bluuebunny/crossref_metadata_2025 huggingface dataset:
The Penalty of Party on Black Homeownership: The Impacts of Judicial Institutional Settings on the Black Political Economy
Authors: Roberson Kendrick B.
Published: January 2024

Black homeownership declines across the U.S.A. at significantly higher rates than white, Hispanic, or Asian homeownership. Although the cost to own a home is lower in Republican states, Black Americans are much less likely to maintain homeownership in those areas. This article attempts to gain leverage on the following question: “what is the penalty of political parties on Black homeownership in America?” The findings presented here provide support to the notion that there is a nationwide penalty of political parties on Black homeownership. The variation in this penalty is dependent on a given state’s opportunity structure for institutional racism, which changes based on the state’s foreclosure laws and partisan leanings. To support the nationwide findings, this article provides a case study on Black homeownership across the state of New York’s judicial districts with 221 partisan-elected judges, revealing that there remains a penalty in Republican judicial districts. Previous scholarship has analyzed the relationship between parties and foreclosures, as well as the relationship between race and foreclosures. This article assesses the intertwined relationship of parties, race, and foreclosures.
The seeds of success: the pivotal role of first round cooperation in public goods games
Authors: Gürdal Mehmet Y. , Torul Orhan , Yahşi Mustafa
Published: January 2024

This paper examines cooperation and punishment in a public goods game in Istanbul. Unlike prior within-subject designs, we use a between-subject design with separate no-punishment and punishment conditions. This approach reveals that punishment significantly increases contributions, demonstrating the detrimental effect of having prior experience without sanctions. We highlight two critical factors—heterogeneous initial contributions across groups and how subjects update their contributions based on prior contributions and received punishment. An agent-based model verifies that the interaction between these two factors leads to a strong persistence of contributions over time. Analysis of related data from comparable cities shows similar patterns, suggesting our findings likely generalize if using a between-subject design. We conclude that overlooking within-group heterogeneity biases cross-society comparisons and subsequent policy implications.
Mechanically Joined Extrusion Profiles for Battery Trays
Authors: Kneuper Florian , Neumann Stefan , Schulze André , Otroshi Mortaza , Tekkaya A. Erman , Meschut Gerson
Published: January 2024

In the context of electromobility, ensuring the leak tightness of assemblies is of paramount importance, particularly in battery housings. Current battery housings, often featuring base assemblies crafted from extruded aluminum profiles, address the challenge of leak tightness at joints through methods like friction stir welding, a process known for its time and cost intensiveness. The aim of this study is to develop and implement a new type of extruded profile concept to produce tight base assemblies for battery housings by a longitudinal mechanical single stroke joining process. The geometry, the process and the properties of the aluminum profiles are investigated to get a joint that meets the tightness requirements and achieve high load-bearing capacities in agreement with the high homologation requirements set to vehicles with high-voltage systems. The joint is formed by means of a single stage press stroke, which eliminates the need for complex tool designs that are necessary for continuous joining (roll joining). Flat steel contact surfaces are used as joining tools. To evaluate the joint quality, force curves from the joining process are analyzed and the resulting joint geometries are assessed using micrographs. The resulting leak tightness of the linear joints is measured by a helium sniffer leak detector and the load-bearing capacities are investigated by shear lap and bending tests and fatigue strength test. The study also explores whether a difference in strength between the two joining partners has a positive effect on the joint properties.
Preparation and evaluation of ecofriendly nanocreams containing some plant essential oils and monoterpenes against adults of Culex pipiens L. with some biochemical and histological studies on albino rat
Authors: Taktak Nehad E. M. , Badawy Mohamed E. I. , Awad Osama M. , Abou El-Ela Nadia E. , Aborhyem Samar M.
Published: January 2024

