bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvements in September Arctic Sea Ice Predictions Via Assimilation of Summer CryoSat‐2 Sea Ice Thickness Observations
Authors: Zhang Yong‐Fei , Bushuk Mitchell , Winton Michael , Hurlin Bill , Gregory William , Landy Jack , Jia Liwei 
Published: December 2023

AbstractBecause of a spring predictability barrier, the seasonal forecast skill of Arctic summer sea ice is limited by the availability of melt‐season sea ice thickness (SIT) observations. The first year‐round SIT observations, retrieved from CryoSat‐2 from 2011 to 2020, are assimilated into the GFDL ocean–sea ice model. The model's SIT anomaly field is brought into significantly better agreement with the observations, particularly in the Central Arctic. Although the short observational period makes forecast assessment challenging, we find that the addition of May–August SIT assimilation improves September local sea ice concentration (SIC) and extent forecasts similarly to SIC‐only assimilation. Although most regional forecasts are improved by SIT assimilation, the Chukchi Sea forecasts are degraded. This degradation is likely due to the introduction of negative correlations between September SIC and earlier SIT introduced by SIT assimilation, contrary to the increased correlations found in other regions.
PhaseFIT: live-organoid phase-fluorescent image transformation via generative AI
Authors: Zhao Junhan , Wang Xiyue , Zhu Junyou , Chukwudi Chijioke , Finebaum Andrew , Zhang Jun , Yang Sen , He Shijie , Saeidi Nima 
Published: December 2023

AbstractOrganoid models have provided a powerful platform for mechanistic investigations into fundamental biological processes involved in the development and function of organs. Despite the potential for image-based phenotypic quantification of organoids, their complex 3D structure, and the time-consuming and labor-intensive nature of immunofluorescent staining present significant challenges. In this work, we developed a virtual painting system, PhaseFIT (phase-fluorescent image transformation) utilizing customized and morphologically rich 2.5D intestinal organoids, which generate virtual fluorescent images for phenotypic quantification via accessible and low-cost organoid phase images. This system is driven by a novel segmentation-informed deep generative model that specializes in segmenting overlap and proximity between objects. The model enables an annotation-free digital transformation from phase-contrast to multi-channel fluorescent images. The virtual painting results of nuclei, secretory cell markers, and stem cells demonstrate that PhaseFIT outperforms the existing deep learning-based stain transformation models by generating fine-grained visual content. We further validated the efficiency and accuracy of PhaseFIT to quantify the impacts of three compounds on crypt formation, cell population, and cell stemness. PhaseFIT is the first deep learning-enabled virtual painting system focused on live organoids, enabling large-scale, informative, and efficient organoid phenotypic quantification. PhaseFIT would enable the use of organoids in high-throughput drug screening applications.
Social epidemiology of the Mediterranean-dietary approaches to stop hypertension intervention for neurodegenerative delay (MIND) diet among early adolescents: the Adolescent Brain Cognitive Development Study
Authors: Nagata Jason M. , Bashir Ammal , Weinstein Shayna , Al-Shoaibi Abubakr A. A. , Shao Iris Yuefan , Ganson Kyle T. , Testa Alexander , Garber Andrea K. 
Published: December 2023

Abstract
Background
The purpose of our study was to understand the relationship between sociodemographic factors and adherence to the MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension] Intervention for Neurodegenerative Delay) diet in a demographically diverse national population-based sample of 9–12-year-olds in the US.

Methods
We analyzed data from the Adolescent Brain and Cognitive Development (ABCD) Study (Year 1, N = 8333). Multivariable linear regression analysis was used to identify associations between MIND diet score and sociodemographic factors, including race/ethnicity, household income, parent education level, age, sex, and sexual minority status.

Results
Compared to White adolescents, Latino adolescents showed the greatest adherence to the MIND diet. Boys had lower adherence to the MIND diet than girls. Lower household income was associated with lower adherence to the MIND diet. Older age was associated with lower adherence to the MIND diet. Sexual minorities had a lower adherence to the MIND diet when compared to their heterosexual counterparts.

Discussion
Female sex, Latino ethnicity, Asian and Black race, high household income, heterosexual sexual orientation, and younger age were associated with higher adherence to the MIND diet. These sociodemographic differences can inform targeted screening and counseling for clinicians and public health organizations among diverse adolescent populations.

Impact Statement

Sociodemographic disparities in diet quality have been documented, but none have explored adherence to the MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension] Intervention for Neurodegenerative Delay) diet in early adolescence.

In this demographically diverse sample of 9–12-year-old early adolescents in the U.S., we found notable and nuanced sociodemographic disparities in adherence to the MIND diet.

