bluuebunny/crossref_metadata_2025 huggingface dataset:
A rare case of granular cell tumor of gall bladder
Authors: Dhakal Sunil , Bhandari Sapana , Kandangwa Avinam H
Published: February 2025

Granular cell tumor is common over skin and subcutaneous and oral cavity. However, lesion is rare in biliary tract and ever more uncommon in gall bladder. These lesions are often misdiagnosed until proven by histology and immunohistochemistry where tumor is positive for CD 68, S 100 which points them toward neural origin of tumor. We report a case of 69-year-old male referred with a suspected gall bladder mass in Computed tomographic scan of abdomen. Laparotomy was done through Kocher’s incision and extended cholecystectomy was performed. Histopathology and immunohistochemical study helped in determining gall bladder lesion to be granular cell tumor. Therefore, granular cell tumor can be considered a possible differential diagnosis of all the gall bladder lesion suspected of cholecystitis and carcinoma. Margin negative excision of the tumor is a curative approach for the patient.
Precise gene expression deconvolution in spatial transcriptomics with STged
Authors: Tu Jia-Juan , Yan Hong , Zhang Xiao-Fei , Lin Zhixiang
Published: February 2025

Spatially resolved transcriptomics (SRT) has transformed tissue biology by linking gene expression profiles with spatial information. However, sequencing-based SRT methods aggregate signals from multiple cell types within capture locations (“spots”), masking cell-type-specific gene expression patterns. Traditional cell-type deconvolution methods estimate cell compositions within spots but fail to resolve cell-type-specific gene expression, limiting their ability to uncover critical biological processes such as cellular interactions and microenvironmental dynamics. Here, we present STged (spatial transcriptomic gene expression deconvolution), a novel computational framework that goes beyond traditional deconvolution by reconstructing cell-type-specific gene expression profiles from mixed spots. STged integrates graph-based spatial correlations and reference-derived gene signatures using a non-negative least-squares regression framework, achieving precise and biologically meaningful deconvolution. Comprehensive simulations show that STged consistently outperforms existing methods in accuracy and robustness. Applications to human pancreatic ductal adenocarcinoma and human squamous cell carcinoma datasets reveal its capacity to identify microenvironment-specific highly variable genes, reconstruct spatial cell–cell communication networks, and resolve tissue architecture at near-single-cell resolution. In mouse kidney tissues, STged uncovers dynamic spatial gene expression patterns and distinct gene programs, advancing our understanding of tissue heterogeneity and cellular dynamics.
Modifying the TL1-BINDING FACTOR upstream open reading frame coordinates plant growth and defense in rice
Authors: Tian Jingjing , Liu Yingshuang , Chen Dan , Xu Guoyong , Yuan Meng
Published: February 2025

Redesigning upstream open reading frames could fine-tune target gene translation, thereby facilitating an optimal balance between plant growth and defense.
Approaching or avoiding? Gender asymmetry in reactions to prior job search outcomes by gig workers in female- versus male-typed job domains
Authors: Yang Tiantian , Bao Jiayi , Leung Ming D
Published: February 2025

Despite recent increases in females entering male-typed job domains, women are more likely to exit these jobs than men, leading to a “leaky-pipeline” phenomenon and contributing to continued occupational gender segregation. Extant work has demonstrated that women are less likely to reapply to employers who previously rejected them for jobs in male-typed job domains. However, these studies leave unexamined whether women will reapply to other employers in those job domains and, if so, whether this pattern differs in female-typed job domains, hampering our confidence in the contribution of these patterns to gender segregation. This paper investigates whether employer rejection dampens women’s job-seeking persistence more than men’s for all employers and across male versus female job domains. Regression analyses of more than 700,000 applications for over 200,000 job postings by roughly 70,000 freelancers in an online contract labor market demonstrate that women are more likely than men to reduce job-seeking activity from all employers following rejections in the male-typed IT and programming job domain. Women are also more likely than men to seek jobs in other domains outside IT and programming following job-seeking rejection. By contrast, female freelancers in female-typed writing and translation jobs do not exhibit similar gendered behavior patterns. Implications for research on gender segregation, careers, and hiring are discussed.
Comprehensive Analysis of Class III Peroxidase Genes Revealed PePRX2 Enhanced Lignin Biosynthesis and Drought Tolerance in Phyllostachys edulis
Authors: Jia Yuhan , Li Mengyun , Xu Jing , Chen Shuxin , Han Xiaojiao , Qiu Wenmin , Lu Zhuchou , Zhuo Renying , Qiao Guirong
Published: February 2025

Class III peroxidase (PRX) is the key enzyme in lignin biosynthesis and critical for maintaining the redox balance in plants to respond to stress. In moso bamboo (Phyllostachys edulis), a globally significant non-timber forestry species, the potential roles of PRX genes remain largely unknown. In this research, a total of 179 PePRXs was identified on a genome-wide scale in moso bamboo. Phylogenic relationship, conserved motifs, gene structure, collinearity, and cis-acting elements were investigated. Analysis of gene expression indicated that PePRXs exhibited tissue-specific expression and different response patterns to hormones and abiotic stresses. Based on the transcriptome data, ten PePRXs with positive correlations between expression levels and lignification degree were screened out. Among them, PePRX2 was selected as a candidate gene according to the co-expression network. Y1H and Dual-Luc assays demonstrated that PeMYB61 could bind to the promoter of PePRX2 and enhance its transcription. The result of in situ hybridization showed that PePRX2 was specifically expressed in the vascular bundle sheath cells of bamboo shoot. As a secreted protein, PePRX2 was located on the cell wall. Overexpression of PePRX2 led to a significant increase in lignin content in transgenic poplar, indicating that PePRX2 could promote lignin polymerization. In comparison to the wild type, the PePRX2-OE poplar lines exhibited increased peroxidase activity and decreased levels of MDA, O2−, and H2O2 under drought stress, indicating enhanced drought resistance. This thorough analysis of the PRX family in moso bamboo provided new insight into the roles of PePRXs in lignin biosynthesis and drought adaptation.
Vertebral Artery Dissections
Authors: Purohit Shashvat , Filo Jean , Ramirez-Velandia Felipe , Ogilvy Christopher S.
Published: February 2025

