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Explosive growth of big data demands efficient and fast algorithms for nearest neighbor search. Deep learning-based hashing methods have proved their efficacy to learn advanced hash functions that suit the desired goal of nearest neighbor search in large image-based data-sets. In this work, we present a comprehensive review of different deep learning-based supervised hashing methods particularly for image data-sets suggested by various researchers till date to generate advanced hash functions. We categorize prior works into a five-tier taxonomy based on: (i) the design of network architecture, (ii) training strategy based on nature of data-set, (iii) the type of loss function, (iv) the similarity measure and, (v) the nature of quantization. Further, different data-sets used in prior works are reported and compared based on various challenges in the characteristics of images that are part of the data-sets. Lastly, different future directions such as incremental hashing, cross-modality hashing and guidelines to improve design of hash functions are discussed. Based on our comparative review, it has been observed that generative adversarial networks-based hashing models outperform other methods. This is due to the fact that they leverage more data in the form of both real world and synthetically generated data. Furthermore, it has been perceived that triplet-loss-based loss functions learn better discriminative representations by pushing similar patterns together and dis-similar patterns away from each other. This study and its observations shall be useful for the researchers and practitioners working in this emerging research field.

There is an urgent need to validate new drug targets and identify small molecules that possess activity against both drug-resistant and drug-sensitive bacteria. The enzymes belonging to amino acid biosynthesis have been shown to be essential for growth in vitro, in vivo and have not been exploited much for the development of anti-tubercular agents. Here, we have identified small molecule inhibitors targeting homoserine acetyl transferase (HSAT, MetX, Rv3341) from M. tuberculosis . MetX catalyses the first committed step in L-methionine and S-adenosyl methionine biosynthesis resulting in the formation of O-acetyl-homoserine. Using CRISPRi approach, we demonstrate that conditional repression of metX resulted in inhibition of M. tuberculosis growth in vitro. We have determined steady state kinetic parameters for the acetylation of L-homoserine by Rv3341. We show that the recombinant enzyme followed Michaelis–Menten kinetics and utilizes both acetyl-CoA and propionyl-CoA as acyl-donors. High-throughput screening of a 2443 compound library resulted in identification of small molecule inhibitors against MetX enzyme from M. tuberculosis . The identified lead compounds inhibited Rv3341 enzymatic activity in a dose dependent manner and were also active against HSAT homolog from S. aureus . Molecular docking of the identified primary hits predicted residues that are essential for their binding in HSAT homologs from M. tuberculosis and S. aureus . ThermoFluor assay demonstrated direct binding of the identified primary hits with HSAT proteins. Few of the identified small molecules were able to inhibit growth of M. tuberculosis and S. aureus in liquid cultures. Taken together, our findings validated HSAT as an attractive target for development of new broad-spectrum anti-bacterial agents that should be effective against drug-resistant bacteria.

Objectives We describe an unusual patient with self‐limited epilepsy in childhood to aid in the accurate diagnosis and timely treatment of an atonic variant of self‐limited focal epilepsy of childhood with centrotemporal spikes. Methods We reviewed the medical records documenting the clinical presentation, diagnostic evaluation, and treatment. We also reviewed the relevant video electroencephalograms (EEGs). Patient Description This 3‐year‐old girl with self‐limited focal epilepsy of childhood (formerly called benign rolandic epilepsy) began having recurrent falls. Multiple clinical seizures were recorded on video EEG. The video documented generalized loss of tone resulting in falls, while the ictal EEG revealed one‐second paroxysms of 4 Hz spike‐slow‐wave discharges in the left centrotemporal region, followed by a brief generalized electrodecrement for 400 milliseconds. These findings support the diagnosis of an atypical variant of benign epilepsy with centrotemporal spikes (BECTS), known as atonic‐BECTS. Valproic acid was maximized. On follow‐up, the patient was seizure‐free with a normal EEG and normal development. Discussion Few prior publications describe atonic‐BECTS. We present a child with atonic‐BECTS whose ictal video EEG confirms atonic seizures. While atonic seizures typically occur with generalized epilepsies, our report highlights that they can present as an atypical manifestation of self‐limited focal epilepsy in childhood.

Objective A newborn with GRIN1‐related early infantile developmental and epileptic encephalopathy (DEE) with striking pharmacoresistance is described with emphasis on potential therapy with memantine and vigabatrin. Methods The term neonate manifested electrographic and electroclinical seizures from the first day of life with focal tonic seizures with apnea, bradycardia, and desaturations and later developed epileptic spasms and a hyperkinetic movement disorder. Multiple antiseizure medication trials were unsuccessful. Brain magnetic resonance imaging displayed extensive malformations of cortical development. Results Whole‐exome sequencing demonstrated a de novo novel GRIN1 variant (1916T > G,p.Phe639Cys), which can be associated with NMDA receptor dysfunction. Gain‐of‐function mutation was suspected based on phenotype correlation. Seizures markedly improved after initiation of memantine, an NMDA‐receptor antagonist. Memantine was complemented by the concurrent use of vigabatrin, initiated 4 days earlier due to emergence of epileptic spasms. Significant reduction in seizures facilitated discharge from neonatal intensive care unit. Interpretation GRIN1‐related disorders occur due to NMDA receptor dysfunction. Patients with gain‐of‐function GRIN1 mutations who present with the phenotype of DEE with extensive bilateral polymicrogyria may benefit from a trial of NMDA‐receptor antagonist therapy and vigabatrin. Further research is warranted to better understand this markedly pharmacoresistant condition and to investigate targeted therapies in GRIN1 DEE.

