bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug repurposing: a retrospective revolution in breast cancer medicine
Authors: Shivani Dave , Misari Patel , Anand Nanavaty , Nandita Chawla , Jignesh Shah 
Published: July 2024

AbstractBreast cancer is a complex disease involving numerous pathways, making effective treatment quite challenging. Among the current scenario, drug repurposing serves as one of the best alternatives for drug discovery as a time-efficient and cost-effective strategy to determine new therapeutic indications for previously approved drug molecules. This is the reason behind the increased popularity of drug repurposing not only in the pharma industry but also in the civil sector and academics as a faster and less expensive way to increase the repertoire of licensed cancer therapies. In the current review, we have tried to perform an in-depth review of the current state of repurposed medications available for the treatment of breast cancer. Studies conducted on various noncancer medications showing possible anticancer effects were also included. Furthermore, the various repurposed drugs available for breast cancer treatment have been further segregated according to their indicative class and possible mechanism of action.
Phylogenetic analysis of virulent strains of the Newcastle disease virus isolated from deceased chickens in Tanzania's Morogoro and Iringa regions
Authors: Amoia Charlie F. , Hakizimana Jean N. , Chengula Augustino A. , Makange Mariam R. , Weger-Lucarelli James , Misinzo Gerald 
Published: July 2024

AbstractBackgroundNewcastle disease (ND) is a viral disease affecting a wide range of bird species and has a considerable financial impact on the world's poultry market. The ND virus (NDV) strains currently circulating in poultry throughout Africa, and especially in East Africa, exhibit significant genetic variation.ObjectivesThe primary objective of the present investigation was to investigate the NDV genotypes in chickens raised in backyards in Tanzania's Morogoro and Iringa districts, which were associated with ND outbreaks.MethodsTwo tissue samples from chickens taken during a suspected ND outbreak in Tanzania's Morogoro (Eastern zone) and Iringa (Southern highlands zone) were subjected to reverse transcription polymerase chain reaction targeting the fusion (F) and hemagglutinin-neuraminidase (HN) genes, followed by sequencing.ResultsBased on comprehensive analysis of the entire F and HN gene sequences, the viruses were categorized as genotype VII and displayed significant genetic similarity with NDV strains previously identified in Mozambique, South Africa, Zambia, Zimbabwe, Botswana, Southeast Asia, and China. The uniformity in the amino acid cleavage site motif of the F protein across the examined NDV isolates, characterized by 112R–R–Q/K–K–R–F117, indicates their classification as virulent strains.ConclusionRegularly characterizing circulating strains and expanding the study to other parts of Tanzania may help to enhance disease control by giving a more precise picture of the situation regarding ND, especially in light of the issues posed by NDV genotype VII elsewhere.
Building Successful Partnerships Between State Health Departments and Attorney General Offices: The Minnesota Example
Authors: Farley Dana , Leone Carman , Palmer Caroline 
Published: July 2024

AbstractIn recent years, the Minnesota Attorney General’s Office and the Minnesota Department of Health have cultivated a productive partnership to strengthen the state’s multidisciplinary response to overlapping health equity and social justice issues. This article describes shared efforts in three areas: post-conviction justice, drug overdose, and human trafficking/exploitation.
State Driving Under the Influence of Drugs Laws
Authors: Origenes Alexandra N. , White Sarah A. , McGinty Emma E. , Vernick Jon S. 
Published: July 2024

AbstractDrug-impaired driving is a growing problem in the U.S. States regulate drug-impaired driving in different ways. Some do not name specific drugs or amounts. Others do identify specific drugs and may regulate cannabis separately. We provide up-to-date information about these state laws.
Unlocking Public Health Data: Navigating New Legal Guardrails and Emerging AI Challenges
Authors: Cochlin Fallon J. , Curran Charles D. , Schmit Cason D. 
Published: July 2024

AbstractHere, we analyze the public health implications of recent legal developments — including privacy legislation, intergovernmental data exchange, and artificial intelligence governance — with a view toward the future of public health informatics and the potential of diverse data to inform public health actions and drive population health outcomes.
Local Public Health Departments at the Intersection of Climate Change, Health Equity, and Public Health Laws and Policies
Authors: Agahi Massoud , Bartlett Erika , Lawton Betsy , McAdams Jennie , Roy Rachel , Salehi Cameron 
Published: July 2024

AbstractPublic health laws and policies are uniquely able to mitigate the adverse and inequitable health impacts of climate change. This article summarizes some key considerations in developing such laws and policies and a variety of approaches local public health departments are using to increase climate resilience and health equity.
Upholding Tribal Sovereignty in Federal, State, and Local Emergency Vaccine Distribution Plans
Authors: Erb Heather , Peterson Kristin , Sunshine Brittany , Sunshine Gregory ,   the CDC COVID-19 Vaccine Task Force Federal Entities Team
Published: July 2024

