bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring large-scale gene coexpression networks in peach (Prunus persica L.): a new tool for predicting gene function
Authors: de los Cobos Felipe Pérez , García-Gómez Beatriz E , Orduña-Rubio Luis , Batlle Ignasi , Arús Pere , Matus José Tomás , Eduardo Iban 
Published: January 2024

Abstract
Peach is a model for Prunus genetics and genomics, however, identifying and validating genes associated to peach breeding traits is a complex task. A gene coexpression network (GCN) capable of capturing stable gene–gene relationships would help researchers overcome the intrinsic limitations of peach genetics and genomics approaches and outline future research opportunities. In this study, we created four GCNs from 604 Illumina RNA-Seq libraries. We evaluated the performance of every GCN in predicting functional annotations using an algorithm based on the ‘guilty-by-association’ principle. The GCN with the best performance was COO300, encompassing 21 956 genes. To validate its performance predicting gene function, we performed two case studies. In case study 1, we used two genes involved in fruit flesh softening: the endopolygalacturonases PpPG21 and PpPG22. Genes coexpressing with both genes were extracted and referred to as melting flesh (MF) network. Finally, we performed an enrichment analysis of MF network and compared the results with the current knowledge regarding peach fruit softening. The MF network mostly included genes involved in cell wall expansion and remodeling, and with expressions triggered by ripening-related phytohormones, such as ethylene, auxin, and methyl jasmonate. In case study 2, we explored potential targets of the anthocyanin regulator PpMYB10.1 by comparing its gene-centered coexpression network with that of its grapevine orthologues, identifying a common regulatory network. These results validated COO300 as a powerful tool for peach and Prunus research. This network, renamed as PeachGCN v1.0, and the scripts required to perform a function prediction analysis are available at https://github.com/felipecobos/PeachGCN.
The Ability of a 3-Gene Host Signature in Blood to Distinguish Tuberculous Meningitis From Other Brain Infections
Authors: Huynh Julie , Nhat Le Hoang Thanh , Bao Nguyen Le Hoai , Hai Hoang Thanh , Thu Do Dang Anh , Tram Trinh Thi Bich , Dung Vu Thi Mong , Vinh Do Dinh , Ngoc Nghiem My , Donovan Joseph , Phu Nguyen Hoan , Van Thanh Dang , Thu Nguyen Thi Anh , Bang Nguyen Duc , Ha Dang Thi Minh , Nghia Ho Dang Trung , Van Tan Le , Van Le Hong , Thwaites Guy , Thuong Nguyen Thuy Thuong 
Published: January 2024

Abstract

Background
Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections.

Methods
The expression of 3 genes (dual specificity phosphatase 3 [DUSP3], guanylate-binding protein [GBP5], krupple-like factor 2 [KLF2]) was analyzed by RNA sequencing of archived whole blood from 4 cohorts of Vietnamese adults: 281 with TBM, 279 with pulmonary tuberculosis, 50 with other brain infections, and 30 healthy controls. Tuberculosis scores (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC).

Results
GBP5 was upregulated in TBM compared to other brain infections (P &lt; .001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC, 0.74; 95% confidence interval [CI], .67–.81) was slightly better than the 3-gene tuberculosis score (AUC, 0.66; 95% CI, .58–.73) in TBM. Both GBP5 expression and tuberculosis score were higher in participants with human immunodeficiency virus (HIV; P &lt; .001), with good diagnostic performance of GBP5 alone (AUC, 0.86; 95% CI, .80–.93).

Conclusions
The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in individuals with HIV. Validation in large prospective diagnostic study is now required.
The role of IFN-γ-mediated host immune responses in monitoring and the elimination of Toxoplasma gondii infection
Authors: Ihara Fumiaki , Yamamoto Masahiro 
Published: January 2024

