bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRSC-04 DE NOVO GTP SYNTHESIS IS A METABOLIC VULNERABILITY FOR THE INTERCEPTION OF BRAIN METASTASES
Authors: Kieliszek Agata , Mobilio Daniel , Bassey-Archibong Blessing , Johnson Jarrod , Piotrowski Mathew , Aghaei Nikoo , Escudero Laura , Gwynne William , de Araujo Elvin , Sedighi Abootaleb , Chafe Shawn , Zhai Kui , Zhang Cunjie , Quaile Andrew , McKenna Dillon , Subapanditha Minomi , Gunning Patrick , Tokar Tomas , Montenegro-Burke J Rafael , Venugopal Chitra , Magolan Jakob , Singh Sheila 
Published: August 2024

Abstract
Patients with brain metastases (BM) face a 90% mortality rate within one year of diagnosis and the current standard of care is mainly palliative. Targeting BM-initiating cells (BMIC) is a feasible strategy to treat BM, but druggable targets are still very limited. Here, we applied Connectivity Map analysis to lung-, breast-, and melanoma- pre-metastatic BMIC gene expression signatures and identified inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo GTP synthesis pathway, as a target for BM. We showed that pharmacological and genetic perturbation of IMPDH attenuates BMIC proliferation in vitro and the formation of BM in vivo. Furthermore, we used medicinal chemistry to develop novel brain penetrant IMPDH-inhibitors with enhanced in vivo efficacy. Metabolomic analyses and CRISPR knockout studies confirmed that de novo GTP synthesis is a potent metabolic vulnerability in BM. Overall, our work employed a phenotype-guided therapeutic strategy to uncover IMPDH as a relevant target for attenuating BM outgrowth, which may provide an alternative treatment strategy for patients who are otherwise limited to palliation.
TRSC-06 CHARACTERIZATION OF A NON-SMALL CELL LUNG CANCER ROS1-FUSION BRAIN METASTASIS MODEL
Authors: Rijmers Jamie , Bui Viët , Heijningen Caroline van , Lebre Maria , Tellingen Olaf van , Beijnen Jos , Schinkel Alfred 
Published: August 2024

Abstract

BACKGROUND
Non-small cell lung cancer (NSCLC) represents 85 percent of all lung cancers. Among NSCLC patients, 1-2 percent harbor mutations in the ROS1 proto-oncogene (ROS1). The most prevalent fusion mutations observed include SLC34A2-, CD74- and EZR-ROS1. Approximately 30 percent of the NSCLC patients with these ROS1 fusions develop brain metastases over time, posing significant challenges in treatment efficacy, due to the blood-brain barrier (BBB). ATP-binding cassette (ABC) transporters in the BBB restrict the penetration of compounds into the brain, reducing treatment effectiveness. To address this critical gap in treatment efficacy, a model that accurately mimics NSCLC brain metastases might be of great value. Currently, no SLC34A2-ROS1 driven intracranial tumor model exists, which might limit the clinical development of targeted agents in ROS1-fusion brain metastases. Therefore, the development and characterization of a mouse intracranial brain tumor model utilizing HCC78 cells, which have an intrinsic ROS1-SLC34A2 fusion, could provide valuable insights into targeted therapy efficacy and enhance understanding of NSCLC disease progression.

METHOD
The publicly available HCC78 cells will be transduced with a mCherry-Luciferase tag, to enable tumor growth visualization over time. Nude FVB mice will be injected with 250.000 HCC78 cells intracranially. Tumor growth will be assessed using IVIS imaging and MRI scanning. When the tumor size reaches its endpoint, the mice will be sacrificed and perfused with Texas Red. The brain will be stained for different markers, to assess tumor proliferation, immune infiltration, ROS1 status and the presence of ABC-transporters.

RESULTS
Preliminary results show that HCC78 cells are able to grow intracranially. No significant side effects have been observed in the mice. Further characterization of this model is ongoing.
Effectiveness of digital health interventions for perinatal depression: a systematic review and meta-analysis
Authors: Anyanwu Ifunanya Stellamaris , Jenkins Judy 
Published: August 2024

Abstract
Pregnant women and new mothers within 1 year after delivery are at a high risk of depression, yet many do not get the help they need due to wide reasons heralding stigma, access, cost, time, and shortage of human resources. Hence, compelling the exploration of alternate and potentially cost-effective means of delivering care, including the leverage of digital tools. This review aimed to evaluate the effectiveness of digital health interventions in reducing depressive symptoms among perinatal women. Literatures were sought from seven academic databases alongside the references of previous reviews. Included studies were all quantitative study types involving the use of digital health interventions for perinatal women not more than 1-year post-delivery. Standardized mean difference and standard error were used to perform random-effect model meta-analysis. Sensitivity and subgroup analyses were performed to determine certainty and modifiers of the findings, respectively. Forty-eight studies were included in this review with 28 studies used for meta-analyses. Numerous digital channels were identified; however, none specified the use of a digital health theory in its development. The digital health interventions showed a small positive significant effect over the controls (standardized mean difference = 0.29, P = 0.003, I2 = 34%), and this was significantly influenced by intervention delivery and facilitation modes, time of initiation of the intervention, and period covered by the intervention. Although digital health interventions may hold some potential for perinatal depression, scaling the interventions may be challenging sequel to overlooked influences from the interactions within the human–computer–society complex.
Loneliness and brain rhythmic activity in resting state: an exploratory report
Authors: Hu Xin , Wang Xufang , Long Changquan , Lei Xu 
Published: August 2024

Abstract
Recent studies using resting-state functional magnetic resonance imaging have shown that loneliness is associated with altered blood oxygenation in several brain regions. However, the relationship between loneliness and changes in neuronal rhythm activity in the brain remains unclear. To evaluate brain rhythm, we conducted an exploratory resting-state electroencephalogram (EEG) study of loneliness. We recorded resting-state EEG signals from 139 participants (94 women; mean age = 19.96 years) and analyzed power spectrum density (PSD) and functional connectivity (FC) in both the electrode and source spaces. The PSD analysis revealed significant correlations between loneliness scores and decreased beta-band powers, which may indicate negative emotion, attention, reward, and/or sensorimotor processing. The FC analysis revealed a trend of alpha-band FC associated with individuals’ loneliness scores. These findings provide new insights into the neural basis of loneliness, which will facilitate the development of neurobiologically informed interventions for loneliness.
Privacy, Decisional Autonomy, and the Right to Intimate Association—Insights on the Cost of Being in Live-In Relationships in India Under New Legislation
Authors: Sriram Akshay 
Published: August 2024

ABSTRACT
The trend of states actively policing intimate arrangements does not remain unseen in the context of illiberal democracies. The prioritization of societal morality has continuously been a consideration within the conservative fold, whether it is in the denial of marriage rights to same-sex couples or active state intrusion into the intimacies of interpersonal relationships. The passage of the Uniform Civil Code (“UCC”) Bill in the State of Uttarakhand in India forms a segment of this concerning trend. Being a part of the ruling Bharatiya Janata Party’s (“BJP”) lofty aspirations, the UCC brings about a peculiar requirement. Couples in live-in relationships are now required to undergo a ‘mandatory’ registration procedure. As the implementation of a nationwide UCC becomes more imminent, the mandatory registration of live-in relationships raises important constitutional questions regarding the extent of state interference in private decision-making. Indian jurisprudence around the concept of ‘decisional autonomy’ peaked in Justice K.S. Puttaswamy v. Union of India. (“Puttaswamy”) But in the backdrop of the newly reconceptualized ‘Right to Intimate Association’ in Supriyo@Supriya Chakraborty v. Union of India (“Supriyo”), the Registration of live-in relationships is yet another peculiar constitutional conundrum to be explored.
Miniscule Mollicutes: Current hurdles to bacteriophage identification
Authors: Catchpowle Jody , Maynard Julia , Chang Barbara J , Payne Matthew S , Beeton Michael L , Furfaro Lucy L 
Published: August 2024

Abstract
Mollicutes are a diverse class of bacteria with a variety of unique characteristics that have allowed them to adapt to a range of hosts and often evade routine cultivation techniques. The focus of previous work has been on the major human pathogens; however, here we present a holistic introduction to the many other different genera that constitute the Mollicutes. They represent a significant One Health concern with limited available treatment options given their intrinsic and acquired resistance to many antibiotics. Bacteriophages (phages) are a promising therapeutic and one poorly explored in these bacteria and an avenue to understand gene transfer and resistance development. This review aims to emphasize the many unique and diverse qualities of the Mollicutes and synthesize our current understanding of phages of these bacteria and the challenges that have hindered their isolation and characterization.
Effect of SeaFeed, a canola oil infused with Asparagopsis armata, on methane emissions, animal health, performance, and carcass characteristics of Angus feedlot cattle
Authors: George Melissa M , Platts Samuel V , Berry Brent A , Miller Markus F , Carlock Anna M , Horton Taylor M , George Matthew H 
Published: August 2024

Abstract
The objectives of this project were to measure the effect of SeaFeed, a canola oil infused with Asparagopsis armata, on methane emissions, animal health, performance, and carcass characteristics of feedlot cattle. Angus steers (n = 160) with an initial body weight of 474.4 kg were fed a steam-flaked wheat and barley ration for 200 d in a large, commercial feedlot. A single-blinded randomized complete block design compared two treatments including control and SeaFeed included at a rate of 25 mg bromoform per kg dry matter intake (DMI). Monthly testing of bromoform levels in the canola demonstrated that SeaFeed maintained a stable bromoform concentration for 6 mo. The inclusion of SeaFeed had no effect on daily DMI. However, steers fed SeaFeed were more efficient with a 6.6% higher (P &lt; 0.01) gain-to-feed ratio as compared to control steers over the 200-d feeding period. This improved efficiency resulted in 0.094 kg higher (P &lt; 0.01) average daily gain and 19.7 kg higher (P &lt; 0.01) live exit weight in steers fed SeaFeed as compared to control steers. Steers fed SeaFeed produced 51.7% less (P &lt; 0.01) methane and yielded 50.5% less (P &lt; 0.01) methane over the 200-d feeding period as compared to cattle fed the control ration. Peak methane inhibition occurred on day 29 on feed with 90.6% less methane production in cattle fed SeaFeed as compared to control animals. SeaFeed reduced (P &lt; 0.01) methane intensity by 55.4% over the 200-d feeding period. Hot carcass weight tended (P = 0.097) to be 6.9 kg heavier in cattle fed SeaFeed as compared to controls. Cattle fed SeaFeed had similar (P &gt; 0.20) marbling, meat color, eye muscle, area, and ultimate pH to control cattle. Interestingly, cattle fed SeaFeed tended (P = 0.054) to have slightly higher fat color scores. Rumen papillae from cattle fed SeaFeed were more (P &lt; 0.01) gray in color and more oval (P &lt; 0.01) in shape as compared to control animals; however, rumen damage was not different between treatment groups. In regards to food safety and residues, all muscle, fat, and kidney samples were free from bromoform residues. Bromine residues in kidney and meat samples were higher (P &lt; 0.01) in the SeaFeed group as compared to controls. Cattle fed SeaFeed produced strip loin steaks similar (P &gt; 0.05) in eating quality to control cattle. These results demonstrate that SeaFeed reduced methane emissions, improved performance, and produced safe beef with similar eating quality to conventional beef.
Hypoxia activates macrophage‐NLRP3 inflammasome promoting atherosclerosis via PFKFB3‐driven glycolysis
Authors: Wang Xuan , Liu Xiangbin , Wu Wanzhou , Liao Longshen , Zhou Ming , Wang Xiaobo , Tan Zeming , Zhang Guogang , Bai Yongping , Li Xiang , Zhao Min 
Published: August 2024

AbstractThe onset and progression of atherosclerosis are closely linked to the involvement of macrophages. While the contribution of NLRP3 inflammasome activation to the creation of a local highly inflammatory microenvironment is well recognized, the precise triggers remain unclear. In this study, we aimed to investigate the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia‐induced glycolysis involving PFKFB3 in the development of atherosclerosis. To develop an atherosclerosis model, we selected ApoE knockout mice treated with a high‐fat western diet. We then quantified the expression of HIF‐1α, PFKFB3, and NLRP3. In addition, we administered the PFKFB3 inhibitor PFK158 during atherosclerosis modeling. The glycolytic activity was subsequently determined through 18F‐FDG micro‐PET/CT, ex vivo glucose uptake, and ECAR analysis. Furthermore, we employed lipopolysaccharide (LPS) and TNF‐α to induce the differentiation of bone marrow‐derived macrophages (BMDMs) into M1‐like phenotypes under both hypoxic and normoxic conditions. Our histological analyses revealed the accumulation of PFKFB3 in human atherosclerotic plaques, demonstrating colocalization with NLRP3 expression and macrophages. Treatment with PFK158 reduced glycolytic activity and NLRP3 inflammasome activation, thereby mitigating the occurrence of atherosclerosis. Mechanistically, hypoxia promoted glycolytic reprogramming and NLRP3 inflammasome activation in BMDMs. Subsequent blocking of either HIF‐1α or PFKFB3 downregulated the NLRP3/Caspase‐1/IL‐1β pathway in hypoxic BMDMs. Our study demonstrated that the HIF‐1α/PFKFB3/NLRP3 axis serves as a crucial mechanism for macrophage inflammation activation in the emergence of atherosclerosis. The therapeutic potential of PFKFB3 inhibition may represent a promising strategy for atheroprotection.
Translatome analysis in acute ischemic stroke: Astrocytes and microglia exhibit differences in poststroke alternative splicing of expressed transcripts
Authors: Jin Bingxue , Han Yilai , Xu Fang , Wang Junjie , Zhao Yunzhi , Liu Haijie , Wang Fei , Wang Ze , Lu Wanting , Wang Mingyang , Cui Lili , Zhao Yinan , Hao Junwei , Chai Guoliang 
Published: August 2024

AbstractAstrocytes and microglia undergo dynamic and complex morphological and functional changes following ischemic stroke, which are instrumental in both inflammatory responses and neural repair. While gene expression alterations poststroke have been extensively studied, investigations into posttranscriptional regulatory mechanisms, specifically alternative splicing (AS), remain limited. Utilizing previously reported Ribo‐Tag‐seq data, this study analyzed AS alterations in poststroke astrocytes and microglia from young adult male and female mice. Our findings reveal that in astrocytes, compared to the sham group, 109 differential alternative splicing (DAS) events were observed at 4 h poststroke, which increased to 320 at day 3. In microglia, these numbers were 316 and 266, respectively. Interestingly, the disparity between DAS genes and differentially expressed genes is substantial, with fewer than 10 genes shared at both poststroke time points in astrocytes and microglia. Gene ontology enrichment analysis revealed the involvement of these DAS genes in diverse functions, encompassing immune response (Adam8, Ccr1), metabolism (Acsl6, Pcyt2, Myo5a), and developmental cell growth (App), among others. Selective DAS events were further validated by semiquantitative RT‐PCR. Overall, this study comprehensively describes the AS alterations in astrocytes and microglia during the hyperacute and acute phases of ischemic stroke and underscores the significance of certain hub DAS events in neuroinflammatory processes.
Coping Mechanisms and Their Associations With Depression and Anxiety Among Healthcare Workers in the Aftermath of COVID-19 Pandemic
Authors: Mohamed Nihal , He Celestine , Rahman Nimra , Faherty Cara , Chan Chi , DePierro Jonathan M. , Clark Uraina , Peccoralo Lauren A. , Ripp Jonathan H. 
Published: August 2024

Objective
This study investigated the associations between anxiety, depression, and coping in healthcare workers during coronavirus disease 2019.

Methods
A survey used the Generalized Anxiety Disorder 2 to assess anxiety, the Patient Health Questionnaire 2 to assess depression, and the Brief Coping Orientation to Problems Experienced (COPE) scale to evaluate coping mechanisms.

Results
Of the 1172 participants who provided data, 24.7% screened positive for anxiety and 15.7% for depression. Logistic regression indicated that avoidance coping (odds ratio [OR], 3.92 [95% confidence interval (CI), 2.91–5.29]; P < 0.001) and substance use coping (OR, 1.39 [95% CI, 1.00–1.90]; P = 0.049) were associated with higher odds of depression. Avoidance coping (OR, 2.81 [95% CI, 2.15–3.67]; P < 0.001) and social support coping (OR, 1.59 [95% CI, 1.22–2.08]; P = 0.001) were associated with higher odds of anxiety.

Conclusions
Interventions are needed to improve healthcare workers' coping and well-being.
Microplastics as a novel facilitator for antimicrobial resistance: Effects of concentration, composition, and size onEscherichia colimultidrug resistance
Authors: Gross Neila , Muhvich Johnathan , Ching Carly , Gomez Bridget , Horvath Evan , Nahum Yanina , Zaman Muhammad H. 
Published: August 2024

AbstractMicroplastics (MPs) have emerged as a significant environmental pollutant with profound implications for public health, particularly as substrates to facilitate bacterial antimicrobial resistance (AMR). Recently, studies have shown that MPs may accommodate microbial communities, chemical contaminants and genetic material containing AMR genes. This study investigated the effects of MP concentration, composition, and size on the development of multidrug resistance inEscherichia coli. Specifically, we exposedE. colito varying concentrations of different MP types, including polyethylene (PE), polystyrene (PS), and polypropylene (PP), across a range of sizes (3-10 µm, 10-50 µm, and 500 µm). Results indicated a direct correlation between MP presence and elevated multidrug-resistant (MDR) inE. coli.Notably, MPs exhibited a higher propensity for facilitating resistance than control substrates such as glass, likely due to their hydrophobicity, greater adsorption capacities, and surface chemistries. Furthermore, we observed that co-culture with MPs resulted in biofilm formation. Notably, we found that the bacteria from passaged MPs formed stronger biofilms once the MPs were removed, associated with changes in motility. Thus, we find that MPs also select for cells that are better at forming biofilms, which can lead to recalcitrant infections in the environment and healthcare setting. Our study highlights the immediate need for comprehensive environmental management strategies to mitigate the risk posed by MPs.ImportanceAntimicrobial resistance is one of the world’s most pressing global health crises, with an estimated 10 million deaths per year forecasted by 2050. With the pipeline of antibiotics running dry, it is imperative that mitigation strategies understand the mechanisms that drive the genesis of antimicrobial resistance. One emerging dimension of antimicrobial resistance is the environment. This study highlights the relationship between a widespread environmental pollutant, (MPs), and the rise of drug-resistant bacteria. While it is known that MPs facilitate resistance through several modes (biofilm formation, plastic adsorption rates, etc.), this study fills the knowledge gap on how different types of MPs are contributing to antimicrobial resistance.
The phage protein paratox is a multifunctional metabolic regulator ofStreptococcus
Authors: Muna Tasneem Hassan , Rutbeek Nicole R. , Horne Julia , Lao Ying Wen , Krokhin Oleg V. , Prehna Gerd 
Published: August 2024

ABSTRACTStreptococcus pyogenes, or Group A Streptococcus (GAS), is a commensal bacteria and human pathogen. Central to GAS pathogenesis is the presence of prophage encoded virulence genes. The conserved phage gene for the protein paratox (Prx) is genetically linked to virulence genes, but the reason for this linkage is unknown. Prx inhibits GAS quorum sensing and natural competence by binding the transcription factor ComR. However, inhibiting ComR does not explain the virulence gene linkage. To address this, we took a mass-spectrometry approach to search for other Prx interaction partners. The data demonstrates that Prx binds numerous DNA binding proteins and transcriptional regulators. We show binding of Prxin vitrowith the GAS protein EndoS1 (SpyM3_0890) and the phage protein JM3 (SpyM3_1246). An EndoS1:Prx complex X-ray crystal structure reveals that EndoS1 and ComR possess a conserved Prx binding helix. Computational modelling predicts that the Prx binding helix is present in several, but not all, binding partners. Namely, JM3 lacks the Prx binding helix. As Prx is conformationally dynamic, this suggests partner-dependent binding modes. Overall, Prx acts as a metabolic regulator of GAS to maintain the phage genome. As such, Prx maybe a direct contributor to the pathogenic conversion of GAS.
Cross-feeding options define eco-evolutionary dynamics of deep oligotrophic groundwater microbiome
Authors: Somee Maryam Rezaei , González-Rosales Carolina , Gralka Matti , Turner Stephanie , Bertilsson Stefan , Dopson Mark , Mehrshad Maliheh 
Published: August 2024

AbstractDeep groundwaters populated by diverse and active microbes are among the most energy and nutrient-limited ecosystems. Characteristics of this ecosystem including nutrient and dispersal limitations, low cell densities, and episodic growth strategy interactively underpin the so far elusive eco-evolutionary dynamics of its microbiome. Here we applied a modular metabolic analyses on genome-resolved reconstructed community of disconnected deep groundwaters in the Fennoscandian Shield. In the community of deeper groundwaters despite their highly oligotrophic nature, lineages with larger genomes maintained larger populations which we hypothesize to be connected with their limited cross-feeding options. Thus providing an extension on the streamlining theory emphasizing the importance of ecological interactions in genome evolution which is further supported by the observed decrease in abundance of lineages with known metabolic dependencies, such as Patescibacteria and DPANN, with depth. The modular metabolic analyses showed that remarkably common niches based on same cross-feeding interactions are also available in different groundwaters, in addition to common niches for primary production. While these shared niches are critical for community assembly in this ecosystem, in different boreholes different lineages populated them. Our results provided new insights into the role of metabolic cross-feeding in genome evolution and community assembly of deep groundwater microbiome.