bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of introducing somatic mitochondria into an early embryo on zygotic gene activation
Authors: Hayashi Yoshihiro , Bai Hanako , Takahashi Masashi , Mitani Tomohiro , Kawahara Manabu 
Published: January 2025

Abstract
Unlike differentiated somatic cells, which possess elongated mitochondria, undifferentiated cells, such as those of preimplantation embryos, possess round, immature mitochondria. Mitochondrial morphology changes dynamically during cell differentiation in a process called mitochondrial maturation. The significance of the alignment between cell differentiation and mitochondrial maturity in preimplantation development remains unclear. In this study, we analyzed mouse embryos into which liver-derived somatic mitochondria were introduced (SM-embryos). Most SM-embryos were arrested at the two-cell stage. Some of the introduced somatic mitochondria became round, while others remained elongated and large. RNA-sequencing revealed a disruption of both minor and major zygotic gene activation (ZGA) in SM-embryos. Minor ZGA did not terminate before major ZGA, and the onset of major ZGA was inhibited, as shown by histone modification analyses of histone H3 lysine 4 trimethylation and histone H3 lysine 27 acetylation. Further analysis of metabolites involved in histone modification regulation in SM-embryos showed a significantly lower NAD+/NADH ratio in SM-embryos than in control embryos. Additionally, the mitochondrial membrane potential, an indicator of mitochondrial function, was lower in SM-embryos than in control embryos. Our results demonstrated that introducing somatic mitochondria into an embryo induces mitochondrial dysfunction, thereby disrupting metabolite production, leading to a disruption in ZGA and inducing developmental arrest. Our findings reveal that the alignment between cell differentiation and mitochondrial maturity is essential for early embryonic development.
Improving UTI Diagnostics in Oncology: Reliability of Reflex Urine Culture in Immunosuppressed Neutropenic and Non-neutropenic Cancer Patients
Authors: Laracy Justin C , Chan June L , Kodama Rich , Yan Judy , Raible Kevin M , Sepkowitz Kent , McVoy Lauren , Babady N Esther , Kamboj Mini 
Published: January 2025

Abstract

Background
Urinary tract infections are prone to overdiagnosis, and reflex urine culture protocols offer a valuable opportunity for diagnostic stewardship in this arena. However, there is no recommended standard testing approach. Patients with cancer are often excluded from reflex urine culture protocols, especially if they are severely immunosuppressed or neutropenic. The aim of this study was to evaluate the performance characteristics of urine screening studies, including dipstick urinalysis for nitrite and leukocyte esterase and urine microscopy for white blood cell count, to detect significant pathogen growth.

Methods
A retrospective study of 58 098 urine cultures with a paired dipstick urinalysis with or without urine microscopy was performed at Memorial Sloan Kettering Cancer Center in New York City, evaluating data from 1 January 2018 to 31 December 2020. A dipstick urinalysis was considered negative only if leukocyte esterase and nitrite were undetected.

Results
A negative dipstick urinalysis had a negative predictive value of 98% for clinically significant bacteriuria in voided urine and 95% for catheterized urine. Notably, a negative urine dipstick test screen maintained a high negative predictive value among patients with neutropenia and in those with antibiotic exposure before testing. Finally, the presence of pyuria ≥10 white blood cells per high-power field on urine microscopy offered negligible incremental diagnostic benefit in samples with a negative dipstick urinalysis.

Conclusions
Reflex urine culture protocols contingent upon a screening dipstick urinalysis are a safe and effective platform for diagnostic stewardship in patients with cancer including those with neutropenia.
Left bundle branch area pacing in patients with transthyretin cardiac amyloidosis: a case series
Authors: Miyajima Keisuke , Kobayashi Wakaba , Hakamata Shogo , Takazawa Yasukazu , Kawaguchi Yoshitaka , Wakabayashi Yasushi , Maekawa Yuichiro 
Published: January 2025

Abstract

Background
Transthyretin cardiac amyloidosis is associated with various arrhythmias, including atrioventricular block. Despite this correlation, established treatments for transthyretin cardiac amyloidosis-associated arrhythmias are lacking. Left bundle branch area pacing is a promising physiological pacing technique.

Case summary
This case series describes three instances of successful left bundle branch area pacing in patients with transthyretin cardiac amyloidosis presenting with atrioventricular block. Despite significant ventricular septal hypertrophy across all cases, left bundle branch area pacing was implemented effectively without complications.

