Response Factor Research Articles

Genome-wide identification and characterization of transcription factors involved in defense responses against Sclerotinia sclerotiorum in Brassica juncea

Sclerotinia sclerotiorum could cause significant yield losses of up to 70% in rapeseed cultivation. Nevertheless, the availability of immune or highly resistant germplasm and mechanisms to combat S. sclerotiorum, particularly in B. juncea, remains insufficient. Transcription factors (TFs) are recognized for their critical role in plant defense against S. sclerotiorum. In the present study, a total of 4807 TFs from 48 families were expressed and identified at 12, 24, and 36 h after inoculation (HAI) in two B. juncea lines: G21-912, exhibiting higher S. sclerotiorum resistance (HR), and G21-853, displaying lower S. sclerotiorum resistance (LR). The number of differentially expressed TFs (DETs) between the HR and the LR lines peaked at 24 HAI, with 202 upregulated and 105 downregulated TFs. Through expression and subcellular localization analyses, three candidate DETs, namely BjuA037408 (ETHYLENE RESPONSIVE FACTOR 59, ERF59), BjuB028842 (RELATED TO ABI3/VP1 1, RAV1), and BjuA016484 (WRKY25), were identified as the primary TFs in defense against S. sclerotiorum inoculation. The expression of these three genes was validated in the double haploid lines of BC3 (the third backcrossing generation) derived from the HR×LR cross. This study serves as a valuable case study for the characterization of TFs associated with defense mechanisms against S. sclerotiorum in B. juncea. The confirmed resistant B. juncea line of HR, along with the three key DETs, is expected to significantly contribute to future breeding efforts aimed at developing Sclerotinia-resistant varieties.

Identification of a central regulator of ginkgolide biosynthesis in Ginkgo biloba that integrates jasmonate and light signaling

Ginkgolides are secondary metabolites unique to Ginkgo biloba with the potential to prevent and treat cardiovascular and cerebrovascular diseases. Although the biosynthetic pathways of ginkgolides have been partly uncovered, the mechanism regulating their biosynthesis is still largely unknown. Here, using multiomic and genetic analyses, we report the identification of a transcription factor, named ETHYLENE RESPONSE FACTOR ASSOCIATED WITH GINKGOLIDE BIOSYNTHESIS (GbEAG), as a critical regulator of ginkgolide biosynthesis. GbEAG is highly expressed in the roots of G. biloba, and its expression is significantly induced by methyl jasmonate (MeJA). Ginkgolide content was significantly increased in roots by overexpressing GbEAG using a "cut-dip-regeneration" system. GbEAG positively regulates ginkgolide biosynthesis by directly binding to the GCC-boxes in the promoter regions of genes involved in the biosynthesis of ginkgolides, such as ISOPENTENYL DIPHOSPHATE ISOMERASE (GbIDI) and CYTOCHROME P450 7005C3 (GbCYP7005C3). GbEAG mediates the jasmonic acid (JA)-activated ginkgolide synthesis through its direct interaction with the JASMONATE ZINC-FINGER INFLORESCENCE MERISTEM DOMAIN 3 (GbJAZ3) repressor. Importantly, we also found that the central light-response regulator ELONGATED HYPOCOTYL 5 (GbHY5) mediates light induction of ginkgolide biosynthesis by binding to the G-box in the GbEAG promoter. Our findings provide mechanistic insights into the coordinated regulation of ginkgolide biosynthesis via JA and light signals, with GbEAG as a central regulator in G. biloba, and shed light on the potential to develop ginkgolide-rich varieties through molecular breeding and gene editing.

Effect of selenium supplementation on hemodialysis patients: a meta-analysis.

