Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles

Lipid and polymer stabilized microbubbles are used in medicine as contrast agents for ultrasound imaging and are being developed for the delivery of water soluble drugs to diseased areas of the body. However, many new therapeutics exhibit poor water solubility or stability, which has led to the requirement for the development of effective hydrophobic drug delivery systems. This study presents a new method to produce microbubbles coated with an oil layer capable of encapsulating hydrophobic drugs and suitable for targeted, triggered drug release. This new method utilizes highly controllable flow-focusing microfluidics with lipid oil nanodroplets self-assembling and spreading at gas–aqueous interfaces. Oil layer inside microbubbles were produced with diameters of 2.4±0.3 μm (s.d., 1.6 μm) and at concentrations up to 106 bubbles per milliliter. The mechanism of oil layer inside microbubble assembly and stability were characterized using methods including contact angle measurements, quartz crystal microbalance with dissipation monitoring and fluorescence resonance energy transfer imaging

Physical biomarkers of disease progression:on-chip monitoring of changes in mechanobiology of colorectal cancer cells

Disease can induce changes to subcellular components, altering cell phenotype and leading to measurable bulk-material mechanical properties. The mechanical phenotyping of single cells therefore offers many potential diagnostic applications. Cells are viscoelastic and their response to an applied stress is highly dependent on the magnitude and timescale of the actuation. Microfluidics can be used to measure cell deformability over a wide range of flow conditions, operating two distinct flow regimes (shear and inertial) which can expose subtle mechanical properties arising from subcellular components. Here, we investigate the deformability of three colorectal cancer (CRC) cell lines using a range of flow conditions. These cell lines offer a model for CRC metastatic progression; SW480 derived from primary adenocarcinoma, HT29 from a more advanced primary tumor and SW620 from lymph-node metastasis. HL60 (leukemia cells) were also studied as a model circulatory cell, offering a non-epithelial comparison. We demonstrate that microfluidic induced flow deformation can be used to robustly detect mechanical changes associated with CRC progression. We also show that single-cell multivariate analysis, utilising deformation and relaxation dynamics, offers potential to distinguish these different cell types. These results point to the benefit of multiparameter determination for improving detection and accuracy of disease stage diagnosis

Developing a Raman spectroscopy-based tool to stratify patient response to pre-operative radiotherapy in rectal cancer

Rectal cancer patients frequently receive pre-operative radiotherapy (RT), prior to surgical resection. However, colorectal cancer is heterogeneous and the degree of tumour response to pre-operative RT is highly variable. There are currently no clinically approved methods of predicting response to RT, and a significant proportion of patients will show no clinical benefit, despite enduring the side-effects. We evaluated the use of Raman spectroscopy (RS), a non-destructive technique able to provide the unique chemical fingerprint of tissues, as a potential tool to stratify patient response to pre-operative RT. Raman measurements were obtained from the formalin-fixed, paraffin-embedded (FFPE) pre-treatment biopsy specimens of 20 rectal cancer patients who received pre-operative RT. A principal component analysis and linear discriminant analysis algorithm was able to classify patient response to pre-operative RT as good or poor, with an accuracy of 86.04 ± 0.14% (standard error). Patients with a good response to RT showed greater contributions from protein-associated peaks, whereas patients who responded poorly showed greater lipid contributions. These results demonstrate that RS is able to reliably classify tumour response to pre-operative RT from FFPE biopsies and highlights its potential to guide personalised cancer patient treatment

Tandem fluorescence and Raman (fluoRaman) characterisation of a novel photosensitiser in colorectal cancer cell line SW480

The development of new imaging tools, molecules and modalities is crucial to understanding biological processes and the localised cellular impact of bioactive compounds. A small molecule photosensitiser, DC473, has been designed to be both highly fluorescent and to exhibit a strong Raman signal in the cell-silent region of the Raman spectrum due to a diphenylacetylene structure. DC473 has been utilised to perform a range of novel tandem fluorescence and Raman (fluoRaman) imaging probe experiments, enabling a thorough examination of the compound’s cellular localisation, exemplified in colorectal cancer cells (SW480). This multifunctional fluoRaman imaging modality has revealed the presence of the compound in lipid droplets and only weak signal in the cytosol, where both Raman and fluorescence results show the presence of the fluoRaman imaging probe. In addition, Raman microscopy detected the compound in a cell compartment we labelled as the nucleolus, where fluorescence microscopy did not detect the fluoRaman probe due to solvatochromatic effects in a local polar environment. This last finding was only possible with the use of tandem confocal Raman and fluorescence methods. By following the approach detailed herein, incorporation of strong Raman functional groups into fluorophores can enable a plethora of fluoRaman experiments, shedding further light on an imaging probe or potential drug compound’s cellular behaviour and biological activity

Highly Scalable, Wearable Surface‐Enhanced Raman Spectroscopy

The last two decades have witnessed a dramatic growth of wearable sensor technology, mainly represented by flexible, stretchable, on-skin electronic sensors that provide rich information of the wearer's health conditions and surroundings. A recent breakthrough in the field is the development of wearable chemical sensors based on surface-enhanced Raman spectroscopy (SERS) that can detect molecular fingerprints universally, sensitively, and noninvasively. However, while their sensing properties are excellent, these sensors are not scalable for widespread use beyond small-scale human health monitoring due to their cumbersome fabrication process and limited multifunctional sensing capabilities. Here, a highly scalable, wearable SERS sensor is demonstrated based on an easy-to-fabricate, low-cost, ultrathin, flexible, stretchable, adhesive, and biointegratable gold nanomesh. It can be fabricated in any shape and worn on virtually any surface for label-free, large-scale, in situ sensing of diverse analytes from low to high concentrations (10–106 × 10−9 m). To show the practical utility of the wearable SERS sensor, the sensor is tested for the detection of sweat biomarkers, drugs of abuse, and microplastics. This wearable SERS sensor represents a significant step toward the generalizability and practicality of wearable sensing technology

Responses to 10 common criticisms of anti-racism action in STEMM

The wrongful murders of Black individuals during 2020 (including George Floyd, Breonna Taylor, Ahmaud Aubery, and others), compounded by a long history of similar incidents, inspired protests around the world against racism and police brutality. The growing anti-racism movement sparked conversations within science, technology, engineering, mathematics, and medicine (STEMM) surrounding ways to combat racial bias in our respective fields. A spotlight was placed on the discriminatory history of scientific research and medical practice, as well as the problematic modern-day policies that perpetuate the lack of racial diversity and equity in STEMM. While observing and participating in recent discussions about the racism that pervades institutions, departments, and scientific discourse, we have noticed a set of standard arguments against anti-racism action within STEMM. Ten of these arguments are laid out in this manuscript and paired with evidence-based counterarguments. Notably, while this manuscript is primarily centered around a United States perspective, most of our arguments and suggested actions remain applicable to other countries as well. It is crucial for a STEMM anti-racism movement to extend beyond national borders, reflecting the international nature of scientific research and collaboration. This team of authors represents a collaboration between scientists from historically marginalized groups and their allies. By compiling published academic literature, we hope to directly confront racist ideology in STEMM with evidence-based arguments while simultaneously amplifying the research and perspectives of scholars of color. Our broad goal in articulating this information is to facilitate more productive conversations (and, in turn, tangible systemic changes) toward addressing racial discrimination within STEMM

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study

Background: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. Aim: To assess the daily clinical practice approach to LyP and the response to first-line treatments. Methods: This was a retrospective study enrolling 252 patients with LyP. Results: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. Conclusions: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks