[Key microbial monitoring and clinical analysis of bloodstream infections and CRO colonization after hematopoietic stem cell transplantation in hematological patients].

Objective: To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients. Methods: We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison. Results: The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM (P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM (P=0.035) . Conclusion: This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

Efficacy and Safety of Preoperative Transcatheter Rectal Arterial Chemoembolisation in Patients with Locally Advanced Rectal Cancer: Results from a Prospective, Phase II PCAR Trial.

AIMS: The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. RESULTS: In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival. CONCLUSION: The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

[Preliminary evaluation of immunogenicity and protective effect of multicomponent recombinant protein vaccine EPRHP014 against tuberculosis].

Objective: To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB. Methods: Three full-length Mycobacterium (M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M. tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results: Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance (P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group (P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group (P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group (P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group (P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups (P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant (P>0.05). Conclusion: Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Development and deployment of a supply-chain digital tool to predict fluid-milk spoilage due to psychrotolerant sporeformers.

Psychrotolerant sporeformers pose a challenge to maintaining fluid milk quality. Dynamic temperature changes along the supply chain can favor the germination and growth of these bacteria and lead to fluid milk spoilage. In this study, we aim to expand on our previous work on predicting milk spoilage due to psychrotolerant sporeformers. The key model innovations include (1) the ability to account for changing temperatures along the supply chain, and (2) a deployed user-friendly interface to allow easy access to the model. Using the frequencies and concentrations of 8 Bacillales subtypes specific to fluid milk collected in New York, the model simulated sporeformer growth in half-gallons of high-temperature, short-time (HTST) pasteurized fluid milk transported from processing facility to retail store and then to consumer. The Monte Carlo simulations predicted that 44.3% of half-gallons of milk were spoiled (defined as having a bacterial concentration >20,000 cfu/mL, a conservative estimate that represents the Pasteurized Milk Ordinance regulatory limit) after 21 d of refrigerated storage at consumer's home. Model validations showed that the model was the most accurate in predicting the mean sporeformer concentration at low temperatures (i.e., at 3°C and 4°C; compared with higher temperatures at 6°C and 10°C) within the first 21 d of consumer storage, with a root mean square error of 0.29 and 0.34 log10 cfu/mL, respectively. Global sensitivity analyses indicated that home storage temperature, facility-to-retail transportation temperature, and initial spore concentration were the 3 most influential factors for predicting milk spoilage on d 21 of shelf life. What-if scenarios indicated that microfiltration was predicted to be the most effective strategy to reduce spoilage. The implementation of this strategy (assumed to reduce initial spore concentration by 2.2 log10 cfu/mL) was predicted to reduce the percentage of spoiled milk by 17.0 percentage points on d 21 of storage and could delay the date by which 50% of half-gallons of milk were spoiled, from d 25 to 35. Overall, the model is readily deployed as a digital tool for assessing fluid milk spoilage along the supply chain and evaluating the effectiveness of intervention strategies, including those that target storage temperatures at different supply chain stages.

What surprises the Mona Lisa? The relative importance of the eyes and eyebrows for detecting surprise in briefly presented face stimuli.

The classification image (CI) technique has been used to derive templates for judgements of facial emotion and reveal which facial features inform specific emotional judgements. For example, this method has been used to show that detecting an up- or down-turned mouth is a primary strategy for discriminating happy versus sad expressions. We explored the detection of surprise using CIs, expecting widened eyes, raised eyebrows, and open mouths to be dominant features. We briefly presented a photograph of a female face with a neutral expression embedded in random visual noise, which modulated the appearance of the face on a trial-by-trial basis. In separate sessions, we showed this face with or without eyebrows to test the importance of the raised eyebrow element of surprise. Noise samples were aggregated into CIs based on participant responses. Results show that the eye-region was most informative for detecting surprise. Unless attention was specifically directed to the mouth, we found no effects in the mouth region. The eye effect was stronger when the eyebrows were absent, but the eyebrow region was not itself informative and people did not infer eyebrows when they were missing. A follow-up study was conducted in which participants rated the emotional valence of the neutral images combined with their associated CIs. This verified that CIs for 'surprise' convey surprised expressions, while also showing that CIs for 'not surprise' convey disgust. We conclude that the eye-region is important for the detection of surprise.

Organizing Pneumonia Secondary to Infection with Coxiella Burnetii: a Case Report.

