Genome variation and LTR-RT analyses of an ancient peach landrace reveal mechanism of blood-flesh fruit color formation and fruit maturity date advancement.

Peach (Prunus persica) landrace has typical regional characteristics, strong environmental adaptability, and contains many valuable genes that provide the foundation for breeding excellent varieties. Therefore, it is necessary to assemble the genomes of specific landraces to facilitate the localization and utilization of these genes. Here, we de novo assembled a high-quality genome from an ancient blood-fleshed Chinese landrace Tianjin ShuiMi (TJSM) that originated from the China North Plain. The assembled genome size was 243.5 Mb with a contig N50 of 23.7 Mb and a scaffold N50 of 28.6 Mb. Compared with the reported peach genomes, our assembled TJSM genome had the largest number of specific structural variants (SVs) and long terminal repeat-retrotransposons (LTR-RTs). Among the LTR-RTs with the potential to regulate their host genes, we identified a 6688 bp LTR-RT (named it blood TE) in the promoter of NAC transcription factor-encoding PpBL, a gene regulating peach blood-flesh formation. The blood TE was not only co-separated with the blood-flesh phenotype but also associated with fruit maturity date advancement and different intensities of blood-flesh color formation. Our findings provide new insights into the mechanism underlying the development of the blood-flesh color and determination of fruit maturity date and highlight the potential of the TJSM genome to mine more variations related to agronomic traits in peach fruit.

Pendelluft in patients with acute respiratory distress syndrome during trigger and reverse triggering breaths.

Pendelluft, the shift of air from non-dependent to dependent lung regions, is known to occur during active breathing in ventilated patients. However, information about pendelluft in ARDS patients under assisted mechanical ventilation is limited. In this prospectively collected and retrospectively analyzed study, we combined electrical impedance tomography and respiratory mechanics monitoring to quantitatively examine pendelluft in trigger and reverse triggering breaths in 20 mechanically ventilated patients with ARDS during the transition from controlled to active breaths under volume-cycled ventilation. Besides the 10 resting breaths in each patient, 20% of the counted active breaths were selected based on three levels of esophageal pressure swing (∆Pes): low (< 5 cm H2O, breaths = 471), moderate (≥ 5, < 10 cm H2O, breaths = 906), and high effort (≥ 10 cm H2O, breaths = 565). The pendelluft response to breathing efforts was significantly greater in trigger breaths than in reverse triggering breaths (p < 0.0001). Based on the pendelluft-∆Pes slope (ml/cmH2O), there were two distinct patterns of effort-related pendelluft (high vs. low pendelluft group). For trigger breaths, the high pendelluft group (n = 9, slope 0.7-2.4 ml/cmH2O) was significantly associated with lower peak airway/plateau pressure and lower respiratory system/lung elastance than the low pendelluft group (n = 11, slope - 0.1 to 0.3 ml/cmH2O). However, there was no difference in respiratory mechanics between high and low pendelluft groups for reverse triggering breathes. The use of ∆Pes to predict pendelluft was found to have a low positive predictive value.

Synthesis and performance study of PAM-g-PAA/PHEA and its application in purifying tellurium aerosol.

In this study, grafted polymers (PAM-g-PAA/PHEA) with different grafting rates are prepared by solution method grafting polymer with polyacrylamide as the main chain, acrylic acid (AA) and 2-hydroxyethyl acrylate (HEA) as the modified monomers. Evidence of graft polymerization of AA and HEA on polyacrylamide side chains is obtained by FT-IR and 1HNMR. Scanning electron microscopy and thermogravimetric characterization further confirm the synthesis of grafted polymers. The properties of the grafting polymer are evaluated using grafting rate, viscosity, and surface tension measurements. The performance of polymer aqueous solution as an aerosol fixative for capturing and removing tellurium aerosol as a simulated polonium aerosol is examined. According to the results, grafting two monomers, acrylic acid, and 2-hydroxyethyl acrylate, effectively improve the cross-sectional structure of the polymer, increase the thermal stability of the polymer, and reduced the surface tension of the aqueous polymer solution to 42.47 mN/m. In addition, aerosol settling and fixation experiments showed that PAM-g-PAA/PHEA had a trapping and scavenging effect on tellurium aerosols with an immobilization rate of 94.86%, which revealed the immobilization mechanism of the immobilizer with tellurium aerosols.

