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The effect of vaccination on severity of subsequent COVID-19 in patients with hematologic malignancies (HMs) is unknown. In this single-center retrospective cohort study, we found no difference in severity of COVID-19 disease in vaccinated (n=16) versus unvaccinated (n=54) HM patients using an adjusted multiple logistic regression model. Recent anti-B-cell therapy was associated with more severe illness.

Background Pneumonia is the most common infectious cause of morbidity and excess mortality complicating hematopoietic cell transplantation (HCT) and treatment of hematologic malignancy. Standard bronchoscopic and noninvasive microbiologic testing identify causative pathogens in less than half of cases. The Karius Test, a plasma next-generation sequencing assay of microbial cell-free DNA, may improve diagnostic yield in these patients. Methods Patients with active hematologic malignancy or recent HCT undergoing bronchoscopy for suspected pneumonia were prospectively enrolled in this observational study conducted at 10 United States medical centers. A panel of expert clinicians blinded to Karius Test results reviewed a standardized panel of microbiologic and molecular testing from bronchoalveolar lavage and blood samples for bacterial and fungal testing, nasopharyngeal swab for respiratory viral testing, imaging results, clinical documentation, and any additional microbiologic or molecular testing collected per usual standard of care to adjudicate a probable cause of pneumonia. The panel then adjudicated whether a probable cause of pneumonia or other clinically relevant infection was identified by the Karius Test. Results Between January 3, 2020 and February 4, 2022, 257 patients were enrolled. A planned interim analysis of the first 69 sequentially enrolled patients in the per protocol population was conducted. An adjudicated probable cause of pneumonia was identified by standard care in 18/69 (26%) patients. The Karius Test identified an adjudicated probable cause of pneumonia in 10/51 (20%) patients when no cause of pneumonia was identified by standard care testing. The combination of standard care and the Karius Test together identified a probable cause of pneumonia in 28/69 (41%) patients. At least one additional pathogen adjudicated as a probable cause of pneumonia was identified by the Karius Test in 6/18 (33%) of patients with positive standard care testing. Conclusion The Karius Test notably increased the probability of identifying a pathogenic cause of pneumonia among immunocompromised patients undergoing bronchoscopy. The additive diagnostic value of the Karius Test may significantly enhance management of this common condition. Disclosures Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support Radha Duttagupta, PhD, Karius Inc: Stocks/Bonds Sanjeet S. Dadwal, MD, FACP, FIDSA, AlloVir: Advisor/Consultant|AlloVir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope: Advisor/Consultant|Aseptiscope: Stocks/Bonds|Astellas: Speaker's Bureau|Cidara: Advisor/Consultant|Gilead: Grant/Research Support|Karius: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Speaker's Bureau|Takeda: Speaker's Bureau Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Ghady Haidar, MD, Karius, Allovir, and AstraZeneca: Grant/Research Support Alfred Luk, MD, Karius: Grant/Research Support Jamie Todd, MD, Altavant Sciences: Advisor/Consultant|AstraZeneca: Grant/Research Support|Boehringer Ingelheim: Grant/Research Support|CareDx: Grant/Research Support|Cellarity: Advisor/Consultant|Natera: Advisor/Consultant Genovefa Papanicolaou, MD, AlloVir: Board Member|AlloVir: Serve as member of DSMC|Amplyx: Board Member|Amplyx: Serve as member of DSMC|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|CSL Behring: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Investigator for Merck|MSD: Advisor/Consultant|Octapharma: Advisor/Consultant|Octapharma: Board Member|Octapharma: Serve as EAC member|Partners RX: Advisor/Consultant|SymBio: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Takeda: Investigator for Takeda|Vera: Board Member|Vera: Serve as member of DSMC Elena Nemirovich-Danchenko, MD PhD, Karius: Stocks/Bonds Mona Mughar, BS, Karius: Stocks/Bonds Sudeb Dalai, MD, Karius: Stocks/Bonds Sudeb Dalai, MD, Karius: Stocks/Bonds Yuen Cho, MS, CLS(CA-DPH), Karius: Stocks/Bonds Asim A. Ahmed, MD, Karius: Employee|Karius: Stocks/Bonds Desiree Hollemon, MSN, MPH, Karius: Stocks/Bonds David K. Hong, MD, Janssen Pharmaceutical Companies of Johnson & Johnson: Employee|Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Marla Lay Vaughn, BS, MT(ASCP), Karius: Employee|Karius: Stocks/Bonds Tim Blauwkamp, PhD, Karius: Board Member|Karius: Ownership Interest Zivjena Vucetic, MD, Karius: Stocks/Bonds Rina Romano, BS, Karius Inc: Stocks/Bonds|Karius Inc: Stocks/Bonds Rina Romano, BS, Karius Inc: Stocks/Bonds|Karius Inc: Stocks/Bonds Rina Romano, BS, Karius Inc: Stocks/Bonds|Karius Inc: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Thomas L. Holland, MD, Aridis: Advisor/Consultant|Lysovant: Advisor/Consultant.

