Differentiating Radiation Necrosis and Metastatic Progression in Brain Tumors Using Radiomics and Machine Learning.

OBJECTIVES: Distinguishing between radiation necrosis (RN) and metastatic progression is extremely challenging due to their similarity in conventional imaging. This is crucial from a therapeutic point of view as this determines the outcome of the treatment. This study aims to establish an automated technique to differentiate RN from brain metastasis progression using radiomics with machine learning. METHODS: Eighty-six patients with brain metastasis after they underwent stereotactic radiosurgery as primary treatment were selected. Discrete wavelets transform, Laplacian-of-Gaussian, Gradient, and Square were applied to magnetic resonance post-contrast T1-weighted images to extract radiomics features. After feature selection, dataset was randomly split into train/test (80%/20%) datasets. Random forest classification, logistic regression, and support vector classification were trained and subsequently validated using test set. The classification performance was measured by area under the curve (AUC) value of receiver operating characteristic curve, accuracy, sensitivity, and specificity. RESULTS: The best performance was achieved using random forest classification with a Gradient filter (AUC=0.910±0.047, accuracy 0.8±0.071, sensitivity=0.796±0.055, specificity=0.922±0.059). For, support vector classification the best result obtains using wavelet_HHH with a high AUC of 0.890±0.89, accuracy of 0.777±0.062, sensitivity=0.701±0.084, and specificity=0.85±0.112. Logistic regression using wavelet_HHH provides a poor result with AUC=0.882±0.051, accuracy of 0.753±0.08, sensitivity=0.717±0.208, and specificity=0.816±0.123. CONCLUSION: This type of machine-learning approach can help accurately distinguish RN from recurrence in magnetic resonance imaging, without the need for biopsy. This has the potential to improve the therapeutic outcome.

Mixed Organic Cations Promote Ambient Light-Induced Formation of Metallic Lead in Lead Halide Perovskite Crystals.

One major concern toward the performance and stability of halide perovskite-based optoelectronic devices is the formation of metallic lead that promotes nonradiative recombination of charge carriers. The origin of metallic lead formation is being disputed whether it occurs during the perovskite synthesis or only after light, electron, or X-ray beam irradiation or thermal annealing. Here, we show that the quantity of metallic lead detected in perovskite crystals depends on the concentration and composition of the precursor solution. Through a controlled crystallization process, we grew black-colored mixed dimethylammonium (DMA)/methylammonium (MA) lead tribromide crystals. The black color is suggested to be due to the presence of small lead clusters. Despite the unexpected black coloring, the crystals show higher crystallinity and less defect density with respect to the standard yellow-colored DMA/MAPbBr3 crystals, as indicated by X-ray rocking curve and dark current measurements, respectively. While the formation of metallic lead could still be induced by external factors, the precursor solution composition and concentration can facilitate the formation of metallic lead during the crystallization process. Our results indicate that additional research is required to fully understand the perovskite precursor solution chemistry.

Fluorescence-Based Portable Assays for Detection of Biological and Chemical Analytes.

Fluorescence-based detection techniques are part of an ever-expanding field and are widely used in biomedical and environmental research as a biosensing tool. These techniques have high sensitivity, selectivity, and a short response time, making them a valuable tool for developing bio-chemical assays. The endpoint of these assays is defined by changes in fluorescence signal, in terms of its intensity, lifetime, and/or shift in spectrum, which is monitored using readout devices such as microscopes, fluorometers, and cytometers. However, these devices are often bulky, expensive, and require supervision to operate, which makes them inaccessible in resource-limited settings. To address these issues, significant effort has been directed towards integrating fluorescence-based assays into miniature platforms based on papers, hydrogels, and microfluidic devices, and to couple these assays with portable readout devices like smartphones and wearable optical sensors, thereby enabling point-of-care detection of bio-chemical analytes. This review highlights some of the recently developed portable fluorescence-based assays by discussing the design of fluorescent sensor molecules, their sensing strategy, and the fabrication of point-of-care devices.