Hemodialysis (HD) patients commonly experience enhanced oxidative stress and inflammation, potentially increasing the risk of malnutrition. Selenium levels are typically lower in HD individuals. Selenium deficiency has been identified as a risk factor for oxidative stress and inflammatory responses. Therefore, we intended to perform a meta-analysis to assess the impact of selenium supplementation on HD patients. PubMed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) on the effect of selenium supplementation on HD patients until September 31, 2024. The data analysis was conducted using Stata15.0 software. Seven RCTs, with 2080 participants, were finally included, with 1029 in the selenium group and 1051 in the control group. The meta-analysis unraveled no statistically significant impact of selenium supplementation on body mass index (SMD = 0.15, 95% CI (- 0.20, 0.49), triglyceride [(SMD = - 0.02, 95% CI (- 0.44, 0.41)], total cholesterol [(SMD = - 0.18, 95%CI (- 0.41, 0.05)], low-density lipoprotein [(SMD = - 0.37, 95% CI (- 1.04, 0.31)], high-density lipoprotein cholesterol [(SMD = 0.15, 95% CI (- 0.54, 0.84)], C-reactive protein [(SMD = - 0.10, 95% CI (- 0.46, 0.27)], ferritin [(SMD = - 0.02, 95% CI (- 0.29, 0.26)], Hx-C reactive protein [(SMD = 0.00, 95% CI (- 1.02, 1.03)], and hemoglobin [(SMD = 0.01, 95% CI (- 0.57,0.59)]. Only selenium levels were significantly increased after selenium supplementation [SMD = 2.83, 95% CI (2.43, 3.24)]. Selenium supplementation can increase selenium levels in HD patients, without notable impacts on weight, triglycerides, and total cholesterol.

Biosorption of Chromium and Nickel from Industrial Oil Mill Wastewater Using Groundnut Pod Waste Activated Carbon

Groundnut shell activated carbon was developed and characterized by chemical activation using phosphoric acid (H3PO4) for the uptake of Cr and Ni in a batch biosorption process. The purpose of this study was to reduce the spread of heavy metals in industrial oil mill wastewater. In this study characterization of activated carbon using, surface chemistry (FTI-IR), surface area (BET), surface morphology, and elemental identification (SEM/EDX) were all carried out, and the BET surface area was 689.41 m2/g for groundnut shell activated carbon. This study was also executed to determine the optimum biosorption efficiency parameters for Cr and Ni removal using Response Surface Methodology (RSM) to obtain maximum biosorption efficiency. The factors considered were temperature (25-55oC), adsorbent dosage (1-3 g) and contact time (1-2 hrs). Biosorption efficiency was the response. ANOVA analysis was carried out to analyse the most effective factor in experimental design response. The optimum conditions for removal of Cr and Ni were adsorbent dosage 0.40 g, contact time 1.1 hr and temperature 42.02 oC, which shows the maximum biosorption efficiency of 97.1% for Cr removal and 94.8% for Ni removal. Isotherm models analyses showed that the biosorption process was best fitted to Langmuir model and was physical. Results of the kinetic studies and thermodynamic parameters revealed that the biosorption process followed a pseudo-second-order, endothermic, and spontaneous in nature.

Comprehensive genome-wide analysis of ARF transcription factors in orchardgrass (Dactylis glomerata): the positive regulatory role of DgARF7 in drought resistance

Auxin response factor (ARF), a transcription factor, is crucial in controlling growth, development, and response to environmental stress. Orchardgrass (Dactylis glomerata) is an economically significant, widely cultivated forage grass. However, information on the genome-wide information and functional characterization of ARFs in orchardgrass is limited. This study identified 27 ARF genes based on the orchardgrass genome database. These DgARFs were unevenly distributed across the seven orchardgrass chromosomes and clustered into four classes. Phylogenetic analysis with multispecies of ARF proteins indicated that the ARFs exhibit a relatively conserved evolutionary path. Focusing on hormone signaling responses, DgARF7 demonstrated a potential positive regulatory role in response to 3-indole acetic acid, methyl jasmonate, gibberellin, salicylic acid, and abscisic acid signals. Additionally, exposure to drought stress induced noticeable oscillatory changes in DgARF7 gene. Notably, DgARF7 enhanced drought tolerance through heterologous expression in yeast and overexpression in Arabidopsis. Overexpressed Arabidopsis lines of DgARF7 exhibited a markedly higher relative water content and superoxide dismutase activity, while the malondialdehyde content was significantly decreased compared to wild type under drought stress. DgARF7 also accelerated flowering time by inducing the flowering-related gene expression levels in Arabidopsis. This research provides important insights into the role of DgARF7 in orchardgrass and provides further understanding in molecular breeding.