Abstract
Toxoplasma gondii is a pathogenic protozoan parasite of the Apicomplexa family that affects approximately 30% of the world’s population. Symptoms are usually mild in immunocompetent hosts, but it can pose significant health risks to immunosuppressed patients and pregnant women. Current treatment options are limited, and new therapies and vaccines are needed. The innate immune system is the first to recognize T. gondii infection and activates pro-inflammatory cytokines and chemokines to promote acquired immunity. The IL-12/IFN-γ axis is particularly important, and when this pathway is inhibited, infection becomes uncontrolled and lethal. In mice, receptors such as Toll-like receptor 11 (TLR11), TLR12, and chemokine receptors are involved in T. gondii recognition and the modulation of immune responses. In humans, where TLR11 and TLR12 are absent, other mechanisms have been reported as the innate immune sensing system in T. gondii infection. Immune cells activated in response to infection produce interleukin (IL)-12, which stimulates the proliferation of natural killer cells and T cells and promotes the production of interferon (IFN)-γ. Several IFN-γ-induced anti-T. gondii defense mechanisms inhibit parasite growth. These include nitric oxide (NO) production, indoleamine 2,3-dioxygenase, and the destruction of parasitophorous vacuoles by IFN-γ-inducible immunity related GTPase groups (IRGs and GBPs). Recent studies focusing on the diversity of IRGs in rodents and effector molecules in T. gondii suggest that host immune mechanisms and pathogen immune evasion mechanisms have co-evolved. Furthermore, it has been suggested that cysts are not simply dormant during chronic infection. This review summarizes recent findings on anti-T. gondii innate, adaptive, and cell-autonomous immune responses.
Effective Approaches to Diagnostic Stewardship of Syndromic Molecular Panels
Authors: Hitchcock Matthew M , Gomez Carlos A , Pozdol Joseph , Banaei Niaz 
Published: January 2024

Abstract

Background
Syndromic molecular panels for the diagnosis of gastroenteritis, meningitis/encephalitis, and pneumonia are becoming routinely used for patient care throughout the world.

Content
These rapid, sample-to-answer assays have great potential to improve patient care, infection control, and antimicrobial stewardship. However, diagnostic stewardship is essential for their optimal use and accuracy, and interventions can be applied at all phases of the diagnostic process.

Summary
The aim of this review article is to describe effective approaches to diagnostic stewardship for syndromic molecular panels to ensure appropriate test utilization and quality assured results.
Elucidating the Clinical Interpretation and Impact of a Positive Plasma Cell-Free DNA Metagenomics Test Result—A Single Center Retrospective Study
Authors: Vinh Dong Huan , Saleh Tawny , Kaur Ishminder , Yang Shangxin 
Published: January 2024

Abstract

Background
The Karius Test (KT), a cell-free DNA metagenomic next-generation sequencing assay, has potential to improve diagnostic evaluation of infectious diseases. Published data describing clinical impact of positive KT results are limited. We attempt to elucidate the clinical interpretation and impact of positive KT results based on types and patterns of detected pathogens and patient characteristics.

Methods
All positive KT results from a single institution in 2022 were screened. Patients with results that met predefined categories were included for review by a panel of 3 infectious diseases physicians and one clinical microbiologist. Predefined categories included reports with fungal, parasitic, notable bacterial, notable viral pathogens, or polybacterial results (≥3 bacteria). Polybacterial results were further classified into patterns of microbiome detected. Clinical impact and its correlation with result or patient characteristics were explored.

Results
Ninety-two patients met the inclusion criteria, most were immunocompromised (73%). Positive KT results that met predefined categories had the following clinical impact: positive in 30.4%, negative in 2.2%, and none in 65.2%. Polybacterial results, especially interpreted as oral flora had lowest clinical impact (7.1% and 0.0%, respectively), while detection of parasites or notable bacterial pathogens had the highest clinical impact (100% and 77.8%, respectively). There was no correlation between patient characteristics and clinical impact.

Conclusions
Among a cohort of largely immunocompromised patients, we were able to demonstrate clinical impact of specific KT result types and patterns but did not find correlation between patient characteristics and clinical impact. Our results should be confirmed in future larger cohorts.
Evaluation of a New NT-proBNP Immunoassay on an Automated Core Laboratory System
Authors: Logan Samantha , Di Meo Ashley , Shapero Stacey , Fabros Anselmo , Taher Jennifer , Kulasingam Vathany 
Published: January 2024

Abstract

Background
Heart failure remains a major cause of morbidity and mortality despite improvements in treatment. This study aimed to evaluate the Alere N-terminal pro B-type natriuretic peptide (NT-proBNP) immunoassay on the Abbott Alinity i platform.

Methods
The analytical performance including precision, linearity, limit of quantitation (LOQ), carryover, dilution-recovery, and stability was evaluated. A method comparison between the Abbott Alere NT-proBNP assay and Roche Elecsys proBNP II assay was performed using 70 residual plasma samples.

Results
Total imprecision was 4.1%, 3.5%, and 2.3% for low (120.9 ng/L), medium (333.9 ng/L), and high (4767.4 ng/L) QC levels, respectively. The manufacturer’s claimed LOQ of 8.3 ng/L was verified. Method comparison between the Alere NT-proBNP assay and the Elecsys proBNP II assay showed good agreement between assays with an R value of 0.998, a slope of 1.05 (95% CI, 1.03–1.06), and an intercept of 45.81 (95% CI, −46.6.84 to 138.22). The Bland–Altman plot showed an absolute bias of 250 ng/L or 6.02%. Subrange analysis (NT-proBNP &lt;2000 ng/L) showed good agreement with an R value of 0.998, a slope of 1.04 (95% CI, 1.02–1.06), and an intercept of −4.83 (95% CI, −26.95 to 17.28), with a mean bias of 26 ng/L or 3.2%. The stability of NT-proBNP was also verified in lithium heparin plasma samples stored at 4°C over a 7-day period. Hemolysis and lipemia interference thresholds were verified, but icterus impacted NT-proBNP recovery by &gt;20% at low analyte concentrations.