Oxyanions of selenium, selenite (SeO3)2− and selenate (SeO4)2− are toxic to terrestrial and aquatic biota but few microorganisms including cyanobacteria are resistant to high levels of selenite. Cyanobacteria evade selenite toxicity through bioreduction and synthesis of selenium nanoparticles (SeNPs). In this study, extracellular biosynthesis of SeNPs (Se0) using cyanobacterium, Anabaena sp. PCC 7120 on exposure to sodium selenite and characterization was done by using UV–visible spectroscopy, SEM–EDX, TEM and FTIR analyses which confirmed spherical shape with size range of 5–50 nm diameter. These biogenic SeNPs demonstrated significant antibacterial and anti-biofilm activity against bacterial pathogens. Furthermore, these SeNPs showed high antioxidant activity at minimum concentration of 50 µg/mL and significant anti-proliferative activity against HeLa cell line with IC50 value of 5.5 µg/mL. The SeNPs also induced accumulation of cancer cells in the sub-G1 phase which was clearly observed in cellular and nuclear morphology. These biofabricated SeNPs also reduced and decolorized toxic methylene blue dye significantly through photocatalytic degradation. Therefore Anabaena sp. PCC 7120 may be employed as a green bioresource to synthesize SeNPs with potential applications in medicine and environmental bioremediation.

Water quality assessment relies mostly on physico-chemical-based characterization; however, eutrophication and climate change advocate the abundance of toxic microcystins (MCs) producing cyanobacteria as emerging bio-indicator. In the present study, a spatial-temporal analysis was carried out at ten sampling sites of Prayagraj and Varanasi during June 2017 and March 2018 to determine the Ganga River water quality using physico-chemical parameters, cyanobacteria diversity, detection of MCs producing strains and MC-LR equivalence. Coliform bacteria, COD, NO3-N, and phosphate are the significant contaminated parameters favoring the growth of putative MCs producing cyanobacteria. National Sanitation Foundation WQI (NSFWQI) indicates water quality, either bad or medium category at sampling points. The morphological analysis confirms the occurrence of diverse cyanobacterial genera such as Microcystis, Anabaena, Oscillatoria, and Phormidium. PCR amplification affirmed the presence of toxic microcystin (mcy) genes in uncultured cyanobacteria at all the sampling sites. The concentration of MC-LR equivalence in water samples by protein phosphatase 1 inhibition assay (PPIA) and high-performance liquid chromatography (HPLC) methods was observed in the range of 23.4–172 ng/L and 13.2–97.5 ng/L respectively which is lower than the harmful exposure limit by World Health Organization (WHO). Ganga isolate 1 was identified as Microcystis based on partial 16S rDNA sequence and its toxicity was confirmed due to presence of mcy genes and MCs production potential. These findings suggest the presence of MCs producers as new emerging parameter to monitor water quality index and identification up to species level will be valuable for restoration strategies of river Ganga.

BACKGROUND Stereotactic radiosurgery (SRS) is a cornerstone in the management of Breast Cancer Metastases to the Brain (BCMB). While control rates are high following SRS, radiation necrosis is a rare but potentially devastating long-term toxicity. There is a clinical need for automated/semi-automated methods to assess tumor response and optimize the RT plans for local control with minimal long-term toxicity. Multiparametric MRI (mpMRI), particularly Apparent Diffusion Coefficient of water (ADC) maps, contain information that is mechanistically relatable to voxel-level tumor response to RT. We report a deep learning-based approach to predict post-SRS ADC maps, FLAIR, T2-weighted (T2W), T1-weighted unenhanced (T1W) and contrast-enhanced (T1WCE) images, from pre-SRS T1W, T1WCE, T2W and FLAIR images, ADC maps, and the delivered RT dose map. These “forward models” will enable the radiation oncologist to simulate radiologic outcomes and iteratively optimize RT plans for local control with minimal toxicity. METHODS We trained a variant of the pix2pix Generative Adversarial Network (GAN) on MRI and RT dose map data from 18 BCMB patients treated with stereotactic radiation with confirmed controlled and locally recurrent metastases. Patients were treated with stereotactic radiation dose of 1-40 Gy between 2013-2019. RESULTS On test data from 6 BCMB patients, the trained forward model predicted post-SRS ADC values within the Gross Tumor Volume (GTV) that were broadly in agreement with ground truth post-SRS ADC maps. In agreement with expectations, the forward model also predicts increasing post-RT ADC within the GTV with increasing simulated RT doses in the range of 1-71 Gy. We have also explored an inverse model to predict the RT dose map required to produce “prescribed” post-SRS ADC values within the GTV. CONCLUSIONS We envision that the forward models will assist the radiation oncologist in initial RT dose plan optimization, while the inverse model may be useful for daily RT plan optimization.

Background: Usnic Acid has been progressively reported in the literature as one of the chiefly significant lichen metabolites exemplified by an ample diversity of applications such as antimicrobial, antifungal, antiviral, antiprotozoal agents, etc. Herein, we shed a light on nosocomial infections and formulated topical microspheres loaded with Usnic acid for improved antimicrobial activity. Recent patents and novel researches were referred to pursue the present work. Methods: Usnic acid embedded Eudragit microspheres were designed applying solvent evaporation method, investigated for topography and drug-polymer compatibility studies. Dialysis bag method was utilized for studying drug release kinetics. In vitro antibacterial assay was carried out against the virulent bacterial strain of Staphylococcus aureus using the disc diffusion method. Results: Topography studies revealed the formation of regular, micro-sized, smooth surface microspheres. Well defined and specific structural peaks were obtained from FTIR and TGA studies, revealing drugpolymer compatibility. The dissolution profile suggested Korsmeyer Peppas kinetic and Fickian kind of diffusion from microspheres. The pre-eminent activity of formulated microspheres was visualized from the disc diffusion study against Staphylococcus aureus. Conclusion: The strong biological activity of Usnic acid –loaded Eudragit RS and Eudragit RL microspheres provides a promising application for corresponding material as a bactericidal agent for the alleviation of nosocomial infection. Findings paid attention to the potential of usnic acid microspheres for effective treatment of dermal and nosocomial infections caused by S. aureus.