Role of Interferon Regulatory Factor 1 in acute and chronic virus infections.

Decades of research have defined the function of interferon regulatory factors (IRFs) in the antiviral immune response. Interferon regulatory factor-1 (IRF-1) is the founding member of the IRF family, with recognized antiviral effects across diverse virus infections. While most antiviral activities of IRF-1 were defined in vitro, fewer studies examined the role of IRF-1 during viral infection of an intact host. Taking advantage of mouse models of global or cell type-specific IRF-1 deficiency, recent studies demonstrate intriguing virus- and cell type-specific functions of IRF-1 during in vivo infection, underlining the complexity of this ancient transcription factor. Here, we review the role of IRF-1 during acute and chronic viral infections of an intact host, with particular focus on relating observations found in mouse models to those observed in a recent study of pediatric patients with IRF-1 insufficiency. By appreciating the complexity of IRF-1 in the immune response, we highlight several virus- and cell type-specific functions of IRF-1 in contributing to host antiviral immunity.

Transcriptomic features of Epstein-Barr virus-associated gastric cancer based on PD-L1 status.

489 Background: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) accounts for 5-10% of all gastric cancers and has a relatively favorable prognosis compared to other subtypes. While the genomic profile of EBVaGC has been previously reported to exhibit extensive CpG island methylation, elevated levels of PD-L1/2, and an absence of TP53 mutations, transcriptomic features remain less explored. The response to immunotherapy of EBVaGC has been various. This study comprehensively investigates the transcriptomic characteristics of EBVaGC in relation to PD-L1 status. Methods: RNA sequencing was conducted on formalin-fixed, paraffin-embedded samples from 27 EBV-positive and 12 EBV-negative patients with HER2-negative gastric cancer. Gene expression was quantified using the RSEM package. Predict-IO, a machine learning-based predictive algorithm developed at Auristone Pte Ltd based on initial work done at the Genome Institute of Singapore (GIS), assessed the likelihood of a patient responding to immunotherapy based on transcriptome expression data. PD-L1 immunohistochemistry was performed using the 22C3 pharmDx assay, and status was classified by CPS. Results: A total of 200 differentially expressed genes (DEGs; log2FC > 2, FDR < 0.05) were identified in EBV-positive versus negative samples, with 157 genes down-regulated and 43 genes up-regulated. Upregulated genes included immune response related genes such as DMBT1, IDO1, PLA2G2A, and IL13RA2, while downregulated genes were primarily associated with cell adhesion, including LAMA1 and CCN6. In the EBV positive group, immune response pathways were enriched; however, within the PD-L1-Low group (CPS < 1), activated signaling pathways such as MYC, E2F, and MTORC1 were observed. Conversely, the PD-L1-High group (CPS ≥ 5) exhibited upregulated snoRNAs. In the EBV negative group, the PD-L1-Low cohort displayed suppressed immune response and ECM remodeling factors, whereas the PD-L1-High cohort showed enrichment of ECM remodeling factors. The Predict-IO Score, which predicts immunotherapy response, was significantly higher in EBV-positive compared to EBV-negative samples ( p = 0.003), and scores were elevated in the PD-L1-High group compared to the PD-L1-Low group. Conclusions: In summary, EBVaGC includes subsets of different PD-L1 expression patterns with distinct activated signaling pathways, differences in ECM remodeling factors, and varying Predict-IO Scores. With these information, we could properly select the responsive patients to immunotherapy among EBVaGC.

