bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rethinking AI for Science: An Evolution From Data‐Driven to Data‐Centric Framework
Authors: Maskey Manil 
Published: December 2023

AbstractThe rapid advancements in Artificial Intelligence (AI) have found applications across a multitude of disciplines, including the scientific domain. Yet, the dominant focus on model‐centric AI often overlooks the critical role that data plays, thereby limiting its effectiveness in scientific investigations. This paper advocates for a transition to a data‐centric viewpoint, especially within the framework of AI applied to scientific advancements. The paper outlines the contrasting philosophies of model‐centric and data‐centric AI, highlighting the latter's commitment to data strategies. It explores a range of techniques that bolster the data‐centric framework. Furthermore, the paper presents an overview of key milestones in AI technology, the significance and the changing role of data‐centric AI, and the current state of research in this emerging field.
Monitoring of over-the-counter (OTC) and COVID-19 treatment drugs complement wastewater surveillance of SARS-CoV-2
Authors: Lee Cheng-Shiuan , Wang Mian , Nanjappa Deepak , Lu Yi-Ta , Meliker Jaymie , Clouston Sean , Gobler Christopher J. , Venkatesan Arjun K. 
Published: December 2023

Abstract
Background
The application of wastewater-based epidemiology to track the outbreak and prevalence of coronavirus disease (COVID-19) in communities has been tested and validated by several researchers across the globe. However, the RNA-based surveillance has its inherent limitations and uncertainties.

Objective
This study aims to complement the ongoing wastewater surveillance efforts by analyzing other chemical biomarkers in wastewater to help assess community response (hospitalization and treatment) during the pandemic (2020–2021).

Methods
Wastewater samples (n = 183) were collected from the largest wastewater treatment facility in Suffolk County, NY, USA and analyzed for COVID-19 treatment drugs (remdesivir, chloroquine, and hydroxychloroquine (HCQ)) and their human metabolites. We additionally monitored 26 pharmaceuticals including common over-the-counter (OTC) drugs. Lastly, we developed a Bayesian model that uses viral RNA, COVID-19 treatment drugs, and pharmaceuticals data to predict the confirmed COVID-19 cases within the catchment area.

Results
The viral RNA levels in wastewater tracked the actual COVID-19 case numbers well as expected. COVID-19 treatment drugs were detected with varying frequency (9–100%) partly due to their instability in wastewater. We observed a significant correlation (R = 0.30, p < 0.01) between the SARS-CoV-2 genes and desethylhydroxychloroquine (DHCQ, metabolite of HCQ). Remdesivir levels peaked immediately after the Emergency Use Authorization approved by the FDA. Although, 13 out of 26 pharmaceuticals assessed were consistently detected (DF = 100%, n = 111), only acetaminophen was significantly correlated with viral loads, especially when the Omicron variant was dominant. The Bayesian models were capable of reproducing the temporal trend of the confirmed cases.

Impact
In this study, for the first time, we measured COVID-19 treatment and pharmaceutical drugs and their metabolites in wastewater to complement ongoing COVID-19 viral RNA surveillance efforts. Our results highlighted that, although the COVID-19 treatment drugs were not very stable in wastewater, their detection matched with usage trends in the community. Acetaminophen, an OTC drug, was significantly correlated with viral loads and confirmed cases, especially when the Omicron variant was dominant. A Bayesian model was developed which could predict COVID-19 cases more accurately when incorporating other drugs data along with viral RNA levels in wastewater.
Oxytocin activity in the paraventricular and supramammillary nuclei of the hypothalamus is essential for social recognition memory in rats
Authors: Thirtamara Rajamani Keerthi , Barbier Marie , Lefevre Arthur , Niblo Kristi , Cordero Nicholas , Netser Shai , Grinevich Valery , Wagner Shlomo , Harony-Nicolas Hala 
Published: December 2023

AbstractOxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating short- and long-term forms of social recognition memory has not been fully investigated. In this study, we employed a chemogenetic approach to target the activity of PVH oxytocin neurons in male rats and found that specific silencing of this neuronal population led to an impairment in short- and long-term social recognition memory. We combined viral-mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus as a target of PVH oxytocinergic axonal projections in rats. We used multiplex fluorescence in situ hybridization to label oxytocin receptors in the SuM and determined that they are predominantly expressed in glutamatergic neurons, including those that project to the CA2 region of the hippocampus. Finally, we used a highly selective oxytocin receptor antagonist in the SuM to examine the involvement of oxytocin signaling in modulating short- and long-term social recognition memory and found that it is necessary for the formation of both. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforced the specific role of PVH oxytocin neurons in regulating this form of memory.
Geraniol reverses obesity by improving conversion of WAT to BAT in high fat diet induced obese rats by inhibiting HMGCoA reductase
Authors: Chand Shushmita , Tripathi Alok Shiomurti , Hasan Tabinda , Ganesh Kavitha , Cordero Mary Anne W. , Yasir Mohammad , Zaki Magdi E. A. , Tripathi Pankaj , Mohapatra Lucy , Maurya Rahul Kumar 
Published: December 2023

Abstract
Objectives
Present report evaluates the protective effect of geraniol on high fat diet (HFD) induced obesity in rats and also determines the molecular mechanism of it.

Methods
Rats were induced with obesity with administration of HFD for four weeks and geraniol 200 and 400 mg/kg p.o. was administered for the next four week in the respective groups. Blood glucose and oral glucose tolerance test (OGTT), lipid profile was estimated in the geraniol treated HFD induced obesity in rats. Moreover, docking study was performed to determine the specific mechanism of geraniol by targeting HMG-CoE A reductase (in silico).

Results
There was significant increase in body weight and amelioration in altered serum glucose and lipid profile were observed in the geraniol treated group than negative control group. Weight of organs and adipose tissue isolated from different regions of the body was reduced in geraniol treated group than negative control. Moreover, geraniol interact with HMG-CoA reductase having binding energy −5.13.

Conclusions
In conclusion, data of the report reveals that geraniol reduces obesity by promoting the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT), as it interacts with HMG-CoA reductase in HFD induced obesity in rats.
RPLP2 activates TLR4 in an autocrine manner and promotes HIF-1α-induced metabolic reprogramming in hepatocellular carcinoma
Authors: Yang Qingqing , Meng Xiangrui , Chen Jin , Li Xiangsu , Huang Yang , Xiao Xueyi , Li Rongqing , Wu Xudong 
Published: December 2023

AbstractMetabolic reprogramming is a major feature of cancer, and aerobic glycolysis is one of the most widely studied metabolic reprogramming processes. Acidic ribosome protein P2 (RPLP2) is associated with both tumorigenesis and endoplasmic reticulum stress. However, limited knowledge exists regarding the role of RPLP2 in hepatocellular carcinoma (HCC) progression. In the present study, we observed a significant upregulation of RPLP2 in HCC tissues. Moreover, RPLP2 expression is closely correlated with patient prognosis and survival. The subsequent experimental validation demonstrated that RPLP2 exerted a regulatory effect on the expression of glycolytic enzymes and lactate production, thereby facilitating HCC cell proliferation. Mechanistically, the PI3K/AKT signalling pathway was found to play an important role in the regulation of hypoxia-inducible factor-1α (HIF-1α)-mediated aerobic glycolysis and cell growth. RPLP2 activates TLR4 on the surface of HCC cells and the downstream PI3K/AKT pathway through autocrine signalling. This activation then facilitates the entry of HIF-1α into the nucleus, enabling it to fulfil its transcriptional function. In conclusion, our findings suggested that RPLP2 induces a metabolic shift towards aerobic glycolysis and facilitates the progression of HCC through TLR4-dependent activation of the PI3K/AKT/HIF-1α pathway. Our study revealed the novel mechanism by which the ribosomal protein RPLP2 regulates glycolysis to promote HCC progression. These findings may offer a potential therapeutic target for HCC treatment.
Investigation of monoclonal antibody CSX-1004 for fentanyl overdose
Authors: Bremer Paul T. , Burke Emily L. , Barrett Andrew C. , Desai Rajeev I. 
Published: December 2023