Conclusions
The Alere NT-proBNP assay demonstrated acceptable analytical performance and very good clinical concordance with the Elecsys proBNP II assay.
RNA-based bone histomorphometry: method and its application to explaining postpubertal bone gain in a G610C mouse model of osteogenesis imperfecta
Authors: Makareeva Elena , Sousa Megan , Kent Tristan , de Castro Luis F , Collins Michael T , Leikin Sergey 
Published: January 2024

Abstract
Bone histomorphometry is a well-established approach to assessing skeletal pathology, providing a standard evaluation of the cellular components, architecture, mineralization, and growth of bone tissue. However, it depends in part on the subjective interpretation of cellular morphology by an expert, which introduces bias. In addition, diseases like osteogenesis imperfecta (OI) and fibrous dysplasia are accompanied by changes in the morphology and function of skeletal tissue and cells, hindering consistent evaluation of some morphometric parameters and interpretation of the results. For instance, traditional histomorphometry combined with collagen turnover markers suggested that reduced bone formation in classical OI is accompanied by increased bone resorption. In contrast, the well-documented postpubertal reduction in fractures would be easier to explain by reduced bone resorption after puberty, highlighting the need for less ambiguous measurements. Here we propose an approach to histomorphometry based on in situ mRNA hybridization, which uses Col1a1 as osteoblast and Ctsk as osteoclast markers. This approach can be fully automated and eliminates subjective identification of bone surface cells. We validate these markers based on the expression of Bglap, Ibsp, and Acp5. Comparison with traditional histological and tartrate-resistant acid phosphatase staining of the same sections suggests that mRNA-based analysis is more reliable. Unlike inconclusive traditional histomorphometry of mice with α2(I)-Gly610 to Cys substitution in the collagen triple helix, mRNA-based measurements reveal reduced osteoclastogenesis in 11-wk-old animals consistent with the postpubertal catch-up osteogenesis observed by microCT. We optimize the technique for cryosections of mineralized bone and sections of paraffin-embedded decalcified tissue, simplifying and broadening its applications. We illustrate the application of the mRNA-based approach to human samples using the example of a McCune-Albright syndrome patient. By eliminating confounding effects of altered cellular morphology and the need for subjective morphological evaluation, this approach may provide a more reproducible and accessible evaluation of bone pathology.
Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men
Authors: Svensson Johan , Ohlsson Claes , Karlsson Magnus K , Herlitz Hans , Lorentzon Mattias , Lewerin Catharina , Mellström Dan 
Published: January 2024

Abstract
Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2 yr) elderly men (n = 1825; mean age 75, range 69–81 yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n = 479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05–1.24) and hip fractures (n = 207; HR 1.18, 95% CI, 1.04–1.33). Also, in men with normal TSH (n = 1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04–2.02 and HR 1.51, 95% CI, 1.07–2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.
Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study
Authors: Brown Janet , Paggiosi Margaret A , Rathbone Emma , Gregory Walter , Bertelli Gian , Din Omar , McCloskey Eugene , Dodwell David , Cameron David , Eastell Richard , Coleman Robert 
Published: January 2024

Abstract
Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites. One hundred twenty had previously been randomized to zoledronate (19 doses of 4 mg over 5 yr) and 104 to the control arm. BMD and BTMs were assessed at sub-study entry, 6 (BTMs only), 12, 24, and 60 mo following the completion of AZURE. As expected, mean BMD, T-scores, and Z-scores at sub-study entry were higher in the zoledronate vs the control arm. At the lumbar spine, the mean (SD) standardized BMD (sBMD) was 1123 (201) and 985 (182) mg/cm2 in the zoledronate and control arms, respectively (P &lt; .0001). The baseline differences in sBMD persisted at all assessed skeletal sites and throughout the 5-yr follow-up period. In patients completing zoledronate treatment, BTMs were significantly lower than those in the control arm (α- and β-urinary C-telopeptide of type-I collagen, both P &lt; .00001; serum intact pro-collagen I N-propeptide, P &lt; .00001 and serum tartrate-resistant acid phosphatase 5b, P = .0001). Some offset of bone turnover inhibition occurred in the 12 mo following the completion of zoledronate treatment. Thereafter, during the 60 mo of follow-up, all BTMs remained suppressed in the zoledronate arm relative to the control arm. In conclusion, in addition to the known anti-cancer benefits of adjuvant zoledronate, there are likely to be positive, lasting benefits in BMD and bone turnover.
Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice
Authors: Hofstee Marloes I , Siverino Claudia , Saito Motoo , Meghwani Himanshu , Tapia-Dean James , Arveladze Samson , Hildebrand Maria , Rangel-Moreno Javier , Riool Martijn , Zeiter Stephan , Zaat Sebastian A J , Moriarty T Fintan , Muthukrishnan Gowrishankar 
Published: January 2024