Identification, annotation and toxicity estimation of organic pollutants in human serum via non-target analysis.

Environmental organic pollution causes a threat to the ecological environment, constrains social development and can also potentially harm human health. We applied non-target analysis to screen organic pollutants from the serum of 89 individuals, identifying 67 pollutants in the categories of industrial intermediates, plasticizers, surfactants, pharmaceuticals, pesticides, and exogenous pollutant metabolites. The detection rate of chemicals for industrial use (50.3%; 95% CI: 39.7, 60.8) was higher, reflecting the environmental exposure characteristics of the surrounding functional areas. In addition, 1168 potential pollutant features were annotated to 10 superclasses. Exposure levels of identified pollutants were semi-quantified by predicting response factors via machine learning model. Highly exposed pollutants involved various categories, especially pharmaceuticals due to their property of being easily absorbed by human body cross biological barriers. Toxicity of developmental toxicity, bioconcentration, mutagenicity and oral rat median lethal dose (LD50) were predicted with the occurrence rates of 62.7%, 10.4%, 11.9% and 11.9% of the identified pollutants respectively. 4-[3-(Trifluoromethyl)benzyl]piperidine (industrial intermediate), risperidone (pharmaceutical), and aminocarb (insecticide) were predicted to have multiple toxic effects, which deserved attention and further hazard assessment. This study provides a comprehensive pattern of human exposure to organic pollutants, contributing to evaluate the health risks caused by pollutants to the population, thus providing data support for the monitoring and management of pollutants.

Melatonin-Induced Transcriptome Variation of Sweet Potato Under Heat Stress

Melatonin (MT) has been widely recognized for its ability to mitigate the effects of abiotic stress and regulate plant development. In this study, we investigated the role of exogenous MT in enhancing heat tolerance in sweet potato, with a particular focus on its capacity to alleviate heat stress-induced damage. MT treatment significantly reduced oxidative stress, as evidenced by decreased levels of hydrogen peroxide, superoxide ions, and malondialdehyde (MDA), all of which were elevated under heat stress. To uncover the underlying mechanisms, RNA sequencing was performed on three experimental groups: control (CK), heat stress alone (HS), and MT pre-treatment followed by heat stress (MH). A total of 3491, 3280, and 1171 differentially expressed genes (DEGs) were identified in the CK vs. HS, CK vs. MH, and HS vs. MH comparisons, respectively. MT treatment notably modulated the expression of genes involved in redox regulation and nicotinate and nicotinamide metabolism. Moreover, MT enhanced the expression of genes associated with key signaling pathways, including mitogen-activated protein kinases (MPK3) and plant hormone signal transduction components, such as ethylene response factor (ERF). These findings offer novel insights into the mechanisms by which exogenous MT enhances heat tolerance in sweet potato, highlighting its role in regulating antioxidant systems, metabolic pathways, and hormone signaling. This study presents valuable strategies for improving crop resilience to heat stress.

An eco-friendly and stable capillary zone electrophoresis method for the analysis of metadoxine based on accurate molar response factor obtained from crystal

An eco-friendly and stable capillary zone electrophoresis method for the analysis of metadoxine based on accurate molar response factor obtained from crystal

Identification and characterization of the auxin-response factor family in moso bamboo reveals that PeARF41 negatively regulates second cell wall formation.

Auxin response factors (ARFs) are key transcriptional factors mediating the transcriptional of auxin-related genes that play crucial roles in a range of plant metabolic activities. The characteristics of 47 PeARFs, identified in moso bamboo and divided into three classes, were evaluated. Structural feature analysis showed that intron numbers ranged from 3 to 14, while Motif 1, 2, 7 and 10 were highly conserved, altogether forming DNA-binding and ARF domains. Analysis of RNA-seq from different tissues revealed that PeARFs showed tissue-specificity. Additionally, abundant hormone-response and stress-related elements were enriched in promoters of PeARFs, supporting the hypothesis that the expression of PeARFs was significantly activated or inhibited by ABA and cold treatments. Further, PeARF41 overexpression inhibited SCW formation by reducing hemicellulose, cellulose and lignin contents. Moreover, a co-expression network, containing 28 genes with PeARF41 at its core was predicted, and the results of yeast one hybridization (Y1H), electrophoretic mobility shift assay (EMSA) and dual-luciferase (Dul-LUC) assays showed that PeARF41 bound the PeSME1 promoter to inhibit its expression. We conclude that a 'PeARF41-PeSME1' regulatory cascade mediates SCW formation. Our findings provided a solid theoretical foundation for further research on the role of PeARFs.

