Socioeconomic disparities and the genomic landscape of gastric cancer.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

Disentangling the drivers of urban bird diversity in the non-breeding season: A general synthesis.

Current knowledge about the impacts of urbanisation on bird assemblages is based on evidence from studies partly or wholly undertaken in the breeding season. In comparison, the non-breeding season remains little studied, despite the fact that winter conditions at higher latitudes are changing more rapidly than other seasons. During the non-breeding season, cities may attract or retain bird species because they offer milder conditions or better feeding opportunities than surrounding habitats. However, the range of climatic, ecological and anthropogenic mechanisms shaping different facets of urban bird diversity in the non-breeding season are poorly understood. We explored these mechanisms using structural equation modelling to assess how urbanisation affects the taxonomic, phylogenetic and functional diversity of avian assemblages sampled worldwide in the non-breeding season. We found that minimum temperature, elevation, urban area and city age played a critical role in determining taxonomic diversity while a range of factors-including productivity, precipitation, elevation, distance to coasts and rivers, socio-economic (as a proxy of human facilitation) and road density-each contributed to patterns of phylogenetic and functional diversity. The structure and function of urban bird assemblages appear to be predominantly shaped by temperature, productivity and city age, with effects of these factors differing across seasons. Our results underline the importance of considering multiple hypotheses, including seasonal effects, when evaluating the impacts of urbanisation on biodiversity.

Idiopathic Multicentric Castleman Disease With Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Insufficiency, and Organomegaly (TAFRO) Syndrome in a Liver Transplant Recipient.

Idiopathic multicentric Castleman disease is a rare lymphoproliferative disorder that can be potentially fatal without timely diagnosis and treatment. We describe the first-ever reported occurrence of idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever, reticulin fibrosis/renal insufficiency, and organomegaly syndrome in a liver transplant recipient. The diagnosis was challenging as the clinical presentation closely mimicked decompensated cirrhosis, and the profound thrombocytopenia limited tissue diagnosis. However, we were able to establish the diagnosis and treat it effectively. This case report signifies that a high index of suspicion and aggressive treatment can be lifesaving in liver transplant recipients presenting with this rare disorder.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

OBJECTIVES: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING: Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

Uncovering further diversity of Ochoterenatrema Caballero, 1943 (Digenea: Lecithodendriidae) in South American bats.

Ochoterenatrema Caballero, 1943 is a genus of lecithodendriid digeneans that prior to this study included 8 species parasitic in bats in the Western Hemisphere. Species of Ochoterenatrema possess a unique morphological feature in form of the pseudogonotyl on the sinistral side of the ventral sucker. In this study, we describe 2 new species of Ochoterenatrema from bats in Ecuador. The new species are readily differentiated from their congeners by a combination of morphological characters, including the distribution of vitelline follicles, length of oesophagus, sucker ratio and the body shape, among other features. We have generated partial nuclear 28S rDNA and mitochondrial cox1 gene DNA sequences from both new species. The newly obtained sequences were used to differentiate among species and study the phylogenetic interrelationships among Ochoterenatrema spp. The internal topology of the clade was weakly supported, although the cox1 tree was much better resolved than the 28S tree. Comparison of sequences revealed 0-1.2% interspecific divergence in 28S and 3.3-20.5% interspecific divergence in cox1 among Ochoterenatrema spp. The new findings demonstrate that bats in South America likely harbor multiple additional undescribed species of Ochoterenatrema. More extensive sampling from broader geographic and host ranges, especially in North America, should allow for a better understanding of the evolution of host associations and morphological traits of this lineage of lecithodendriid digeneans.

Young Plasma Rejuvenates Blood DNA Methylation Profile, Extends Mean Lifespan, and Improves Physical Appearance in Old Rats.

There is converging evidence that young blood conveys cells, vesicles, and molecules able to revitalize function and restore organ integrity in old individuals. We assessed the effects of young plasma on the lifespan, epigenetic age, and healthspan of old female rats. Beginning at 25.6 months of age, a group of 9 rats (group T) was intraperitoneally injected with plasma from young rats until their natural death. A group of 8 control rats of the same age received no treatment (group C). Blood samples were collected every other week. Survival curves showed that from age 26 to 30 months, none of the group T animals died, whereas the survival curve of group C rats began to decline at age 26 months. Blood DNAm age versus chronological age showed that DNAm age in young animals increased faster than chronological age, then slowed down, entering a plateau after 27 months. The DNAm age of the treated rats fell below the DNAm age of controls and, in numerical terms, remained consistently lower until natural death. When rats were grouped according to the similarities in their differential blood DNA methylation profile, samples from the treated and control rats clustered in separate groups. Analysis of promoter differential methylation in genes involved in systemic regulatory activities revealed specific GO term enrichment related to the insulin-like factors pathways as well as to cytokines and chemokines associated with immune and homeostatic functions. We conclude that young plasma therapy may constitute a natural, noninvasive intervention for epigenetic rejuvenation and health enhancement.

Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia.