Vertebral artery dissections (VADs) are an important potential cause of ischemic stroke and subarachnoid hemorrhage. The pathophysiology of VAD involves an intimal tear, leading to intramural hematoma and luminal stenosis, which can subsequently lead to occlusion or rupture of the vessel. Diagnostic challenges stem from the often subtle clinical presentation, typically involving unilateral head and neck pain. Management ranges from antithrombotic therapy to endovascular and surgical interventions, depending on severity. Despite advances in diagnostic imaging and treatment, outcomes vary, underscoring the need for prompt diagnosis and tailored therapeutic approaches.
Prediction of Palatoplasty Timing for Infants With Cleft Lip and Palate Using Machine Learning Algorithm
Authors: Jeon Sungmi , Jang Jiwoo , Chakraborty Sabyasachi , Kim So Hee , Oh Seoyoung , Kim Sukwha , Moon Jin Soo , Chung Jee Hyeok , Baek Seung-Hak
Published: February 2025

This study aims to predict the timing of palatoplasty in infants with cleft lip and palate (CLP) using a machine learning (ML) algorithm. The study included 111 patients with nonsyndromic CLP. Patient subgroups were classified based on birth weight (criterion: -1 SD, low birth weight versus normal birth weight) and cheiloplasty timing (criterion: 5 mo, early cheiloplasty versus late cheiloplasty). Growth trajectories at T2 were compared using T0-weight z-scores between the birth weight subgroups. Changes in the z-scores of weight and height from T1 to T2 were compared between the cheiloplasty timing subgroups. After training the tree-based ML models using cleft type, age, height, and weight at T0, T1, and T2, the palatoplasty timing was predicted with cleft type, weight at T0, and age, height, and weight at T1. The low-birth weight subgroup showed significant catch-up growth during T0-T1 and T0-T2 (all P<0.0001), resulting in no significant difference from the normal birth weight subgroup at T2. Compared with the late cheiloplasty subgroup, the early cheiloplasty subgroup underwent palatoplasty earlier (13.1 versus 14.3 mo; P<0.0001) and showed higher growth rates of weight and height and a greater increase in weight z-scores from T1 to T2 (all P<0.001). The CatBoost algorithm, with a root mean square error of 1.6 months, accurately predicted the palatoplasty timing (mean: actual, 12.8±1.8 mo versus prediction, 12.8±1.0 mo). Use of ML-assisted prediction method may help clinicians decide the timing of personalized palatoplasty in infants with CLP.
Medications used among Non-Hospitalized Pregnant Women with COVID-19: a Prospective Individual Patient Data Meta-analysis in Europe and North America
Authors: de Bruin Odette , Maisonneuve Emeline , Hurley Eimir , Nordeng Hedvig ME , Bérard Anick , Sheehy Odile , Kaul Padma , Shinde Mayura U , Cosgrove Austin , Lyons Jennifer G , Messenger-Jones Elizabeth , Kempner Maria E , Toh Sengwee , Hua Wei , Hernández-Muñoz José J , Sahin Leyla , Cesta Carolyn E , Hägg David , Gini Rosa , Paoletti Olga , Poblador-Plou Beatriz , Jordan Sue , Thayer Daniel , Rodríguez-Bernal Clara L , Sánchez-Sáez Francisco , Lassalle Régis , Bernard Marie-Agnès , Alsina Ema , Ahmadizar Fariba , Favre Guillaume , Panchaud Alice , Bloemenkamp Kitty WM , Plueschke Kelly , de Vries Corinne , Siiskonen Satu J , Sturkenboom Miriam CJM
Published: February 2025

Aim

To estimate the prevalence of medication use in non-hospitalized pregnant women with COVID-19

Methods

A prospective two-stage individual patient meta-analysis across 10 data sources in Europe and North America studied medication use among non-hospitalized pregnant women with COVID-19 between January 2020 to December 2022. Comparisons were made between medication use within 30 days pre- and post-COVID-19 diagnosis in this cohort and two comparator groups: pregnant women without COVID-19, and non-pregnant women with COVID-19. Prevalence estimates were pooled using a random-effects model stratified by trimester.

