bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combination of conserved and diverged responses underlies Theobroma cacao’s defense response to Phytophthora palmivora
Authors: Winters Noah P. , Wafula Eric K. , Knollenberg Benjamin J. , Hämälä Tuomas , Timilsena Prakash R. , Perryman Melanie , Zhang Dapeng , Sheaffer Lena L. , Praul Craig A. , Ralph Paula E. , Prewitt Sarah , Leandro-Muñoz Mariela E. , Delgadillo-Duran Diego A. , Altman Naomi S. , Tiffin Peter , Maximova Siela N. , dePamphilis Claude W. , Marden James H. , Guiltinan Mark J. 
Published: February 2024

AbstractBackgroundPlants have complex and dynamic immune systems that have evolved to resist pathogens. Humans have worked to enhance these defenses in crops through breeding. However, many crops harbor only a fraction of the genetic diversity present in wild relatives. Increased utilization of diverse germplasm to search for desirable traits, such as disease resistance, is therefore a valuable step towards breeding crops that are adapted to both current and emerging threats. Here, we examine diversity of defense responses across four populations of the long-generation tree cropTheobroma cacaoL., as well as four non-cacaoTheobromaspecies, with the goal of identifying genetic elements essential for protection against the oomycete pathogenPhytophthora palmivora.ResultsWe began by creating a new, highly contiguous genome assembly for theP. palmivora-resistant genotype SCA 6 (Additional file 1: Tables S1-S5), deposited in GenBank under accessions CP139290-CP139299. We then used this high-quality assembly to combine RNA and whole-genome sequencing data to discover several genes and pathways associated with resistance. Many of these are unique, i.e., differentially regulated in only one of the four populations (diverged 40 k–900 k generations). Among the pathways shared across all populations is phenylpropanoid biosynthesis, a metabolic pathway with well-documented roles in plant defense. One gene in this pathway, caffeoyl shikimate esterase (CSE), was upregulated across all four populations following pathogen treatment, indicating its broad importance for cacao’s defense response. Further experimental evidence suggests this gene hydrolyzes caffeoyl shikimate to create caffeic acid, an antimicrobial compound and known inhibitor ofPhytophthora spp.ConclusionsOur results indicate most expression variation associated with resistance is unique to populations. Moreover, our findings demonstrate the value of using a broad sample of evolutionarily diverged populations for revealing the genetic bases of cacao resistance toP. palmivora. This approach has promise for further revealing and harnessing valuable genetic resources in this and other long-generation plants.
ADARs regulate cuticle collagen expression and promote survival to pathogen infection
Authors: Dhakal Alfa , Salim Chinnu , Skelly Mary , Amichan Yarden , Lamm Ayelet T. , Hundley Heather A. 
Published: February 2024

Abstract
Background
In all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA-binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking.

Results
Here, by analyzing adr-1 and adr-2 null mutants in well-established slow-killing assays, we find that both Caenorhabditis elegans ADARs are important for organismal survival to gram-negative and gram-positive bacteria, all of which are pathogenic to humans. Furthermore, our high-throughput sequencing and genetic analysis reveal that ADR-1 and ADR-2 function in the same pathway to regulate collagen expression. Consistent with this finding, our scanning electron microscopy studies indicate adr-1;adr-2 mutant animals also have altered cuticle morphology prior to pathogen exposure.

Conclusions
Our data uncover a critical role of the C. elegans ADAR family of RNA-binding proteins in promoting cuticular collagen expression, which represents a new post-transcriptional regulatory node that influences the extracellular matrix. In addition, we provide the first evidence that ADAR mutant animals have altered susceptibility to infection with several opportunistic human pathogens, suggesting a broader role of ADARs in altering physical barriers to infection to influence innate immunity.
Prognostic effect of stress hyperglycemia ratio on patients with severe aortic stenosis receiving transcatheter aortic valve replacement: a prospective cohort study
Authors: Hu Xiangming , Feng Dejing , Zhang Yuxuan , Wang Can , Chen Yang , Niu Guannan , Zhou Zheng , Zhao Zhenyan , Zhang Hongliang , Wang Moyang , Wu Yongjian 
Published: February 2024

Abstract
Background
Stress hyperglycemia ratio (SHR) has recently been recognized as a novel biomarker that accurately reflects acute hyperglycemia status and is associated with poor prognosis of heart failure. We evaluated the relationship between SHR and clinical outcomes in patients with severe aortic stenosis receiving transcatheter aortic valve replacement (TAVR).

