bluuebunny/crossref_metadata_2025_split huggingface dataset:
The developing pig respiratory microbiome harbors strains antagonistic to common respiratory pathogens
Authors: Vlasblom Abel A. , Duim Birgitta , Patel Shriram , Luiken Roosmarijn E. C. , Crespo-Piazuelo Daniel , Eckenberger Julia , Huseyin Chloe E. , Lawlor Peadar G. , Elend Christian , Wagenaar Jaap A. , Claesson Marcus J. , Zomer Aldert L. 
Published: September 2024

ABSTRACT

In the global efforts to combat antimicrobial resistance and reduce antimicrobial use in pig production, there is a continuous search for methods to prevent and/or treat infections. Within this scope, we explored the relationship between the developing piglet nasal microbiome and (zoonotic) bacterial pathogens from birth until 10 weeks of life. The nasal microbiome of 54 pigs was longitudinally studied over 16 timepoints on 9 farms in 3 European countries (Germany, Ireland, and the Netherlands) using amplicon sequencing targeting the V3-V4 16S rRNA region as well as the
tuf
gene for its staphylococcal discrimination power. The piglets’ age, the farm, and the litter affected the nasal microbiome, with piglets’ age explaining 19% of the variation in microbial composition between samples. Stabilization of the microbiome occurred around 2 weeks post-weaning. Notably, while opportunistic pathogens were ubiquitously present, they did not cause disease. The piglet nasal microbiome often carried species associated with gut, skin, or vagina, which suggests that contact with the vaginal and fecal microbiomes shapes the piglet nasal microbiome. We identified bacterial co-abundance groups of species that were present in the nasal microbiomes in all three countries over time. Anti-correlation between these species and known bacterial pathogens identified species that might be exploited for pathogen reduction. Further experimental evidence is required to confirm these findings. Overall, this study advances our understanding of the piglet nasal microbiome, the factors influencing it, and its longitudinal development, providing insights into its role in health and disease.

IMPORTANCE
Our study on the nasal microbiota development in piglets across farms in three European countries found that the microbiomes developed similarly in all locations. Additionally, we observed that the colonization of porcine pathogens was either positively or negatively associated with the presence of other bacterial species. These findings enhance our knowledge of co-colonizing species in the nasal cavity and the identified microbial interactions that can be explored for the development of interventions to control pathogens in porcine husbandry.
Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China
Authors: Wu Jing , Jiang Mingzheng , Li Jiwei , Hu Xiaoyi , Long Qiuyue , Song Shixu , Ye Hongli , He Yukun , Ma Xinqian , Yu Wenyi , Chen Xi , Zhao Lili , Wu Fangfang , Chen Xiaoyong , Zheng Jianshi , Wang Minghui , Zheng Binghan , Yang Shuoqi , Bu Liang , Chen Qin , Li Ke , Zheng Yali , Gao Zhancheng 
Published: September 2024

ABSTRACT

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.

IMPORTANCE
The study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.
Use of commercial or indigenous yeast impacts the
S. cerevisiae
transcriptome during wine fermentation
Authors: Whiteley Lauren E. , Rieckh Georg , Diggle Frances L. , Alaga Zach M. , Nachbaur Elizabeth H. , Nachbaur William T. , Whiteley Marvin 
Published: September 2024

ABSTRACT

Grapes have been cultivated for wine production for millennia. Wine production involves a complex biochemical process where sugars in grape must are converted into alcohol and other compounds by microbial fermentation, primarily by the yeast
Saccharomyces cerevisiae
. Commercially available
S. cerevisiae
strains are often used in winemaking, but indigenous (native) strains are gaining attention for their potential to contribute unique flavors. Recent advancements in high-throughput DNA sequencing have revolutionized our understanding of microbial communities during wine fermentation. Indeed, transcriptomic analysis of
S. cerevisiae
during wine fermentation has revealed a core gene expression program and provided insights into how this yeast adapts to fermentation conditions. Here, we assessed how the age of vines impacts the grape fungal microbiome and used transcriptomics to characterize microbial functions in grape must fermented with commercial and native
S. cerevisiae
. We discovered that ~130-year-old Zinfandel vines harbor higher fungal loads on their grapes compared to 20-year-old Zinfandel vines, but fungal diversity is similar. Additionally, a comparison of inoculated and uninoculated fermentations showed distinct fungal dynamics, with uninoculated fermentations harboring the yeasts
Metschnikowia
and
Pichia
. Transcriptomic analysis revealed significant differences in gene expression between fermentations inoculated and not inoculated with a commercial
S. cerevisiae
strain. Genes related to metabolism, stress response, and cell adhesion were differentially expressed, indicating varied functionality of
S. cerevisiae
in these fermentations. These findings provide insights into
S. cerevisiae
function during fermentation and highlight the potential for indigenous yeast to contribute to wine diversity.