Gram-negative bacillary meningitis in an immunocompetent adult.

Escherichia coli is a rare cause of community-acquired meningitis comprising about 1% of adult cases. However, it is a common pathogen in neonatal meningitis and in nosocomial setting (especially after penetrating craniocerebral injury or subsequent to neurosurgical procedures). We report a middle-aged woman, who was admitted with features of acute meningitis and subsequent investigations revealed E. coli growth in cerebrospinal fluid culture. The case is distinctive as no additional predisposing risk factors associated with gram-negative bacillary meningitis (traumatic brain injury, neurosurgical procedures, malignancy, immunosuppressive therapy, HIV infection, chronic alcoholism and diabetes) were present. She was treated with intravenous antibiotics as per sensitivity reports and discharged in clinically stable condition, without any residual neurological deficit.

Membrane stretching activates calcium permeability of a putative channel Pkd2 during fission yeast cytokinesis.

Pkd2 is the fission yeast homologue of polycystins. This putative ion channel localizes to the plasma membrane. It is required for the expansion of cell volume during interphase growth and cytokinesis, the last step of cell division. However, the channel activity of Pkd2 remains untested. Here, we examined the calcium permeability and mechanosensitivity of Pkd2 through in vitro reconstitution and calcium imaging of pkd2 mutant cells. Pkd2 was translated and inserted into the lipid bilayers of giant unilamellar vesicles using a cell-free expression system. The reconstituted Pkd2 permeated calcium when the membrane was stretched via hypoosmotic shock. In vivo, inactivation of Pkd2 through a temperature-sensitive mutation pkd2-B42 reduced the average intracellular calcium level by 34%. Compared with the wild type, the hypomorphic mutation pkd2-81KD reduced the amplitude of hypoosmotic shock-triggered calcium spikes by 59%. During cytokinesis, mutations of pkd2 reduced the calcium spikes, accompanying cell separation and the ensuing membrane stretching, by 60%. We concluded that fission yeast polycystin Pkd2 allows calcium influx when activated by membrane stretching, representing a likely mechanosensitive channel that contributes to the cytokinetic calcium spikes.

A Clinical Comparison along with Prediction of the Outcome and Prognosis of Anterior and Posterior Circulation Stroke Patients Admitted in Tertiary Care Hospital.

INTRODUCTION: Stroke is the third common cause of death in India after ischemic heart disease and chronic obstructive pulmonary disease. Clinical features and outcomes vary in different types of strokes. OBJECTIVES: To compare the National Institutes of Health Stroke Scale (NIHSS) score of anterior and posterior circulation stroke patients (confirmed by neuroimaging) on the day of admission, admitted in Department of General Medicine, R. G. Kar Medical College and Hospital (RGKMCH), Kolkata and to predict the prognosis and outcome of the two types of strokes based on the modified Rankin Scale (mRS) on day 5 of admission. METHODOLOGY: After approval from Institutional Ethics Committee and taking written informed consent from participants an observational cross-sectional study was conducted in the Department of General Medicine of a tertiary care hospital over 1.5 years. Clinical features, outcome, and prognosis between anterior and posterior circulation stroke group are compared and results are analyzed. RESULTS: In anterior circulation, the mean of age (mean ± SD) of patients was 59.2875 ± 6.7790 years; 25 (31.3%) patients were female and 55 (68.8%) patients were male; three (3.8%) patients were Christian, 39 (48.8%) patients were Hindu, and 38 (47.5%) patients were Muslim; the mean of BMI (mean ± SD) of patients was 24.7038 ± 2.3695 kg/m2 ; 71 (88.8%) patients were from rural area and nine (11.3%) patients were from urban area; 73 (91.3%) patients had hypertension, 51 (63.8%) patients had diabetes mellitus, 24 (30.0%) patients had hypothyroidism, and 56 (70.0%) patients had ischemic heart disease; the mean of NIHSS score on day 0 (mean ± SD) of patients was 13.9875 ± 4.0362, the mean of mRS score on day 5 (mean ± SD) of patients was 2.1125 ±.9936. In posterior circulation, the mean of age (mean ± SD) of patients was 59.2167 ± 6.7826 years; 20 (33.2%) patients were female and 40 (66.7%) patients were male; two (3.3) patients were Christian, 29 (48.3%) patients were Hindu, and 29 (48.3%) patients were Muslim; the mean of BMI (mean ± SD) of patients was 24.7017 ± 2.3265 kg/m2 ; 51 (85.0%) patients were from rural area and nine (15.0%) patients were from urban area; 54 (90.0%) patients had hypertension, 37 (61.7%) patients had diabetes mellitus, 18 (30.0%) patients had hypothyroidism, and 42 (70.0%) patients had ischemic heart disease; the mean of NIHSS score on day 0 (mean ± SD) of patients was 23.8833 ± 4.5737, the mean of mRS score on day 5 (mean ± SD) of patients was 4.6333 ± .8227. CONCLUSION: Symptoms of PCI stroke patients are more severe than that of ACI stroke patients. The outcome and prognosis of PCI stroke patients are worse compared to the ACI stroke patients.

Structural properties of defective (CH3NH3)2Cu(Cl1-xBrx)4 compounds.

The crystal structures of (CH3NH3)2Cu(Cl1-xBrx)4 compounds have been investigated by means of synchrotron powder X-ray diffraction and pair distribution function analysis at room temperature. As a result, new insights are gained about the structural properties of these compounds, suggesting a monoclinic symmetry (space group No. 14: P21/c - C_{2h}^{5}) induced by the co-operative orbital ordering produced by the Jahn-Teller distortion characterizing the 3d9 Cu2+ ion. In contrast to previous studies, a significant amount of vacancies is found at halogen positions, a feature that can be likely ascribed to the synthesis technique adopted in the present study. Br atoms preferentially occupy axial positions, likely on account of reduced steric hindrance at these sites.

Automated detection of apoptotic versus nonapoptotic cell death using label-free computational microscopy.

Identification of cell death mechanisms, particularly distinguishing between apoptotic versus nonapoptotic pathways, is of paramount importance for a wide range of applications related to cell signaling, interaction with pathogens, therapeutic processes, drug discovery, drug resistance, and even pathogenesis of diseases like cancers and neurogenerative disease among others. Here, we present a novel high-throughput method of identifying apoptotic versus necrotic versus other nonapoptotic cell death processes, based on lensless digital holography. This method relies on identification of the temporal changes in the morphological features of mammalian cells, which are unique to each cell death processes. Different cell death processes were induced by known cytotoxic agents. A deep learning-based approach was used to automatically classify the cell death mechanism (apoptotic vs necrotic vs nonapoptotic) with more than 93% accuracy. This label free approach can provide a low cost (<$250) alternative to some of the currently available high content imaging-based screening tools.

Mixed Dimethylammonium/Methylammonium Lead Halide Perovskite Crystals for Improved Structural Stability and Enhanced Photodetection.

The solvent acidolysis crystallization technique is utilized to grow mixed dimethylammonium/methylammonium lead tribromide (DMA/MAPbBr3 ) crystals reaching the highest dimethylammonium incorporation of 44% while maintaining the 3D cubic perovskite phase. These mixed perovskite crystals show suppression of the orthorhombic phase and a lower tetragonal-to-cubic phase-transition temperature compared to MAPbBr3 . A distinct behavior is observed in the temperature-dependent photoluminescence properties of MAPbBr3 and mixed DMA/MAPbBr3 crystals due to the different organic cation dynamics governing the phase transition(s). Furthermore, lateral photodetectors based on these crystals show that, at room temperature, the mixed crystals possess higher detectivity compared to MAPbBr3 crystals caused by structural compression and reduced surface trap density. Remarkably, the mixed-crystal devices exhibit large enhancement in their detectivity below the phase-transition temperature (at 200 K), while for the MAPbBr3 devices only insignificant changes are observed. The high detectivity of the mixed crystals makes them attractive for visible-light communication and for space applications. The results highlight the importance of the synthetic technique for compositional engineering of halide perovskites that governs their structural and optoelectronic properties.

