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High intensity focused ultrasound (HIFU) is a form of thermal ablation technique, which can treat a variety of medical afflictions. One promising therapeutic use is the permanent destruction of nerves non-invasively in patients with severe spasticity or certain types of pain (e.g., phantom limb pain). To this end, HIFU requires ultrasound guidance, which allows the non-invasive, target-specific deposition of thermal energy to the targeted nerve, thereby blocking axonal conduction. In this paper, a composite system comprising both ultrasound-imaging and HIFU therapy was developed and used to induce localized non-invasive nerve blockage in an in vivo large animal study. Five pigs were used with the femoral nerve as the target. Calibrated needle thermocouples inserted at the target site were employed to monitor the target tissue temperature. The degree of nerve blockage was assessed by measuring compound action potential (CAP) signal with a clinical nerve electrophysiology system before and after HIFU exposures. An average CAP signal amplitude reduction of 49% of baseline with a standard deviation of 9% was observed after 20–30 min post exposure. These results demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a potential non-invasive nerve ablation method., The complete portable HIFU/Imaging system is shown on the left. A close up of the applicator is shown on the right. The imaging probe in the middle of the HIFU transducer. The clear acrylic cylinder is the water jacket which can be sealed with a latex membrane.

Purpose: A real-time noninvasive thermometry technique is required to estimate the temperature distribution during hyperthermia to monitor and control the treatment. The main objective of this study is to demonstrate the possibility of detecting change in backscatter energy (CBE) of acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues in which the temperature was locally increased within the hyperthermia regime. Materials and Methods: A peristaltic pump was used to circulate hot water through a needle inserted inside the samples to locally increase the temperature from 26?C to 46 ?C. The CBE of acoustic harmonics were used to identify the location of temperature changes in the samples. A conventional echo-shift technique was also implemented for comparison. Data collection was performed for two conditions to investigate the effect of motion on both techniques by: (1) inducing vibration in the sample through the peristatic pump and, (2) subsequently with no sample vibration while the pump was off. Results: Harmonics were able to determine the location of temperature rise in the presence and absence of vibration. In gel phantom, the mean contrast to noise ratio (CNR) in CBE maps reduced by a factor of 0.86 due to vibration whereas in gradient maps the CNR reduced by a factor of 8.3. Conclusions: The findings of this study suggest that the change in backscatter energy of acoustic harmonics can potentially be used to develop a noninvasive ultrasound-based thermometry technique with lower susceptibility to motion artifacts compared to the echo-shift method.

Background Natural biomaterials from bone-like minerals derived from avian eggshells have been considered as promising bone substitutes owing to their biodegradability, abundance, and lower price in comparison with synthetic biomaterials. However, cell adhesion to bulk biomaterials is poor and surface modifications are required to improve biomaterial-cell interaction. Three-dimensional (3D) nanostructures are preferred to act as growth support platforms for bone and stem cells. Although there have been several studies on generating nanoparticles from eggshells, no research has been reported on synthesizing 3D nanofibrous structures. Results In this study, we propose a novel technique to synthesize 3D calcium carbonate interwoven nanofibrous platforms from eggshells using high repetition femtosecond laser irradiation. The eggshell waste is value engineered to calcium carbonate nanofibrous layer in a single step under ambient conditions. Our striking results demonstrate that by controlling the laser pulse repetition, nanostructures with different nanofiber density can be achieved. This approach presents an important step towards synthesizing 3D interwoven nanofibrous platforms from natural biomaterials. Conclusion The synthesized 3D nanofibrous structures can promote biomaterial interfacial properties to improve cell-platform surface interaction and develop new functional biomaterials for a variety of biomedical applications.

Background Recently, a novel single-switch access technology based on infrared thermography was proposed. The technology exploits the temperature differences between the inside and surrounding areas of the mouth as a switch trigger, thereby allowing voluntary switch activation upon mouth opening. However, for this technology to be clinically viable, it must be validated against a gold standard switch, such as a chin switch, that taps into the same voluntary motion. Methods In this study, we report an experiment designed to gauge the concurrent validity of the infrared thermal switch. Ten able-bodied adults participated in a series of 3 test sessions where they simultaneously used both an infrared thermal and conventional chin switch to perform multiple trials of a number identification task with visual, auditory and audiovisual stimuli. Participants also provided qualitative feedback about switch use. User performance with the two switches was quantified using an efficiency measure based on mutual information. Results User performance (p = 0.16) and response time (p = 0.25) with the infrared thermal switch were comparable to those of the gold standard. Users reported preference for the infrared thermal switch given its non-contact nature and robustness to changes in user posture. Conclusions Thermal infrared access technology appears to be a valid single switch alternative for individuals with disabilities who retain voluntary mouth opening and closing.

Ultrasonography (US) and dual-energy computed tomography (DECT) are useful and sensitive diagnostic tools to identify monosodium urate deposits in joints and soft tissues. The purpose of this review is to overview the imaging findings obtained by US and DECT in patients with gout, to understand the strengths and weaknesses of each imaging modality, and to evaluate the added value of using both modalities in combination.

Background Carvedilol, the anti-hypertensive drug, has poor bioavailability when administered orally. Ethosomes-mediated transdermal delivery is considered a potential route of administration to increase the bioavailability of carvedilol. The central composite design could be used as a tool to optimize ethosomal formulation. Thus, this study aims to optimize carvedilol-loaded ethosomes using central composite design, followed by incorporation of synthesized ethosomes into hydrogels for transdermal delivery of carvedilol. Results The optimized carvedilol-loaded ethosomes were spherical in shape. The optimized ethosomes had mean particle size of 130 ± 1.72 nm, entrapment efficiency of 99.12 ± 2.96%, cumulative drug release of 97.89 ± 3.7%, zeta potential of − 31 ± 1.8 mV, and polydispersity index of 0.230 ± 0.03. The in-vitro drug release showed sustained release of carvedilol from ethosomes and ethosomal hydrogel. Compared to free carvedilol-loaded hydrogel, the ethosomal gel showed increased penetration of carvedilol through the skin. Moreover, ethosomal hydrogels showed a gradual reduction in blood pressure for 24 h in rats. Conclusions Taken together, central composite design can be used for successful optimization of carvedilol-loaded ethosomes formulation, which can serve as the promising transdermal delivery system for carvedilol. Moreover the carvedilol-loaded ethosomal gel can extend the anti-hypertensive effect of carvedilol for a longer time, as compared to free carvedilol, suggesting its therapeutic potential in future clinics.

Introduction: Emicizumab is a first-in-class monoclonal antibody, recently authorized for the treatment of hemophilia A with inhibitors. This study aims to estimate the direct and indirect costs of the management of hemophilia A with inhibitors, in adult and pediatric patients, including the prophylaxis with emicizumab. Methods: We calculated the costs of the on-demand and prophylactic treatments with bypassing agents (activated prothrombin complex concentrate and recombinant activated factor VII) and the emicizumab prophylaxis, from the societal perspective, over 1 year. The study considered direct healthcare costs (drugs, visits, tests, and hospitalizations), direct non-healthcare costs (informal caregivers), and indirect costs (productivity loss). Data were obtained from a literature review and were validated by an expert group. Costs were expressed in 2019 euros. Results: Our results showed that the annual costs of the prophylactic treatment per patient varied between (SIC)543,062.99 and (SIC)821,415.77 for adults, and (SIC)182,764.43 and (SIC)319,826.59 for children, while on-demand treatment was (SIC)532,706.84 and (SIC)789,341.91 in adults, and (SIC)167,523.05 and (SIC)238,304.71 in pediatric patients. In relation to other prophylactic therapies, emicizumab showed the lowest costs, with up to a 34% and 43% reduction in the management cost of adult and pediatric patients, respectively. It reduced the bleeding events and administration costs, as this drug is less frequently administered by subcutaneous route. Emicizumab prophylaxis also decreased the cost of other healthcare resources such as visits, tests, and hospitalizations, as well as indirect costs. Conclusion: In comparison to prophylaxis with bypassing agents, emicizumab reduced direct and indirect costs, resulting in cost savings for the National Health System and society.

