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Surgical Management of Extradural Tumors at the Craniovertebral Junction – Insights from a Tertiary Care Center
No full textBackground
Craniovertebral junction (CVJ) tumors are challenging due to their unique anatomical location. This study aimed to evaluate the complexities in dealing with such precarious CVJ extradural lesions over the decade.
Methods
Twenty-seven patients of extradural CVJ tumors operated between 2009 and 2018 were included. The demographic details, neurological status, surgical approach, extent of resection, type of fixation, complications, and outcome at final follow-up were recorded for each patient.
Results
The mean age of the patients was 39.5 ± 20 years. Most (17/27) of the patients had involvement of a single level. Clivus was the most common (9/17) involved region followed by atlas (7/17) vertebrae. Majority of the patients (13/27) were operated through the posterior-only approach. About 15 patients (55.5%) had instability or extensive lesions that necessitated posterior fixation. None of the patients underwent anterior fixation. Gross and near total excision were achieved in 10 patients (37%) and 3 patients (11%) respectively while 14 patients underwent subtotal excision of tumor. On histopathological analysis, clival chordoma (8/27) was found to be the most common pathology followed by giant cell tumor (6/27), plasmacytoma (4/27), and multiple myeloma (2/27). Most patients (13 out of 27) had the same neurological status after the surgery. Six patients (22%) improved post-operatively with decreased weakness and spasticity. Thirteen (48%) patients underwent adjuvant radiotherapy.
Conclusions
This retrospective study provides valuable insights into managing extradural CVJ tumors and highlights the importance of individualized approaches for optimal outcome
Frequency sweep study on the generation of dual-mode second harmonics (DMSH) on an isotropic nonlinear elastic cylindrical rod by T(0,1) mode
No full textNonlinear ultrasonic (NLU) guided wave (GW) measurements are more sensitive to microscale defects than linear measurements. This nonlinear phenomenon is helpful for early-stage damage detection in material for nondestructive evaluation (NDE) and structural health monitoring (SHM) applications. The amplitude of the higher harmonics generated in the material serves as the basis for the NLU measurement. Recent studies have reported the presence of dual-mode second harmonic (DMSH) on an isotropic nonlinear elastic plate and cylindrical structures. The fundamental non-dispersive mode shear horizontal SH0 and torsional T(0,1) modes can generate simultaneously propagating dual-mode second harmonic(DMSH) on plate and cylindrical guided media respectively. For the case of cylinders, at phase matching condition two dominant second harmonic fundamental longitudinal (l(0,1)) and orthogonal torsional (t(0,1)┴) mode are generated with significant amplitude. The particle vibration of the t(0,1)┴ mode was present in both orthogonal directions compared to conventional T(0,1) mode and hence called orthogonal torsional mode. The present work aims to study the behaviour of DMSH at different frequencies through a frequency sweep study on a weakly nonlinear elastic cylinder of circular cross-section via numerical simulations and validated experimentally for some selected cases. The wave propagation of the T(0,1) mode at several selected frequencies from 300 kHz to 2.2 MHz is chosen to explore the second harmonic mode for better understanding. At frequencies below 1.25 MHz, l(0,1) mode is faster than t(0,1)┴ mode; above 1.25 MHz, it was the other way around. The behaviour of harmonics was observed to be in accordance with the group and phase velocities at the corresponding frequencies in the dispersion curves. The evidence for the presence of DMSH was validated experimentally for some selected frequency cases at different propagation distances. The significance of DMSH is explored via numerical simulations and found that t(0,1)┴ mode is sensitive towards material degradation, while all other generated wave modes were not affected. Research shows that enough energy is available in the generated DMSH to be noticed experimentally and in numerical simulations. This improved understanding of the generation of DMSH across different frequencies would be helpful in new advanced NLU-based NDE and SHM applications
Automorphisms and generalized projections on spaces of analytic functions
No full textWe present complete classifications of automorphisms of two closed subalgebras of the space of bounded analytic functions on the open unit disc D, namely, the subalgebra of functions vanishing at the origin, and the subalgebra of functions whose first derivative vanishes at the origin. The later subalgebra is known as the Neil algebra. We also characterize generalized tri-circular projections on and HP,(D2), 1≤P ≥∞P,≠2
On the quantum dynamical treatment of surface vibrational modes for reactive scattering of H<sub>2</sub> from Cu(111) at 925 K