Plant essential oils (EOs) are considered a vital tool of novel natural mosquito repellents and botanical adulticides. Five plant EOs (cinnamon, cypress, lavender, lemon eucalyptus and tea tree) and their major constituents (cinnamaldehyde, citronellal, β-cymene, (R)-linalool, and α-terpinyl acetate) were investigated against adults of Culex pipiens. The efficacy of the tested compounds was manipulated as mortality and knockdown using a fumigation technique. After that, the most active compounds against adults (lemon eucalyptus oil and linalool) were investigated once more as repellents after incorporating them on a cream base against C. pipiens adults compared to their nano-cream using arm-in-cage technique. In addition, the biochemical and histological effects of dermal treatment of linalool, lemon eucalyptus,, and their nanoemulsions (NEs) were studied on male albino rats. Total protein assay, acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), and liver and kidney functions were determined in blood serum. Complete blood count (CBC) was determined in whole blood. The results showed that lemon eucalyptus oil and (R)-linalool caused the highest knockdown activity against C. pipiens adults with Kt50 40.29 s and 12.73 s, respectively. The repellent effect (RC50) of nanocream formulations of lemon eucalyptus oil (10.03 mg/L) and (R)-linalool (68.11 mg/L) were higher than the original effects of these compounds with RC50 values = 100.82 mg/L and 998.54 mg/L, respectively. There are no obvious harmful side effects of the dermal topical treatments of (R)-linalool and lemon eucalyptus oil on the tested biochemical parameters of treated albino rats compared with the control. Furthermore, there are no obvious effects of the dermal topical treatments of (R)-linalool and lemon eucalyptus oil on the histological status of the treated skin of albino rats compared with untreated treatment. The tested oils and monoterpenes could be considered promising candidates for botanical adulticides against C. pipiens. Also, nano-cream of lemon eucalyptus oil and (R)-linalool could be considered promising ecofriendly repellents for C. pipiens adults.
A LDA-Based Social Media Data Mining Framework for Plastic Circular Economy
Authors: Xue Yangyimin , Kambhampati Chandrasekhar , Cheng Yongqiang , Mishra Nishikant , Wulandhari Nur , Deutz Pauline
Published: January 2024

The mass production of plastic waste has caused an urgent worldwide public health crisis. Although government policies and industrial innovation are the driving forces to meet this challenge, trying to understand public attitudes may improve the efficiency of this process. Social media has become the main ways for the public to obtain information and express opinions and feelings. This motivated us to mine the perceptions and behavioral responses towards plastic usage using social media data. In this paper, we proposed a framework for data collection and analysis based on mainstream media in the UK to obtain public opinions on plastics. An unsupervised machine learning model based on Latent Dirichlet Allocation (LDA) has been employed to analyse and cluster the topics to deal with the lack of annotation of the data contents. An additional dictionary method was then proposed to evaluate the sentiment of the comments. The framework also provides tools to visualise the model and results to stimulate insightful understandings. We validated the framework's effectiveness by applying it to analyse three mainstream social media, where 6 first-level topic categories and 13 second-level topic categories from the comment texts related to plastics have been identified. The results show that public sentiment towards plastic products is generally stable. The spatiotemporal distribution of each topic's sentiment is highly correlated with the number of occurrences.
Investigating the past, present and future responses of Shallap and Zongo Glaciers, Tropical Andes, to the El Niño Southern Oscillation
Authors: Richardson Alasdair , Carr Rachel , Cook Simon
Published: January 2024

Tropical Andean glaciers are highly sensitive to climate change and are impacted by the El Niño Southern Oscillation (ENSO). However, glaciological data are scarce, meaning that there are substantial knowledge gaps in the response of Andean glaciers to future anthropogenic and ENSO forcing and these are crucial to address, as glaciers represent a key water source for downstream populations and ecosystems. Here we integrated data from glaciological field studies, remote sensing, statistical analysis and glacier modelling to analyse the response of two Andean glaciers (Zongo and Shallap) to ENSO and their potential sensitivity to a range of climate forcing scenarios. Both glaciers retreated and experienced increasingly negative mass balance between the 1990s and the 2010s and responded strongly and rapidly to contemporary ENSO forcing, although this relationship evolved over time. Sensitivity experiments demonstrate that Shallap and Zongo are highly sensitive to ENSO forcing scenarios and the combination of ENSO and climate warming can cause rapid ice loss under the most extreme scenarios. Results also demonstrate the strong sensitivity of both glaciers to changes in the equilibrium line altitude, whereby rapid ice loss occurred when melt extended into present-day accumulation areas.
Fortification or biofortification: complimentary strategies or duplication of effort?
Authors: Lowe Nicola Mary
Published: January 2024

Micronutrient deficiencies continue to be a global concern, with the most common deficiencies being vitamin A, iron, zinc and B vitamins (folate and B12). Addressing this requires strategies that are scalable and equitable such that they reach all members of a population irrespective of socioeconomic status and geography. Fortification and biofortification offer potential large-scale solutions, however each have strengths and limitations depending on the context, particularly the cultural and political factors that may create barriers or opportunities for effectiveness. Planning how to target scarce resources for maximum impact requires an in-depth knowledge and understanding of local food systems and market dynamics, alongside strong government policy and legislative support. A food fortification programme was launched in Pakistan in 2016, supported by UK Aid and designed to address the high prevalence of vitamin A, iron and zinc deficiency, particularly in women and children. In the same year, the first zinc biofortified variety of wheat, Zincol-2016, was released in Pakistan, supported and developed through the HarvestPlus programme in collaboration with the Pakistan National Agriculture Research Centre. This review explores the challenges faced by fortification and biofortification, initiated independently, (but around the same time) in Pakistan.
Licit or Illicit? Encroachments on ‘the Lord’s Waste’ in North-east Scotland, c.1400 – c.1800
Authors: Shepherd Colin
Published: January 2024