BACKGROUND: Organizing pneumonia is a non-specific inflammatory response to various types of damage to the lungs. It is usually considered bacterial pneumonia that has not been absorbed for more than 4 weeks, accompanied by granulomas and fibrosis. Lung lesions in patients with organizing pneumonia are usually irreversible and the prognosis is relatively poor. Coxiella burnetii can cause Q fever. Acute Q fever usually presents as a self-limiting febrile illness with a good prognosis, but there are few cases of coexisting organizing pneumonia. We report a case of organizing pneumonia secondary to Coxiella burnetii infection. METHODS: Percutaneous lung biopsy, Next-generation sequencing (NGS). RESULTS: Percutaneous lung biopsy showed the existence of organizing pneumonia, and external examination of NGS showed the existence of Coxiella burnetii infection. After symptomatic treatment with azithromycin and glucocorticoids, the patient improved and was discharged from the hospital. CONCLUSIONS: For lesions with obvious heterogeneous enhancement on chest CT imaging, percutaneous lung biopsy or bronchoscopy should be performed promptly to obtain pathological tissue, and NGS should be used for definite diagnosis if necessary.

Mycobacterium Tuberculosis Infection in AECOPD Combined with Pulmonary Embolism: a Case Report.

BACKGROUND: Mycobacterium tuberculosis belongs to the group of mycobacteria, most of which can cause a delayed hypersensitivity reaction in the body and is a bacterium that causes tuberculosis. Mycobacterium tuberculosis infection often presents with symptoms of tuberculosis toxicity and rarely with respiratory distress. At the same time, chest imaging often shows an ill-defined solid shadow in the apical and posterior segments of the upper lobe and, less frequently, in the dorsal segment of the lower lobe, and less frequently a diffuse nodular shadow. We report a case of AECOPD combined with pulmonary embolism infected with Mycobacterium tuberculosis. METHODS: Bronchoscopy, Next-generation sequencing (NGS). RESULTS: Antacid staining of bronchoalveolar lavage fluid suggested that a small amount of Mycobacterium antacid was visible. NGS was sent for examination and it suggested the presence of Mycobacterium tuberculosis with a sequence number of 5 (reference range ≥ 0). Treatment such as bronchodilation and antituberculosis was given. CONCLUSIONS: In patients with dyspnea, it is crucial to find the causative agent and to promptly improve relevant examinations such as pulmonary arteriography and bronchoscopy, and if necessary, to make a definitive diagnosis by NGS.

Rare Co-Infection of the Lungs with EBV and Pneumocystis Carinii in a Patient with Kidney Cancer: a Case Report.

BACKGROUND: Epstein-Barr virus (EBV) is the primary agent of infectious mononucleosis, lymphoma, and naso-pharyngeal carcinoma, but rarely involves the lungs. Pneumocystis carinii is commonly found in patients with HIV infection and is not pathogenic when the host is healthy, but opportunistic infections can occur when the body is immunocompromised, causing pneumocystis pneumonia (PCP). It is rare for both diseases to occur in the lungs of the same patient. METHODS: Next-generation sequencing (NGS), laboratory examination, chest CT scan, electronic bronchoscopy, and pathogenetic examination were used in this study. RESULTS: Laboratory tests showed (1-3)-ß-D-glucan of 889.47 pg/mL, negative human immunodeficiency virus (HIV) antibody, and negative Aspergillus immunological test. Chest CT showed multiple high-density shadows in both lungs, and EBV infection combined with Pneumocystis carinii pneumonia was confirmed by bronchoscopic biopsy and NGS examination. CONCLUSIONS: Elevated serum (1-3)-ß-D-glucan is not a specific index for infectious diseases. Bronchoscopy and the NGS has high specificity in pathogen detection of infectious diseases.

D-Dimer and Procalcitonin Improve the Sensitivity of BAP-65 Score in Predicting AECOPD Patients Admission to ICU.

