bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review
Authors: Szwec Sylwia , Kapłucha Zuzanna , Chamberlain Jeffrey S. , Konieczny Patryk 
Published: November 2023

Abstract
Duchenne muscular dystrophy is a devastating disease that leads to progressive muscle loss and premature death. While medical management focuses mostly on symptomatic treatment, decades of research have resulted in first therapeutics able to restore the affected reading frame of dystrophin transcripts or induce synthesis of a truncated dystrophin protein from a vector, with other strategies based on gene therapy and cell signaling in preclinical or clinical development. Nevertheless, recent reports show that potentially therapeutic dystrophins can be immunogenic in patients. This raises the question of whether a dystrophin paralog, utrophin, could be a more suitable therapeutic protein. Here, we compare dystrophin and utrophin amino acid sequences and structures, combining published data with our extended in silico analyses. We then discuss these results in the context of therapeutic approaches for Duchenne muscular dystrophy. Specifically, we focus on strategies based on delivery of micro-dystrophin and micro-utrophin genes with recombinant adeno-associated viral vectors, exon skipping of the mutated dystrophin pre-mRNAs, reading through termination codons with small molecules that mask premature stop codons, dystrophin gene repair by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated genetic engineering, and increasing utrophin levels. Our analyses highlight the importance of various dystrophin and utrophin domains in Duchenne muscular dystrophy treatment, providing insights into designing novel therapeutic compounds with improved efficacy and decreased immunoreactivity. While the necessary actin and β-dystroglycan binding sites are present in both proteins, important functional distinctions can be identified in these domains and some other parts of truncated dystrophins might need redesigning due to their potentially immunogenic qualities. Alternatively, therapies based on utrophins might provide a safer and more effective approach.
Mechanical Behavior of Seamless Pipes Using Ring Expansion Technique and Novel Hoop Stress Correlation Factor (K)
Authors: Abdelgawad K. , Nassef A. , Eraky Mohamed T. , Saber M. 
Published: November 2023

AbstractThis study investigated the stress–strain behavior of seamless pipes in the hoop direction using the ring expansion test, which is a non-standardized mechanical testing technique used for evaluating the mechanical properties of round tubes. However, this technique has limitations, such as unidentified specimen geometry, strain measurement, and the estimation of friction coefficients. The study employed experimental, numerical, and analytical methodologies to address these limitations and throughout the study, a novel hoop stress correlation factor (K) was identified to be multiplied by the hoop stress derived equation for reduced section ring specimens. The experimental strain was measured using a newly derived analytical equation, and a mathematical predictive model was developed to estimate the K-factor using the Design of Experiment (DoE) and Design-Expert statistical software. The study concluded that the ring expansion test is a promising technique for evaluating the mechanical properties of seamless pipes similar to the unified axial tensile stress–strain behavior. However, future research is needed to estimate the hoop stress correlation value (K) for all ring geometries. The study's finding of the novel hoop stress correlation factor (K) in the case of a reduced section ring specimen is particularly noteworthy, as it addresses a significant research gap in the field.
Alternative construction materials from industrial side streams: Are they safe?
Authors: Adhikary Suman Kumar , D’Angelo Antonio , Viola Veronica , Catauro Michelina , Perumal Priyadharshini 
Published: November 2023

AbstractThe global population is continually generating vast amounts of waste materials across various sectors, leading to environmental challenges associated with landfill disposal. This study aims to examine the leachate and the antimicrobial properties of several waste materials to explore their potential applicability in the construction industry. Here, ICP-OES analysis and Kirby Bauer test were conducted on ready-mix concrete plant (powder residues), precast industries, recycled alkali-activated materials, municipal solid waste incinerated (MSWI) bottom ash, MSWI fly ash, High alumina tailing, and High magnesia tailing, to explore their potential applicability in the construction industry. Aluminium, calcium, silicon, potassium, and magnesium were the major ions leached from the waste materials, with MSWI fly ash and bottom ash showing higher levels of heavy metal leaching. The levels of leached aluminium, barium, chromium, lead, and zinc from MSWI fly ash and bottom ash were quantified, with values reaching up to 28.7 ppm, 4 ppm, 3.9 ppm, 11 ppm, and 25 ppm, respectively. Additionally, all samples demonstrated some level of antimicrobial activity against Escherichia coli and Staphylococcus aureus, which could be related to their alkaline pH and the release of certain ions. Improper disposal of waste materials in an open environment can potentially lead to contamination by heavy metals and harmful bacteria, which can pose a significant health risk during handling. This study results provided valuable information regarding the safety of using these wastes in the construction industry.
Basisarbeit bei älteren Beschäftigten in Deutschland – eine Übersicht
Authors: Hasselhorn Hans Martin , Müller Bernd Hans 
Published: November 2023

