Salivary Lipids of Patients with Non-Small Cell Lung Cancer Show Perturbation with Respect to Plasma.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. This study investigated 297 and 202 lipids in saliva and plasma samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (>2-fold, p < 0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes. Total triglycerides (TGs) increased (>2-3-fold) in plasma and saliva samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC for both sample types. A common ceramide species (d18:1/24:0) and phosphatidylinositol 38:4 decreased in both plasma and saliva by approximately two-fold. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. We identified 27 salivary and 10 plasma lipids as candidate markers for NSCLC through statistical evaluations. Moreover, this study highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

Fluorescent bioassay for SARS-CoV-2 detection using polypyrene-g-poly(ε-caprolactone) prepared by simultaneous photoinduced step-growth and ring-opening polymerizations.

The construction of a rapid and easy immunofluorescence bioassay for SARS-CoV-2 detection is described. We report for the first time a novel one-pot synthetic approach for simultaneous photoinduced step-growth polymerization of pyrene (Py) and ring-opening polymerization of ε-caprolactone (PCL) to produce a graft fluorescent copolymer PPy-g-PCL that was conjugated to SARS-CoV-2-specific antibodies using EDC/NHS chemistry. The synthesis steps and conjugation products were fully characterized using standard spectral analysis. Next, the PPy-g-PCL was used for the construction of a dot-blot assay which was calibrated for applications to human nasopharyngeal samples. The analytical features of the proposed sensor showed a detection range of 6.03-8.7 LOG viral copy mL-1 (Ct Scores: 8-25), the limit of detection (LOD), and quantification (LOQ) of 1.84 and 6.16 LOG viral copy mL-1, respectively. The repeatability and reproducibility of the platform had a coefficient of variation (CV) ranging between 1.2 and 5.9%. The fluorescence-based dot-blot assay was tested with human samples. Significant differences were observed between the fluorescence intensity of the negative and positive samples, with an overall correct response of 93.33%. The assay demonstrated a high correlation with RT-PCR data. This strategy opens new insights into simplified synthesis procedures of the reporter molecules and their high potential sensing and diagnosis applications.

Rapid Point-of-Care COVID-19 Diagnosis with a Gold-Nanoarchitecture-Assisted Laser-Scribed Graphene Biosensor.

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has revealed the urgent need for accurate, rapid, and affordable diagnostic tests for epidemic understanding and management by monitoring the population worldwide. Though current diagnostic methods including real-time polymerase chain reaction (RT-PCR) provide sensitive detection of SARS-CoV-2, they require relatively long processing time, equipped laboratory facilities, and highly skilled personnel. Laser-scribed graphene (LSG)-based biosensing platforms have gained enormous attention as miniaturized electrochemical systems, holding an enormous potential as point-of-care (POC) diagnostic tools. We describe here a miniaturized LSG-based electrochemical sensing scheme for coronavirus disease 2019 (COVID-19) diagnosis combined with three-dimensional (3D) gold nanostructures. This electrode was modified with the SARS-CoV-2 spike protein antibody following the proper surface modifications proved by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) characterizations as well as electrochemical techniques. The system was integrated into a handheld POC detection system operated using a custom smartphone application, providing a user-friendly diagnostic platform due to its ease of operation, accessibility, and systematic data management. The analytical features of the electrochemical immunoassay were evaluated using the standard solution of S-protein in the range of 5.0-500 ng/mL with a detection limit of 2.9 ng/mL. A clinical study was carried out on 23 patient blood serum samples with successful COVID-19 diagnosis, compared to the commercial RT-PCR, antibody blood test, and enzyme-linked immunosorbent assay (ELISA) IgG and IgA test results. Our test provides faster results compared to commercial diagnostic tools and offers a promising alternative solution for next-generation POC applications.

Simple workflow to repurpose SARS-CoV-2 swab/serum samples for the isolation of cost-effective antibody/antigens for proteotyping applications and diagnosis.

