Search

Purpose: To evaluate the feasibility of sparing the dysphagia-aspiration-related structures (DARS) in various head and neck cancer sites treated with definitive DARS-optimized intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. Materials and Methods: Target volumes, organs at risk, and in addition, individual DARS were delineated, including the superior, middle, and inferior pharyngeal constrictor muscles, supraglottic and glottic larynx, the base of the tongue, esophageal inlet muscles and cervical esophagus in 35 patients with head and neck squamous cell carcinoma. Volume-based dose constraints were applied to the DARS outside the planning target volume (PTV). An IMRT plan was then generated to limit doses to DARS without compromising PTV dose coverage. Results: Twelve (34.3) patients had an oropharyngeal primary (OPX), 18 (51.4) had a laryngeal, and 5 (14.3) patients had hypopharyngeal primary. The mean dose to the DARS was 47.93 Gy for the entire group, while it was 54.6 Gy in oropharyngeal primaries and 44.4 Gy in laryngopharyngeal primaries. DARS mean dose of ≤45 Gy could be achieved in a significantly lesser number of patients with oropharyngeal primaries (P < 0.02). Similarly, DARS mean dose was 42.25 Gy in patients with N0 disease, 49.6 Gy with ipsilateral involved nodes, and 55 Gy with bilateral disease. Sparing of DARS was feasible when the volume of PTV was ≤150 cc (P < 0.025). Conclusion: Sparing of DARS structures appears to be challenging in patients with oropharyngeal cancers without compromising the dose to the PTVs while it is feasible in laryngopharyngeal cancers. DARS sparing is feasible when the PTV volume is < 150 cc and in patients with negative or unilateral nodal disease. Keywords: Aspiration, DARS, DARS optimized RT, dysphagia, head neck cancer, Author(s): Adnan Calcuttawala [1,2]; Abhishek Shinghal [1,3]; Ashwini N. Budrukkar (corresponding author) [1]; Monali Swain [1]; Vedang Murthy [1]; Sarbani G. Laskar [1]; Tejpal Gupta [1]; Rituraj Upereti [4]; Shrikant [...]

Purpose: This study aimed to evaluate the volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy (IGRT) for locally advanced oropharyngeal cancers. Materials and Methods: Twenty patients receiving radiotherapy using IGRT at a dose of 70 Gy/35 fractions/7 weeks for locally advanced oropharyngeal cancers were accrued. Radiotherapy planning computed tomography (CT) scans were performed at pre-radiotherapy (RT), 20, 40, and 60 Gy for each patient. Volume changes in target and parotids along with shifts of parotids were assessed with respect to pre-RT scan after co-registration. In study scans, GTVp and GTVn were recontoured as per particular CT. CTV and PTV were copied from planning CT to study CT. CTV was edited from anatomical barriers, and PTV was edited only from the skin in the study CT. The parotids were recontoured on each study scan. The center of mass (COM) of C2 vertebral body was considered as the reference to evaluate its shifts. Results: There was a statistically significant percentage regression of ipsilateral and contralateral parotid mean volumes at the rate of 0.85/0.207 cc and 0.98/0.26 cc per day, respectively. We observed the mean medial shift of center of mass of ipsilateral parotid of 2.23 mm (p = 0.011) and contralateral parotid of 2.67 mm (p = 0.069) at the end of 60 Gy. GTVp (mean) reduced from 41.87 cc at 0 Gy to 31.13 cc (25.65) at 60 Gy (p = 0.003), while GTVn (mean) reduced from 19.98 cc at 0 Gy to 10.79 cc (45.99) at 60 Gy (p = 0.003). There was a statistically significant reduction in CTV and PTV volumes at 60 Gy. Conclusion: Statistically significant volumetric and geometric changes occurred during intensity-modulated radiation (IMRT), which were most prominent after 40 Gy and were maximum at 60 Gy. There was a medial shift of parotid glands toward the high-dose region. This study can be useful to devise an adaptive radiotherapy strategy. Keywords: Head and neck IGRT, parotid movement, volumetric geometric changes, Author(s): Sagar Gayakwad [1,2]; Ashwini Budrukkar (corresponding author) [1]; Vedang Murthy [1]; Sarbani G. Laskar [1]; Ritu Raj Upreti [3]; Udita Upreti [3]; Tejpal Gupta [1]; Jai Prakash Agarwal [1] [...]