IMPORTANCE

Understanding microbial functions during wine fermentation, particularly the role of
Saccharomyces cerevisiae
, is crucial for enhancing wine quality. While commercially available
S. cerevisiae
strains are commonly used, indigenous strains can offer unique flavors, potentially reflecting vineyard terroir. By leveraging high-throughput DNA sequencing and transcriptomic analysis, we explored the impact of vine age on the grape mycobiome and characterized microbial functions during grape fermentation. Our findings revealed that older vines harbor higher fungal loads, but fungal diversity remains similar across vine ages. Additionally, uninoculated fermentations exhibited diverse fungal dynamics, including the beneficial wine yeasts Metschnikowia and Pichia. Transcriptomic analysis uncovered significant differences in
S. cerevisiae
gene expression between inoculated and uninoculated fermentations, highlighting the potential of indigenous yeast to enhance wine diversity and inform winemaking practices.
A drug repurposing screen identifies decitabine as an HSV-1 antiviral
Authors: Bautista Laura , Sirimanotham Cody , Espinoza Jason , Cheng Dillon , Tay Savaş , Drayman Nir 
Published: September 2024

ABSTRACT

Herpes simplex virus type 1 (HSV-1) is a highly prevalent human pathogen that causes a range of clinical manifestations, including oral and genital herpes, keratitis, encephalitis, and disseminated neonatal disease. Despite its significant health and economic burden, there is currently only a handful of approved antiviral drugs to treat HSV-1 infection. Acyclovir and its analogs are the first-line treatment, but resistance often arises during prolonged treatment periods, such as in immunocompromised patients. Therefore, there is a critical need to identify novel antiviral agents against HSV-1. Here, we performed a drug repurposing screen, testing the ability of 1,900 safe-in-human drugs to inhibit HSV-1 infection
in vitro
. The screen identified decitabine, a cytidine analog that is used to treat myelodysplastic syndromes and acute myeloid leukemia, as a potent anti-HSV-1 agent. We show that decitabine is effective in inhibiting HSV-1 infection in multiple cell types, including human keratinocytes, that it synergizes with acyclovir, and acyclovir-resistant HSV-1 is still sensitive to decitabine. We further show that decitabine causes G > C and C > G transversions across the viral genome, suggesting it exerts its antiviral activity by lethal mutagenesis, although a role for decitabine’s known targets, DNA methyl-transferases, has not been ruled out.

IMPORTANCE
Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen with a limited arsenal of antiviral agents, resistance to which can often develop during prolonged treatment, such as in the case of immunocompromised individuals. Development of novel antiviral agents is a costly and prolonged process, making new antivirals few and far between. Here, we employed an approach called drug repurposing to investigate the potential anti-HSV-1 activity of drugs that are known to be safe in humans, shortening the process of drug development considerably. We identified a nucleoside analog named decitabine as a potent anti-HSV-1 agent in cell culture and investigated its mechanism of action. Decitabine synergizes with the current anti herpetic acyclovir and increases the rate of mutations in the viral genome. Thus, decitabine is an attractive candidate for future studies in animal models to inform its possible application as a novel HSV-1 therapy.
Were Late Jurassic climatic fluctuations responses to Pangea breakup? Evidence from isotopic analyses of belemnite rostra from the eastern Tethyan Ocean
Authors: Wang Tianyang , He Songlin , Chen Yichao , Aitchison Jonathan C. , Zhang Qinghai , Li Guobiao , Xi Dangpeng , Wu Chen , Wang Licheng , Xie Jing , Ding Lin 
Published: September 2024