No full textWe construct the effective Hartree potential for H2 on Cu(111) as introduced in our earlier work starting from the same gas-metal interaction potential obtained for 0 K. Unlike in that work, we now explicitly account for surface expansion at 925 K and investigate different models to describe the surface vibrational modes: (i) a cluster model yielding harmonic normal modes at 0 K and (ii) slab models resulting in phonons at 0 and 925 K according to the quasi-harmonic approximation-all consistently calculated at the density functional theory level with the same exchange-correlation potential. While performing dynamical calculations for the H2 (v = 0, j = 0)-Cu(111) system employing Hartree potential constructed with 925 K phonons and surface temperature, (i) the calculated chemisorption probabilities are the highest compared to the other approaches over the energy domain and (ii) the threshold for the reaction probability is the lowest, in close agreement with the experiment. Although the survival probabilities (v’ = 0) depict the expected trend (lower in magnitude), the excitation probabilities (v’ = 1) display a higher magnitude since the 925 K phonons and surface temperature are more effective for the excitation process compared to the phonons/normal modes obtained from the other approaches investigated to describe the surface
A Mycobacterium tuberculosis secreted virulence factor disrupts host snRNP biogenesis
No full textMycobacterium tuberculosis (Mtb) infection of human macrophages triggers extensive dysregulation of host alternative splicing (AS). Here, we present an unexpected mechanism exploited by the Mtb to achieve the same. We identify several bacterial secretory proteins that interact with the host splicing factors (SFs) and alter select RNA splicing events in vitro , in cell and during ex vivo infections. We show bacterial proteins disrupt AS by impairing Small nuclear ribonucleoprotein (snRNP) biogenesis, primarily by interacting with and sequestering U5snRNA and SNRPF, key spliceosome constituents. These interactions are driven, in part, by one of the identified Mtb proteins, Hsr1, whose access to the host cytosol is ESX1-dependent. The Mtb Δhsr1 is unable to interact and sequester U5snRNA or SNRPF and fails to alter host AS. Consequently, Mtb Δhsr1 shows compromised survival and pathogenesis in macrophages and mice. Lungs of infected mice show distinct SNRPF staining, which is hsr1 dependent. Similar distinctive SNRPF staining is also noted in human tuberculous granulomas. Moreover, monocytes from tuberculosis patients show substantial splicing dysregulation, indicating splicing defects as a key determinant behind systemic tuberculosis pathology. We propose mycobacterial exploitation of the evolutionarily conserved mechanism of snRNP biogenesis, aided its adaptation for human pathogenesis and provides a unique therapeutic opportunity
Effect of AC electric field in mass transport of a neutral solute in a microtube with porous wall
No full textElectroosmotic flow actuation is one the most active research area in microfluidics. The advantages of microfluidic systems with porous walls are improvement of heat and mass transport, selective separation of solutes and tailored drug delivery. The novelty of this work is investigating impact of electroosmotic flow under AC electric field on mass transport of neutral solute through porous walled microtube. Higher frequency (522 kHz) makes the velocity field stagnant for 80 % of tube cross-section leading better permeation. Effect of frequency is marginal on permeation flux but is significant for permeate concentration. At pseudo-steady state, Sherwood number approaches 2.5 irrespective of operating conditions. It is observed that solute permeation flux increases 13 % by manipulating frequency compared to DC field. The optimum frequency for solute delivery increases with Re.Sc.d/L. The findings of this study helps in better understanding of tailored drug delivery by microfluidic channels and nutrient transport in physiological systems
Theoretical quantification of pH-responsiveness of blend membrane
No full textIn this work, a simple predictive mathematical model has been presented that quantifies the membrane parameters, e.g., permeability, effective pore diameter and number of charged units in a polymer chain in a pH-varying environment devoid of added salt. This has been validated experimentally for the case of poly(vinylidene fluoride) (PVDF) membranes blended with poly(methyl methacrylate)-co-poly(acrylic acid) (PMMA-co-PAA) additive copolymer. The effect of Donnan potential was incorporated into the model and estimated using electrokinetic characterizations. It varied considerably from 0.25 to −1.93 units (dimensionless) from pH 2 to 11. Variations of surface morphology and the electronic structure of the blend membrane with pH were studied in detail. Molecular simulations were performed to estimate the effective distance between the neighboring units in the charged/uncharged states and for confirming the copolymer chain behavior in different pH environments. Adsorption experiments were conducted to compare the variation of the number of uncharged units with pH with those estimated using the model. A pH-dependent permeability hysteresis behavior was observed which was explained using an intermolecular hydrogen bonding mechanism. About 80 % variation in the permeability of the blend membrane was observed between the pH limits which was in close agreement with the model results
Fuzzy Deep Learning for the Diagnosis of Alzheimer's Disease: Approaches and Challenges
No full textAlzheimer's disease (AD) is the leading neurodegenerative disorder and primary cause of dementia. Researchers are increasingly drawn to automated diagnosis of AD using neuroimaging analyses. Conventional deep learning (DL) models excel in constructing learning classifiers in early-stage AD diagnosis. However, they often struggle with AD diagnosis due to uncertainties stemming from unclear annotations by experts, challenges in data collection, such as data harmonization issues, and limitations in equipment resolution. These factors contribute to imprecise data, hindering accurate analysis, interpretation of obtained results, and understanding of complex symptoms. In response, the integration of fuzzy logic into DL, forming fuzzy deep learning (FDL), effectively manages imprecise data and provides interpretable insights, offering a valuable advancement in AD. Therefore, exploring recent advancements in integrating DL with fuzzy logic is crucial for improving AD diagnosis. In this review, we explore the contributions of fuzzy logic within FDL models, focusing on fuzzy-based image preprocessing, segmentation, and classification. Moreover, in exploring research directions, we discuss the possibility of the fusion of multimodal data with fuzzy logic, addressing challenges in AD diagnosis. Leveraging fuzzy logic and membership while integrating diverse datasets, such as genomics, proteomics, and metabolomics may provide an effective development of a DL classifier. In addition, fuzzy explainable DL promises more accurate and linguistically interpretable decision support systems for AD diagnosis. The primary objective of this article is to serve as a comprehensive and authoritative resource for newcomers, researchers, and clinicians interested in employing FDL models for AD diagnosis
Biotinylated theranostic amphiphilic polyurethane for targeted drug delivery.
No full textIn the area of drug delivery aided by stimuli-responsive polymers, the biodegradability of nanocarriers is one of the major challenges that needs to be addressed with the utmost sincerity. Herein, a hydrogen sulfide (H2S) responsive hydrophobic dansyl-based trigger molecule is custom designed and successfully incorporated into the water-soluble polyurethane backbone, which is made of esterase enzyme susceptible urethane bonds. The amphiphilic polyurethanes, PUx (x = 2 and 3) with a biotin chain end, formed self-assembled nanoaggregates. A hemolysis and cytotoxicity profile of doxorubicin (DOX)-loaded biotinylated PU3 nanocarriers revealed that it is nonhemolytic and has excellent selectivity toward HeLa cells (biotin receptor-positive cell lines) causing ∼60% cell death while maintaining almost 100% cell viability for HEK 293T cells (biotin receptor-negative cell lines). Furthermore, better cellular internalization of DOX-loaded fluorescent nanocarriers in HeLa cells than in HEK 293T cells confirmed receptor-mediated endocytosis. Thus, this work ensures that the synthesized polymers serve as biodegradable nanocarriers for anticancer therapeutics
Amyloid β-peptide segment conjugated side-chain proline-based polymers as potent inhibitors in lysozyme amyloidosis.
No full textDeveloping effective amyloidosis inhibitors poses a significant challenge due to the dynamic nature of the protein structures, the complex interplay of interfaces in protein–protein interactions, and the irreversible nature of amyloid assembly. The interactions of amyloidogenic polypeptides with other peptides play a pivotal role in modulating amyloidosis and fibril formation. This study presents a novel approach for designing and synthesizing amyloid interaction surfaces using segments derived from the amyloid-promoting sequence of amyloid β-peptide [VF(Aβ(18–19)/FF(Aβ(19–20)/LVF(Aβ(17–19)/LVFF(Aβ(17–20)], where VF, FF, LVF and LVFF stands for valine phenylalanine dipeptide, phenylalanine phenylalanine dipeptide, leucine valine phenylalanine tripeptide and leucine valine phenylalanine phenylalanine tetrapeptide, respectively. These segments are conjugated with side-chain proline-based methacrylate polymers serving as potent lysozyme amyloidosis inhibitors and demonstrating reduced cytotoxicity of amyloid aggregations. Di-, tri-, and tetra-peptide conjugated chain transfer agents (CTAs) were synthesized and used for the reversible addition–fragmentation chain transfer polymerization of tert-butoxycarbonyl (Boc)-proline methacryloyloxyethyl ester (Boc-Pro-HEMA). Deprotection of Boc-groups from the side-chain proline pendants resulted in water-soluble polymers with defined peptide chain ends as peptide–polymer bioconjugates. Among them, the LVFF-conjugated polymer acted as a potent inhibitor with significantly suppressed lysozyme amyloidosis, a finding supported by comprehensive spectroscopic, microscopic, and computational analyses. These results unveil the synergistic effect between the segment-derived amyloid β-peptide and side-chain proline-based polymers, offering new prospects for targeting lysozyme amyloidosis