Optimizing Root Canal Therapy: An In Vitro Comparative Study of Innovative File Systems on Mandibular Premolar Fracture Resistance.

INTRODUCTION AND AIM:  Root canal therapy is a vital procedure for saving teeth by removing infection and cleaning the complex root canal system. However, a delicate balance exists between thorough cleaning and preserving tooth strength. The study aims to evaluate the instrumentation effect of three innovative file systems, XP-endo® shaper, Reciproc®, and Self-adjusting file (SAF) on fracture resistance of mandibular premolars. MATERIALS AND METHODS: Thirty single-rooted mandibular premolars were collected; a standard access cavity was prepared and the working length was established 1 mm short of the apex. The teeth were randomly divided into three groups(n=10). In Group 1, the shaping of the specimens was achieved using XP-endo® shaper; in Group 2, it was instrumented using Reciproc® file; and in Group 3, it was instrumented using SAF. All samples were decoronated and the roots were mounted vertically in acrylic resin and subjected to fracture resistance under a universal testing machine. RESULTS: Intergroup analysis was done by one-way ANOVA followed by Bonferroni post hoc test, which did not report a statistically significant difference (p>0.05). CONCLUSION: All three tested file systems were similar in fracture resistance. XP-endo® shaper exhibited better fracture resistance on root canal instrumentation when compared to Reciproc® and SAF although they are not statistically significant.

Selection of an alternate cementitious mortar using ceramic tile dust waste: a hybrid MCDM approach.

Selection of a suitable alternative material from a pool of alternatives with many conflicting criteria becomes a Multi-Criteria Decision Making (MCDM) problem. In the present study, ternary blended mortars were prepared using ceramic tile dust waste (CTD), fly ash (FA), and ground granulated blast furnace slag (GGBFS) as binder components. Crusher dust (CD) was used as a fine aggregate component. Binder to aggregate ratios of 1:3 and 1:1 were prepared considering suitable flow. A total of 16 mortar mixes were cast. These mortars were tested for various conflicting criteria compressive strength, flexural strength, porosity, water absorption, bulk density, thermal conductivity, specific heat, thermal diffusivity, and thermal effusivity whose weightages obtained were 29.09%, 20.08%, 12.77%, 10.60%, 8.74%, 6.74%, 5.54%, 4.47%, and 1.97%, respectively, as per AHP analysis. Later, considering these different criteria and alternate mortars, it was observed that a 1:1 mortar with 20% CTD, 30% FA, and 50% GGBFS (RC20F30G50) is found to be the suitable mortar with the highest relative closeness coefficient of 0.861 and the highest net outranking flow of 0.316 with respect to MCDM techniques: technique for order of preference by similarity to ideal solution (TOPSIS) and preference ranking organization method for enrichment of evaluations (PROMETHEE-II), respectively. The ranking of the mortar in both methods complies with the relative weightages of the criteria and the performance of the mortars with respect to the above criteria.

Evaluation of a panel of furochromenones as the activator and inhibitor of tyrosinase.

Tyrosinase is a copper-containing enzyme involved in the biosynthesis of melanin pigment. While the excess production of melanin causes hyperpigmentation of human skin, hypopigmentation results in medical conditions like vitiligo. Tyrosinase inhibitors could be used as efficient skin whitening agents and tyrosinase agonists could be used for enhanced melanin synthesis and skin protection from UV exposure. Among a wide range of tyrosinase-regulating compounds, natural and synthetic derivatives of furochromenones, such as 8-methoxypsoralen (8-MOP), are known to both activate and inhibit tyrosinase. We recently reported a synthetic approach to generate a variety of dihydrofuro[3,2-c]chromenones and furo[3,2-c]chromenones in a metal-free condition. In the present study, we investigated these compounds for their potential as antagonists or agonists of tyrosinase. Using fungal tyrosinase-based in vitro biochemical assay, we obtained one compound (3k) which could inhibit tyrosinase activity, and the other compound (4f) that stimulated tyrosinase activity. The kinetic studies revealed that compound 3k caused 'mixed' type tyrosinase inhibition and 4f stimulated the catalytic efficiency. Studying the mechanisms of these compounds may provide a basis for the development of new effective tyrosinase inhibitors or activators.

Banana peel nanocellulose and soy protein hydrolysate complexed colloidal nanoparticles synthesis using ultrasonic interventions: characterization and stable pickering emulsion formation.