Abstract
Late Jurassic paleogeographic patterns were influenced by the growth of the Pacific plate and the breakup of Pangea, impacting the global paleoclimate during this warm and equable greenhouse period. However, the use of different proxies may introduce bias in seawater temperature reconstructions. In this study, we reconstructed midlatitude Tethyan seawater paleotemperatures in the Northern Hemisphere using carbonate clumped isotopes (Δ47) in well-preserved parts of belemnite rostra from the Upper Jurassic Hongqilafu Formation in the Taxkorgan Basin, southwest Xinjiang, China. Throughout the entire studied section, an increase in the 87Sr/86Sr ratio was observed. Comparison of this ratio with the published global seawater 87Sr/86Sr curve suggests a good correlation with the biostratigraphic and U-Pb age assignments of the Oxfordian–Tithonian interval. The Δ47-derived paleotemperature estimates indicate a long-term, relatively stable, and warm seawater temperature of ~27 °C within the epipelagic zone of the eastern Tethyan Ocean during the Late Jurassic. Cooler seawater temperatures were recorded at the Oxfordian–Kimmeridgian boundary and in the late Tithonian, likely reflecting changes in paleogeography and paleoceanography resulting from the breakup of Pangea and/or variations in belemnite habitat depth. When compared with global seawater temperature data from different proxies, the results suggest that elevated atmospheric pCO2 levels during the Late Jurassic may have caused warmer conditions in midlatitude and polar regions. The reconstructed δ18Osea values exhibit a remarkably modern midlatitude seawater character and are more positive than values traditionally assumed for the Jurassic ice-free world. Given that the Taxkorgan Basin was located in a semi-enclosed basin and was dominated by evaporation in the Late Jurassic, the reconstructed δ18Osea values may represent regional seawater signals. Consequently, they cannot be used to support the existence of ice sheets in both polar regions. Our results suggest that climatic changes in the Jurassic greenhouse world may have been overprinted by local factors, potentially masking broader climatic trends.
Ab initio investigation of the structural, mechanical, electronic, thermodynamic, and optical properties of V2FeNiGe2 and Hf2FeNiSb2 double half-Heusler compounds
Authors: Diaf Mohamed , Righi Haroun , Beddiaf Raouf , Djaballah Yassine , Rached Habib 
Published: September 2024

In the present work, using ab initio density-functional theory methods based on the Quantum ESPRESSO package, we have investigated the structural, elastic, electronic, and optical properties of 18-electron V2FeNiGe2 and Hf2FeNiSb2 double half-Heusler alloys. The calculated elastic properties suggest a ductile behavior with metallic bonding for V2FeNiGe2 and a brittle behavior with covalent bonding for Hf2FeNiSb2. The thermodynamic properties (Debye temperature, melting temperature) are also predicted and discussed for the studied alloys. The alloys are found to be semiconducting with indirect band gaps of 0.53 eV for V2FeNiGe2 and 0.47 eV for Hf2FeNiSb2. We also computed and analyzed their optical properties (dielectric function, optical conductivity, refractive index, absorption index, and reflectance) and our calculations suggest that both materials have high absorption coefficient and optical conductivity in the UV as well as visible region. The results make them potential candidates for the manufacture of opto-electronic devices.
Incorporating the cosmological constant in a modified uncertainty principle
Authors: Ahmadi S. , Yusofi E. , Ramzanpour M. A. 
Published: September 2024

This study explores the cosmological constant problem and modified uncertainty principle within a unified framework inspired by a void-dominated scenario for cosmology. In a recent paper [E. Yusofi, M. Khanpour, B. Khanpour, M. A. Ramzanpour and M. Mohsenzadeh, Mon. Not. R. Astron. Soc. 511, L82 (2022)], voids were modeled as spherical bubbles of similar average sizes, and the surface energy on the voids’ borders was calculated across various scales in a heuristic manner. We show that these result in a significant discrepancy of approximately [Formula: see text] between the cosmological constant values from the minimum to the maximum radii of bubbles. Furthermore, when considering the generalized form of the uncertainty principle with both minimum and maximum lengths, i.e. [Formula: see text], a similar order of discrepancy is observed between [Formula: see text] and [Formula: see text], indicating that [Formula: see text]. As a primary outcome of this finding, we offer a novel uncertainty principle that incorporates a nonzero cosmological constant.
Topological photon, spin, and Euclidean group E(2)
Authors: Tiwari S. C. 
Published: September 2024

The proposition that photon is a topological object [S. C. Tiwari, J. Math. Phys. 49, 032303 (2008)] is given rigorous foundation based on pure vector field theory independent of the electromagnetic fields. Holomorphy of 4-dimensional spacetime and the nature of topological obstructions are investigated to articulate singular vortex model for photon. The utility of the Euclidean symmetry group is discussed in detail for the proposed photon model.
mLumiOpto Is a Mitochondrial-Targeted Gene Therapy for Treating Cancer
Authors: Chen Kai , Ernst Patrick , Sarkar Anusua , Kim Seulhee , Si Yingnan , Varadkar Tanvi , Ringel Matthew D. , Liu Xiaoguang “Margaret” , Zhou Lufang 
Published: September 2024