ZusammenfassungDer Beitrag beschreibt die Arbeits- und Lebenssituation älterer Beschäftigter in Deutschland in Hinblick auf Basisarbeit (BA). Grundlage ist Welle 4 der repräsentativen lidA-Studie. Von 7279 Erwerbstätigen (Jg. 1959, 1965, 1971) waren 1651 (22,7 %) der Gruppe der BA zuzuordnen. Die Befunde zur BA-Gruppe Level 2 („längere Einarbeitung erforderlich“, 14,3 % aller) lagen bei zahlreichen Faktoren näher an der Gruppe der Nicht-Basisarbeitenden als an denen der BA-Gruppe Level 1 („kurze Einweisung reicht“, 8,4 %). Letztere Gruppe stellt nach unseren Ergebnissen eine besondere Risikogruppe in Bezug auf Gesundheit, Arbeit, Beschäftigung und auch materielle Umstände dar. Diese Gruppe ist vor allem weiblich sowie im Vergleich eher älter, unqualifiziert, alleinstehend, in Teilzeit und in kleineren Betrieben tätig. Die Ergebnisse unterstreichen Handlungsbedarf auf politischer, betrieblicher und gesellschaftlicher Ebene.
The role of International Financial Institutions in conflict, recovery, and transitions in Africa: a focus on Ethiopia and Sudan
Authors: Kifle Alagaw Ababu , Olonisakin Funmi 
Published: November 2023

AbstractSuccessive socio-economic shocks in the past three years have undermined Africa’s development gains, impeding the economic convergence of Africa and the developed world. While these shocks originated externally, internal factors within Africa are reinforcing their impact. One such factor is conflict and instability. Nearly half of the African states are either fragile or conflict-affected. Although international organizations claim to support Africa in overcoming fragility and conflict, how they engage Africa has remained a major policy and scholarly concern. International Financial Institutions (IFIs), for instance, are being asked to help address the economic dimensions of fragility and conflict. However, there is little consensus about whether they are indeed helping. Divergent responses are often offered wherein the IFIs argue that they are assisting by adopting adaptive strategies to correct past mistakes while experimenting with new strategies based on extensive monitoring and research. Scholarly debates on these IFI narratives, and by extension the IFIs’ interests and agenda, are not yet settled. This paper approaches these debates by examining IFIs’ engagement in the recent conflict and transitions of Ethiopia and Sudan, arguing that these examples call into question the IFIs’ claims of strategic adaptiveness. The paper, along with previous studies, argues that the inner core of neo-liberal economic vision has animated the IFIs’ prescription, often complemented by a focus on social safety nets to varying degrees and with varying effects. In Sudan, the IFI offered coordinated support for economic reform with some successes in directly targeting sources of fragility and conflict. In Ethiopia, such coordinated engagement was lacking, and reform measures did not directly target the sources of conflict. The cases demonstrate the importance of continuous and coordinated engagement in fragile and conflict-affected states (FCS) of Africa in a way that acknowledges the nexus between security and development issues, especially at critical junctures. The cases also underscore the importance of adaptive and pragmatic engagements with FCS undertaken in coordination with relevant global actors and institutions.
Norms for Academic Writing in the Era of Advanced Artificial Intelligence
Authors: Friederich Simon , Symons Jonathan 
Published: November 2023