BACKGROUND: The study aimed at investigating the effectiveness of the BAP-65 score combined with D-dimer and procalcitonin (PCT) in predicting admission of acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients to the intensive care unit (ICU). METHODS: We conducted a retrospective study. We analyzed data from 369 patients over the age of 40 years ad-mitted to our hospital with AECOPD. All patients received blood routine measurements and BAP-65 score calculation on admission. Receiver operating characteristic curves (ROC) were used to assess the sensitivity and specificity of D-dimer, PCT, and BAP-65 scores and combined metrics in predicting the risk of admissions to the ICU of AECOPD patients. RESULTS: We found that the percentage of patients with AECOPD admitted to the ICU was 32.25% (119/369). The area under the curve (AUC) of D-dimer, PCT, and BAP-65 score in individually predicting the probability of entering the ICU of AECOPD patients were 0.74 (95% CI 0.68 - 0.80), 0.83 (95% CI 0.78 - 0.88), and 0.72 (95% CI 0.66 - 0.79), respectively. The sensitivities of D-dimer, PCT, and BAP-65 score were 0.51, 0.65, and 0.52, respectively. The specificities of D-dimer, PCT, and BAP-65 score were 0.90, 0.91, and 0.92, respectively. The AUC of D-dimer and PCT combined with BAP-65 score was 0.90 (95% CI 0.86 - 0.94), the sensitivity and specificity were 0.90 and 0.80, respectively. CONCLUSIONS: D-dimer and procalcitonin improve the sensitivity of the BAP-65 score in predicting the probability of AECOPD patients entering the ICU while having a good specificity.

Procalcitonin (PCT) Improves the Accuracy and Sensitivity of CURB-65 Score in Predicting CAP Patients Admission to ICU.

BACKGROUND: The CURB-65 scoring system is a simple tool for assessment and prognosis prediction for community-acquired pneumonia (CAP) patients. However, the variations in the performance of CURB-65 in young and elderly patients, underestimation, or overestimation of the severity have often been reported. It is worth noting that the application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attention to procalcitonin (PCT) in respiratory infectious diseases, and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the CURB-65 score combined with PCT in predicting admission of CAP patients to intensive care units (ICU). METHODS: We conducted a retrospective study. We analyzed data from 520 non-immune individuals over the age of 18 in this study. All patients received blood indicators measurement and CURB-65 score calculation on admission. The primary outcome used to assess the probability of a CAP patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of the CURB-65 model and PCT combined CURB-65 augmented model in predicting the main outcomes. RESULTS: After analyzing the data from 520 patients, we found that the probability of entering the ICU was 22.1% (115/520). The AUC of Combination 1 (PCT&CURB-65 scores), Combination 2 (WBC&CURB-65 scores), Combination 3 (hs-CRP&CURB-65 scores) and Combination 4 (D-dimer&CURB-65 scores) for predicting CAP patients entering the ICU was 0.92 (95% CI 0.88 - 0.95), 0.91 (95% CI 0.87 - 0.94), 0.89 (95% CI 0.85 - 0.92), and 0.90 (95% CI 0.87 - 0.94), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.83, 0.82, 0.77 and 0.77, respectively, and the specificities were 0.92, 0.84, 0.90 and 0.91, respectively. PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score. CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the CURB-65 score in predicting the probability of CAP patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score.

Butyric acid-producing bacterial spore levels in conventional raw milk vary by farm.

Anaerobic butyric acid-producing sporeforming bacteria (BAB) are important microbial contaminants in raw milk that may lead to premature spoilage of certain cheeses during aging. A study was conducted to determine the baseline levels of these spores in raw milk from 7 conventional Northeast United States dairy farms over a 1-yr period. The overall mean BAB concentration was 1.79 log10 most probable number per liter with spore levels differing significantly by farm. A post-hoc farm management practices survey was conducted to determine if there was an association between farm practices on BAB levels in raw milk from these farms. Survey questions included variables related to bedding, milking preparation procedures, teat and udder cleanliness scoring, holding area cleaning procedures, and udder clipping or flaming frequency. Each variable was fitted with a linear mixed-effects model, which revealed no significant association between farm-level factors and the initial BAB concentrations in raw milk; this finding was likely due to the small sample size in this study. To demonstrate the usefulness of our data beyond the initial baseline levels of BAB spores in raw milk, we used this data set to calculate minimum number of individual samples that would be needed to be collected in future studies, which was determined to be 96 to 126 samples, to evaluate the association between farm-level factors and BAB spore concentrations in raw milk. Overall, this study provides dairy industry stakeholders with baseline data on BAB spore levels in raw milk, along with a demonstration on how these data could be used in future studies to calculate sample sizes needed to assess the effect of farm management practices on BAB levels in raw milk.

How Can AI Help Improve Food Safety?

With advances in artificial intelligence (AI) technologies, the development and implementation of digital food systems are becoming increasingly possible. There is tremendous interest in using different AI applications, such as machine learning models, natural language processing, and computer vision to improve food safety. Possible AI applications are broad and include, but are not limited to, (a) food safety risk prediction and monitoring as well as food safety optimization throughout the supply chain, (b) improved public health systems (e.g., by providing early warning of outbreaks and source attribution), and (c) detection, identification, and characterization of foodborne pathogens. However, AI technologies in food safety lag behind in commercial development because of obstacles such as limited data sharing and limited collaborative research and development efforts. Future actions should be directed toward applying data privacy protection methods, improving data standardization, and developing a collaborative ecosystem to drive innovations in AI applications to food safety.