Supply shortage for the development and production of preventive, therapeutic, and diagnosis tools during the COVID-19 pandemic is an important issue affecting the wealthy and poor nations alike. Antibodies and antigens are especially needed for the production of immunological-based testing tools such as point-of-care tests. Here, we propose a simple and quick magnetic nanoparticle (MNP)-based separation/isolation approach for the repurposing of infected human samples to produce specific antibodies and antigen cocktails. Initially, an antibody cocktail was purified from serums via precipitation and immunoaffinity chromatography. Purified antibodies were conjugated onto MNPs and used as an affinity matrix to separate antigens. The characterization process was performed by ELISA, SDS-PAGE, electrochemistry, isothermal titration calorimetry, and LC-Q-TOF-MS/MS analyses. The MNP-separated peptides can be used for mass spectrometry-based as well as paper-based lateral flow assay diagnostic. The exploitation of the current workflow for the development of efficient diagnostic tools, specific treatments, and fundamental research can significantly impact the present or eventual pandemic. This workflow can be considered as a two birds, one stone-like strategy.

[Immunotherapy and multidisciplinary approach to treatment in lung cancer]. / Akciger kanserinde immünoterapi ve tedavide multidisipliner yaklasim.

Lung cancer remains as the main cause of cancer-related deaths worldwide. Over the last two decades, information about biology and pathogenesis of cancer has increased, immune checkpoint inhibitors (ICIs) have been introduced, and thus a significant period has started in treatment of solid cancers. This review discussed lung cancer in the framework of innovations in treatment, immunotherapy, and multidisciplinary approach to treatment. Non-small cell lung cancer (NSCLC) was the focal point of this article as it is the most frequent lung cancer type and the type of lung cancer which can ideally benefit from ICI treatment due to its characteristics. This review is the first review in Turkish language, which aimed to raise the multidisciplinary awareness about immunotherapy approach in lung cancer treatment in all branches, primarily in chest diseases, and to provide information about its management. Moreover, this review has importance as it presents the remarkable results of recent clinical trials on the use of ICIs in NSCLC treatment. Immunotherapy has initiated a new era in cancer treatment; the specific mechanism of action of ICIs has resulted in a group of some new adverse events, among which pneumonitis is particularly important and when necessary, patients are needed to be consulted with relevant specialties about adverse events. Lung cancer treatment should be planned specific to each patient by considering patient characteristics, histological features, and genetic status and specialty areas of chest diseases, thoracic surgery, medical oncology, radiation oncology, pathology, and radiology should collaborate together for diagnostic evaluation and optimal treatment of a lung cancer patient. Moreover, family physicians may have an important role in early diagnosis of lung cancer and in preventing lung cancer by encouraging their patients regarding tobacco cessation. Moreover, screening studies for lung cancer should be targeted to create awareness in society and for early diagnosis.

Achieving Thoracic Oncology data collection in Europe: a precursor study in 35 Countries.

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.

Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial.

BACKGROUND: Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. We aimed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer (NSCLC) after platinum-based therapy. METHODS: In this multicentre, double-blind, randomised phase 3 trial (REVEL), we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen. Patients were randomly allocated (1:1) with a centralised, interactive voice-response system (stratified by sex, region, performance status, and previous maintenance therapy [yes vs no]) to receive docetaxel 75 mg/m(2) and either ramucirumab (10 mg/kg) or placebo on day 1 of a 21 day cycle until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was overall survival in all patients allocated to treatment. We assessed adverse events according to treatment received. This study is registered with ClinicalTrials.gov, number NCT01168973. FINDINGS: Between Dec 3, 2010, and Jan 24, 2013, we screened 1825 patients, of whom 1253 patients were randomly allocated to treatment. Median overall survival was 10·5 months (IQR 5·1-21·2) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months (4·2-18·0) for 625 patients who received placebo plus docetaxel (hazard ratio 0·86, 95% CI 0·75-0·98; p=0·023). Median progression-free survival was 4·5 months (IQR 2·3-8·3) for the ramucirumab group compared with 3·0 months (1·4-6·9) for the control group (0·76, 0·68-0·86; p<0·0001). We noted treatment-emergent adverse events in 613 (98%) of 627 patients in the ramucirumab safety population and 594 (95%) of 618 patients in the control safety population. The most common grade 3 or worse adverse events were neutropenia (306 patients [49%] in the ramucirumab group vs 246 [40%] in the control group), febrile neutropenia (100 [16%] vs 62 [10%]), fatigue (88 [14%] vs 65 [10%]), leucopenia (86 [14%] vs 77 [12%]), and hypertension (35 [6%] vs 13 [2%]). The numbers of deaths from adverse events (31 [5%] vs 35 [6%]) and grade 3 or worse pulmonary haemorrhage (eight [1%] vs eight [1%]) did not differ between groups. Toxicities were manageable with appropriate dose reductions and supportive care. INTERPRETATION: Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC. FUNDING: Eli Lilly.

Hypersensitivity to chemotherapeutics: a cross sectional study with 35 desensitisations.

BACKGROUND: Chemotherapy is one of the main treatments for lung cancer, and in these patients, discontinuation of treatment due to uncontrollable hypersensitivity reactions (HSRs) is an important problem. AIM: To determine the frequency of HSRs during chemotherapy and to review current approaches. METHODS: We did a cross sectional study in patients undergoing chemotherapy for lung cancer in a reference chemotherapy unit from January 2012 to January 2013. Patients who developed immediate-HSRs or delayed-HSRs to chemotherapeutics and gave consent were included into study. The effectiveness of a standardised 12-step "rapid drug desensitisation" (RDD) procedure was investigated in patients with immediate-HSRs. RESULTS: In total, 1,099 cycles of chemotherapy were administered to 292 patients in 1 year. We observed ten HSRs, during ten cycles in ten patients (~3 % of the patients). Two HSRs were delayed-type, eight were immediate-type at grade 1-3. Of those with immediate-type HSR, five patients with grade 2-3, and additional two referred patients with grade 4 HSRs were successfully given their culprit drug in 35 cycles of chemotherapy with 12-step or modified 20-step RDD protocol. CONCLUSIONS: HSRs to chemotherapeutics are not so rare. Premedication alone does not prevent such reactions. The results of RDD treatment look promising for continuing treatment with the culprit chemotherapeutic agent.

An unexpected cause of hemoptysis: endobronchial lipomatous hamartoma.

Hamartomas are the most common benign tumors of the lung. Endobnronchial hamartomas are even rarer and infrequently causes hemoptysis. We report a case of endobronchial hamartoma that was originating from a segment bronchus and invisible in chest X-ray. A 63-year-old man was admitted to hospital with hemoptysis. A CT scan revealed endobronchial mass obstructing anterior bronchus of the right lower lob of the right lung. It wasn't radiographically presented. Flexible bronchoscopy detected a polypoid mass (1.5 x 1.0 cm) that arising from the posterior wall of the anterior segment of right lower lob. Histopathologic examination revealed lipoumatous hamartoma. It was resected with an electro-surgical snare. Cryotherapy was applied to residual lesion on surface of the bronchus. The patient was successfully recovered. In conclusion, lipoumatous hamartoma may presented as rare cause of hemoptysis. Endoscopic treatment is safe and currently modality used for select cases.

Organotypic lung tissue culture as a preclinical model to study host- influenza A viral infection: A case for repurposing of nafamostat mesylate.