CRF12 specifically regulates the flowering time of Arabidopsis thaliana under non-inductive conditions.

The flowering time of Arabidopsis thaliana, a model plant, is significantly accelerated when exposed to long-day (LD) conditions, as it is a typical LD plant. Consequently, the investigation of the flowering regulatory network in A. thaliana under LD conditions has garnered considerable attention in the study of flowering signals, resulting in a significant breakthrough. While many LD plants, including A. thaliana, exhibit delayed flowering under non-inductive short-day (SD) conditions, they are still capable of flowering. Nevertheless, research on the regulation of flowering induction in LD plants under non-inductive SD conditions has been limited. This study demonstrated the involvement of CYTOKININ RESPONSE FACTORS 12 (CRF12) in the regulation of flowering in A. thaliana under non-inductive conditions. Analysis of the expression patterns revealed that the activation of CRF12 expression and protein stability occurred exclusively in non-inductive environments. Molecular and genetic analyses revealed that under a non-inductive photoperiod of 12 h of light and 12 h of darkness, CRF12, CONSTANS (CO), and TARGET OF EAT 1/2 (TOE1/2) engage in competitive interactions to regulate flowering time, while in a SD photoperiod of 8 h of light and 16 h of darkness, CRF12 modulates flowering time by inhibiting the activity of TOE1/2.

Responsivity research: Informing psychological services for justice systems that work.

Public service psychologists engage their research competencies to explore the psychological health needs of underserved populations and the justice systems that deliver them psychological services. In late June 2023. the Criminal Justice Section of Division 18 of the American Psychological Association cosponsored the Fifth North American Correctional and Criminal Justice Psychology Conference: Towards a Justice System That Works, Toronto, Canada. This is the fourth time our journal, Psychological Services, has engaged to develop a section of peer-reviewed articles from the original empirical research presented at the North American Correctional and Criminal Justice Psychology Conference. Supplemented with additional justice-related articles featuring a theme of responsivity, this brief introduction outlines the importance of responsivity research-knowledge that informs unique aspects of a subpopulation so clinicians might better inform the services they deliver. Articles span a range of justice settings domestically and internationally and examine issues of gender, ethnicity, and the workforce to increase the empirically informed responsivity factors that deepen provider understandings of treatment needs. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Pepper (Capsicum annuum L.) AP2/ERF transcription factor, CaERF2 enhances salt stress tolerance through ROS scavenging.

The AP2/ERF transcription factor CaERF2 in pepper enhanced salt tolerance by scavenging reactive oxygen species. The effects of salt stress on plant development and progression are substantial. Ethylene response factor transcription factors (TFs) play a crucial role in responses to salt stress. Their functions in the salt response, particularly in pepper, are still mostly unknown. This study revealed the function of CaERF2 in salt tolerance of pepper plants. CaERF2 expression was dramatically increased in pepper plants following salt stress treatment. Under salinity treatment, CaERF2-silenced pepper showed decreased activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), as well as reduced transcription levels of reactive oxygen species (ROS) scavenging-related genes, resulting in increased O2- and H2O2 accumulation and enhanced salt sensitivity. In contrast, overexpression of CaERF2 (OE) in Nicotiana benthamiana resulted in improved salt tolerance. Under salt stress, the OE lines outperformed the wild type in terms of seed germination rates, root lengths, the activity of SOD, POD, and CAT, and ROS-scavenging-related gene transcription. This study demonstrates that CaERF2 effectively enhances the salt tolerance in pepper by adjusting ROS homeostasis. This finding offers fresh perspectives on the significance of plant ERF2 and key candidate genes in the molecular breeding of salt-tolerant crops.