A New Prediction Model for Prolonged Hospitalization in Adult Community-Acquired Pneumonia (CAP) Patients.

BACKGROUND: As a serious and common out-of-hospital infectious disease, community-acquired pneumonia (CAP) ranks among the leading causes of death in both developing and developed countries. In recent years, the increasing incidence of CAP has led to an increase in the number of hospitalizations. Although CURB-65 (or CRB-65) and pneumonia severity Index (PSI) scoring systems are widely used in CAP prognostic scoring systems, each score had some limitations in predicting whether patients with CAP would require prolonged hospitalization. The aim of this study was to analyze serum inflammatory biomarkers combined with age to establish a novel predictive model for predicting prolonged hospitalization in patients with CAP. METHODS: In a retrospective study, serum inflammatory biomarkers were collected from all enrolled CAP patients, including white blood cell count (WBC), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), D-dimer, procalcitonin (PCT), fibrinogen (FIB), and ICU treatment. Length of hospital stay and age were also recorded. The 75th percentile of length of stay in the enrolled population was defined as long hospitalization over time, and the primary predictor of outcome was prolonged hospitalization. Univariate analysis and binary logistic regression analysis were used to explore the independent risk factors which could be components of a new predicting model for prolonged hospitalization in CAP patients. ROC curves were used to evaluate the sensitivity and specificity of the new model, which consisted of the combination of all independent risk factors in predicting the main outcomes. RESULTS: The results showed that among 364 patients with CAP, 85 had extended hospitalization (85/364). Further analysis showed that age, white blood cell, fibrinogen, and high-sensitivity C-reactive protein were independent risk factors for extended hospitalization in patients with CAP. Finally, the AUC of the ROC curve of the new prediction model (the joint model consists of age, WBC, FIB, and hs-CRP) was 0.93 (95% CI 0.90 - 0.96), and the sensitivity and specificity were 87.1% and 87.8%, respectively. CONCLUSIONS: Serum inflammatory biomarkers combined age have high specificity and sensitivity in predicting prolonged hospitalization in adult CAP patients.

Carcinoembryonic Antigen Elevation in Broncholithiasis Patients Initially Misdiagnosed as Lung Cancer: a Case Report.

BACKGROUND: We report a case of broncholithiasis with recurrent pulmonary infection accompanied by blood in the sputum, which was initially misdiagnosed as lung cancer after laboratory examination indicating elevated carcinoembryonic antigen. METHODS: Laboratory examination, enhanced chest CT scan, electronic bronchoscopy, and ultra-thin bronchoscopy were performed to diagnose broncholithiasis. RESULTS: Carcinoembryonic antigen levels were elevated. Chest CT scan showed dense nodules and calcification in the middle lobe of the right lung. Ultrathin bronchoscopy demonstrates calcification of the distal bronchus of the lateral middle lobe of the right lung. The symptoms were relieved after the removal of the calculi by electronic bronchoscopy. CONCLUSIONS: It is necessary to pay attention to the calcification of the trachea and the differential diagnosis of lung cancer, especially when the level of carcinoembryonic antigen is increased.

[Comparison of a new thermosensitive rhAm carrier versus traditional PGA carrier for in vitro antibacterial activity and biocompatibility].

OBJECTIVE: To compare a new thermosensitive recombinant human amelogenin (rhAm) carrier and traditional propylene glycol alginate (PGA) carrier for their characteristics, antibacterial activity, and biocompatibility with human periodontal membrane fibroblasts. METHODS: PGA-rhAm was prepared by mixing 3.3% PGA and rhAm, and CS-ßGP-rhAm was prepared by mixing 2% chitosan (CS) with rhAm and then with 60% ß-sodium glycerophosphate solution (ßGP) as the crosslinking agent. The biophysical properties of the prepared carriers were characterized, and their antibacterial activity was assessed by observing Staphylococcus aureus growth. The biocompatibility of the carriers was evaluated in human periodontal membrane fibroblasts (hPDLFs) using CCK8 assay and scratch test, and mRNA and protein expressions of osteogenic genes of the cells incubated with the carriers were detected using RT-qPCR and Western blotting; osteogenic differentiation of the cells was detected using alkaline phosphatase staining. RESULTS: PGA-rhAm had a viscosity value of 3.262±0.055 Pa.s. CS-ßGP-rhAm had a solidification capacity of 6 min at 37 ℃ with a pH value close to that of the oral cavity and a swelling rate of about 90%. CS-ß GP-rhAm maintained sustained release of rhAm for over 2 weeks with a self-degradation time over 3 weeks. CS-ßGPrhAm more effectively inhibited the growth of S. aureus than rhAm-loaded PGA. While PGA did not obviously affect the proliferation of hPDLFs, both CS-ßGP and CS-ßGP-rhAm significantly promoted the cell proliferation(P < 0.001). Scratch test showed that after rhAm loading, both CS-ßGP and PGA promoted cell migration (P < 0.01). CS-ßGP-rhAm significantly enhanced the mRNA expressions of RUNX2 and OCN mRNA level and the protein expressions of Ki67, RUNX2, collagen I, and ß-catenin (P < 0.05); PGA-rhAm only enhanced RUNX2 (P < 0.05) and OCN (P < 0.01) mRNA expressions without significant effects on the protein expressions. Alkaline phosphatase staining results showed that CS-ßGP, but not PGA, promoted osteogenic differentiation of hPDLFs. CONCLUSION: CS-ßGP carrier is capable of sustained release of rhAm, inhibiting the growth of S. aureus, and improving the biological activity of hPDLFs without affecting the bioactivity of rhAm after drug loading.

Monte Carlo simulation model predicts bactofugation can extend shelf-life of pasteurized fluid milk, even when raw milk with low spore counts is used as the incoming ingredient.

Bacterial spores from raw milk that survive the pasteurization process are responsible for half of all the spoilage of fluid milk. Bactofugation has received more attention as a nonthermal method that can reduce the presence of bacterial spores in milk and with it the spoilage of fluid milk. The objective of this work was to determine the effectiveness of bactofugation in removing spores from raw milk and estimate the effect the spore removal could have on shelf-life of fluid milk. The study was conducted in a commercial fluid milk processing facility where warm spore removal was performed using one-phase bactofuge followed by warm cream separation and high temperature, short time pasteurization. Samples from different stages of fluid milk processing with and without the use of bactofuge were tested for total plate count, mesophilic spore count, psychrotolerant spore count (PSC), and somatic cell count. Results were evaluated to determine the count reductions during different stages of fluid milk processing and compare counts in fluid milk processed with and without bactofugation. Bactofugation on average reduced the total plate count by 1.81 ± 0.72 log cfu/mL, mesophilic spore count by 1.08 ± 0.71 log cfu/mL, PSC by 0.86 ± 0.59 log cfu/mL, and somatic cell count by 135,881 ± 43,942 cells/mL. Psychrotolerant spore count in final pasteurized skim milk processed with and without bactofugation was used to predict the shelf-life of the pasteurized skim milk using the Monte Carlo simulation model. Although PSC in the initial raw milk was already low (-0.63 ± 0.47 log cfu/mL), the predicted values from the simulation model showed that bactofugation would extend the shelf-life of pasteurized skim milk by approximately 2 d. The results of this study will directly help fluid milk processors evaluate the benefits of using bactofugation as an intervention in their plants, and also demonstrate the benefits of using mathematical modeling in decision making.

[Clinical characteristics of Mycoplasma pneumoniae infection and factors associated with co-infections in children].