Methods
There were 582 patients with severe native aortic stenosis who underwent TAVR consecutively enrolled in the study. The formula used to determine SHR was as follows: admission blood glucose (mmol/L)/(1.59×HbA1c[%]–2.59). The primary endpoint was defined as all-cause mortality, while secondary endpoints included a composite of cardiovascular mortality or readmission for heart failure, and major adverse cardiovascular events (MACE) including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox regression and restricted cubic spline analysis were employed to assess the relationship between SHR and endpoints, with hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
During a median follow-up of 3.9 years, a total of 130 cases (22.3%) of all-cause mortality were recorded. Results from the restricted cubic spline analysis indicated a linear association between SHR and all endpoints (p for non-linearity > 0.05), even after adjustment for other confounding factors. Per 0.1 unit increase in SHR was associated with a 12% (adjusted HR: 1.12, 95% CI: 1.04–1.21) higher incidence of the primary endpoint, a 12% (adjusted HR: 1.12, 95% CI: 1.02–1.22) higher incidence of cardiovascular mortality or readmission for heart failure, and a 12% (adjusted HR: 1.12, 95% CI: 1.01–1.23) higher incidence of MACE. Subgroup analysis revealed that SHR had a significant interaction with diabetes mellitus with regard to the risk of all-cause mortality (p for interaction: 0.042). Kaplan-Meier survival analysis showed that there were significant differences in the incidence of all endpoints between the two groups with 0.944 as the optimal binary cutoff point of SHR (all log-rank test: p < 0.05).

Conclusions
Our study indicates linear relationships of SHR with the risk of all-cause mortality, cardiovascular mortality or readmission for heart failure, and MACE in patients with severe aortic stenosis receiving TAVR after a median follow-up of 3.9 years. Patients with an SHR exceeding 0.944 had a poorer prognosis compared to those with lower SHR values.
Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p
Authors: Lu Dongdong , Liu Yisi , Kang Luyuan , Zhang Xiangyu , Hu Jie , Ye Hao , Huang Bingxu , Wu Yujun , Zhao Jinbiao , Dai Zhaolai , Wang Junjun , Han Dandan 
Published: February 2024

Abstract
Backgrounds
The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs.

Results
In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development.

Conclusion
These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-β-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.

Graphical Abstract
Feasibility of paying people who use drugs cash to distribute naloxone within their networks
Authors: Lewis Nikki M. , Smeltzer Rebecca P. , Baker Trevor J. , Sahovey Andrea C. , Baez Justine , Hensel Erika , Poole Brandon , Stewart Cecelia , Cogan Allyson G. , Bullard Mackenzie , Taylor Jessica L. 
Published: February 2024

Abstract
Introduction
Immediate access to naloxone is needed to prevent fatal opioid-related overdoses in the presence of fentanyl analogs saturating the opioid supply. Peer models engage impacted populations who are not accessing naloxone through standard venues, yet compensating peers who utilize syringe service programs with cash stipends to distribute naloxone within networks of people who use drugs is not well described.

Methods
As part of the HEALing Communities Study, syringe service program-based interventions were developed in Holyoke and Gloucester, MA, which paid people who use drugs (“peers”) cash to distribute naloxone. Early program outcomes were evaluated for the time each program was funded within the HCS study period.

Results
During 22 study-months of observation, peers in two communities distributed 1104 naloxone kits. The total cost of peer compensation for program delivery was $10,510. The rate of peer-distributed naloxone per 100 K population reached 109 kits/mo and 222 kits/mo in the two communities. Participating peers addressed gaps in harm reduction outreach and distributed naloxone and other harm reduction equipment to individuals who were not syringe service program participants, expanding organizational reach. Being compensated with unrestricted cash stipends supported dignity and acknowledged peers’ work in overdose prevention.