AbstractThe opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.
Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells
Authors: Maimaitili Muyesier , Chen Muwan , Febbraro Fabia , Ucuncu Ekin , Kelly Rachel , Niclis Jonathan Christos , Christiansen Josefine Rågård , Mermet-Joret Noëmie , Niculescu Dragos , Lauritsen Johanne , Iannielli Angelo , Klæstrup Ida H. , Jensen Uffe Birk , Qvist Per , Nabavi Sadegh , Broccoli Vania , Nykjær Anders , Romero-Ramos Marina , Denham Mark 
Published: December 2023

AbstractCurrent differentiation protocols for generating mesencephalic dopaminergic (mesDA) neurons from human pluripotent stem cells result in grafts containing only a small proportion of mesDA neurons when transplanted in vivo. In this study, we develop lineage-restricted undifferentiated stem cells (LR-USCs) from pluripotent stem cells, which enhances their potential for differentiating into caudal midbrain floor plate progenitors and mesDA neurons. Using a ventral midbrain protocol, 69% of LR-USCs become bona fide caudal midbrain floor plate progenitors, compared to only 25% of human embryonic stem cells (hESCs). Importantly, LR-USCs generate significantly more mesDA neurons under midbrain and hindbrain conditions in vitro and in vivo. We demonstrate that midbrain-patterned LR-USC progenitors transplanted into 6-hydroxydopamine-lesioned rats restore function in a clinically relevant non-pharmacological behavioral test, whereas midbrain-patterned hESC-derived progenitors do not. This strategy demonstrates how lineage restriction can prevent the development of undesirable lineages and enhance the conditions necessary for mesDA neuron generation.
Evolution of high-molecular-mass hyaluronic acid is associated with subterranean lifestyle
Authors: Zhao Yang , Zheng Zhizhong , Zhang Zhihui , Xu Yandong , Hillpot Eric , Lin Yifei S. , Zakusilo Frances T. , Lu J. Yuyang , Ablaeva Julia , Biashad Seyed Ali , Miller Richard A. , Nevo Eviatar , Seluanov Andrei , Gorbunova Vera 
Published: December 2023

AbstractHyaluronic acid is a major component of extracellular matrix which plays an important role in development, cellular response to injury and inflammation, cell migration, and cancer. The naked mole-rat (Heterocephalus glaber) contains abundant high-molecular-mass hyaluronic acid in its tissues, which contributes to this species’ cancer resistance and possibly to its longevity. Here we report that abundant high-molecular-mass hyaluronic acid is found in a wide range of subterranean mammalian species, but not in phylogenetically related aboveground species. These subterranean mammalian species accumulate abundant high-molecular-mass hyaluronic acid by regulating the expression of genes involved in hyaluronic acid degradation and synthesis and contain unique mutations in these genes. The abundant high-molecular-mass hyaluronic acid may benefit the adaptation to subterranean environment by increasing skin elasticity and protecting from oxidative stress due to hypoxic conditions. Our work suggests that high-molecular-mass hyaluronic acid has evolved with subterranean lifestyle.
Prostate cancer genetic risk and associated aggressive disease in men of African ancestry
Authors: Soh Pamela X. Y. , Mmekwa Naledi , Petersen Desiree C. , Gheybi Kazzem , van Zyl Smit , Jiang Jue , Patrick Sean M. , Campbell Raymond , Jaratlerdseri Weerachai , Mutambirwa Shingai B. A. , Bornman M. S. Riana , Hayes Vanessa M. 
Published: December 2023