Results

50,335 non-hospitalized pregnant women with COVID-19 were identified. The pooled prevalence of antibacterial use in 3rdtrimester was higher post-COVID-19 diagnosis (6.8%, 95%CI 5.5-8.4, I2=94%) compared with the same women pre-COVID-19 (3.9%, 95%CI 3.1-4.9, I2=89%). Overall, pregnant women with COVID-19 had higher medication use compared to pregnant women without COVID-19, although these differences were not statistically significant. Post-COVID-19, antithrombotics prevalence was 4.5% (95%CI 1.1-16.5, I2=100%) among pregnant women with COVID-19 in 3rdtrimester, compared to 2.1% (95%CI 1.2-3.6, I2=99%) among those without COVID-19 in 3rdtrimester. Compared to non-pregnant women with COVID-19, pregnant women with COVID-19 were less likely to be prescribed analgesics, antiprotozoals, corticosteroids, psychoanaleptics and psycholeptics, and more likely to be prescribed antithrombotics, cough and cold and nasal preparations across all trimesters. High heterogeneity existed in nearly all analyses.

Conclusion

This international meta-analysis reveals low medication use and country-specific variations, enhancing insight into the management of COVID-19 in non-hospitalized pregnant women. Higher antithrombotics use post-COVID-19 suggests prophylactic treatment in this population.
Survival benefits of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma: evidence from a SEER-based retrospective cohort study
Authors: Peng Xiongwu , Duan Lingxing , Shi Runlin
Published: February 2025

Background

Metastatic renal cell carcinoma (mRCC) is associated with poor prognosis, with a 5-year survival rate of less than 15%. Cytoreductive nephrectomy (CN) has historically played a critical role in mRCC management, potentially enhancing systemic therapy efficacy by reducing tumor burden. However, its relevance in the era of targeted therapies and immune checkpoint inhibitors (ICIs) has been questioned.

Objective

This study evaluates the survival benefits of CN in mRCC patients using real-world, population-based data from the SEER database.

Methods

A retrospective cohort analysis of 6,030 mRCC patients was performed using data from 2010 to 2017. Propensity score matching (PSM) minimized selection bias, yielding 1,350 matched patients. Kaplan-Meier survival curves and multivariate Cox proportional hazards models assessed the impact of CN on overall survival (OS) and RCC-specific survival (CSS), stratified by demographic and clinical characteristics.

Results

CN was associated with a 71% reduction in all-cause mortality (HR = 0.29, 95% CI = 0.25–0.33) and RCC-specific mortality (HR = 0.29, 95% CI = 0.25–0.34). Five-year OS rates were 31.5% in the CN group versus 3.6% in the non-CN group. Survival benefits were consistent across subgroups, including patients with high-grade or advanced-stage tumors, underscoring the role of CN within multimodal treatment strategies.

Conclusion

CN confers significant survival advantages in mRCC, even in challenging clinical scenarios. These findings reinforce the importance of integrating CN into multimodal therapeutic frameworks, particularly alongside modern systemic therapies. Further prospective studies are warranted to optimize patient selection and treatment sequencing.
Interparticle Crosslinked Ion-responsive Microgels for 3D and 4D (Bio)printing Applications
Authors: Pal Vaibhav , Gupta Deepak , Liu Suihong , Namli Ilayda , Rizvi Syed Hasan Askari , Yilmaz Yasar Ozer , Haugh Logan , Gerhard Ethan Michael , Ozbolat Ibrahim T.
Published: February 2025

Abstract

Microgels offer unique advantages over bulk hydrogels due to their improved diffusion limits for oxygen and nutrients. Particularly, stimuli-responsive microgels with inherently bioactive and self-supporting properties emerge as highly promising biomaterials. This study unveils the development of interparticle-crosslinked, self-supporting, ion-responsive microgels tailored for 3D and 4D (bio)printing applications. A novel strategy was proposed to develop microgels that enabled interparticle crosslinking, eliminating the need for filler hydrogels and preserving essential microscale void spaces to support cell migration and vascularization. Additionally, these microgels possessed unique, ion-responsive shrinking behavior primarily by the Hofmeister effect, reversible upon the removal of the stimulus. Two types of microgels, spherical (µS) and random-shaped (µR), were fabricated, with µR exhibiting superior mechanical properties and higher packing density. Fabricated microgel-based constructs supported angiogenesis with tunable vessel size based on interstitial void spaces while demonstrating excellent shear-thinning and self-healing properties and high print fidelity. Various bioprinting techniques were employed and validated using these microgels, including extrusion-based, embedded, intraembedded, and aspiration-assisted bioprinting, facilitating the biofabrication of scalable constructs. Multi-material 4D printing was achieved by combining ion-responsive microgels with non-responsive microgels, enabling programmable shape transformations upon exposure to ionic solutions. Utilizing 4D printing, complex, dynamic structures were generated such as coiling filaments, grippers, and folding sheets, providing a foundation for the development of advanced tissue models and devices for regenerative medicine and soft robotics, respectively.
Repurposing statins and phenothiazines to treat chemoresistant neuroblastoma
Authors: Radke Katarzyna , Aaltonen Kristina , Muciño-Olmos Erick A. , Esfandyari Javanshir , Mañas Adriana , Seger Alexandra , Adamska Aleksandra , Hansson Karin , Rogova Oksana , Mason Daniel J. , O’Donovan Daniel J. , Roberts Ian , Lock Antonia , Brennan Jane , Davies Emma J. , Spégel Peter , Bedoya-Reina Oscar C. , Brown David , Thompson Neil T. , Spadoni Cesare , Bexell Daniel
Published: February 2025

Relapse and treatment resistance are common in children with high-risk neuroblastoma, and novel therapies are needed. Conventional drug discovery is slow, expensive, often fails in practice, and consequently falls short in addressing pediatric and rare conditions. In such instances, drug repurposing is a promising strategy. Here, we used two independentin silicoprediction tools including machine learning to identify approved drugs for repurposing against neuroblastoma. The combination of statins and phenothiazines showed strong synergistic effects in human neuroblastoma organoids, decreased tumor growth and prolonged survival inMYCN-amplified neuroblastoma patient-derived xenografts. The drug combination altered cholesterol metabolism through a dual-hit mechanism and induced a phenotypic switch towards an adrenergic cell state accompanied by increased sensitivity to chemotherapy. Integration of the drug combination into standard-of-care chemotherapy regressed tumors and prolonged survival in chemoresistant patient-derived xenografts. Thus, a combination of safe and approved medications added to standard-of-care chemotherapy outperforms chemotherapy alone in chemoresistant neuroblastoma.