Reliable and effective models for recapitulation of host-pathogen interactions are imperative for the discovery of potential therapeutics. Ex vivo models can fulfill these requirements as the multicellular native environment in the tissue is preserved and be utilized for toxicology, vaccine, infection and drug efficacy studies due to the presence of immune cells. Drug repurposing involves the identification of new applications for already approved drugs that are not related to the prime medical indication and emerged as a strategy to cope with slow pace of drug discovery due to high costs and necessary phases to reach the patients. Within the scope of the study, broad-spectrum serine protease inhibitor nafamostat mesylate was repurposed to inhibit influenza A infection and evaluated by a translational ex vivo organotypic model, in which human organ-level responses can be achieved in preclinical safety studies of potential antiviral agents, along with in in vitro lung airway culture. The safe doses were determined as 10 µM for in vitro, whereas 22 µM for ex vivo to be applied for evaluation of host-pathogen interactions, which reduced virus infectivity, increased cell/tissue viability, and protected total protein content by reducing cell death with the inflammatory response. When the gene expression levels of specific pro-inflammatory, anti-inflammatory and cell surface markers involved in antiviral responses were examined, the significant inflammatory response represented by highly elevated mRNA gene expression levels of cytokines and chemokines combined with CDH5 downregulated by 5.1-fold supported the antiviral efficacy of NM and usability of ex vivo model as a preclinical infection model.

A randomized, double-blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel.

: The effect of repeated doses of aflibercept on ventricular repolarization in cancer patients was evaluated in an intensive electrocardiogram trial. This randomized, placebo-controlled, double-blind trial was conducted in 87 treated solid tumor patients. Treatment was with 6 mg/kg aflibercept, 1-hour intravenous (n = 43), or placebo (n = 44), combined with ≤75 mg/m docetaxel, every 3 weeks. Electrocardiograms were collected for 6 hours posttreatment using digital 12-lead Holter recorders, at day 1, in cycles 1 and 3. Free and vascular endothelial growth factor-bound aflibercept concentrations were assessed at similar time points. Eighty-four patients (43 placebo and 41 aflibercept) were evaluable for QT interval, Fridericia correction (QTcF) at cycle 1 and 59 (31 placebo and 28 aflibercept) at cycle 3. During cycle 3, from 30 minutes to 6 hours after the start of aflibercept, the maximum observed upper limit of the QTcF 90% confidence interval was 16 ms, for a mean of 8.4 ms. QTcF prolongation above 480 ms and 60 ms above baseline was observed in 1 aflibercept patient (2%). The slope of the relationship between free aflibercept concentration and QTcF was 0.048 (95% confidence interval, 0.013-0.082), corresponding to a 5-ms increase per 100 µg/mL increase in concentration. These results exclude a clinically important effect of aflibercept on ventricular repolarization.

Conversion of specific lncRNAs to biomarkers in exhaled breath condensate samples of patients with advanced stage non-small-cell lung cancer.

Objectives: Lung cancer (LC) is one of the most prevalent cancers with the highest fatality rate worldwide. Long noncoding RNAs (lncRNAs) are being considered potential new molecular targets for early diagnosis, follow-up, and individual treatment decisions in LC. Therefore, this study evaluated whether lncRNA expression levels obtained from exhaled breath condensate (EBC) samples play a role in the occurrence of metastasis in the diagnosis and follow-up of patients with advanced lung adenocarcinoma (LA). Methods: A total of 40 patients with advanced primary LA and 20 healthy controls participated in the study. EBC samples were collected from patients (during diagnosis and follow-up) and healthy individuals for molecular analysis. Liquid biopsy samples were also randomly obtained from 10 patients with LA and 10 healthy people. The expression of lncRNA genes, such as MALAT1, HOTAIR, PVT1, NEAT1, ANRIL, and SPRY4-IT1 was analyzed using cfRNA extracted from all clinical samples. Results: In the diagnosis and follow-up of patients with LA, lncRNA HOTAIR (5-fold), PVT1 (7.9-fold), and NEAT1 (12.8-fold), PVT1 (6.8-fold), MALAT1 (8.4-fold) expression levels were significantly higher than those in healthy controls, respectively. Additionally, the distinct lncRNA expression profiles identified in EBC samples imply that decreased ANRIL-NEAT1 and increased ANRIL gene expression levels can be used as biomarkers to predict the development of bone and lung metastases, respectively. Conclusion: EBC is an innovative, easily reproducible approach for predicting the development of metastases, molecular diagnosis, and follow-up of LC. EBC has shown potential in elucidating the molecular structure of LC, monitoring changes, and discovering novel biomarkers.

