Proteomic profiling of antibiotic-resistant Escherichia coli GW-AmxH19 isolated from hospital wastewater treated with physical plasma.

Microorganisms which are resistant to antibiotics are a global threat to the health of humans and animals. Wastewater treatment plants are known hotspots for the dissemination of antibiotic resistances. Therefore, novel methods for the inactivation of pathogens, and in particular antibiotic-resistant microorganisms (ARM), are of increasing interest. An especially promising method could be a water treatment by physical plasma which provides charged particles, electric fields, UV-radiation, and reactive species. The latter are foremost responsible for the antimicrobial properties of plasma. Thus, with plasma it might be possible to reduce the amount of ARM and to establish this technology as additional treatment stage for wastewater remediation. However, the impact of plasma on microorganisms beyond a mere inactivation was analyzed in more detail by a proteomic approach. Therefore, Escherichia coli GW-AmxH19, isolated from hospital wastewater in Germany, was used. The bacterial solution was treated by a plasma discharge ignited between each of four pins and the liquid surface. The growth of E. coli and the pH-value decreased during plasma treatment in comparison with the untreated control. Proteome and antibiotic resistance profile were analyzed. Concentrations of nitrite and nitrate were determined as long-lived indicative products of a transient chemistry associated with reactive nitrogen species (RNS). Conversely, hydrogen peroxide served as indicator for reactive oxygen species (ROS). Proteome analyses revealed an oxidative stress response as a result of plasma-generated RNS and ROS as well as a pH-balancing reaction as key responses to plasma treatment. Both, the generation of reactive species and a decreased pH-value is characteristic for plasma-treated solutions. The plasma-mediated changes of the proteome are discussed also in comparison with the Gram-positive bacterium Bacillus subtilis. Furthermore, no effect of the plasma treatment, on the antibiotic resistance of E. coli, was determined under the chosen conditions. The knowledge about the physiological changes of ARM in response to plasma is of fundamental interest to understand the molecular basis for the inactivation. This will be important for the further development and implementation of plasma in wastewater remediation.

Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells.

BACKGROUND: Circulating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening of larger blood volumes. To leverage DLA's full potential, this study introduces a novel approach for CTC enrichment from DLAs. METHODS: DLA was applied to six advanced stage NSCLC patients. For an unbiased CTC enrichment, a two-step approach based on negative depletion of hematopoietic cells was used. Single-cell (sc) whole-transcriptome sequencing was performed, and CTCs were identified based on gene signatures and inferred copy number variations. RESULTS: Remarkably, this innovative approach led to the identification of unprecedented 3,363 CTC transcriptomes. The extensive heterogeneity among CTCs was unveiled, highlighting distinct phenotypes related to the epithelial-mesenchymal transition (EMT) axis, stemness, immune responsiveness, and metabolism. Comparison with sc transcriptomes from primary NSCLC cells revealed that CTCs encapsulate the heterogeneity of their primary counterparts while maintaining unique CTC-specific phenotypes. CONCLUSIONS: In conclusion, this study pioneers a transformative method for enriching CTCs from DLA, resulting in a substantial increase in CTC numbers. This allowed the creation of the first-ever single-cell whole transcriptome in-depth characterization of the heterogeneity of over 3,300 NSCLC-CTCs. The findings not only confirm the diagnostic value of CTCs in monitoring tumor heterogeneity but also propose a CTC-specific signature that can be exploited for targeted CTC-directed therapies in the future. This comprehensive approach signifies a major leap forward, positioning CTCs as a key player in advancing our understanding of cancer dynamics and paving the way for tailored therapeutic interventions.

PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms.

As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression groups with general tumor groups and primary localization. PITX2 expression (all expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite frequently weak or moderately positive. The specificity rose to 99.5% for a midgut origin of NET if only a strong PITX2 expression was considered, which was found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 12.5% moderate), whereas CDX2 was negative or only weakly expressed in 31.3% of the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 expression, which was not associated with a specific tumor localization. Our study independently validates PITX2 as a very sensitive and specific immunohistochemical marker of midgut-derived NET in a very large collective of neuroendocrine neoplasms. Therefore, our data argue toward implementation into diagnostic panels applied for NET as a firstline midgut marker.

