Mold Infections Research Articles

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant. All patients engrafted, and all but one GT recipient had neutrophil recovery and evidence of functional correction. Eighteen patients (69%) are currently alive and 19 patients (73% of total, 90% of patients with repeat imaging performed) had evidence of radiographic improvement. With 3 exceptions, deaths were not principally related to the fungal infection and duration of antecedent infection did not correlate with death. Aspergillus species accounted for the majority of disease (50%), followed by Phellinus species (18%). Osteomyelitis and disseminated disease were common, as only 11 patients (42%) had disease restricted to pneumonia. Triazole therapy was used in all 26 patients, with combination therapy used in 25 (96%). HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD.

Influence of vitamin D supplementation and the vaginal microenvironment on human papillomavirus infection

This was a retrospective study, mainly explored the mediating role of vaginal microenvironment and the influence of vitamin D addition on human papillomavirus (HPV) infection. Five hundred and twelve participants were chosen in this study, followed by dividing into HPV positive (212 cases) and negative groups (300 cases) based on HPV 23 typing results. The high-risk human papillomavirus (HR-HPV) positive group showed higher abnormal rates of lactobacillus, catalase, cleanliness, sialidosidase, and proline aminopeptidase than the HPV negative group. No significant differences were found in pH value, leukocyte esterase, and Acetylglucosaminidase abnormality between 2 groups. The HR-HPV positive group presented a higher percentage of patients with cleanliness III and IV. Relative to low-grade squamous intraepithelial lesion (LSIL) group, HSIL group presented a higher HPV positive infection rate. Mould infection, Gardnerella infection, and catalase were identified as independent risk elements for HR-HPV infection. Vitamin D supplementation was found to potentially reduce HR-HPV infection persistence post-Loop Electrosurgical Excision Procedure (LEEP), improve nutritional health, reduce insulin, insulin resistance (HOMA-IR) and triglyceride levels, as well as reduce high-sensitivity C-reactive protein (hs-CRP) along with malondialdehyde (MDA) levels. Our results indicate that HR-HPV infection is intimately associated with the condition of the vaginal microenvironment, and vitamin D addition potentially reduces the persistence of HR-HPV infection post-LEEP, improves nutritional and metabolic health, reduces inflammation, and be well-tolerated.

Label-Free Optical Transmission Tomography for Direct Mycological Examination and Monitoring of Intracellular Dynamics

Live-cell imaging generally requires pretreatment with fluorophores to either monitor cellular functions or the dynamics of intracellular processes and structures. We have recently introduced full-field optical coherence tomography for the label-free live-cell imaging of fungi with potential clinical applications for the diagnosis of invasive fungal mold infections. While both the spatial resolution and technical set up of this technology are more likely designed for the histopathological analysis of tissue biopsies, there is to our knowledge no previous work reporting the use of a light interference-based optical technique for direct mycological examination and monitoring of intracellular processes. We describe the first application of dynamic full-field optical transmission tomography (D-FF-OTT) to achieve both high-resolution and live-cell imaging of fungi. First, D-FF-OTT allowed for the precise examination and identification of several elementary structures within a selection of fungal species commonly known to be responsible for invasive fungal infections such as Candida albicans, Aspergillus fumigatus, or Rhizopus arrhizus. Furthermore, D-FF-OTT revealed the intracellular trafficking of organelles and vesicles related to metabolic processes of living fungi, thus opening new perspectives in fast fungal infection diagnostics.

Concordance of Chest Radiography and Chest Computed Tomography Findings in Patients with Hematologic Malignancy and Invasive Mucormycosis: What Are the Prognostic Implications?

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging. Therefore, we reviewed 44 consecutive HM patients with probable/proven IPM at MD Anderson Cancer Center in 2000-2020 who had concurrent CCT and CXR studies performed. All 44 patients had abnormal CCTs and 39 (89%) had anormal CXR findings at IPM diagnosis. However, only 26 patients (59%) showed CCT-matching IPM-suspicious lesions on CXR. Acute Physiology and Chronic Health Evaluation II score > 18 at IPM diagnosis and breakthrough infection to Mucorales-active antifungals were the only independent risk factors for 42-day and/or 84-day mortality. Absence of neutropenia at IPM diagnosis, neutrophil recovery in neutropenic patients, and surgical revision of mucormycosis lesions were protective factors. Although not reaching significance on multivariable analysis, visualization of CCT-matching lesions on CXR was associated with significantly increased 84-day mortality (log-rank test, p = 0.033), possibly as a surrogate of extensive lesions and tissue necrosis. This observation supports the exploration of radiologic lesion kinetics as a prognostic staging tool in IPM patients.