Multispectral analysis of coregistered multiparametric magnetic resonance (MR) images provides a powerful method for tissue phenotyping and segmentation. Acquisition of a sufficiently varied set of multicontrast MR images and parameter maps to objectively define multiple normal and pathologic tissue types can require long scan times. Accelerated MRI on clinical scanners with multichannel receivers exploits techniques such as parallel imaging, while accelerated preclinical MRI scanning must rely on alternate approaches. In this work, tumor-bearing mice were imaged at 7 T to acquire k-space data corresponding to a series of images with varying T1-, T2- and T2*-weighting. A joint reconstruction framework is proposed to reconstruct a series of T1-weighted images and corresponding T1 maps simultaneously from undersampled Cartesian k-space data. The ambiguity introduced by undersampling was resolved by using model-based constraints and structural information from a reference fully sampled image as the joint total variation prior. This process was repeated to reconstruct T2-weighted and T2*-weighted images and corresponding maps of T2 and T2* from undersampled Cartesian k-space data. Validation of the reconstructed images and parameter maps was carried out by computing tissue-type maps, as well as maps of the proton density fat fraction (PDFF), proton density water fraction (PDwF), fat relaxation rate ( R 2 f * ) and water relaxation rate ( R 2 w * ) from the reconstructed data, and comparing them with ground truth (GT) equivalents. Tissue-type maps computed using 18% k-space data were visually similar to GT tissue-type maps, with dice coefficients ranging from 0.43 to 0.73 for tumor, fluid adipose and muscle tissue types. The mean T1 and T2 values within each tissue type computed using only 18% k-space data were within 8%-10% of the GT values from fully sampled data. The PDFF and PDwF maps computed using 27% k-space data were within 3%-15% of GT values and showed good agreement with the expected values for the four tissue types.

Nanotechnology is one of the most promising and advanced disciplines of science that deals with synthesis, characterization and applications of different types of Nanomaterials (NMs) viz. nanospheres, nanoparticles, nanotubes, nanorods, nanowires, nanocomposites, nanoalloys, carbon dots and quantum dots. These nanosized materials exhibit different physicochemical characteristics and act as a whole unit during its transport. The unique characteristics and vast applications of NMs in diverse fields viz. electronics, agriculture, biology and medicine have created huge demand of different type of NMs. Conventionally physical and chemical methods were adopted to manufacture NMs which are expensive and end up with hazardous by-products. Therefore, green synthesis exploiting biological resources viz. algae, bacteria, fungi and plants emerged as a better and promising alternative due to its cost effective and ecofriendly approach and referred as nanobiotechnology. Among various living organisms, cyanobacteria have proved one of the most favourable bioresources for NMs biosynthesis due to their survival in diverse econiches including metal and metalloid contaminated sites and capability to withstand high levels of metals. Biosynthesis of metallic NMs is accomplished through bioreduction of respective metal salts by various capping agents viz. alkaloids, pigments, polysaccharides, steroids, enzymes and peptides present in the biological systems. Advancement in the field of Nanobiotechnology has produced large number of diverse NMs from cyanobacteria which have been used as antimicrobial agents against Gram positive and negative human pathogens, anticancer agents, luminescent nanoprobes for imaging of cells, antifungal agents against plant pathogens, nanocatalyst and semiconductor quantum dots in industries and in bioremediation in toxic pollutant dyes. In the present communication, we have reviewed cyanobacteria mediated biosynthesis of NMs and their applications in various fields.

In recent time, world have seen a rapid growth in wireless communication. Development in antenna from single band to dual band and multi band had made the antenna system more compact. A frequency reconfigurable microstrip antenna using a PIN diode for multiband operation is using many application and hot research area. In this paper, reconfigurable microstrip patch antennas and their types like frequency, polarization, radiation pattern and gain are described.

Functional tuning of T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced TCR sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity down-regulate TCR sensitivity more slowly during positive selection, and suggest that modulation of membrane ion channel function may play a role in regulating TCR tuning throughout development.Impact StatementDeveloping T cells whose TCRs have relatively low reactivity experience very brief TCR signaling events, delayed positive selection, and do not fully down regulate their TCR sensitivity as they mature.

In this paper we have implemented and designed an accurate and robust automatic speaker verification (ASV) system. There is a constant need for improving the performance of the ASV because of its many advantages over other biometric means. In this work we have experimented with the VoxCeleb dataset. The VoxCeleb Dataset which has more than 1200 individuals and around 300–500 utterances each. We have proposed a new approach to authenticate users at a text independent level. Firstly the audio files are converted to spectrograms which are pre-processed and then are classified using Convolutional Neural Networks (CNN) and a model is created at a text independent level. The classification of the individual speakers are made on the bases of Spectrogram. Finally, the performance evaluation is done using the training and validation accuracy plots.