AbstractAfrican ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a panel of roughly 20 pathogenic genes. Based on this knowledge, we are unable to determine polygenic risk or differentiate prostate cancer status interrogating whole genome data for 113 Black South African men. To further assess for potentially functional common and rare variant associations, here we interrogate 247,780 exomic variants for 798 Black South African men using a case versus control or aggressive versus non-aggressive study design. Notable genes of interest include HCP5, RFX6 and H3C1 for risk, and MKI67 and KLF5 for aggressive disease. Our study highlights the need for further inclusion across the African diaspora to establish African-relevant risk models aimed at reducing prostate cancer health disparities.
Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening
Authors: Ramos Azucena , Koch Catherine E. , Liu-Lupo Yunpeng , Hellinger Riley D. , Kyung Taeyoon , Abbott Keene L. , Fröse Julia , Goulet Daniel , Gordon Khloe S. , Eidell Keith P. , Leclerc Paul , Whittaker Charles A. , Larson Rebecca C. , Muscato Audrey J. , Yates Kathleen B. , Dubrot Juan , Doench John G. , Regev Aviv , Vander Heiden Matthew G. , Maus Marcela V. , Manguso Robert T. , Birnbaum Michael E. , Hemann Michael T. 
Published: December 2023

AbstractCAR-T therapy is a promising, novel treatment modality for B-cell malignancies and yet many patients relapse through a variety of means, including loss of CAR-T cells and antigen escape. To investigate leukemia-intrinsic CAR-T resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screens in an immunocompetent murine model of B-cell acute lymphoblastic leukemia (B-ALL) utilizing a modular guide RNA library. We identified IFNγR/JAK/STAT signaling and components of antigen processing and presentation pathway as key mediators of resistance to CAR-T therapy in vivo; intriguingly, loss of this pathway yielded the opposite effect in vitro (sensitized leukemia to CAR-T cells). Transcriptional characterization of this model demonstrated upregulation of these pathways in tumors relapsed after CAR-T treatment, and functional studies showed a surprising role for natural killer (NK) cells in engaging this resistance program. Finally, examination of data from B-ALL patients treated with CAR-T revealed an association between poor outcomes and increased expression of JAK/STAT and MHC-I in leukemia cells. Overall, our data identify an unexpected mechanism of resistance to CAR-T therapy in which tumor cell interaction with the in vivo tumor microenvironment, including NK cells, induces expression of an adaptive, therapy-induced, T-cell resistance program in tumor cells.
Transition between distinct hybrid skyrmion textures through their hexagonal-to-square crystal transformation in a polar magnet
Authors: Singh Deepak , Fujishiro Yukako , Hayami Satoru , Moody Samuel H. , Nomoto Takuya , Baral Priya R. , Ukleev Victor , Cubitt Robert , Steinke Nina-Juliane , Gawryluk Dariusz J. , Pomjakushina Ekaterina , Ōnuki Yoshichika , Arita Ryotaro , Tokura Yoshinori , Kanazawa Naoya , White Jonathan S. 
Published: December 2023

AbstractMagnetic skyrmions, topological vortex-like spin textures, garner significant interest due to their unique properties and potential applications in nanotechnology. While they typically form a hexagonal crystal with distinct internal magnetisation textures known as Bloch- or Néel-type, recent theories suggest the possibility for direct transitions between skyrmion crystals of different lattice structures and internal textures. To date however, experimental evidence for these potentially useful phenomena have remained scarce. Here, we discover the polar tetragonal magnet EuNiGe3 to host two hybrid skyrmion phases, each with distinct internal textures characterised by anisotropic combinations of Bloch- and Néel-type windings. Variation of the magnetic field drives a direct transition between the two phases, with the modification of the hybrid texture concomitant with a hexagonal-to-square skyrmion crystal transformation. We explain these observations with a theory that includes the key ingredients of momentum-resolved Ruderman–Kittel–Kasuya–Yosida and Dzyaloshinskii-Moriya interactions that compete at the observed low symmetry magnetic skyrmion crystal wavevectors. Our findings underscore the potential of polar magnets with rich interaction schemes as promising for discovering new topological magnetic phases.
Sub-50 nm perovskite-type tantalum-based oxynitride single crystals with enhanced photoactivity for water splitting
Authors: Xiao Jiadong , Nakabayashi Mamiko , Hisatomi Takashi , Vequizo Junie Jhon M. , Li Wenpeng , Chen Kaihong , Tao Xiaoping , Yamakata Akira , Shibata Naoya , Takata Tsuyoshi , Inoue Yasunobu , Domen Kazunari 
Published: December 2023