Teaser

Usingin silicoprediction tools we repurposed statins and phenothiazines as a combination with translational potential in high-risk neuroblastoma.
Metabolic modeling reveals synergistic growth benefits of engineering maize symbiosis with rhizobia and arbuscular mycorrhizal fungi
Authors: Kaste Joshua A.M. , Ji Rourou , Sydow Patrick , Sawers Ruairidh J. H. , Matthews Megan L.
Published: February 2025

Engineering N2-fixing rhizobia symbiosis in cereals and enhancing association with arbuscular mycorrhizal fungi (AMF) are two strategies being pursued to improve agricultural sustainability. However, the metabolic fluxes and consequent costs and benefits of these strategies in a cereal crop have not been examined. We developed a metabolic model describing how the relative growth rate ofZea maysis impacted by hypothetical association with the rhizobiumBradyrhizobium diazoefficiensand the AMFRhizophagus irregularis. We found that the lower N content of cereal crops makes the relative growth rate cost associated with acquiring nitrogen from N2-fixing rhizobia smaller than in legumes. Our model also predicts positive synergies between rhizobia and AMF under nutrient-limited conditions but negative synergies under nutrient, particularly phosphorus, replete conditions. These findings indicate that these bioengineering strategies could improve cereal crop yields and may achieve greater gains in tandem, but soil nutrient status of target sites should be considered.

Significance Statement

Fertilizer application is responsible for substantial environmental impacts and represents a significant cost to farmers, both barriers to sustainable agricultural development. Engineering cereal crops to associate with N2-fixing rhizobia and enhancing existing associations between crops and arbuscular mycorrhizal fungi (AMF) are two strategies that could address these challenges. However, quantitative predictions of their potential effectiveness have not been determined. We use metabolic modeling to demonstrate that engineering maize to associate with N2-fixing rhizobia could be a highly metabolic and cost-effective strategy for sustainably supplying nitrogen to cereal crops. We also develop and experimentally validate a model of plant-AMF carbon and nutrient exchanges and demonstrate that AMF and rhizobia symbioses can act synergistically under nitrogen– and phosphorus-deprivation to improve crop growth.
Lower Bounds on the Sample Complexity of Species Tree Estimation when Substitution Rates Vary Across Loci
Authors: Hill Max , Roch Sebastien
Published: February 2025

In this paper we analyze the effect of substitution rate heterogenity on the sample complexity of species tree estimation. We consider a model based on the multi-species coalescent (MSC), with the addition that gene trees exhibit random i.i.d. rates of substitution. Our first result is a lower bound on the number of loci needed to distinguish 2-leaf trees (i.e., pairwise distances) with high probability, when substitution rates satisfy a growth condition. In particular, we show that to distinguish two distances differing by lengthfwith high probability, one requiresO(f−2) loci, a significantly higher bound than the constant rate case. The second main result is a lower bound on the amount of data needed to reconstruct a 3-leaf species tree with high probability, when mutation rates are gamma distributed. In this case as well, we show that the number of gene trees must grow asO(f−2).
Investigation of immune response to Mesenchymal Stromal Cell-derived Extracellular Vesicles in the cancer setting
Authors: Gilligan Katie E , Treacy Oliver , ’Neill Clodagh P O , McCarthy Elan C , McDermott Emma , Mammen Elma , Dockery Peter , Ryan Aideen E , Dwyer Róisín M
Published: February 2025

Mesenchymal Stromal Cell derived extracellular vesicles (MSC-EVs) may retain the cancer targeting and immune privilege of MSCs. The immense potential MSC-EVs hold as tumour-targeted therapeutics warrants an understanding of potential adverse events to support clinical translation. This study aimed to determine whether MSC-EVs would elicit an immune response following administration in tumour-bearing immunocompetent animals. Secreted EVs were isolated from both human and murine bone marrow derived MSCs and characterized. hMSC-EVs or mMSC-EVs were administered intravenously into 4T1 breast tumour-bearing Balb/c mice or healthy controls. Tumour tissue, draining lymph nodes and spleens were harvested, dissociated into a single cell suspension and flow cytometry performed targeting T cells, myeloid derived suppressor cells (MDSCs), macrophages, dendritic cells and natural killer (NK) cells. The 4T1 model immune profile was first determined by comparing the spleen of tumour-bearing animals to healthy controls. T cells were increased in tumour-bearing animals (CD4+/CD25+ p=0.041; CD8+/CD25+ p=0.02). A significant elevation of GR-1+ MDSCs (p=0.002), CD11b+ macrophages (p=0.023) and CD11c+ dendritic cells (p=0.001) was also observed. In contrast, CD27+ NK cells were significantly decreased compared to the spleen of healthy animals (p=0.006). Collectively this data validated the immune profile and supported the determination of any changes in response to hMSC-EVs or mMSC-EVs administration. No significant activation of CD4+ (p=0.20) or CD8+ (p=0.57) T cells were seen in tumour tissue in both groups. The percentage of GR-1+ MDSCs (28% vs 27%, p=0.92), CD11b+, CD11c+ and CD27+ cells were similar regardless of EV origin. No significant changes in T cells, MDSCs, macrophages, dendritic or NK cells were observed in the lymph node or spleen of animals that received hMSC-EV versus mMSC-EVs. In conclusion, human MSC-EVs elicited no discernible immune response in mice, supporting the hypothesis that MSC-EVs retain the immune privilege of the secretory cell. This reinforces the therapeutic potential of MSC-EVs.
Overcoming Immune Checkpoint Inhibitor Resistance via Potent and Selective Dual αvβ6/8 Inhibitors Based on Engineered Lasso Peptides
Authors: Lechner Anna , Jordan Peter A. , da Cruz Gabriella Costa Machado , Lamson Jacob , Gordon Jessica , Okada Bethany K. , Anderson Kelsey , Chaudhari Rajan , Rosario Christopher J. , Mikesell Jasmine , McPhee Scott A. , Burk Mark J.
Published: February 2025

Integrins αvβ6 and αvβ8 in the tumor microenvironment (TME) have been shown to activate immunosuppressive TGF-β, which serves as an important mechanism for immune checkpoint inhibitor resistance in a range of tumors. In this study, we demonstrate the utility of lasso peptides as versatile scaffolds for designing new therapeutics. A series of highly potent and selective dual αvβ6/8 inhibitors were engineered through a combination of epitope scanning, computational design, and directed evolution. Several analogs, such as lassotides36and47, were fully characterized and physicochemical, in vitro pharmacological, and in vivo data are reported. Lassotide47, a half-life extended derivative of36, was shown to strongly sensitize anti-mPD-1-resistant tumors in mice when dosed in combination with the checkpoint inhibitor. The47/anti-mPD-1 combination was shown to halt tumor growth and regress tumors in mouse models of triple negative breast and ovarian cancers. Dual inhibition of αvβ6/8 integrins expressed in the TME thus represents a promising tumor-specific strategy to overcome TGF-β-driven resistance and enhance the anti-tumor efficacy of immune checkpoint inhibitors.
Divergent ecological selection causes partial reproductive isolation and vast genomic instability in yeast
Authors: Bendixsen Devin P. , Gilchrist Ciaran , Haberkorn Chloé , Persson Karl , Geijer Cecilia , Warringer Jonas , Stelkens Rike
Published: February 2025

Populations evolving independently in divergent environments accumulate genetic differences and potentially evolve reproductive isolation as a by-product of divergence. The speed and mechanisms underlying this process are difficult to investigate because we rarely get the opportunity to witness them in natural settings, and histories of selection and gene flow between populations are often unknown. Here, we experimentally evolved yeast for 1000 generations of evolution in both divergent and parallel environments. At regular time points during experimental evolution, we made crosses between parallel- and divergent-evolving populations to measure postzygotic reproductive isolation (gamete viability). We used whole genome population sequencing to determine the mutational load, the number and types of structural variation, and other genomic features of the parent, F1, and F2 intraspecific hybrids. We found evidence for large scale phenotypic and genome-wide differentiation in response to divergent laboratory selection. Divergent-selected populations produced hybrids with reduced gamete viability - a classic signature of postzygotic reproductive isolation in the form of hybrid breakdown. Parallel-selected populations on the other hand remained reproductively compatible. We found that F2 hybrid genomes contained vast genomic instability, i.e., new structural variants (especially insertions, deletions, and interchromosomal translocations) that were not observed in parent and F1 genomes, which is likely a result of chromosome missegregation and recombination errors in hybrid meiosis. Our results provide phenotypic and genomic evidence that partial reproductive isolation evolved due to adaptation to divergent environments, consistent with predictions of ecological speciation theory.
The interplay of sexual selection and hybridization can drive sexual radiation
Authors: Kagawa Kotaro
Published: February 2025

Sexual selection is considered a major driver of species diversification, but little is known about whether and how sexual selection may contribute to the incipient stages of speciation and sexual radiation. Based on evolutionary simulations, here I propose that an interplay of sexual selection and hybridization can drive the rapid formation of multiple species with diverse exaggerated sexual displays within a lineage. Existing theories suggest that sexual selection can cause evolutionary dynamics with multiple stable equilibria, with which multiple species with distinct sexual displays and mate preferences can persist stably. However, the stability of each equilibrium hinders the formation of new species from an existing species that is already occupying one of the stable equilibria. In such situations, hybridization between phenotypically similar but genetically distinct lineages can catalyze speciation. Hybridization can generate genetic variation by recombining alleles from different lineages. I provide evolutionary simulations demonstrating that hybridization that gives rise to genetic variation in mate preference can modify the sexual selection regime to open up opportunities for the evolution of sexually selected displays toward previously unoccupied stable equilibria. Hybridization thus can trigger evolutionary shifts between alternative evolutionary equilibria that sexual selection generates, driving the incipient formation of sexual radiation.
Estimation of total mediation effect for a binary trait in a case-control study for high-dimensional omics mediators
Authors: Kang Zhiyu , Chen Li , Wei Peng , Xu Zhichao , Li Chunlin , Yang Tianzhong
Published: February 2025