Conclusion
The underutilization of compensated peer models is often attributed to funding and organizational barriers. These programs demonstrate that providing cash stipends to peers is feasible and expanded naloxone distribution at two existing syringe service programs. Providing cash stipends for peers who engage in secondary naloxone distribution offers promise in delivering naloxone to people not accessing syringe services.
Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy
Authors: Yang Enyu , Fan Xiaowei , Ye Haihan , Sun Xiaoyang , Ji Qing , Ding Qianyun , Zhong Shulian , Zhao Shuo , Xuan Cheng , Fang Meiyu , Ding Xianfeng , Cao Jun 
Published: February 2024

AbstractUBXD family (UBXDF), a group of proteins containing ubiquitin regulatory X (UBX) domains, play a crucial role in the imbalance of proliferation and apoptotic in cancer. In this study, we summarised bioinformatics proof on multi-omics databases and literature on UBXDF’s effects on cancer. Bioinformatics analysis revealed that Fas-associated factor 1 (FAF1) has the largest number of gene alterations in the UBXD family and has been linked to survival and cancer progression in many cancers. UBXDF may affect tumour microenvironment (TME) and drugtherapy and should be investigated in the future. We also summarised the experimental evidence of the mechanism of UBXDF in cancer, both in vitro and in vivo, as well as its application in clinical and targeted drugs. We compared bioinformatics and literature to provide a multi-omics insight into UBXDF in cancers, review proof and mechanism of UBXDF effects on cancers, and prospect future research directions in-depth. We hope that this paper will be helpful for direct cancer-related UBXDF studies.
Association between dietary vitamin B1 intake and cognitive function among older adults: a cross-sectional study
Authors: Jia Weiai , Wang Hemei , Li Chao , Shi Jingpu , Yong Fangfang , Jia Huiqun 
Published: February 2024

Abstract
Background
This study aims to investigate the relationship between vitamin B1 intake and cognitive function in older adults.

Methods
This cross-sectional observational study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. A total of 2422 participants were included in the analysis, with dietary vitamin B1 intake being determined by averaging two 24-h dietary recalls. Cognitive function was assessed using three cognitive function tests: the Digit Symbol Substitution Test (DSST) for processing speed, the Animal Fluency Test (AFT) for executive function, a Consortium to Establish a Registry for Alzheimer's disease (CERAD) subtest for memory. Test-specific and global cognition z score was created. Multivariate linear regression models were used to explore the association between vitamin B1 and cognitive function.

Results
2422 participants, aged 60 years and older, were included from NHANES across two survey cycles (2011–2014). Higher vitamin B1 intake was associated with higher DSST, AFT scores (P < 0.001) as well as the global cognition z score (P = 0.008).
In the fully adjusted model, as compared to the lowest quartile (Q1), the highest quartile (Q4) of vitamin B1 intake was related to higher DSST score (β = 2.23, 95% CI 0.79 ~ 3.67) and global cognition z sore (β = 0.09, 95% CI 0.02 ~ 0.16). The association between dietary vitamin B1 intake and cognitive function scores in US adults is linear. There was no detected significant statistical interaction between these variables.

Conclusions
Increased dietary intake of vitamin B1 was associated with better cognitive function in individuals aged over 60.
Phage vB_Ec_ZCEC14 to treat antibiotic-resistant Escherichia coli isolated from urinary tract infections
Authors: Ismael Nedaa M. , Azzam Mohamed , Abdelmoteleb Mohamed , El-Shibiny Ayman 
Published: February 2024

AbstractEscherichia coli is a commensal bacterial species in the human gastrointestinal tract; however, it could be pathogenic and cause severe infections in intra and extra-intestinal sites. Uropathogenic E. coli accounts for 80–90% of urinary tract infections that can result in urosepsis and septic shock. Consequently, multidrug-resistant uropathogenic E. coli poses a considerable risk to the healthcare system worldwide. Phage therapy is demonstrated as an optimistic solution to over-the-counter antibiotics that contribute to the global issue of multidrug-resistant bacteria. This study aims to isolate a novel phage that could be implemented to cure urinary tract infections mediated by multidrug-resistant E. coli. Twenty-seven E. coli isolates were collected from patients with urinary tract infections to assess the antibacterial efficacy of phage vB_Ec_ZCEC14. Phage kinetics were encountered against the E. coli strain (EC/4), in addition to evaluating phage stability under various temperatures, pH values, and UV exposure periods. Full genome sequencing and morphological analysis were conducted for further phage characterization, which revealed that phage vB_Ec_ZCEC14 belongs to the family Straboviridae. Phage vB_Ec_ZCEC14 showed thermal tolerance at 80 ℃, pH stability between pH 3 and pH 12, and endurance to UV exposure for 45 min. The phage-host interaction results revealed that phage vB_Ec_ZCEC14 has strong and steady antibacterial action at lower concentrations (MOI 0.1). The study findings strongly indicate that phage vB_Ec_ZCEC14 holds significant promise as a potential therapeutic alternative for treatment of antibiotic-resistant uropathogenic E. coli.
Evaluating the effects of curcumin nano-chitosan on miR-221 and miR-222 expression and Wnt/β-catenin pathways in MCF-7, MDA-MB-231 and SKBR3 cell lines
Authors: Eslaminejad Touba , Nematollahi-Mahani Seyed Noureddin , Sargazi Marzieh Lotfian , Ansari Mehdi , Mirzaie Vida 
Published: February 2024