Fungal Keratitis in Northwestern Spain: Epidemiology, Risk Factors and Outcomes.

To review the clinical features, risk factors, microbiological profile, and treatment regimens of fungal keratitis in Galicia, a region in Northwestern Spain with temperate humid weather. A retrospective case series was employed, including patients with fungal keratitis from nine hospitals within the region of Galicia, Spain, between 2010 and 2020. Data obtained from clinical records were analysed. Out of 654 cases of infectious keratitis, 77 cases (9.9%) were identified as fungal keratitis. The median age of affected patients was 68.0 years, with a higher incidence in rural areas (62.3%). Candida spp. infections were the most frequent type (55.8%) and were associated with a higher median age than were the non-dermatophyte mould infections. The primary risk factors included steroid eyedrop use (29.9%), recent keratoplasty (18.2%), ocular trauma (19.5%), and contact with vegetable matter (11.7%). Most ulcers displayed stromal involvement, and 37.7% presented corneal thinning. The median duration of infection was longer in fungal than in bacterial keratitis, and surgical intervention was required in 48.1% of cases. Fungal keratitis, mainly involving Candida spp., accounted for 9.9% of microbial keratitis cases in Galicia, Spain, with significant risk factors being topical steroid use, ocular trauma, and contact with vegetable matter. Delayed diagnosis often resulted in poor outcomes, highlighting the need for early detection through awareness and new technologies to improve prognosis.

Monocentric evaluation of the Novaplex dermatophyte multiplex qPCR assay in the diagnosis of dermatophytoses.

Superficial fungal infections caused by dermatophytes are a prevalent global health concern. Rapid and accurate diagnosis of these pathogens through molecular tools would offer a substantial advantage for early detection and effective treatment. The conventional fungal culture presents inherent limitations, including extended result delivery delay and variable sensitivity. This study aimed to evaluate the performance of the multiplex real-time PCR Novaplex dermatophyte assay (Seegene) in comparison to traditional mycological methods including direct examination and culture. A total of 312 nail, skin, and scalp samples collected from patients with suspected superficial fungal infections for mycological diagnosis were retrospectively subjected to the Novaplex dermatophyte assay. Overall, 170 (54.6%) and 186 (59.6%) samples tested positive for dermatophyte culture and dermatophyte PCR, respectively. The concordance between PCR and culture for dermatophyte detection was 87.2%. There were 158 culture-positive/PCR-positive samples, 12 culture-positive/PCR-negative samples, and 28 culture-negative/PCR-positive samples. The sensitivity of PCR against culture varied according to the dermatophyte target, ranging from 90.5% (Trichophyton mentagrophytes/interdigitale/benhamiae), 91.2% (Trichophyton rubrum), to 100% (Microsporum spp. and Trichophyton tonsurans). When considering the final diagnosis using composite criteria, the sensitivity and specificity for the diagnosis of dermatophytosis were 92.9% and 96.6% for PCR, 86.7% and 100% for culture, and 95.4% and 92.2% for direct examination and culture combined, respectively. The Seegene Novaplex dermatophyte assay is an easy-to-use automated one-step extraction-PCR system that offers satisfactory performance for routine diagnosis of dermatophytoses in clinical laboratories, particularly in non-specialized centers. However, it cannot fully replace conventional mycology due to its inability to detect mold infections and to identify dermatophytes at the species level.

Corticosteroids and invasive fungal infections in hospitalized COVID-19 patients – A single-center cross-sectional study

Background: During the coronavirus disease 2019 (COVID-19) epidemic, an increase in the incidence of fungal infections was observed. However, the real magnitude of these fungal infections and their risk factors among COVID-19 patients in the Indian population is unknown. Aim: To study the frequency, and spectrum of invasive fungal infections (IFI) among hospitalized COVID-19 patients, and the risk factors associated with invasive fungal infections. Methods: We performed a retrospective, cross-sectional study; including all adult patients, admitted to Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), a tertiary care hospital in Southern India between April 2020 and August 2021, with COVID-19. Based on clinical-radiological features, patients with fungal infections were grouped into three diagnostic categories. Demographics, clinical, and laboratory features of patients with fungal infections were analyzed to identify the risk factors. Results: About 10% (449 out of 4650) of the admitted patients with recent COVID-19, had some form of IFI. Among the patients with IFI, 80% (366 out of 449) were hospitalized for active COVID-19, whereas almost all the patients admitted with post-COVID complications had IFI. Of the 449 patients with IFI, 377 had mold infections and 88 had invasive candidiasis. Mucormycosis was the most common mold infection. Diabetes and diabetic ketoacidosis were strong independent predictors of IFI. We also found an association between end-stage renal disease, central venous catheterization, antibiotic usage, prior stroke, and corticosteroid therapy with IFI. Conclusions: The frequency of fungal infections among hospitalized COVID-19 patients was high. Special precautions in COVID-19 patients with diabetes mellitus, corticosteroid therapy, and prior antibiotic usage may help to reduce invasive fungal infections.

Glucose-responsive carboxymethyl chitosan/ sodium alginate film protects against mechanical wound on postharvest blueberry

Fresh fruits and vegetables, particularly berries, are highly susceptible to mechanical damage, which results in nutrient loss, reduced quality, and increased decay from microbial infections, ultimately leading to significant losses. Here, a biodegradable polysaccharide film was employed to encapsulate glucose oxidase (Gox), thereby creating a glucose/wounding-responsive active package that reduced fruit respiration, promoted healing and protected blueberry wounds from mold infection. The combination of carboxymethyl chitosan and sodium alginate resulted in the formation of the polysaccharides film CSF that effectively restricted the permeation of oxygen, water, and carbon dioxide around the surface of the fruit. The encapsulation of Gox in the CSF film (CSFG) reduced glucose levels through enzymatic reaction in surface wounds of the fruit, thereby competing for glucose to establish a starvation-like microenvironment for the pathogenic fungus Botrytis cinerea. The enzymatic reaction also facilitated the production of hydrogen peroxide, which functioned as a fungicide that inhibits the growth of B. cinerea and served as a secondary messenger in fruit immunity. The CSFG film increased beta-glucanase activity, and decreased lipid peroxidation in wounds of blueberries. Therefore, this glucose-responsive CSFG barrier significantly reduced the decay rates of gray mold, caused by B. cinerea in wounded blueberries, by 66.7% compared to the control at 6 d of storage. Taken together, the glucose-responsive active packaging film provides an alternative package for safeguarding blueberries against mechanical damage.

Progress on nonculture based diagnostic tests for invasive mould infection.

This review describes the current status of diagnosing invasive mould disease and Pneumocystis pneumonia using nonconventional diagnostics methods. There has been significant development in the range of nonculture mycological tests. Lateral flow tests (LFTs) for diagnosing aspergillosis complement galactomannan ELISA testing, and LFTs for other fungal diseases are in development. Rapid and low through-put B-D-Glucan assays increase access to testing and there has been significant progress in the standardization/development of molecular tests. Despite this, no single perfect test exists and combining tests (e.g., antigen and molecular testing) is likely required for the optimal diagnosis of most fungal diseases. Based on established clinical performance few mycological tests can be used alone for optimal diagnosis of fungal disease (FD) and combining tests, including classical approaches is the preferred route for confirming and excluding disease. Next-generation sequencing will likely play an increasing role in how we diagnose disease, but optimization, standardization and validation of the entire molecular process is needed and we must consider how host biomarkers can stratify risk. Given the burden of FD in low- and medium-income countries, improved access to novel but more so existing diagnostic testing is critical along with simplification of testing processes.

Reassessment of the role of combination antifungal therapy in the current era.

Given the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use. In infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going. There is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.