This paper seeks to show that encroachments in the North-east resulted from a range of social and economic drivers. Encroachments were enacted by members of a wide social spectrum, resulting in both top-down and bottom-up manifestations of engrossment of holdings. In this respect, it may be argued, North-east encroachments have a distinctive nature compared to English enclosures. The factors effecting encroachment can be seen to relate to topographic opportunism, demographic fluctuation, and a socio-agricultural environment that was already well-attuned to utilising dynamic settlement fluctuations for social and economic benefits. Only after the enactment of the 1695 Division of the Commonties Act did the socially diverse nature of such encroachment become increasingly monopolised by the landed gentry and began to reflect more closely English enclosure.
Solving heterogeneous-belief asset pricing models with short-selling constraints and many agents
Authors: Hatcher Michael
Published: January 2024

Short-selling constraints are common in financial markets, while physical assets such as housing often lack markets for short-selling altogether. As a result, investment decisions are often restricted by such constraints. This paper studies asset prices in behavioral heterogeneous-belief models with short-selling constraints and arbitrarily many belief types. We provide conditions on beliefs such that short-selling constraints bind for different types, along with analytic expressions for price and demands that allow us to construct fast solution algorithms relevant for a wide range of models. An application studies how an alternative uptick rule, as in the United States, affects price dynamics and wealth distribution in a market with many belief types in evolutionary competition. In a numerical example, we highlight a scenario in which a modified version of the alternative uptick rule, triggered by smaller percentage falls in price, reduces both asset mispricing and wealth inequality relative to the current regulation. As extensions, we show how our method applies to multiple asset markets with short-selling constraints, additional heterogeneities, and price setting by a market maker.
Cross-language semantic-affective interaction – with evidence from Chinese EFL learners
Authors: Ye Xuanchen , Zhao Cuilian
Published: January 2024

Semantic and affective priming have long been treated separately in psycholinguistic studies. Recently, however, the question of whether and how these two primings interact has become controversial, especially in cross-language contexts where such discussions are rare. In the present study, four mixed-design experiments were conducted with Chinese EFL learners to investigate cross-language semantic-affective interactions: 3 (prime valence: negative, positive, neutral) × 2 (semantic relatedness: related, unrelated). Results show that semantic priming effects occurred in the L1L1 and L1L2 conditions, whereas affective priming effects were observed in the L2L2 condition. In the L2L1 priming condition, only emotion primes induced cross-language priming. These results suggest that semantic and emotional accesses are activated automatically and separately, but can facilitate cross-language word processing mutually. The results support the hierarchical representation of semantic features of emotion words from L1 to L2 in the unbalanced bilingual mental lexicon, while affective attributes are spread across a distributed network.
Global Impact of Sea Level Rise on Coastal Fresh Groundwater Resources
Authors: Zamrsky Daniel , Oude Essink Gualbert H. P. , Bierkens Marc F. P.
Published: January 2024

Groundwater is the main freshwater source in many densely populated and industrialized coastal areas around the world. Growing future freshwater demand is likely to increase the water stress in these coastal areas, possibly leading to groundwater overexploitation and salinization. This situation will likely be aggravated by climate change and the associated projected sea level rise. Here, we assess the impact of sea level rise exclusively on coastal fresh groundwater resources worldwide (limited to areas with unconsolidated sedimentary systems) by estimating future decline in inland fresh groundwater volumes under three sea level rise scenarios following Representative Concentration Pathway (RCP) 2.6, 4.5, and 8.5. For that, 2D groundwater models in 1,200 coastal regions estimate the past, present and future groundwater salinity. Our results show that roughly 60 (range 16–96) million people living within 10 km from current coastline could lose more than 5% of their fresh groundwater resources by 2100 according to RCP 8.5 scenario compared to only 8 (range 0–50) million people based on RCP 2.6 scenario. We conclude that sea level rise will have severe consequences for many coastal populations heavily dependent on fresh groundwater.
Spacecraft Outgassing Observed by the BepiColombo Ion Spectrometers
Authors: Fränz M. , Rojo M. , Cornet T. , Hadid L. Z. , Saito Y. , André N. , Varsani A. , Schmid D. , Krüger H. , Krupp N. , Delcourt D. , Katra B. , Harada Y. , Yokota S. , Verdeil C. , Aizawa S. , Millilo A. , Orsini S. , Mangano V. , Fiethe B. , Benkhoff J. , Murakami G.
Published: January 2024