SGCL: Spatial guided contrastive learning on whole-slide pathological images.

Self-supervised representation learning (SSL) has achieved remarkable success in its application to natural images while falling behind in performance when applied to whole-slide pathological images (WSIs). This is because the inherent characteristics of WSIs in terms of gigapixel resolution and multiple objects in training patches are fundamentally different from natural images. Directly transferring the state-of-the-art (SOTA) SSL methods designed for natural images to WSIs will inevitably compromise their performance. We present a novel scheme SGCL: Spatial Guided Contrastive Learning, to fully explore the inherent properties of WSIs, leveraging the spatial proximity and multi-object priors for stable self-supervision. Beyond the self-invariance of instance discrimination, we expand and propagate the spatial proximity for the intra-invariance from the same WSI and inter-invariance from different WSIs, as well as propose the spatial-guided multi-cropping for inner-invariance within patches. To adaptively explore such spatial information without supervision, we propose a new loss function and conduct a theoretical analysis to validate it. This novel scheme of SGCL is able to achieve additional improvements over the SOTA pre-training methods on diverse downstream tasks across multiple datasets. Extensive ablation studies have been carried out and visualizations of these results have been presented to aid understanding of the proposed SGCL scheme. As open science, all codes and pre-trained models are available at https://github.com/HHHedo/SGCL.

Genome-wide presence/absence variation discovery and its application in Peach (Prunus persica).

Gene presence/absence variation (PAV) is an important contributor to the studies of genetic diversity, gene identification, and molecular marker development in plants. In the present study, 100 peach (Prunus persica) accessions were used for genome resequencing to identify PAVs. Alignmentwith a reference genome yielded a total of 2.52 Mb non-reference sequences and 923 novel genes were identified. The dispensable PAVs were enriched in resistance, perhaps reflecting their roles in plant adaptation to various environments. Furthermore, selection sweeps associated with peach domestication and improvement were identified based on PAV data. Only 4.3% and 13.4% of domestication and improvement sweeps, respectively, were identified simultaneously using single nucleotide polymorphism (SNP) data, suggesting flexible identification between the different methods. To further verify the applicability of PAV identification, a genome-wide association study was conducted using 21 agronomic traits. Some of the identified loci were consistent with those reported in previous studies, while some were mapped for the first time; the latter included petiole length, petiole gland shape, and petiole gland number. Through tissue-specific expression analysis and gene transformation experiments, a novel gene, evm.model.Contig322_A94.1, was identified and found to be involved in chilling requirements. We speculated that this novel gene might regulate the trait by participating in the ABA signaling pathway. The PAVs identified in P. persica provide valuable resources for mapping the entire gene set and identifying optional markers for molecular selection in future studies.

MADS-box protein PpDAM6 regulates chilling requirement-mediated dormancy and bud break in peach.

Bud dormancy is crucial for winter survival and is characterized by the inability of the bud meristem to respond to growth-promotive signals before the chilling requirement (CR) is met. However, our understanding of the genetic mechanism regulating CR and bud dormancy remains limited. This study identified PpDAM6 (DORMANCY-ASSOCIATED MADS-box) as a key gene for CR using a genome-wide association study analysis based on structural variations in 345 peach (Prunus persica (L.) Batsch) accessions. The function of PpDAM6 in CR regulation was demonstrated by transiently silencing the gene in peach buds and stably overexpressing the gene in transgenic apple (Malus × domestica) plants. The results showed an evolutionarily conserved function of PpDAM6 in regulating bud dormancy release, followed by vegetative growth and flowering, in peach and apple. The 30-bp deletion in the PpDAM6 promoter was substantially associated with reducing PpDAM6 expression in low-CR accessions. A PCR marker based on the 30-bp indel was developed to distinguish peach plants with non-low and low CR. Modification of the H3K27me3 marker at the PpDAM6 locus showed no apparent change across the dormancy process in low- and non-low- CR cultivars. Additionally, H3K27me3 modification occurred earlier in low-CR cultivars on a genome-wide scale. PpDAM6 could mediate cell-cell communication by inducing the expression of the downstream genes PpNCED1 (9-cis-epoxycarotenoid dioxygenase 1), encoding a key enzyme for ABA biosynthesis, and CALS (CALLOSE SYNTHASE), encoding callose synthase. We shed light on a gene regulatory network formed by PpDAM6-containing complexes that mediate CR underlying dormancy and bud break in peach. A better understanding of the genetic basis for natural variations of CR can help breeders develop cultivars with different CR for growing in different geographical regions.