ABSTRACT: Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of or treat relapsed disease after initial CAR T-cell infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti-CD19/4-1BB CAR T cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention (peripheral B-cell recovery [BCR] or marrow hematogones ≤6 months after CARTi), minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n = 44; huCART19, n = 26; tisagenlecleucel, n = 11), representing 79 patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40 [38%]; hematogones, 18/23 [78%]). Lymphodepletion was associated with response to CARTr for BCR (odds ratio [OR], 33.57; P = .015) but not hematogones (OR, 0.30; P = .291). The cumulative incidence of relapse was 29% at 24 months for CR vs 61% for nonresponse to CARTr (P = .259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only grade ≥3 cytokine release syndrome (n = 6) or neurotoxicity (n = 1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19+ relapse.

Extraordinary levels of per- and polyfluoroalkyl substances (PFAS) in vertebrate animals at a New Mexico desert oasis: Multiple pathways for wildlife and human exposure.

Per- and polyfluoroalkyl substances (PFAS) in the environment pose persistent and complex threats to human and wildlife health. Around the world, PFAS point sources such as military bases expose thousands of populations of wildlife and game species, with potentially far-reaching implications for population and ecosystem health. But few studies shed light on the extent to which PFAS permeate food webs, particularly ecologically and taxonomically diverse communities of primary and secondary consumers. Here we conducted >2000 assays to measure tissue-concentrations of 17 PFAS in 23 species of mammals and migratory birds at Holloman Air Force Base (AFB), New Mexico, USA, where wastewater catchment lakes form biodiverse oases. PFAS concentrations were among the highest reported in animal tissues, and high levels have persisted for at least three decades. Twenty of 23 species sampled at Holloman AFB were heavily contaminated, representing middle trophic levels and wetland to desert microhabitats, implicating pathways for PFAS uptake: ingestion of surface water, sediments, and soil; foraging on aquatic invertebrates and plants; and preying upon birds or mammals. The hazardous long carbon-chain form, perfluorooctanosulfonic acid (PFOS), was most abundant, with liver concentrations averaging >10,000 ng/g wet weight (ww) in birds and mammals, respectively, and reaching as high 97,000 ng/g ww in a 1994 specimen. Perfluorohexanesulfonic acid (PFHxS) averaged thousands of ng/g ww in the livers of aquatic birds and littoral-zone house mice, but one order of magnitude lower in the livers of upland desert rodent species. Piscivores and upland desert songbirds were relatively uncontaminated. At control sites, PFAS levels were strikingly lower on average and different in composition. In sum, legacy PFAS at this desert oasis have permeated local aquatic and terrestrial food webs across decades, severely contaminating populations of resident and migrant animals, and exposing people via game meat consumption and outdoor recreation.

Host-Pathogen Interaction: Biology and Public Health.

Interactions between host and pathogenic microorganisms are common in nature and have a significant impact on host health, often leading to several types of infections. These interactions have evolved as a result of the ongoing battle between the host's defense mechanisms and the pathogens' invasion strategies. In this chapter, we will explore the evolution of host-pathogen interactions, explore their molecular mechanisms, examine the different stages of interaction, and discuss the development of pharmacological treatments. Understanding these interactions is crucial for improving public health, as it enables us to develop effective strategies to prevent and control infectious diseases. By gaining insights into the intricate dynamics between pathogens and their hosts, we can work towards reducing the burden of such diseases on society.

Proteomic analysis of boar seminal plasma: Putative markers for fertility based on capacity of semen preservation at 17°C.

Boar seminal plasma (SP) proteins were associated with differences on sperm resistance to cooling at 17°C. However, information about seminal plasma proteins in boars classified by capacity of semen preservation and in vivo fertility remains lacking. Thus, the objective was to evaluate the SP proteome in boars classified by capacity of semen preservation and putative biomarkers for fertility. The ejaculates from high-preservation (HP) showed higher progressive motility during all 5 days than the low-preservation (LP) boars. There was no difference for farrowing rate between ejaculates from LP (89.7%) and HP boars (88.4%). The LP boars presented lower total piglets born (14.0 ± 0.2) than HP (14.8 ± 0.2; p < 0.01). A total of 257 proteins were identified, where 184 were present in both classes of boar, and 41 and 32 were identified only in LP and HP boars, respectively. Nine proteins were differently expressed: five were more abundant in HP (SPMI, ZPBP1, FN1, HPX, and C3) and four in LP boars (B2M, COL1A1, NKX3-2, and MPZL1). The HP boars had an increased abundance of SP proteins related to sperm resistance and fecundation process which explains the better TPB. LP boars had a higher abundance of SP proteins associated with impaired spermatogenesis.

International Medical Graduates in US Orthopedic Residency Programs: A Comprehensive Analysis.

