Luo Jia , Patel Manish R. , Choi Yoonha , Shi Zhen , Mandlekar Sandhya , Lin Mark T. , Royer-Joo Stephanie , Chang Julie , Jun Tomi , Dharia Neekesh V. , Schutzman Jennifer L. ,   GO42144 Investigator and Study Group, Han Sae-Won
Published: December 2023

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS–MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC. Here, we report on divarasib plus cetuximab (epidermal growth factor receptor inhibitor) in patients with KRAS G12C-positive CRC (n = 29) from arm C of an ongoing phase 1b trial. The primary objective was to evaluate safety. Secondary objectives included preliminary antitumor activity. The safety profile of this combination was consistent with those of single-agent divarasib and cetuximab. Treatment-related adverse events led to divarasib dose reductions in four patients (13.8%); there were no treatment withdrawals. The objective response rate was 62.5% (95% confidence interval: 40.6%, 81.2%) in KRAS G12C inhibitor-naive patients (n = 24). The median duration of response was 6.9 months. The median progression-free survival was 8.1 months (95% confidence interval: 5.5, 12.3). As an exploratory objective, we observed a decline in KRAS G12C variant allele frequency associated with response and identified acquired genomic alterations at disease progression that may be associated with resistance. The manageable safety profile and encouraging antitumor activity of divarasib plus cetuximab support the further investigation of this combination in KRAS G12C-positive CRC.

ClinicalTrials.gov identifier: NCT04449874