Mediation analysis helps uncover how exposures impact outcomes through intermediate variables. Traditional mean-based total mediation effect measures can suffer from the cancellation of opposite component-wise effects and existing methods often lack the power to capture weak effects in high-dimensional mediators. Additionally, most existing work has focused on continuous outcomes, with limited attention to binary outcomes, particularly in case-control studies. To fill in this gap, we propose anR2total mediation effect measure under the liability framework, providing a causal interpretation and applicable to various high-dimensional mediation models. We develop a cross-fitted, modified Haseman-Elston regression-based estimation procedure tailored for case-control studies, which can also be applied to cohort studies with reduced efficiency. Our estimator remains consistent with non-mediators and weak effect sizes in extensive simulations. Theoretical justification on consistency is provided under mild conditions. In the Women’s Health Initiative of 2150 individuals, we found that 89% (CI: 73% 91%) of the variation in the underlying liability for coronary heart disease associated with BMI can be explained by metabolomics.
Exploring the implemented guidelines for dyslipidemia treatment and care among nurses and physicians in Jordanian hospitals
Authors: bani Salameh Rana K. , Al-Smadi Ahmed M. , Gammoh Omar , Shajrawi Abedalmajeed M. , Ashour Ala , Alrfooh Omar , Fitzsimons Donna , Hatahet Taher , Binsaleh Ammena Yahia , Shilbayeh Sireen Abdul Rahim
Published: February 2025

Background

Dyslipidemia is a major risk factor for ischemic heart disease in the world. The last updated ACC/AHA and ESC/EAS guidelines for dyslipidemia management aimed to control blood cholesterol and reduce cardiovascular risk. In Jordan, no national guidelines have been published to date, so these guidelines are commonly used. There are a few studies exploring the implementation of these guidelines in Jordan.

purpose

To explore the implementation of updated ACC/AHA and ESC/EAS guidelines for the treatment and care of dyslipidemia among nurses and physicians in Jordan.

Method

Semi-structured interviews (three focus group) with open-ended questions was conducted to gain deeper understanding of implemented practice and guidelines among nurses and physicians.

Results

Focus group interviews revealed that health care professionals try to implement specific guidelines and reach for optimal goals, but many barriers prevent them from reaching therapeutic goals, like workload, limited resources, and a lack of support from health institutions. They reported many suggestions that may enhance their ability to implement dyslipidemia management guidelines and wanted to improve specific guidelines in Jordan for dyslipidemia management.

Conclusions

Results indicated limited implementation of any dyslipidemia management guidelines among Jordanian nurses and physicians in their clinical practices.
Improving Post Kidney Transplant Related Outcomes through Video Based Educational Platforms
Authors: Byrns Jennifer , Bodner Jason , Watson Michael , Conca Tresa , Roberts John
Published: February 2025

PURPOSE

Kidney transplant recipients’ medical knowledge and comprehension of transplant care are critical to successful long-term outcomes. While transplant centers focus on pre-transplant patient education, post-transplant education receives less emphasis. At Duke University Hospital, an online digital library of short patient-centric videos was created to provide transplant education. The purpose of this study was to evaluate the impact of these videos on improving patient outcomes and patient perceived ability to effectively manage their own care.

METHODS

This was a prospective, single center study, evaluating the impact of education via patient-centric videos on medical knowledge, medication adherence, hospital readmissions, and patient satisfaction. Patients were randomized to receive education via online videos versus standard of care (in person and written education). Ten videos were created to cover the entire transplant process. A survey was conducted to assess outcomes. Descriptive statistics were used to compare groups with absolute numbers (%) and means (SD).

RESULTS

There were a total of 83 patients enrolled. Response rates to the surveys was 61.4%. Patients who completed the survey were evaluated. Twenty seven patients were included in the video group and there were 24 control patients. The video group expressed extreme satisfaction with the videos. All patients reported that they would recommend the videos to other patients, and 84% stated that they would return to watch the videos to gain additional transplant knowledge. Patients in the video group reported confidence in their ability and the medical team’s ability to manage their health. The assessment of transplant knowledge was similar between groups, but limited by video completion rates and timing of survey completion. Readmission rates were no different.

CONCLUSIONS

Transplant education provided via video based format helped to improve patients’ confidence in their ability to maintain their own self-care. The videos were well received and helped give patients a method to learn about transplant. These videos are now used institution wide to help improve patient outcomes
Characterization of the Cellular Immune Response to Group B Streptococcal Vaginal Colonization
Authors: Spencer Brady L. , Nguyen Dustin T. , Marroquin Stephanie M. , Gapin Laurent , O’Brien Rebecca L. , Doran Kelly S.
Published: February 2025

Introduction

Group BStreptococcus(GBS) asymptomatic colonizes the female genital tract (FGT) but can contribute to adverse pregnancy outcomes including pre-term birth, chorioamnionitis, and neonatal infection. We previously observed that GBS elicits FGT cytokine responses, including IL-17, during murine vaginal colonization; yet the anti-GBS cellular immune response during colonization remained unknown. We hypothesized that GBS may induce cellular immunity, resulting in FGT clearance.

Methods

Herein, we utilize depleting antibodies and knockout mice and performed flow cytometry to investigate cellular immunes responses during GBS colonization.