Sociodemographic factors associated with higher adherence to the MIND diet included female sex, Latino ethnicity, high household income, heterosexual sexual orientation, and younger age.
Pre-clinical indications of brain stimulation treatments for non-affective psychiatric disorders, a status update
Authors: Benster Lindsay L. , Weissman Cory R. , Stolz Louise A. , Daskalakis Zafiris J. , Appelbaum Lawrence G. 
Published: December 2023

AbstractOver the past two decades noninvasive brain stimulation (NIBS) techniques have emerged as powerful therapeutic options for a range of psychiatric and neurological disorders. NIBS are hypothesized to rebalance pathological brain networks thus reducing symptoms and improving functioning. This development has been fueled by controlled studies with increasing size and rigor aiming to characterize how treatments induce clinically effective change. Clinical trials of NIBS for specific indications have resulted in federal approval for unipolar depression, bipolar depression, smoking cessation, and obsessive-compulsive disorder in the United States, and several other indications worldwide. As a rapidly emerging field, there are numerous pre-clinical indications currently in development using a variety of electrical and magnetic, non-convulsive, and convulsive approaches. This review discusses the state-of-the-science surrounding promising avenues of NIBS currently in pre-approval stages for non-affective psychiatric disorders. We consider emerging therapies for psychosis, anxiety disorders, obsessive-compulsive disorder, and borderline personality disorder, utilizing transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and magnetic seizure therapy (MST), with an additional brief section for early-stage techniques including transcranial focused ultrasound stimulation (tFUS) and transcranial alternating current stimulation (tACS). As revealed in this review, there is considerable promise across all four psychiatric indications with different NIBS approaches. Positive findings are notable for the treatment of psychosis using tDCS, MST, and rTMS. While rTMS is already FDA approved for the treatment of obsessive-compulsive disorder, methodologies such as tDCS also demonstrate potential in this condition. Emerging techniques show promise for treating non-affective disorders likely leading to future regulatory approvals.
Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats
Authors: Reinwald Jonathan R. , Schmitz Christian N. , Skorodumov Ivan , Kuchar Martin , Weber-Fahr Wolfgang , Spanagel Rainer , Meinhardt Marcus W. 
Published: December 2023

AbstractAlcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin’s general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.
Compartment-specific multiomic profiling identifies SRC and GNAS as candidate drivers of epithelial-to-mesenchymal transition in ovarian carcinosarcoma
Authors: Herrington C. Simon , Oswald Ailsa J. , Stillie Lorna J. , Croy Ian , Churchman Michael , Hollis Robert L. 
Published: December 2023

Abstract
Background
Ovarian carcinosarcoma (OCS) is an exceptionally aggressive and understudied ovarian cancer type harbouring distinct carcinomatous and sarcomatous compartments. Here, we seek to identify shared and compartment-specific events that may represent potential therapeutic targets and candidate drivers of sarcomatous compartment formation through epithelial-to-mesenchymal transition (EMT).

Methods
We performed multiomic profiling (exome sequencing, RNA-sequencing, microRNA profiling) of paired carcinomatous and sarcomatous components in 12 OCS cases.

Results
While paired sarcomatous and carcinomatous compartments demonstrate substantial genomic similarities, multiple loci are recurrently copy number-altered between components; regions containing GNAS and SRC are recurrently gained within the sarcomatous compartment. CCNE1 gain is a common event in OCS, occurring more frequently than in high grade serous ovarian carcinoma (HGSOC). Transcriptomic analysis suggests increased MAPK activity and subtype switching toward poor prognosis HGSOC-derived transcriptomic subtypes within the sarcomatous component. The two compartments show global differences in microRNA profiles, with differentially expressed microRNAs targeting EMT-related genes (SIRT1, ZEB2) and regulators of pro-tumourigenic pathways (TGFβ, NOTCH); chrX is a highly enriched target of these microRNAs and is also frequently deleted across samples. The sarcomatous component harbours significantly fewer CD8-positive cells, suggesting poorer immune engagement.

Conclusion
CCNE1 gain and chrX loss are frequent in OCS. SRC gain, increased GNAS expression and microRNA dysregulation represent potential mechanisms driving sarcomatous compartment formation.
Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses
Authors: La Marca John E. , Aubrey Brandon J. , Yang Bruce , Chang Catherine , Wang Zilu , Kueh Andrew , Tai Lin , Wilcox Stephen , Milla Liz , Heinzel Susanne , Vremec David , Whelan Lauren , König Christina , Kaloni Deeksha , Voss Anne K. , Strasser Andreas , Diepstraten Sarah T. , Herold Marco J. , Kelly Gemma L. 
Published: December 2023