Purpose: To report clinical profiles of multiple sclerosis (MS)-associated uveitis in seven cases from a single tertiary eye care center in South India. Methods: Retrospective case series 2013-2023. Results: Seven cases of MS-associated uveitis were retrieved from our databases. There were five females and two males. The diagnosis of MS was made by the neurologist in all cases. Bilaterality was seen in all cases. Intermediate uveitis was the most common presentation (five cases). It was associated with peripheral retinal vasculitis (two cases) and disc pallor (two cases). Fuchs heterochromic iridocyclitis (one case) and incomplete Vogt-Koyanagi-Harada (VKH)-like presentation with a peripapillary choroidal neovascular membrane (one case) were the other presentations. In the case with incomplete VKH-like presentation, whole genome sequencing revealed a heterozygous non-synonymous variation (c.1228C>T) in exon 10 of TNFRSF1A, suggestive of susceptibility to multiple sclerosis 5 due to mutation in the TNFRS1A gene on chromosome 12p13.31. All cases received systemic steroids. Azathioprine (three cases) and rituximab (three cases) were the commonly used immunomodulatory drugs. The visual outcome was good in all cases at the last follow-up. Conclusion: MS-associated uveitis is underreported in India. This series highlights the clinical profile of MS-associated uveitis in India. Keywords: Fuchs heterochromic iridocyclitis, incomplete VKH-like presentation, intermediate uveitis, multiple sclerosis, retinal vasculitis, uveitis, Author(s): Kalpana Babu (corresponding author) [1]; Geethanjali C Janardhana [2]; Krishna R Murthy [1,2] In patients with MS, the frequency of uveitis ranges from 0.4 to 26.9%, and in patients [...]

Il y a 30 ans, David Moher a defendu l'importance d'obliger l'enregistrement des essais cliniques dans les pages du JAMC (1). Au Canada, les exigences liees a l'enregistrement des essais [...]

Author(s): Gazella Bruce Warjri [1]; Somasheila I Murthy [2]; Anthony Vipin Das [3,4]; Sirisha Senthil (corresponding author) [1] Dear Editor, We would like to thank the authors for their insightful [...]

Byline: Maneck. Nicholson, Vivek. Singh, Somasheila. Murthy, Damien. Gatinel, Savio. Pereira, Aditya. Pradhan, Shail. Vasavada, Prajakta. Dandekar, Mekhla. Naik, Supriya. Sharma This review analyzed all pertinent articles on keratoconus (KCN) [...]

Byline: Arundhati. Dvivedi, Somasheila. Murthy, Vidhyadhar. Akkulugari, Hasnat. Ali To evaluate the surgical and visual outcomes of flap repositioning for various post-laser-assisted in-situ keratomileusis (LASIK) flap pathologies. Retrospective review of [...]

Byline: Raghav. Peraka, Somasheila. Murthy, Varsha. Rathi Purpose: This study aimed to report the strategies that evolved in managing Mooren's ulcer (MU) at a resource-limited center in rural India during [...]

Byline: Anthony. Das, Rashmi. Deshmukh, Jagadesh. Reddy, Vineet. Joshi, Vivek. Singh, Pratik. Gogri, Somasheila. Murthy, Sunita. Chaurasia, Merle. Fernandes, Aravind. Roy, Sujata. Das, Pravin. Vaddavalli Purpose: This paper aims to [...]

Byline: Shilpa. Das, Somasheila. Murthy, Tapas. Padhi, Himansu. Behera, Saumya. Jakati, Savitri. Sharma, Sujata. Das Atypical mycobacteria or non-tuberculous mycobacteria (NTM) are a group of acid-fast bacteria that are pathogenic [...]

Byline: Shalaka. Somayaji, Sangana. Reddy, Mamatha. Murthy, Vinayak. Maka Background: Plant alkaloids remain an essential part of many chemotherapeutic regimens. Although many adverse effects have been studied with appropriate management [...]

Byline: Ravina. Todi, Gowri. Murthy, Praveen. Murthy, Dhwani. Shah, Priyanka. Sudhakar We report a case of a 74 years old patient with both eye angle-closure glaucoma, and central retinal vein [...]

Thirty years ago, David Moher made the case for mandatory registration of clinical trials in the pages of CMAJ. (1) In Canada, requirements to both register trials and report their [...]

Byline: Jacqueline. Hamati, Sai. Prashanthi, Raja. Narayanan, Niroj. Sahoo, Anthony. Das, Padmaja. Rani, Umesh. Behera, Rohit. Khanna, Gudlavalleti. Murthy Purpose: To report a big data analysis of risk and protective [...]

Byline: G. Murthy The World Sight Day is an important event on the global eye care calendars yearly. It is celebrated on the 2 Thursday of October. It was first [...]