During the first flyby of the BepiColombo composite spacecraft at Mercury in October 2021 ion spectrometers observed two intense spectral lines with energies between 10 and 70 eV. The spectral lines persisted also at larger distances from Mercury and were observed again at lower intensity during cruise phase in March 2022 and at the second and third Mercury flyby as a single band. The ion composition indicates that water is the dominant gas source. The outgassing causes the composite spacecraft to charge up to a negative potential of up to −50 V. The distribution and intensity of the lower energy signal depends on the intensity of low energy electron fluxes around the spacecraft which again depend on the magnetic field orientation. We interpret the observation as being caused by water outgassing from different source locations on the spacecraft being ionized in two different regions of the surrounding potential. The interpretation is confirmed by two dimensional particle‐in‐cell simulations.
Lithosphere Removal in the Sierra Nevada de Santa Marta, Colombia
Authors: Quiroga D. E. , Currie C. A. , Pearse J.
Published: January 2024

The Sierra Nevada de Santa Marta (SNSM) in northwestern Colombia is one of the world's highest coastal mountains, with an elevation above 5 km. Gravity measurements show that the SNSM has a positive Bouguer anomaly (>+130 mGal), indicating that the mountain lacks a crustal root. In this work, we test the hypothesis that these observations can be explained by gravitational removal of the dense lower lithosphere. We use 2D numerical models to examine the dynamics of lithosphere removal and its effect on surface elevation and gravity anomaly. The models consist of continental lithosphere that includes a pre‐thickened crustal region, representing the SNSM. In our preferred model, the dense mantle lithosphere and crustal root are gravitationally unstable and undergo removal as local drips within ∼10 Ma from the onset of foundering. This creates an area of thinned crust (∼38 km) underlain by a buoyant sublithospheric mantle where melting and low seismic velocities are predicted. Subsequent non‐isostatic forces maintain a topography of 3.3 km with a 2D Bouguer gravity anomaly of +103 mGal. Parameter tests show that a strong lower‐crustal rheology provides greater support for the high topography and that a weak mantle lithosphere rheology produces faster removal. The models demonstrate that local lithosphere dynamics can explain the first‐order observations in the SNSM. We propose that lithosphere removal could have occurred recently (∼2 Ma), explaining the localized low seismic velocity zone below the SNSM, or at 56–40 Ma, inducing anomalous short‐lived Eocene magmatism.
The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer
Authors: Kang Ye-Lim , Kim Jiyoung , Kwak Su-Bin , Kim Yi-Sook , Huh June , Park Jong-Wan
Published: January 2024

Diabetes might be associated with increased cancer risk, with several studies reporting hyperglycemia as a primary oncogenic stimulant. Since glucose metabolism is linked to numerous metabolic pathways, it is difficult to specify the mechanisms underlying hyperglycemia-induced cancer progression. Here, we focused on the polyol pathway, which is dramatically activated under hyperglycemia and causes diabetic complications. We investigated whether polyol pathway-derived fructose facilitates hyperglycemia-induced gastric cancer metastasis. We performed bioinformatics analysis of gastric cancer datasets and immunohistochemical analyses of gastric cancer specimens, followed by transcriptomic and proteomic analyses to evaluate phenotypic changes in gastric cancer cells. Consequently, we found a clinical association between the polyol pathway and gastric cancer progression. In gastric cancer cell lines, hyperglycemia enhanced cell migration and invasion, cytoskeletal rearrangement, and epithelial-mesenchymal transition (EMT). The hyperglycemia-induced acquisition of metastatic potential was mediated by increased fructose derived from the polyol pathway, which stimulated the nuclear ketohexokinase-A (KHK-A) signaling pathway, thereby inducing EMT by repressing the CDH1 gene. In two different xenograft models of cancer metastasis, gastric cancers overexpressing AKR1B1 were found to be highly metastatic in diabetic mice, but these effects of AKR1B1 were attenuated by KHK-A knockdown. In conclusion, hyperglycemia induces fructose formation through the polyol pathway, which in turn stimulates the KHK-A signaling pathway, driving gastric cancer metastasis by inducing EMT. Thus, the polyol and KHK-A signaling pathways could be potential therapeutic targets to decrease the metastatic risk in gastric cancer patients with diabetes.
Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder
Authors: Walsh Sharon L. , Comer Sandra D. , Zdovc Jurij Aguiar , Sarr Céline , Björnsson Marcus , Strandgården Kerstin , Hjelmström Peter , Tiberg Fredrik
Published: January 2024