AbstractWhole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a new mediator of TRP53-mediated suppression of tumour expansion, and this discovery may open new avenues to harness this process for cancer therapy.
Targeting AKT induced Ferroptosis through FTO/YTHDF2-dependent GPX4 m6A methylation up-regulating and degradating in colorectal cancer
Authors: Zhang Ge , Mi Wunan , Wang Chuyue , Li Jiehan , Zhang Yizheng , Liu Nannan , Jiang Meimei , Jia Guiyun , Wang Feng , Yang Ge , Zhang Lingling , Wang Jiangang , Fu Yang , Zhang Yingjie 
Published: December 2023

AbstractFerroptosis is a new type of iron-dependent programmed cell death induced by lipid peroxidation. However, the underlying mechanisms and function in tumor therapy still remain undisclosed especially in post-transcription regulation. Here, we found that targeting AKT significantly induced GPX4 dependent ferroptosis and suppressed colorectal cancer growth both in vitro and in vivo. During this process, demethylase FTO was downregulated, which increased the m6A methylation level of GPX4, subsequently recognized by YTHDF2 and degraded. Prediction results showed that there are three potential methylated sites (193/647/766), and 193 site was identified as the right one, which was demethylated by FTO and read by YTHDF2. In parallel, AKT inhibition caused the accumulation of ROS which had a negative feedback on GPX4 expression. In addition, protective autophagy was initiated by MK2206 stimulation, while blocking autophagy further increased ferroptosis and markedly enhanced the anti-tumor activity of MK2206. In a word, inhibiting AKT activated ferroptosis through FTO/YTHDF2/GPX4 axis to suppress colon cancer progression, which raised FTO/GPX4 as potential biomarkers and targets in colorectal cancer therapy.
Lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor antagonist, ameliorates disease progression in amyotrophic lateral sclerosis model mice
Authors: Ikeda Takuya , Takahashi Keita , Higashi Minatsu , Komiya Hiroyasu , Asano Tetsuya , Ogasawara Akihiro , Kubota Shun , Hashiguchi Shunta , Kunii Misako , Tanaka Kenichi , Tada Mikiko , Doi Hiroshi , Takeuchi Hideyuki , Takei Kohtaro , Tanaka Fumiaki 
Published: December 2023

AbstractNogo–Nogo receptor 1 (NgR1) signaling is significantly implicated in neurodegeneration in amyotrophic lateral sclerosis (ALS). We previously showed that lateral olfactory tract usher substance (LOTUS) is an endogenous antagonist of NgR1 that prevents all myelin-associated inhibitors (MAIs), including Nogo, from binding to NgR1. Here we investigated the role of LOTUS in ALS pathogenesis by analyzing G93A-mutated human superoxide dismutase 1 (SOD1) transgenic (Tg) mice, as an ALS model, as well as newly generated LOTUS-overexpressing SOD1 Tg mice. We examined expression profiles of LOTUS and MAIs and compared motor functions and survival periods in these mice. We also investigated motor neuron survival, glial proliferation in the lumbar spinal cord, and neuromuscular junction (NMJ) morphology. We analyzed downstream molecules of NgR1 signaling such as ROCK2, LIMK1, cofilin, and ataxin-2, and also neurotrophins. In addition, we investigated LOTUS protein levels in the ventral horn of ALS patients. We found significantly decreased LOTUS expression in both SOD1 Tg mice and ALS patients. LOTUS overexpression in SOD1 Tg mice increased lifespan and improved motor function, in association with prevention of motor neuron loss, reduced gliosis, increased NMJ innervation, maintenance of cofilin phosphorylation dynamics, decreased levels of ataxin-2, and increased levels of brain-derived neurotrophic factor (BDNF). Reduced LOTUS expression may enhance neurodegeneration in SOD1 Tg mice and ALS patients by activating NgR1 signaling, and in this study LOTUS overexpression significantly ameliorated ALS pathogenesis. LOTUS might serve as a promising therapeutic target for ALS.
Swift 4D printing of thermoresponsive shape-memory polymers using vat photopolymerization
Authors: Alam Fahad , Ubaid Jabir , Butt Haider , El-Atab Nazek 
Published: December 2023

AbstractShape-memory polymers (SMPs) are smart materials that have gained significant attention in recent years owing to their widespread application in smart structures and devices. Digital light processing (DLP), a vat-photopolymerization-based technique, is a significantly faster technology for printing a complete layer in a single step. The current study reports a facile and fast method for the 3D printing of SMP-based smart structures using a DLP 3D printer and a customized resin. A liquid crystal (LC, RM257) was combined with the resin to introduce shape-memory properties. The combination of LCs in photocurable resin provides the opportunity to directly 3D-print thermoresponsive structures, avoiding the complexity of SMP resin preparation. The structures were printed with different geometries, and the shape-memory response was measured. Lattice structures were fabricated and programmed to obtain tunable mechanical properties. Furthermore, the strain-sensing response was measured to demonstrate the utility of these lattice structures as smart patches for joint-movement sensing. The SMPs can be prepared conveniently and can potentially be used for various applications, such as smart tools, toys, and meta-material sensors.
Spinal cord injury-induced gut dysbiosis influences neurological recovery partly through short-chain fatty acids
Authors: Jing Yingli , Yang Degang , Bai Fan , Wang Qiuying , Zhang Chao , Yan Yitong , Li Zihan , Li Yan , Chen Zhiguo , Li Jianjun , Yu Yan 
Published: December 2023

