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In an asymmetric-key cryptosystem, the secure storage of private keys is a challenging task. This paper proposes a novel approach for generating the same public and private key pair on a need basis. Hence, the need for secure storage of the private key is done away with. The proposed approach for generating the key pair is based on two factors: fingerprint biometrics and password. A stable binary string is generated from the distances among pairs of minutiae points in a fingerprint using a gray code-based method. Experiments show that gray code representation significantly reduces the number of inconsistencies between the generated bit strings from two instances of the same fingerprint as against the binary code representation. Hence, the Reed–Solomon error correction code successfully corrects errors due to variations in multiple instances of the same fingerprint to induce stability in the generated string. Hash of the stable string generated from the fingerprint and the string generated from hashed password are XORed to derive a stable seed value. The proposed approach uses this seed value to generate two large prime numbers. These prime numbers are used to generate the public and private key pair using the RSA key generation method. This seed value ensures the generation of the same key pair every time. The experimental results show that the proposed approach can ensure a stable generation of the key. It is not required to store either the fingerprint template or the password. Moreover, the generated private key is also not stored. It can be regenerated on a need basis.

ObjectiveAssess the impact of introducing a consensus guideline incorporating an adapted Sepsis Risk Calculator (SRC) algorithm, in the management of early onset neonatal sepsis (EONS), on antibiotic usage and patient safety.DesignMulticentre prospective studySettingTen perinatal hospitals in Wales, UK.PatientsAll live births ≥34 weeks’ gestation over a 12-month period (April 2019–March 2020) compared with infants in the preceding 15-month period (January 2018–March 2019) as a baseline.MethodsThe consensus guideline was introduced in clinical practice on 1 April 2019. It incorporated a modified SRC algorithm, enhanced in-hospital surveillance, ongoing quality assurance, standardised staff training and parent education. The main outcome measure was antibiotic usage/1000 live births, balancing this with analysis of harm from delayed diagnosis and treatment, disease severity and readmissions from true sepsis. Outcome measures were analysed using statistical process control charts.Main outcome measuresProportion of antibiotic use in infants ≥34 weeks’ gestation.Results4304 (14.3%) of the 30 105 live-born infants received antibiotics in the baseline period compared with 1917 (7.7%) of 24 749 infants in the intervention period (45.5% mean reduction). All 19 infants with culture-positive sepsis in the postimplementation phase were identified and treated appropriately. There were no increases in sepsis-related neonatal unit admissions, disease morbidity and late readmissions.ConclusionsThis multicentre study provides evidence that a judicious adaptation of the SRC incorporating enhanced surveillance can be safely introduced in the National Health Service and is effective in reducing antibiotic use for EONS without increasing morbidity and mortality.

Background Age-related macular degeneration (AMD) is a result of degeneration/damage of the retinal pigment epithelium (RPE) while retinitis pigmentosa (RP), an inherited early-onset disease, results from premature loss of photoreceptors. A promising therapeutic approach for both is the replacement of lost/damaged cells with human induced pluripotent stem cell (hiPSC)-derived retinal cells. Methods The aim of this study was to investigate the in vivo functionality of RPE and photoreceptor progenitor (PRP) cells derived from a clinical-grade hiPSC line through a unified protocol. De novo-generated RPE and PRP were characterized extensively to validate their identity, purity, and potency. Results RPE expressed tight junction proteins, showed pigmentation and ciliation, and secreted polarization-related factors vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). PRP expressed neural retina proteins and cone and rod markers, and responded to KCl-induced polarization. Transcriptomic analysis demonstrated an increase in the expression of mature retinal tissue-specific genes coupled with concomitant downregulation of genes from undesired lineages. RPE transplantation rescued visual function in RCS rats shown via optokinetic tracking and photoreceptor rescue. PRP transplantation improved light perception in NOD.SCID-rd1 mice, and positive electroretinography signals indicated functional photoreceptor activity in the host’s outer nuclear layer. Graft survival and integration were confirmed using immunohistochemistry, and no animals showed teratoma formation or any kind of ectopic growth in the eye. Conclusions To our knowledge, this is the first demonstration of a unified, scalable, and GMP-adaptable protocol indicating strong animal efficacy and safety data with hiPSC-derived RPE and PRP cells. These findings provide robust proof-of-principle results for IND-enabling studies to test these potential regenerative cell therapies in patients.

Fraudsters often alter handwritten contents in a document in order to achieve illicit purposes. At times, this may result in financial and mental loss to an individual or an organization. Hence, ink analysis is necessary to identify such an alteration. Convolution Neural Network (CNN) can be used to identify such cases of alteration, as CNN has emerged as a monumental success in the field of computer vision for varieties of classification tasks. But, CNN requires large amount of labeled data for training. Hence, there is a need to generate a large dataset for the experiments relating to handwritten word alteration detection. Collection, digitization, and cropping of a large number of altered and unaltered handwritten words are tedious and time consuming. To overcome such an issue, an approach for synthetic word data generation is presented in this paper for handwritten word alteration detection experiments. This scheme is designed in such a way that the synthetically generated words are very similar to the original ones. In order to achieve this, handwritten character data set is prepared using 10 blue and 10 black pens. These handwritten characters are used for creating synthetic word alteration data set. The presented approach uses relatively less number of handwritten character images to create a huge word alteration data set. Further, deep learning models are trained on the synthetically generated data set for word alteration detection.

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lung, particularly the proximal airway and distal alveolar cells. NKX2.1+ primordial lung progenitors of the foregut (anterior) endoderm are the developmental precursors to all adult lung epithelial lineages and are postulated to play an important role in viral tropism. Here, we show that SARS-CoV-2 readily infected and replicated in human-induced pluripotent stem cell-derived proximal airway cells, distal alveolar cells, and lung progenitors. In addition to the upregulation of antiviral defense and immune responses, transcriptomics data uncovered a robust epithelial cell-specific response, including perturbation of metabolic processes and disruption in the alveolar maturation program. We also identified spatiotemporal dysregulation of mitochondrial heme oxygenase 1 (HMOX1), which is associated with defense against antioxidant-induced lung injury. Cytokines, such as TNF-α, INF-γ, IL-6, and IL-13, were upregulated in infected cells sparking mitochondrial ROS production and change in electron transport chain complexes. Increased mitochondrial ROS then activated additional proinflammatory cytokines leading to an aberrant cell cycle resulting in apoptosis. Notably, we are the first to report a chemosensory response resulting from SARS-CoV-2 infection similar to that seen in COVID-19 patients. Some of our key findings were validated using COVID-19-affected postmortem lung tissue sections. These results suggest that our in vitro system could serve as a suitable model to investigate the pathogenetic mechanisms of SARS-CoV-2 infection and to discover and test therapeutic drugs against COVID-19 or its consequences.

Objective: Poor ergonomic posture during interventional procedures might lead to increased physical discomfort and work-related musculoskeletal disorders. Adjunctive equipment such as lead aprons (LAs) has been shown to increase ergonomic posture risk (EPR). The objective of this study was to evaluate the effectiveness of StemRad MD (StemRad Ltd., Tel Aviv, Israel), a weightless exoskeleton-based radiation protective ensemble, in reducing EPR on the operator using wearable inertial measurement unit (IMU) sensors. Methods: A prospective, observational study was conducted at an academic hospital. Inertial measurement unit sensors were affixed to the upper back of 9 interventionalists to assess ergonomic risk posture during endovascular procedures while wearing a traditional LA or the StemRad MD radiation protection system. Total fluoroscopy time, procedure type, and ergonomic risk postures were recorded and analyzed. Results: Twenty-one cases were performed with StemRad MD and 30 with LAs. Mean procedure time for the StemRad MD procedures was 48.4±23.3 minutes (range: 24–106 min), and for LA procedures, it was 34.66±25.83 minutes (range: 6–100 min) (p=.060). The operators assumed low-risk ergonomic positions in 96.1% of StemRad MD cases and in 62.9% of LA cases (p=.001), and high-risk ergonomic positions in 0% and 6.2%, respectively (p=.80). Mean EPR score for StemRad MD was 1.16, and for the LA, it was 1.49 (p=.001). Conclusions: StemRad MD significantly reduces the EPR to the torso compared with a LA-based radiation protection system. Clinical Impact Poor ergonomic posture during interventional procedures might leas to work-related musculoskeletal disorders for healthcare workers. StemRad MD, a weightless, exoskeleton-based radiation protection system was shown to significantly reduce ergonomic posture risk to the torso compared to conventional lead aprons. This might lead to reduced physical discomfort for procedure-based specialists.

Neural precursor cells (NPCs), derived from pluripotent stem cells (PSCs), with their unique ability to generate multiple neuronal and glial cell types are extremely useful for understanding biological mechanisms in normal and diseased states. However, generation of specific neuronal subtypes (mature) from NPCs in large numbers adequate for cell therapy is challenging due to lack of a thorough understanding of the cues that govern their differentiation. Interestingly, neural stem cells (NSCs) themselves are in consideration for therapy given their potency to form different neural cell types, release of trophic factors, and immunomodulatory effects that confer neuroprotection. With the recent COVID-19 outbreak and its accompanying neurological indications, the immunomodulatory role of NSCs may gain additional significance in the prevention of disease progression in vulnerable populations. In this regard, small-molecule mediated NPC generation from PSCs via NSC formation has become an important strategy that ensures consistency and robustness of the process. The development of the mammalian brain occurs along the rostro-caudal axis, and the establishment of anterior identity is an early event. Wnt signaling, along with fibroblast growth factor and retinoic acid, acts as a caudalization signal. Further, the increasing amount of epigenetic data available from human fetal brain development has enhanced both our understanding of and ability to experimentally manipulate these developmental regulatory programs in vitro. However, the impact on homing and engraftment after transplantation and subsequently on therapeutic efficacy of NPCs based on their derivation strategy is not yet clear. Another formidable challenge in cell replacement therapy for neurodegenerative disorders is the mode of delivery. In this Perspective, we discuss these core ideas with insights from our preliminary studies exploring the role of PSC-derived NPCs in rat models of MPTP-induced Parkinson's disease following intranasal injections.