Investigating the mildew and yeast in the bakeries of Abhar City, Iran

The presence of mold and yeast in bread leads to contamination in bread. Cancer and estrogenic abnormalities in humans are among the diseases caused by fungal and mold mycotoxins in bread.Bread production waste was estimated at about 30 % in Iran country. A comprehensive and specific image study of the sanitary condition of bread and bakeries in Abhar city has not been done. The purpose of this study was to determine the contamination resulting in yeast and mildew on bread supplied in Abhar City bakeries, to examine the sanitary condition of bakeries, and to provide the food security of Iranians. As well as determining the impact of health status variables and the location of bakeries on mold and fungal contamination. This research was done in the bakeries of Abhar in the period of February 1, 2022 to July 1, 2022. Evaluation of mold and yeast load of 61 breads from 61 bakeries was done using sterile potato dextrose agar with Chloramphenicol plates. In order to check the hygiene status of the bakery environment, modified form of Article 13 with 56 items equal to 56 scores was completed. Variables such as baking soda, sodium dithionite, salt percentage, to evaluate mildew and yeast, and the sanitary condition of bakeries were analyzed. After evaluating health status, the score range was divided based on a 4-point Likert scale. All results were compared with the standard and contamination level of each restaurant. 31 of 60 samples (51.6 %) showed mold and yeast infection. 17 bakeries of the 61 bakeries surveyed (43 %) received 100 % points in the five sections (individual health of 14 items, food hygiene of 10 items, tools and equipment of 16 items, building sanitation of 16 items, and disinfection). 49 samples (80.3 %) of 61 breads evaluated by chemical standard such as amount of baking soda were favorable. Sixty samples (98.4 %) of 61 breads complied with the chemical standard of sodium dithionite. 5 samples (8.3 %) of the 61 breads had excess salt levels. 33 samples out of 61 tested (54.1 %) were infected with mold and yeast. Of these, 26 (78.7 %) belonged to serotypes producing toxin A. The bread quality in some bakeries in Abhar City is poor and infected with mold and yeast. Careful monitoring and monitoring of the health status of bakeries, along with training sessions for bakery staff, will lead to improved baking health.

WITHDRAWN: Grape defense against gray mold involves VvBZR1-mediated autophagy

Brassinosteroids (BRs) are a class of polyhydroxylated steroidal phytohormones that effectively affect the disease resistance in grape. However, the molecular mechanism of BR signaling networks responsible for activation of host defense against gray mold infection remained to be elucidated. The induced resistance mechanism of eBR treatment on table grapes (Vitis vinifera L. cv. Thompson Seedless) was conducted by an artificial inoculation trial. Grape berries were soaked in 0.5 mg L-1 24-epibrassinolide solution, and Botrytis cinerea suspension was injected after 6 hours. We reported a novel defense mechanism that BR-regulated autophagy in grape berry against B. cinerea. Exogenous application of 24-epibrassinolide (eBR) enhanced the grape disease resistance. The eBR-treated berries activated an oxidation-reduction (redox), polyamines metabolism, and autophagy during Botrytis infection. Transcript of BR signaling pathway genes were up-regulated within 12 h. In addition, transcriptome analysis in EBR-treated grapes infected with gray mold showed that the differentially expressed genes (DEGs) were enriched in the metabolic pathway of BR signaling pathway and autophagy. Meanwhile, the endogenous BR, SA and JA accumulated transiently. Overexpressing and silencing VvBZR1 in grape significantly affected oxidation, autophagy, and defense response. DNA affinity purification sequencing (Dap-seq), Yeast one-hybrid assay (Y1H) and dual luciferase assays (LUC) verified VvBZR1 transcriptionally regulated the autophagy related gene VvATG18a. Overexpressing VvATG18a improved the resistance of grapes to gray mold. Overall, this study sheds light on the immune mechanisms underlying the involvement of the BR signal transduction pathway in grape innate immunity, highlighting the pivotal role of VvBZR1-mediated autophagy in enhancing disease resistance.

Rare mold infections from a tertiary care institute in South India: A case series

Rare mold infections from a tertiary care institute in South India: A case series

Invasive mould infection in immunocompromised children: Pulmonary computed tomography findings from two multicentre paediatric cohorts

BackgroundInvasive fungal disease (IFD) can cause significant morbidity in immunocompromised children. The lung is the most common site for IFD caused by moulds. Timely diagnosis is key to facilitate initiation of appropriate treatment. As clinical manifestations are non-specific, initial diagnosis relies on computed tomography (CT) imaging, yet there are limited recent data documenting imaging changes in paediatric pulmonary IFD. In this study, CT images of children with proven/probable pulmonary IFD from two multi-centre cohorts were assessed to document typical changes, including a comparison between causative pathogens, and to measure reliability of radiological reporting in this context. MethodsPulmonary IFD cases diagnosed between 2003–2013 and 2017–2020 were identified from two respective Australian multi-centre cohort studies of immunocompromised children. Proven/probable IFD was defined according to the EORTC/MSG definitions. Initial CT images at the time of IFD diagnosis were independently reviewed by two board-certified paediatric radiologists. Presence of EORTC/MSG-defined and other changes was documented. Inter-rater reliability was assessed. Impact of specific imaging features on outcome at 6 months was assessed using multivariate regression. ResultsA total of 99 cases were included (65 aspergillosis, 19 non-aspergillus moulds (NAM) and 15 histopathological-mould cases). Median age was 9.6 years (IQR 5.1–13.6); 89.9 % had an underlying haematological malignancy. Nodules (85.4 %), the halo sign (49.5 %) and wedge shaped/segmental consolidation (35.9 %) were the most frequent EORTC/MSG-defined features. Cavitation and air-crescent sign were uncommon. Agreement between radiologists was fair to moderate for most common imaging features. No specific radiological finding differentiated aspergillosis from NAM infection. The presence of mass on initial CT and NAM infection were independently associated with poor outcome. ConclusionsIn proven/probable pulmonary IFD in immunocompromised children, nodules with or without halo sign are the most frequent finding. Agreement between radiologists was variable for common imaging features, and specific findings did not correlate with the causative pathogen. Microbiological confirmation remains vital in children with suspected pulmonary IFD.

