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Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer.

Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non–small-cell lung cancer. SCLC has high metastatic potential, resulting in a clinically poor prognosis. Early concurrent chemo-radiation is the standard of care for limited-stage SCLC (LS-SCLC). Prophylactic cranial irradiation (PCI) is recommended for patients with LS-SCLC without progression of disease after initial therapy. A combination of etoposide and cisplatin or carboplatin remains the mainstay of first-line treatment for ES-SCLC, with the addition of atezolizumab, now becoming standard. Most SCLCs initially respond to therapy but almost invariably recur. Topotecan and amrubicin (in Japan) remain the primary chemotherapy options for relapsed SCLC. Immunotherapy, including nivolumab with or without ipilimumab, is now available for refractory disease. In general, the poor prognosis of SCLC has not improved significantly for more than 3 decades. Recently, next-generation molecular profiling studies have identified new therapeutic targets for SCLC. A variety of proapoptotic agents, compounds capitalizing on DNA-repair defects, immunotherapy agents, and antibody–drug conjugates are being evaluated in SCLC, with a number of them showing early promise.

The handling of single cells is of great importance in applications such as cell line development or single-cell analysis, e.g., for cancer research or for emerging diagnostic methods. This review provides an overview of technologies that are currently used or in development to isolate single cells for subsequent single-cell analysis. Data from a dedicated online market survey conducted to identify the most relevant technologies, presented here for the first time, shows that FACS (fluorescence activated cell sorting) respectively Flow cytometry (33% usage), laser microdissection (17%), manual cell picking (17%), random seeding/dilution (15%), and microfluidics/lab-on-a-chip devices (12%) are currently the most frequently used technologies. These most prominent technologies are described in detail and key performance factors are discussed. The survey data indicates a further increasing interest in single-cell isolation tools for the coming years. Additionally, a worldwide patent search was performed to screen for emerging technologies that might become relevant in the future. In total 179 patents were found, out of which 25 were evaluated by screening the title and abstract to be relevant to the field.

Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. A well described biomarker of non-responsiveness to immune checkpoint inhibitors is the absence or low presence of lymphocytes in the tumour microenvironment, so-called cold tumours. There are five mechanisms of action that have the potential to turn cold tumours into so-called hot and inflamed tumours, hence increasing the tumour's responsiveness to immunotherapy—increasing local inflammation, neutralising immunosuppression at the tumour site, modifying the tumour vasculature, targeting the tumour cells themselves, or increasing the frequency of tumour-specific T cells. In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.

Globally, there is growing concern about the health risks of water and air pollution. The U.S. Environmental Protection Agency (EPA) has developed a list of priority pollutants containing 129 different chemical compounds. All of these chemicals are of significant interest due to their serious health and safety issues. Permanent exposure to some concentrations of these chemicals can cause severe and irrecoverable health effects, which can be easily prevented by their early identification. Molecularly imprinted polymers (MIPs) offer great potential for selective adsorption of chemicals from water and air samples. These selective artificial bio(mimetic) receptors are promising candidates for modification of sensors, especially disposable sensors, due to their low-cost, long-term stability, ease of engineering, simplicity of production and their applicability for a wide range of targets. Herein, innovative strategies used to develop MIP-based sensors for EPA priority pollutants will be reviewed.

Purpose Anterior knee pain (AKP) is common following total knee arthroplasty. The tibial tuberosity trochlear groove distance (TTTG) influences patellofemoral joint loading in the native knee. Increased TTTG may lead to maltracking of the patella and anterior knee pain. The purpose of this study was to investigate potential changes in TTTG following total knee arthroplasty (TKA). Methods TTTG was measured on preoperative CT data on a consecutive series of patients scheduled to receive TKA with patient-specific instrumentation, and compared to a computer simulation of the postoperative TTTG. Preoperative TTTG was measured with a 3D planning software in 250 knees. The postoperative result was simulated and TTTG measured within the software. Three different groups were analysed: neutral (180° ± 3) ( n  = 50), valgus (> 190°) ( n  = 100), and varus (< 170°) ( n  = 100). Results Median preoperative to simulated postoperative TTTG decreased from 15.0 [interquartile range (IQR) 6.0] mm to 6.5 (IQR 5.0) mm for all axes combined. A significant postoperative reduction of TTTG was found in each group ( p  < 0.001). The mean change in TTTG did not differ significantly between the groups [− 8.8 (IQR 5.5) mm neutral, − 8.3 (IQR 7.0) mm valgus, − 7.5 (IQR 5.8) mm varus, p  = 0.223]. Conclusion This computer-based study suggests that mechanically aligned TKA significantly decreases TTTG distance in neutral, valgus and varus knees, assuming that the postoperative result coincides with the preoperative planning. Further study is warranted to evaluate the clinical relevance of this finding.