QCA (Quantum Dot Cellular Automata) is an emerging and pioneer technology, which is a paradigm for computing with interacting quantum dots. Many eminent researchers have well thought of eloquent work in the existing areas of the sequential circuit. However, this paper proclaims three new approaches to design JK and T flip-flop. Since flip-flops and memory design are the crucial building blocks of digital circuits, therefore we concern the underlying principle of fundamental design of JK and T flip-flop and then work out to model the new structure favorable with the forthcoming excellence required. This new concept places elsewhere the need of using feedback path in flip flop design. Also two algorithms have been shown for explanatory purpose. The proposed structure is able to establish the validity and genuineness than earlier design. By using the proposed T flip-flop, a 2-bit and 3-bit counter is also designed in the paper. The simulation result of the proposed design proves their vigorousness and correctness in the output.

In this paper, an efficient procedure to identify vital bio-signals from the Fetal Phonocardiogram (FPCG) signal is presented. FPCG signal is rich in physiological bio-signals. However, extracting these bio-signals with fidelity is a challenging task since they overlap in time and frequency and as well as corrupted by noise induced from the maternal and fetal movements. While current approaches use a two-step process of de-noising the signal and then extract the vital bio-signals, Empirical Mode Decomposition (EMD) algorithm can efficiently de-noise and extract the maternal and fetal heart sounds in a single step. Frequency range obtained from the Short Time Fourier Transform (STFT) is used to validate the algorithm. It is observed that the bandwidths of extracted FHS and MHS signals are consistent with the existing gold standards.

This study presents a cluster analysis framework for acoustic signals of the novel catheter stethoscope. The objective of the current study is to collect the blood flow sounds from a body site of a Yorkshire pig using the novel acoustic catheter stethoscope and further recognize any changes in the sinus rhythm patterns. Initially the collected blood flow sounds are preprocessed with noise cancellation and wavelet source separation to result in acoustic heart and respiratory pulses. Then, the extracted acoustic heart pulses are post processed to recognize the patterns of the sinus rhythm based on a novel feature extraction technique and cluster analysis. Finally, the developed framework is qualitatively and quantitatively validated by providing visual results of the clustering and by computing the clustering accuracy, sensitivity and specificity. The cross validation results show that the developed framework consistently recognizes the patterns of the sinus rhythms with an accuracy rate of 94.37%.

Starting from the times of barter system to today's modern era of plastic money, the mankind has trodden a remarkably long path. Undoubtedly "profitability" has always been the driving force and an undercurrent behind all this development; but as every coin has two facets; growing cut throat competition and business rivalries started taking heavy toll on the quality, transparency, environment and the society in general endangering the peaceful coexistence of business and society. The businesses houses started realizing that they would have to rise over and above the profitability and take care of all those associated with their survival in the society directly or indirectly. This realization resulted into the concept of Corporate Social Responsibility (CSR). This research paper moves around developing an understanding about the corporate social responsibility (CSR), delving into its concept and finding out its scope taking the case study of the TATA Group under Mr. Ratan Tata who has exemplified the sense of responsibility towards the upliftment of common masses and protection of the environment and development of the nation.

Ethosomes, a kind of soft, ductile vesicular drug delivery system are widely used in cosmetic and pharmaceutical formulations to capsulate bioactive agent, its protection from degradation, enhancement of bioavailability and also to boost up the therapeutic efficacy. Ethosomes are popular field for researcher owing to its exceptionally skin permeation property and pronounced entrapment efficiency. The present study, a sincere attempt has been made to foreground the properties ,characterstics, evaluation parameters, methodology and patents till date regarding ethosomes. Ethosomes have also been put- upon in systemic drug delivery for the treatment of HIV infections, shaking palsy, angiocardiopathy and for manifestation of malignant melanoma.