Purpose The sonographic differential diagnosis of umbilical polyps and granulomas in children based on correlations with pathologic findings. Methods We retrospectively analyzed the ultrasonographic findings of twenty-two umbilical masses in children that were pathologically confirmed as umbilical polyps or umbilical granulomas by surgery. We analyzed size, depth, echogenicity, internal content, intralesional vascularity, and the presence of unobliterated medial umbilical ligament. Pathologic correlation was performed for all of the umbilical masses. Results Twenty-two masses consisted of eight umbilical polyps and fourteen umbilical granulomas. The mean age of the children with umbilical polyps was 30.13 months (range, 2 to 108 months) and it was 1.33 months (range, 0.6 to 3 months) for the children with umbilical granulomas. The average mass sizes were 10.25 mm (range, 5 to 35 mm) for umbilical polyps and 6.21 mm (range, 3 to 10 mm) for umbilical granulomas. The umbilical polyps were manifested as cystic lesions with thick echogenic walls in five patients (62.5%), which were associated with the intestinal mucosa (four lesions) and ectopic pancreatic tissue (one lesion) on pathology. Umbilical granulomas were superficially located in 13 (92.9%) and solid in thirteen (92.9%), which correlated with prominent granulation tissues on pathology. Seven (87.5%) of the eight umbilical granulomas were hypervascular and correlated with neovascularization on pathologic examination. Conclusion The umbilical polyps revealed deep-seated, hypovascular nodules with cyst formation surrounded by thick echogenic walls. In contrast, the umbilical granulomas revealed superficially located hypervascular hypoechoic solid nodules in young infants.

Abstract In recent years, synthetic and semi-synthetic polymer materials have been widely used in various applications. Especially concerning biomedical applications, their biocompatibility, biodegradability, and non-toxicity have increased the interest of researchers to discover and develop new products for the well-being of humanity. Among the synthetic and semi-synthetic materials, the use of natural bio-based monomeric materials presents a possible novel avenue for the development of new biocompatible, biodegradable, and non-toxic products. The purpose of this article is to review the information on the role of natural bio-based monomers in biomedical applications. Increased eco-friendliness, biocompatibility, biodegradability, non-toxicity, and intrinsic biological activity are some of the attributes which make itaconic, succinic, citric, hyaluronic, and glutamic acids suitable potential materials for biomedical applications. Herein, we summarize the most recent advances in the field over the past ten years and specifically highlight new and interesting discoveries in biomedical applications. Graphical abstract Natural origin acid-based bio-monomers for biomedical applications

Introduction: Dose banding is an original approach that manages intravenous (IV) chemotherapy preparation by generating on a weekly basis a series of bags containing scaled dosages of the active agent. These predetermined, fixed dosage bags are intended to replace the traditional bags prepared daily that contain fully individualized dosages. Methods: Three different scenarios were examined: (1) the current method of daily preparation of individualized bags at the hospital pharmacy; (2) the weekly preparation at the hospital pharmacy of non-individualized bags containing discrete, predefined doses covering an adequate range of doses (dose banding); (3) the use of commercial ready-to-use bags based on the same approach of dose banding. The objective of this study was to compare these three different approaches in terms of cost per patient. We considered five cancer drugs (gemcitabine, oxaliplatin, paclitaxel, trastuzumab and 5-fluorouracil) that were suitable for the dose ranging approach. Appropriate dose bands for these five agents were identified. Costs were estimated for each of the three approaches. Results: A total of 13,490 fully individualized bags were studied, which corresponded to the real bags prepared at our institution for these five agents in 2018. Dose banding was predicted to determine savings ranging from €10,998 (−0.84%) for trastuzumab to €169,429.60 (−8.39%) for paclitaxel. Conclusion: The introduction of dose banding can determine economic savings along with other advantages, such as improved work conditions, management reorganization and containment of waste. The pharmaceutical industry can hopefully support these experiences by producing ready-to-use bags in predetermined dosages.

Background Hyperthermia is one of the promising cancer treatment strategies enabled by local heating with the use of tumor-targeting magnetic nanoparticles (MNP) under a non-invasive magnetic field. However, one of the remaining challenges is how to achieve therapeutic levels of heat (without causing damages to regular tissues) in tumors that cannot be effectively treated with anti-tumor drug delivery. Results In this work, we report a facile method to fabricate magnetic nanorods for hyperthermia by one-step wet chemistry synthesis using 3-Aminopropyltrimethoxysilane (APTMS) as the shape-controlling agent and ferric and ferrous ions as precursors. By adjusting the concentration of APTMS, hydrothermal reaction time, ratios of ferric to ferrous ions, magnetic nanorods with aspect ratios ranging from 4.4 to 7.6 have been produced. At the clinically recommended field strength of 300 Oe (or less) and the frequency of 184 kHz, the specific absorption rate (SAR) of these nanorods is approximately 50 % higher than that of commercial Bionized NanoFerrite particles. Conclusions This increase in SAR, especially at low field strengths, is crucial for treating deep tumors, such as pancreatic and rectal cancers, by avoiding the generation of harmful eddy current heating in normal tissues.

The Sociedad de Caucho Colombo Argentina (SOCCA) collected natural rubber (NR) from Yarima, Colombia, for seven months spanning two years. The unvulcanized NR was used to conduct a preliminary study, part of a long-term study, to uncover some underlying mechanisms in charge of imparting variation between NR batches, such as the collection site's rainfall conditions and storage period by using calorimetry, rheometry, and a dynamic mechanical analyzer. The ultrasound study found that an increase in monthly rainfall increased the material's elastic constant at 10 MHz, and the crystallization study uncovered that the amount of crystallization decreased with increased rain while remaining relatively constant if rainfall was within the recommended rainfall amount for the tree. Additionally, stress relaxation measurements revealed that an increase in rainfall suggested an increase in the material's temperature sensitivity. The temperature sensitivity relates to the material's processability in which an increase in temperature with high sensitivity will have a more drastic decrease in stress during a relaxation test compared to a material with low sensitivity.

Background Chest radiograph (CXR) prescribing pattern and practice vary widely among pediatric intensive care units (PICU). ‘On demand’ approach is increasingly recommended as against daily ‘routine’ CXRs; however, the real-world practice is largely unknown. Methods This was a prospective observational study performed in children younger than 12 years admitted to PICU of a tertiary care teaching hospital in India. Data were collected on all consecutive CXRs performed between December 2016 and April 2017. The primary outcome was to assess the factors that were associated with higher chest radiograph prescriptions in PICU. Secondary outcomes were to study the indications, association with mechanical ventilation, image quality and avoidable radiation exposure. Results Of 303 children admitted during the study period, 159 underwent a total of 524 CXRs in PICU. Median (IQR) age of the study cohort was 2 (0.6–5) years. More than two thirds [n = 115, 72.3%] were mechanically ventilated. Most CXRs (n = 449, 85.7%) were performed on mechanically ventilated patients, amounting to a median (IQR) of 3 (2–5) radiographs per ventilated patient. With increasing duration of ventilation, the number of CXRs proportionately increased in the first two weeks of mechanical ventilation. In non-ventilated children, about two thirds (68%) underwent only one CXR. Majority of the prescriptions were on demand (n = 461, 88%). Most common indications were peri-procedure prescriptions (37%) followed by evaluation for respiratory disease status (24%). About 40% CXRs resulted in interventions; adjustment in ventilator settings (13.5%) was the most frequent intervention. In 26% (n = 138) of radiographs, image quality required improvement. One or more additional body part exposure other than chest and upper abdomen were noted 336 (64%) images. Children with > 3 CXR had higher PRISM III score, more often mechanically ventilated, had higher number of indwelling devices [mean (SD) 2.6 (1.2) vs. 1.7 (1.0)] and stayed longer in PICU [median (IQR) 11(7.5–18.5) vs. 6 (3–9)]. Conclusion On demand prescription was the prevalent practice in our PICU. Most non-ventilated children underwent only one CXR while duration of PICU stay and the number of devices determined the number of CXRs in mechanically ventilated children. Quality improvement strategies should concentrate on the process of acquisition of images and limiting the radiation exposure to unwanted body parts.

