bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic, tactical, complex and simple changes to farm systems
Authors: Kaine Geoff , Wright Vic , Vallance Suzanne
Published: June 2024

Pressure has grown to reconfigure commercial farm systems to ameliorate resource degradation as governments have increasingly sought to halt or reverse the damaging effects of agriculture on the environment. Now, climate change is creating additional pressure to redesign farm systems to withstand more variable, and historically more extreme, seasonal conditions. Meeting these pressures is thought to require a combination of responses ranging from incremental adjustments to farm systems through to their complete transformation into entirely new enterprises. Implementing each of these entails different resources, time horizons, skills, knowledge and planning, and this has corresponding consequences for any government or industry policies intended to promote adoption or compliance. While there is an extensive literature on the adoption of technology and management practices in agriculture, the literature on different types of change to farm systems, and the criteria for distinguishing between types, is limited. We describe a novel approach to classifying changes to farm systems by integrating a method for describing the strategic and tactical flexibility of farm systems with a method for describing the complexity of changes to farm systems. The resulting classification provides a framework for inferring the nature of the resources, skills, knowledge, planning and time needed to implement the different types of change. We provide illustrative examples drawn from a series of interviews with farmers of each type of change and discuss the implications for extension, agricultural and environmental policy and policy regarding adaptation to climate change. We found that heterogeneity in farm systems translates into heterogeneity in adoption processes. We believe that our approach provides a practical way of translating commonly used broad descriptors of adaptation, such as ‘incremental’, ‘systems’ and ‘transformational’, into the specific type of the change that farmers must make to their farm systems to enact adaptations, with consequent implications for the effective policy support of adaptation.
The scientific rules, roles, and values that life sciences doctoral students want to see upheld by undergraduate researchers
Authors: Busch Carly A. , Nadile Erika M. , Mohammed Tasneem F. , Gin Logan E. , Brownell Sara E. , Cooper Katelyn M.
Published: June 2024

Articulating the rules, roles, and values that are expected of undergraduate researchers is important as we strive to create a more accessible path into the scientific community. Rules refer to skills required of scientists, roles refer to behaviors consistent with the expectations of a scientist, and values refer to beliefs of the scientific community. Doctoral student mentors have great potential to serve as agents of influence for undergraduate researchers as undergraduates engage in the process of learning to be a scientist through legitimate peripheral participation. As such, we argue that doctoral students are partially responsible for identifying and promoting the rules, roles, and values that undergraduate researchers develop in scientific research. However, few studies have examined what rules, roles, and values are appreciated, or perceived as desirable, by doctoral students and thus expected of undergraduate research mentees. To address this gap, we surveyed 835 life sciences doctoral students who had mentored or would eventually mentor undergraduate researchers. We assessed what qualities and beliefs they appreciate in undergraduate researchers and what advice they would give to undergraduates to maximize their experiences in research. We analyzed their open‐ended responses using inductive coding and identified specific rules (e.g., effectively communicate), roles (e.g., demonstrate a strong work ethic), and values (e.g., be driven by intrinsic passion) that doctoral students wrote about. We used logistic regression to determine whether demographics predicted differences among doctoral student responses. We found that gender, race/ethnicity, and college generation status predicted what rules, roles, and values doctoral students appreciated and advised undergraduates to adopt. This research illuminates what rules, roles, and values undergraduate researchers are expected to uphold and identifies relationships between mentor identities and the advice they pass on to students.
Versorgungsrealität des Ösophaguskarzinoms im Bundesland Brandenburg
Authors: Loew Andreas , Schneider Constanze , Pflüger Maren , Mantke René , Weylandt Karsten H. , Gretschel Stephan
Published: June 2024

Hintergrund

Klinische Krebsregister sollen durch differenzierte Datenauswertung die Versorgungsrealität abbilden und ggf. Ansätze für Verbesserung der Versorgung bieten.

Methode

Für die Jahre 2000 bis 2018 wurden die Daten des klinisch-epidemiologischen Krebsregisters Brandenburg-Berlin bezüglich Epidemiologie und Versorgungsrealität getrennt nach Adeno- und Plattenepithelkarzinom untersucht.