Pickering based emulsion system are been gaining interest in active delivery of encapsulated molecules in food system. In the present study, cellulose nanoparticles (CNPs) were isolated from food waste (banana peel) using acid hydrolysis followed by high-intensity ultrasonication. The complex colloidal nanoparticles (CNPSPH) were fabricated using hydrogen bonding and electrostatic interactions between cellulose nanoparticles and soy protein hydrolysates. With 400 W power level for 30 min, size of 53.11 ± 1.45 nm with polydispersity index of 0.21 ± 0.21 and Zeta potential of - 34.33 ± 0.77 were noted for generated CNPs. The three-phase contact angle (o/w) of CNPSPH at a mass ratio of 1:1 CNPs to SPHs (CNPSPH 1:1) was approximately 89.07°, indicating as effective Pickering emulsifiers. Furthermore, the stability of the Pickering emulsion stabilised by CNPSPH complex was investigated under various pH and temperature conditions. The findings will provide solution in development of nanocellulose-soy protein complex particles for a stabilized Pickering emulsion formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01477-w.

Occurrence and Severity of Deformational Plagiocephaly in Infants: A Single Center Experience.

OBJECTIVE: To estimate the occurrence and severity of deformational plagiocephaly among infants. METHODS: A hospital-based, cross-sectional study was done in the pediatric ward of a tertiary care hospital between April 1, 2022 to October 31, 2022. Cranial Vault Asymmetry Index (CVAI) and Argenta Clinical Classification were applied to consecutive infants aged 1 month to 1 year till the calculated sample size was achieved. RESULTS: 67 infants were recruited and the occurrence of deformational plagiocephaly in the sample was estimated to be 46.3%. Level 2 severity of deformational plagiocephaly was the commonest, while as per the Argenta classification, majority belonged to type I (39.2%). Male gender and developmental delay were the significant risk factors for plagiocephaly with an odds ratio (95% CI) of 3.73 (1.23, 11.26) and 19.25 (2.31, 160.3), respectively. CONCLUSION: A high occurrence of deformational plagiocephaly was found in infants studied. There is a need for more studies to further corroborate these findings and study its associated factors.

A Case Report of an Atypical Situation Arising During Typical Ryle's Tube Removal Procedure.

Placement of Ryle's tube is a rather blind outpatient procedure which has documented minor and major complications during insertion like nasal irritation, epistasis, pharyngeal trauma, tracheal trauma, intravascular penetration, intracranial penetration etc. However, removal of Ryle's tube is a rather straightforward procedure with rarely any complication. In this case report, we encountered an unusual situation of Ryle's tube being kinked and stuck at Left Fossa of Rosenmuller, near the skull base with subsequent erosion, emphasising the fact that forceful removal should not be attempted. Thorough examination and meticulous removal are necessitated in a stuck/kinked Ryle's tube to prevent dreaded complications.

Assessing generalisability of deep learning-based polyp detection and segmentation methods through a computer vision challenge.

Polyps are well-known cancer precursors identified by colonoscopy. However, variability in their size, appearance, and location makes the detection of polyps challenging. Moreover, colonoscopy surveillance and removal of polyps are highly operator-dependent procedures and occur in a highly complex organ topology. There exists a high missed detection rate and incomplete removal of colonic polyps. To assist in clinical procedures and reduce missed rates, automated methods for detecting and segmenting polyps using machine learning have been achieved in past years. However, the major drawback in most of these methods is their ability to generalise to out-of-sample unseen datasets from different centres, populations, modalities, and acquisition systems. To test this hypothesis rigorously, we, together with expert gastroenterologists, curated a multi-centre and multi-population dataset acquired from six different colonoscopy systems and challenged the computational expert teams to develop robust automated detection and segmentation methods in a crowd-sourcing Endoscopic computer vision challenge. This work put forward rigorous generalisability tests and assesses the usability of devised deep learning methods in dynamic and actual clinical colonoscopy procedures. We analyse the results of four top performing teams for the detection task and five top performing teams for the segmentation task. Our analyses demonstrate that the top-ranking teams concentrated mainly on accuracy over the real-time performance required for clinical applicability. We further dissect the devised methods and provide an experiment-based hypothesis that reveals the need for improved generalisability to tackle diversity present in multi-centre datasets and routine clinical procedures.

Disruption of hypoxia-inducible factor-2α in neutrophils decreases colitis-associated colon cancer.

Neutrophils are abundant immune cells in the colon tumor microenvironment. Studies have shown that neutrophils are recruited into hypoxic foci in colon cancer. However, the impact of hypoxia signaling on neutrophil function and its involvement in colon tumorigenesis remain unclear. To address this, we generated mice with a deletion of hypoxia-inducible factor (HIF)-1α or HIF-2α in neutrophils driven by the MRP8Cre (HIF-1αΔNeu) or (HIF-2αΔNeu) and littermate controls. In an azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colon cancer, the disruption of neutrophils-HIF-1α did not result in any significant changes in body weight, colon length, tumor size, proliferation, or burden. However, the disruption of HIF-2α in neutrophils led to a slight increase in body weight, a significant decrease in the number of tumors, and a reduction in tumor size and volume compared with their littermate controls. Histological analysis of colon tissue from mice with HIF-2α-deficient neutrophils revealed notable reductions in proliferation as compared with control mice. In addition, we observed reduced levels of proinflammatory cytokines, such as TNF-α and IL-1ß, in neutrophil-specific HIF-2α-deficient mice in both the tumor tissue as well as the neutrophils. Importantly, it is worth noting that the reduced tumorigenesis associated with HIF-2α deficiency in neutrophils was not evident in already established syngeneic tumors or a DSS-induced inflammation model, indicating a potential role of HIF-2α specifically in colon tumorigenesis. In conclusion, we found that the loss of neutrophil-specific HIF-2α slows colon tumor growth and progression by reducing the levels of inflammatory mediators.NEW & NOTEWORTHY Despite the importance of hypoxia and neutrophils in colorectal cancer (CRC), the contribution of neutrophil-specific HIFs to colon tumorigenesis is not known. We describe that neutrophil HIF-1α has no impact on colon cancer, whereas neutrophil HIF-2α loss reduces CRC growth by decreasing proinflammatory and immunosuppressive cytokines. Furthermore, neutrophil HIF-2α does not reduce preestablished tumor growth or inflammation-induced colitis. The present study offers novel potential of neutrophil HIF-2α as a therapeutic target in CRC.

Characteristics of rice starches modified by single and dual heat moisture and osmotic pressure treatments.

The effect of osmotic pressure treatment (OPT), heat moisture treatment (HMT), and their dual combination as HMT-OPT and OPT-HMT on functional and pasting properties, gel texture, crystallinity, thermal, morphological, and rheological properties, and in vitro digestibility of modified starches were investigated. HMT was done with 29 % moisture at 111 °C for 45 min while OPT was performed at 117 °C for 35 min with saturated sodium sulphate solution. All modifications increased amylose content, improved pasting stability, and reduced swelling power and solubility. Dual modifications caused higher morphological changes than single modified starches. HMT and OPT increased pasting temperature, setback and final viscosity while decreased peak viscosity and breakdown, whereas HMT-OPT and OPT-HMT reduced all pasting parameters except pasting temperature. 1047/1022 and 995/1022 ratios and relative crystallinity decreased. V-type polymorphs were formed, and gelatinization temperature range increased with lower gelatinization enthalpy. Starch gel elasticity, RS and SDS content were enhanced to a greater extent after HMT-OPT and OPT-HMT. HMT as a single and dual form with OPT showed prominent effect on pasting, thermal, crystalline, and rheological properties. Application of HMT, OPT and dual modified starches with improved functionalities may be targeted for suitable food applications such as noodles.

TransResU-Net: A Transformer based ResU-Net for Real-Time Colon Polyp Segmentation.

Colorectal cancer (CRC) is one of the most common causes of cancer and cancer-related mortality worldwide. Performing colon cancer screening in a timely fashion is the key to early detection. Colonoscopy is the primary modality used to diagnose colon cancer. However, the miss rate of polyps, adenomas and advanced adenomas remains significantly high. Early detection of polyps at the precancerous stage can help reduce the mortality rate and the economic burden associated with colorectal cancer. Deep learning-based computer-aided diagnosis (CADx) system may help gastroenterologists to identify polyps that may otherwise be missed, thereby improving the polyp detection rate. Additionally, CADx system could prove to be a cost-effective system that improves long-term colorectal cancer prevention. In this study, we proposed a deep learning-based architecture for automatic polyp segmentation called Transformer ResU-Net (TransResU-Net). Our proposed architecture is built upon residual blocks with ResNet-50 as the backbone and takes advantage of the transformer self-attention mechanism as well as dilated convolution(s). Our experimental results on two publicly available polyp segmentation benchmark datasets showed that TransResU-Net obtained a highly promising dice score and a real-time speed. With high efficacy in our performance metrics, we concluded that TransResU-Net could be a strong benchmark for building a real-time polyp detection system for the early diagnosis, treatment, and prevention of colorectal cancer. The source code of the proposed TransResU-Net is publicly available at https://github.com/nikhilroxtomar/TransResUNet.