BACKGROUND: This study aims to provide insight regarding the different qualities of international medical graduates (IMGs) involved in US orthopedic residency programs. METHODS: Orthopedic residency programs accredited by the ACGME and listed in the AMA database were screened. Data on program size and location, IMG year of training, the geographic region of IMG's medical schools, their research experiences and number of gap years were included. RESULTS: A total of 167(80.3%) orthopedic residency programs were included. A total of 3838 residents were identified, of which 44 (1.15%) were IMGs. The United Kingdom and Ireland had the highest number of matched IMGs with four (9.1%) each. Massachusetts was the state with the highest number of enrolled IMGs. On average, IMGs had 26.3 publications and joined US orthopedic residency 4.66 years following medical school graduation. CONCLUSION: Despite the many hurdles experienced by IMGs, a decent number succeeds in matching into US orthopedic residency programs each year.

Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development.

PURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression. EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.

Viral Detection by Reverse Transcriptase Polymerase Chain Reaction in Upper Respiratory Tract and Metagenomic RNA Sequencing in Lower Respiratory Tract in Critically Ill Children With Suspected Lower Respiratory Tract Infection.

OBJECTIVES: Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs). DESIGN: This is an analysis of of a seven-center prospective cohort study. SETTING: Seven PICUs within academic children's hospitals in the United States. PATIENTS: Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours. INTERVENTIONS: We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement. MEASUREMENTS AND MAIN RESULTS: Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001). CONCLUSIONS: Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.

Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines.

ABSTRACT: Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.

Single-cell transcriptional landscape of long non-coding RNAs orchestrating mouse heart development.

Long non-coding RNAs (lncRNAs) comprise the most representative transcriptional units of the mammalian genome. They are associated with organ development linked with the emergence of cardiovascular diseases. We used bioinformatic approaches, machine learning algorithms, systems biology analyses, and statistical techniques to define co-expression modules linked to heart development and cardiovascular diseases. We also uncovered differentially expressed transcripts in subpopulations of cardiomyocytes. Finally, from this work, we were able to identify eight cardiac cell-types; several new coding, lncRNA, and pcRNA markers; two cardiomyocyte subpopulations at four different time points (ventricle E9.5, left ventricle E11.5, right ventricle E14.5 and left atrium P0) that harbored co-expressed gene modules enriched in mitochondrial, heart development and cardiovascular diseases. Our results evidence the role of particular lncRNAs in heart development and highlight the usage of co-expression modular approaches in the cell-type functional definition.

Subacromial Balloon Spacer: When to Use This?

The subacromial balloon spacer is a novel treatment option for the management of massive irreparable rotator cuff tears. This device is introduced into the glenohumeral joint and acts to alleviate the acromiohumeral impingement, caused by the massive irreparable rotator cuff tear. The device also redistributes the tension around the adjacent muscles in the joint, allowing them to compensate for the torn rotator cuff tendons. By doing so, the balloon can act as a "rehabilitation accelerator", ultimately resulting in improved shoulder pain and function. Adherence to balloon indications when selecting the appropriate patient is necessary, and these include an irreparable posterosuperior rotator cuff tear, with preserved subscapularis function, minimal to no osteoarthritis, and the ability to forward flex to 90 degrees. Clinical studies have demonstrated promising potential regarding the benefit of the balloon, with numerous studies demonstrating great outcomes after its implantation. Nevertheless, future research remains necessary to render the evidence behind its utility unequivocal.

Subpopulation treatment effect pattern plot analysis: a prognostic model for distant recurrence-free survival to estimate delayed adjuvant chemotherapy initiation effect in triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups. Materials and methods: We analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days). Results: In univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0-31), intermediate (score:32-64), and high-risk (score: 65-100) cohorts; meanwhile, Model N°02: low (score: 0-26), intermediate (score: 27-55), and high (score: 56-100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set. Conclusions: We developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups.

Metabolic Profiling and Comparative Proteomic Insight in Respect of Amidases during Iprodione Biodegradation.

The fungicide iprodione (IPR) (3-(3,5-dichlorophenyl) N-isopropyl-2,4-dioxoimidazolidine-1-carboxamide) is a highly toxic compound. Although IPR has been restricted, it is still being applied in many places around the world, constituting an environmental risk. The biodegradation of IPR is an attractive option for reducing its residues. In this study, we isolated thirteen IPR-tolerant bacteria from a biopurification system designed to treat pesticides. A study of biodegradation using different strains was comparatively evaluated, and the best degradation rate of IPR was presented by Achromobacter sp. C1 with a half-life (T1/2) of 9 days. Based on a nano-LC-MS/MS analysis for the strains, proteins solely expressed in the IPR treatment were identified by highlighting the strain Achromobacter sp. C1, with 445 proteins primarily involved in the biosynthesis of secondary metabolites and microbial metabolism in diverse environments. Differentially expressed protein amidases were involved in six metabolic pathways. Interestingly, formamidase was inhibited while other cyclases, i.e., amidase and mandelamide hydrolase, were overexpressed, thereby minimizing the effect of IPR on the metabolism of strain C1. The dynamic changes in the protein profiles of bacteria that degrade IPR have been poorly studied; therefore, our results offer new insight into the metabolism of IPR-degrading microorganisms, with special attention paid to amidases.