Results

We found that neutrophils (effectors of the IL-17 response) are important for GBS mucosal control as neutrophil depletion promoted increased GBS burdens in FGT tissues. Flow cytometric analysis of immune populations in the vagina, cervix, and uterus revealed, however, that GBS colonization did not induce a marked increase in FGT CD45+ immune cells. We also found that that Vγ6+ γδ T cells comprise a primary source of FGT IL-17. Finally, using knockout mice, we observed that IL-17-producing γδ T cells are important for the control of GBS in the FGT during murine colonization.

Conclusions

Taken together, this work characterizes FGT cellular immunity and suggests that GBS colonization does not elicit a significant immune response, which may be a bacterial directed adaptive outcome. However, certain FGT immune cells, such as neutrophils and ɣδ T cells, contribute to host defense and control of GBS colonization.
Somatostatin Receptor 2 Overexpression in Hepatocellular Carcinoma: Implications for Cancer Biology and Theranostic Applications
Authors: Momeny Majid , Vargas Servando Hernandez , AghaAmiri Solmaz , Adams Jack T. , Bateman Tyler M. , Ghosh Sukhen C. , Acidi Belkacem , Khalaj Vahid , Kaseb Ahmed O. , Cao Hop S. Tran , Azhdarinia Ali
Published: February 2025

(1)

Background

Somatostatin receptor 2 (SSTR2) is overexpressed in various tumors, including hepatocellular carcinoma (HCC), yet its role in tumorigenesis remains unclear. This study examines the roles of SSTR2 in the molecular pathology of HCC and explores its potential as a target for SSTR2-directed radiopharmaceuticals in this malignancy.

(2)

Methods

SSTR2 expression was analyzed across 22 malignancies using TNMplot and specifically in HCC through The Human Protein Atlas. Transcriptomic data, protein expression, and copy number alterations in HCC patients with varying SSTR2 levels were compared using The Cancer Genome Atlas (TCGA). Gene Ontology (GO) enrichment analysis was performed using SRplot, while survival analysis was conducted with GEO datasets.

(3)

Results

Most HCC patients exhibit moderate levels of SSTR2 expression. Elevated SSTR2 expression is associated with worse overall and disease-specific survival, as well as the activation of pathways involved in tumor growth and metastasis. Furthermore, SSTR2 expression is linked to key oncogenes and receptor tyrosine kinases.

(4)

Conclusions

SSTR2 in HCC signifies an oncogenic network and represents a promising therapeutic target to inhibit tumor invasion and serve as a theranostic biomarker. HCC patients with elevated SSTR2 expression could benefit from SSTR2-targeted theranostics, enabling enhanced tumor detection and more effective therapy.
How Does Sampling Affect the AI Prediction Accuracy of Peptides’ Physicochemical Properties?
Authors: Yan Meiru , Abuduhebaier Ankeer , Zhou Haojin , Wang Jiaqi
Published: February 2025

Accurate AI prediction of peptide physicochemical properties is essential for advancing peptide-based biomedicine, biotechnology, and bioengineering. However, the performance of predictive AI models is significantly affected by the representativeness of the training data, which depends on the sample size and sampling methods employed. This study addresses the challenge of determining the optimal sample size and sampling methods to enhance the predictive accuracy and generalization capacity of AI models for estimating the aggregation propensity, hydrophilicity, and isoelectric point of tetrapeptides. Four sampling methods were evaluated: Latin Hypercube Sampling (LHS), Uniform Design Sampling (UDS), Simple Random Sampling (SRS), and Probability-Proportional-to-Size Sampling (PPS), across sample sizes ranging from 100 to 20,000. A sample size of approximately 12,000 (7.5% of the total tetrapeptide dataset) marks a key threshold for stable and consistent model performance. This study provides valuable insights into the interplay between sample size, sampling strategies, and model performance, offering a foundational framework for optimizing data collection and AI model training for the prediction of peptides’ physicochemical properties, especially for prediction in the complete sequence space of longer peptides with more than four amino acids.
BIOCHEMICAL COMPOSITION OF SPECIALTY TEA EXTRACTS FROM MULTISTAGE EXTRACTIONS USING SOLVENTS TREATMENTS
Authors: Kipsura Emily , Koech Robert , Mwangi Simon , Kamunya Samson , Ngeno Victor , Koech Joel , Bii Christine
Published: February 2025