Discovery of a key gene associated with fruit maturity date and analysis of its regulatory pathway in peach.

Fruit maturity is an important agronomic trait of fruit crops. Although in previous studies, several molecular markers are developed for the trait, the knowledge about its candidate genes is particularly limited. In this study, a total of 357 peach accessions were re-sequenced to obtain 949,638 SNPs. Combing with 3-year fruit maturity dates, a genome-wide association analysis was performed, and 5, 8, and 9 association loci were identified. To screen the candidate genes for those year-stable loci on chromosomes 4 and 5, two maturity date mutants were used for transcriptome sequencing. Gene expression analysis indicated that Prupe.4G186800 and Prupe.4G187100 on chromosome 4 were essential to fruit ripening in peaches. However, the expression analysis of different tissues showed that the first gene has no tissue-specific character, but transgenic studies showed that the latter is more likely to be a key candidate gene than the first for the maturity date in peach. The yeast two-hybrid assay showed that the proteins encoded by the two genes interacted and then regulated fruit ripening. Moreover, the previously identified 9 bp insertion in Prupe.4G186800 may affect their interaction ability. This research is of great significance for understanding the molecular mechanism of peach fruit ripening and developing practical molecular markers in a breeding program.

Spontaneous Breathing and Pendelluft in Patients with Acute Lung Injury: A Narrative Review.

Acute respiratory distress syndrome (ARDS) is characterized by acute-onset rapid-deteriorating inflammatory lung injury. Although the preservation of spontaneous breathing may have physiological benefits in oxygenation, increasing evidence shows that vigorous spontaneous breathing may aggravate lung injury (i.e., patient self-inflicted lung injury). Increased lung stress and pendelluft, which is defined as intrapulmonary gas redistribution without a significant change in tidal volume, are important mechanisms of patient self-inflicted lung injury. The presence of pendelluft may be considered a surrogate marker of vigorous inspiratory effort, which can cause the dependent lung to overstretch. In this review, we summarized three major methods for electrical impedance tomography-based pendelluft monitoring. Future studies are warranted to compare and validate the different methods of pendelluft estimation in patients with ARDS.

Betulin, Synthesized by PpCYP716A1, Is a Key Endogenous Defensive Metabolite of Peach against Aphids.

Wild pest-resistant germplasms employ secondary metabolites to withstand insect attacks. A close wild relative of the cultivated peach, Prunus davidiana, displays strong resistance to green peach aphids by utilizing metabolites to cope with aphid infestation; however, the underlying mechanism of aphid resistance remains mostly unknown. Here, metabolomic analysis was performed to explore the changes in metabolite levels in P. davidiana after aphid infestation. The data revealed that betulin is a key defensive metabolite in peaches that protects against aphids and possesses potent aphidicidal activity. Further toxicity tests demonstrated that betulin was toxic to pests but not to beneficial insects. Additionally, transcriptomic and phylogenetic analyses revealed that the cytochrome P450 gene PpCYP716A1 was responsible for betulin synthesis─this finding was confirmed by the heterologous expression of this gene. This study revealed a strategy whereby plants harness defense metabolites to develop resistance to pests. These findings may facilitate controlling such pests.

Combined nature and human selections reshaped peach fruit metabolome.