AbstractCross jurisdictional collaboration efforts and emergency vaccine plans that are consistent with Tribal sovereignty are essential to public health emergency preparedness. The widespread adoption of clearly written federal, state, and local vaccine plans that address fundamental assumptions in vaccine distribution to Tribal nations is imperative for future pandemic response.
On the Move: 2023 Observations on Real Time Graben Formation, Grindavík, Iceland
Authors: De Pascale Gregory P. , Fischer Tomáš J. , Moreland William Michael , Geirsson Halldór , Hrubcová Pavla , Drouin Vincent , Forester Danielle , Payet‐‐Clerc Méline , da Silveira Diana Brum , Vlček Josef , Ófeigsson Benedikt G. , Höskuldsson Ármann , Torfadóttir Helga Kristín , Valdimarsdóttir Iðunn Kara , Blöndal Birta Dís Jónsdóttir , Jónsdóttir Ingibjörg , Jónsson Sigurjón , Thordarson Thor 
Published: July 2024

AbstractGrabens, or valleys formed during extensional tectonic events, are common but rarely observed during formation. In November 2023, inelastic surface deformation formed abruptly along Iceland's plate boundary in Grindavík. We documented graben formation in real‐time through satellite mapping (InSAR), seismicity, GNSS data, repeated lidar surveys, and field mapping. Five normal faults and ∼12 fissures ruptured the surface delineating two grabens separated by a horst, a context not present in other contemporary case studies. The graben normal faults slipped rapidly (over hours) and maximum surface motions coincided with the occurrence of turbulent seismic swarms in both space and time. Although 3 eruptions took place ∼15 km northeast of Grindavík from 2021 to 2023, attributed to magma intrusions (i.e., dikes), none of these also formed grabens. Thus, the Grindavík grabens shows evidence for tectonic origins. Real‐time monitoring of these phenomena provide insight into graben formation on Earth and potentially on other planets.
Extended Energy Conversion and Electron Acceleration Behind Dipolarization Front
Authors: Xing X. N. , Liu C. M. , Liu Y. Y. , Zhao B. N. 
Published: July 2024

AbstractEnergy transfer and transport in the terrestrial magnetotails are primarily driven by dipolarization fronts (DFs) embedded inside plasma jets. The DF‐driven energy transfer has hitherto been believed to occur locally at the fronts. Different from the traditional knowledge, here we present the first observation of persistent energy conversion extended far behind a DF. The persistent energy conversion, which was dominated by energy loads and mainly contributed by electron currents, developed inside a turbulent, decaying flux pileup region (FPR), nearly 10 dDF (DF’s thickness) behind the DF. The energy transfer chain may be initiated by interaction between the ion flow and ambient plasmas and closed by electron dynamics, leading to electron acceleration perpendicular to magnetic field. These results highlight that electron physics in turbulent FPRs plays a crucial role in the energy transport in the planetary magnetospheres.
Wearable cuffless blood pressure tracking: when will they be good enough?
Authors: Schutte Aletta E. 
Published: July 2024

AbstractWearable health monitoring is a multibillion-dollar industry. But the holy grail is probably getting it right for blood pressure monitoring without a cuff, because raised blood pressure is very common and the leading cause of death in the world. Many have tried and failed, but industry is persisting: numerous cuffless wearable blood pressure devices are on the market, several technologies have been developed, hundreds of patents are registered every year, and some devices already have regulatory approval. However, to convince the die-hard blood pressure critic is a different ball game. To understand the challenges of currently accepted methods and cuffless devices, I performed a 24-h blood pressure monitoring self-test, including measurements when awake, asleep and watching an intense match of the Rugby World Cup final, with the purpose to demonstrate the challenges and opportunities we face. Blood pressure was monitored using five different devices simultaneously: validated left and right arm cuff blood pressure, and three cuffless wearable devices (wrist-band, chest patch and a ring). Whilst none of these devices proved to be perfect in capturing a physiologically challenging measure, namely blood pressure, it emphasised that our current practice of a single blood pressure measurement in clinical practice should be revisited. It further begs the question of when cuffless measurements will be good enough to incorporate in clinical decision-making.
An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer
Authors: Lin Bing-Biao , Huang Qingqing , Yan Binyuan , Liu Mingcheng , Zhang Zhiqian , Lei Hanqi , Huang Ronghua , Dong Jin-Tang , Pang Jun 
Published: July 2024

Abstract
Background
The prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood.