Design of Polymeric Surfaces as Platforms for Streamlined Cancer Diagnostics in Liquid Biopsies.

Minimally invasive approaches for cancer diagnosis are an integral step in the quest to improve cancer survival. Liquid biopsies such as blood samples are matrices explored to extract valuable information about the tumor and its state through various indicators, such as proteins, peptides, tumor DNA, or circulating tumor cells. Although these markers are scarce, making their isolation and detection in complex matrices challenging, the development in polymer chemistry producing interesting structures, including molecularly imprinted polymers, branched polymers, nanopolymer composites, and hybrids, allowed the development of enhanced platforms with impressive performance for liquid biopsies analysis. This review describes the latest advances and developments in polymer synthesis and their application for minimally invasive cancer diagnosis. The polymer structures improve the operational performances of biosensors through various processes, such as increased affinity for enhanced sensitivity, improved binding, and avoidance of non-specific interactions for enhanced specificity. Furthermore, polymer-based materials can be a tremendous help in signal amplification of usually low-concentrated targets in the sample. The pros and cons of these materials, how the synthesis process affects their performance, and the device applications for liquid biopsies diagnosis will be critically reviewed to show the essentiality of this technology in oncology and clinical biomedicine.

Prognostic and predictive role of liquid biopsy in lung cancer patients.

Introduction: Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC. Methods: One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene. Results: Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy. Discussion: The results showed that "liquid biopsy" is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS: Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. CONCLUSION: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

A drug-responsive multicellular human spheroid model to recapitulate drug-induced pulmonary fibrosis.

Associated with a high mortality rate, pulmonary fibrosis (PF) is the end stage of several interstitial lung diseases. Although many factors are linked to PF progression, initiation of the fibrotic process remains to be studied. Current research focused on generating new strategies to gain a better understanding of the underlying disease mechanism as the animal models remain insufficient to reflect human physiology. Herein, to account complex cellular interactions within the fibrotic tissue, a multicellular spheroid model where human bronchial epithelial cells incorporated with human lung fibroblasts was generated and treated with bleomycin (BLM) to emulate drug-induced PF. Recapitulating the epithelial-interstitial microenvironment, the findings successfully reflected the PF disease, where excessive alpha smooth muscle actin and collagen type I secretion were noted along with the morphological changes in response to BLM. Moreover, increased levels of fibrotic linked COL13A1, MMP2, WNT3 and decreased expression level of CDH1 provide evidence for the model reliability on fibrosis modelling. Subsequent administration of the Food and Drug Administration approved nintedanib and pirfenidone anti-fibrotic drugs proved the drug-responsiveness of the model.

Indiscriminate SARS-CoV-2 multivariant detection using magnetic nanoparticle-based electrochemical immunosensing.