Diagnosis of Herpes Simplex Virus: Laboratory and Point-of-Care Techniques.

Herpes is a widespread viral infection caused by the herpes simplex virus (HSV) that has no permanent cure to date. There are two subtypes, HSV-1 and HSV-2, that are known to cause a variety of symptoms, ranging from acute to chronic. HSV is highly contagious and can be transmitted via any type of physical contact. Additionally, viral shedding can also happen from asymptomatic infections. Thus, early and accurate detection of HSV is needed to prevent the transmission of this infection. Herpes can be diagnosed in two ways, by either detecting the presence of the virus in lesions or the antibodies in the blood. Different detection techniques are available based on both laboratory and point of care (POC) devices. Laboratory techniques include different biochemical assays, microscopy, and nucleic acid amplification. In contrast, POC techniques include microfluidics-based tests that enable on-spot testing. Here, we aim to review the different diagnostic techniques, both laboratory-based and POC, their limits of detection, sensitivity, and specificity, as well as their advantages and disadvantages.

Intracellular detection of singlet oxygen using fluorescent nanosensors.

Detection of singlet oxygen is of great importance for a range of therapeutic applications, particularly photodynamic therapy, plasma therapy and also during photo-endosomolytic activity. Here we present a novel method of intracellular detection of singlet oxygen using biocompatible polymeric nanosensors, encapsulating the organic fluorescent dye, Singlet Oxygen Sensor Green (SOSG) within its hydrophobic core. The singlet oxygen detection efficiency of the nanosensors was quantified experimentally by treating them with a plasma source and these results were further validated by using Monte Carlo simulations. The change in fluorescence intensity of the nanosensors serves as a metric to detect singlet oxygen in the local micro-environment inside mammalian cancer cells. We used these nanosensors for monitoring singlet oxygen inside endosomes and lysosomes of cancer cells, during cold plasma therapy, using a room-temperature Helium plasma jet.

A Novel Thienopyrimidine Analog, TPH104, Mediates Immunogenic Cell Death in Triple-Negative Breast Cancer Cells.

Enhancing the tumor immunogenic microenvironment has been suggested to circumvent triple-negative breast cancer (TNBC) resistance and increase the efficacy of conventional chemotherapy. Here, we report a novel chemotherapeutic compound, TPH104, which induces immunogenic cell death in the TNBC cell line MDA-MB-231, by increasing the stimulatory capacity of dendritic cells (DCs), with an IC50 value of 140 nM. TPH104 (5 µM) significantly increased ATP levels in the supernatant and mobilized intracellular calreticulin to the plasma membrane in MDA-MB-231 cells, compared to cells incubated with the vehicle. Incubating MDA-MB-231 cells for 12 h with TPH104 (1-5 µM) significantly increased TNF-α mRNA levels. The supernatants of dying MDAMB-231 cells incubated with TPH104 increased mouse bone marrow-derived DC maturation, the expression of MHC-II and CD86 and the mRNA expression of TNF-α, IL-6 and IL-12. Overall, these results indicate that TPH104 induces immunogenic cell death in TNBC cells, in part, by activating DCs.

Calcium spikes accompany cleavage furrow ingression and cell separation during fission yeast cytokinesis.