Peri- and postoperative morbidity and mortality in older patients with non-small cell lung cancer: a matched-pair study.

BACKGROUND: Reports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (< 75 years) and identify independent predictive risk factors. METHODS: We identified 2015 patients with postoperative stages IA to IIIA according to AJCC/UICC 7th edition who had undergone NSCLC surgery with curative intent at a single specialized lung cancer center from January 2010 to December 2015. A matched-pair analysis was performed on 227 older patients and corresponding 227 younger patients. Short-term surgical outcomes were postoperative morbidity, length of hospital stay, 30-day and 90-day mortality. Long-term operative outcomes were disease-free and overall survival. RESULTS: 454 patients were included in the matched-pair analysis. 36% of younger patients developed postoperative complications versus 42% in older patients (p = 0.163). Age was not significantly associated with the occurrence of postoperative complications. Median length of hospital stay was 14 days in older patients and 13 days in younger patients (p = 0.185). 90-day mortality was 2.2% in younger patients compared to 4% in older patients (p = 0.424). In patients aged 75 and older impaired performance status (ECOG ≥ 1) was associated with decreased overall survival (HR = 2.15, CI 1.34-3.46), as were preoperative serum C-reactive protein / albumin ratio ≥ 0.3 (HR = 1.95, CI 1.23-3.11) and elevated preoperative serum creatinine levels ≥ 1.1 mg/dl (HR = 1.84, CI 1.15-2.95). In the younger cohort male sex (HR = 2.26, CI 1.17-4.36), postoperative stage III disease (HR 4.61, CI 2.23-9.54) and preoperative anemia (hemoglobin < 12 g/dl) (HR 2.09, CI 1.10-3.96) were associated with decreased overall survival. CONCLUSIONS: Lung resection for NSCLC in older patients is associated with postoperative morbidity and mortality comparable to those of younger patients. In older patients, physical activity, comorbidities and nutritional status are related to survival and should influence the indication for surgery rather than age alone.

[Tracheal Tumours]. / Trachealtumoren.

Malignant primary tracheal tumours are rare. The most common histological subtypes are squamous cell carcinoma and adenoid cystic carcinoma. These two entities have different prognoses and growth patterns. Tracheobronchoscopy and thoracic sectional imaging are standard diagnostic tools for tumour staging and local evaluation. Complete surgical resection of the affected tracheal segment is the treatment of choice for limited disease without distant metastases. Incomplete gross tumour resection with additional irradiation is an acceptable therapeutic option for adenoid cystic carcinoma. Interventional endoscopy with tumour debulking or tracheal stenting and/or definitive mediastinal radiotherapy are treatment alternatives in either a locally advanced or palliative setting.

[Anatomical Lung Resection Following Neoadjuvant Chemoimmunotherapy: Technical Aspects and Case Reports]. / Anatomische Lungenresektion nach neoadjuvanter Chemo-Immuntherapie: technische Aspekte und klinische Fallbeispiele.

Since the approval of neoadjuvant chemo-immunotherapy in Europe, treatment options for resectable stage II-III NSCLC have also significantly improved in clinical routine. Surgical excision of the tumour by anatomic lung resection still remains the most essential component of multimodal therapy. However, with the increasing use of the new treatment concepts in clinical routine, questions also arise regarding safety, adverse events and technical resectability following neoadjuvant chemo-immunotherapy. This review summarises the current data on perioperative safety following neoadjuvant chemo-immunotherapy and discusses aspects of surgical technique, the extent of resection and intraoperative challenges illustrated by clinical case reports.

[Modern individualized diagnostics and treatment of non-small cell lung cancer]. / Moderne individualisierte Diagnostik und Behandlung des nichtkleinzelligen Lungenkarzinoms.