PCR-Based Microarray Enhances Diagnosis of Culture-Negative Biopsied Tissue in Patients with Invasive Mold Infections: Real-World Experience in a Tertiary Medical Center.

A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.

New Diagnostic Strategy for Onychomycosis: First-Line Utilization of DermaGenius® PCR and Calcofluor Microscopy Combined with Selective Culturing.

Onychomycosis (OM) is a widespread infection requiring prolonged treatment with potential side effects. Diagnostic certainty is therefore essential before initiating antifungal therapy. Molecular biology has already shown benefits in reducing the time to diagnosis, providing technical ease, and increasing sensitivity for the respective species that molecular tests can detect. Nevertheless, causative agents are numerous, and culture remains essential, particularly for detecting non-dermatophytes mold infections. This study compared the performance of three different diagnostic strategies: conventional culture technique, the multiplex DermaGenius® 2.0 PCR (DG), and a mixed PCR/culture algorithm guided by the result of direct examination with calcofluor (DEC). The mixed algorithm (MA) prioritizes DG PCR and DEC as the primary diagnostic tools, supplemented by selective sample inoculation when mycelial elements are visualized in DEC and when DG PCR fails to detect any fungus or identifies a fungus with morphology differing from that observed in DEC (filamentous fungi versus yeasts). With only 13% of samples requiring inoculation, MA emerged as the most effective strategy, demonstrating significantly higher sensitivity (98.18%; p < 0.001) compared to single-method approaches (78.18% for DG PCR alone and 74.55% for culture alone) while maintaining a specificity comparable to DG PCR (100%). This new approach saves time in result delivery, requires fewer human resources, and increases diagnostic accuracy to better meet the needs of clinicians.

Epidemiology, Clinical Manifestations, Treatment, and Outcome of Mucormycosis: A Review of 77 Cases From a Single Center in France.

The aim of this study was to assess the epidemiology, clinical manifestations, and outcome of mucormycosis over 15 years in a single center in France. We conducted a retrospective analysis of all mucormycosis cases in our institution from 1 January 2006 to 31 December 2020 and analyzed patients' medical records, laboratory results, and treatment to describe the epidemiology, clinical manifestations, diagnosis, treatment, and outcome. Mucorales quantitative polymerase chain reaction (qPCR) for the diagnosis was implemented in 2015. Seventy-seven mucormycosis cases were analyzed in 77 patients, with a median age of 54 years (60% male). Identified risk factors were hematological diseases (46 cases [60%]), solid malignancies (2 cases), solid organ transplants (3), burns (18), diabetes only (7), and trauma (1). Sites of infection were lungs (42%), sinus (36%), skin (31%), central nervous system (9%), liver (8%), others (6%), and disseminated (12%). Diagnosis remained difficult and qPCR contributed to mucormycosis diagnosis in 30% of cases. Among hematology patients, serum qPCR was the only positive test in 15% of cases. A mixed mold infection was diagnosed in 24 of 77 (31%) patients. Surgical treatment was undertaken in 43 (56%) cases. Most patients received liposomal amphotericin B (89%), with a combination therapy in 18 of 77 cases (23%). Three-month survival rate was 40% (95% confidence interval [CI], .30-.53]). As for treatment, adjunction of surgery (hazard ratio, 0.47 [95%CI, .25-.91); P = 0.02) was associated with lower mortality. Mucormycosis remained associated with high mortality, especially in the hematological and burn populations. Surgery in combination with antifungal treatment was associated with improved survival.

Impact of Antifungal Prophylaxis Continuation or Discontinuation After Allogeneic Hematopoietic Cell Transplant on the Incidence of Invasive Mold Infection.