BACKGROUND: Plant metabolites reshaped by nature and human beings are crucial for both their lives and human health. However, which metabolites respond most strongly to selection pressure at different evolutionary stages and what roles they undertake on perennial fruit crops such as peach remain unclear. RESULTS: Here, we report 18,052 significant locus-trait associations, 12,691 expression-metabolite correlations, and 294,676 expression quantitative trait loci (eQTLs) for peach. Our results indicate that amino acids accumulated in landraces may be involved in the environmental adaptation of peaches by responding to low temperature and drought. Moreover, the contents of flavonoids, the major nutrients in fruits, have kept decreasing accompanied by the reduced bitter flavor during both domestication and improvement stages. However, citric acid, under the selection of breeders' and consumers' preference for flavor, shows significantly different levels between eastern and western varieties. This correlates with differences in activity against cancer cells in vitro in fruit from these two regions. Based on the identified key genes regulating flavonoid and acid contents, we propose that more precise and targeted breeding technologies should be designed to improve peach varieties with rich functional contents because of the linkage of genes related to bitterness and acid taste, antioxidant and potential anti-cancer activity that are all located at the top of chromosome 5. CONCLUSIONS: This study provides powerful data for future improvement of peach flavor, nutrition, and resistance in future and expands our understanding of the effects of natural and artificial selection on metabolites.

Body-Weight Gain in Women During Smoking Cessation Is a Sex-Specific Predictor of 6-Month Abstinence: A Retrospective Cohort Study.

Background: Smoking behavior differs between the sexes. Weight control is one of the main reasons leading to tobacco abuse in women but not in men. Studies on the predictive factors of cessation failure between sexes are scarce. This study is aim to investigate whether there are sex differences in the effect of weight gain on smoking cessation rate. Methods: Participants in the smoking-cessation program at a Medical Center in Taiwan between 2018 and 2019 were included. Details of age, sex, comorbidities, depression screening, nicotine dependence, body weight, and cessation medications of the participants were collected. The participants were classified based on their sex, and multivariable logistic regression analyses were conducted. Multivariable logistic regression analyses were performed for sensitivity analysis after stratifying the participants according to their weight loss (weight loss ≥ 1.5 kg and weight loss ≥ 3.0 kg). Results: A total of 1,475 participants were included. The body-weight gain in women was associated with failed abstinence (adjusted odds ratio (OR): 3.10, 95% CI: 1.10-9.04). In contrast, body-weight gain in men was associated with successful 6-month prolonged abstinence (adjusted OR: 0.77, 95% CI: 0.61-0.98). The adjusted ORs for any body-weight loss, body-weight loss ≥1.5 kg, and body-weight loss ≥3.0 kg were 0.28 (95% CI: 0.09-0.88), 0.14 (95% CI: 0.03-0.55), and 0.03 (95% CI: 0.01-0.42), respectively. Conclusion: Body-weight gain in women during a hospital-based smoking-cessation program is associated with abstinence failure. Further multicenter studies, including participants of different races and cultural backgrounds, are warranted.

Chromosome-level genome assemblies of four wild peach species provide insights into genome evolution and genetic basis of stress resistance.

