Diabetic foot ulcers segmentation challenge report: Benchmark and analysis.

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation.

Clinical significance of mutations in dihydropteroate synthase in Pneumocystis jirovecii pneumonia among non-HIV-infected patients.

BACKGROUND: Dihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significance of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear. METHODS: Patients with PCP in three tertiary referral hospitals in Taiwan between 2016 and 2020 were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein were analysed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonisation, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival. RESULTS: A total of 215 patients were analysed. Mutants inside DHPS were found in 78 patients (36.3%) and 68 patients (31.6%) died within 30 days. A total of 214 patients (99.5%) received trimethoprim-sulfamethoxazole as the first-line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH > 500 µ/L (adjusted hazard ratio [aHR] = 2.448, P = 0.001), pneumonia severity index > 135 mg/dL (aHR = 1.689, P = 0.049), and having solid tumours (aHR = 1.832, P = 0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients aged > 65 years (P = 0.049), with lymphopenia (P = 0.040), and those without solid tumour (P = 0.045). CONCLUSIONS: In non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.

Leveraging the Dielectric Barrier Discharge Plasma Process to Create Regenerative Biocidal ePTFE Membranes.

The utilization of dielectric barrier discharge (DBD) plasma treatment for modifying substrate surfaces constitutes an easy and simple approach with a potential for diverse applications. This technique was used to modify the surface of a commercial porous expanded poly(tetrafluoroethylene) (ePTFE) film with either dimethylaminoethyl methacrylate (DMAEMA) or (trimethylamino)ethyl methacrylate chloride (TMAEMA) monomers, aiming to obtain antibacterial ePTFE. Physicochemical analyses of the membranes revealed that DBD successfully enhanced the surface energy and surface charge of the membranes while maintaining high porosity (>75%) and large pore size (>1.0 µm). Evaluation of the bacteria killing-releasing (K-R) function revealed that both DMAEMA and TMAEMA endowed ePTFE with the ability to kill Escherichia coli bacteria. However, only TMAEMA-grafted ePTFE allowed for the release of dead bacteria from the surface upon washing with sodium hexametaphosphate (SHMP) saline solution, owing to its cationic charge derived from the quaternary amine. Washing with SHMP disturbed the electrostatic force between the polymer brushes and dead bacteria, which caused the release of the dead bacteria. Lastly, dead-end bacteria filtration showed that the TMAEMA-grafted ePTFE was able to kill 99.78% of the bacteria, while approximately 61.55% of bacteria were killed upon contact. The present findings support the feasibility of using DBD plasma treatment for designing surfaces that target bacteria and aid in the containment of disease-causing pathogens.

Association of pulmonary nontuberculous mycobacteria with the outcomes of patients with lung cancer: A retrospective matched cohort study with a special emphasis on the impact of chemotherapy.

INTRODUCTION: Nontuberculous mycobacteria (NTM) may be present in the respiratory tract of patients with lung cancer. We investigated the association of pulmonary NTM with the clinical features and outcomes of patients with lung cancer. METHODS: Between 2015 and 2019, the data of patients diagnosed with lung cancer at a medical center in northern Taiwan were analyzed. Patients whose respiratory specimens were culture-positive for NTM were identified (NTM group). For each patient in the NTM group, a matched control was selected (control group). The survival of the two groups was compared using the Kaplan-Meier method and Cox proportional hazards regression analysis. RESULTS: Among 8718 patients with lung cancer, 5418 (62.1%) underwent a sputum mycobacterial culture. At least one NTM species was isolated from 138 (2.5%) patients. The median age was 72 years (range: 64-80). In the NTM group, 19.8% fulfilled both the microbiological and radiographic criteria for the diagnosis of NTM lung disease. Compared with the control group, the NTM group exhibited a lower body mass index (22.4 vs. 23.6, p = 0.025) and a higher prevalence of structural lung disease (38.9% vs. 22.2%, p = 0.004). The two-year survival was not significantly different between the two groups (hazard ratio [HR]: 1.110; 95% confidence interval [CI]: 0.702-1.754, p = 0.656). In patients receiving chemotherapy, pulmonary NTM was associated with worse survival (HR: 2.497, 95% CI: 1.262-4.943, p = 0.009). CONCLUSIONS: Except in patients receiving chemotherapy, pulmonary NTM may not be clinically relevant in patients with lung cancer.