Background There is a great interest in the efficient intracellular delivery of Cas9-sgRNA ribonucleoprotein complex (RNP) and its possible applications for in vivo CRISPR-based gene editing. In this study, a nanoporous mediated gene-editing approach has been successfully performed using a bi-functionalized aminoguanidine-PEGylated periodic mesoporous organosilica (PMO) nanoparticles (RNP@AGu@PEG1500-PMO) as a potent and biocompatible nanocarrier for RNP delivery. Results The bi-functionalized MSN-based nanomaterials have been fully characterized using electron microscopy (TEM and SEM), nitrogen adsorption measurements, thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and dynamic light scattering (DLS). The results confirm that AGu@PEG1500-PMO can be applied for gene-editing with an efficiency of about 40% as measured by GFP gene knockdown of HT1080-GFP cells with no notable change in the morphology of the cells. Conclusions Due to the high stability and biocompatibility, simple synthesis, and cost-effectiveness, the developed bi-functionalized PMO-based nano-network introduces a tailored nanocarrier that has remarkable potential as a promising trajectory for biomedical and RNP delivery applications.

The green microalgae Chlorella vulgaris can be used in diverse applications from food to biofuel production. Growing them in suspension leads to challenging harvesting and processing. One possibility to overcome these problems is growing them as biofilms, i.e. adhering on a surface. While previous experiments of several research groups concentrated on flat, rigid surfaces, partly chemically modified, here the possibility to grow them on different textile substrates was investigated which were shown to be suitable as substrates for germination and growth of higher plants. Microalgae were counted after one week, subdivided into adhered and suspended ones, to evaluate the ideal substrate for cultivation and harvesting. The results show clear differences between the different woven and knitted fabrics from diverse materials, indicating that especially an open-pore jute woven fabric increased the overall algae concentration by approx. a factor of 2 and increased the adhesion of C. vulgaris by a factor of 5-10, as compared to most other textile substrates under investigation, followed by two other hairy knitted fabrics. Such textile fabrics can thus be suggested as possible substrates for improved growth and harvesting of this microalga.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019. At the time of writing (October 2020), the number of cases of COVID-19 had been approaching 38 million and more than 1 million deaths were attributable to it. SARS-CoV-2 appears to be highly transmissible and could rapidly spread in hospital wards.The work undertaken aimed to estimate the clinical effectiveness and cost-effectiveness of viral detection point-of-care tests for detecting SARS-CoV-2 compared with laboratory-based tests. A further objective was to assess occupancy levels in hospital areas, such as waiting bays, before allocation to an appropriate bay.The perspective was that of the UK NHS in 2020. The setting was a hypothetical hospital with an accident and emergency department.An individual patient model was constructed that simulated the spread of disease and mortality within the hospital and recorded occupancy levels. Thirty-two strategies involving different hypothetical SARS-CoV-2 tests were modelled. Recently published desirable and acceptable target product profiles for SARS-CoV-2 point-of-care tests were modelled. Incremental analyses were undertaken using both incremental cost-effectiveness ratios and net monetary benefits, and key patient outcomes, such as death and intensive care unit care, caused directly by COVID-19 were recorded.A SARS-CoV-2 point-of-care test with a desirable target product profile appears to have a relatively small number of infections, a low occupancy level within the waiting bays, and a high net monetary benefit. However, if hospital laboratory testing can produce results in 6 hours, then the benefits of point-of-care tests may be reduced. The acceptable target product profiles performed less well and had lower net monetary benefits than both a laboratory-based test with a 24-hour turnaround time and strategies using data from currently available SARS-CoV-2 point-of-care tests. The desirable and acceptable point-of-care test target product profiles had lower requirement for patients to be in waiting bays before being allocated to an appropriate bay than laboratory-based tests, which may be of high importance in some hospitals. Tests that appeared more cost-effective also had better patient outcomes.There is considerable uncertainty in the values for key parameters within the model, although calibration was undertaken in an attempt to mitigate this. The example hospital simulated will also not match those of decision-makers deciding on the clinical effectiveness and cost-effectiveness of introducing SARS-CoV-2 point-of-care tests. Given these limitations, the results should be taken as indicative rather than definitive, particularly cost-effectiveness results when the relative cost per SARS-CoV-2 point-of-care test is uncertain.Should a SARS-CoV-2 point-of-care test with a desirable target product profile become available, this appears promising, particularly when the reduction on the requirements for waiting bays before allocation to a SARS-CoV-2-infected bay, or a non-SARS-CoV-2-infected bay, is considered. The results produced should be informative to decision-makers who can identify the results most pertinent to their specific circumstances.More accurate results could be obtained when there is more certainty on the diagnostic accuracy of, and the reduction in time to test result associated with, SARS-CoV-2 point-of-care tests, and on the impact of these tests on occupancy of waiting bays and isolation bays. These parameters are currently uncertain.This report was commissioned by the National Institute for Health Research (NIHR) Evidence Synthesis programme as project number 132154. This project was funded by the NIHR Health Technology Assessment programme and will be published in full inSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 is highly infectious, and this can cause problems in hospitals, where the virus can spread quickly. Laboratory-based tests can determine whether or not a patient has SARS-CoV-2, but these tests are not perfect and can require a considerable time to provide a result. Point-of-care tests to detect SARS-CoV-2 are being developed that may have much shorter times to a test result, although these are likely to be less accurate than laboratory-based tests. The benefit of quicker tests is that a decision to put a patient in a SARS-CoV-2-infected bay or in a non-SARS-CoV-2-infected bay can be made sooner, limiting contact between patients with SARS-CoV-2 and patients without SARS-CoV-2 and reducing the risk of infection transmission. The disadvantage of reduced accuracy is that some patients may be allocated to the wrong bay, increasing the risk of SARS-CoV-2 infection. A computer model was built to explore the impact of using SARS-CoV-2 point-of-care tests for people admitted to hospital. This model estimated the number of infections and deaths due to COVID-19, the costs of testing, and the number of people waiting to be put in an appropriate bay. Strategies were run using different values, including the time to get a test result, the accuracy of tests and whether or not staff who do not have symptoms should be tested. The results of the model indicated that point-of-care tests could be good if there was a large reduction in the time to get a test result and if accuracy was high. However, it is not certain whether or not such tests will become available. When newer SARS-CoV-2 tests are available, the model will allow an estimate of the clinical effectiveness and cost-effectiveness of the test to be made.

Background Assessment of tibiofibular reduction presents an intra- and postoperative challenge. Numerous two-dimensional measurement methods have been described, most of them highly dependent on leg orientation and rater. Aim of the present work was to develop a standardized and orientation-independent 3D based method for the assessment of syndesmotic joint position. Methods In a retrospective single center study, 3D models of bilateral ankle joints, either after unilateral syndesmosis stabilization (operative group) or with no injury (native group) were superimposed (best fit matching) and aligned uniformly. Based on center of gravity calculations three orientation- and rater-independent parameters were determined: tibiofibular clears space (CS), vertical offset between both fibulae, and translation angle of the fibulae about tibia axis. Results Bilateral CT datasets of 57 native and 47 postoperative patients were analyzed. In the native group mean CS was 2.7 (SD, 0.8; range, 0.7–4.9) mm, mean CS side difference was 0.62 (SD, 0.45) mm and mean translation angle was 1.6 (SD, 1.4) degrees regarding absolute values. The operative group was found to show a significantly higher CS side difference of 0.88 (SD, 0.75) mm compared to native group (P = .046). Compared to the healthy contralateral side, operated fibulae showed mean proximal displacement of 0.56 (SD, 1.67) mm (P = .025), dorsal displacement of 1.5 (SD 4.1) degrees (P = .017). Conclusion By using 3D best fit matching, orientation- and rater-dependent errors can be minimized. Large interindividual and small intraindividual differences of uninjured couples support previous recommendations for bilateral imaging. Trial registration: AZ 131/18-ek; AZ 361/19-ek Level of evidence Level III.