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (Imax) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (Emax) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking Emax VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-‍linear mixed-effects modeling (NONMEM®). The final Imax model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking Emax VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking Emax VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC90) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking.
Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents
Authors: Giurini Eileena F. , Godla Aishvarya , Gupta Kajal H.
Published: January 2024

Cancer treatment remains a significant challenge due to issues such as acquired resistance to conventional therapies and the occurrence of adverse treatment-related toxicities. In recent years, researchers have turned their attention to the microbial world in search of novel and effective drugs to combat this devastating disease. Microbial derived secondary metabolites have proven to be a valuable source of biologically active compounds, which exhibit diverse functions and have demonstrated potential as treatments for various human diseases. The exploration of these compounds has provided valuable insights into their mechanisms of action against cancer cells. In-depth studies have been conducted on clinically established microbial metabolites, unraveling their anticancer properties, and shedding light on their therapeutic potential. This review aims to comprehensively examine the anticancer mechanisms of these established microbial metabolites. Additionally, it highlights the emerging therapies derived from these metabolites, offering a glimpse into the immense potential they hold for anticancer drug discovery. Furthermore, this review delves into approved treatments and major drug candidates currently undergoing clinical trials, focusing on specific molecular targets. It also addresses the challenges and issues encountered in the field of anticancer drug research and development. It also presents a comprehensive exposition of the contemporary panorama concerning microbial metabolites serving as a reservoir for anticancer agents, thereby illuminating their auspicious prospects and the prospect of forthcoming strides in the domain of cancer therapeutics.
Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder
Authors: Albuainain Fatimah , Shi Yuwei , Lor-Zade Sarah , Hüffmeier Ulrike , Pauly Melissa , Reis André , Faivre Laurence , Maraval Julien , Bruel Ange-Line , Them Frédéric Tran Mau , Haack Tobias B. , Grasshoff Ute , Horber Veronka , Schot Rachel , van Slegtenhorst Marjon , Wilke Martina , Barakat Tahsin Stefan
Published: January 2024

Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.
Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study
Authors: Stahl Andreas , Azuma Noriyuki , Wu Wei-Chi , Lepore Domenico , Sukgen Emine , Nakanishi Hidehiko , Mazela Jan , Leal Sergio , Pieper Alexander , Schlief Sarah , Eissing Thomas , Turner Kenneth C. , Zhao An , Winkler Julia , Höchel Joachim , Köfüncü Evra , Zimmermann Torsten ,   on behalf of the FIREFLEYE Study Group
Published: January 2024

Background

There are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy of prematurity (ROP). FIREFLEYE compared aflibercept 0.4 mg/eye and laser photocoagulation in infants with acute-phase ROP requiring treatment.

Methods

Infants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 2:1 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in this 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity.

Results

Of 113 treated infants, 75 received aflibercept 0.4 mg per eye at baseline (mean chronological age: 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants. There was no pattern between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (1:30), non-neutralizing, treatment-emergent anti-drug antibody response was reported in 1 infant, though was not clinically relevant.

Conclusions

24-week data suggest intravitreal aflibercept for treatment of acute-phase ROP is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity.

ClinicalTrials.gov Identifier

NCT04004208.
Silica-associated proteins from hexactinellid sponges support an alternative evolutionary scenario for biomineralization in Porifera
Authors: Shimizu Katsuhiko , Nishi Michika , Sakate Yuto , Kawanami Haruka , Bito Tomohiro , Arima Jiro , Leria Laia , Maldonado Manuel
Published: January 2024

Metazoans use silicon traces but rarely develop extensive silica skeletons, except for the early-diverging lineage of sponges. The mechanisms underlying metazoan silicification remain incompletely understood, despite significant biotechnological and evolutionary implications. Here, the characterization of two proteins identified from hexactinellid sponge silica, hexaxilin and perisilin, supports that the three classes of siliceous sponges (Hexactinellida, Demospongiae, and Homoscleromorpha) use independent protein machineries to build their skeletons, which become non-homologous structures. Hexaxilin forms the axial filament to intracellularly pattern the main symmetry of the skeletal parts, while perisilin appears to operate in their thickening, guiding extracellular deposition of peripheral silica, as does glassin, a previously characterized hexactinellid silicifying protein. Distant hexaxilin homologs occur in some bilaterians with siliceous parts, suggesting putative conserved silicifying activity along metazoan evolution. The findings also support that ancestral Porifera were non-skeletonized, acquiring silica skeletons only after diverging into major classes, what reconciles molecular-clock dating and the fossil record.
The selection landscape and genetic legacy of ancient Eurasians
Authors: Irving-Pease Evan K. , Refoyo-Martínez Alba , Barrie William , Ingason Andrés , Pearson Alice , Fischer Anders , Sjögren Karl-Göran , Halgren Alma S. , Macleod Ruairidh , Demeter Fabrice , Henriksen Rasmus A. , Vimala Tharsika , McColl Hugh , Vaughn Andrew H. , Speidel Leo , Stern Aaron J. , Scorrano Gabriele , Ramsøe Abigail , Schork Andrew J. , Rosengren Anders , Zhao Lei , Kristiansen Kristian , Iversen Astrid K. N. , Fugger Lars , Sudmant Peter H. , Lawson Daniel J. , Durbin Richard , Korneliussen Thorfinn , Werge Thomas , Allentoft Morten E. , Sikora Martin , Nielsen Rasmus , Racimo Fernando , Willerslev Eske
Published: January 2024