Impact of ventilator settings during venovenous extracorporeal membrane oxygenation on clinical outcomes in influenza-associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown. Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes. Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs. 12 breaths/min, p = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p = 0.034). Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population.

Treatment of electronic cigarette or vaping product use-associated lung injury (EVALI) by corticosteroid and low-dose pirfenidone: Report of a case.

Electronic (e)-cigarette or vaping product use-associated lung injury (EVALI) is a novel and potentially lethal disease first reported in the United States. We report the case of a 56-year-old man who presented to our hospital with dyspnoea and cough lasting for 2 months after using an e-cigarette for approximately 50 puffs over 2 weeks. Physical examination revealed crackles in the left lower lung. High-resolution computed tomography (HRCT) showed consolidation and ground-glass opacities in both lungs. The baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were 65.7% and 63.9% of the predicted, respectively. Lung biopsy revealed organizing pneumonia with focal fibrosis. In addition to prednisolone, he was treated with a low-dose pirfenidone (200 mg three times per day) due to the persistence of a mild cough, exertional dyspnoea and basal crackles after discharge. His symptoms and FVC significantly improved, but the recovery of the DLCO was slow. The follow-up HRCT demonstrated only minimal fibrotic changes. To our knowledge, this was the first reported case of EVALI successfully treated with a combination of corticosteroid and antifibrotic agents.

Mucosa-associated lymphoid tissue lymphoma with isolated endobronchial involvement.

Primary pulmonary lymphoma is an uncommon disease, and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common type of pulmonary lymphoma. The most frequent pattern observed in chest computed tomography (CT) is consolidation, followed by nodules and mass. The differentiation of pulmonary MALT lymphoma from other lung diseases is critical for disease management and treatment. However, pulmonary MALT lymphoma with isolated endobronchial manifestation has seldomly been reported. Here, we report a case of an elderly woman who presented with a four-month history of cough, dyspnoea, and haemoptysis. Chest CT scan revealed left main bronchus narrowing without lung parenchymal lesion. Bronchoscopic examination was performed, and the diagnosis of primary pulmonary MALT lymphoma with isolated endobronchial involvement was made. She has been successfully treated with rituximab.

Noise-like pulse generation around 1.3-µm based on cascaded Raman scattering.

Based on cascaded Raman scattering, near-infrared (NIR) noise-like pulses (NLPs) were successfully demonstrated using a Yb-doped fiber amplifier system. Through a nonlinear fiber amplifier using a germanium-zirconia-silica Yb3+-doped single mode fiber as a gain fiber, the fourth-order Stokes wave (4th-SW) can be excited to extend the emission peak of approximately 1.2-µm and a 3-dB bandwidth of approximately 130 nm. To further shift the wavelength more efficiently toward 1.3 µm, filtered NLPs with an emission peak at 1075 nm were adopted as seeded pulses to excite the fifth-order Stokes wave (5th-SW) because of the better conversion efficiency of stimulated Raman scattering without gain competition with Yb-doped fiber. The generated NIR NLPs were shown to be an excellent light source for the photoluminescence emission from three photon absorption of perovskite to illustrate the red shift of the emission peak owing to the reabsorption effect.

Expression of Exogenous Antigens in the Mycobacterium bovis BCG Vaccine via Non-genetic Surface Decoration with the Avidin-biotin System.

Tuberculosis (TB) is a serious infectious disease and the only available vaccine M. bovis bacillus Calmette-Guérin (BCG) is safe and effective for protection against children's severe TB meningitis and some forms of disseminated TB, but fails to protect against pulmonary TB, which is the most prevalent form of the disease. Promising strategies to improve BCG currently rely either on its transformation with genes encoding immunodominant M. tuberculosis (Mtb)-specific antigens and/or complementation with genes encoding co-factors that would stimulate antigen presenting cells. Major limitations to these approaches include low efficiency, low stability, and the uncertain level of safety of expression vectors. In this study, we present an alternative approach to vaccine improvement, which consists of BCG complementation with exogenous proteins of interest on the surface of bacteria, rather than transformation with plasmids encoding corresponding genes. First, proteins of interest are expressed in fusion with monomeric avidin in standard E. coli expression systems and then used to decorate the surface of biotinylated BCG. Animal experiments using BCG surface decorated with surrogate ovalbumin antigen demonstrate that the modified bacterium is fully immunogenic and capable of inducing specific T cell responses. Altogether, the data presented here strongly support a novel and efficient method for reshaping the current BCG vaccine that replaces the laborious conventional approach of complementation with exogenous nucleic acids.