Methods
We investigated associations of EC heterogeneity with PCa recurrence and castration resistance in 8 bulk transcriptomic and 4 single-cell RNA-seq cohorts. A recurrence-associated EC (RAEC) signature was constructed by comparing 11 machine learning algorithms through nested cross-validation. Functional relevances of RAEC-specific genes were also tested.

Results
A subset of ECs was significantly associated with recurrence in primary PCa and named RAECs. RAECs were characteristic of tip and immature cells and were enriched in migration, angiogenesis, and collagen-related pathways. We then developed an 18-gene RAEC signature (RAECsig) representative of RAECs. Higher RAECsig scores independently predicted tumor recurrence and performed better or comparably compared to clinicopathological factors and commercial gene signatures in multiple PCa cohorts. Of the 18 RAECsig genes, FSCN1 was upregulated in ECs from PCa with higher Gleason scores; and the silencing of FSCN1, TMEME255B, or GABRD in ECs either attenuated tube formation or inhibited PCa cell proliferation. Finally, higher RAECsig scores predicted castration resistance in both primary and castration-resistant PCa.

Conclusion
This study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance.
Structural basis of tethered agonism and G protein coupling of protease-activated receptors
Authors: Guo Jia , Zhou Yun-Li , Yang Yixin , Guo Shimeng , You Erli , Xie Xin , Jiang Yi , Mao Chunyou , Xu H. Eric , Zhang Yan 
Published: July 2024

AbstractProtease-activated receptors (PARs) are a unique group within the G protein-coupled receptor superfamily, orchestrating cellular responses to extracellular proteases via enzymatic cleavage, which triggers intracellular signaling pathways. Protease-activated receptor 1 (PAR1) is a key member of this family and is recognized as a critical pharmacological target for managing thrombotic disorders. In this study, we present cryo-electron microscopy structures of PAR1 in its activated state, induced by its natural tethered agonist (TA), in complex with two distinct downstream proteins, the Gq and Gi heterotrimers, respectively. The TA peptide is positioned within a surface pocket, prompting PAR1 activation through notable conformational shifts. Contrary to the typical receptor activation that involves the outward movement of transmembrane helix 6 (TM6), PAR1 activation is characterized by the simultaneous downward shift of TM6 and TM7, coupled with the rotation of a group of aromatic residues. This results in the displacement of an intracellular anion, creating space for downstream G protein binding. Our findings delineate the TA recognition pattern and highlight a distinct role of the second extracellular loop in forming β-sheets with TA within the PAR family, a feature not observed in other TA-activated receptors. Moreover, the nuanced differences in the interactions between intracellular loops 2/3 and the Gα subunit of different G proteins are crucial for determining the specificity of G protein coupling. These insights contribute to our understanding of the ligand binding and activation mechanisms of PARs, illuminating the basis for PAR1’s versatility in G protein coupling.
Orchestration of antiviral responses within the infected central nervous system
Authors: Pavlou Andreas , Mulenge Felix , Gern Olivia Luise , Busker Lena Mareike , Greimel Elisabeth , Waltl Inken , Kalinke Ulrich 
Published: July 2024

AbstractMany newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8+ T cells, which critically contribute to protection against viral CNS infection. By illuminating the prerequisites of myeloid and T cell activation, discussing new discoveries regarding their transcriptional signatures, and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS, we aim to further delineate the complexity of antiviral responses within the infected CNS. Moreover, we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.
Twist angle-dependent transport properties of twisted bilayer graphene
Authors: Kim Jin Hong , Kang Seoung-Hun , Yoon Duhee , Kim Hakseong , Kim Jin-Soo , Haidari Mohd Musaib , Jang Dong Jin , Ko Jin-Yong , Son Young-Woo , Park Bae Ho , Choi Jin Sik 
Published: July 2024

Abstract
Twisted bilayer graphene (tBLG) with small twist angles has attracted significant attention because of its unique electronic properties arising from the formation of a moiré superlattice. In this study, we systematically characterized the twist-angle-dependent electronic and transport properties of tBLG grown via chemical vapor deposition. This characterization included parameters such as the charge-neutral point voltage, carrier concentration, resistance, and mobility, covering a wide range of twist angles from 0° to 30°. We experimentally demonstrated that these parameters exhibited twist-angle-dependent moiré period trends, with high twist angles exceeding 9°, revealing more practically useful features, including improved mobilities compared to those of single-layer graphene. In addition, we demonstrated that the doping states and work functions were weakly dependent on the twist angles, as confirmed by additional first-principles calculations. This study provides valuable insights into the transport properties of tBLG and its potential for practical applications in the emerging field of twistronics.
Amplified warming of North American cold extremes linked to human-induced changes in temperature variability
Authors: Blackport Russell , Fyfe John C. 
Published: July 2024