AbstractSpinal cord injury (SCI) can reshape gut microbial composition, significantly affecting clinical outcomes in SCI patients. However, mechanisms regarding gut–brain interactions and their clinical implications have not been elucidated. We hypothesized that short-chain fatty acids (SCFAs), intestinal microbial bioactive metabolites, may significantly affect the gut–brain axis and enhance functional recovery in a mouse model of SCI. We enrolled 59 SCI patients and 27 healthy control subjects and collected samples. Thereafter, gut microbiota and SCFAs were analyzed using 16 S rDNA sequencing and gas chromatography–mass spectrometry, respectively. We observed an increase in Actinobacteriota abundance and a decrease in Firmicutes abundance. Particularly, the SCFA-producing genera, such as Faecalibacterium, Megamonas, and Agathobacter were significantly downregulated among SCI patients compared to healthy controls. Moreover, SCI induced downregulation of acetic acid (AA), propionic acid (PA), and butyric acid (BA) in the SCI group. Fecal SCFA contents were altered in SCI patients with different injury course and injury segments. Main SCFAs (AA, BA, and PA) were administered in combination to treat SCI mice. SCFA supplementation significantly improved locomotor recovery in SCI mice, enhanced neuronal survival, promoted axonal formation, reduced astrogliosis, and suppressed microglial activation. Furthermore, SCFA supplementation downregulated NF-κB signaling while upregulating neurotrophin-3 expression following SCI. Microbial sequencing and metabolomics analysis showed that SCI patients exhibited a lower level of certain SCFAs and related bacterial strains than healthy controls. SCFA supplementation can reduce inflammation and enhance nourishing elements, facilitating the restoration of neurological tissues and the improvement of functional recuperation. Trial registration: This study was registered in the China Clinical Trial Registry (www.chictr.org.cn) on February 13, 2017 (ChiCTR-RPC-17010621).
Effective protection of photoreceptors using an inflammation-responsive hydrogel to attenuate outer retinal degeneration
Authors: Kim Hyerim , Roh Hyeonhee , Kim Sang-Heon , Lee Kangwon , Im Maesoon , Oh Seung Ja 
Published: December 2023

AbstractRetinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration. The injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitors, was loaded into the hydrogel to attenuate inflammatory factors. On-demand anti-inflammatory effects of microglia cells via the drug-loaded IRH were verified in vitro and in vivo retinal degeneration 10 (rd10) mice model. Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest the IRH reported here can be used to considerably delay vision loss caused by RP.
Mathematical discoveries from program search with large language models
Authors: Romera-Paredes Bernardino , Barekatain Mohammadamin , Novikov Alexander , Balog Matej , Kumar M. Pawan , Dupont Emilien , Ruiz Francisco J. R. , Ellenberg Jordan S. , Wang Pengming , Fawzi Omar , Kohli Pushmeet , Fawzi Alhussein 
Published: December 2023

AbstractLarge language models (LLMs) have demonstrated tremendous capabilities in solving complex tasks, from quantitative reasoning to understanding natural language. However, LLMs sometimes suffer from confabulations (or hallucinations), which can result in them making plausible but incorrect statements1,2. This hinders the use of current large models in scientific discovery. Here we introduce FunSearch (short for searching in the function space), an evolutionary procedure based on pairing a pretrained LLM with a systematic evaluator. We demonstrate the effectiveness of this approach to surpass the best-known results in important problems, pushing the boundary of existing LLM-based approaches3. Applying FunSearch to a central problem in extremal combinatorics—the cap set problem—we discover new constructions of large cap sets going beyond the best-known ones, both in finite dimensional and asymptotic cases. This shows that it is possible to make discoveries for established open problems using LLMs. We showcase the generality of FunSearch by applying it to an algorithmic problem, online bin packing, finding new heuristics that improve on widely used baselines. In contrast to most computer search approaches, FunSearch searches for programs that describe how to solve a problem, rather than what the solution is. Beyond being an effective and scalable strategy, discovered programs tend to be more interpretable than raw solutions, enabling feedback loops between domain experts and FunSearch, and the deployment of such programs in real-world applications.