Background Collecting (Bellini) duct carcinoma (CDC) is a highly malignant and rare kidney tumor. We report our 12-year experience with CDC and the results of a retrospective analysis of patients and tumor characteristics, clinical manifestations, and imaging features by computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Methods Retrospective examination of tumors between January 2007 and December 2019 identified 13 cases of CDC from three medical centers in northern China. All 13 patients underwent CT scan, among which eight underwent dynamic enhanced CT scan, two underwent PET/CT scan, and one underwent magnetic resonance cholangiopancreatography (MRCP) examination. The lesions were divided into nephritis type and mass type according to the morphology of the tumors. Results The study group included ten men and three women with an average age of 64.23 ± 10.74 years. The clinical manifestations were gross hematuria, flank pain, and waist discomfort. The mean tumor size was 8.48 ± 2.48 cm. Of the 13 cases, six (46.2%) were cortical-medullary involved type and seven (53.8%) were cortex–medullary–pelvis involved type. Eleven (84.6%) cases were nephritis type and two (15.4%) were mass type. The lesions appeared solid or complex solid and cystic on CT and MRI. The parenchymal area of the tumors showed isodensity or slightly higher density on unenhanced CT scan in the 13 cases. PET/CT in two cases showed increased radioactivity intake. Evidence of intra-abdominal metastatic disease was present on CT in nine (69.2%) cases. Conclusions The imaging characteristics of CDC differ from those of other renal cell carcinomas. In renal tumors located in the junction zone of the renal cortex and medulla that show unclear borders, slight enhancement, and metastases in the early stage, a diagnosis of CDC needs to be considered. PET/CT provides crucial information for the diagnosis of CDC, as well as for designing treatment strategies including surgery.

Arabinoxylans (AX) are gelling polysaccharides with potential applications as colon-targeted biomaterials. Nevertheless, the fermentation of highly cross-linked AX particles (AXP) by colonic bacteria and the effect of its fermentation supernatants on the proliferation of human colon cancer cells have not been investigated so far. In this study, electrosprayed AXP were fermented by Bifidobacterium longum , Bifidobacterium adolescentis , and Bacteroides ovatus . The effect of AXP fermentation supernatant (AXP-fs) on the inhibition of the human colon cancer cell line Caco-2 proliferation was investigated. AXP presented a mean diameter of 533 µm, a spherical shape, and a cross-linking content (dimers and trimers of ferulic acid) of 1.65 µg/mg polysaccharide. After 48 h of bacteria exposure, AXP were only partly fermented, probably due to polymeric network steric hindrance that limits the access of bacterial enzymes to the polysaccharide target sites. AXP partial fermentation was evidenced by a moderate short-chain fatty acid production (SCFA) (23 mM) and a collapsed and disintegrated microstructure revealed by scanning electron microscopy. AXP-fs exerted slight inhibition of Caco-2 cell proliferation (11%), which could be attributed to the SCFA generated during partly polysaccharide fermentation. These findings indicate that electrosprayed AXP are a slow-fermentable biomaterial presenting slight anti-cancer properties and potential application in colon cancer prevention.

Background End-stage heart failure is a major risk of mortality. The conductive super-aligned carbon nanotubes sheets (SA-CNTs) has been applied to restore the structure and function of injured myocardium through tissue engineering, and developed as efficient cardiac pacing electrodes. However, the interfacial interaction between SA-CNTs and the surface cells is unclear, and it remains challenge to restore the diminished contraction for a seriously damaged heart. Results A concept of a multifunctional power assist system (MPS) capable of multipoint pacing and contraction assisting is proposed. This device is designed to work with the host heart and does not contact blood, thus avoiding long-term anticoagulation required in current therapies. Pacing electrode constructed by SA-­CNTs promotes the epithelial-mesenchymal transition and directs the migration of pro-regenerative epicardial cells. Meanwhile, the power assist unit reveals an excellent frequency response to alternating voltage, with natural heart mimicked systolic/diastolic amplitudes. Moreover, this system exhibits an excellent pacing when attached to the surface of a rabbit heart, and presents nice biocompatibility in both in vitro and in vivo evaluation. Conclusions This MPS provides a promising non-blood contact strategy to restore in situ the normal blood-pumping function of a failed heart.

This review highlights current developments, challenges, and future directions for the use of invasive and noninvasive biosample-based small biosensors for early diagnosis of Alzheimer’s disease (AD) with biomarkers to incite a conceptual idea from a broad number of readers in this field. We provide the most promising concept about biosensors on the basis of detection scale (from femto to micro) using invasive and noninvasive biosamples such as cerebrospinal fluid (CSF), blood, urine, sweat, and tear. It also summarizes sensor types and detailed analyzing techniques for ultrasensitive detection of multiple target biomarkers (i.e., amyloid beta (Aβ) peptide, tau protein, Acetylcholine (Ach), microRNA137, etc.) of AD in terms of detection ranges and limit of detections (LODs). As the most significant disadvantage of CSF and blood-based detection of AD is associated with the invasiveness of sample collection which limits future strategy with home-based early screening of AD, we extensively reviewed the future trend of new noninvasive detection techniques (such as optical screening and bio-imaging process). To overcome the limitation of non-invasive biosamples with low concentrations of AD biomarkers, current efforts to enhance the sensitivity of biosensors and discover new types of biomarkers using non-invasive body fluids are presented. We also introduced future trends facing an infection point in early diagnosis of AD with simultaneous emergence of addressable innovative technologies.

Background Liver cancer is the sixth most common cancer worldwide. It is mostly diagnosed with a computed tomography scan. Nowadays deep learning methods have been used for the segmentation of the liver and its tumor from the computed tomography (CT) scan images. This research mainly focused on segmenting liver and tumor from the abdominal CT scan images using a deep learning method and minimizing the effort and time used for a liver cancer diagnosis. The algorithm is based on the original UNet architecture. But, here in this paper, the numbers of filters on each convolutional block were reduced and new batch normalization and a dropout layer were added after each convolutional block of the contracting path. Results Using this algorithm a dice score of 0.96, 0.74, and 0.63 were obtained for liver segmentation, segmentation of tumors from the liver, and the segmentation of tumor from abdominal CT scan images respectively. The segmentation results of liver and tumor from the liver showed an improvement of 0.01 and 0.11 respectively from other works. Conclusion This work proposed a liver and a tumor segmentation method using a UNet architecture as a baseline. Modification regarding the number of filters and network layers were done on the original UNet model to reduce the network complexity and improve segmentation performance. A new class balancing method is also introduced to minimize the class imbalance problem. Through these, the algorithm attained better segmentation results and showed good improvement. However, it faced difficulty in segmenting small and irregular tumors.

Cell growth on three-dimensional objects is of high interest for bioprocess engineering of adherent cells, tissue engineering and other biomedical applications. 3D printing by fusion deposition modeling (FDM) is a cheap possibility to generate tailor-made substrates for cell growth. Nevertheless, not all materials are chemically attractive for cells. Polylactic acid (PLA) and polyethylene terephthalate glycol (PETG) have been reported to be suitable polymers for tissue engineering. Thus, they might also be applicable for cost-effective bioprocessing of adherent cell lines. Here we report on the influence of printing material, surface structure, and sterilization method on Chinese hamster ovary (CHO) cell adhesion on a modified, high temperature resistant PLA, a PETG blend, and unmodified PETG, respectively. Our study revealed that CHO cells grew on all polymers tested without further surface modification. Samples could be efficiently chemically sterilized. Additional acid treatment had no significant effect on cell adhesion.

Background Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. Objectives To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related. Design A series of 200 double-blinded N-of-1 trials. Setting Participants were recruited from 50 general practices in England and Wales. Participants Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms. Interventions Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo. Main outcome measures The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant’s belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant’s decision about statin treatment following the trial, and whether or not they found their own trial result helpful. Results A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo –0.11, 95% confidence interval –0.36 to 0.14; p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods. Conclusions Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial. Future work We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications. Limitations This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations. Trial registration Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.

