Hybrid optimization assisted channel selection of EEG for deep learning model-based classification of motor imagery task.

OBJECTIVES: To design and develop an approach named HC + SMA-SSA scheme for classifying motor imagery task. METHODS: The offered model employs a new method for classifying motor imagery task. Initially, down sampling is deployed to pre-process the incoming signal. Subsequently, "Modified Stockwell Transform (ST) and common spatial pattern (CSP) based features are extracted". Then, optimal channel selection is made by a novel hybrid optimization model named as Spider Monkey Assisted SSA (SMA-SSA). Here, "Long Short Term Memory (LSTM) and Bidirectional Gated Recurrent Unit (BI-GRU)" models are used for final classification, whose outcomes are averaged at the end. At last, the improvement of SMA-SSA based model is proven over different metrics. RESULTS: A superior sensitivity of 0.939 is noted for HC + SMA-SSA that was higher over HC with no optimization and proposed with traditional ST. CONCLUSIONS: The proposed method achieved effective classification performance in terms of performance measures.

Emerging Therapeutic Targets in Diffuse Large B-Cell Lymphoma.

OPINION STATEMENT: The standard front-line treatment of Diffuse Large B-Cell Lymphoma (DLBCL) remains Rituximab combined with multi-agent cytotoxic chemotherapy. In spite of high response rates to this therapy, relapsed/refractory disease is observed in up to 40% of patients. It is our opinion that additional chemoimmunotherapy, followed by high-dose therapy with autologous stem cell transplant (HDT-ASCT) for responsive disease, is the optimal therapy for these patients. However, many patients cannot tolerate HDT-ASCT, or have relapsed/refractory disease in spite of it. These patients have a poor overall prognosis, and there is no clear consensus as to how these patients should be treated. Over the past decade, significant advances have been made in the understanding of the molecular genesis and subtyping of DLBCL, leading to the identification of multiple pathways and molecules that can be targeted for clinical benefit. Examples include Bcl-2, Bcl-6, cell surface markers, and myriad molecules in both the B-Cell receptor and PI3K/Akt/mTOR pathways. As agents targeting these molecules and pathways progress from preclinical models to early clinical trials, more is learned about what might predict for response to these agents, such as cell of origin classification, and/or expression of relevant molecular markers, as measured by immunohistochemistry or gene expression profiling. Both the successes and failures of these novel targeted agents promise to dramatically refine, improve, and individualize the classification and treatment of DLBCL. Therefore, it is our opinion that patients with relapsed/refractory DLBCL are an ideal population for clinical trials due to both the lack of standardized treatment, and the recent advancements in pathobiology and early-phase treatment options.

Slow dynamics in a liquid crystal: 1H and 19F NMR relaxometry.

Spin-lattice relaxation rates (R(1H) and R(1F)) of two nuclear species ((1)H and (19)F) are measured at different temperatures in the isotropic phase of a liquid crystal (4(')-butoxy-3(')-fluoro-4-isothiocyanatotolane-4OFTOL), over a wide range of Larmor frequency (10 kHz-50 MHz). Their dispersion profiles are found to be qualitatively very different, and the R(1F) in particular shows significant dispersion (varying over two orders of magnitude) in the entire isotropic range, unlike R(1H). The proton spin-lattice relaxation, as has been established, is mediated by time modulation of magnetic dipolar interactions with other protons (case of like spins), and the discernable dispersion in the mid-frequency range, observed as the isotropic to nematic transition is approached on cooling, is indicative of the critical slowing of the time fluctuations of the nematic order. Significant dispersion seen in the R(1F) extending to very low frequencies suggests a distinctly different relaxation path which is exclusively sensitive to the ultra slow modes apparently present in the system. We find that under the conditions of our experiment at low Zeeman fields, spin-rotation coupling of the fluorine with the molecular angular momentum is the dominant mechanism, and the observed dispersion is thus attributed to the presence of slow torques experienced by the molecules, arising clearly from collective modes. Following the arguments advanced to explain similar slow processes inferred from earlier detailed ESR measurements in liquid crystals, we propose that slowly relaxing local structures representing such dynamic processes could be the likely underlying mechanism providing the necessary slow molecular angular momentum correlations to manifest as the observed low frequency dispersion. We also find that the effects of the onset of cross-relaxation between the two nuclear species when their resonance lines start overlapping at very low Larmor frequencies (below ~400 kHz), provide an additional relaxation contribution.