Abstract
Mitochondria are important in various aspects of cancer development and progression. Targeting mitochondria in cancer cells holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we developed mitochondrial luminoptogenetics (mLumiOpto), an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial membrane potential and induce cancer cell death. The therapeutic approach included synthesis of a blue light–gated cationic channelrhodopsin in the inner mitochondrial membrane and coexpression of a blue bioluminescence-emitting nanoluciferase in the cytosol of the same cells. The mLumiOpto genes were selectively delivered to cancer cells in vivo by an adeno-associated virus carrying a cancer-specific promoter or cancer-targeted mAB-tagged exosome-associated adeno-associated virus. Induction with nanoluciferase luciferin elicited robust endogenous bioluminescence, which activated cationic channelrhodopsin, triggering cancer cell mitochondrial depolarization and subsequent cell death. Importantly, mLumiOpto demonstrated remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastoma and triple-negative breast cancer xenograft mouse models. Furthermore, the approach induced an antitumor immune response, increasing infiltration of dendritic cells and CD8+ T cells in the tumor microenvironment. These findings establish mLumiOpto as a promising therapeutic strategy by targeting cancer cell mitochondria in vivo.
Significance: mLumiOpto is a next generation optogenetic approach that employs selective delivery of genes to cancer cells to trigger mitochondrial depolarization, effectively inducing cell death and reducing tumor burden.
Clonal Hematopoiesis and Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer Patients Given Androgen Receptor Pathway Inhibitors (Alliance A031201)
Authors: Jensen Jeffrey L. , Bobek Olivia , Chan Irenaeus C. C. , Miller Brian C. , Hillman David W. , Heller Glenn , Druley Todd , Armstrong Andrew J. , Morris Michael J. , Milowsky Matthew I. , Beltran Himisha , Bolton Kelly L. , Coombs Catherine C. 
Published: September 2024

Abstract

Purpose:
Mutations in hematopoietic progenitor cells accumulate with age leading to clonal expansion, termed clonal hematopoiesis (CH). CH in the general population is associated with hematopoietic neoplasms and reduced overall survival (OS), predominantly through cardiovascular adverse events (CVAE). Because androgen receptor pathway inhibitors (ARPI) used in metastatic castration-resistant prostate cancer (mCRPC) are also associated with CVAEs and because CH negatively impacted survival in an advanced solid tumor cohort, we hypothesized that CH in mCRPC may be associated with increased CVAEs and inferior survival.

Experimental Design:
A targeted DNA sequencing panel captured common CH mutations in pretreatment blood samples from 957 patients enrolled in Alliance A031201: a randomized trial of enzalutamide ± abiraterone/prednisone in the first-line mCRPC setting. The primary outcome was the impact of CH on OS; the secondary outcomes were progression-free survival (PFS) and CVAEs.

Results:
Baseline comorbidities were similar by CH status. No differences in OS/progression-free survival were detected regardless of treatment arm or the variant allele frequency threshold used to define CH [primary: 2% (normal-CH, N-CH); exploratory: 0.5% (low-CH) and 10% (high-CH, H-CH)]. Patients with H-CH (7.2%) and TET2-mutated N-CH (6.0%) had greater odds of any CVAE (14.5% vs. 4.0%; P = 0.0004 and 12.3% vs. 4.2%; P = 0.010, respectively). More major CVAEs were observed in patients with H-CH (5.8% vs. 1.9%; P = 0.042) and N-CH (3.4% vs. 1.8%; P = 0.147).

Conclusions:
CH did not affect survival in patients with mCRPC treated with ARPIs in A031201. H-CH and TET2-mutated CH were associated with more CVAEs. These findings inform the risk/benefit discussion about ARPIs in mCRPC.
Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis
Authors: Starrett Gabriel J. , Baikie Brittany C. , Stoff Benjamin K. , Grossniklaus Hans E. , Van Buren Inga , Berry Elizabeth G. , Novoa Roberto A. , Rieger Kerri E. , Sarin Kavita Y. , Lynch Charles F. , Royer Michael C. , Piaskowski Mary L. , Brownell Isaac , Chu Emily Y. , Godse Rama , Chen Suephy C. , Yu Kelly J. , Goldstein Alisa M. , Engels Eric A. , Sargen Michael R. 
Published: September 2024

Abstract

Purpose:
Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment.

Experimental Design:
We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021.

Results:
We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (&gt;10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions.

Conclusions:
The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.