Ergebnisse

Zwischen 2000 und 2018 wurden 3207 Ösophaguskarzinome im Krebsregister dokumentiert, davon waren 2182 Plattenepithelkarzinome (ESCC), 843 Adenokarzinome (EAC) und 182 verschiedene andere oder fehlende Histologien. Im Beobachtungszeitraum zeigte sich eine deutliche Dominanz der ESCC, jedoch mit einer signifikanten Zunahme der EAC bei beiden Geschlechtern. Die Neuerkrankungsrate war insgesamt für Männer 5fach höher als für Frauen. Die relative 5‑Jahres-Überlebenswahrscheinlichkeit aller Ösophaguskarzinome lag bei Männern bei 17,4 % und bei Frauen bei 22,5 %. Patienten mit EAC überlebten signifikant länger als mit ESCC. Als Therapiemethoden kamen überwiegend Strahlen- und Chemotherapie, einzeln oder in Kombination, zum Einsatz. Operiert wurden 19 % der Plattenepithel- und 42 % der Adenokarzinome.

Schlussfolgerung

Der Anteil der ESCC ist in Brandenburg immer noch deutlich höher als der der EAC, wobei für Letztere, insbesondere bei Männern, ein signifikanter Anstieg zu verzeichnen ist. Obwohl lokal fortgeschrittene Tumoren deutlich häufiger auftraten, sind moderne neoadjuvante Konzepte bisher selten dokumentiert und obwohl die Qualität der Operationen mit dem internationalen Standard vergleichbar ist, werden nur relativ wenige Patienten operiert.
Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC
Authors: Kono Yuko , Piscaglia F. , Wilson S. R. , Medellin A. , Rodgers S. K. , Planz V. , Kamaya A. , Fetzer D. T. , Berzigotti A. , Sidhu P. S. , Wessner C. E. , Bradigan K. , Kuon Yeng Escalante Cristina M. , Siu Xiao T. , Eisenbrey J. R. , Forsberg F. , Lyshchik A. ,   CEUS LI-RADS Trial Group, Yusuf Gibran T. , Suddle Abid , Rafailidis Vasileios D. , Mulazzani Lorenzo , Granito Alessandro , Terzi Eleonora , Forgione Antonella , Giamperoli Alice , Stefanini Bernardo , Radu Iuliana-Pompilia , Finch Lisa , Singal Amit G.
Published: June 2024

Background

Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive.

Methods

A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3).

Results

75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct.

Conclusion

CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging.

ClinicalTrials.gov number, NCT03318380.
A new deep neural network for forecasting: Deep dendritic artificial neural network
Authors: Egrioglu Erol , Bas Eren
Published: June 2024

Deep artificial neural networks have become a good alternative to classical forecasting methods in solving forecasting problems. Popular deep neural networks classically use additive aggregation functions in their cell structures. It is available in the literature that the use of multiplicative aggregation functions in shallow artificial neural networks produces successful results for the forecasting problem. A type of high-order shallow artificial neural network that uses multiplicative aggregation functions is the dendritic neuron model artificial neural network, which has successful forecasting performance. In this study, the transformation of the dendritic neuron model turned into a multi-output architecture. A new dendritic cell based on the multi-output dendritic neuron model and a new deep artificial neural network is proposed. The training of this new deep dendritic artificial neural network is carried out with the differential evolution algorithm. The forecasting performance of the deep dendritic artificial neural network is compared with basic classical forecasting methods and some recent shallow and deep artificial neural networks over stock market time series. As a result, it has been observed that deep dendritic artificial neural network produces very successful forecasting results for the forecasting problem.
Photobiomodulation in the aging brain: a systematic review from animal models to humans
Authors: Rodríguez-Fernández Lucía , Zorzo Candela , Arias Jorge L.
Published: June 2024

Aging is a multifactorial biological process that may be associated with cognitive decline. Photobiomodulation (PBM) is a non-pharmacological therapy that shows promising results in the treatment or prevention of age-related cognitive impairments. The aim of this review is to compile the preclinical and clinical evidence of the effect of PBM during aging in healthy and pathological conditions, including behavioral analysis and neuropsychological assessment, as well as brain-related modifications. 37 studies were identified by searching in PubMed, Scopus, and PsycInfo databases. Most studies use wavelengths of 800, 810, or 1064 nm but intensity and days of application were highly variable. In animal studies, it has been shown improvements in spatial memory, episodic-like memory, social memory, while different results have been found in recognition memory. Locomotor activity improved in Parkinson disease models. In healthy aged humans, it has been outlined improvements in working memory, cognitive inhibition, and lexical/semantic access, while general cognition was mainly enhanced on Alzheimer disease or mild cognitive impairment. Anxiety assessment is scarce and shows mixed results. As for brain activity, results outline promising effects of PBM in reversing metabolic alterations and enhancing mitochondrial function, as evidenced by restored CCO activity and ATP levels. Additionally, PBM demonstrated neuroprotective, anti-inflammatory, immunomodulatory and hemodynamic effects. The findings suggest that PBM holds promise as a non-invasive intervention for enhancing cognitive function, and in the modulation of brain functional reorganization. It is necessary to develop standardized protocols for the correct, beneficial, and homogeneous use of PBM.
Finding Value in Emergency General Surgery
Authors: Follette Craig J. , Grimes Arthur D. , Detelich Danielle M. , Martin R. Shayn
Published: June 2024