Discussion
Traditional pacing strategies in transthyretin cardiac amyloidosis, such as right ventricular pacing, have been associated with a reduced left ventricular ejection fraction and worsening heart failure. Although biventricular pacing has been explored, the supporting evidence remains limited and inconclusive. Recent studies have suggested that left bundle branch area pacing poses a lower risk of inducing heart failure than biventricular pacing. Our findings support the safety and efficacy of the left bundle branch area pacing in patients with transthyretin cardiac amyloidosis-related atrioventricular blocks and underscore its viability as a pacing strategy.
Echocardiography of the right heart in pulmonary arterial hypertension: insights from the ULTRA RIGHT VALUE study
Authors: Lo Giudice Francesco , Escribano-Subias Pilar , Tello Khodr , Kopec Grzegorz , Ghio Stefano , Giannakoulas George , D’Alto Michele , Filomena Domenico , Manzi Giovanna , Orlando Antonio , Greco Alessandra , Recchioni Tommaso , Yildiz Selin , López-Guarch Carmen Jiménez , Cruz-Utrilla Alejandro , Psochias Polykarpos , Patsiou Vasiliki , Stępniewski Jakub , Jonas Kamil , Scelsi Laura , Kremer Nils , Vergara Andrea , Vizza Carmine Dario , Naeije Robert , Badagliacca Roberto 
Published: January 2025

Abstract

Aims
Outcome in pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to increased afterload. Echocardiography is easily available to assist bedside evaluation of the RV. However, no agreement exists about the feasibility and most relevant measurements. We therefore examined the feasibility, quality, and clinical correlations of standard echocardiographic variables in the evaluation of PAH.

Methods and results
The present multicentric study collected echocardiographic examinations with centralized reading in 401 patients with prevalent PAH. Clinical variables, as World Health Organization (WHO) functional class (FC), 6 min walk distance (6MWD), brain natriuretic peptide (BNP)/NT-proBNP, invasive haemodynamics, the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines-derived four-strata score, and the United States Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) 2.0 score, were also collected. Echocardiographic measurements showed variable degrees of dilation of the right heart as assessed by right atrial and RV areas, altered indices of systolic function such as tricuspid annular plane systolic excursion (TAPSE), fractional area change, or 2D strain, and derived estimates of RV to pulmonary artery (PA) coupling by referring these measurements to systolic PA pressure (sPAP). All these measurements were feasible. All measurements of right heart dimensions and function, particularly TAPSE/sPAP, were correlated with WHO-FC, 6MWD, BNP/NT-proBNP, invasive haemodynamics, and ESC/ERS and REVEAL 2.0 scores.

Conclusion
The present quality-controlled data from a network of PAH referral centres offer the background needed for further evaluation of the added value of echocardiography to currently recommended risk assessments in PAH.
Cardiovascular diseases, prevention and management of complications in older adults and frail patients treated for elective or post-traumatic hip orthopaedic interventions
Authors: Guasti Luigina , Fumagalli Stefano , Afilalo Jonathan , Geisler Tobias , Abreu Ana , Ambrosetti Marco , Gevaert Sofie , Christodorescu Ruxandra , Richter Dimitri , Aboyans Victor , Chastaingt Lucie , Barisone Michela , Severgnini Paolo , Asteggiano Riccardo , Ferrini Marc 
Published: January 2025

Abstract
Due to the aging population, focusing on healthy aging has become a global priority.
Cardiovascular diseases (CVDs) and frailty, characterized by increased vulnerability to adverse stress and health events, interact synergistically in advanced age. In older adults, hip fractures are a frequent dramatic “life-transition” event. Conditions such as arrhythmias, orthostatic hypotension, heart failure, peripheral artery disease and adverse drug reactions may facilitate falls and thus bone fractures in older adults. Cardiovascular complications or the worsening of previous CVDs may increase the degree of frailty and disability following this surgery.
The close relationship between older age, CVDs, frailty and orthopaedic surgery leads to the need to focus on the various phases of interventions in a multidisciplinary approach.
This document aims to provide practical support to prevent cardiovascular complications in older and frail patients undergoing hip procedures by suggesting specific assessments and interventions.
In particular, in pre-operative care the focus should be on the assessment and management of concomitant CVD and frailty, while immediate peri- and post-operative care should highlight specific concerns for anesthesia, prevention and management of thrombotic complications, specific nursing needs, including the prevention of infections and delirium, and the establishment of an integrated rehabilitation program focusing on CVDs and the risk of new falls, with a positive role for care-givers.
Furthermore, by optimizing the “hip surgery pathway” the objective is to help avoid the deterioration of health and loss of independence that often result from this surgery through the correct management of cardiovascular patients in this peculiar context.
Air quality and the risk of acute atrial fibrillation (EP-PARTICLES study): a nationwide study in Poland
Authors: Kurasz Anna , Lip Gregory Y H , Święczkowski Michał , Tomaszuk-Kazberuk Anna , Dobrzycki Sławomir , Kuźma Łukasz 
Published: January 2025

Abstract

Aims
Air pollution remains the single largest environmental health risk factor, while atrial fibrillation (AF) is the most prevalent arrhythmia globally. The study aimed to investigate the relationship between short-term exposure to air pollution and acute AF admissions.