Approximately one half of patients with non-small cell lung cancer (NSCLC) are diagnosed at resectable tumor stages (I-IIIA), which can potentially be curatively treated. In the early tumor stages (tumor diameter ≤2 cm) sublobar resection (segmentectomy or atypical wedge resection) leads to a 5­year long-term survival comparable to lobectomy. The use of immunotherapy, especially within the framework of neoadjuvant treatment, is anticipated to change the surgical treatment of NSCLC in the future. With the introduction of lung cancer screening for certain risk groups in Germany planned for 2024, lung tumors can be expected to be diagnosed at earlier stages and more frequently curatively treated. This article provides an overview of the potential impact of lung cancer screening, modern minimally invasive surgical techniques and neoadjuvant treatment concepts for the surgical treatment of NSCLC.

Clinical effectiveness of robotic-assisted compared to open or video-assisted lobectomy in Germany: a real-world data analysis.

OBJECTIVES: Despite robotic-assisted thoracic surgery (RATS) lobectomy being on the rise in Europe, the majority of lobectomies in Germany are still performed with an open or thoracoscopic [video-assisted thoracic surgery (VATS)] approach. Empirical evidence in favour of RATS lobectomy is inconsistent. This retrospective cohort study investigates the impact of RATS lobectomy compared with open thoracic surgery (OPEN) and VATS lobectomy on short-term outcomes in Germany using multicentre real-world data. METHODS: Anonymized routine data from Germany from 2018 to 2020 were retrospectively analysed. These data were provided by 61 German hospitals. Propensity score matching with subsequent generalized linear models was performed for statistical analysis. Additionally, in order to test the robustness of the results, multivariable regression analyses with cluster-robust standard errors were used. RESULTS: A total of 2498 patients with lobectomy were identified: in 1345 patients OPEN, in 983 VATS and 170 a RATS lobectomy was performed. RATS-compared to OPEN and VATS-reduced length of stay (LOS) by 28% or 4.2 days [confidence interval: 2.9; 5.4] and by 13% or 1.6 days [confidence interval: 0.2; 3.0], respectively. The risk of pneumonia was reduced by 5.3 percentage points in the RATS group compared to both OPEN and VATS (P = 0.07/0.01). RATS-compared to an open approach-reduces the risk of blood transfusions by 8.8 percentage points (P < 0.001) and LOS on the intensive care unit (P < 0.001). CONCLUSIONS: This study provides strong support that RATS lobectomy outperforms OPEN or VATS lobectomy in terms of hospital LOS, and short-term in-hospital postoperative complications in the real-world scenario in Germany.

Deep Impact: Shifts of Native Cultivable Microbial Communities on Fresh Lettuce after Treatment with Plasma-Treated Water.

Foods consumed raw, such as lettuce, can host food-borne human-pathogenic bacteria. In the worst-case, these diseases cause to death. To limit illness and industrial losses, one innovative sanitation method is non-thermal plasma, which offers an extremely efficient reduction of living microbial biomass. Unfortunately, the total viable count (TVC), one of the most common methods for quantifying antimicrobial effects, provides no detailed insights into the composition of the surviving microbial community after treatment. To address this information gap, different special agars were used to investigate the reduction efficiency of plasma-treated water (PTW) on different native cultivable microorganisms. All tested cultivable microbial groups were reduced using PTW. Gram-negative bacteria showed a reduction of 3.81 log10, and Gram-positive bacteria showed a reduction of 3.49 log10. Fungi were reduced by 3.89 log10. These results were further validated using a live/dead assay. MALDI-ToF (matrix-assisted laser-desorption-ionization time-of-flight)-based determination was used for a diversified overview. The results demonstrated that Gram-negative bacteria were strongly reduced. Interestingly, Gram-positive bacteria and fungi were reduced by nearly equal amounts, but could still recover from PTW treatment. MALDI-ToF mainly identified Pseudomonas spp. and groups of Bacillus on the tested lettuce. These results indicate that the PTW treatment could efficiently achieve a ubiquitous, spectrum-wide reduction of microbial life.

Robotic thoracic surgery for neurogenic tumors.