Purpose of Review

Surgical practice in the United States is evolving rapidly, driven in part by high-impact technological developments, the proliferation of surgical specialization and an aging population with high demand for medical services. This has been accompanied by an unsustainable rise in healthcare costs. Hospital systems are under immense economic pressure to contain costs, maximize reimbursement while also providing high quality patient care. It is in this context that the following article describes both the development of dedicated emergency general surgery (EGS) services and the unique and essential role they have in this ever-changing healthcare system.

Recent Findings

Emergency surgical care is both costly and in high demand, placing a significant burden on providers and the overall care system. Rather than serving as a mere stopgap, EGS services function to provide expedient, specialized, and comprehensive care for critically ill patients while also reducing the burden on other surgical subspecialties.

Emergency General Surgery services are in the unique position to maximize value, without compromising quality, for the benefit of patients, providers, and the healthcare system.
Alloy modification and ultrasonic-assisted milling of wear-resistant alloys with defined surfaces
Authors: Giese M. , Graebner M. , Schroepfer D. , Treutler K. , Lorenz S. , Kannengiesser T. , Wesling V.
Published: June 2024

The reduction of CO2 emissions is closely linked to the development of highly efficient and economical steel components in plant and process engineering. To withstand the high combined corrosive, tribological, thermal, and mechanical stresses, wear-resistant coatings tailored to the application and steel grade are used. In addition to the increasing demand to substitute conventional cobalt alloys with nickel alloys, there is also a growing need for defined or functional surfaces of high integrity. Due to high tool wear, milling operations required to produce the complex geometries of the components are often not economically feasible for SMEs. By means of alloy modification of the filler metals for nickel-based plasma build-up welded wear-resistant coatings and by the use of innovative ultrasonic-assisted milling processes more favourable machinability shall be achieved without reducing the wear protection potential. In this paper, the influence of the microstructure and precipitation morphology adjusted by means of alloy modification on the machinability is investigated. This is done based on a wear protection alloy NiCrMoSiFeB (trade name: Colmonoy 56 PTA) typically used for screw machines, which substitutes conventional CoCr alloys (Stellite). Metallurgical investigations and in-situ measurements of occurring process forces and temperatures at the tool cutting edge during milling as well as subsequent investigations of tool wear and surface integrity allow a detailed analysis and correlation between microstructural properties and machinability. For the cast samples, a clear change in the microstructure and hardness can be seen through the addition of Al, Ti, or Nb. These differences lead to an improvement in the machining process for Nb. Al and Ti cause long-needled or star-shaped precipitations and hardness increases, which lead to higher cutting forces and increased tool wear.
Grandparents “on board”: How they translate into the households’ fertility decisions
Authors: Chybalski Filip , Marcinkiewicz Edyta
Published: June 2024

We test whether the co-residence of older parents with their adult children of reproductive age increases the chance of them forming a multichild family. Using data from Wave X of the Luxembourg Wealth Study (LWS) and multinomial logistic regression, we model the number of children using the binary variable informing if there is an older household member (or not) as the main predictor and controlling for other socio-economic household attributes. Our data set covers 11 European countries. The results do not support the view that intergenerational households in which an elderly person lives include more children. Thus, we do not find evidence that the co-residence of two adult generations of pensioner parents and their working-age children translates into the households’ fertility decisions and stimulates growth in the number of multichild families. What can affect it is the gender equality policy facilitating solving the motherhood–work conflict for families and women.
Spatial modelling of present and future groundwater potentials in Nigeria; towards a sustainable water demand and supply
Authors: Ibrahim Esther Shupel , Chiroma Joseph Timothy , Abubakar Musa Akin , Ojih Samuel Achonu , Waziri Edmond Sunabiji , Daffi Rose Edwin , Yenne Ezekiel
Published: June 2024