Certain applications require a contactless measurement to eliminate the risk of sensor-induced sample contamination. Examples can be found in chemical process control, biotechnology or medical technology. For instance, in critically ill patients requiring renal replacement therapy, continuous in-line monitoring of blood conductivity as a measure for sodium should be considered. A differential inductive sensing system based on a differential transformer using a specific flow chamber has already proven suitable for this application. However, since the blood in renal replacement therapy is carried in plastic tubing, a direct measurement through the tubing offers a contactless method. Therefore, in this work we present a differential transformer for measuring directly through electrically non-conductive tubing by winding the tube around the ferrite core of the transformer. Here, the dependence of the winding type and the number of turns of the tubing on the sensitivity has been analyzed by using a mathematical model, simulations and experimental validation. A maximum sensitivity of 364.9 mV/mol/L is measured for radial winding around the core. A longitudinal winding turns out to be less effective with 92.8 mV/mol/L. However, the findings prove the ability to use the differential transformer as a truly contactless sensing system.

Amino acids belong to the most important compounds for life. They are structural components of proteins and required for growth and maintenance of cells. Essential amino acids cannot be produced by the organism and must be ingested through the nutrition. Therefore, the detection of amino acids is of great interest when analyzing cell culture media and nutrition. In this work, we present a split-ring resonator as a simple but sensitive detector for amino acids. Split-ring resonators are RLC resonant circuits with a split capacitance and thus a resonance frequency that depends on the electromagnetic properties of a liquid sample at the split capacitance. Here, the split capacitance is an interdigital structure for highest sensitivity and covered with a fluidic channel for flow through experiments. First measurements with a vector network analyzer show detection limits in the range from 105 µM for glutamic acid to 1564 µM for isoleucine, depending on the electromagnetic properties of the tested amino acids. With an envelope detector for continuous recording of the resonance frequency, the split-ring resonator can be used in ion chromatography. At a flow rate of 0.5 mL/min, it reaches limits of detection of 485 µM for aspartic acid and 956 µM for lysine.

Purpose Recent data suggest that individual morphologic factors should be respected to restore preoperative patellofemoral alignment and thus reduce the likelihood of anterior knee pain. The goal of this study was to investigate the effect of excessive femoral torsion (FT) on clinical outcome of TKA. Methods Patients who underwent TKA and complete preoperative radiographic evaluation including a long-leg radiograph and CT scan were included. 51 patients showed increased FT of > 20° and were matched for age/sex to 51 controls (FT < 20°). Thirteen patients were lost to follow-up. Thirty-eight matched pairs were compared after a 2 year follow-up clinically (Kujala and patellofemoral score for TKA) and radiographically (FT, frontal leg axis, TT-TG, patellar thickness, patellar tilt, and lateral displacement of patella). Functional alignment of TKA was performed (hybrid-technique). All patellae were denervated but no patella was resurfaced. Results There was no significant difference between clinical scores two years after surgery between patients with normal and excessive FT (n.s.). Kujala score was 64.3 ± 16.7 versus 64.8 ± 14.4 (n.s.), and patellofemoral score for TKA was 74.3 ± 21 versus 78.5 ± 20.7 (n.s.) for increased FT group and control group, respectively. There was no correlation between preoperative FT and clinical scores. Other radiographic parameters were similar between both groups. No correlations between clinical outcomes and preoperative/postoperative frontal leg axis or total leg axis correction were found (n.s.). Conclusion If the leg axis deformity is corrected to a roughly neutral alignment during cemented TKA, including patellar denervation, then excessive FT was not associated with patellofemoral pain or instability. Level of evidence. Prospective comparative study, level II.

The electrical and dielectric properties of liquids can be used for sensing. Specific applications, e.g., the continuous in-line monitoring of blood conductivity as a measure of the sodium concentration during dialysis treatment, require contactless measuring methods to avoid any contamination of the medium. The differential transformer is one promising approach for such applications, since its principle is based on a contactless, magnetically induced conductivity measurement. The objective of this work is to investigate the impact of the geometric parameters of the sample or medium under test on the sensitivity and the noise of the differential transformer to derive design rules for an optimized setup. By fundamental investigations, an equation for the field penetration depth of a differential transformer is derived. Furthermore, it is found that increasing height and radius of the medium is accompanied by an enhancement in sensitivity and precision.