Objective: To describe the clinical characteristics of Mycoplasma pneumoniae infection and analyze the factors associated with co-infections with other pathogens in children, and provide evidence for improvement of community acquired pneumonia (CAP) prevention and control in children. Methods: Based on the surveillance of hospitalized acute respiratory infections cases conducted in Soochow University Affiliated Children's Hospital (SCH), the CAP cases aged <16 years hospitalized in SCH between 2018 and 2021 were screened. The pathogenic test results of the cases were obtained through the laboratory information system, and their basic information, underlying conditions, and clinical characteristics were collected using a standardized questionnaire. The differences in clinical characteristics between M. pneumoniae infection and bacterial or viral infection and the effect of the co-infection of M. pneumoniae with other pathogens on clinical severity in the cases were analyzed; logistic regression was used to analyze the factors associated with the co-infections with other pathogens. Results: A total of 8 274 hospitalized CAP cases met the inclusion criteria. Among them, 2 184 were positive for M. pneumoniae (26.4%). The M. pneumoniae positivity rate increased with age (P<0.001), and it was higher in girls (P<0.001) and in summer and autumn (P<0.001). There were statistically significant differences in the incidence of wheezing, shortness of breath, wheezing sounds and visible lamellar faint shadow on chest radiographs, as well as fever and hospitalization days among M. pneumoniae, bacterial, and viral infection cases (all P<0.05). In the cases aged <60 months years, co-infection cases had higher rates of wheezing, gurgling with sputum and stridor; and in the cases aged ≥60 months, co-infection cases had a higher rate of shortness of breath (all P<0.05). Multifactorial logistic regression analysis showed that being boys (aOR=1.38,95%CI:1.15-1.67), being aged <6 months (aOR=3.30,95%CI:2.25-4.89), 6-23 months (aOR=3.44,95%CI:2.63-4.51), 24-47 months (aOR=2.50,95%CI:1.90-3.30) and 48-71 months (aOR=1.77,95%CI:1.32-2.37), and history of respiratory infection within 3 months (aOR=1.28,95%CI:1.06-1.55) were factors associated with co-infections of M. pneumoniae with other pathogens. Conclusions: M. pneumoniae was the leading pathogen in children hospitalized due to CAP. M. pneumoniae infections could cause fever for longer days compared with bacterial or viral infections; M. pneumoniae was often co-detected with virus or bacteria. Being boys, being aged <72 months and history of respiratory infection within 3 months were associated factors for co-infections.

Treatment-related toxicities associated with hospitalization in children, adolescents, and young adults with acute lymphoblastic leukemia: population level analysis.

Treatment-related toxicities (TRTs) are a potential cause of survival disparities in patients with acute lymphoblastic leukemia (ALL). We aimed to identify the most frequent TRTs associated with hospitalizations at a population level in children, adolescents and young adults (AYAs). We used the California Cancer Registry linked to a statewide hospital discharge database to identify children and AYAs with TRTs within 3 years of diagnosis. We assessed the frequency of TRTs, length of stay (LOS), admission rates associated with TRTs and TRTs impact on survival. Febrile neutropenia, hypertension, and thrombocytopenia were the most common TRTs for both children and AYAs. AYAs had longer median LOS compared to children for most toxicities. AYAs at non-specialized cancer centers (SCCs) had higher frequency of admissions associated with TRTs compared to non-SCC. Cardiovascular, respiratory, gastrointestinal, renal, and infectious TRTs were associated with worse survival. This study demonstrates the burden of TRTs in patients with ALL.

Development of a risk assessment model to predict the occurrence of late blowing defect in Gouda cheese and evaluate potential intervention strategies.

Late blowing defect (LBD) is an important spoilage issue in semi-hard cheese, with the outgrowth of Clostridium tyrobutyricum spores during cheese aging considered to be the primary cause. Although previous studies have explored the microbial and physicochemical factors influencing the defect, a risk assessment tool that allows for improved and rational management of LBD is lacking. The purpose of this study was to develop a predictive model to estimate the probability of LBD in Gouda cheese and evaluate different intervention strategies. The spore concentration distribution of butyric acid bacteria (BAB) in bulk tank milk was obtained from 8 dairy farms over 12 mo. The concentration of C. tyrobutyricum from raw milk to the end of aging was simulated based on Gouda brined for 2 d in saturated brine at 8°C and aged at 13°C. Predicted C. tyrobutyricum concentrations during aging and estimated concentration thresholds in cheese at onset of LBD were used to predict product loss due to LBD during a simulated 1-yr production. With the estimated concentration thresholds in cheese ranging from 4.36 to 4.46 log most probable number (MPN)/kg of cheese, the model predicted that 9.2% (±1.7%) of Gouda cheese showed LBD by d 60; cheeses predicted to show LBD at d 60 showed a mean pH of 5.39 and were produced with raw milk with a mean BAB spore count of 143 MPN/L. By d 90, 36.1% (±3.4%) of cheeses were predicted to show LBD, indicating that LBD typically manifests between d 60 and 90, which is consistent with observations from the literature and the cheese industry. Sensitivity analysis indicated that C. tyrobutyricum maximum growth rate as well as concentration threshold in cheese at onset of LBD are the most important variables, identifying key data needs for development of more accurate models. The implementation of microfiltration or bactofugation of raw milk (assumed to show 98% efficiency of spore removal) in our model prevented occurrence of LBD during the first 60 d of aging. Overall, our findings provide a framework for predicting the occurrence of LBD in Gouda as well as other cheeses and illustrate the value of developing digital tools for managing dairy product quality.