BACKGROUND: Peach (Prunus persica) is an economically important stone fruit crop in Rosaceae and widely cultivated in temperate and subtropical regions, emerging as an excellent material to study the interaction between plant and environment. During its genus, there are four wild species of peach, all living in harsh environments. For example, one of the wild species, P. mira, originates from the Qinghai-Tibet Plateau (QTP) and exhibits strong cold/ultraviolet ray environmental adaptations. Although remarkable progresses in the gene discovery of fruit quality-related traits in peach using previous assembled genome were obtained, genomic basis of the response of these wild species to different geographical environments remains unclear. RESULTS: To uncover key genes regulating adaptability in different species and analyze the role of genetic variations in resistance formation, we performed de novo genome assembling of four wild relatives of peach (P. persica), P. mira, P. davidiana, P. kansuensis, and P. ferganensis and resequenced 175 peach varieties. The phylogenetic tree showed that the divergence time of P. mira and other wild relatives of peach was 11.5 million years ago, which was consistent with the drastic crustal movement of QTP. Abundant genetic variations were identified in four wild species when compared to P. persica, and the results showed that plant-pathogen interaction pathways were enriched in genes containing small insertions and deletions and copy number variations in all four wild relatives of peach. Then, the data were used to identify new genes and variations regulating resistance. For example, presence/absence variations which result from a hybridization event that occurred between P. mira and P. dulcis enhanced the resistance of their putative hybrid, P. davidiana. Using bulked segregant analysis, we located the nematode resistance locus of P. kansuensis in chromosome 2. Within the mapping region, a deletion in the promoter of one NBS-LRR gene was found to involve the resistance by regulating gene expression. Furthermore, combined with RNA-seq and selective sweeps analysis, we proposed that a deletion in the promoter of one CBF gene was essential for high-altitude adaptation of P. mira through increasing its resistance to low temperature. CONCLUSIONS: In general, the reference genomes assembled in the study facilitate our understanding of resistance mechanism of perennial fruit crops, and provide valuable resources for future breeding and improvement.

SABA prescriptions and asthma management practices in patients treated by specialists in Taiwan: Results from the SABINA III study.

PURPOSE: Limited data exist on asthma medication patterns in Taiwan. The objectives of the SABINA III cross-sectional study in Taiwan were thus, to describe patient demographics and clinical features and estimate short-acting ß2-agonist (SABA) and inhaled corticosteroids (ICS) prescriptions per patient. METHODS: Patients (≥18 years) with asthma were classified by investigator-defined asthma severity per the 2017 Global Initiative for Asthma (GINA) recommendations. Data on asthma symptom control (per GINA 2017 recommendations), severe exacerbation history, and prescribed treatments in the 12 months before study visit were collected using electronic case-report forms. Analyses were descriptive. RESULTS: Overall, all 294 analyzed patients (mean [SD] age, 57.9 [15.6] years; female, 69%) were enrolled by specialists and had fully reimbursed healthcare. Most patients were classified with moderate-to-severe asthma (93.2%; GINA steps 3-5), were obese (53.4%) and nonsmokers (79.6%), reported high school or university and/or postgraduate education (61.9%), and had ≤2 comorbidities (89.1%). Mean (SD) asthma duration was 8.3 (10.0) years, with 37.8% of patients experiencing ≥1 severe exacerbation 12 months before the study visit. Overall, 62.2%, 26.2%, and 11.6% of patients had well-controlled, partly controlled, and uncontrolled asthma, respectively. Crucially, 19.3% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (overprescription). ICS, ICS + long-acting ß2-agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 6.5%, 97.3%, and 31.6% of patients, respectively. CONCLUSION: Despite treatment by specialists and fully reimbursed healthcare, findings indicate room for improvement in asthma control and SABA prescription practices in Taiwan, emphasizing the need to adhere to latest evidence-based guidelines.

Multiple in-hospital counseling increases six-month smoking abstinence among individuals participating in a hospital-initiated smoking cessation program.

BACKGROUND: A cessation program for hospitalized smokers is an effective strategy to achieve smoking abstinence. The effects of multiple in-hospital counseling sessions on 6-month smoking abstinence require further investigation. METHODS: We retrospectively analyzed the data of smokers who participated in hospital-initiated cessation programs at a medical center between 2017 and 2019. Data on age, sex, comorbidities, daily number of cigarettes, cessation motivation, nicotine dependence, cessation medications, discharge diagnosis, length of hospitalization, and intensive care unit admission were collected. We conducted multiple logistic regression analysis to investigate the effect of multiple in-hospital counseling sessions on 6-month sustained smoking abstinence. Sensitivity analyses were carried out excluding participants who underwent post-discharge cessation programs and assuming that the loss to follow-up participants had failure in 6-month smoking abstinence. RESULTS: A total of 1943 participants aged ≥ 20 years were analyzed. Compared with single in-hospital counseling session, the adjusted odds ratios (ORs) for 2 and ≥ 3 counseling sessions were 1.44 (95% confidence interval [CI] 1.05 to 1.98) and 2.02 (95% CI 1.27 to 3.22), respectively, with a significant trend for increasing the number of counseling sessions (P < 0.001). The results remained significant after excluding participants who underwent a post-discharge cessation program or when assuming that lost to follow-up participants had failure in smoking abstinence. CONCLUSION: Multiple in-hospital counseling sessions were associated with a higher 6-month sustained smoking abstinence rate. This strategy could be used to reduce the prevalence of smoking.