Abstract
Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections. The involvement of PVL in S. aureus pathogenesis during bone infections has not been studied extensively yet. To investigate this, humanized BALB/c Rag2−/−Il2rg−/−SirpaNODFlk2−/− (huBRGSF) mice were subjected to transtibial implant-associated osteomyelitis with community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 wild type strain (WT), an isogenic mutant lacking lukF/S-PV (Δpvl), or complemented mutant (Δpvl+pvl). Three days post-surgery, Δpvl-infected huBRGSF mice had a less severe infection compared to WT-infected animals as characterized by 1) improved clinical outcomes, 2) lower ex vivo bacterial bone burden, 3) absence of staphylococcal abscess communities (SACs) in their bone marrow, and 4) compromised MRSA dissemination to internal organs (liver, kidney, spleen, heart). Interestingly, Δpvl-infected huBRGSF mice had fewer human myeloid cells, neutrophils, and HLA-DR+ monocytes in the bone niche compared to WT-infected animals. Expectedly, a smaller fraction of human myeloid cells were apoptotic in the Δpvl-infected huBRGSF animals. Taken together, our study highlights the pivotal role of PVL during acute implant-associated osteomyelitis in humanized mice.
A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss
Authors: de la Bastide Christopher , Soares Lissa , Lui Li-Yung , Harrington James , Cawthon Peggy , Orwoll Eric , Kado Deborah , Meliker Jaymie 
Published: January 2024

Abstract
Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long–term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross–sectional studies, this will be the first well–powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long–term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.
Insect frass composition and potential use as an organic fertilizer in circular economies
Authors: Amorim Helen C S , Ashworth Amanda J , Arsi Komala , Rojas M Guadalupe , Morales-Ramos Juan A , Donoghue Annie , Robinson Kelsy 
Published: January 2024

Abstract
Insect manure or “frass” has emerged as an alternative nutrient source for alleviating the dependence on fossil fuel-based fertilizers, reducing food waste, and promoting food security. Yet, research on insect frass chemical composition is in its infancy. Here, we assessed the chemical properties of yellow mealworm (Tenebrio molitor L.) frass compared with poultry litter (PL). Insect frass was obtained from the National Biological Control Laboratory (NBCL; IF-L) and an insect-rearing company (IF-C). PL was collected from facilities in Arkansas (PL-AR) and North Carolina (PL-NC). Samples were analyzed for pH, electrical conductivity, macro- and micronutrients, heavy metals, pathogens, and indicator microorganisms. On average, insect frass had 43% and 47% higher C and N than PL, respectively (P &lt; 0.05). Considering a 5 mg/ha application rate, IF-C can supply 159 kg N/ha, twice the N supply of PL-AR (78 kg/ha). IF-L had a 53% higher P supply than PL-NC. Mean K, Ca, S, and micronutrient contents were higher in PL than in frass (P &lt; 0.05), whereas As, Cd, Cr, and Pb were nearly absent in frass. Chemical composition and pathogens in fertilizer sources were largely affected by insect-rearing substrate and supplements used in poultry and insect production. Insect frass utilized in this study had optimum C and N rates relative to PL, suggesting a promising soil amendment for improving soil health and C sequestration, thus contributing to sustainable agricultural intensification and reuse of food waste in circular economies.
Transmission Patterns of Norovirus From Infected Children to Household Members in León, Nicaragua
Authors: Vielot Nadja A , Zepeda Omar , Reyes Yaoska , González Fredman , Toval-Ruíz Christian , Munguia Nancy , Picado Yorling , Becker-Dreps Sylvia , Bucardo Filemon 
Published: January 2024

Abstract
Norovirus is a common and highly transmissible gastrointestinal pathogen. Among 34 Nicaraguan households with a norovirus-infected child, 48% experienced norovirus transmission within 1 week, infecting 18% of household members; GII norovirus was more commonly transmitted than GI. Pediatric norovirus vaccines could prevent both index cases and transmission to close contacts.