Diversification and value addition in tea has received considerable attention in recent past. This has been occasioned by increased tea volumes in the world market, especially the aerated product that has led to over flooding. Additionally, health benefits associated with diversified products such as green tea and extracts has elicited a lot of interests in both the industry and external players in finding out alternative ways of tea consumption. The aim of this study was to determine biochemical composition of the various tea extract products generated at different points of a multistage extraction process. The extraction process consisted of hot distilled water, methylene chloride and ethyl acetate steps. The products of purple, yellow, green, black orthodox teas, matcha and the semi aerated oolong were used as raw materials for the extracts. Total polyphenols content, individual catechins and caffeine content were assayed using UV-spectrophotometer and High Performance Liquid Chromatography-Photo diode array HPLC-PDA. Analysis of variance (ANOVA) was used for statistical purposes to detect significant differences between the extraction methods with the least significant difference (LSD) used to separate the means in the assayed tea samples. Results generated indicated that total polyphenols, individual catechins and caffeine content were significantly different (p≤0.05) in the assayed tea samples. Water extracts showed high total yield (82.2%), while methylene chloride recorded the least (2.63%). Ethyl acetate tea extracts showed high phenolic content that ranged from 11. 4% to78.1%. Ethyl acetate extract was rich in total catechins content (46.6% to 75.9%). Water extracts had significantly (p≤0.05) high amounts of total catechins (12.3% to 27.6%) compared to residual extracts (5.4% to 8.9%) contrary to methylene chloride extracts which had low total catechin contents (1.2% to 4.5%). Caffeine was predominant in methylene chloride tea extracts and ranged from 29.97% to 58.99% pointing to high solvent affinity. Based on this results, ethyl acetate proved to be the ideal solvent for obtaining extract rich in polyphenols, and methylene chloride for isolation of natural caffeine. For high yield of all polyphenols, water was found to be the solvent of choice of tea extracts without regarding the specific class of compound to be isolated. This study confirmed that specialty tea extracts are a promising source of bioactive compounds, suggesting they could be very attractive for use as dietary supplements, cosmetic ingredients and in food industries.
Genetic evidence for a fall spawning group of Gulf sturgeon (Acipenser oxyrinchus desotoi) in the Apalachicola River, Florida
Authors: Zona Jacob O. , Kreiser Brian R. , Kaeser Adam J. , Fox Adam G. , D’Ercole Mark J.
Published: February 2025

The Gulf sturgeon (Acipenser oxyrinchus desotoi) is a large, long-lived, anadromous fish inhabiting the northern Gulf of Mexico. This charismatic fish was hunted to near extinction in the early 1900’s and in 1991 was listed as threatened under the Endangered Species Act. Recovery continues to be challenged by threats such as habitat destruction, fisheries bycatch, and climate change. There are seven known natal rivers, historically thought to each contain a single, spring-spawning group. In recent years, multiple rivers (Suwannee, Choctawhatchee) have been shown to contain a second, fall-spawning group. This study utilizes genetic techniques to investigate the proposed existence of a fall-spawning group in the Apalachicola River, Florida. This river once supported one of the largest Gulf sturgeon populations, but post-exploitation faces a difficult path to recovery. The Jim Woodruff Lock and Dam blocks access to the majority of historic habitat in the system, with the only known remaining spawning grounds located immediately downriver. Tissue samples from juvenile Gulf sturgeon were collected between 2013 and 2022 and used to assess genetic population structure within the Apalachicola River. Analyses suggested two distinct genetic groups (FST= 0.085). Based on dates of capture, length frequency distributions, and genetic assignment of spawning adults, these were identified as spring- and fall-spawning groups. Approximately 90% of juveniles collected were assigned to the spring, but only slight differences in genetic diversity were detected between groups. The temperature window for spawning was found to be three weeks shorter on average in the fall than the spring, highlighting the need for additional research into differing environmental or anthropogenic influences on these populations. The discovery of a fall-spawning group of Gulf sturgeon in the Apalachicola River improves our understanding of the representation, redundancy, and resiliency of the species and provides critical information for improved management of this river system.
B-cell-SpecificWwoxDeletion Promotes Plasmablastic Tumor Development and Pro-Inflammatory Signatures in a Myeloma Mouse Model
Authors: Hussain Tabish , Bramble Matthew D. , Liu Bin , Abba Martin C. , Chesi Marta , Aldaz C. Marcelo
Published: February 2025

Deletions and translocations affectingWWOXaccompanied by loss of expression are frequently observed in B cell neoplasms and are linked to poor prognosis. Our previous research showed thatWwoxdeletion early in B cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossingCd19 Wwoxknockout (KO) withVk*MYCmyeloma model mice, we generated a model with concurrentWwoxdeletion andMYCactivation, reproducing two common oncogenic alterations in B and plasma cell cancers. We observed thatVk*MYC:Wwox KOmice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived Cd138+ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation uponWwoxdeletion inVk*MYCmice.Wwox KOplasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B cell specificWwoxdeletion and support a relevant role for WWOX loss of function in B cell neoplastic progression towards more aggressive phenotypes.
MAJIQ-CLIN: A novel tool for the identification of Mendelian disease-causing variants from RNA-Seq data
Authors: Aicher Joseph K , Issakova Dina , Slaff Barry , Jewell San , Lahens Nicholas F , Grant Gregory R , Baralle Diana , Rosenfeld Jill A , Scott Daryl A ,   Undiagnosed Diseases Network, Bhoj Elizabeth J , Barash Yoseph
Published: February 2025

The current diagnostic rate for patients with suspected Mendelian genetic disorders is only 25 to 58%, even though whole exome sequencing (WES) is part of the standard of care. One reason for the low diagnostic rate is that traditional WES analysis methods struggle to detect RNA splicing aberrations. It is estimated that 15-50% of human pathogenic variants alter splicing, with numerous splice-altering variants being causal for known Mendelian disorders. Developing reliable diagnostic tools to detect, quantify, prioritize, and visualize RNA splicing aberrations from patient RNA sequencing is therefore crucial. We present MAJIQ-CLIN, a method to address this need to augment clinical diagnostic using RNA-Seq and compare it to existing tools. We include the first systematic evaluation of the accuracy of such tools using synthetic data across several aberration types and transcript inclusion levels; we also evaluate accuracy on several datasets of biologically validated solved test cases. We show that MAJIQ-CLIN compares favorably to existing tools in both accuracy and efficiency, then use MAJIQ-CLIN to investigate several unsolved patient cases from the Undiagnosed Diseases Network.