Multi-omics approaches identify a key gene, PpTST1, for organic acid accumulation in peach.

Organic acid content in fruit is an important determinant of peach organoleptic quality, which undergoes considerable variations during development and maturation. However, its molecular mechanism remains largely unclear. In this study, an integrative approach of genome-wide association studies and comparative transcriptome analysis were applied to identify candidate genes involved in organic acid accumulation in peach. A key gene PpTST1, encoding tonoplast sugar transporter, was identified and the genotype of PpTST1 with a single-base transversion (G1584T) in the third exon which leads to a single amino acid substitution (Q528H) was associated with low level of organic acid content in peach. Overexpression of PpTST1His resulted in reduced organic acid content along with increased sugar content both in peach and tomato fruits, suggesting its dual function in sugar accumulation and organic acid content reduction. Two V-type proton ATPases interact with PpTST1 in yeast two-hybridization assay. In addition, the G1584T transversion appeared and gradually accumulated during domestication and improvement, which indicated that PpTST1 was under selection. The identification and characterization of PpTST1 would facilitate the improvement of peach fruit quality.

Clinical and Microbiological Characteristics of Culture-Positive, Influenza-Associated Pulmonary Aspergillosis: A Single-Center Study in Southern Taiwan, 2016-2019.

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016-2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

The occurrence of and risk factors for developing acute critical illness during quarantine as a response to the COVID-19 pandemic.

BACKGROUND/PURPOSE: Early detection and timely quarantine measures are necessary to control disease spread and prevent nosocomial outbreaks of Coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the impact of a quarantine strategy on patient safety and quality of care. METHODS: This retrospective cohort study enrolled patients admitted to the quarantine ward in a tertiary hospital in southern Taiwan. The incidence and causes of acute critical illness, including clinical deterioration and unexpected complications during the quarantine period, were reviewed. Further investigation was performed to identify risk factors for acute critical illness during quarantine. RESULTS: Of 320 patients admitted to the quarantine ward, more than two-thirds were elderly, and 37.8% were bedridden. During the quarantine period, 68 (21.2%) developed acute critical illness, which more commonly occurred among patients older than 80 years and with a bedridden status, nasogastric tube feeding, or dyspnea symptoms. Bedridden status was an independent predictor of acute critical illness. Through optimization of sampling for COVID-19 and laboratory schedules, both the duration of quarantine and the proportion of acute critical illness among bedridden patients during quarantine exhibited a decreasing trend. There was no COVID-19 nosocomial transmission during the study period. CONCLUSION: The quarantine ward is a key measure to prevent nosocomial transmission of COVID-19 but may carry a potential negative impact on patient care and safety. For patients with multiple comorbidities and a bedridden status, healthcare workers should remain alert to rapid deterioration and unexpected adverse events during quarantine.

Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study.

BACKGROUND/PURPOSE: Cytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown. METHODS: We retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression. RESULTS: A total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26-12.60 and 2.64-28.82; p value = 0.019 and <0.001, respectively.). Patients with detectable CMV in BAL fluid did not have higher IPA risk (crude odds ratio, 0.95; 95% CI, 0.33-2.79; p value = 0.933). After stratifying patients by CMV viral load, the IPA risk is higher for patients with higher viral loads. There is an additive synergistic effect on IPA risk between CMV viremia and influenza infection. CONCLUSION: For critically ill patients, CMV viremia is an independent risk factor of IPA. Patients with higher blood CMV viral loads have a higher risk of IPA. CMV viremia and influenza have an additive synergistic effect for IPA risk in critically ill patients.