In utero gene editing with mRNA-based therapeutics has the potential to revolutionize the treatment of neurodevelopmental disorders. However, a critical bottleneck in clinical application has been the lack of mRNA delivery vehicles that can efficiently transfect cells in the brain. In this report, we demonstrate that in utero intracerebroventricular (ICV) injection of densely PEGylated lipid nanoparticles (ADP-LNPs) containing an acid-degradable PEG–lipid can safely and effectively deliver mRNA for gene editing enzymes to the fetal mouse brain, resulting in successful transfection and editing of brain cells. ADP-LNPs containing Cre mRNA transfected 30% of the fetal brain cells in Ai9 mice and had no detectable adverse effects on fetal development and postnatal growth. In addition, ADP-LNPs efficiently transfected neural stem and progenitor cells in Ai9 mice with Cre mRNA, which subsequently proliferated and caused over 40% of the cortical neurons and 60% of the hippocampal neurons to be edited in treated mice 10 weeks after birth. Furthermore, using Angelman syndrome, a paradigmatic neurodevelopmental disorder, as a disease model, we demonstrate that ADP-LNPs carrying Cas9 mRNA and gRNA induced indels in 21% of brain cells within 7 days postpartum, underscoring the precision and potential of this approach. These findings demonstrate that LNP/mRNA complexes have the potential to be a transformative tool for in utero treatment of neurodevelopmental disorders and set the stage for a frontier in treating neurodevelopmental disorders that focuses on curing genetic diseases before birth.

We investigate the impact of multiple distributed intelligent reflecting surfaces (IRSs), which are deployed and optimized by a mobile operator (MO), on the performance of user equipments (UEs) served by other co-existing out-of-band (OOB) MOs that do not control the IRSs. We show that, under round-robin scheduling, in mmWave frequencies, the ergodic sum spectral efficiency (SE) of an OOB MO increases logarithmically in the total number of IRS elements with a pre-log factor that increases with the ratio of the number of OOB paths through the IRS to the number of elements at an IRS. Further, the maximum achievable SE of the OOB MO scales log-linearly with the total IRS elements, with a pre-log factor of 1. We specify the minimum number of IRSs as a function of the channel parameters and design a distributed IRS system in which an OOB MO almost surely obtains the maximum SE. Finally, we prove that the outage probability at an OOB UE decreases exponentially as the number of IRSs increases, even though they are randomly configured from the OOB UE’s viewpoint. We numerically verify our theory and conclude that distributed IRSs always help every MO, but the MO controlling the IRSs benefits the most.

Analog integrated circuit (IC) design and its automation pose significant challenges due to the time-consuming mathematical computations and complexity of circuit design. Though efforts have been made to automate the analog design flow, the current approach falls short in meeting the exact design requirements and plagued by inaccuracies, highlighting the necessity for a more robust approach capable of accurately predicting circuits. In addition, there is a need for an improved dataset collection technique to enhance the overall performance of the automation process. The power management unit (PMU) is a crucial block in any IC that requires the design of low-dropout regulator (LDO) for which amplifiers are fundamental blocks. This research harnesses the capabilities of deep neural networks (DNNs) to automate essential amplifier blocks, such as the differential amplifier (DiffAmp) and two-stage operational amplifier (OpAmp). In addition, it proposes an automation framework for the higher level circuitry of the LDO. This article introduces a novel “TriNet” architecture designed for various parameters of amplifiers, including gain, bandwidth, and power facilitating precise predictions for DiffAmp and OpAmp, and presents a decoder architecture tailored for LDO. A notable aspect is the development of an efficient technique for acquiring larger datasets in a condensed timeframe. The presented methodologies demonstrate high accuracy rates, achieving 97.3% for DiffAmp and OpAmp circuits and 94.3% for LDO design.

Macrophages exhibit remarkable functional plasticity, a requirement for their central role in tissue homeostasis. During chronic inflammation, macrophages acquire sustained inflammatory ‘states’ that contribute to disease, but there is limited understanding of the regulatory mechanisms that drive their generation. Here we describe a systematic functional genomics approach that combines genome-wide phenotypic screening in primary murine macrophages with transcriptional and cytokine profiling of genetic perturbations in primary human macrophages to uncover regulatory circuits of inflammatory states. This process identifies regulators of five distinct states associated with key features of macrophage function. Among these regulators, loss of the N6-methyladenosine (m6A) writer components abolishes m6A modification of TNFtranscripts, thereby enhancing mRNA stability and TNF production associated with multiple inflammatory pathologies. Thus, phenotypic characterization of primary murine and human macrophages describes the regulatory circuits underlying distinct inflammatory states, revealing post-transcriptional control of TNFmRNA stability as an immunosuppressive mechanism in innate immunity.