The development of water resources in Nigeria has not risen alongside population increase. Although groundwater is the available source of water at all locations in Nigeria, groundwater aquifer is becoming deeper due to increased groundwater harvest, especially in urban areas. There is a need for continuous groundwater modelling using geological, climatic, environmental data, and spatial tools especially under climate change and intense landcover conversions. The Spatial Multi-Criteria Analysis (SMCA) was adopted in this study to model the current groundwater potential in Nigeria. The multi-criteria analysis tool in ArcGIS was explored to overlay the nine factor maps to model historic and futuristic groundwater potentials. Our groundwater factor maps show an interesting pattern across Nigeria, the southern parts show more potential considering suitability factors like; surface water density, rainfall, temperature, soil, land cover and elevation in the region. Whereas the upland regions even with higher rainfall and lower temperatures suitable for groundwater recharge, are disadvantaged by geomorphological factors. Northern part of Nigeria shows high potentials, considering the geology, soil, lineament density and slope, but disadvantaged by other factors like lower rainfall and higher temperatures. This informed the final groundwater potential maps; results for the historic potential revealed that, no location in Nigeria has optimal (9–10), very poor or no (1–2) groundwater potential. The results further revealed that areas with higher groundwater potentials are largely within the corridors of major rivers in Nigeria (Niger and Benue), covering about 17.6% of the Nigerian landmass, while 2.6%, 33.7, 44% and 2.2% are occupy areas with very low, low, moderate and very high groundwater potentials respectively. Further analysis highlighs locations of concern due to climatic and environmental changes. Interestingly, our groundwater projection results show a persistent increase in groundwater potential from 2021 to 2100 if current landuses and environmental factors are maintained, and if the projected increase in rainfall is true. Despite these groundwater potentials, the recent issues of shallow aquifers have been cautioned by scientists, especially due to groundwater uncertainties in Nigeria especially with intense landcover conversions, combined with accelerated water demands due to increase in population, and incessant groundwater extractions. Therefore, there is a need to seek caution in the pattern of unregulated and incessant groundwater harvest in Nigeria and we recommend frequent updates of the groundwater potential using geospatial tools to inform governing policies on a centralised consolidated sustainable water supply in Nigeria.
World of the Right
Authors: Abrahamsen Rita , Drolet Jean-François , Williams Michael C. , Vucetic Srdjan , Narita Karin , Gheciu Alexandra
Published: June 2024

The contemporary radical Right is not merely a series of nationalist projects but a global phenomenon. This book shows how radical conservative thinkers have developed long-term counter-hegemonic strategies that challenge prevailing social and political orders both nationally and internationally. At the heart of this ideological project is a critique of liberal globalisation that seeks to mobilise transversal alliances against a common enemy: the 'New Class' of global managerial elites who are accused of undermining national sovereignty, traditional values, and cultures. 'World of the Right' argues that while the radical Right is far from a unified political movement, its calls for sovereignty, civilisational orders, and multipolarity enable complex, strategic convergences with illiberal states such as China and Russia, as well as states and people in the Global South. The potential consequences for the future of the liberal world order are profound and wide-ranging.
Impact of Dust Source Patchiness on the Existence of a Constant Dust Flux Layer During Aeolian Erosion Events
Authors: Dupont S. , Klose M. , Irvine M. R. , González‐Flórez C. , Alastuey A. , Bonnefond J.‐M. , Dagsson‐Waldhauserova P. , Gonzalez‐Romero A. , Hussein T. , Lamaud E. , Meyer H. , Panta A. , Querol X. , Schepanski K. , Vergara Palacio S. , Wieser A. , Yus‐Díez J. , Kandler K. , Pérez García‐Pando C.
Published: June 2024

Dust emission fluxes during wind soil erosion are usually estimated using a dust concentration vertical gradient, by assuming a constant dust flux layer between the surface and the dust measurement levels. Here, we investigate the existence of this layer during erosion events recorded in Iceland and Jordan. Size‐resolved dust fluxes were estimated at three levels between 2 and 4 m using the eddy‐covariance method. Dust fluxes were found mainly constant only between the two upper levels in Iceland, the lower dust flux being often stronger and richer in coarse particles, while dust fluxes in Jordan were nearly constant across all levels. The wind dynamics could not explain the absence of a constant dust flux layer in Iceland. We show that the presence of stationary dust source patches in Iceland, related to surface humidity, created a non‐uniform dust layer near the surface, named dust roughness sublayer (DRSL), where individual plumes behind each patch interact but do not fully mix. The lowest dust measurement level was probably located within this sublayer while the upper ones were located above, such that there the emitted dust became spatially well‐mixed. This explains near the surface in Iceland, the more intermittent dust concentration, its low correlation with the dust concentrations above, and the richer dust flux in coarse particles due to their lower deposition contribution. Our findings highlight the importance of estimating dust fluxes above a dust blending height whose characteristics depend on the dust source patchiness caused by surface humidity or the presence of sparse non‐erosive elements.
Viewing Soil Moisture Flash Drought Onset Mechanism and Their Changes Through XAI Lens: A Case Study in Eastern China
Authors: Feng Jiajin , Li Jun , Xu Chong‐Yu , Wang Zhaoli , Zhang Zhenxing , Wu Xushu , Lai Chengguang , Zeng Zhaoyang , Tong Hongfu , Jiang Shijie
Published: June 2024