Chimeric gene construct coding for bi-functional enzyme endowed with endoglucanase and phytase activities.

Phytase and endoglucanase enzymes are being widely used as feed additives in poultry industry. In our earlier studies, the Bacillus phytase, when expressed in Escherichia coli, was found in inclusion bodies, whereas endoglucanase was found in active soluble form. Herein, we report the development of a chimeric gene construct coding for ~73 kDa fusion protein and its over-expression in E. coli in soluble form. The novel enzyme exhibited both endoglucanase and phytase activities across broad pH (4.0-8.0) and temperature (25-75 degrees C) ranges. As such, the bi-functional enzyme seems promising and might serve as a potential feed additive for enhanced nutrition uptake in monogastric animals.

Nonlinear effect of GdnHCl on hydration dynamics of proteins: a 1H magnetic relaxation dispersion study.

Proton magnetic relaxation dispersion investigations with aqueous solutions of lysozyme and bovine serum albumin (BSA) in the 0-5 M range of guanidine hydrochloride (GdnHCl), pH 4.4, 27 degrees C, were taken up with the objective of examining the hydration dynamics of internal cavity waters as the protein is held under increasingly destabilizing conditions. Field cycling NMR and conventional pulsed NMR techniques were employed to cover a frequency range of 100 kHz to 50 MHz. Analyses of dispersion profiles at different concentrations of GdnHCl were carried out considering the contributions from internal and surface waters. The denaturant-dependent variation of internal water contribution indicates that the reorientational disorder of internal waters decreases with increments of the denaturant up to its subdenaturing limit. For both proteins, the variation of effective correlation time with GdnHCl apparently shows a marginal shrink in hydrodynamic volumes under the subdenaturing condition. These results suggest that subdenaturing amounts of GdnHCl restrict the motional freedom of the internal waters, and can have considerable influence on the surface hydration. On increasing the denaturant concentration further, the dispersion amplitude drops sharply, indicating that the chaotropic action of the denaturant now runs over its own cavity water-ordering effect operative in the subdenaturing limit. The results are fundamentally important for the understanding of the susceptibility of protein structure and hydration to denaturants.

Is there an association between oral submucous fibrosis and ABO blood grouping?

BACKGROUND: Oral submucous fibrosis (OSMF) is one of the most common premalignant conditions in Indian subcontinent due to the traditional use of Areca nut and its various preparations. The genetic predisposition has also been reported in its etiopathogenesis. The rate of malignant transformation is between 7% to 14%. AIM: To evaluate whether ABO blood group is related to OSMF risk. SUBJECTS AND METHODS: It was a cross-sectional hospital-based study. A convenient sample of 164 study subjects constituted the cases and 180 subjects constituted the comparison group. STATISTICAL ANALYSIS USED: The results were analyzed using chi-square test and odds ratio. RESULTS: The chi-square analysis could not establish any significant relationship between OSMF and ABO blood group. But, when the strength of the association was measured using odds ratio, subjects with blood group A had 1.181 times higher risk of developing OSMF in comparison to other groups. CONCLUSION: The subjects with blood group A were at higher risk of developing OSMF in comparison to others. By performing blood group determination using a routine method at outreach programs, the susceptible individuals can be identified and counselled to quit the habit, thereby avoiding potential complications.

Rotational atherectomy for in-stent restenosis: acute and long-term results of the first 100 cases.