AbstractIf and when artificial intelligence systems become superhuman in more aspects of analytic reasoning, this will inevitably have a strong impact on the social organisation of science, including academic writing, reviewing, and publishing. We consider how norms of academic publishing should be adjusted as this happens. To do so, we propose four intuitively plausible desiderata that norms of academic publishing should fulfil in the age of increasingly advanced artificial intelligence (AI) and argue that there are no “quick fixes” to current norms that fulfil these desiderata. To indicate the scale of change needed to prepare academic publishing for the era of increasingly advanced AI, we tentatively sketch a more promising novel system of norms. Our proposal centres around the idea that AI systems should “sign off’’ on statements that outline the human and AI contributions to academic research. We discuss possible challenges for this proposal and highlight the type of technological and regulatory infrastructure that would be needed to enable it.
Southern Alaska's Forest Landscape Integrity, Habitat, and Carbon Are Critical for Meeting Climate and Conservation Goals
Authors: Law B. E. , Berner L. T. , Wolf C. , Ripple W. J. , Trammell E. J. , Birdsey R. A. 
Published: November 2023

AbstractThe interdependent crises of climate change and biodiversity losses require strategic policies to protect, manage, and restore essential ecosystems. Here, we evaluate the relative importance of US national forests (NFs) for protection and conservation as natural climate and biodiversity solutions. We compared landscape integrity (degree of modification by humans), habitat for three keystone species, forest carbon density, accumulation, and total biomass carbon stocks across 154 NFs in the United States. Southern Alaska's Tongass and Chugach NFs hold disproportionally large amounts of high landscape integrity area among all NFs with 25.3% and 5.6% (total 30.9%) of all high (≥9.6) landscape integrity found on NF lands. The Tongass and Chugach store approximately 33% and 3% of all biomass carbon stocks that occur in NFs with high landscape integrity. These two NFs together account for about 49%, 37%, and 18% of all bald eagle, brown bear, and gray wolf habitat found on NF lands. Gray wolf habitat extent was 4% of the total or less on remaining NFs. The Tongass and Chugach were historically wetter and cooler among NFs, and are projected to experience much larger increases in precipitation and much lower increases in maximum temperatures over the coming century. Combined with relatively low recent occurrence of wildfire, this makes permanence more likely. The Tongass and Chugach forests, along with the Pacific Northwest's high carbon density forests should be a high priority for protection and conservation to meet climate and biodiversity goals given their landscape‐scale scarcity and high value.
Do Two Climate Wrongs Make a Right?
Authors: Schimel David , Miller Charles 
Published: November 2023

AbstractAs the planet approaches local and global exceedance of the 1.5°C stabilization target, damages from climate change, mostly due to extremes, are growing far faster than projected. While assessment models have largely estimated high costs of mitigation, the cost of green energy is dropping faster than projected. Climate policy has assumed that damage costs are manageable while decarbonization is expensive. Both these assumptions are wrong, potentially leading to a tipping point in human behavior: scientists need to explore options aligned with this emerging reality.
Microstructural Controls on the Uniaxial Compressive Strength of Porous Rocks Through the Granular to Non‐Granular Transition
Authors: Carbillet Lucille , Wadsworth Fabian B. , Heap Michael J. , Baud Patrick 
Published: November 2023

AbstractUnder uniaxial compression, a porous rock fails by coalescence of stress‐induced microcracks. The micromechanical models developed to analyze uniaxial compressive strength data consider a single mechanism for the initiation and propagation of microcracks and a fixed starting microstructure. Because the microstructure of clastic porous rock transitions from granular to non‐granular as porosity decreases during diagenesis, their strength cannot be captured by a single model. Using synthetic samples with independently controlled porosity and initial grain radius we show that high‐porosity granular samples, where microcracks grow at grain‐to‐grain contacts, are best described by a grain‐based model. Low‐porosity non‐granular samples, where microcracks grow from pores, are best described by a pore‐based model. The switch from one model to the other depends on porosity and grain radius. We propose a regime plot that indicates which micromechanical model may be more suitable to predict strength for a given porosity and grain radius.
Rapid Acceleration of Dangerous Compound Heatwaves and Their Impacts in a Warmer China
Authors: Dong Wei , Jia XiaoJing , Qian QiFeng , Li XiuMing 
Published: November 2023