Soil moisture flash droughts often pose significant challenges to humans and ecosystems, with wide‐ranging socioeconomic consequences. However, the underlying mechanisms of flash droughts and their changes remain unquantified. Taking China as a case study, we present a novel framework that combines machine learning with interpretable and cluster techniques to investigate flash drought mechanisms from 1980 to 2018. We first quantified the temporal contribution of drivers and further identified different mechanisms during drought onsets. We subsequently investigated the temporal changes in different mechanisms and classified drought event types. We identified four driving mechanism types triggering drought: Concurrent precipitation, Antecedent‐concurrent precipitation, Antecedent temperature‐concurrent precipitation, and Antecedent transpiration‐concurrent precipitation. The total effects from vegetation transpiration contributed to around 50% of the impacts for mechanisms involving antecedent transpiration and concurrent precipitation, highlighting the non‐neglectable role of vegetation water consumption in drought occurrences. Remarkably, about 60% of flash drought onsets exhibited close association with the antecedent anomalies, which contribute approximately 50% of overall effects, emphasizing the importance of the cumulative effects of drivers. Moreover, driving mechanisms associated with temperature and transpiration increased significantly over time, implying an elevated influence of these factors on droughts. Our classification of drought events reveals that nearly 70% of events were driven by at least two mechanisms, underscoring a complex time‐varying pattern of driving factors during drought events. The proposed holistic framework not only sheds insight into the multifaceted mechanisms driving flash droughts within China but also extends its potential applicability to broader geographical contexts.
The Essential Role of Local Context in Shaping Risk and Risk Reduction Strategies for Snowmelt‐Dependent Irrigated Agriculture
Authors: Gordon Beatrice L. , Boisrame Gabrielle F. S. , Carroll Rosemary W. H. , Ajami Newsha K. , Leonard Bryan , Albano Christine , Mizukami Naoki , Andrade Manuel A. , Koebele Elizabeth , Taylor Michael H. , Harpold Adrian A.
Published: June 2024

Climate change‐induced shifts in snow storage and snowmelt patterns pose risks for adverse impacts to people, the environment, and irrigated agriculture. Existing research primarily focuses on evaluating these risks to irrigated agriculture at large scales, overlooking the role of local context in shaping risk dynamics. Consequently, many “at‐risk” areas lack insight into how adaptation strategies for managing risk through water supply augmentation or water conservation vary across contexts and over time. To address this gap, we develop a comprehensive index for evaluating irrigated agriculture's risk and adaptation potential to changes in snow at local scales and apply it throughout the western US. Results confirm trends toward escalating risk for changes in snow storage and snowmelt patterns over the century. However, substantial heterogeneity in the extent and drivers of risk exists due to variability in localized interactions between declines in water supply (approximately −9% ± 13% by 2100) and increased agricultural demand (approximately 7% ± 5% by 2100). Despite an existing focus on supply augmentation as a critical adaptation strategy to reduce risk, we show its effectiveness diminishes for many areas over time, declining to an average of −54% of historical augmentation potential by 2100. Conserving water through historical changes in crop acreage and type emerges as a more stable adaptation measure, reducing demand by 7%–8% regardless of time. While particularly relevant for higher elevation, less intensive agricultural settings in snowmelt‐dependent regions, findings underscore the need for strategies that support local‐scale, context‐appropriate adaptation to effectively manage escalating risk as snow changes.
How Tiny Cracks Lead to Large-Scale Faults
Authors: Stanley Sarah
Published: June 2024

Researchers could soon gain new insights into fault development in Earth’s brittle crust, thanks to a computational approach that harnesses experimental observations of microscale rock damage.
Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer
Authors: Yang Yun , Liu Qingya , Wang Meng , Li Lang , Yu Yan , Pan Meng , Hu Danrong , Chu Bingyang , Qu Ying , Qian Zhiyong
Published: June 2024

Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens, including prolonged circulation in the bloodstream, specific cell recognition and targeting capabilities, and potential for immunotherapy. Herein, we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM NPs. Comprising microporous Prussian blue nanoparticles (MPB NPs) serving as both a photothermal sensitizer and carrier for 3-bromopyruvate (3BP), these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory protein α (SIRPα) with enhanced affinity to CD47. As a result, MPB-3BP@CM NPs inherit the characteristics of the original cell membrane, exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer (CRC) cells. Notably, blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by macrophages. Additionally, 3BP, an inhibitor of hexokinase II (HK2), suppresses glycolysis, leading to a reduction in adenosine triphosphate (ATP) levels and lactate production. Besides, it promotes the polarization of tumor-associated macrophages (TAMs) towards an anti-tumor M1 phenotype. Furthermore, integration with MPB NPs-mediated photothermal therapy (PTT) enhances the therapeutic efficacy against tumors. These advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for CRC. Concurrently, it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.
Single-cell sequencing depicts tumor architecture and empowers clinical decision in metastatic conjunctival melanoma
Authors: Shi Hanhan , Tian Hao , Zhu Tianyu , Liao Qili , Liu Chang , Yuan Peng , Li Yongyun , Yang Jie , Zong Chunyan , Jia Shichong , Ruan Jing , Ge Shengfang , Jia Renbing , Chai Peiwei , Xu Shiqiong , Fan Xianqun
Published: June 2024

Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8+ T cells and an increase in the proportion of naive CD8+ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.
DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics
Authors: Rahimi Arezou , Vale-Silva Luis A. , Fälth Savitski Maria , Tanevski Jovan , Saez-Rodriguez Julio
Published: June 2024

Single-cell transcriptomics and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. However, they suffer from lack of spatial information and a trade-off of resolution and gene coverage, respectively. We propose DOT, a multi-objective optimization framework for transferring cellular features across these data modalities, thus integrating their complementary information. DOT uses genes beyond those common to the data modalities, exploits the local spatial context, transfers spatial features beyond cell-type information, and infers absolute/relative abundance of cell populations at tissue locations. Thus, DOT bridges single-cell transcriptomics data with both high- and low-resolution spatially-resolved data. Moreover, DOT combines practical aspects related to cell composition, heterogeneity, technical effects, and integration of prior knowledge. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data.
Space radiation damage rescued by inhibition of key spaceflight associated miRNAs
Authors: McDonald J. Tyson , Kim JangKeun , Farmerie Lily , Johnson Meghan L. , Trovao Nidia S. , Arif Shehbeel , Siew Keith , Tsoy Sergey , Bram Yaron , Park Jiwoon , Overbey Eliah , Ryon Krista , Haltom Jeffrey , Singh Urminder , Enguita Francisco J. , Zaksas Victoria , Guarnieri Joseph W. , Topper Michael , Wallace Douglas C. , Meydan Cem , Baylin Stephen , Meller Robert , Muratani Masafumi , Porterfield D. Marshall , Kaufman Brett , Mori Marcelo A. , Walsh Stephen B. , Sigaudo-Roussel Dominique , Mebarek Saida , Bottini Massimo , Marquette Christophe A. , Wurtele Eve Syrkin , Schwartz Robert E. , Galeano Diego , Mason Christopher E. , Grabham Peter , Beheshti Afshin
Published: June 2024

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.
Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling
Authors: Saunders Nell , Monel Blandine , Cayet Nadège , Archetti Lorenzo , Moreno Hugo , Jeanne Alexandre , Marguier Agathe , Buchrieser Julian , Wai Timothy , Schwartz Olivier , Fréchin Mathieu
Published: June 2024

Assessing the impact of SARS-CoV-2 on organelle dynamics allows a better understanding of the mechanisms of viral replication. We combine label-free holotomographic microscopy with Artificial Intelligence to visualize and quantify the subcellular changes triggered by SARS-CoV-2 infection. We study the dynamics of shape, position and dry mass of nucleoli, nuclei, lipid droplets and mitochondria within hundreds of single cells from early infection to syncytia formation and death. SARS-CoV-2 infection enlarges nucleoli, perturbs lipid droplets, changes mitochondrial shape and dry mass, and separates lipid droplets from mitochondria. We then used Bayesian network modeling on organelle dry mass states to define organelle cross-regulation networks and report modifications of organelle cross-regulation that are triggered by infection and syncytia formation. Our work highlights the subcellular remodeling induced by SARS-CoV-2 infection and provides an Artificial Intelligence-enhanced, label-free methodology to study in real-time the dynamics of cell populations and their content.
Lanthanide-regulating Ru-O covalency optimizes acidic oxygen evolution electrocatalysis
Authors: Li Lu , Zhang Gengwei , Zhou Chenhui , Lv Fan , Tan Yingjun , Han Ying , Luo Heng , Wang Dawei , Liu Youxing , Shang Changshuai , Zeng Lingyou , Huang Qizheng , Zeng Ruijin , Ye Na , Luo Mingchuan , Guo Shaojun
Published: June 2024