OBJECTIVES: This study evaluated the clinical safety and long-term results of rotational atherectomy (RA) followed by low-pressure balloon dilatation (percutaneous transluminal coronary angioplasty [PTCA]) for the treatment of in-stent restenosis (ISR). BACKGROUND: In-stent restenosis is associated with a high incidence of recurrence after interventional treatment. Because ISR is due to neointimal hyperplasia, rotational ablation may be a more effective treatment than PTCA. METHODS: Between November 1995 and November 1996, 100 consecutive patients with first-time ISR were treated by RA. Quantitative coronary angiography and intravascular ultrasound (IVUS) were used to analyze the acute procedural results. The incidence of repeat in-stent restenosis and target vessel revascularization (TVR) at follow-up was determined. RESULTS: Procedural success without any major in-hospital complications was achieved in 100% of cases. Slow flow was observed in 3% and creatine kinase-MB enzyme elevation >3x normal occurred in 2%. The mean burr-to-artery ratio was 0.68+/-0.18 and adjuvant balloon dilatation was performed at 4.2+/-2.1 atm. Minimum luminal diameter increased from 0.86+/-0.28 mm to 1.89< or =0.21 mm after RA and to 2.56+/-0.29 mm after adjunct PTCA. Quantitative IVUS analysis showed that 77% of the luminal gain occurred due to rotational ablation of the restenotic tissue and only 23% occurred after adjunct balloon dilation, and further stent expansion did not contribute to the luminal enlarge. ment. At a mean follow-up of 13+/-5 months, repeat in-stent restenosis occurred in 28% of patients with TVR of 26%. Univariate predictors of repeat restenosis were burr-to-artery ratio <0.6, ISR in <90 days of stenting, ostial lesion, stent for a restenotic lesion and diffuse type ISR. CONCLUSIONS: Rotational atherectomy is a safe and feasible technique for treatment of ISR and is associated with a relatively low recurrent restenosis in comparison to historical controls of balloon angioplasty.

Kinetics of DNA hydration.

The hydration of the d(CGCGAATTCGCG) B-DNA duplex in solution was studied by nuclear magnetic relaxation dispersion (NMRD) of the water nuclei 1H, 2H, and 17O, and by nuclear Overhauser effects (NOEs) in high-resolution two-dimensional 1H NMR spectra. By comparing results from the free duplex with those from its complex with netropsin, water molecules in the "spine of hydration" in the AATT region of the minor groove could be distinguished from hydration water elsewhere in the duplex. The 2H and 17O relaxation dispersions yield a model-independent residence time of 0.9(+/-0.1) ns at 4 degrees C for five highly ordered water molecules in the spine. When corrected for frequency offset effects, the NOE data yield the same residence time as the NMRD data, giving credence to both methods. At 27 degrees C, the residence time is estimated to 0.2 ns, a factor of 40 shorter than the tumbling time of the duplex. The NMRD data show that all water molecules associated with the duplex, except the five molecules in the spine, have residence times significantly shorter than 1 ns at 4 degrees C. There is thus no long-lived hydration structure associated with the phosphate backbone. In contrast to 2H and 17O, the 1H relaxation dispersion is dominated by labile DNA protons and therefore provides little information about DNA hydration.

Water molecules in DNA recognition I: hydration lifetimes of trp operator DNA in solution measured by NMR spectroscopy.

The present NMR study investigates the residence times of the hydration water molecules associated with uncomplexed trp operator DNA in solution by measuring intermolecular nuclear Overhauser effects (NOE) between water and DNA protons, and the nuclear magnetic relaxation dispersion (NMRD) of the water 2H and 17O resonances. Both methods indicate that the hydration water molecules exchange with bulk water on the sub-nanosecond time scale at 4 degreesC. No evidence was obtained for water molecules bound with longer residence times. In particular, the water molecules at the sites of interfacial hydration in the trp repressor/operator complex do not seem kinetically stabilized in the uncomplexed DNA. Analysis of the crystal structures of two different trp repressor/operator complexes shows very similar structural environments for the water molecules mediating specific contacts between the protein and the DNA, whereas much larger variations are observed for the location of corresponding water molecules detected in the crystal structure of an uncomplexed trp operator DNA duplex. Therefore, it appears unlikely that the hydration characteristics of the uncomplexed DNA target would be a major determinant of trp repressor/operator recognition.

Model-free analysis of stretched relaxation dispersions.

Nuclear magnetic relaxation dispersion (NMRD) measurements can provide valuable information about the dynamics and structure of macromolecular solutions and other complex fluids. A large number of 1H NMRD studies of water in concentrated protein solutions and in semisolid biological samples have been reported. The observed dispersion usually extends over a wide frequency range and then cannot be described by a Lorentzian spectral density function. We propose here a model-free approach for analyzing such stretched dispersion profiles. Unlike the traditional empirical fitting procedures, the model-free approach is based on rigorous theory and produces parameters with well-defined physical significance. The model-free approach is validated with the aid of synthetic relaxation data, showing that it is robust and accurate, and is then applied to new water 1H NMRD data from solutions of the protein bovine pancreatic trypsin inhibitor (BPTI). By separating the static and dynamic information content of the relaxation dispersion, the model-free analysis shows that the dramatic salt effect observed in BPTI solutions is due almost entirely to a slowing down of protein rotation with little change of protein structure. An analysis of the same data in terms of the empirical dispersion function used in most 1H NMRD studies leads to a qualitatively different picture. We demonstrate that this widely used dispersion function is unphysical and that its parameters do not have the physical meaning usually ascribed to them.

Breast cancer bone metastasis in femur: surgical considerations and reconstruction with Long Gamma Nail.

AIM: The femur is the most common long bone involved in metastatic breast cancer. Several studies have been published on the surgical management of metastatic disease of the femur. However, only few studies have been published specifically on the outcomes following reconstruction of femoral metastasis from breast cancer using a third generation intramedullary nail. The aim of this study is to review the outcomes after intramedullary surgical stabilization of femoral metastases from breast cancer. This is often associated with significant bone destruction. METHODS: A retrospective study of 18 femoral metastatic lesions in 15 patients treated with a Long Gamma Nail over a 6-year period was carried out. Pain relief, mobilization status and implant related complications were the main outcome measures analyzed. RESULTS: Thirteen out of 15 patients had complete pain relief and all patients regained their preoperative mobilization status with or without walking aids. There were no implant failures or perioperative deaths. Four (26%) patients developed minor complications. Ten patients died with an average survival of 9 months and five patients are alive with an average survival of 32 months. CONCLUSION: Stabilization of femoral metastases due to breast cancer with Long Gamma Nail is a safe and effective method with acceptable risks.

Molecular reorientations in liquid crystals pentyloxybenzylidine hexylanilene (PBHA) and butyloxybenzylidine octylanilene (BBOA).

Molecular reorientational motions in undeuterated pentyloxybenzylidine hexylanilene (PBHA or 5O.6) and butyloxybenzylidine octylanilene (BBOA or 4O.8) as studied by the quasielastic neutron scattering (QENS) technique in their different mesophases are reported. Models are built up in stages to account for the experimental elastic incoherent structure factor (EISF). It is found that there exist simultaneous reorientational motions of the chain group and the reorientational motions of the whole molecule around its molecular axis in the smectic- G, smectic- B, and smectic- C phases. In smectic- A and nematic phases, additional body axis fluctuations are found to exist in both 5O.6 and 4O.8 systems. The average amplitude of body axis fluctuations is found to be approximately 15 degrees and 25 degrees, respectively, in the smectic- A and nematic phases of 5O.6, and approximately 14 degrees and 29 degrees, respectively, in 4O.8.

Treatment of patello-femoral arthritis using the Lubinus patello-femoral arthroplasty: a retrospective review.

There are few published results in the literature on patello-femoral arthroplasty. The aim of this study was to help to define the place of patello-femoral arthroplasty in the treatment of isolated patello-femoral arthritis. All patients who underwent patello-femoral arthroplasty using the Lubinus prosthesis for patello-femoral arthritis between 1992 and 1998 in two neighbouring district general hospitals were studied. There were 34 patients who underwent 45 arthroplasties. The modified Hungerford and Kenna scoring system and the Insall and Crosby scoring system were used to clinically evaluate the patients. Serial radiographs were assessed for patellar malalignment, mechanical failure and progressive arthritic change. Twenty-three knees (64%) had a good or excellent result, six (17%) had an unsatisfactory result and seven (19%) were revised to either a total knee arthroplasty (5 knees) or patellofemoral arthroplasty (2 knees). Although the results do not compare favourably with those of total knee replacement for generalised arthritis of the knee; we believe that with careful patient selection coupled with careful surgical technique, patello-femoral arthroplasty can be successfully used to treat isolated patello-femoral osteoarthritis.

Proximal interphalangeal joint release in Dupuytren's disease of the little finger.

We present a prospective study, with 3-year follow-up, of the role and outcome of fasciectomy plus sequential surgical release of structures of the proximal interphalangeal joint in Dupuytren's contracture of the little finger. Our treatment programme involves fasciectomy for all patients followed by sequential release of the accessory collateral ligament and volar plate as necessary. Of the 19 fingers in the study, eight achieved a full correction by fasciectomy alone, and in these cases there was a fixed flexion deformity of 6 degrees at 3 months and 8 degrees at 3 years. The remaining 11 fingers (initial mean deformity 70 degrees flexion) were left with a fixed flexion deformity of 42 degrees after fasciectomy which reduced to 7 degrees with capsulo-ligamentous release. This increased to 26 degrees at 3 months but then remained relatively stable, increasing only to 29 degrees at 3 years. In our experience sequential proximal interphalangeal joint release has led to consistently good results with few complications in the correction of severe Dupuytren's disease of the little finger.

Carcinoid tumour: laser therapy.

A 31-year-old female, pregnant (I trimester), presented with symptoms and signs of bronchial asthma. Chest roentgenogram and computerized tomography of the chest revealed right mid and lower zone opacity (collapse). Bronchoscopic examination revealed intrabronchial growth in the right middle and lower lobe bronchus. Biopsy and histopathological examination confirmed carcinoid tumour. These symptoms and signs disappeared after laser therapy. The lesion, however, recurred two years later.

Integrative genomic analysis of temozolomide resistance in diffuse large B-cell lymphoma.

PURPOSE: Despite advances, there is an urgent need for effective therapeutics for relapsed diffuse large B-cell lymphoma, particularly in elderly patients and primary central nervous system (CNS) lymphoma. Temozolomide (TMZ), an oral DNA-alkylating agent routinely used in the therapy of glioblastoma multiforme, is active in patients with primary CNS lymphoma but the response rates are low. The mechanisms contributing to TMZ resistance are unknown. EXPERIMENTAL DESIGN: We undertook an unbiased and genome-wide approach to understand the genomic methylation and gene expression profiling differences associated with TMZ resistance in diffuse large B-cell lymphoma cell lines and identify mechanisms to overcome TMZ resistance. RESULTS: TMZ was cytotoxic in a subset of diffuse large B-cell lymphoma cell lines, independent of MGMT promoter methylation or protein expression. Using Connectivity Map (CMAP), we identified several compounds capable of reversing the gene expression signature associated with TMZ resistance. The demethylating agent decitabine (DAC) is identified by CMAP as capable of reprogramming gene expression to overcome TMZ resistance. Treatment with DAC led to increased expression of SMAD1, a transcription factor involved in TGF-ß/bone morphogenetic protein (BMP) signaling, previously shown to be epigenetically silenced in resistant diffuse large B-cell lymphoma. In vitro and in vivo treatment with a combination of DAC and TMZ had greater antilymphoma activity than either drug alone, with complete responses in TMZ-resistant diffuse large B-cell lymphoma murine xenograft models. CONCLUSIONS: Integrative genome-wide methylation and gene expression analysis identified novel genes associated with TMZ resistance and demonstrate potent synergy between DAC and TMZ. The evidence from cell line and murine experiments supports prospective investigation of TMZ in combination with demethylating agents in diffuse large B-cell lymphoma.

T-cell recognition of iron-regulated culture filtrate proteins of Mycobacterium tuberculosis in tuberculosis patients and endemic normal controls.

BACKGROUND: Culture filtrate proteins (CFPs) of Mycobacterium tuberculosis are potential vaccine candidates. OBJECTIVE: The aim was to study the influence of iron levels on CFPs and assess the immuno-protective potential of defined antigenic fractions from high (8 µg Fe/mL) and low iron (0.02 µg Fe / mL) cultures of M. tuberculosis. MATERIALS AND METHODS: The CFPs of M. tuberculosis from high (CFP-high) and low (CFP-low) iron conditions were first compared to identify iron-regulated proteins and then fractionated to obtain ten antigen pools (CF-Ags H1- H5 and L1-L5) that were used to assess the immune response of TB patients and normal healthy controls. RESULTS: Iron limitation resulted in the up-regulation of two novel iron-regulated low-molecular-weight proteins Irp-1 (in CF-Ag L4) and Irp-2 (in CF-Ag L5) and repression of two ESAT proteins (identified with monoclonal antibody HYB 76.8). The median stimulation indices (SIs) against most of the CF-Ags were high in pulmonary TB patients. The CF-Ags L1 and L2 showed statistically significant SI (P values of 0.0027 and 0.0029 respectively); the % case recognition was high with these antigens as well as with L4 ( P = 0.0275). IFN-γ in response to these CF-Ags was significantly high in the endemic normals; maximal expression was seen with CF-Ag L5 (median value of 233 pg mL -1 ) that was higher than the corresponding H5 (140 pg mL -1 ) and H3 and L3 (205 and 206 pg mL -1 respectively). CONCLUSIONS: CF-Ags L5, H3 and L3 showed immuno-protective potential in this geographical location.

Akt inhibitors MK-2206 and nelfinavir overcome mTOR inhibitor resistance in diffuse large B-cell lymphoma.

PURPOSE: The mTOR pathway is constitutively activated in diffuse large B-cell lymphoma (DLBCL). mTOR inhibitors have activity in DLBCL, although response rates remain low. We evaluated DLBCL cell lines with differential resistance to the mTOR inhibitor rapamycin: (i) to identify gene expression profile(s) (GEP) associated with resistance to rapamycin, (ii) to understand mechanisms of rapamycin resistance, and (iii) to identify compounds likely to synergize with mTOR inhibitor. EXPERIMENTAL DESIGN: We sought to identify a GEP of mTOR inhibitor resistance by stratification of eight DLBCL cell lines with respect to response to rapamycin. Then, using pathway analysis and connectivity mapping, we sought targets likely accounting for this resistance and compounds likely to overcome it. We then evaluated two compounds thus identified for their potential to synergize with rapamycin in DLBCL and confirmed mechanisms of activity with standard immunoassays. RESULTS: We identified a GEP capable of reliably distinguishing rapamycin-resistant from rapamycin-sensitive DLBCL cell lines. Pathway analysis identified Akt as central to the differentially expressed gene network. Connectivity mapping identified compounds targeting Akt as having a high likelihood of reversing the GEP associated with mTOR inhibitor resistance. Nelfinavir and MK-2206, chosen for their Akt-inhibitory properties, yielded synergistic inhibition of cell viability in combination with rapamycin in DLBCL cell lines, and potently inhibited phosphorylation of Akt and downstream targets of activated mTOR. CONCLUSIONS: GEP identifies DLBCL subsets resistant to mTOR inhibitor therapy. Combined targeting of mTOR and Akt suppresses activation of key components of the Akt/mTOR pathway and results in synergistic cytotoxicity. These findings are readily adaptable to clinical trials.