Continuing antifungal prophylaxis (AFPx) to prevent invasive mold infections (IMIs) in recipients of allogeneic hematopoietic cell transplantation (alloHCT) after primary hospital discharge from alloHCT admission varies among transplant centers despite recommendations to continue prophylaxis through day +75. Characteristics driving AFPx prescribing at hospital discharge and outcomes are unknown. In this retrospective analysis, we reviewed patients continuing AFPx vs no AFPx at hospital discharge. We included patients with a hospital stay ≥7 days and ≤40 days. We excluded patients with a history of IMI prior to alloHCT, new IMI during admission, or death prior to discharge. Our primary objective was incidence of probable or proven IMI per the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Our secondary objectives were nonrelapse mortality at day +100, overall survival at day +100, and characteristics driving AFPx discontinuation at hospital discharge. Of the 430 patients identified, 387 met inclusion criteria. At discharge, 56% (217/387) continued AFPx, and 44% (170/387) had no AFPx. At day +100, 3 probable IMI cases occurred in the group with continued AFPx vs 1 probable IMI case in the no-AFPx group (no proven IMI). Univariate analysis showed no difference in cumulative incidence of probable IMI (P = .440), nonrelapse mortality (P = .072), and overall survival (P = .855) between groups. Multivariable logistic regression demonstrated that patients were less likely to continue AFPx if they had a diagnosis other than acute myeloid leukemia, a length of stay ≤30 days, acute graft-vs-host disease grade 0 or 1, and corticosteroid use ≤5 days. There was no difference in probable IMI at day +100 after alloHCT based on continuing vs discontinuing AFPx at hospital discharge after alloHCT admission supporting a risk-adapted prophylaxis approach.

Ozone Treatment as a Sustainable Alternative for Suppressing Blue Mold in Mandarins and Extending Shelf Life

Citrus fruits, particularly mandarins, are highly valued globally for their nutritional benefits and versatile culinary uses. However, the challenge of post-harvest decay, primarily due to blue mold (Penicillium italicum) infections, results in significant food losses and necessitates effective preservation strategies. Traditional methods often rely on fungicides, raising concerns about chemical residues and environmental impact. This study investigates the efficacy of ozone as an alternative approach to controlling blue mold in mandarins. Various gaseous ozone treatments were tested, including single, double, and triple treatments, with durations ranging from 10 to 60 min and concentrations from 3.3 to 20 ppm. Additionally, ozonated water treatments were evaluated with concentrations of 2, 4, and 6 ppm. To simulate a realistic infestation scenario, mandarins were artificially infected with P. italicum spores before undergoing both gaseous ozone and ozonated water treatments. The storage conditions for the mandarins were meticulously controlled, maintaining a humidity level of 50–60% and a temperature range of 10–12 °C. Each fruit was analyzed, and the presence of P. italicum infection was determined two and three weeks after the ozonation. Results indicated that ozone treatments significantly reduced mold growth, with gaseous ozone demonstrating efficacy rates up to 97.5% and ozonated water treatments achieving preservation rates between 95% and 97%. These results underscore ozone’s potential as a safe, efficient, and sustainable alternative to conventional fungicides, offering promising solutions for extending the shelf life of mandarins. Further research is recommended to optimize ozone treatment parameters, assess long-term effects on fruit quality and nutritional content, and refine application techniques to harness ozone’s potential in citrus fruit preservation fully. This approach not only addresses food security challenges but also aligns with global efforts to reduce chemical inputs in agriculture and promote environmentally sustainable practices.

Active Discovery of the Allosteric Inhibitor Targeting Botrytis cinerea Chitinase Based on Neural Relational Inference for Food Preservation.

Currently, allosteric inhibitors have emerged as an effective strategy in the development of preservatives against the drug-resistant Botrytis cinerea (B. cinerea). However, their passively driven development efficiency has proven challenging to meet the practical demands. Here, leveraging the deep learning Neural Relational Inference (NRI) framework, we actively identified an allosteric inhibitor targeting B. cinerea Chitinase, namely, 2-acetonaphthone. 2-Acetonaphthone binds to the crucial domain of Chitinase, forming the strong interaction with the allosteric sites. Throughout the interaction process, 2-acetonaphthone diminished the overall connectivity of the protein, inducing conformational changes. These findings align with the results obtained from Chitinase activity experiments, revealing an IC50 value of 67.6 μg/mL. Moreover, 2-acetonaphthone exhibited outstanding anti-B. cinerea activity by inhibiting Chitinase. In the gray mold infection model, 2-acetonaphthone significantly extended the preservation time of cherry tomatoes, positioning it as a promising preservative for fruit storage.