The role of calcium signaling in cytokinesis has long remained ambiguous. Past studies of embryonic cell division discovered that calcium concentration increases transiently at the division plane just before cleavage furrow ingression, suggesting that these calcium transients could trigger contractile ring constriction. However, such calcium transients have only been found in animal embryos and their function remains controversial. We explored cytokinetic calcium transients in the fission yeast Schizosaccharomyces pombe by adopting GCaMP, a genetically encoded calcium indicator, to determine the intracellular calcium level of this model organism. We validated GCaMP as a highly sensitive calcium reporter in fission yeast, allowing us to capture calcium transients triggered by osmotic shocks. We identified a correlation between the intracellular calcium level and cell division, consistent with the existence of calcium transients during cytokinesis. Using time-lapse microscopy and quantitative image analysis, we discovered calcium spikes both at the start of cleavage furrow ingression and the end of cell separation. Inhibition of these calcium spikes slowed the furrow ingression and led to frequent lysis of daughter cells. We conclude that like the larger animal embryos, fission yeast triggers calcium transients that may play an important role in cytokinesis (197).

Mobile Diagnostic Devices for Digital Transformation in Personalized Healthcare.

Mobile devices have increasingly become an essential part of the healthcare system worldwide [...].

Detection of Bacterial and Viral Pathogens Using Photonic Point-of-Care Devices.

Infectious diseases caused by bacteria and viruses are highly contagious and can easily be transmitted via air, water, body fluids, etc. Throughout human civilization, there have been several pandemic outbreaks, such as the Plague, Spanish Flu, Swine-Flu, and, recently, COVID-19, amongst many others. Early diagnosis not only increases the chance of quick recovery but also helps prevent the spread of infections. Conventional diagnostic techniques can provide reliable results but have several drawbacks, including costly devices, lengthy wait time, and requirement of trained professionals to operate the devices, making them inaccessible in low-resource settings. Thus, a significant effort has been directed towards point-of-care (POC) devices that enable rapid diagnosis of bacterial and viral infections. A majority of the POC devices are based on plasmonics and/or microfluidics-based platforms integrated with mobile readers and imaging systems. These techniques have been shown to provide rapid, sensitive detection of pathogens. The advantages of POC devices include low-cost, rapid results, and portability, which enables on-site testing anywhere across the globe. Here we aim to review the recent advances in novel POC technologies in detecting bacteria and viruses that led to a breakthrough in the modern healthcare industry.

Measurement of serum phosphate levels using a mobile sensor.

The measurement of serum phosphate concentration is crucial for patients with advanced chronic kidney disease (CKD) and those on maintenance dialysis, as abnormal phosphate levels may be associated with severe health risks. It is important to monitor serum phosphate levels on a regular basis in these patients; however, such measurements are generally limited to every 0.5-3 months, depending on the severity of CKD. This is due to the fact that serum phosphate measurements can only be performed at regular clinic visits, in addition to cost considerations. Here we present a portable and cost-effective point-of-care device capable of measuring serum phosphate levels using a single drop of blood (<60 µl). This is achieved by integrating a paper-based microfluidic platform with a custom-designed smartphone reader. This mobile sensor was tested on patients undergoing dialysis, where whole blood samples were acquired before starting the hemodialysis and during the three-hour treatment. This sampling during the hemodialysis, under patient consent, allowed us to test blood samples with a wide range of phosphate concentrations, and our results showed a strong correlation with the ground truth laboratory tests performed on the same patient samples (Pearson coefficient r = 0.95 and p < 0.001). Our 3D-printed smartphone attachment weighs about 400 g and costs less than 80 USD, whereas the material cost for the disposable test is <3.5 USD (under low volume manufacturing). This low-cost and easy-to-operate system can be used to measure serum phosphate levels at the point-of-care in about 45 min and can potentially be used on a daily basis by patients at home.

Holographic detection of nanoparticles using acoustically actuated nanolenses.

The optical detection of nanoparticles, including viruses and bacteria, underpins many of the biological, physical and engineering sciences. However, due to their low inherent scattering, detection of these particles remains challenging, requiring complex instrumentation involving extensive sample preparation methods, especially when sensing is performed in liquid media. Here we present an easy-to-use, high-throughput, label-free and cost-effective method for detecting nanoparticles in low volumes of liquids (25 nL) on a disposable chip, using an acoustically actuated lens-free holographic system. By creating an ultrasonic standing wave in the liquid sample, placed on a low-cost glass chip, we cause deformations in a thin liquid layer (850 nm) containing the target nanoparticles (≥140 nm), resulting in the creation of localized lens-like liquid menisci. We also show that the same acoustic waves, used to create the nanolenses, can mitigate against non-specific, adventitious nanoparticle binding, without the need for complex surface chemistries acting as blocking agents.

Computational cytometer based on magnetically modulated coherent imaging and deep learning.

Detecting rare cells within blood has numerous applications in disease diagnostics. Existing rare cell detection techniques are typically hindered by their high cost and low throughput. Here, we present a computational cytometer based on magnetically modulated lensless speckle imaging, which introduces oscillatory motion to the magnetic-bead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions (3D). In addition to using cell-specific antibodies to magnetically label target cells, detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network (P3D CNN), which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force. To demonstrate the performance of this technique, we built a high-throughput, compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples. Through serial dilution experiments, we quantified the limit of detection (LoD) as 10 cells per millilitre of whole blood, which could be further improved through multiplexing parallel imaging channels within the same instrument. This compact, cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications.

Computational Image Analysis of Guided Acoustic Waves Enables Rheological Assessment of Sub-nanoliter Volumes.

We present a method for the computational image analysis of high frequency guided sound waves based upon the measurement of optical interference fringes, produced at the air interface of a thin film of liquid. These acoustic actuations induce an affine deformation of the liquid, creating a lensing effect that can be readily observed using a simple imaging system. We exploit this effect to measure and analyze the spatiotemporal behavior of the thin liquid film as the acoustic wave interacts with it. We also show that, by investigating the dynamics of the relaxation processes of these deformations when actuation ceases, we are able to determine the liquid's viscosity using just a lens-free imaging system and a simple disposable biochip. Contrary to all other acoustic-based techniques in rheology, our measurements do not require monitoring of the wave parameters to obtain quantitative values for fluid viscosities, for sample volumes as low as 200 pL. We envisage that the proposed methods could enable high throughput, chip-based, reagent-free rheological studies within very small samples.

Green-Emitting Powders of Zero-Dimensional Cs4PbBr6: Delineating the Intricacies of the Synthesis and the Origin of Photoluminescence.

A detailed investigation into the synthesis of green-emitting powders of Cs4PbBr6 and CsPbBr3 materials by antisolvent precipitation from CsBr-PbBr2 precursor solutions in dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) is reported. Various solvated lead bromide and polybromide species (PbBr2, [PbBr3]-, [PbBr4]2-, and possibly [PbBr5]3-or [PbBr6]4-) are detected in the precursor solutions by optical absorbance and emission spectroscopies. The solvodynamic size of the species in solution is strongly solvent-dependent: ~1 nm species were detected in DMSO, while significantly larger species were observed in DMF by dynamic light scattering. The solvodynamic size of the lead bromide species plays a critical role in determining the Cs-Pb-Br composition of the precipitated powders: smaller species favor the precipitation of Cs4PbBr6, while larger species template the formation of CsPbBr3 under identical experimental conditions. The powders have been characterized by 133Cs and 207Pb solid-state nuclear magnetic resonance, and 133Cs sensitivity toward the different Cs environments within Cs4PbBr6 is demonstrated. Finally, the possible origins of green emission in Cs4PbBr6 samples are discussed. It is proposed that a two-dimensional Cs2PbBr4 inclusion may be responsible for green emission at ~520 nm in addition to the widely acknowledged CsPbBr3 impurity, although we found no conclusive experimental evidence supporting such claims.