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.
The demise of the giant ape Gigantopithecus blacki
Authors: Zhang Yingqi , Westaway Kira E. , Haberle Simon , Lubeek Juliën K. , Bailey Marian , Ciochon Russell , Morley Mike W. , Roberts Patrick , Zhao Jian-xin , Duval Mathieu , Dosseto Anthony , Pan Yue , Rule Sue , Liao Wei , Gully Grant A. , Lucas Mary , Mo Jinyou , Yang Liyun , Cai Yanjun , Wang Wei , Joannes-Boyau Renaud
Published: January 2024

The largest ever primate and one of the largest of the southeast Asian megafauna, Gigantopithecus blacki1, persisted in China from about 2.0 million years until the late middle Pleistocene when it became extinct2–4. Its demise is enigmatic considering that it was one of the few Asian great apes to go extinct in the last 2.6 million years, whereas others, including orangutan, survived until the present5. The cause of the disappearance of G. blacki remains unresolved but could shed light on primate resilience and the fate of megafauna in this region6. Here we applied three multidisciplinary analyses—timing, past environments and behaviour—to 22 caves in southern China. We used 157 radiometric ages from six dating techniques to establish a timeline for the demise of G. blacki. We show that from 2.3 million years ago the environment was a mosaic of forests and grasses, providing ideal conditions for thriving G. blacki populations. However, just before and during the extinction window between 295,000 and 215,000  years ago there was enhanced environmental variability from increased seasonality, which caused changes in plant communities and an increase in open forest environments. Although its close relative Pongo weidenreichi managed to adapt its dietary preferences and behaviour to this variability, G. blacki showed signs of chronic stress and dwindling populations. Ultimately its struggle to adapt led to the extinction of the greatest primate to ever inhabit the Earth.
The CRISPR effector Cam1 mediates membrane depolarization for phage defence
Authors: Baca Christian F. , Yu You , Rostøl Jakob T. , Majumder Puja , Patel Dinshaw J. , Marraffini Luciano A.
Published: January 2024

Prokaryotic type III CRISPR–Cas systems provide immunity against viruses and plasmids using CRISPR-associated Rossman fold (CARF) protein effectors1–5. Recognition of transcripts of these invaders with sequences that are complementary to CRISPR RNA guides leads to the production of cyclic oligoadenylate second messengers, which bind CARF domains and trigger the activity of an effector domain6,7. Whereas most effectors degrade host and invader nucleic acids, some are predicted to contain transmembrane helices without an enzymatic function. Whether and how these CARF–transmembrane helix fusion proteins facilitate the type III CRISPR–Cas immune response remains unknown. Here we investigate the role of cyclic oligoadenylate-activated membrane protein 1 (Cam1) during type III CRISPR immunity. Structural and biochemical analyses reveal that the CARF domains of a Cam1 dimer bind cyclic tetra-adenylate second messengers. In vivo, Cam1 localizes to the membrane, is predicted to form a tetrameric transmembrane pore, and provides defence against viral infection through the induction of membrane depolarization and growth arrest. These results reveal that CRISPR immunity does not always operate through the degradation of nucleic acids, but is instead mediated via a wider range of cellular responses.
Distributional reinforcement learning in prefrontal cortex
Authors: Muller Timothy H. , Butler James L. , Veselic Sebastijan , Miranda Bruno , Wallis Joni D. , Dayan Peter , Behrens Timothy E. J. , Kurth-Nelson Zeb , Kennerley Steven W.
Published: January 2024

The prefrontal cortex is crucial for learning and decision-making. Classic reinforcement learning (RL) theories center on learning the expectation of potential rewarding outcomes and explain a wealth of neural data in the prefrontal cortex. Distributional RL, on the other hand, learns the full distribution of rewarding outcomes and better explains dopamine responses. In the present study, we show that distributional RL also better explains macaque anterior cingulate cortex neuronal responses, suggesting that it is a common mechanism for reward-guided learning.
Long non-coding RNAs and their potential function in response to postharvest senescence of Sparassis latifolia during cold storage
Authors: Weng Mengting , Zhang Di , Wang Hongyu , Yang Chi , Lin Hongyi , Pan Yanfang , Lin Yanquan
Published: January 2024

Long non-coding RNAs (lncRNAs) have been shown to play crucial roles in response to aging processes. However, how lncRNAs regulate postharvest senescence of Sparassis latifolia (S. latifolia) with oriented polypropylene (OPP) film packing during cold storage remains unclear. In this study, we performed RNA-seq using the fruiting bodies of S. latifolia stored at 4 ℃ for 0, 8, 16 and 24 days after harvest, and profiled the lncRNA and mRNA transcriptome, respectively. In total, 1003 putative lncRNAs were identified, and there were 495, 483 and 162 differentially expressed (DE) lncRNAs, and 3680, 3941 and 1870 differentially expressed mRNAs after 8, 16 and 24 days of storage, respectively, compared to 0 day of storage. Target genes of differentially expressed lncRNAs were found to significantly associate with carbon and energy metabolism, response to abiotic stimulus, amino acid biosynthesis and metabolism, and protein synthesis and transcription. In addition, DE-lncRNA-mRNA co-expression networks in response to aging stress were also constructed. Taken together, these results confirm the regulatory role of lncRNAs in postharvest senescence of S. latifolia and will facilitate for improving preservation method.
Structural basis for the activity and specificity of the immune checkpoint inhibitor lirilumab
Authors: Lorig-Roach Nicholas , Harpell Nina M. , DuBois Rebecca M.
Published: January 2024

The clinical success of immune checkpoint inhibitors has underscored the key role of the immune system in controlling cancer. Current FDA-approved immune checkpoint inhibitors target the regulatory receptor pathways of cytotoxic T-cells to enhance their anticancer responses. Despite an abundance of evidence that natural killer (NK) cells can also mediate potent anticancer activities, there are no FDA-approved inhibitors targeting NK cell specific checkpoint pathways. Lirilumab, the most clinically advanced NK cell checkpoint inhibitor, targets inhibitory killer immunoglobulin-like receptors (KIRs), however it has yet to conclusively demonstrate clinical efficacy. Here we describe the crystal structure of lirilumab in complex with the inhibitory KIR2DL3, revealing the precise epitope of lirilumab and the molecular mechanisms underlying KIR checkpoint blockade. Notably, the epitope includes several key amino acids that vary across the human population, and binding studies demonstrate the importance of these amino acids for lirilumab binding. These studies reveal how KIR variations in patients could influence the clinical efficacy of lirilumab and reveal general concepts for the development of immune checkpoint inhibitors targeting NK cells.
How article category in Wikipedia determines the heterogeneity of its editors
Authors: Oeberst Aileen , Ridderbecks Till
Published: January 2024

Collaboration is essential to advancing knowledge and, ultimately, entire societies. With the development of Web 2.0, the possibilities have risen to unprecedented levels and allowed for the collaborative creation of the world’s largest compendium of knowledge that ever existed – Wikipedia. Collaboration is not a safeguard of quality per se, however. Rather, the quality of Wikipedia articles rises with the number of editors per article as well as a greater diversity among them. Here, we address a not yet documented potential threat to those preconditions: self-selection of Wikipedia editors to articles. Specifically, we expected articles with a clear-cut link to a specific country (e.g., about its highest mountain, “national” article category) to attract a larger proportion of editors of that nationality when compared to articles without any specific link to that country (e.g., “gravity”, “universal” article category), whereas articles with a link to several countries (e.g., “United Nations”, “international” article category) should fall in between. Across several language versions, hundreds of different articles, and hundreds of thousands of editors, we find the expected effect within Wikipedia: The more exclusively an article topic is linked to a particular nation, the higher the proportion of editors from that country is among the contributors.
The development of an electrochemical immunosensor utilizing chicken IgY anti-spike antibody for the detection of SARS-CoV-2
Authors: Al-Qaoud Khaled M. , Obeidat Yusra M. , Al-Omari Tareq , Okour Mohammad , Al-Omari Mariam M. , Ahmad Mohammad I. , Alshadfan Raed , Rawashdeh AbdelMonem M.
Published: January 2024