AbstractHow global warming is impacting winter cold extremes is uncertain. Previous work has found decreasing winter temperature variability over North America which suggests a reduction in frequency and intensity of cold extremes relative to mean changes. However, others argue that cold air outbreaks are becoming more likely because of Arctic-induced changes in atmospheric circulation. Here we show that cold extremes over North America have warmed substantially faster than the winter mean temperature since 1980. This amplified warming is linked to both decreasing variance and changes in higher moments of the temperature distributions. Climate model simulations with historical forcings robustly capture the observed trends in extremes and variability. A pattern-based detection and attribution analysis shows that the changes in variability are detectable in observations and can be attributed to human influence. Our results highlight that human emissions are warming North American extreme cold temperatures beyond only shifting the winter mean temperature.
KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription
Authors: Hyder Usman , Challa Ashwini , Thornton Micah , Nandu Tulip , Kraus W. Lee , D’Orso Iván 
Published: July 2024

AbstractSignal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.
CoPheScan: phenome-wide association studies accounting for linkage disequilibrium
Authors: Manipur Ichcha , Reales Guillermo , Sul Jae Hoon , Shin Myung Kyun , Longerich Simonne , Cortes Adrian , Wallace Chris 
Published: July 2024

AbstractPhenome-wide association studies (PheWAS) facilitate the discovery of associations between a single genetic variant with multiple phenotypes. For variants which impact a specific protein, this can help identify additional therapeutic indications or on-target side effects of intervening on that protein. However, PheWAS is restricted by an inability to distinguish confounding due to linkage disequilibrium (LD) from true pleiotropy. Here we describe CoPheScan (Coloc adapted Phenome-wide Scan), a Bayesian approach that enables an intuitive and systematic exploration of causal associations while simultaneously addressing LD confounding. We demonstrate its performance through simulation, showing considerably better control of false positive rates than a conventional approach not accounting for LD. We used CoPheScan to perform PheWAS of protein-truncating variants and fine-mapped variants from disease and pQTL studies, in 2275 disease phenotypes from the UK Biobank. Our results identify the complexity of known pleiotropic genes such as APOE, and suggest a new causal role for TGM3 in skin cancer.
Advanced parametrization for the production of high-energy solid-state lithium pouch cells containing polymer electrolytes
Authors: Lee Wonmi , Lee Juho , Yu Taegyun , Kim Hyeong-Jong , Kim Min Kyung , Jang Sungbin , Kim Juhee , Han Yu-Jin , Choi Sunghun , Choi Sinho , Kim Tae-Hee , Park Sang-Hoon , Jin Wooyoung , Song Gyujin , Seo Dong-Hwa , Jung Sung-Kyun , Kim Jinsoo 
Published: July 2024

AbstractLithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg−1 (corresponding to an energy density of 600 Wh L−1) and 310 Wh kg−1 (corresponding to an energy density of 650 Wh L−1) respectively.
Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer
Authors: Zhou Xiaojun , Wang Genxin , Tian Chenhui , Du Lin , Prochownik Edward V. , Li Youjun 
Published: July 2024

AbstractTumor cells reprogram their metabolism to produce specialized metabolites that both fuel their own growth and license tumor immune evasion. However, the relationships between these functions remain poorly understood. Here, we report CRISPR screens in a mouse model of colo-rectal cancer (CRC) that implicates the dual specificity phosphatase 18 (DUSP18) in the establishment of tumor-directed immune evasion. Dusp18 inhibition reduces CRC growth rates, which correlate with high levels of CD8+ T cell activation. Mechanistically, DUSP18 dephosphorylates and stabilizes the USF1 bHLH-ZIP transcription factor. In turn, USF1 induces the SREBF2 gene, which allows cells to accumulate the cholesterol biosynthesis intermediate lanosterol and release it into the tumor microenvironment (TME). There, lanosterol uptake by CD8+ T cells suppresses the mevalonate pathway and reduces KRAS protein prenylation and function, which in turn inhibits their activation and establishes a molecular basis for tumor cell immune escape. Finally, the combination of an anti-PD-1 antibody and Lumacaftor, an FDA-approved small molecule inhibitor of DUSP18, inhibits CRC growth in mice and synergistically enhances anti-tumor immunity. Collectively, our findings support the idea that a combination of immune checkpoint and metabolic blockade represents a rationally-designed, mechanistically-based and potential therapy for CRC.