AbstractA long-standing trade-off exists between improving crystallinity and minimizing particle size in the synthesis of perovskite-type transition-metal oxynitride photocatalysts via the thermal nitridation of commonly used metal oxide and carbonate precursors. Here, we overcome this limitation to fabricate ATaO2N (A = Sr, Ca, Ba) single nanocrystals with particle sizes of several tens of nanometers, excellent crystallinity and tunable long-wavelength response via thermal nitridation of mixtures of tantalum disulfide, metal hydroxides (A(OH)2), and molten-salt fluxes (e.g., SrCl2) as precursors. The SrTaO2N nanocrystals modified with a tailored Ir–Pt alloy@Cr2O3 cocatalyst evolved H2 around two orders of magnitude more efficiently than the previously reported SrTaO2N photocatalysts, with a record solar-to-hydrogen energy conversion efficiency of 0.15% for SrTaO2N in Z-scheme water splitting. Our findings enable the synthesis of perovskite-type transition-metal oxynitride nanocrystals by thermal nitridation and pave the way for manufacturing advanced long-wavelength-responsive particulate photocatalysts for efficient solar energy conversion.
ANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria
Authors: Jang Hyowon , Song Jayeon , Kim Sunjoo , Byun Jung-Hyun , Lee Kyoung G. , Park Kwang-Hyun , Woo Euijeon , Lim Eun-Kyung , Jung Juyeon , Kang Taejoon 
Published: December 2023

AbstractEndonucleases have recently widely used in molecular diagnostics. Here, we report a strategy to exploit the properties of Argonaute (Ago) proteins for molecular diagnostics by introducing an artificial nucleic acid circuit with Ago protein (ANCA) method. The ANCA is designed to perform a continuous autocatalytic reaction through cross-catalytic cleavage of the Ago protein, enabling one-step, amplification-free, and isothermal DNA detection. Using the ANCA method, carbapenemase-producing Klebsiella pneumoniae (CPKP) are successfully detected without DNA extraction and amplification steps. In addition, we demonstrate the detection of carbapenem-resistant bacteria in human urine and blood samples using the method. We also demonstrate the direct identification of CPKP swabbed from surfaces using the ANCA method in conjunction with a three-dimensional nanopillar structure. Finally, the ANCA method is applied to detect CPKP in rectal swab specimens from infected patients, achieving sensitivity and specificity of 100% and 100%, respectively. The developed method can contribute to simple, rapid and accurate diagnosis of CPKP, which can help prevent nosocomial infections.
SAM, SAH and C. elegans longevity: insights from a partial AHCY deficiency model
Authors: Thapa Pankaj , Olek Katarzyna , Kowalska Agata , Serwa Remigiusz A. , Pokrzywa Wojciech 
Published: December 2023

AbstractSupplementation with S-adenosylhomocysteine (SAH) extends the lifespan of model organisms. To explore the impact of SAH on aging, we generated a Caenorhabditis elegans model by introducing the S-adenosylhomocysteine hydrolase (AHCY-1) variant Y145C, corresponding to the human AHCY Y143C pathogenic mutation. This mutation is anticipated to impair SAH hydrolysis, resulting in its increased levels. Our findings revealed that animals with this endogenous mutation exhibited delayed aging, accompanied by decreased S-adenosylmethionine (SAM) and moderately increased SAH levels. The extended lifespan of these worms depends on the AMP-activated protein kinase (AMPK), its activator Vaccinia virus–related kinase (VRK-1), and the DAF-16 transcription factor. The results underline the complex nature of SAH’s influence on aging, proposing that the balance between SAM and SAH might play a pivotal role in defining the lifespan of C. elegans. Moreover, our partial AHCY-1 deficiency model offers a tool for studying the intersection of methionine metabolism and aging.