Genome-wide identification and comparative analysis of the AP2/ERF gene family in Prunus dulcis and Prunus tenella: expression of PdAP2/ERF genes under freezing stress during dormancy

The AP2/ERF (APETALA2/ethylene responsive factor) transcription factor family, one of the largest in plants, plays a crucial role in regulating various biological processes, including plant growth and development, hormone signaling, and stress response. This study identified 114 and 116 AP2/ERF genes in the genomes of 'Wanfeng' almond (Prunus dulcis) and 'Yumin' wild dwarf almond (Prunus tenella), respectively. These genes were categorized into five subfamilies: AP2, DREB, ERF, RAV, and Soloist. The PdAP2/ERF and PtAP2/ERF members both demonstrated high conservation in protein motifs and gene structures. Members of both families were unevenly distributed across eight chromosomes, with 30 and 27 pairs of segmental duplications and 15 and 18 pairs of tandem repeated genes, respectively. The promoter regions of PdAP2/ERF and PtAP2/ERF family members contained numerous important cis-elements related to growth and development, hormone regulation, and stress response. Expression pattern analysis revealed that PdAP2/ERF family members exhibited responsive characteristics under freezing stress at different temperatures in perennial dormant branches. Quantitative fluorescence analysis indicated that PdAP2/ERF genes might be more intensely expressed in the phloem of perennial dormant branches of almond, with the opposite trend observed in the xylem. This study compared the characteristics of PdAP2/ERF and PtAP2/ERF gene family members and initially explored the expression patterns of PdAP2/ERF genes in the phloem and xylem of perennial dormant branches. The findings provide a theoretical foundation for future research on almond improvement and breeding, as well as the molecular mechanisms underlying resistance to freezing stress.

Nomogram based on dual-energy computed tomography to predict the response to induction chemotherapy in patients with nasopharyngeal carcinoma: a two-center study

BackgroundPrevious studies utilizing dual-energy CT (DECT) for evaluating treatment efficacy in nasopharyngeal cancinoma (NPC) are limited. This study aimed to investigate whether the parameters from DECT can predict the response to induction chemotherapy in NPC patients in two centers.MethodsThis two-center retrospective study included patients diagnosed with NPC who underwent contrast-enhanced DECT between March 2019 and November 2023. The clinical and DECT-derived parameters of tumor lesions were calculated to predict the response. We employed univariate and multivariate analysis to identify significant factors. Subsequently, the clinical, DECT, and clinical-DECT nomogram models were developed using independent predictors in the training cohort and validated in the test cohort. Receiver operating characteristic analysis was performed to evaluate the models’ performance.ResultsA total of 321 patients were included in the study, predominantly male [247 (76.9%)] with an average age of 52.04 ± 10.87 years. The training cohort (Center 1) comprised 252 patients, while the test cohort (Center 2) comprised 69 patients. Of these, 233 out of 321 patients (72.6%) were responders to induction chemotherapy. The clinical-DECT nomogram showed an AUC of 0.805 (95% CI, 0.688–0.906), outperforming both the DECT model (Extracellular volume fraction [ECVf]) (AUC, 0.706 [95% CI, 0.571–0.825]) and the clinical model (Ki67) (AUC, 0.693 [95% CI, 0.580–0.806]) in the test cohort.ConclusionsKi67 and ECVf emerged as independent predictive factors for response to induction chemotherapy in NPC patients. The proposed nomogram, incorporating ECVf, demonstrated accurate prediction of treatment response.

