Tumor progression, including metastasis, is significantly influenced by factors in the tumor microenvironment (TME) such as mechanical force, shear stress, chemotaxis, and hypoxia. At present, most ...cancer studies investigate tumor metastasis by conventional cell culture methods and animal models, which are limited in data interpretation. Although patient tissue analysis, such as human patient-derived xenografts (PDX), can provide important clinical relevant information, they may not be feasible for functional studies as they are costly and time-consuming. Thus, in vitro three-dimensional (3D) models are rapidly being developed that mimic TME and allow functional investigations of metastatic mechanisms and drug responses. One of those new 3D models is tumor-on-a-chip technology that provides a powerful in vitro platform for cancer research, with the ability to mimic the complex physiological architecture and precise spatiotemporal control. Tumor-on-a-chip technology can provide integrated features including 3D scaffolding, multicellular culture, and a vasculature system to simulate dynamic flow in vivo. Here, we review a select set of recent achievements in tumor-on-a-chip approaches and present potential directions for tumor-on-a-chip systems in the future for areas including mechanical and chemical mimetic systems. We also discuss challenges and perspectives in both biological factors and engineering methods for tumor-on-a-chip progress. These approaches will allow in the future for the tumor-on-a-chip systems to test therapeutic approaches for individuals through using their cancerous cells gathered through approaches like biopsies, which then will contribute toward personalized medicine treatments for improving their outcomes.
Confocal Raman spectroscopy has emerged as a major, versatile workhorse for the non-invasive characterization of graphene. Although it is successfully used to determine the number of layers, the ...quality of edges, and the effects of strain, doping and disorder, the nature of the experimentally observed broadening of the most prominent Raman 2D line has remained unclear. Here we show that the observed 2D line width contains valuable information on strain variations in graphene on length scales far below the laser spot size, that is, on the nanometre-scale. This finding is highly relevant as it has been shown recently that such nanometre-scaled strain variations limit the carrier mobility in high-quality graphene devices. Consequently, the 2D line width is a good and easily accessible quantity for classifying the crystalline quality, nanometre-scale flatness as well as local electronic properties of graphene, all important for future scientific and industrial applications.
Tuberculosis is currently the single most deadly infectious disease in the world and a public health priority as defined by WHO. Although the disease is in general curable, treatment success is ...hampered by the necessity of a long and side effect prone treatment. Low treatment efficiency may be partly due to the special growth states that mycobacteria enter to avoid being killed by antibiotics and to persist longer within the host. Such growth states have been recently defined as dormant or persistent. We produced dormant model-organism cultures using an acidification model and characterized those by a multilayered approach using mass spectrometry (MALDI-TOF), microscopy (SEM, Raman), and microbiological techniques (CFU, OD600, ATP-levels). With a fast and 96-well-adapted extraction protocol, mycobacteria could be inactivated and extracted for MALDI-TOF analysis. For the first time, we demonstrate growth-state-dependent changes in the mass signatures of the culture, allowing for a reliable differentiation of dormant state and exponential growth. We also demonstrate resuscitation from dormant state back to exponential growth. Viable mycobacteria were immobilized, and single organisms were analyzed individually by Raman microscopy. For single-cell Raman microscopy, Mycobacterium smegmatis cultures were fixed using a new fast and gentle single-step immobilization technique on a hydrophobic glass slide. We were able to distinguish single viable bacteria in the dormant state from their rapidly growing, genetically identical counterparts, identifying the growth state of the culture based on single-organism spectra. This allows for the separation of heterogeneous cultures depending on their growth state using the destruction-free optical method of Raman microscopy.
Worldwide, multiresistant bacterial strains are emerging at unprecedented rates. This development seriously threatens the ability of humanity to treat even common infections, resulting in disability ...and death. Furthermore, this development endangers all medical achievements including cancer therapy or organ transplantations. Therefore, the World Health Organization has endorsed antimicrobial resistance as a great threat to humanity. To still allow effective treatment of patients, rapid, automated, and reliable antibiotic susceptibility testing (AST) of bacterial pathogens is essential. Thereby, speed and sensitivity of the AST results are crucial for improving patient care. Here, Raman spectroscopy as a nondestructive technique providing chemical-specific information is employed to monitor the deuterium uptake of metabolically active bacteria during antibiotic treatment, enabling fast and reliable AST. For this purpose, a bulk sample-preparation method was developed, allowing a high-throughput analysis of a significant number of cells. A protocol was developed for Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli) reference strains and was tested on 51 clinical isolates with well-characterized resistance phenotypes against ampicillin, ciprofloxacin, meropenem, and vancomycin. Borderline resistant and heteroresistant phenotypes were observed and further investigated. This is of critical importance as the sensitive detection of low-frequency heteroresistance in bacterial populations is a huge challenge. Such isolates seem susceptible but are resistant to treatment in vivo. Automatable analysis detects strong phenotypes within 3 h. On the basis of experimental and modeled data, heteroresistance is estimated to be detectable down to frequencies of 10–6 and investigated on clinical isolates as a proof-of-concept study, but requiring longer incubation time.
In this paper, we investigate traces of cycle integrals of certain meromorphic modular forms. By relating them to regularized theta lifts we provide explicit formulae for them in terms of ...coefficients of harmonic Maass forms.
Background
Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug‐resistant organisms ...(MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences.
Materials and methods
One hundred and three culture‐positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well.
Results
The most prevalent Gram‐negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram‐positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression.
Conclusions
The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.
The fingerprint has, with considerable justification, come to be regarded as the acme of forensic identification. Over the last century, millions of cases have been resolved world wide because of ...marks left at crime scenes. The comparison methodology has not evolved greatly during its history and it is universal practice to present fingerprint evidence to a court as a categoric opinion of identification or exclusion, or to classify the evidence as inconclusive and not to report it. There has been a growing movement to supplement the fingerprint examination process by one that has a statistical model, supported by appropriate databases for calculating numerical measures of weight of evidence. The movement calls for the establishment of a logical framework for informing conclusions, based on explicit assumptions and data and open to revision and improvement. The aim is to enable the numerical evaluation of evidence that would currently be reported as a categorical identification and also of evidence that would currently be classified as inconclusive. The paper presents the results of a project carried out by the Forensic Science Service that aims to attain this goal. After a historical review, we describe a formal model for assigning numerical values to configurations of minutiae in fingerprints. We describe how the parameters of the model have been optimized to take account of interoperator variability and distortion of the finger pad, and we present the results of a substantial validation experiment that was based on searches that have been carried out on the US national fingerprint database of approximately 600 million fingerprints.
Electrosurgery is used in the majority of endoscopic therapeutic procedures. An understanding of the fundamental electrosurgical principles and various settings available on electrosurgical units is ...essential for the safe and effective use of electrosurgery during endoscopy. The aims of these technical guidelines are to: (1) expose physical principles relevant to the understanding of electrosurgery during endoscopy; (2) describe and provide practical recommendations regarding electrosurgical units that are commonly in use; (3) discuss the clinical relevance of technologies recently implemented in newer electrosurgical units; and (4) review factors relevant to commonly performed therapeutic procedures, including polypectomy, sphincterotomy, contact thermal hemostasis, and argon plasma coagulation.
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