OBJECTIVE: Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors. METHODS: This retrospective study is based on a prospectively created database that includes all RATS surgeries between 2018 and 2023. All patients with histologically confirmed neurogenic tumors were included in the study. The patients' medical and surgical records as well as radiological and pathological findings were analyzed. RESULTS: During a 5-year period, 27 patients underwent robotic resection of neurogenic tumors at a high-volume thoracic surgery center. Two patients had previously undergone posterior laminectomy for resection of the intraspinal components. The pathologies included schwannomas (18, 64%), ganglioneuromas (8, 29%), 1 paraganglioma, and 1 neurofibroma occurring close to a schwannoma unilaterally in the same patient. The median tumor size was 4.7 cm (range 0.9-11.4 cm). The median operating time was 69 minutes (range 27-169 minutes), and the median postoperative stay was 3 days (range 1-19 days). There was one conversion due to adhesions after a previous surgery. No major bleeding occurred. There was no perioperative mortality. Morbidity included a lymphatic fistula (n = 1), pneumonia (n = 1), prolonged air leak (n = 1), and 4 cases of postoperative pain persisting for more than 4 weeks. Neurological complications were mostly observed in patients with tumors located at the thoracic apex: 2 cases of Horner's syndrome, 2 cases with compensatory hyperhidrosis, 1 patient with paresis of the recurrent laryngeal nerve, and a T1 lesion resulting in a minor motor deficit of the small hand muscles (Medical Research Council grade 4) and hypoesthesia of the respective dermatome. CONCLUSIONS: RATS for thoracic neurogenic tumors is feasible and safe. Tumors at the thoracic apex are at high risk of neurological deficit and should be approached with care. Close interdisciplinary collaboration between neurosurgeons and thoracic surgeons is necessary for optimal patient selection and a good postoperative outcome.

[Deficit of trainees in thoracic surgery : Do we need to adapt or become extinct?] / Nachwuchsmangel in der Thoraxchirurgie : Müssen wir uns anpassen oder aussterben?

BACKGROUND: Although thoracic surgery is a challenging and versatile surgical specialty, a shortage of qualified and motivated thoracic surgery residents is expected in the coming years. In the inpatient setting, a shortage of approximately 7300 surgeons is expected. Therefore, there is an urgent need to attract more interested young medical students and improve the medical training of our next generation of surgeons. METHODS: To assess the current nationwide status quo among medical students, an online survey with 39 questions on participant demographics, medical education, interest in surgical and thoracic surgery training, and attractiveness of residency was designed. RESULTS: In all, 224 questionnaires were analyzed. Overall, there was a high level of interest in (thoracic-) surgery at the start of training. It should be noted that one third of the respondents did not know that the 'thoracic surgeon' is an independent specialist. This statement raises further questions about the presence of thoracic surgery in medical studies. When asked about typical characteristics that students associate with thoracic surgery, the majority answered 'a high level of practical activity'. The main reason they gave for not pursuing further surgical training was the unfavorable work-life balance. CONCLUSION: Students know exactly what they want for their future and where surgery has its weaknesses. They want transparent and practical training, a work-life balance, and recognition of their work and themselves.

Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy.

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

The pregnancy-associated protein glycodelin as a potential sex-specific target for resistance to immunotherapy in non-small cell lung cancer.

Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.

CT-guided needle biopsy is not associated with increased ipsilateral pleural metastasis.