AbstractThis work investigates the possible future changes and impacts in spatiotemporal variation and regional features of multivariate compound heatwaves (CHWs) in China using the latest Universal Thermal Climate Index from the Coupled Model Intercomparison Project Phase 6 simulations (CMIP6). Results indicate both strong CHWs and extremely threatening CHWs in China are projected to increase substantially in both frequency and spatial extent under different future climate scenarios while with discernible regional disparities. The more severe global warming is, and the greater the extremity of the heatwave events is, the faster the increase in CHWs is. These findings are derived from the CMIP6 projections calibrated using the robust empirical quantiles method. Climate change causes more areas and people to be exposed to CHWs. Notably, the population exposure to dangerous CHWs will increase significantly in northwest China and will appear in northeast China after the mid‐21st century under the high emission scenario.
Links Between Orbital Forcing, Antarctic Ice Volume, and the East Asian Hydrological Cycle Over the Pliocene
Authors: Wang Zhixiang , Mao Yongdong , Zhang Rui , Kemp David B. , Huang Chunju 
Published: November 2023

AbstractRevealing the evolution of monsoonal intensity through the Pliocene on orbital timescales is of potential utility for providing insights into the response of Asian monsoons to future high pCO2 scenarios. Here, we report a continuous Pliocene cyclostratigraphic record from lake deposits of the Xinding Basin, Shanxi Graben, North China, and reconstruct the regional hydrological cycle from this location during ∼5.2 to 2.56 Ma. Our results show that regional hydrological cycling was consistently dominated by long‐and short‐eccentricity (405‐and 100‐kyr) forcing over the Pliocene. Gamma‐ray (GR) data (reflecting hydrodynamic changes) show strengthened 100‐kyr eccentricity power after ∼3.5 Ma, whereas 100‐kyr eccentricity power preserved in magnetic susceptibility (MS; interpreted as a proxy of pedogenesis and magnetic mineral dissolution) slightly weakened after ∼3.5 Ma. This orbital power transition at the 100‐kyr eccentricity scale may link to expansion of Antarctic ice volume after ∼3.5 Ma, which enhanced East Asian summer monsoon intensity and thus increased summer rainfall in North China, resulting in changes to hydrological cycling and the expression of eccentricity climate forcing in East Asian basins. In addition, our results demonstrate that the orbital configuration at ∼4.2–4.4 Ma could have been a contributory factor in strengthening the intensity of the East Asian summer monsoon at this time.
Tectono‐Sedimentary Evolution of Shale‐Related Minibasins in the Karvandar Basin (South Sistan, SE Iran): Insights From Magnetostratigraphy, Isotopic Dating, and Sandstone Petrology
Authors: Ruh J. B. , Valero L. , Najafi M. , Etemad‐Saeed N. , Vouga J. , Mohammadi A. , Landtwing F. , Guillong M. , Cobianchi M. , Mancin N. 
Published: November 2023

AbstractSediments deposited into foreland basins can provide valuable insights related to the geological evolution of their hinterlands. Located in the peripheral foreland of the South Sistan Suture Zone (SE Iran), the Karvandar Basin exhibits a several‐kilometer‐thick shallow‐marine to continental clastic sedimentary sequence forming elongated sub‐circular synclines. These synclines overlie a mud‐dominated formation with exotic volcanic blocks that hosts one of Iran's largest mud volcano, known as Pirgel. In this study, we present a ∼3.5‐km‐thick magnetostratigraphic section and U‐Pb zircon ages of interlayered tuffs that constrain a depositional age of the Karvandar Basin of ∼24–17 Ma. Sandstone and microconglomerate framework analyses and paleocurrent directions suggest a first‐cycle active volcanic arc source to the northeast of the basin. We interpret the mud‐dominated lithology with volcanic blocks as an olistostrome originating from a similar source as the overlying clastic sequence. The deposition of the olistostrome is dated at ∼24.5 Ma by a U‐Pb calcite age from a coral block. The absence of large‐scale anticlines and the occurrence of angular unconformities suggest that the sub‐circular synclines in the Karvandar Basin formed by gravity‐driven downbuilding into the unconsolidated fluid‐saturated olistostrome, resembling salt‐related minibasins. Integrated results indicate that a late Oligocene to early Miocene Makran volcanic arc represents the source of the clastic sequence. Hence, our results provide new constraints on the initiation of arc volcanism related to the Makran subduction zone, predating earliest reported ages from the Mirabad pluton (19 Ma) to the northeast of the Karvandar Basin by ∼5 Myr.
Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer
Authors: Hwang Nahee , Yoon Bo Kyung , Chun Kyu-Hye , Kim Hyeonhui , Lee Yoseob , Kim Jae-Won , Jeon Hyeonuk , Kim Tae-Hyun , Kim Mi-Young , Fang Sungsoon , Cheong Jae-Ho , Kim Jae-woo 
Published: November 2023