The increasing mutation frequency of the SARS-CoV-2 virus and the emergence of successive variants have made correct diagnosis hard to perform. Developing efficient and accurate methods to diagnose infected patients is crucial to effectively mitigate the pandemic. Here, we developed an electrochemical immunosensor based on SARS-CoV-2 antibody cocktail-conjugated magnetic nanoparticles for the sensitive and accurate detection of the SARS-CoV-2 virus and its variants in nasopharyngeal swabs. The application of the antibody cocktail was compared with commercially available anti-SARS-CoV-2 S1 (anti-S1) and anti-S2 monoclonal antibodies. After optimization and calibration, the limit of detection (LOD) determination demonstrated a LOD = 0.53-0.75 ng/mL for the antibody cocktail-based sensor compared with 0.93 ng/mL and 0.99 ng/mL for the platforms using anti-S1 and anti-S2, respectively. The platforms were tested with human nasopharyngeal swab samples pre-diagnosed with RT-PCR (10 negatives and 40 positive samples). The positive samples include the original, alpha, beta, and delta variants (n = 10, for each). The polyclonal antibody cocktail performed better than commercial anti-S1 and anti-S2 antibodies for all samples reaching 100% overall sensitivity, specificity, and accuracy. It also showed a wide range of variants detection compared to monoclonal antibody-based platforms. The present work proposes a versatile electrochemical biosensor for the indiscriminate detection of the different variants of SARS-CoV-2 using a polyclonal antibody cocktail. Such diagnostic tools allowing the detection of variants can be of great efficiency and economic value in the fight against the ever-changing SARS-CoV-2 virus.

'All In One' SARS-CoV-2 variant recognition platform: Machine learning-enabled point of care diagnostics.

Point of care (PoC) devices are highly demanding to control current pandemic, originated from severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Though nucleic acid-based methods such as RT-PCR are widely available, they require sample preparation and long processing time. PoC diagnostic devices provide relatively faster and stable results. However they require further investigation to provide high accuracy and be adaptable for the new variants. In this study, laser-scribed graphene (LSG) sensors are coupled with gold nanoparticles (AuNPs) as stable promising biosensing platforms. Angiotensin Converting Enzyme 2 (ACE2), an enzymatic receptor, is chosen to be the biorecognition unit due to its high binding affinity towards spike proteins as a key-lock model. The sensor was integrated to a homemade and portable potentistat device, wirelessly connected to a smartphone having a customized application for easy operation. LODs of 5.14 and 2.09 ng/mL was achieved for S1 and S2 protein in the linear range of 1.0-200 ng/mL, respectively. Clinical study has been conducted with nasopharyngeal swabs from 63 patients having alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) variants, patients without mutation and negative patients. A machine learning model was developed with accuracy of 99.37% for the identification of the SARS-Cov-2 variants under 1 min. With the increasing need for rapid and improved disease diagnosis and monitoring, the PoC platform proved its potential for real time monitoring by providing accurate and fast variant identification without any expertise and pre sample preparation, which is exactly what societies need in this time of pandemic.

[Hemophagocytic syndrome due to lung infection: a case report]. / Akciger infeksiyonuna bagli gelisen hemofagositik sendrom: Olgu sunumu.

A 31-year-old man with pneumonia and ampiema was treated with antibiotics and drainage. Hemophagocytic syndrome, characterized with pancytopenia was arised during this treatment. Nosocomial infection due to pancytopenia was treated with antibiotics. Hemophagocytic syndrome was recovered spontaneously after the treatment of this nosocomial infection. Such a severe hemophagocytic syndrome due to infection is a rare condition.

Quantitative paper-based dot blot assay for spike protein detection using fuchsine dye-loaded polymersomes.

Real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays are the gold standard for virus diagnosis. Point-of-care (POC) technologies have shown great progress during this period. Herein, we propose a novel fuchsine dye-loaded polymersome for a colorimetric paper-based dot blot spike protein diagnostic assay for COVID-19 via smartphone-assisted sensing. The prepared platform aimed to create an adaptable tool that competes with traditional nanoparticle-based assays employing gold and silver. Analytical characterization and application of the testing platform showed high sensitivity (10 times better than gold nanoparticles), stability, fast turnaround, and reproducibility. The potential and possibilities demonstrated by the current platform could be observed in its adaptability for different markers and pathologies. In addition, smartphone-assisted sensing emphasizes the ability to use the tool at home by common peoples which can lower the burden on the healthcare facilities and reach more underdeveloped regions.