Methods and results
Individual data on AF hospitalization in the years 2011–20 were collected from the National Health Fund in Poland (ICD-10: I48.XX). To obtain high-resolution data on air pollution, we applied a modelling method using the GEM-AQ model. Associations between air pollution exposure and acute AF admissions were estimated using generalized additive models with Poisson regression. Over the analysed period, we recorded 252 566 acute admissions due to AF. Each 10 µg/m3 increment of particulate matter with diameters ≤2.5 (PM2.5) and nitrogen dioxide (NO2) concentration, 1 µg/m3 of sulfur dioxide and 10 ng/m3 of benzo(a)pyrene (BaP) concentration on the day of exposure resulted in 1.13% (0.70−1.55%), 1.65% (1.05−2.26%), 0.11% (0.01−0.21%), and 0.3% (0.04−0.55%) increases in acute AF admissions, respectively. The estimates are larger for women and older people. Stronger associations between PM2.5 and BaP concentrations and AF admissions in poorly urbanized areas were noted. Areas with high gross domestic product levels were more affected by the increase in NO2 concentrations, resulting in a 0.2% (1.001–1.003) increase in AF admissions. Exposure-response functions show steeper slopes of the pollutant-outcome associations in the lower ranges of exposures, far below World Health Organization (WHO) air quality guideline norms. For the zero-emission scenario, we estimate avoidable AF admissions—5873 for PM2.5 (95% confidence interval 3679 to 8047) and 3295 for NO2 (2108–4477).

Conclusion
Air pollution acts as a triggering factor and can be associated with acute AF hospitalizations. PM2.5 and NO2 have an impact on AF even at concentrations levels below WHO air quality guideline norms.
Paris in the Eyes of Argentine Women: Paula Wajsman’s Informe de París (1990) and María Moreno’s El Affair Skeffington (1992)
Authors: López Martínez Rodrigo 
Published: January 2025

Abstract
This article examines the fictional rendering of Paris in two Argentine novels published just two years apart but with strongly contrasting receptions: Paula Wajsman’s Informe de París (1990) and María Moreno’s El Affair Skeffington (1992). While Wajsman died in 1995, having published only one novel that went mostly unnoticed in literary and academic circles, Moreno has been a leading figure in the Argentine cultural scene for the past two decades. A comparative study of Wajsman and Moreno allows us to explore how they rewrote the paradigmatic significance of Paris for Argentine culture through a shared feminist lens. Ultimately, I argue that Informe de París and El Affair Skeffington situate their female characters in Paris as a means of turning the so-called ‘literary capital of Latin America’ into a ‘third space’ that enables renewed modes of literature and community beyond the limits of gender and the nation.
PhWRKY30 activates salicylic acid biosynthesis to positively regulate antiviral defense response in petunia
Authors: Wang Meiling , Yuan Yanping , Zhao Yike , Hu Zhuo , Zhang Shasha , Luo Jianrang , Jiang Cai-Zhong , Zhang Yanlong , Sun Daoyang 
Published: January 2025