AbstractDespite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.
Neuronal TIMP2 regulates hippocampus-dependent plasticity and extracellular matrix complexity
Authors: Ferreira Ana Catarina , Hemmer Brittany M. , Philippi Sarah M. , Grau-Perales Alejandro B. , Rosenstadt Jacob L. , Liu Hanxiao , Zhu Jeffrey D. , Kareva Tatyana , Ahfeldt Tim , Varghese Merina , Hof Patrick R. , Castellano Joseph M. 
Published: November 2023

AbstractFunctional output of the hippocampus, a brain region subserving memory function, depends on highly orchestrated cellular and molecular processes that regulate synaptic plasticity throughout life. The structural requirements of such plasticity and molecular events involved in this regulation are poorly understood. Specific molecules, including tissue inhibitor of metalloproteinases-2 (TIMP2) have been implicated in plasticity processes in the hippocampus, a role that decreases with brain aging as expression is lost. Here, we report that TIMP2 is highly expressed by neurons within the hippocampus and its loss drives changes in cellular programs related to adult neurogenesis and dendritic spine turnover with corresponding impairments in hippocampus-dependent memory. Consistent with the accumulation of extracellular matrix (ECM) in the hippocampus we observe with aging, we find that TIMP2 acts to reduce accumulation of ECM around synapses in the hippocampus. Moreover, its deletion results in hindrance of newborn neuron migration through a denser ECM network. A novel conditional TIMP2 knockout (KO) model reveals that neuronal TIMP2 regulates adult neurogenesis, accumulation of ECM, and ultimately hippocampus-dependent memory. Our results define a mechanism whereby hippocampus-dependent function is regulated by TIMP2 and its interactions with the ECM to regulate diverse processes associated with synaptic plasticity.
Widespread and largely unknown prophage activity, diversity, and function in two genera of wheat phyllosphere bacteria
Authors: Dougherty Peter Erdmann , Nielsen Tue Kjærgaard , Riber Leise , Lading Helen Helgå , Forero-Junco Laura Milena , Kot Witold , Raaijmakers Jos M , Hansen Lars Hestbjerg 
Published: November 2023

Abstract
Environmental bacteria host an enormous number of prophages, but their diversity and natural functions remain largely elusive. Here, we investigate prophage activity and diversity in 63 Erwinia and Pseudomonas strains isolated from flag leaves of wheat grown in a single field. Introducing and validating Virion Induction Profiling Sequencing (VIP-Seq), we identify and quantify the activity of 120 spontaneously induced prophages, discovering that some phyllosphere bacteria produce more than 108 virions/mL in overnight cultures, with significant induction also observed in planta. Sequence analyses and plaque assays reveal E. aphidicola prophages contribute a majority of intraspecies genetic diversity and divide their bacterial hosts into antagonistic factions engaged in widespread microbial warfare, revealing the importance of prophage-mediated microdiversity. When comparing spontaneously active prophages with predicted prophages we also find insertion sequences are strongly correlated with non-active prophages. In conclusion, we discover widespread and largely unknown prophage diversity and function in phyllosphere bacteria.