AbstractNS3-4A, a serine protease, is a primary target for drug development against Hepatitis C Virus (HCV). However, the effectiveness of potent next-generation protease inhibitors is limited by the emergence of mutations and resulting drug resistance. To address this, in this study a structure-based drug design approach is employed to screen a large library of 7320 natural compounds against both wild-type and mutant variants of NS3-4A protease. Telaprevir, a widely used protease inhibitor, was recruited as the control drug. The top 10 compounds with favorable binding affinities underwent drug-likeness evaluation. Based on ADMET studies, complexes of NP_024762 and NP_006776 were selected for molecular dynamic simulations. Principal component analysis (PCA) was employed to explore the conformational space and protein dynamics of the protein-ligand complex using a Free Energy Landscape (FEL) approach. The cosine values obtained from FEL analysis ranged from 0 to 1, and eigenvectors with cosine values below 0.2 were chosen for further analysis. To forecast binding free energies and evaluate energy contributions per residue, the MM-PBSA method was employed. The results highlighted the crucial role of amino acids in the catalytic domain for the binding of the protease with phytochemicals. Stable associations between the top compounds and the target protease were confirmed by the formation of hydrogen bonds in the binding pocket involving residues: His1057, Gly1137, Ser1139, and Ala1157. These findings suggest the potential of these compounds for further validation through biological evaluation.Communicated by Ramaswamy H. Sarma

Herein, we report nickel(0)-catalyzed cross-coupling reactions of NHC/CAAC-based carbodicarbene (NHC = N-heterocyclic carbene and CAAC = cyclic(alkyl)(amino)carbene) with different aryl chlorides, bromides, and iodides. The resulting aryl-substituted cationic carbodicarbene derivatives are prone to one-electron oxidation yielding radical-dications, which, depending on the aryl motif employed, follow different modes of radical–radical dimerization and constitute an entry point to carbon/nitrogen- and nitrogen/nitrogen-centered diradicaloids. Subsequently, this coupling strategy was strategically applied to the synthesis of p-phenylene- and p,p′-biphenylene-bridged carbon/carbon-centered electron-deficient diradicaloids. The employed π-conjugated spacer plays a crucial role in determining the triplet population at room temperature by modulation of the singlet–triplet gap: EPR inactive for p-phenylene vs EPR active for p,p′-biphenylene. Nearly two decades after the disclosure of carbodicarbenes as donor-stabilized atomic carbon equivalents by Tonner and Frenking in 2007, we demonstrate their cross-couplings with a series of aryl halides/dihalides and, based on this, developed a modular methodology for the systematic synthesis of various electron-deficient diradicaloids.

A novel photoinduced Fe(OTf)2/2,4,6-collidine-catalyzed alkylation of Morita–Baylis–Hillman (MBH) acetates using carboxylic acids in a regio- and stereoselective manner is reported. This method demonstrates a broad scope, encompassing various carboxylic acids and MBH acetates, including drugs and bioactive molecules, to synthesize densely functionalized cinnamates and acrylates. The reactions are performed in the green solvent dimethyl carbonate under oxidant-free conditions. Based on control experiments, a plausible mechanism involving an Fe(II)–Fe(III)–Fe(II) cycle is proposed.

ABSTRACTA novel low-melting-temperature chemical flux method was used to synthesise a Ca2La2O5lattice doped with Eu3+ions in the range of 0.5-2.5 mol-%. The phosphors were characterised by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy, particle size distribution, photoluminescence (PL), and Fourier transform infrared spectroscopy, respectively. The PXRD pattern revealed the hexagonal crystal structure with the space group P63/m. The microstrain (ϵ) was found to not vary with different concentrations of dopant and the negative means compression in the lattice. Particles of varying sizes and irregular shapes were observed from the SEM micrographs. The EDAX mapping revealed that all the constituent elements were found to be in appropriate ratios. Interestingly, the Ca2La2O5:xEu3+(x = 0.5-2.5 mol-%) phosphor samples were excited at 590 nm, showing a Stokes-shifted red-PL with significant intensities at 615 and 627 nm. Unconventionally, when the phosphor is excited at 590 nm, the Eu3+ion-characteristic luminescence owing to 5D0→7FJ(J = 0, 1, 2, 3, 4) transitions are manifested. Another remarkable observation is that the PL at 627 nm corresponding to 5D0→7F3transition was much stronger than the 615 nm emission of Eu3+corresponding to 5D0→7F3transition, indicating high colour purity among the available red-emitting phosphors.

A goal of neuroscience is to obtain a causal model of the nervous system. The recently reported whole-brain fly connectome1–3specifies the synaptic paths by which neurons can affect each other, but not how strongly they do affect each other in vivo. To overcome this limitation, we introduce a combined experimental and statistical strategy for efficiently learning a causal model of the fly brain, which we refer to as the ‘effectome’. Specifically, we propose an estimator for a linear dynamical model of the fly brain that uses stochastic optogenetic perturbation data to estimate causal effects and the connectome as a prior to greatly improve estimation efficiency. We validate our estimator in connectome-based linear simulations and show that it recovers a linear approximation to the nonlinear dynamics of more biophysically realistic simulations. We then analyse the connectome to propose circuits that dominate the dynamics of the fly nervous system. We discover that the dominant circuits involve only relatively small populations of neurons—thus, neuron-level imaging, stimulation and identification are feasible. This approach also re-discovers known circuits and generates testable hypotheses about their dynamics. Overall, we provide evidence that fly whole-brain dynamics are generated by a large collection of small circuits that operate largely independently of each other. This implies that a causal model of a brain can be feasibly obtained in the fly.

The fruit fly Drosophila melanogasterhas emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome1with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome2, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics.

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1–6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107chemical synapses7between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10–12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome—a map of projections between regions—from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Studies on the genetic yield of developmental and epileptic encephalopathy and Epileptic encephalopathies using next‐generation sequencing techniques are sparse from the Indian subcontinent. Hence, the study was conducted to assess the yield of genetic testing and the proportion of children where a positive genetic yield influenced treatment decisions. In this retrospective observational study, electronic medical records of children (0–12 years) with suspected genetic epilepsy who underwent genetic testing using whole exome sequencing, focused exome sequencing and epilepsy gene panels were retrieved. Genetic yield was ascertained based on the detection of pathogenic and likely pathogenic variants. A total of 100 patients with epilepsy underwent genetic testing. A yield of 53.8% (42/78) was obtained. Pathogenic variants were identified in 18 (42.8%) cases and likely pathogenic variants in 24 (57.1%) cases. Yield was 66.6% each through whole exome sequencing, focused exome sequencing and 40% through Epilepsy gene panels (p= .07). Yield was not statistically significant across different age groups (p= .2). It was however found to significantly vary across different epilepsy syndromes with maximum yield in Epilepsy in infancy with migrating focal seizures in 2 (100%), followed by developmental and epileptic encephalopathy unspecified in 14 (77.7%), Dravet syndrome in 14 (60.8%), early infantile developmental and epileptic encephalopathy in 3 (60%), infantile epileptic spasm syndrome in 5 (35.7%), and other epileptic encephalopathies in 4 (30.7%) cases (p= .04). After genetic diagnosis and drug optimization, drug‐refractory proportion reduced from 73.8% to 45.3%. About half of the cases achieved seizure control. A reasonably high yield of 53.8% was obtained irrespective of the choice of panel or exome or age group using next‐generation sequencing‐based techniques. Yield was however higher in certain epilepsy syndromes and low in Infantile epileptic spasms syndrome. A specific genetic diagnosis facilitated tailored treatment leading to seizure freedom in 28.6% and marked seizure reduction in 54.7% cases.

Sodium–glucose co-transporter-2 (SGLT2) inhibitors have been proposed as a potential treatment for adults hospitalised with COVID-19, due to their potential anti-inflammatory and endothelial protective effects. Published evidence from randomised control trials (RCTs) does not provide evidence of benefit. We aimed to estimate the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo in adults hospitalised with COVID-19.

This study presents an improved understanding of the stress distribution in the joint region of weak-axis connections in steel MRFs, and based on this understanding, connection configurations have been proposed for the column-to-foundation connections Columns in MRFs are subjected to lateral forces along their strong and weak axes. To ensure ductile response, analysis, and requisite provisions of column foundation connections along the strong axis have been dealt with in detail. In this study, preliminary inelastic finite element analyses are conducted to study the flow of forces near the weak axis column-to-foundation connection. Theoretical axial load Pin the column that produces the worst V-M (shear-moment)loading is identified. Based on these loads a cover plated and ribbed configuration is proposed for the weak- axis column-base (WACB) connection. Nonlinear finite element analyses are performed under monotonic, and FEMA recommended multi-cycle loadings using ABAQUS software to evaluate the performance of the proposed connection configurations and the associated design procedures. The performance of the new weak-axis connections (WACs) is compared with that of the existing connections in terms of von Mises stress, shear stress, normal stress, load deformation response, energy dissipated, and cumulative plastic strain excursion. It was observed that WACB connections in steel MRFs need to be reinforced to keep the stress in CJP welds connecting the column to the base plate below the yield stress even at the lateral drift levels much lower than those expected of about 4–6% lateral drifts. The proposed configuration results in increased moment of inertia of the column about the weak axis and hence enhances the seismic response.

•Patients with limited (<5 disease sites) pre-CART B-cell NHL are at high risk of local relapse/progression.•BRT before CART for patients with R/R NHL and limited disease (<5 involved sites) improves outcomes without causing significant toxicities.

GNE myopathy is a rare slowly progressive adult-onset distal myopathy with autosomal recessive inheritance. It has distinctive features of quadriceps sparing with preferential anterior tibial involvement. Most patients eventually become wheelchair bound by 10–20 years after onset. This study analyzes the phenotype-genotype characteristics and disease progression in a large cohort of GNEM patients from India. Retrospective observational study on GNEM from a quaternary neurology referral hospital in southern India. Data was collected from clinical phenotyping, serum creatine kinase levels, muscle biopsy histopathology, genetic analysis and functional assessment scales – IBMFRS and MDFRS. 157 patients were included with mean age at onset and diagnosis: 26.5±6.2 years and 32.8±7.8 years, respectively. M:F ratio was 25 : 13. Most common presenting symptom: foot drop (46.5%) and limb girdle weakness (19.1%). Wasting and weakness of small muscles of hand and finger flexors seen in 66.2% and as an initial symptoms in 5.2%. Though tibialis anterior involvement was most common (89.2%), early quadriceps weakness was noted in 3.2% and Beevor’s sign in 59.2%. Rimmed vacuoles were present in 75% of patients with muscle biopsy. Most common variant was the Indian Founder variant identified in 129 patients (c.2179 G>A, p.Val727Met - 82.2%) and most common zygosity being compound heterozygous state (n = 115, 87.5%). Biallelic kinase domain variations predisposed to a more severe phenotype. Wheelchair bound state noted in 8.9% with a mean age and duration of 32.0±7.1 and 6.3±4.9 years respectively, earlier than previous studies on other ethnic groups. This is the largest GNEM cohort reported from South Asia. The p.Val727Met variant in compound heterozygous state is noted in majority (82.2%) of the cases. Observed relationships between genotype and clinical parameters shows that severity of the disease might be attributable to specific GNE genotype and thus could aid in predicting the disease progression.

Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking. This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation. A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed. A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1–8) years and 6.0(IQR:3–10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1(29.0%), DNM2(19.4%), SELENON(12.9%), KBTBD13(9.7%), NEB(6.5%), and MYPN(6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5–11) years and 13 (Range 3–35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON). This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1followed by DNM2gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.

Background: This review examines the historical developments, current state of training, existing challenges, and opportunities for undergraduate, postgraduate, and super specialty psychiatry education in India.Methods: For this narrative review, we examined information from the published literature, along with key documents from the Indian Psychiatric Society, the National Medical Commission, and other relevant sources.Conclusions: In India, psychiatry training has seen significant advancements since independence, particularly in the past decade, driven by the recommendations of the Indian Psychiatric Society and the introduction of competency-based medical education by the National Medical Commission. This transformation has redefined undergraduate and postgraduate training across all medical disciplines, including psychiatry. The shift has moved away from traditional, time-bound frameworks toward a focus on acquiring specific competencies essential for effective clinical practice. This approach ensures that trainees gain theoretical knowledge and develop practical skills and professional attitudes crucial for patient care. However, a major challenge highlighted in this review is the transition of senior residents to faculty roles without adequate training in teaching, research, academia, and leadership. Despite this, they are expected to excel in these areas upon assuming faculty positions. To address this gap, we emphasize the urgent need for a comprehensive faculty development program for early career faculty. Our proposed initiative aims to bridge these gaps and support the development of future leaders and educators in psychiatry. The recommendations outlined in this review seek to create a robust educational environment that will cultivate the next generation of psychiatrists in India.

Background: Indian medical graduates are expected to be lifelong learners, and medical teachers need to find newer and more engaging ways to help them hone their lifelong learning skills. Online learning can be a stepping stone toward this goal.Methods: We conducted a pre-post design interventional study in which 22 phase two MBBS students rated their self-directedness in learning using the Self-Rating Scale of Self-directed Learning (SRSSDL) at two points in time—before and after completing a 10-week online basic psychopharmacology module. Participant feedback was obtained regarding various aspects of the online modular learning experience.Results: The participants’ mean SRSSDL scores before and after the intervention were 231.31 ± 26.64 and 227.31 ± 31.33. The difference is not significant. The students’ scores at both points in time placed them in the “high” range of level of self-directed learning, leaving less realistic scope for a large change in the given time frame. Participant feedback was encouraging, with 19 out of 22 reporting that the overall learning experience was a “positive” one.Conclusions: Second-year medical students’ self-reported self-directedness is high. Online modular learning may be a feasible addition to medical education, even though it may not increase self-directedness in the short term. A limited sample size can lead to type 2errors.

The time varying nature of the wireless propagation channel causes a mismatch between the true channel at the time of data transmission and its available estimate based on previously received pilot symbols, and is known to impair the performance of the massive multiple input multiple output (MIMO) systems. In this paper, we develop and evaluate adaptive data aided channel tracking and data detection algorithms to counter the effects of channel aging for uplink and downlink massive MIMO systems. We first present a recursive least squares (RLS) algorithm for tracking the matrix uplink channel at the base station (BS), and derive bounds on its MSE performance. We also derive a linear complexity stochastic gradient descent (SGD) algorithm for tracking the uplink channel, along with its performance bounds. Following this, we develop RLS and SGD based algorithms for tracking the scalar effective downlink channel at each UE, and derive their performance guarantees. Finally, via Monte Carlo simulations, we validate the efficacy of the algorithms in terms of their mean squared error performance, and demonstrate the gains achievable by channel tracking in the form of the improvement in the symbol error rates.

Purpose: Equity, Diversity, and Inclusion (EDI) initiatives within critical care research are limited by a lack of resources and inconsistent and rapidly changing language. The Canadian Critical Care Trials Group (CCCTG) is committed to modelling EDI for the critical care community through its programming, communications, protocols, and policies. The objective of developing the EDI glossary of sociodemographic determinants of health described here was to provide a resource for critical care professionals to support broader equity initiatives and to promote education and awareness about inclusive language. Methods: Through literature review, we identified EDI-related sociodemographic determinants of health, defined as sociodemographic factors that are associated with disparities in health care and health outcomes, with a focus on critical care medicine. For each sociodemographic determinant of health, we identified umbrella terms (defined as domains) and subterms/constructs that are related to these domains. We designed the glossary collaboratively with the CCCTG EDI working group, patient and family partnerships committee, and executive committee, which included diverse knowledge users such as researchers, clinicians, and patient and family partners. Results: We report on 12 sociodemographic determinants of health domains including age, sex, gender, sexuality, race and ethnicity, income, education, employment status, marital status, language, disability, and migration status. Each domain (e.g., sex) contains relevant subterms such as male, female, intersex. For each domain, we provide examples of disparities in health care and health outcomes with a focus on critical care medicine. Conclusions: This EDI glossary of sociodemographic determinants of health serves as a nonexhaustive resource that may be referenced by critical care researchers, research coordinators, clinicians, and patient and family partners. The glossary is an essential step to raising awareness about inclusive terminology and to fostering and advancing equity in critical care medicine.

In this paper, we investigate on feasibility analysis of various modulation formats in different seawater types. We have simulated various baseband modulation schemes like Pulse Position Modulation (PPM), Pulse Interval Modulation (PIM) and Dual Header—Pulse Interval modulation (DHPIM) in addition to conventional On–Off Keying (OOK) with data speeds 200Mbps. We have tested these modulation schemes under different seawater types with different downwelling diffuse attenuation coefficients (kd). These simulation results show the performance of the modulation formats in terms of Probability of Error (PoE) and Signal-to-Noise Ratio (SNR). Different seawater types considered in the simulations. All the simulations were carried out up to the range of 30 m to match the practical possibilities. SNR shows variation from 105to 10 for the range of 1–30 m. Moreover, the difference in SNR values is higher for different seawater types and is significant at longer ranges. The Probability of Error, the indicator for reliability of communication has more dependence on the type of modulation scheme, and DHPIM has shown significant improvement even for long ranges more than 20 m whereas other modulation schemes offer better than 10–6PoE but are limited to distances less than 15 m. Further, to validate the simulations and to practically verify, a real-time experiment with a 532nm green laser was performed on a UWOC testbed with various modulation schemes, and both the simulations and UWOC testbed experiment results were compared. To correct additional effects of window losses that are inevitable in real-time implementation, additional simulations were carried out and PoE was presented.

Cf-ZrB2-SiC based ultra-high-temperature ceramic matrix composites (UHTCMCs) are an Emerging material system. This work aims to fabricate a carbon fibre (Cf) reinforced ZrB2-SiC composite through an in-situ ZrB2-SiC matrix formation technique, using zircon, B4C, and phenolic resin as raw materials via the boro/carbo thermal reduction (BCTR) method. In the initial step, a slurry of zircon (ZrSiO4), B4C, and phenolic resin was infiltrated into a carbon fibre preform, followed by curing, pyrolysis, and heat treatment at 1600 °C. This resulted in a porous Cf-ZrB2-SiC composite. This process enables the in-situ formation of a matrix containing uniformly dispersed submicron-sized ZrB2& SiC particles in the composite without damaging the fibres. To further increase the density, samples were subjected to two different processing routes: (a) sintering the composite at 2000 °C and (b) chemical vapour infiltration (CVI) of SiC in the composite. The densification behavior and Young’s modulus of the composites were analysed.

Actinobacteria, pervasive in aquatic and terrestrial environments, exhibit a filamentous morphology, possess DNA with a specific G + C content and production of numerous secondary metabolites. This study, focused on actinobacteria isolated from marine seagrass, investigating their antibacterial activity against fish pathogens. Among 28 isolates, Streptomyces argenteolusTMA13 displayed the maximum zone of inhibition against fish pathogens—Aeromonas hydrophila(10 mm), Aeromonas caviae(22 mm), Edwardsiella tarda(17 mm), Vibrio harveyi(22 mm) and Vibrio anguillarum(12 mm) using the agar plug method. Optimization of this potent strain involved with various factors, including pH, temperature, carbon source and salt condition to enhance both yield production and antibacterial efficacy. In anti-biofilm assay shows the maximum percentage of inhibition while increasing concentration of TMA13 extract. Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) assays with TMA13 crude extract demonstrated potent activity against fish pathogens at remarkably low concentrations. Time-kill kinetics assay showcased growth curve variations over different time intervals for all fish pathogens treated with a 100 µg/ml concentration of crude extract, indicating a decline in cells viability and progression into the death phase. Additionally, fluorescence microscopic visualization of bacterial cells exposed to the extracts emitting green and red fluorescence, enabling live-dead cell differentiation was also studied. Further characterization of the crude extract through GC–MS and FT-IR analyses performed and identified secondary metabolites with functional groups exhibiting significant antibacterial activity. This study elucidates the capacity of Streptomyces argenteolusTMA13 to enhance the production of antibiotic compounds effective against fish pathogens.

Graphical Abstract:

Byline: Minal. Doularamani, Somasheila. Murthy Indian Journal of Ophthalmology has published an interesting study where the authors have compared the conjunctival bacterial populations in four patients of dry eye disease [...]

Byline: Namratha. Hegde, C. Vidya, Kalika. Bandamwar, Kaushik. Murali, Sowmya. Murthy Purpose: To investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on compliance to amblyopia therapy from the [...]

Byline: Hasna. Kommula, Somasheila. Murthy, Abhinav. Loomba, Ashik. Mohamed, Rashmi. Ranjan Purpose: To establish normative data on anterior scleral thickness using the spectral domain anterior segment optical coherence tomography (AS-OCT). [...]

Byline: Sikha. Misra, Chinthala. Navyasree, Somasheila. Murthy A 32-year-old male was referred from the immunology department with a 3-day history of both eyes (BES) ocular pain with extreme photophobia, oral, [...]

Byline: Rashmi. Deshmukh, Somasheila. Murthy, Christopher. Rapuano, Rasik. Vajpayee Among the various indications for keratoplasty, failed graft is one of the commonest indications in many published series. It is well [...]

Sustainability is a paramount concern around the globe. Numerous countries worldwide have established ambitious targets to curtail their greenhouse gas emissions, either through the Paris Agreement or other methods, complemented [...]

Updated retrospective review of the sonographic appearance of palmar fibromatosis (PF) with evaluation of the utility of the Comb Sign previously described in plantar fibromas. Additional evaluation was conducted on the location relative to the flexor tendon, anatomic proximity of palmar fibromas to the A1 pulley and evaluate any potential association with trigger finger. Medical record and imaging review was performed from 2017 to 2023, for patients with a new onset ultrasound or clinical diagnosis of PF. Clinical associations and imaging morphology were reviewed including presence of the Comb Sign, fibroma association with the A1 pulley, and fibroma association with trigger finger. Exactly 87 total fibromas in 53 patients were evaluated. The Comb Sign was present in 39% of fibromas, usually seen in transverse plane, more prevalent in multifocal disease and larger fibromas. Most (72%) palmar fibromas were within 1 cm of, contacted, or covered the A1 pulley (P< .001). Lateral extension beyond the flexor tendon axis can be seen (44%). Trigger finger and tenosynovitis were rare. However, volume and SI dimension of fibromas were associated with tenosynovitis (P< .0001) and all nine patients with concomitant trigger finger had fibromas within 1 cm from the A1 pulley. The Comb Sign can aid in sonographic diagnosis of PF. Lateral extension of fibromas can occur. Most palmar fibromas have a significant intimate association with the A1 pulley, and presence of trigger finger with adjacent palmar fibroma can exist and is important for hand surgeons to know preoperatively.