Defining neutralization and allostery by antibodies against COVID-19 variants.

The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein. We identified epitope hotspots, and associated changes in Spike dynamics that distinguish weak, moderate and strong neutralizing antibodies. We show the impact of mutations in Wuhan-Hu-1, Delta, and Omicron variants on differences in the antibody-induced conformational changes in Spike and illustrate how these render certain antibodies ineffective. Antibodies with similar binding affinities may induce destabilizing or stabilizing allosteric effects on Spike, with implications for neutralization efficacy. Our results provide mechanistic insights into the functional modes and synergistic behavior of human antibodies against COVID-19 and may assist in designing effective antiviral strategies.

Ethical & Medicolegal Issues in Otology.

ENT professionals are facing the heat of raised number of malpractice complaints against them. Some of them have a direct impact on surgeon's career & life progression. Lawsuits are not new to otology, but with evolution of education, social media & media trials etc., negativity is being generated against doctors each day. This article considers the causes, types & prevention of medicolegal malpractice claims/lawsuits against the doctors with incorporation of recent NMC guidelines for the same. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04078-5.

CDK5: an oncogene or an anti-oncogene: location location location.

Recent studies have uncovered various physiological functions of CDK5 in many nonneuronal tissues. Upregulation of CDK5 and/or its activator p35 in neurons promotes healthy neuronal functions, but their overexpression in nonneuronal tissues is causally linked to cancer of many origins. This review focuses on the molecular mechanisms by which CDK5 recruits diverse tissue-specific substrates to elicit distinct phenotypes in sixteen different human cancers. The emerging theme suggests that CDK5's role as an oncogene or anti-oncogene depends upon its subcellular localization. CDK5 mostly acts as an oncogene, but in gastric cancer, it is a tumor suppressor due to its unique nuclear localization. This indicates that CDK5's access to certain nuclear substrates converts it into an anti-oncogenic kinase. While acting as a bonafide oncogene, CDK5 also activates a few cancer-suppressive pathways in some cancers, presumably due to the mislocalization of nuclear substrates in the cytoplasm. Therefore, directing CDK5 to the nucleus or exporting tumor-suppressive nuclear substrates to the cytoplasm may be promising approaches to combat CDK5-induced oncogenicity, analogous to neurotoxicity triggered by nuclear CDK5. Furthermore, while p35 overexpression is oncogenic, hyperactivation of CDK5 by inducing p25 formation results in apoptosis, which could be exploited to selectively kill cancer cells by dialing up CDK5 activity, instead of inhibiting it. CDK5 thus acts as a molecular rheostat, with different activity levels eliciting distinct functional outcomes. Finally, as CDK5's role is defined by its substrates, targeting them individually or in conjunction with CDK5 should create potentially valuable new clinical opportunities.

Post-quantum distributed ledger technology: a systematic survey.

Blockchain technology finds widespread application across various fields due to its key features such as immutability, reduced costs, decentralization, and transparency. The security of blockchain relies on elements like hashing, digital signatures, and cryptography. However, the emergence of quantum computers and supporting algorithms poses a threat to blockchain security. These quantum algorithms pose a significant threat to both public-key cryptography and hash functions, compelling the redesign of blockchain architectures. This paper investigates the status quo of the post-quantum, quantum-safe, or quantum-resistant cryptosystems within the framework of blockchain. This study starts with a fundamental overview of both blockchain and quantum computing, examining their reciprocal influence and evolution. Subsequently, a comprehensive literature review is conducted focusing on Post-Quantum Distributed Ledger Technology (PQDLT). This research emphasizes the practical implementation of these protocols and algorithms providing extensive comparisons of characteristics and performance. This work will help to foster further research at the intersection of post-quantum cryptography and blockchain systems and give prospective directions for future PQDLT researchers and developers.

Screening COVID-19 by Swaasa AI platform using cough sounds: a cross-sectional study.