Genetic background and microbiome drive susceptibility to epicutaneous sensitization and food allergy in adjuvant-free mouse model

BackgroundThe dual allergen exposure hypothesis states that sensitization to food antigens occurs through a damaged skin barrier in individuals with no previous oral tolerance to certain foods. However, the resulting allergic reaction could depend on factors such as the host’s genetic predisposition as well as the skin and gut microbiota.MethodsSpecific-pathogen-free BALB/c and C57BL/6 and germ-free (GF) BALB/c mice were epicutaneously sensitized with ovalbumin (OVA) via dorsal tape-stripped skin and challenged with OVA by intragastric gavage. The development of food allergy (FA) symptoms, the Th2 and mast cell immune response and differences in the skin and gut microbiota were investigated.ResultsBALB/c mice, but not C57BL/6 mice, showed severe clinical signs of FA (hypothermia, diarrhea) as well as a stronger serum antibody response and Th2 cytokine secretion in the spleen and jejunum after OVA-treatment. The increased mast cell count correlated with higher MCPT-1 production and histidine decarboxylase mRNA expression in the jejunum of these mice. The 16S rRNA sequencing analysis revealed lower abundance of short-chain fatty acids producing bacteria in the gut microbiome of OVA-treated BALB/c mice. Changes in the β-diversity of the gut microbiome reflect both the genetic background as well as the OVA treatment of experimental mice. Compared to SPF mice, GF mice developed more severe anaphylactic hypothermia but no diarrhea, although they had a higher mast cell count, increased MCPT-1 production in the jejunum and serum, and increased arachidonate 5-lipoxygenase mRNA expression.ConclusionsWe show that the BALB/c mice are a mouse strain of choice for model of adjuvant-free epicutaneous sensitization through the disrupted skin barrier and following food allergy development. Our results highlight the significant influence of genetic background and microbiota on food allergy susceptibility, emphasizing the complex interplay between these factors in the allergic response.

P-1553. Impact of Urinary Tract Infection due to Carbapenem Resistant Gram Negative Bacteria in Patients with Kidney Transplant

Abstract Background Carbapenem resistance is a fearsome reality, especially in transplant patients, and urinary tract infections may cause severe illness and graft loss. Methods In this 10-year retrospective cohort we analyzed kidney transplanted patients with gram-negative carbapenem-resistant urinary tract infection (UTI). We evaluated overall prevalence, risk factors for 14-day clinical response and development of acute kidney injury or graft loss during infection. Patients ≥ 18 years old with symptomatic infections or loss of renal function attributed to UTI were included. We excluded patients with kidney abscesses or intra-abdominal complications, death within 24 h, non-active antimicrobial treatment. Results From urocultures collected from 2013 – 2023, 11.583 isolated gram-negative bacteria, of which 14.2% were carbapenem resistant. From these, 87 patients were included. 72.4% were male, aged 56.9 ± 13.6 years old and median transplant time was 15.8 (2 - 89.6) months; 83.9% had upper UTI. The most prevalent bacteria was Klebsiella pneumoniae, with 75 samples (86.2%). 41 (47.1%) were carbapenemase producers: 29.8% serino and 18.3% metallo-beta lactamases. Patients were treated with: amikacin (58.6%) polymyxin B (47.1%), polymyxin E (32.2%), tigecycline (5.7%) ceftazidime-avibactam (8.0%). In 46.0% of the cases, these drugs were combined. 82.8% had complete resolution of symptoms and negative follow-up urine cultures in 14 days. Independent risk factors for non-response were baseline hemodynamic instability (p< 0.01) and polymyxin B treatment (p< 0.01). Control urocultures were collected from 79 (90.8%); 15 (18.9%) had the same bacteria. Sixty-eight patients (79.1%) who were not in dialysis at baseline were evaluated for AKI,from which 45 (66.1%) developed AKI during therapy and 8 (11.7%) had renal graft loss. 12 (13.8%) patients died in 30-days. Conclusion Carbapenem resistant bacteria are increasingly prevalent in renal transplant patients and associated to AKI and graft loss potentially due to the use of nephrotoxic drugs. Polymyxin B and hemodynamic instability were independent preditors non-clinical response in 14-days, which should be further evaluated due to the non-urinary concentration of this antibiotic. Disclosures All Authors: No reported disclosures