Characteristics of noise-like pulse with broad bandwidth based on cascaded Raman scattering.

A noise-like pulse (NLP) with broadband emission spectrum and superior beam quality from a dispersion managed mode-locked Yb-doped fiber laser has been demonstrated based on stimulated Raman scattering. After insertion of a 150 m long single mode fiber into the laser cavity, the second order stoke wave from 1.3 MHz repetition rate of NLP can be excited. With a 320 mW pump power, the highest pulse energy of NLP was about 35.1 nJ and the emission spectrum was extended from 1000 to 1160 nm. Through a multi-mode fiber laser, the broad bandwidth NLP can produce relatively low speckle noise imaging with contrast below 0.04. The generated NLPs can be used as a superior light source for the biomedical diagnosis and laser projection in the near future.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Mycobacterial nucleoside diphosphate kinase blocks phagosome maturation in murine RAW 264.7 macrophages.

BACKGROUND: Microorganisms capable of surviving within macrophages are rare, but represent very successful pathogens. One of them is Mycobacterium tuberculosis (Mtb) whose resistance to early mechanisms of macrophage killing and failure of its phagosomes to fuse with lysosomes causes tuberculosis (TB) disease in humans. Thus, defining the mechanisms of phagosome maturation arrest and identifying mycobacterial factors responsible for it are key to rational design of novel drugs for the treatment of TB. Previous studies have shown that Mtb and the related vaccine strain, M. bovis bacille Calmette-Guérin (BCG), disrupt the normal function of host Rab5 and Rab7, two small GTPases that are instrumental in the control of phagosome fusion with early endosomes and late endosomes/lysosomes respectively. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that recombinant Mtb nucleoside diphosphate kinase (Ndk) exhibits GTPase activating protein (GAP) activity towards Rab5 and Rab7. Then, using a model of latex bead phagosomes, we demonstrated that Ndk inhibits phagosome maturation and fusion with lysosomes in murine RAW 264.7 macrophages. Maturation arrest of phagosomes containing Ndk-beads was associated with the inactivation of both Rab5 and Rab7 as evidenced by the lack of recruitment of their respective effectors EEA1 (early endosome antigen 1) and RILP (Rab7-interacting lysosomal protein). Consistent with these findings, macrophage infection with an Ndk knocked-down BCG strain resulted in increased fusion of its phagosome with lysosomes along with decreased survival of the mutant. CONCLUSION: Our findings provide evidence in support of the hypothesis that mycobacterial Ndk is a putative virulence factor that inhibits phagosome maturation and promotes survival of mycobacteria within the macrophage.

A broad-range of recombination cloning vectors in mycobacteria.

The increased incidence of tuberculosis (TB) gave impetus for the increased interest in the study of mycobacterial genetics, which culminated in the publication of the full genome sequence of many mycobacterial strains. Since then, many genes and open reading frames of unknown function have been described and the expression of their encoded proteins is critical toward understanding the pathogenesis of TB and developing therapeutic and preventive strategies. Therefore there is an increased need for highly efficient methods for cloning of mycobacterial genes, as the limited cloning flexibility of current Escherichia coli-mycobacteria shuttle vectors remains a frequent impediment in genetic manipulation of mycobacteria. In order to overcome this limitation, we have converted representative extrachromosomal and integrative vectors into multiple destination mycobacterial vectors for one-step and restriction enzyme-free recombination cloning methodology that uses in vitro site-specific recombination. We provide several examples that highlight the potential of recombination cloning for gene expression in slow and fast-growing mycobacteria. Thus, a gene of interest can be transferred by simple recombination into our mycobacterial destination vectors, which serve a multitude of functional genomic studies.