INTRODUCTION: Histological confirmation of a lung tumor is the prerequisite for treatment planning. It has been suspected that CT-guided needle biopsy (CTGNB) exposes the patient to a higher risk of pleural recurrence. However, the distance between tumor and pleura has largely been neglected as a possible confounder when comparing CTGNB to bronchoscopy. METHODS: All patients with lung cancer histologically confirmed by bronchoscopy or CTGNB between 2010 and 2020 were enrolled and studied. Patients' medical histories, radiologic and pathologic findings and surgical records were reviewed. Pleural recurrence was diagnosed by pleural biopsy, fluid cytology, or by CT chest imaging showing progressive pleural nodules. RESULTS: In this retrospective unicenter analysis, 844 patients underwent curative resection for early-stage lung cancer between 2010 and 2020. Median follow-up was 47.5 months (3-137). 27 patients (3.2 %) with ipsilateral pleural recurrence (IPR) were identified. The distance of the tumor to the pleura was significantly smaller in patients who underwent CTGNB. A tendency of increased risk of IPR was observed in tumors located in the lower lobe (HR: 2.18 [±0.43], p = 0.068), but only microscopic pleural invasion was a significant independent predictive factor for increased risk of IPR (HR: 5.33 [± 0.51], p = 0.001) by multivariate cox analysis. Biopsy by CTGNB did not affect IPR (HR: 1.298 [± 0.39], p = 0.504). CONCLUSION: CTGNB is safe and not associated with an increased incidence of IPR in our cohort of patients. This observation remains to be validated in a larger multicenter patient cohort.

Combination of calretinin, MALAT1, and GAS5 as a potential prognostic biomarker to predict disease progression in surgically treated mesothelioma patients.

BACKGROUND: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival. METHODS: Between 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival. RESULTS: MALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %. CONCLUSION: MALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.

An International Registry Study of Early-Stage NSCLC treatment variations (LUCAEUROPE) in Europe and the USA highlighting variations.

OBJECTIVE: Harmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear. SUMMARY BACKGROUND DATA: Surgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization. METHODS: The retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010-2015. RESULTS: The study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes. CONCLUSIONS: Resection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment.

Diagnostic Potential of Supplemental Static and Dynamic 68Ga-FAPI-46 PET for Primary 18F-FDG-Negative Pulmonary Lesions.

PET using 68Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, 18F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently 18F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic 68Ga-FAPI-46 PET in the 18F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic 68Ga-FAPI-46 PET in addition to 18F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUVmax, SUVmean, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (68Ga-FAPI-46 in relation to18F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k 1, k 2, k 3, and k 4) were extracted from dynamic 68Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated 68Ga-FAPI-46 uptake, higher TBRs, and higher 68Ga-FAPI-46-to-18F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative 68Ga-FAPI-46-to-18F-FDG ratios regarding SUVmax and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: 68Ga-FAPI-46 PET is a powerful new tool for the assessment of single 18F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.

miR-Blood - a small RNA atlas of human blood components.

miR-Blood is a high-quality, small RNA expression atlas for the major components of human peripheral blood (plasma, erythrocytes, thrombocytes, monocytes, neutrophils, eosinophils, basophils, natural killer cells, CD4+ T cells, CD8+ T cells, and B cells). Based on the purified blood components from 52 individuals, the dataset provides a comprehensive repository for the expression of 4971 small RNAs from eight non-coding RNA classes.

Influence of plasma-treated air on surface microbial communities on freshly harvested lettuce.

Plant-based foods like lettuce are an important part of the human diet and worldwide industry. On a global scale, the number of food-associated illnesses increased in the last decades. Conventional lettuce sanitation methods include cleaning either with tap or chloritized water. Beside these water-consuming strategies, physical plasma is an innovative and effective possibility for food sanitation. Recent studies with plasma-treated water showed an effective reduction of the microbial load. Plasma-processed air (PPA) is another great opportunity to reduce the microbial load and save water. To test the efficiency of PPA, the surface microbiome of treated lettuce was analyzed via proliferation assays with special agars, live/dead assays and tests for respiratory activity of the microorganisms. PPA showed a reduction of the colony forming units (CFU/mL) on all tested microbial groups (Gram-negative and Gram-positive bacteria, yeasts and molds). These results were supported by the live/dead assay. For further insights, the PPA-ingredients were detected with Fourier Transformation Infrared Spectroscopy (FTIR), which revealed NO2, NO and N2O5 as the main reactive species in the PPA. In the future, PPA could be an outstanding, on-demand sanitation step for higher food safety standards, especially in situations where humidity and high temperature should be avoided.