This paper introduces a novel approach for detecting the SARS-CoV-2 recombinant spike protein combining a label free electrochemical impedimetric immunosensor with the use of purified chicken IgY antibodies. The sensor employs three electrodes and is functionalized with an anti-S IgY antibody, ELISA and immunoblot assays confirmed the positive response of chicken immunized with SARS-CoV2 S antigen. The developed immunosensor is effective in detecting SARS-CoV-2 in nasopharyngeal clinical samples from suspected cases. The key advantage of this biosensor is its remarkable sensitivity, and its capability of detecting very low concentrations of the target analyte, with a detection limit of 5.65 pg/mL. This attribute makes it highly suitable for practical point-of-care (POC) applications, particularly in low analyte count clinical scenarios, without requiring amplification. Furthermore, the biosensor has a wide dynamic range of detection, spanning from 11.56 to 740 ng/mL, which makes it applicable for sample analysis in a typical clinical setting.
Association of early cleavage, morula compaction and blastocysts ploidy of IVF embryos cultured in a time-lapse system and biopsied for genetic test for aneuploidy
Authors: De Martin H. , Bonetti T. C. S. , Nissel C. A. Z. , Gomes A. P. , Fujii M. G. , Monteleone P. A. A.
Published: January 2024

IVF embryos have historically been evaluated by morphological characteristics. The time-lapse system (TLS) has become a promising tool, providing an uninterrupted evaluation of morphological and dynamic parameters of embryo development. Furthermore, TLS sheds light on unknown phenomena such as direct cleavage and incomplete morula compaction. We retrospectively analyzed the morphology (Gardner Score) and morphokinetics (KIDScore) of 835 blastocysts grown in a TLS incubator (Embryoscope+), which were biopsied for preimplantation genetic testing for aneuploidy (PGT-A). Only the embryos that reached the blastocyst stage were included in this study and time-lapse videos were retrospectively reanalysed. According to the pattern of initial cleavages and morula compaction, the embryos were classified as: normal (NC) or abnormal (AC) cleavage, and fully (FCM) or partially compacted (PCM) morulae. No difference was found in early cleavage types or morula compaction patterns between female age groups (< 38, 38–40 and > 40 yo). Most of NC embryos resulted in FCM (≅ 60%), while no embryos with AC resulted in FCM. Aneuploidy rate of AC-PCM group did not differ from that of NC-FCM group in women < 38 yo, but aneuploidy was significantly higher in AC-PCM compared to NC-FCM of women > 40 yo. However, the quality of embryos was lower in AC-PCM blastocysts in women of all age ranges. Morphological and morphokinetic scores declined with increasing age, in the NC-PCM and AC-PCM groups, compared to the NC-FCM. Similar aneuploidy rates among NC-FCM and AC-PCM groups support the hypothesis that PCM in anomalous-cleaved embryos can represent a potential correction mechanism, even though lower morphological/morphokinetic scores are seen on AC-PCM. Therefore, both morphological and morphokinetic assessment should consider these embryonic development phenomena.
Utilizing industrial byproducts for the manufacture of clay-cellulose nanocomposite cements with enhanced sustainability
Authors: El-Feky M. S. , Badawy Amr H. , Youssef Passant , Kohail Mohamed
Published: January 2024

This study investigates the influence of different nano clay contents (0, 1, 3, and 5 wt% of cement) on the microstructure and the mechanical properties of cement composites reinforced with varying Nano cellulose fiber contents (0, 0.5, 0.75, and 1 wt% of cement). Unlike previous research that employed sonication to improve dispersion in the cement matrix, this study explores the effects of unsonicated nano-cellulose addition and the combined incorporation of nano-cellulose and nano-clay. The results demonstrate that these additions significantly enhance the compressive strength, abrasion resistance, and water absorption ratios of the cement composites. Furthermore, the inclusion of nano-clay improves the microstructure of the cement matrix, strengthening the interfacial transition zone and reinforcing the bond between nano-cellulose and the cement matrix. The microstructural analysis using scanning electron microscopy (SEM) reveals the presence of a dense interconnected structure characterized by rod-like crystals. This research contributes to the development of sustainable construction materials by examining the effects of nano-cellulose and nano-clay on the properties and microstructure of cement composites. The utilization of industrial byproducts, such as wood sawdust, for the extraction of nano-cellulose offers an eco-friendly approach to enhance the performance of cement-based materials. The maximum compressive strength obtained, after 28 days, was at mix with 0.75% NCL + 5%NC with a gain of 53.5% than that of the control mix. In mixes containing only nano-clay (NCL), the increase in NCL content led to a higher rate of water absorption in the cement matrix, which reaches 4%. Confirming the results obtained from compressive strength and water absorption, mix with 0.75% NCL and 5% NC had obtained the optimum values with an improvement of 20% than that of the control mix.