Predictive factors for axillary pathological complete response to neoadjuvant therapy in elderly breast cancer patients

PurposeThis study explores the predictive factors for axillary pathological complete response(apCR) during neoadjuvant therapy(NAT) for elderly breast cancer patients to supplement the indications for retaining the axilla.MethodsComprehensive clinical information was gathered from November 2016 to July 2023 from elderly patients with pathology-confirmed invasive breast cancer who underwent NAT and surgery in the Breast Department of Sichuan Cancer Hospital. The relationships between clinicopathological characteristics and apCR were investigated via retrospective analysis. Univariate analysis of the clinicopathological parameters and efficacy was performed via the chi-square test or Fisher’s exact test, while multivariate analysis was conducted via binary logistic regression.ResultsThis study included 109 elderly patients with breast cancer, with an overall apCR rate of 46.8%. The univariate analysis results showed that the initial clinical lymph nodes negative(cN0) stage, Human Epidermal Growth Factor Receptor 2(HER2) positivity and breast pathological complete response(bpCR) were significantly correlated with high apCR rates(all P < 0.05). Multivariate analysis revealed that apCR exhibited a significant association with initial cN0 stage and HER2 positivity. The apCR rate for HER2-positive elderly patients with initial cN0 disease is 100.0%,whereas the lowest apCR rate is observed in HER2-negative and clinical lymph nodes positive(cN+) patients(36.0%). Subgroup analysis revealed a close relationship between molecular subtypes and apCR.ConclusionThis study indicates that initial cN0 stage and HER2 positivity can serve as independent predictive factors for apCR after NAT in elderly breast cancer patients. HER2-positive elderly patients with initial cN0 stage can be considered exempt from axillary lymph node dissection(ALND) after standard NAT.

Predictive factors for treatment responses to baricitinib in severe alopecia areata: A retrospective, multivariate analysis of 70 cases from a single center.

Alopecia areata (AA) is a chronic, autoimmune skin disease characterized by non-scarring hair loss. Baricitinib, a Janus kinase inhibitor (JAKi), prevents hair loss and promotes hair regrowth by inhibiting the inflammatory Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway involved in cytotoxic T cell responses targeting hair follicles. The introduction of JAKi has transformed treatment against severe AA. However, treatment responses to JAKi are highly variable among patients, and the predictors of responsiveness remain insufficiently elucidated. This study aimed to identify independent predictive factors for the efficacy of baricitinib in patients with severe AA using multivariate analyses. A retrospective study was conducted on 70 severe AA patients who started baricitinib treatment at Tohoku University Hospital between July 2022 and August 2023. The primary outcome was the percentage of patients achieving a Severity of Alopecia Tool (SALT) score of ≤20 after 9 months of baricitinib treatment. Multivariate analysis assessed potential predictors of baricitinib treatment responses, including AA type, sex, age, disease duration, history of atopic dermatitis, intravenous methylprednisolone pulse (IVMP) therapy, and Clinician-Reported Outcome (ClinRO) measures for eyebrows and eyelashes. Achievement of a SALT score of ≤20 and SALT score improvement rates were used as objective variables in the multivariate analyses. Among the 70 patients completing 9 months of baricitinib treatment, 41% achieved a SALT score of ≤20. Multivariate analyses identified several independent predictors for positive outcomes, including shorter disease duration (≤4 years), history of IVMP, therapy SALT score of ≤95 at baricitinib initiation, and female sex. Further, we found differential response patterns based on AA type and sex. Specifically, AA type significantly influenced treatment responses, with ophiasis alopecia (OA) associated with the poorest improvement rate. In summary, the response to baricitinib in AA is significantly influenced by sex, AA type, disease duration, history of IVMP, and pre-treatment SALT score.