Abstract
Petunia (Petunia hybrida) plants are highly threatened by a diversity of viruses, causing substantial damage to ornamental quality and seed yield. However, the regulatory mechanism of virus resistance in petunia is largely unknown. Here, we revealed that a member of petunia WRKY transcription factors, PhWRKY30, was dramatically up-regulated following Tobacco rattle virus (TRV) infection. Down-regulation of PhWRKY30 through TRV-based virus-induced gene silencing increased green fluorescent protein (GFP)-marked TRV RNA accumulation and exacerbated the symptomatic severity. In comparison to wild-type (WT) plants, PhWRKY30-RNAi transgenic petunia plants exhibited a compromised resistance to TRV infection, whereas an enhanced resistance was observed in PhWRKY30-overexpressing (OE) transgenic plants. PhWRKY30 affected salicylic acid (SA) production and expression of arogenate dehydratase 1 (PhADT1), phenylalanine ammonia-lyase 1 (PhPAL1), PhPAL2b, non-expressor of pathogenesis-related proteins 1 (PhNPR1), and PhPR1 in SA biosynthesis and signaling pathway. SA treatment restored the reduced TRV resistance to WT levels in PhWRKY30-RNAi plants, and application of SA biosynthesis inhibitor 2-aminoindan-2-phosphonic acid inhibited promoted resistance in PhWRKY30-OE plants. The protein-DNA binding assays showed that PhWRKY30 specifically bound to the promoter of PhPAL2b. RNAi silencing and overexpression of PhPAL2b led to decreased and increased TRV resistance, respectively. The transcription of a number of reactive oxygen species- and RNA silencing-associated genes was changed in PhWRKY30 and PhPAL2b transgenic lines. PhWRKY30 and PhPAL2b were further characterized to be involved in the resistance to Tobacco mosaic virus (TMV) invasion. Our findings demonstrate that PhWRKY30 positively regulates antiviral defense against TRV and TMV infections by modulating SA content.
PpERF17 alleviates peach fruit postharvest chilling injury under elevated CO2 by activating jasmonic acid and γ-aminobutyric acid biosynthesis
Authors: Ai Shaojie , Liang Ling , Liu Mengfei , Grierson Don , Chen Kunsong , Xu Changjie 
Published: January 2025

Abstract
Internal browning (IB) is a common chilling injury (CI) feature in peach fruit after prolonged cold storage. Our previous study demonstrated that low O2 and elevated CO2 (eCO2) condition of modified atmosphere (MA) storage alleviated CI by facilitating the accumulation of jasmonic acids (JAs) and γ-aminobutyric acid (GABA) in ‘Zhonghuashoutao’ (‘ZHST’) peach fruit. Here we show that 10 % CO2 alone can improve cold tolerance, with ethylene response factor 17 (PpERF17) identified as a pivotal transcription factor (TF) that promotes biosynthesis of JAs and GABA. Stable transformation of PpERF17 in tobacco resulted in reduced cold damage, attributed to decreased levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA), as well as enhanced accumulation of JAs and GABA. Moreover, under eCO2, PpMYC2.1, the master regulator of JA signaling, was found to activate transcription of 13S-lipoxygenase (Pp13S-LOX), allene oxide synthase (PpAOS), 12-oxophytodienoate reductase 3 (PpOPR3) and glutamate decarboxylase (PpGAD), while also inducing the expression of the upstream TF PpERF17, thereby establishing positive feedback loops upregulating JA and GABA biosynthesis. Finally, application of methyl jasmonate (MeJA) to fruit before shelf transfer from cold storage alleviated chilling injury development, due to increased accumulation of JAs and GABA as a result of raised expression of related biosynthetic genes. Collectively, our results suggest that eCO2-induced PpERF17 enhances JAs and GABA accumulation while activating the JA signaling pathway. This contributes to a positive feedback loop mediated by PpMYC2.1, ultimately alleviating CI of peach fruit through the sustained accumulation of JAs and GABA.
Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition
Authors: Weintraub Yael , Collen Lauren V , Hussey Seamus , Mitrova Katarina , Machta Joseph S , Kang Ben , Granot Maya , D’Arcangelo Giulia , Spencer Elizabeth A , Kolho Kaija-Leena , Yeh Pai-Jui , Sladek Malgorzata , Scarallo Luca , Palomino Laura , Afzal Nadeem Ahmad , de Laffolie Jan , Miele Erasmo , Bramuzzo Matteo , Olén Ola , Russell Richard K , Rohani Pejman , Tzivinikos Christos , Urlep Darja , van Rheenen Patrick F , de Ridder Lissy , Yogev Dotan , Schneider Anna-Maria , Cohen Shlomi , Garcia-Romero Ruth , Dipasquale Valeria , Uhlig Holm H , Shouval Dror S 
Published: January 2025

Abstract

Background and aims
Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset &lt; 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking. We assessed the therapeutic response to help close this gap.

Methods
This retrospective study involved 30 sites worldwide. Demographic, clinical, and laboratory data were collected from patients with VEO-IBD who commenced adalimumab therapy before the age of 6 years.