Precisely modulating the Ru-O covalency in RuOx for enhanced stability in proton exchange membrane water electrolysis is highly desired. However, transition metals with d-valence electrons, which were doped into or alloyed with RuOx, are inherently susceptible to the influence of coordination environment, making it challenging to modulate the Ru-O covalency in a precise and continuous manner. Here, we first deduce that the introduction of lanthanide with gradually changing electronic configurations can continuously modulate the Ru-O covalency owing to the shielding effect of 5s/5p orbitals. Theoretical calculations confirm that the durability of Ln-RuOx following a volcanic trend as a function of Ru-O covalency. Among various Ln-RuOx, Er-RuOx is identified as the optimal catalyst and possesses a stability 35.5 times higher than that of RuO2. Particularly, the Er-RuOx-based device requires only 1.837 V to reach 3 A cm−2 and shows a long-term stability at 500 mA cm−2 for 100 h with a degradation rate of mere 37 μV h−1.
Supercooled erythritol for high-performance seasonal thermal energy storage
Authors: Yang Sheng , Shi Hong-Yi , Liu Jia , Lai Yang-Yan , Bayer Özgür , Fan Li-Wu
Published: June 2024

Seasonal storage of solar thermal energy through supercooled phase change materials (PCM) offers a promising solution for decarbonizing space and water heating in winter. Despite the high energy density and adaptability, natural PCMs often lack the necessary supercooling for stable, long-term storage. Leveraging erythritol, a sustainable mid-temperature PCM with high latent heat, we introduce a straightforward method to stabilize its supercooling by incorporating carrageenan (CG), a bio-derived food thickener. By improving the solid-liquid interfacial energy with the addition of CG the latent heat of erythritol can be effectively locked at a very low temperature. We show that the composite PCM can sustain an ultrastable supercooled state below −30 °C, which guarantees no accidental loss of the latent heat in severe cold regions on Earth. We further demonstrate that the common ultrasonication method can be used as the key to unlocking the latent heat stored in the CG-thickened erythritol, showing its great potential to serve as a high-performance, eco-friendly PCM for long-term seasonal solar energy storage.
Electroreductive alkylations of (hetero)arenes with carboxylic acids
Authors: Wang Bing , Huang Xianshuai , Bi Huihua , Liu Jie
Published: June 2024

Carboxylic acids are widely available and generally inexpensive from abundant biomass feedstocks, and they are suitable and generic coupling partners in synthetic chemistry. Reported herein is an electroreductive coupling of stable and versatile carboxylic acids with (hetero)arenes using protons as the hydrogen source. The application of an earth-abundant titanium catalyst has significantly improved the deoxygenative reduction process. Preliminary mechanistic studies provide insights into the deoxygenative reduction of in-situ generated ketone pathway, and the intermediacy generation of ketyl radical and alkylidene titanocene. Without the necessity of pressurized hydrogen or stoichiometric hydride as reductants, this protocol enables highly selective and straightforward synthesis of various functionalized and structurally diverse alkylbenzenes under mild conditions. The utility of this reaction is further demonstrated through practical and valuable isotope incorporation from readily available deuterium source.
Targeting mosquito X-chromosomes reveals complex transmission dynamics of sex ratio distorting gene drives
Authors: Haber Daniella An , Arien Yael , Lamdan Lee Benjamin , Alcalay Yehonathan , Zecharia Chen , Krsticevic Flavia , Yonah Elad Shmuel , Avraham Rotem Daniel , Krzywinska Elzbieta , Krzywinski Jaroslaw , Marois Eric , Windbichler Nikolai , Papathanos Philippos Aris
Published: June 2024

Engineered sex ratio distorters (SRDs) have been proposed as a powerful component of genetic control strategies designed to suppress harmful insect pests. Two types of CRISPR-based SRD mechanisms have been proposed: X-shredding, which eliminates X-bearing sperm, and X-poisoning, which eliminates females inheriting disrupted X-chromosomes. These differences can have a profound impact on the population dynamics of SRDs when linked to the Y-chromosome: an X-shredder is invasive, constituting a classical meiotic Y-drive, whereas X-poisoning is self-limiting, unable to invade but also insulated from selection. Here, we establish X-poisoning strains in the malaria vector Anopheles gambiae targeting three X-linked genes during spermatogenesis, resulting in male bias. We find that sex distortion is primarily driven by a loss of X-bearing sperm, with limited evidence for postzygotic lethality of female progeny. By leveraging a Drosophila melanogaster model, we show unambiguously that engineered SRD traits can operate differently in these two insects. Unlike X-shredding, X-poisoning could theoretically operate at early stages of spermatogenesis. We therefore explore premeiotic Cas9 expression to target the mosquito X-chromosome. We find that, by pre-empting the onset of meiotic sex chromosome inactivation, this approach may enable the development of Y-linked SRDs if mutagenesis of spermatogenesis-essential genes is functionally balanced.
Characterizing dehydration in short-term spaceflight using evidence from Project Mercury
Authors: Reynolds Robert J. , Shelhamer Mark , Antonsen Erik L. , Carpentier William R.
Published: June 2024