AbstractBackgroundBreast cancer is one of the most common diseases worldwide that affects women of reproductive age.miR-221andmiR-222are two highly homogeneous microRNAs that play pivotal roles in many cellular processes and regulate the Wnt/β-catenin signaling pathway. Curcumin (CUR), a yellow polyphenolic compound, targets numerous signaling pathways relevant to cancer therapy. The main aim of this study was to compare the ability of chitosan curcumin nanoparticle (CC-CUR) formulation with the curcumin in modulatingmiR-221andmiR-222expression through Wnt/β-catenin signaling pathway in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines.MethodChitosan-cyclodextrin-tripolyphosphate containing curcumin nanoparticles (CC-CUR) were prepared. Cytotoxicity of the CUR and CC-CUR was evaluated. Experimental groups including CC-CUR, CUR and negative control were designed. The expression ofmiR-221andmiR-222and Wnt/β-catenin pathway genes was measured.ResultsThe level ofmiR-221andmiR-222andβ-cateningenes decreased in MCF-7 and MDA-MB-231 cells andWIF1gene increased in all cells in CC-CUR group. However, the results in SK-BR-3 cell line were unexpected; since miRs andWIF1gene expressions were increased following CC-CUR administration andβ-catenindecreased by administration of CUR.ConclusionAlthough the composite form of curcumin decreased the expression ofmiR-221andmiR-222in MCF-7 and MDA cells, with significant decreasing ofβ-cateninand increasing ofWIF1gene in almost all three cell lines, we can conclude than this formulation exerts its effect mainly through the Wnt/β-catenin pathway. These preliminary findings may pave the way for the use of curcumin nanoparticles in the treatment of some known cancers.
The business case for carbon farming in the USA
Authors: Plastina Alejandro , Jo Haeun , Wongpiyabovorn Oranuch 
Published: February 2024

AbstractU.S. agricultural producers are increasingly able to participate in private voluntary carbon initiatives that compensate their efforts to sequester CO2, reduce GHG emissions, and provide ecosystem services through eligible conservation practices. This study examines the potential effects of alternative private payment regimes (per practice vs. per output), prices paid to farmers relative to out-of-pocket costs (low vs. high), and the availability of information on CO2 sequestration (limited vs. full), on the adoption of cover crops and no-till in the United States, the resulting CO2 sequestration, and changes in farmers’ net returns. The analysis relies on a highly stylized model of heterogeneous farms calibrated with county-level agronomic data, and simulated for current estimates of GHG impacts of cover crop planting and no-till under different scenarios. Our results indicate that agricultural carbon markets can be profitable for U.S. farmers, although with substantial geographic variability, and that annual carbon sequestration could range between 17 and 75 million mtCO2e. Payments per output would incentivize higher carbon sequestration than payments per practice, but the former regime would be less favored by farmers as a unified group than the latter (due to lower aggregate net returns). However, if operators of farms with high carbon sequestration potential could decide the payment regime to be implemented, they would choose the payment per output regime (due to higher net returns per enrolled hectare). Total projected net changes in GHGs under payments per practice, based solely on county-average net GHG effects of cover crops and no-till, over-estimate actual total GHG sequestration (based on the entire distribution of net effects by county) by 2.1 and 14.2 million mtCO2e, or 18% and 21%, respectively.
Clinical, genetic profile and therapy evaluation of 11 Chinese pediatric patients with Fanconi-Bickel syndrome
Authors: Du Taozi , Xia Yu , Sun Chengkai , Gong Zhuwen , Liang Lili , Gong Zizhen , Wang Ruifang , Lu Deyun , Zhang Kaichuang , Yang Yi , Sun Yuning , Sun Manqing , Sun Yu , Xiao Bing , Qiu Wenjuan 
Published: February 2024

Abstract
Background
Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction.

Methods
Clinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed.

Results
Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3−) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3− and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from − 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient.

Conclusions
Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.