Results
Seventy-eight patients (37 Crohn’s disease, 26 ulcerative colitis, and 15 with IBD-unclassified) were included. Median age of IBD onset was 2.6 (1.3–4.1) years, with 30 (38.5%) patients diagnosed at age &lt;2 years. Median age at adalimumab initiation was 4.2 (2.8-5.1) years. Adalimumab was used as second-line biologic therapy in 45 (57.7%) patients after infliximab. The median time to last follow-up was 63 (22-124) weeks. Significant improvement in clinical scores, CRP, fecal calprotectin, and weight Z-score were observed by Week 52. Adalimumab durability rates were 61.9%, 48.1%, and 35.6% after 1, 2, and 3 years, respectively. Drug discontinuation rates were not dependent on IBD type, age, prior anti-TNF exposure, or concomitant immunomodulatory treatment. Four (5.1%) patients developed serious infections, including 1 patient with TTC7A deficiency who died following adenovirus sepsis.

Conclusion
Adalimumab therapy is a viable therapeutic option in patients with VEO-IBD with an acceptable safety profile.
Reduction of Vancomycin-Associated Acute Kidney Injury With Montelukast
Authors: Teran Nicholas S , Hudson Cole S , Phe Kady , Wang Yunting , Zhang Yang , Chen Hua , Nigo Masayuki , Tam Vincent H 
Published: January 2025

Abstract

Background
Vancomycin ranks among the most utilized antimicrobial agents in the treatment of serious β-lactam–resistant gram-positive infections, but its use has been associated with nephrotoxicity. Reduction of acute kidney injury (AKI) has been reported in preclinical models with adjuvant montelukast. The purpose of the study was to ascertain if montelukast was associated with a reduction in the prevalence of vancomycin-associated AKI.

Methods
This retrospective cohort study examined adult patients who received intravenous vancomycin between January 2020 and January 2024. The RIFLE criteria (risk, injury, failure, loss, and end-stage kidney disease) were employed in identifying cases of AKI. Additionally, a preclinical vancomycin-associated nephrotoxicity model was established to provide insights into possible renal protective mechanisms.

Results
Patients receiving montelukast (n = 110) were compared with controls (n = 330), of which AKI was observed in 3 (2.7%) vs 35 (10.6%), respectively (P = .01). A multivariate logistic regression analysis revealed that weight (odds ratio [OR], 1.02; 95% CI, 1.006–1.03; P = .005) and intensive care unit admission (OR, 6.88; 95% CI, 2.96–18.8; P &lt; .001) were independently associated with AKI, while montelukast (OR, 0.26; 95% CI, .06–.77; P = .03) and male gender were protective (OR, 0.41; 95% CI, .19–.85; P = .02). Our in vitro model also revealed that adjuvant montelukast can reduce injury to proximal tubule cells through activation of the p62/KEAP-1/HO-1 antioxidant pathway.

Conclusions
Our study suggests that montelukast during vancomycin therapy may be protective against AKI, which may reduce patient harm and hospitalization costs. Further studies are warranted to validate our findings prospectively.
Lack of Toll-Like Receptor 9 Exacerbates Ocular Impairment and Visual Loss During Systemic Cryptococcus gattii Infection
Authors: da Silva-Junior Elias Barbosa , Araújo Victor Guedes , Araujo-Silva Carlla Assis , Covre Luciana Polaco , Guimarães-de-Oliveira Joyce Cristina , Diniz-Lima Israel , Freire-de-Lima Leonardo , Morrot Alexandre , de Brito-Gitirana Lycia , Previato Jose Osvaldo , Mendonça-Previato Lucia , Vommaro Rossiane Claudia , Petrs-Silva Hilda , Decote-Ricardo Debora , de Matos Guedes Herbert Leonel , Freire-de-Lima Celio Geraldo 
Published: January 2025

Abstract
Cryptococcus gattii is a saprophytic basidiomycete that grows in the environment and can cause systemic cryptococcosis. Ocular cryptococcosis causes blindness and is commonly associated with central nervous system infection. Toll-like receptor 9 (TLR9) can control cryptococcosis and other mycoses. Here, using C57BL/6 TLR9 knockout mice (TLR9−/−), we evaluated the role of TLR9 signaling in ocular involvement during systemic C. gattii infection. We observed ocular impairment and found a high fungal burden in the retina, vitreous humor, and optic nerve of TLR9−/− mice 3 weeks after infection. Capsular polysaccharide glucuronoxylomannan deposition, astrogliosis, and morphological alterations in retina led to progressive blindness of TLR9−/− mice. The phenomenon observed in our work had not been explored previously in a murine model. These results contribute to the understanding of the role of TLR9 during ocular cryptococcosis. Therapies using TLR9 agonists may be important for the treatment of ocular cryptococcosis.