Background Cadmium (Cd) is amongst the most toxic heavy metals that severely affects crop growth, whereas application of nanoparticles (NPs) to negate the toxic effects of heavy metals could be an effective management approach. In the present study, the seeds of two fragrant rice varieties i.e., Yuxiangyouzhan and Xiangyaxiangzhan under normal and Cd stress conditions i.e., 0 and 100 mg L− 1 applied with four levels of ZnO NPs i.e., 0, 25, 50, and 100 mg L− 1. Results Seed priming with ZnO NPs had no significant effect on the seed germination (p > 0.05) however, it substantially improved the seedling growth and other related physiological attributes under the Cd stress. The mean fresh weight of the shoot, and whole seedling was increased by 16.92–27.88% and by 16.92–27.88% after ZnO NPs application. The root fresh weight, root-shoot length was also substantially improved under ZnO NPs treatment. Moreover, application of ZnO NPs induced modulations in physiological and biochemical attributes e.g., the superoxide dismutase (SOD) activity in root and shoot, the peroxidase (POD) activity and metallothionein contents in root were increased under low levels of ZnO NPs. The α-amylase and total amylase activity were improved by ZnO NPs application under Cd Stress. Besides, modulation in Zn concentration and ZnO NPs uptake in the seedling were detected. The metabolomic analysis indicated that various pathways such as alanine, aspartate and glutamate metabolism, phenylpropanoid biosynthesis, and taurine and hypotaurine metabolism were possibly important for rice response to ZnO NPs and Cd. Conclusion Overall, application of ZnO NPs substantially improved the early growth and related physio-biochemical attributes in rice. Our findings provide new insights regarding the effects of ZnO NPs on seed germination, and early growth of rice, and its potential applications in developing crop resilience against Cd contaminated soils.

Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

Background Blood prostate-specific antigen (PSA) levels are widely used as diagnostic biomarkers for prostate cancer. Lateral-flow immunoassay (LFIA)-based PSA detection can overcome the limitations associated with other methods. LFIAbased PSA detection in clinical samples enables prognosis and early diagnosis owing to the use of high-performance signal reporters. Results Here, a semiquantitative LFIA platform for PSA detection in blood was developed using Au–Ag nanoparticles (NPs) assembled on silica NPs (SiO2@Au–Ag NPs) that served as signal reporters. Synthesized SiO2@Au–Ag NPs exhibited a high absorbance at a wide wavelength range (400–800 nm), with a high scattering on nitrocellulose membrane test strips. In LFIA, the color intensity of the test line on the test strip differed depending on the PSA concentration (0.30–10.00 ng/mL), and bands for the test line on the test strip could be used as a standard. When clinical samples were assessed using this LFIA, a visual test line with particular color intensity observed on the test strip enabled the early diagnosis and prognosis of patients with prostate cancer based on PSA detection. In addition, the relative standard deviation of reproducibility was 1.41%, indicating high reproducibility, and the signal reporter showed good stability for 10 days. Conclusion These characteristics of the signal reporter demonstrated the reliability of the LFIA platform for PSA detection, suggesting potential applications in clinical sample analysis.

Although there has been substantial progress in the research field of gene delivery, there are some challenges remaining, e.g. there are still cell types such as primary cells and suspension cells (immune cells) known to be difficult to transfect. Cationic polymers have gained increasing attention due to their ability to bind, condense and mask genetic material, being amenable to scale up and highly variable in their composition. In addition, they can be combined with further monomers exhibiting desired biological and chemical properties, such as antioxidative, pH- and redox-responsive or biocompatible features. By introduction of hydrophobic monomers, in particular as block copolymers, cationic micelles can be formed possessing an improved chance of transfection in otherwise challenging cells. In this study, the antioxidant biomolecule lipoic acid, which can also be used as crosslinker, was incorporated into the hydrophobic block of a diblock copolymer, poly{[2-(dimethylamino)ethyl methacrylate]101-b-[n-(butyl methacrylate)124-co-(lipoic acid methacrylate)22]} (P(DMAEMA101-b-[nBMA124-co-LAMA22])), synthesized by RAFT polymerization and assembled into micelles (LAMA-mic). These micelles were investigated regarding their pDNA binding, cytotoxicity mechanisms and transfection efficiency in K-562 and HEK293T cells, the former representing a difficult to transfect, suspension leukemia cell line. The LAMA-mic exhibited low cytotoxicity at applied concentrations but demonstrated superior transfection efficiency in HEK293T and especially K-562 cells. In-depth studies on the transfection mechanism revealed that transfection efficiency in K-562 cells does not depend on the specific oncogenic fusion gene BCR-ABL alone. It is independent of the cellular uptake of polymer-pDNA complexes but correlates with the endosomal escape of the LAMA-mic. A comparison of the transfection efficiency of the LAMA-mic with structurally comparable micelles without lipoic acid showed that lipoic acid is not solely responsible for the superior transfection efficiency of the LAMA-mic. More likely, a synergistic effect of the antioxidative lipoic acid and the micellar architecture was identified. Therefore, the incorporation of lipoic acid into the core of hydrophobic-cationic micelles represents a promising tailor-made transfer strategy, which can potentially be beneficial for other difficult to transfect cell types.

Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

Background Non-mass enhancement (NME) is a diagnostic dilemma and highly reliant on the experience of the radiologists. Texture analysis (TA) could serve as an objective method to quantify lesion characteristics. However, it remains unclear what role TA plays in a predictive model based on routine MRI characteristics. The purpose of this study was to explore the value of TA in distinguishing between benign and malignant NME in premenopausal women. Methods Women in whom NME was histologically proven (n = 147) were enrolled (benign: 58; malignant: 89) was retrospective. Then, 102 and 45 patients were classified as the training and validation groups, respectively. Scanning sequences included Fat-suppressed T2-weighted and fat-suppressed contrast-enhanced T1-weighted which were acquired on a 1.5T MRI system. Clinical and routine MR characteristics (CRMC) were evaluated by two radiologists according to the Breast Imaging and Reporting and Data system (2013). Texture features were extracted from all post-contrast sequences in the training group. The combination model was built and then assessed in the validation group. Pearson’s chi-square test and Mann–Whitney U test were used to compare categorical variables and continuous variables, respectively. Logistic regression analysis and receiver operating characteristic curve were employed to assess the diagnostic performance of CRMC, TA, and their combination model in NME diagnosis. Results The combination model showed superior diagnostic performance in differentiating between benign and malignant NME compared to that of CRMC or TA alone (AUC, 0.887 vs 0.832 vs 0.74). Moreover, compared to CRMC, the model showed high specificity (72.5% vs 80%). The results obtained in the validation group confirmed the model was promising. Conclusions With the combined use of TA and CRMC could afford an improved diagnostic performance in differentiating between benign and malignant NME.

Background Sonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as MG@P NPs). Results On account of the peroxidase-like activity of PMnC, MG@P NPs can catalyze hydrogen peroxide (H2O2) in tumor regions to produce oxygen (O2), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (1O2) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusion Multifunctional MG@P NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, MG@P NPs might be a promising nano-platform for highly efficient cancer theranostics. Graphical Abstract

Background Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. Methods Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2′-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC. Results The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency. Conclusion A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC. Graphic abstract

Background The objective of this study was to analyze the accuracy of gadolinium–ethoxybenzyl–diethylenetriamine penta–acetic acid enhanced magnetic resonance imaging (Gd–EOB–DTPA–MRI) for predicting microvascular invasion (MVI) in patients with small hepatocellular carcinoma (sHCC) preoperatively. Methods A total of 60 sHCC patients performed with preoperative Gd–EOB–DTPA–MRI in the Harbin Medical University Cancer Hospital from October 2018 to October 2019 were involved in the study. Univariate and multivariate analyses were performed by chi–square test and logistic regression analysis. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of Gd–EOB–DTPA–MRI were performed by receiver operating characteristic (ROC) curves. Results Univariate analysis indicated that alanine aminotransferase (≥ 39.00U/L), poorly differentiated pathology, and imaging features including grim enhancement, capsule enhancement, arterial halo sign and hepatobiliary features (tumor highly uptake, halo sign, spicule sign and brush sign) were associated with the occurrence of MVI (p p Conclusions The morphologies of hepatobiliary phase imaging, especially the spicule sign, showed high accuracy in diagnosing MVI of sHCC. Rim enhancement played a significant role in diagnosing MVI of sHCC.

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC. Results Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast. Conclusions The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.

BackgroundUnified Parkinson Disease Rating Scale-part III (UPDRS III) is part of the standard clinical examination performed to track the severity of Parkinson’s disease (PD) motor complications. Wearable technologies could be used to reduce the need for on-site clinical examinations of people with Parkinson’s disease (PwP) and provide a reliable and continuous estimation of the severity of PD at home. The reported estimation can be used to successfully adjust the dose and interval of PD medications.MethodsWe developed a novel algorithm for unobtrusive and continuous UPDRS-III estimation at home using two wearable inertial sensors mounted on the wrist and ankle. We used the ensemble of three deep-learning models to detect UPDRS-III-related patterns from a combination of hand-crafted features, raw temporal signals, and their time–frequency representation. Specifically, we used a dual-channel, Long Short-Term Memory (LSTM) for hand-crafted features, 1D Convolutional Neural Network (CNN)-LSTM for raw signals, and 2D CNN-LSTM for time–frequency data. We utilized transfer learning from activity recognition data and proposed a two-stage training for the CNN-LSTM networks to cope with the limited amount of data.ResultsThe algorithm was evaluated on gyroscope data from 24 PwP as they performed different daily living activities. The estimated UPDRS-III scores had a correlation of$$0.79\, (\textit{p}0.79(p<0.0001)and a mean absolute error of 5.95 with the clinical examination scores without requiring the patients to perform any specific tasks.ConclusionOur analysis demonstrates the potential of our algorithm for estimating PD severity scores unobtrusively at home. Such an algorithm could provide the required motor-complication measurements without unnecessary clinical visits and help the treating physician provide effective management of the disease.

Background The visualization of the tibial nerve and its branches in the ankle canal is helpful for the diagnosis of local lesions and compression, and it is also useful for clinical observation and surgical planning. The aim of this study was to investigate the feasibility of three-dimensional dual-excitation balanced steady-state free precession sequence (3D-FIESTA-C) multiplanar reformation (MPR) display of the tibial nerve and its branches in the ankle canal. Methods The subjects were 20 healthy volunteers (40 ankles), aged 22–50 years, with no history of ankle joint disease. The 3D-FIESTA-C sequence was used in the 3.0 T magnetic resonance equipment for imaging. During scanning, each foot was at an angle of 90° to the tibia. The tibial nerve of the ankle canal and its branches were displayed and measured at the same level through MPR. Results Most of the tibial nerve bifurcation points were located in the ankle canal (57.5%), few bifurcation points (42.5%) were located at the proximal end of the ankle canal, and none of them were found away from the distal end. The bifurcation between the medial plantar nerve and the lateral plantar nerve was on the line between the tip of the medial malleolus and the calcaneus, and it’s angle ranged between 6° and 35°. In MPR images, the display rates of both the medial calcaneal nerve and the subcalcaneal nerve were 100%, and the starting point of the subcalcaneal nerve was always at the distal end of the starting point of the medial calcaneal nerve. In 55% of cases, there were more than two medial calcaneal nerve innervations. Conclusion The 3D-FIESTA-C MPR can display the morphological features and positions of the tibial nerve and its branches and the bifurcation point’s projection position can be marked on the body surface. This method not only benefited the imaging diagnosis of the tibial nerve and branch-related lesions in the ankle canal, but it also provided a good imaging basis to plan a clinical operation of the ankle canal and avoid surgical injury.

The latest technological advances in stem cell biology and mechanical engineering provide new opportunities for cardiac tissue engineering, enabling the production of highly efficient differentiated cells and the manufacture of high-resolution complex cardiac tissues. In this review, we summarize the progress of stem cell technology in 3D bioprinting of heart tissue and the latest technological breakthroughs. The main topics discussed include somatic cell reprogramming, differentiation of induced pluripotent stem cells (iPSCs), 3D bioprinting strategies, bioinks, and in vitro vascularization methods. The objective of this review is to explore the possibility of interdisciplinary research to solve the existing challenges in tissue engineering by summarizing the existing work and progress and pointing their current limitations.

Preliminary studies using the FENIX™ (Torax Medical, Minneapolis, MN, USA) magnetic sphincter augmentation device suggest that it is safe to use for the treatment of adult faecal incontinence, but efficacy data are limited.To compare FENIX with sacral nerve stimulation for the treatment of adult faecal incontinence in terms of safety, efficacy, quality of life and cost-effectiveness.Multicentre, parallel-group, unblinded, randomised trial comparing FENIX with sacral nerve stimulation in participants suffering moderate to severe faecal incontinence.Participants were randomised on an equal basis to either sacral nerve stimulation or FENIX. Follow-up occurred 2 weeks postoperatively and at 6, 12 and 18 months post randomisation.The primary outcome was success, defined as device in use and ≥ 50% improvement in Cleveland Clinic Incontinence Score at 18 months post randomisation. Secondary outcomes included complication rates, quality of life and cost-effectiveness. Between 30 October 2014 and 23 March 2017, 99 participants were randomised across 18 NHS sites (50 participants to FENIX vs. 49 participants to sacral nerve stimulation). The median time from randomisation to FENIX implantation was 57.0 days (range 4.0-416.0 days), and the median time from randomisation to permanent sacral nerve stimulation was 371.0 days (range 86.0-918.0 days). A total of 45 out of 50 participants underwent FENIX implantation and 29 out of 49 participants continued to permanent sacral nerve stimulation. The following results are reported, excluding participants for whom the corresponding outcome was not evaluable. Overall, there was success for 10 out of 80 (12.5%) participants, with no statistically significant difference between the two groups [FENIX 6/41 (14.6%) participants vs. sacral nerve stimulation 4/39 (10.3%) participants]. At least one postoperative complication was experienced by 33 out of 45 (73.3%) participants in the FENIX group and 9 out of 40 (22.5%) participants in the sacral nerve stimulation group. A total of 15 out of 50 (30%) participants in the FENIX group ultimately had to have their device explanted. Slightly higher costs and quality-adjusted life-years (incremental = £305.50 and 0.005, respectively) were observed in the FENIX group than in the sacral nerve stimulation group. This was reversed over the lifetime horizon (incremental = -£1306 and -0.23 for costs and quality-adjusted life-years, respectively), when sacral nerve stimulation was the optimal option (net monetary benefit = -£3283), with only a 45% chance of FENIX being cost-effective.The SaFaRI study was terminated in 2017, having recruited 99 participants of the target sample size of 350 participants. The study is, therefore, substantially underpowered to detect differences between the treatment groups, with significant uncertainty in the cost-effectiveness analysis.The SaFaRI study revealed inefficiencies in the treatment pathways for faecal incontinence, particularly for sacral nerve stimulation. The success of both FENIX and sacral nerve stimulation was much lower than previously reported, with high postoperative morbidity in the FENIX group.Further research is needed to clarify the treatment pathways for sacral nerve stimulation and to determine its true clinical and cost-effectiveness.Current Controlled Trials ISRCTN16077538.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inFaecal incontinence is a distressing condition for patients, and surgery is recommended if symptoms are having an effect on quality of life. One of the treatments recommended for faecal incontinence by the National Institute for Health and Care Excellence is sacral nerve stimulation, which aims to improve continence by stimulating the nerves to the back passage. A newer treatment involves surgery to implant a string of magnetic beads around the anal canal using the FENIX™ device (Torax Medical, Minneapolis, MN, USA). The aim of this study was to assess the benefits and risks of the FENIX device compared with sacral nerve stimulation. The SaFaRI study aimed to recruit 350 participants with faecal incontinence, but was stopped early because of the manufacturer withdrawing the FENIX device for strategic reasons. In total, we recruited 99 participants. Fifty participants were allocated to receive the FENIX device and 49 participants were allocated to receive sacral nerve stimulation. The observed success rates with both devices were low: at 18 months following their entry into the study, 6 out of 41 (14.6%) participants in the FENIX group and 4 out of 39 (10.3%) participants in the sacral nerve stimulation group had the device both in use and producing a benefit. A total of 5 out of 50 (10.0%) participants allocated to receive the FENIX device did not have a device implanted, and 15 out of 45 (33.3%) participants who did have the FENIX device implanted needed to have it removed because of complications during the 18-month follow-up period. A total of 21 out of 49 (42.9%) participants allocated to receive sacral nerve stimulation did not have a permanent sacral nerve stimulation device implanted, and 0 of the 28 who did have a permanent sacral nerve stimulation device implanted needed to have it removed during the 18-month follow-up period. The costs associated with the FENIX device were higher because of a greater number of participants experiencing complications, meaning that the FENIX device is unlikely to be cost-effective in the treatment of faecal incontinence compared with sacral nerve stimulation.

Introduction: In March 2020, due to the pandemic caused by COVID-19, a pilot experience of pharmaceutical continuity of care received by hospital outpatients was launched in Cantabria, a Spanish autonomous community. Thanks to this experience, the medication was dispensed by the hospital pharmacy through the community pharmacy of the patient’s choice. Our objective was to estimate the costs avoided by this practice during the months of April and May 2020. Methods: The analysis of the economic impact was carried out in terms of saved costs, from the hospital and from the social perspective. Savings associated with the avoided home delivery of medication and avoided labor productivity losses were calculated, as well as the time associated with avoided trips in monetary terms. Results: A total of 2,249 hospital-dispensed drugs were delivered through the community pharmacy in the analyzed period, with an average of 57.7 daily deliveries. The experience, which involved one hospital and 262 pharmacies of Cantabria, saved patients 93,305 km in trips to the hospital, associated with an average time saving of 1,374 hours. In terms of costs, the hospital saved on shipments by courier, estimated at €30,205, since it was the community pharmacy and the distribution warehouses that delivered the drugs. From a social perspective, this initiative saved €23,309 due to the trips (€8,907) and productivity losses (€14,402) that were avoided. Conclusions: This exceptional situation may be a good opportunity to improve the coordination between hospital pharmacies and community pharmacies in Spain, not only during the pandemic but also in the post-COVID-19 era.

Currently, the majority of treatment strategies reported for coronavirus disease (COVID-19) involve the systemic administration of drugs, in addition to other approaches including convalescent plasma.1,2 The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was believed to be largely localised in the lungs. Retrospective observational studies from Wuhan, China have shown subgroups of patients with symptoms affecting the cardiovascular, renal, nervous, and digestive systems.3,4 Yet the most critical cases largely encompass those suffering from acute respiratory distress syndrome (ARDS). Therefore, the authors propose a combination of local delivery of therapeutics directly to the lungs and adjunct systemic administration (i.e., intravenous infusion).

Purpose: To assess the healthcare resources’ consumption and integrated costs of patients with renal cancer and new metastasis (mRCC), in the perspective of the Italian National Health System (NHS). Methods: From the ReS database, through the administrative data record linkage, adults with a primary/secondary hospital (ordinary/daily admissions) diagnosis (ICD9-CM code) of renal cancer and lymph node and/or distant metastases in the same hospital discharge (index date) were selected in 2015. Metastases were defined new if they were absent in the 2 previous years. Patients were described in terms of gender, age (mean ± SD) and comorbidities of interest. The 2-year survival and annual pharmacological treatments, hospitalization, outpatient specialist services and costs were analysed. Results: Out of >6 million adults in the 2015 ReS database, 133 (2.1 × 100,000) were hospitalized with a diagnosis of RCC and metastasis. Patients with new metastases were 63.2% (1.4 × 100,000; 73.8% males; mean age 68 ± 13). Hypertension was the most common comorbidity (70.2% of mRCC patients). The 2-year survival of mRCC patients was 26.2%. During 1-year follow-up, at least a drug was prescribed to 88.1% of mRCC patients (on average € 12,095/patient), 91.7% were hospitalized (€ 8,897/patient) and 82.1% entrusted the outpatient specialist care (€ 1,075/patient). The mean overall expenditure for the NHS was € 22,067 per capita. Conclusions: This study shows the mRCC burden on the Italian real clinical practice and its economic impact in the perspective of the NHS. Real-world analyses prove to be useful to concretely estimate the overall healthcare responsibility on patients affected by mRCC.

Background The cellular response to nanoparticles (NPs) for the mechanical clue and biochemical changes are unexplored. Here, we provide the comprehensive analysis of the Chinese Hamster Ovary (CHO-K1) cell line to study cell behaviour following the exposure of mesoporous silica nanoparticle (MSN), multiwall carbon nanotubes (MWCNTs), and zinc oxide (ZnO) NPs. Results Through the high-throughput proteomic study, we observed that the effect of NPs is alone not restricted to cell viability but also on cell polarisation. In the case of MSN, no drastic changes were observed in cellular morphology, but it upregulated chaperons that might prevent protein aggregation. However, MWCNT showed elongated cell appearance with numerous cytoplasmic vacuoles, and induce lamellipodia formation through actin polymerisation. The cytoskeleton remodelling was accompanied by the increased expression of Dlc-1, cofilin and Rac1 proteins. While ZnO NPs resulted in the rounded cell morphology along with nuclear abnormalities. The proteome analysis revealed that UBXN11 control cell roundness and DOCK3 leads to actin stress fibre formation and finally, loss of cell adhesion. It enhances the expression of catastrophic DNA damage and apoptotic proteins, which was unrecoverable even after 72 h, as confirmed by the colony formation assay. All three NPs trigger over-expression of the endocytic pathway, ubiquitination, and proteasomal complex proteins. The data indicate that ZnO and MSN entered into the cells through clathrin-mediated pathways; whereas, MWCNT invades through ER-mediated phagocytosis. Conclusions Based on the incubation and concentration of NPs, our work provides evidence for the activation of Rac-Rho signalling pathway to alter cytoskeleton dynamics. Our results assist as a sensitive early molecular readout for nanosafety assessment.

Over the last decades, microRNAs (miRNAs) have emerged as important molecules associated with the regulation of gene expression in humans and other organisms, expanding the strategies available to diagnose and handle several diseases. This paper presents a systematic review of literature of miRNAs related to cancer development and explores the main techniques used to quantify these molecules and their limitations as screening strategy. The bibliographic research was conducted using the online databases, PubMed, Google Scholar, Web of Science, and Science Direct searching the terms “microRNA detection”, “miRNA detection”, “miRNA and prostate cancer”, “miRNA and cervical cancer”, “miRNA and cervix cancer”, “miRNA and breast cancer”, and “miRNA and early cancer diagnosis”. Along the systematic review over 26,000 published papers were reported, and 252 papers were returned after applying the inclusion and exclusion criteria, which were considered during this review. The aim of this study is to identify potential miRNAs related to cancer development that may be useful for early cancer diagnosis, notably in the breast, prostate, and cervical cancers. In addition, we suggest a preliminary top 20 miRNA panel according to their relevance during the respective cancer development. Considering the progressive number of new cancer cases every year worldwide, the development of new diagnostic tools is critical to refine the accuracy of screening tests, improving the life expectancy and allowing a better prognosis for the affected patients.

Background To determine the predictive capability of MRI-based radiomics for extrathyroidal extension detection in papillary thyroid cancer (PTC) pre-surgically. Methods The present retrospective trial assessed individuals with thyroid nodules examined by multiparametric MRI and subsequently administered thyroid surgery. Diagnosis and extrathyroidal extension (ETE) feature of PTC were based on pathological assessment. The thyroid tumors underwent manual segmentation, for radiomic feature extraction. Participants were randomized to the training and testing cohorts, at a ratio of 7:3. The mRMR (maximum correlation minimum redundancy) algorithm and the least absolute shrinkage and selection operator were utilized for radiomics feature selection. Then, a radiomics predictive model was generated via a linear combination of the features. The model’s performance in distinguishing the ETE feature of PTC was assessed by analyzing the receiver operating characteristic curve. Results Totally 132 patients were assessed in this study, including 92 and 40 in the training and test cohorts, respectively). Next, the 16 top-performing features, including 4, 7 and 5 from diffusion weighted (DWI), T2-weighted (T2 WI), and contrast-enhanced T1-weighted (CE-T1WI) images, respectively, were finally retained to construct the radiomics signature. There were 8 RLM, 5 CM, 2 shape, and 1 SZM features. The radiomics prediction model achieved AUCs of 0.96 and 0.87 in the training and testing sets, respectively. Conclusions Our study indicated that MRI radiomics approach had the potential to stratify patients based on ETE in PTCs preoperatively.

Background The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy. Results A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza–boron–dipyrromethene (aza-BODIPY) dyes with donor–acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity. Conclusions Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.

The scale, speed, and impact of the coronavirus disease (COVID-19) pandemic disruption to healthcare services has been unprecedented, placing significant additional pressures on the National Health Service (NHS). COVID-19 presented exceptional challenges to vulnerable families and is placing increasing pressure on children’s services. The child population does not seem to have been severely impacted by COVID-19; however, some will require hospital care in addition to the current caseload. It is imperative that steps are taken to ensure continued delivery of urgent and emergency paediatric services and the associated maternity and neonatal services at local levels throughout the pandemic. A rapid reconfiguration of services was necessary when the pandemic reached the NHS. Healthcare services had to rethink how to deliver care in the short and medium term, better preparing them for future demands and ensuring that safe and effective care was maintained.

Background The purpose of this study was to develop a software tool and evaluate different T1 map calculation methods in terms of computation time in cardiac magnetic resonance imaging. Methods The modified Look-Locker inversion recovery (MOLLI) sequence was used to acquire multiple inversion time (TI) images for pre- and post-contrast T1 mapping. The T1 map calculation involved pixel-wise curve fitting based on the T1 relaxation model. A variety of methods were evaluated using data from 30 subjects for computational efficiency: MRmap, python Levenberg–Marquardt (LM), python reduced-dimension (RD) non-linear least square, C++ single- and multi-core LM, and C++ single- and multi-core RD. Results Median (interquartile range) computation time was 126 s (98–141) for the publicly available software MRmap, 261 s (249–282) for python LM, 77 s (74–80) for python RD, 3.4 s (3.1–3.6) for C++ multi-core LM, and 1.9 s (1.9–2.0) for C++ multi-core RD. The fastest C++ multi-core RD and the publicly available MRmap showed good agreement of myocardial T1 values, resulting in 95% Bland–Altman limits of agreement of (− 0.83 to 0.58 ms) and (− 6.57 to 7.36 ms) with mean differences of − 0.13 ms and 0.39 ms, for the pre- and post-contrast, respectively. Conclusion The C++ multi-core RD was the fastest method on a regular eight-core personal computer for pre- or post-contrast T1 map calculation. The presented software tool (fT1fit) facilitated rapid T1 map and extracellular volume fraction map calculations.

Background The objective of the study was to validate biomechanical characteristics of a 3D-printed, novel-designated fixation plate for treating mandibular angle fracture, and compare it with two commonly used fixation plates by finite element (FE) simulations and experimental testing. Methods A 3D virtual mandible was created from a patient’s CT images as the master model. A custom-designed plate and two commonly used fixation plates were reconstructed onto the master model for FE simulations. Modeling of angle fracture, simulation of muscles of mastication, and defining of boundary conditions were integrated into the theoretical model. Strain levels during different loading conditions were analyzed using a finite element method (FEM). For mechanical test design, samples of the virtual mandible with angle fracture and the custom-designed fixation plates were printed using selective laser sintering (SLS) and selective laser melting (SLM) printing methods. Experimental data were collected from a testing platform with attached strain gauges to the mandible and the plates at different 10 locations during mechanical tests. Simulation of muscle forces and temporomandibular joint conditions were built into the physical models to improve the accuracy of clinical conditions. The experimental vs the theoretical data collected at the 10 locations were compared, and the correlation coefficient was calculated. Results The results show that use of the novel-designated fixation plate has significant mechanical advantages compared to the two commonly used fixation plates. The results of measured strains at each location show a very high correlation between the physical model and the virtual mandible of their biomechanical behaviors under simulated occlusal loading conditions when treating angle fracture of the mandible. Conclusions Based on the results from our study, we validate the accuracy of our computational model which allows us to use it for future clinical applications under more sophisticated biomechanical simulations and testing.

A new coronavirus infection named coronavirus disease (COVID-19) was discovered in Wuhan, China at the end of 2019, and has rapidly progressed. The World Health Organization (WHO) declared COVID-19 a pandemic in March 2020. COVID-19 was characterised by the rapidity of the outbreak that was accelerated by transportation networks worldwide. Researchers have attempted various approaches to manage COVID-19, such as genome analyses, diagnostic methods, treatments, and prevention. An ‘infodemic’ situation has developed, whereby misinformation has caused logistical disruptions and resulted in health hazards and shortages of supplies. In Japan, face masks became difficult to find and toilet paper temporarily disappeared from stores because it was thought that it was made from the same paper as masks.1 Similar panic buying and stockpiling has occurred worldwide, disrupting logistics. In Iran, a false rumour circulated that methanol was effective against COVID-19, which led to nearly 500 deaths.2 In the USA, the President Donald Trump made comments about injecting disinfectant, leading to several people drinking the disinfectant and causing them health problems.3 The International Telecommunication Union (ITU) released a statement to make it known that there is no scientific basis for the claim that 5G network accelerated the COVID-19 pandemic.4 Social unrest has increased the stigma attached to those of Asian ethnicity, people who have recovered from COVID-19, and health care workers.5 Even before the COVID-19 outbreak, smartphone apps were being utilised to combat infectious diseases, and more apps have since been developed to tackle COVID-19. Though information and communication technology (ICT) have the capacity to cause an infodemic, ICT has been widely applied as a tool against the COVID-19 crisis. The Taiwanese government disclosed that their advanced information technology capacity helped them to achieve far greater control of COVID-19 than other countries.6 In this article, the author has reviewed the features of successful ICT approaches against COVID-19 and discussed their effects.

Background CT artifacts induced by orthopedic implants can limit image quality and diagnostic yield. As a number of different strategies to reduce artifact extent exist, the aim of this study was to systematically compare ex vivo the impact of different CT metal artifact reduction (MAR) strategies on spine implants made of either standard titanium or carbon-fiber-reinforced-polyetheretherketone (CFR-PEEK). Methods Spine surgeons fluoroscopically-guided prepared six sheep spine cadavers with pedicle screws and rods of either titanium or CFR-PEEK. Samples were subjected to single- and dual-energy (DE) CT-imaging. Different tube voltages (80, DE mixed, 120 and tin-filtered 150 kVp) at comparable radiation dose and iterative reconstruction versus monoenergetic extrapolation (ME) techniques were compared. Also, the influence of image reconstruction kernels (soft vs. bone tissue) was investigated. Qualitative (Likert scores) and quantitative parameters (attenuation changes induced by implant artifact, implant diameter and image noise) were evaluated by two independent radiologists. Artifact degree of different MAR-strategies and implant materials were compared by multiple ANOVA analysis. Results CFR-PEEK implants induced markedly less artifacts than standard titanium implants (p p p Conclusions CFR-PEEK spine implants induce significantly less artifacts than standard titanium compositions with higher MAR efficiency than any alternate scanning or image reconstruction strategy. DECT ME 130 keV image reconstructions showed least metal artifacts. Reconstruction kernels primarily modulate image noise with minor impact on artifact degree.