Background Melanomas, highly malignant tumors arise from the melanocytes which originate as multipotent neural crest cells during neural tube genesis. The purpose of this study is to assess the pattern of neural differentiation in relation to angiogenesis in VGP melanomas using the tumor as a three dimensional system. Methods Tumor-vascular complexes [TVC] are formed at the tumor-stroma interphase, by tumor cells ensheathing angiogenic vessels to proliferate into a mantle of 5 to 6 layers [L1 to L5] forming a perivascular mantle zone [PMZ]. The pattern of neural differentiation is assessed by immunopositivity for HMB45, GFAP, NFP and synaptophysin has been compared in: [a] the general tumor [b] tumor-vascular complexes and [c] perimantle zone [PC] on serial frozen and paraffin sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test]. Results The cells abutting on the basement membrane acquire GFAP positivity and extend processes. New layers of tumor cells show a transition between L2 to L3 followed by NFP and Syn positivity in L4&L5. The level of GFAP+vity in L1&L2 directly proportionate to the percentage of NFP/Syn+vity in L4&L5, on comparing pigmented PMZ with poorly pigmented PMZ. Tumor cells in the perimantle zone show high NFP [65%] and Syn [35.4%] positivity with very low GFAP [6.9%] correlating with the positivity in the outer layers. Discussion From this study it is seen that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells [GFAP+ve] which further differentiate into neuronal positive cells [NFP&Syn+ve] during angiogenic tumor-vascular interaction, as seen during neurogenesis, to populate the tumor substance.

Objective To describe inpatient resource use in the 2 years following infantile epileptic spasms syndrome (IESS) diagnosis, examine the association between clinical/demographic variables and incidence of readmission, and identify risk factors/reasons for frequent readmissions. Methods Retrospective cohort analysis of readmissions (scheduled/unscheduled) within the first 2 years following IESS diagnosis, details of readmissions (number/time between rehospitalizations, and length of stay), demographic/clinical variables, and reasons for readmissions were collected. Negative binomial regression analysis evaluated associations between incidence of readmissions (both scheduled/unscheduled and unscheduled alone) and demographic/clinical factors. Logistic regression assessed the risk of having recurrent readmissions (≥5 readmissions). Results Among 93 (60% males) new‐onset IESS patients, there were 394 readmissions (56% scheduled and 44% unscheduled) within 2‐years following IESS diagnosis. Mean length of stay was 3.5 days (SD: 5.9). Readmissions occurred in 82 patients (88%) and 37 (40%) experienced ≥5 readmissions. On multivariate regression analysis, readmissions were increased with use of multiple first‐line treatments for IESS (P = 0.006), technology assistance (P ≤ 0.001), and multispecialty care (P = 0.01); seizure freedom (P = 0.015) and known etiology (P = 0.011) lowered the incidence of readmissions. Examining unscheduled readmissions separately, increased readmissions occurred with public insurance (P = 0.013), technology use (P ≤ 0.0.001), and multispecialty care (P = 0.013); seizure freedom decreased unscheduled readmissions (P = 0.006). Technology assistance (G‐tube, NG tube, VP shunt, and tracheostomy use) increased the odds (P = 0.007) for recurrent readmissions. Reasons for readmissions included EEG monitoring (protocol driven for verification of IESS remission/characterization of events/EEG surveillance/presurgical monitoring) (51%), acute medical issues (21%), and seizure exacerbation (15%). Protocol‐driven readmissions declined an estimated 52% following protocol modification during the study. Significance In the 2 years following IESS diagnosis, there is substantial inpatient resource use with nearly 40% experiencing ≥5 readmissions (mostly epilepsy related). Since readmissions are increased by intrinsic patient characteristics such as medical complexity (technology use and multispecialty care) or epilepsy‐related issues, the preventability of readmissions is uncertain, except for protocol‐driven ones.

Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABA A receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA ( N -methyl- d -aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

Variations in dental anatomy and canal morphology are found in all teeth. Knowledge of these variations, particularly the location and treatment of all canals, plays a key role in the success of endodontic therapy. The presence of extra canals, apical ramification, or lateral canals is commonly encountered, and their incidence and significance have been well-documented. However, the clinician should also be aware of the possibility of the existence of fewer root and/or canal numbers. Here is a case report of left maxillary first permanent molar with a single root and single canal. The goal of this clinical article is to report a maxillary molar with single root and single canal and to highlight the role of spiral computed tomography (SCT) as a method to confirm the three-dimensional (3D) anatomy of teeth.