The Advent of Artificial Intelligence (AI) has led to the use of auditory data for detecting various diseases, including COVID-19. SARS-CoV-2 infection has claimed more than six million lives to date and therefore, needs a robust screening technique to control the disease spread. In the present study we created and validated the Swaasa AI platform, which uses the signature cough sound and symptoms presented by patients to screen and prioritize COVID-19 patients. We collected cough data from 234 COVID-19 suspects to validate our Convolutional Neural Network (CNN) architecture and Feedforward Artificial Neural Network (FFANN) (tabular features) based algorithm. The final output from both models was combined to predict the likelihood of having the disease. During the clinical validation phase, our model showed a 75.54% accuracy rate in detecting the likely presence of COVID-19, with 95.45% sensitivity and 73.46% specificity. We conducted pilot testing on 183 presumptive COVID subjects, of which 58 were truly COVID-19 positive, resulting in a Positive Predictive Value of 70.73%. Due to the high cost and technical expertise required for currently available rapid screening methods, there is a need for a cost-effective and remote monitoring tool that can serve as a preliminary screening method for potential COVID-19 subjects. Therefore, Swaasa would be highly beneficial in detecting the disease and could have a significant impact in reducing its spread.

Effect of cryopreservation and capacitation on expression patterns of ATP synthesis associated genes in bubaline spermatozoa.

This study investigated the expression patterns of certain ATP synthesis associated genes (GAPDHS, PGK2, ENO4 and MDH2) in fresh and frozen-thawed bubaline spermatozoa vis-à-vis capacitation. Eight adult Murrah buffalo bulls, aged 5-7 years, were randomly selected from a bull farm and fresh semen was collected once a week for four weeks (n = 32) from the selected bulls. Simultaneously, frozen straws of the same bulls were collected (n = 32, four straws were pooled per sample). The samples were divided into four groups i.e., fresh non capacitated (control/group 1), fresh capacitated (group 2), frozen non capacitated (group 3) and frozen capacitated (group 4). In all groups mRNA extraction was done. The mRNA expression of GAPDHS was significantly higher in group 3 compared to the other groups, whereas the expression of ENO4 was significantly up-regulated in group 2 and 3 compared to the group 4. Similarly, the mRNA expression of PGK2 was significantly up-regulated in group 3 whereas in case of MDH2, it was significantly higher in group 2, 3 and 4 compared group 1. It can be concluded from our study that freezing and capacitation has a significant effect on the expression dynamics of the ATP synthesis-associated genes warranting necessary interventions in handling procedures to minimise the adverse effect of freezing on ATP synthesis process to ensure persistence of fertilizing ability of sperm.

Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.

HACE1 is an ankyrin repeat (AKR) containing HECT-type E3 ubiquitin ligase that interacts with and ubiquitinates multiple substrates. While HACE1 is a well-known tumor suppressor, its structure and mode of ubiquitination are not understood. The authors present the cryo-EM structures of human HACE1 along with in vitro functional studies that provide insights into how the enzymatic activity of HACE1 is regulated. HACE1 comprises of an N-terminal AKR domain, a middle (MID) domain, and a C-terminal HECT domain. Its unique G-shaped architecture interacts as a homodimer, with monomers arranged in an antiparallel manner. In this dimeric arrangement, HACE1 ubiquitination activity is hampered, as the N-terminal helix of one monomer restricts access to the C-terminal domain of the other. The in vitro ubiquitination assays, hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis, mutagenesis, and in silico modeling suggest that the HACE1 MID domain plays a crucial role along with the AKRs in RAC1 substrate recognition.

Structural and functional characterization of Aedes aegypti pupal cuticle protein that controls dengue virus infection.

The pupal cuticle protein from Aedes aegypti (AaPC) inhibits dengue virus (DENV) infection; however, the underlying mechanism of this inhibition remains unknown. Here, we report that AaPC is an intrinsically disordered protein and interacts with domain I/II of the DENV envelope protein via residues Asp59, Asp61, Glu71, Asp73, Ser75, and Asp80. AaPC can directly bind to and cause the aggregation of DENV, which in turn blocks virus infection during the virus-cell fusion stage. AaPC may also influence viral recognition and attachment by interacting with human immune receptors DC-SIGN and CD4. These findings enhance our understanding of the role of AaPC in mitigating viral infection and suggest that AaPC is a potential target for developing inhibitors or antibodies to control dengue virus infection.

Cystic Lymphangioma of Rectum-A Case Report and Review of Literature.

Colorectal cystic lymphangiomas are rare benign lesions. They are characterized by the presence of either single or multi-cystic spaces lined by endothelium. Though there are multiple case reports of right and transverse colonic lymphangioma; only around 10 cases of lymphangioma of the rectum have been reported. We present a case report of rectal lymphangioma with the relevant literature review.