Short-term spaceflight is commonly perceived as posing minimal risk to human health and performance. However, despite their duration, short-term flights potentially induce acute physiological changes that create risk to crews. One such change is dehydration (primarily body water loss) due to a heat-stressed environment. Such loss, if severe and prolonged, can lead to decrements in performance as well as increase the risk of more serious medical conditions. Though the general mechanisms of dehydration are broadly understood, the rate and extent of dehydration in short-term spaceflight has not been characterized. Combining data from the six spaceflights of the US Mercury program with a causal diagram illustrating the mechanisms of dehydration, we fit a path model to estimate the causal effects for all pathways in the causal model. Results demonstrate that Mercury astronauts experienced some degree of dehydration across the range of suited time and that the relationship between suited time and dehydration appears to be logarithmic. We discuss causal interpretations of the results and how the results from this and similar analyses can inform countermeasure development for short-term spaceflight.
Deep-learning-enabled antibiotic discovery through molecular de-extinction
Authors: Wan Fangping , Torres Marcelo D. T. , Peng Jacqueline , de la Fuente-Nunez Cesar
Published: June 2024

Molecular de-extinction aims at resurrecting molecules to solve antibiotic resistance and other present-day biological and biomedical problems. Here we show that deep learning can be used to mine the proteomes of all available extinct organisms for the discovery of antibiotic peptides. We trained ensembles of deep-learning models consisting of a peptide-sequence encoder coupled with neural networks for the prediction of antimicrobial activity and used it to mine 10,311,899 peptides. The models predicted 37,176 sequences with broad-spectrum antimicrobial activity, 11,035 of which were not found in extant organisms. We synthesized 69 peptides and experimentally confirmed their activity against bacterial pathogens. Most peptides killed bacteria by depolarizing their cytoplasmic membrane, contrary to known antimicrobial peptides, which tend to target the outer membrane. Notably, lead compounds (including mammuthusin-2 from the woolly mammoth, elephasin-2 from the straight-tusked elephant, hydrodamin-1 from the ancient sea cow, mylodonin-2 from the giant sloth and megalocerin-1 from the extinct giant elk) showed anti-infective activity in mice with skin abscess or thigh infections. Molecular de-extinction aided by deep learning may accelerate the discovery of therapeutic molecules.
Self-administered mindfulness interventions reduce stress in a large, randomized controlled multi-site study
Authors: Sparacio Alessandro , IJzerman Hans , Ropovik Ivan , Giorgini Filippo , Spiessens Christoph , Uchino Bert N. , Landvatter Joshua , Tacana Tracey , Diller Sandra J. , Derrick Jaye L. , Segundo Joahana , Pierce Jace D. , Ross Robert M. , Francis Zoë , LaBoucane Amanda , Ma-Kellams Christine , Ford Maire B. , Schmidt Kathleen , Wong Celia C. , Higgins Wendy C. , Stone Bryant M. , Stanley Samantha K. , Ribeiro Gianni , Fuglestad Paul T. , Jaklin Valerie , Kübler Andrea , Ziebell Philipp , Jewell Crystal L. , Kovas Yulia , Allahghadri Mahnoosh , Fransham Charlotte , Baranski Michael F. , Burgess Hannah , Benz Annika B. E. , DeSousa Maysa , Nylin Catherine E. , Brooks Janae C. , Goldsmith Caitlyn M. , Benson Jessica M. , Griffin Siobhán M. , Dunne Stephen , Davis William E. , Watermeyer Tam J. , Meese William B. , Howell Jennifer L. , Standiford Reyes Laurel , Strickland Megan G. , Dickerson Sally S. , Pescatore Samantha , Skakoon-Sparling Shayna , Wunder Zachary I. , Day Martin V. , Brenton Shawna , Linden Audrey H. , Hawk Christopher E. , O’Brien Léan V. , Urgyen Tenzin , McDonald Jennifer S. , van der Schans Kim Lien , Blocker Heidi , Ng Tseung-Wong Caroline , Jiga-Boy Gabriela M.
Published: June 2024

Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ; retrospective registration at ClinicalTrials.gov NCT06308744) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = −0.56; 95% confidence interval, −0.43 to −0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries.