bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the roles of ribosomal peptides in prokaryote-phage interactions through deep learning-enabled metagenome mining
Authors: Gao Ying , Zhong Zheng , Zhang Dengwei , Zhang Jian , Li Yong-Xin 
Published: May 2024

Abstract
Background
Microbial secondary metabolites play a crucial role in the intricate interactions within the natural environment. Among these metabolites, ribosomally synthesized and post-translationally modified peptides (RiPPs) are becoming a promising source of therapeutic agents due to their structural diversity and functional versatility. However, their biosynthetic capacity and ecological functions remain largely underexplored.

Results
Here, we aim to explore the biosynthetic profile of RiPPs and their potential roles in the interactions between microbes and viruses in the ocean, which encompasses a vast diversity of unique biomes that are rich in interactions and remains chemically underexplored. We first developed TrRiPP to identify RiPPs from ocean metagenomes, a deep learning method that detects RiPP precursors in a hallmark gene-independent manner to overcome the limitations of classic methods in processing highly fragmented metagenomic data. Applying this method to metagenomes from the global ocean microbiome, we uncover a diverse array of previously uncharacterized putative RiPP families with great novelty and diversity. Through correlation analysis based on metatranscriptomic data, we observed a high prevalence of antiphage defense-related and phage-related protein families that were co-expressed with RiPP families. Based on this putative association between RiPPs and phage infection, we constructed an Ocean Virus Database (OVD) and established a RiPP-involving host-phage interaction network through host prediction and co-expression analysis, revealing complex connectivities linking RiPP-encoding prokaryotes, RiPP families, viral protein families, and phages. These findings highlight the potential of RiPP families involved in prokaryote-phage interactions and coevolution, providing insights into their ecological functions in the ocean microbiome.

Conclusions
This study provides a systematic investigation of the biosynthetic potential of RiPPs from the ocean microbiome at a global scale, shedding light on the essential insights into the ecological functions of RiPPs in prokaryote-phage interactions through the integration of deep learning approaches, metatranscriptomic data, and host-phage connectivity. This study serves as a valuable example of exploring the ecological functions of bacterial secondary metabolites, particularly their associations with unexplored microbial interactions.
Knowledge of fertility period among reproductive age women in Kenya: a multilevel analysis based on 2022 Kenyan demographic and health survey
Authors: Fente Bezawit Melak , Asgedom Yordanos Sisay , Asmare Zufan Alamrie , Kebede Tirusew Nigussie , Damtew Beyene Sisay , Workneh Tadesu Wondu , Beyene Muluken Adamu , Seifu Beminate Lemma 
Published: May 2024

Abstract
Background
Knowledge of the fertility period aids women in refraining and engaging in sexual intercourse to avoid and to get pregnant, respectively. The effect of community-level factors on knowledge of the fertility period was not yet known in Kenya. Therefore, we aimed to investigate the community- and individual-level determinants of knowledge of fertility period among women of childbearing age in Kenya.

Methods
The 2022 Kenyan Demography and Health Survey data was used for the current study. This study included 16,901 women of reproductive age. To account for the clustering effects of DHS data and the binary nature of the outcome variable, a multilevel binary logistic regression model was applied. An adjusted odds ratio with a 95% confidence interval was reported to declare the statistical significance. In addition, the model that had the lowest deviance was the one that best fit the data.

Results
The overall prevalence of knowledge of the fertility period among Kenyan women was 38.1% (95%CI = 37.3, 38.9). Women’s age, women’s education status, heard FP, contraceptive use, media exposure, and distance from health facility significant individual factors while place of residence, and community-level education, were all of factors were found to be strongly associated with knowledge of fertility period.

Conclusion
As per the findings of our study, Knowledge of the fertility period among reproductive women was low in Kenya. In the era of increasing refusal of hormone-based family planning, fertility-awareness-based family planning methods may be an option. Promoting the correct fertility period through education and media outreach may be helpful strategies for enhancing fertility decision-making.
Effects of fluid saturation and viscosity on seismic dispersion characteristics in Berea sandstone
Authors: Wei Qianqian , Han De-Hua , Li Hui , Wang Jianhua , Wang Yang , Chen Jianjun 
Published: May 2024

Despite additional availability of laboratory data from water-saturated sandstone at seismic frequencies, measurements of rock samples saturated with high viscous fluids, particularly at partial saturation, are still rare. To quantify the effects of fluid viscosity and saturation levels on seismic dispersion and attenuation characteristics, we conducted two comparative forced-oscillation measurements in partially saturated sandstone with varying fluid viscosity (e.g., water, glycerin) at seismic frequencies (2–400 Hz). The results demonstrate that fluid viscosity and saturation levels substantially influence the dispersion and attenuation characteristics at the measured frequencies. Significant dispersion and attenuation are observed in the presence of a relatively small amount of gas (approximately 6%–8%) for glycerin and water saturation cases but vary in their magnitudes and characteristic frequencies. Specifically, the maximum extensional attenuation (approximately 0.024) occurs at approximately 200 Hz for water-saturated rock at 94% saturation, whereas at approximately 30 Hz with a peak of 0.032 for glycerin-saturated rock at 92% saturation. Based on theoretical modeling analysis, we suggest that mesoscopic fluid flow might be a dominant mechanism accounting for the observed attenuation in partial water or glycerin saturation, while the microscopic (squirt) flow mechanism possibly dominates the fully saturated cases.
Use of Natural Language Processing to Infer Sites of Metastatic Disease From Radiology Reports at Scale
Authors: Tay See Boon , Low Guat Hwa , Wong Gillian Jing En , Tey Han Jieh , Leong Fun Loon , Li Constance , Chua Melvin Lee Kiang , Tan Daniel Shao Weng , Thng Choon Hua , Tan Iain Bee Huat , Tan Ryan Shea Ying Cong 
Published: May 2024

PURPOSE To evaluate natural language processing (NLP) methods to infer metastatic sites from radiology reports. METHODS A set of 4,522 computed tomography (CT) reports of 550 patients with 14 types of cancer was used to fine-tune four clinical large language models (LLMs) for multilabel classification of metastatic sites. We also developed an NLP information extraction (IE) system (on the basis of named entity recognition, assertion status detection, and relation extraction) for comparison. Model performances were measured by F1 scores on test and three external validation sets. The best model was used to facilitate analysis of metastatic frequencies in a cohort study of 6,555 patients with 53,838 CT reports. RESULTS The RadBERT, BioBERT, GatorTron-base, and GatorTron-medium LLMs achieved F1 scores of 0.84, 0.87, 0.89, and 0.91, respectively, on the test set. The IE system performed best, achieving an F1 score of 0.93. F1 scores of the IE system by individual cancer type ranged from 0.89 to 0.96. The IE system attained F1 scores of 0.89, 0.83, and 0.81, respectively, on external validation sets including additional cancer types, positron emission tomography-CT ,and magnetic resonance imaging scans, respectively. In our cohort study, we found that for colorectal cancer, liver-only metastases were higher in de novo stage IV versus recurrent patients (29.7% v 12.2%; P < .001). Conversely, lung-only metastases were more frequent in recurrent versus de novo stage IV patients (17.2% v 7.3%; P < .001). CONCLUSION We developed an IE system that accurately infers metastatic sites in multiple primary cancers from radiology reports. It has explainable methods and performs better than some clinical LLMs. The inferred metastatic phenotypes could enhance cancer research databases and clinical trial matching, and identify potential patients for oligometastatic interventions.
Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials
Authors: Qi Changsong , Zhang Panpan , Liu Chang , Zhang Jun , Zhou Jun , Yuan Jiajia , Liu Dan , Zhang Miao , Gong Jifang , Wang Xicheng , Li Jian , Zhang Xiaotian , Li Ning , Peng Xiaohui , Liu Zhen , Yuan Daijing , Baffa Raffaele , Wang Yumeng , Shen Lin 
Published: May 2024

PURPOSE CT041 is a chimeric antigen receptor (CAR)–modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC). PATIENTS AND METHODS These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity. RESULTS The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients. CONCLUSION In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.
Multicenter Analysis of Cardiometabolic-Related Diagnoses in Youth With Congenital Adrenal Hyperplasia: A PEDSnet Study
Authors: Chen Li-Min , Valentine Anna , Davis Shanlee M , Graber Evan , Fechner Patricia Y , Furniss Anna , Nahata Leena , Pyle Laura , Vyas Arpita K , Vogiatzi Maria G , Nokoff Natalie J 
Published: May 2024

Abstract

Context
Small cohorts of youth with congenital adrenal hyperplasia (CAH) demonstrate increased risk of obesity and poor cardiometabolic health.

Objective
To determine the odds of cardiometabolic-related diagnoses in youth with CAH compared with matched controls in a cross-sectional analysis in a large, multisite database (PEDSnet).

Methods
Electronic health record data (2009-2019) from 6 PEDSnet sites were used to determine odds of cardiometabolic-related outcomes based on diagnosis, anthropometric, and laboratory data using logistic regression among youth with CAH vs controls. Youth with CAH and ≥1 outpatient visit in PEDSnet (n = 1647) were propensity score–matched on 8 variables to controls (n = 6588). A subset of youth with classic CAH (n = 547, with glucocorticoid and mineralocorticoid prescriptions) were matched to controls (n = 2188). Odds of having cardiometabolic-related diagnoses among youth over 2 years with CAH were compared with matched controls.

Results
Outcomes were calculated for all individuals with CAH (median age at last visit 12.9 years [7.3, 17.6]) and a subset with classic CAH (median age at last visit 11.6 years [4.7, 17.5]) compared with their matched controls. All individuals with CAH had higher odds of overweight/obesity (odds ratio [95% CI] 3.63 [3.24,4.07]), hypertension (3.07 [2.60,3.64]), dysglycemia (1.95 [1.35,2.82], dyslipidemia (2.28 [1.79,2.91]), and liver dysfunction (2.30 [1.91,2.76]) than matched controls. Individuals with classic CAH had higher odds of overweight/obesity (3.21 [2.61,3.93]), hypertension (8.22 [6.71,10.08]), and liver dysfunction (2.11 [1.55,2.89]) than matched controls.

Conclusion
Overall, youth with CAH are at increased risk of diagnoses related to worse cardiometabolic health.
Investigating GABA Neuron–Specific Androgen Receptor Knockout in two Hyperandrogenic Models of PCOS
Authors: Sucquart Irene E , Coyle Chris , Rodriguez Paris Valentina , Prescott Melanie , Glendining Kelly A , Potapov Kyoko , Begg Denovan P , Gilchrist Robert B , Walters Kirsty A , Campbell Rebecca E 
Published: May 2024

Abstract
Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signaling in GABAergic neurons is critical in PCOS pathogenesis in 2 well-characterized hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic peripubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to gonadotropin-releasing hormone (GnRH) neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy, and impaired glucose homeostasis, was not different between GABARKO and wild-type (WT) mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinizing hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signaling in GABA neurons is largely not required for the development of PCOS-like traits in androgenized models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signaling in GABA neurons.
Youth Caregivers of Adults in the United States: Prevalence and the Association Between Caregiving and Education
Authors: Miller Katherine E. M. , Hart Joanna L. , Useche Rosania Mateo , Coe Norma B. 
Published: May 2024

Abstract
A growing proportion of individuals adopt family caregiving roles. Family caregivers are the primary providers of long-term care in the United States yet limited federal policy supports exist, despite the known negative impacts of caregiving. There is also limited information about the prevalence of youth/young adult caregivers and the impacts of caregiving at formative ages in the United States. Our objective is to estimate the prevalence of youth caregivers and examine the association of caregiving with educational investments. We use the American Time Use Survey (2013–2019) to identify and describe youth caregivers (aged 15–18) and young adult caregivers (aged 19–22) and compare them with non-caregiving peers. We estimate that there are approximately 1,623,000 youth caregivers and 1,986,000 young adult caregivers, corresponding to 9.2% and 12.7% of these age groups, respectively. However, there is a wide range in the estimated prevalence per year, from approximately 364,000 to 2.8 million youth caregivers and from 353,000 to 2.2 million young adult caregivers, depending on caregiver definition. Unlike adult caregivers, we find that young men and women were nearly equally likely to provide care. We also find that non-White individuals are disproportionately represented as youth caregivers. Compared with non-caregiving peers, both youth and young adult caregivers are less likely to be enrolled in school and, among those enrolled in school, spend significantly less time on educational activities. Considering the association of caregiving among youth/young adults and education, policies supporting youth and young adult caregivers are critical.
Multiple intersecting pathways are involved in CPEB1 phosphorylation and regulation of translation during mouse oocyte meiosis
Authors: Kunitomi Chisato , Romero Mayra , Daldello Enrico Maria , Schindler Karen , Conti Marco 
Published: May 2024

ABSTRACT
The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in regulating mRNA translation in oocytes. However, the specifics of how and which protein kinase cascades modulate CPEB1 activity are still controversial. Using genetic and pharmacological tools, and detailed time courses, we have re-evaluated the relationship between CPEB1 phosphorylation and translation activation during mouse oocyte maturation. We show that both the CDK1/MAPK and AURKA/PLK1 pathways converge on CPEB1 phosphorylation during prometaphase of meiosis I. Only inactivation of the CDK1/MAPK pathway disrupts translation, whereas inactivation of either pathway alone leads to CPEB1 stabilization. However, CPEB1 stabilization induced by inactivation of the AURKA/PLK1 pathway does not affect translation, indicating that destabilization and/or degradation is not linked to translational activation. The accumulation of endogenous CCNB1 protein closely recapitulates the translation data that use an exogenous template. These findings support the overarching hypothesis that the activation of translation during prometaphase in mouse oocytes relies on a CDK1/MAPK-dependent CPEB1 phosphorylation, and that translational activation precedes CPEB1 destabilization.
KRAP regulates mitochondrial Ca2+ uptake by licensing IP3 receptor activity and stabilizing ER–mitochondrial junctions
Authors: Atakpa-Adaji Peace , Ivanova Adelina , Kujawa Karolina , Taylor Colin W. 
Published: May 2024

ABSTRACT
Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are high-conductance channels that allow the regulated redistribution of Ca2+ from the endoplasmic reticulum (ER) to the cytosol and, at specialized membrane contact sites (MCSs), to other organelles. Only a subset of IP3Rs release Ca2+ to the cytosol in response to IP3. These ‘licensed’ IP3Rs are associated with Kras-induced actin-interacting protein (KRAP, also known as ITPRID2) beneath the plasma membrane. It is unclear whether KRAP regulates IP3Rs at MCSs. We show, using simultaneous measurements of Ca2+ concentration in the cytosol and mitochondrial matrix, that KRAP also licenses IP3Rs to release Ca2+ to mitochondria. Loss of KRAP abolishes cytosolic and mitochondrial Ca2+ signals evoked by stimulation of IP3Rs via endogenous receptors. KRAP is located at ER–mitochondrial membrane contact sites (ERMCSs) populated by IP3R clusters. Using a proximity ligation assay between IP3R and voltage-dependent anion channel 1 (VDAC1), we show that loss of KRAP reduces the number of ERMCSs. We conclude that KRAP regulates Ca2+ transfer from IP3Rs to mitochondria by both licensing IP3R activity and stabilizing ERMCSs.
Bresser-Pereira: a reconstrução política do Brasil à luz das teses centrais do novo-desenvolvimentismo
Authors: Nassif André 
Published: May 2024

Neste ensaio, sintetizo as proposições do novo-desenvolvimentismo, corrente de pensamento econômico da qual o economista brasileiro Luiz Carlos Bresser-Pereira se destaca como o principal formulador. O argumento central do novo-desenvolvimentismo é que, nos países em desenvolvimento, trajetórias bem-sucedidas de alcance de renda per capita e de padrões de bem-estar para níveis médios prevalecentes nos países desenvolvidos (ou seja, a efetivação do catching-up) dependem da harmonização das políticas públicas (particularmente, as políticas industrial e tecnológica lato sensu e o regime macroeconômico), destinadas a sustentar o crescimento econômico e a promover a diversificação da estrutura produtiva e da pauta exportadora. Arranjos inadequados de política econômica podem fazer com que a rota inicialmente exitosa de catching up nos países em desenvolvimento seja desviada para longos períodos de estagnação, como tem sido o caso do Brasil e de diversos outros países em desenvolvimento nas últimas décadas. O artigo mostra que o principal avanço do novo-desenvolvimentismo em relação ao desenvolvimentismo clássico e cepalino é o esforço de integrar a macroeconomia à teoria do desenvolvimento econômico. Neste estudo, analiso as teses principais do novo-desenvolvimentismo, especialmente sua crítica à estratégia de crescimento com poupança externa e à não-neutralização da doença holandesa, “políticas habituais” observadas no Brasil e em outros países em desenvolvimento que, ao sobrevalorizar a moeda doméstica em relação às moedas dos parceiros comerciais, leva à desindustrialização e à estagnação econômica. No final, os comentários críticos a pontos que, a meu juízo, merecem aprimoramento na teoria novo-desenvolvimentista em nada afetam a validade e robustez de suas principais teses analisadas neste ensaio.
Gender Promotion Gaps and Career Aspirations
Authors: Azmat Ghazala , Cuñat Vicente , Henry Emeric 
Published: May 2024

Using a representative survey of U.S. lawyers, we document a sizeable gender gap in early partnership aspirations, which explains half of the later gender promotion gap. We further document that the correlation between aspirations and effort provides a “mechanical link” between aspirations and promotion. Early workplace experiences, such as harassment and demeaning comments, are linked to promotion aspirations. Moreover, early aspirations provide insight into eventual promotion outcomes that goes beyond what can be drawn only from expectations. Our study highlights that measuring aspirations and adapting the corporate culture that shapes them are key components for firms to improve workplace environments. This paper was accepted by Joshua Gans, business strategy. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.00715 .