Correlation of Serum Calcium with Severity and Outcomes in Patients of COVID-19 Pneumonia.

Background: Calcium is an essential electrolyte with critical physiological functions. Recently, it has been implicated in the pathogenesis and outcomes of COVID-19. This retrospective study was conducted to estimate serum ionic calcium and its correlation with clinical severity, inflammatory markers, and in-hospital outcomes in moderate to severe COVID-19 patients. Methods: We retrospectively analyzed data from 377 COVID-19 patients, aged between 23 and 79 years, with a mean age of 54.17±11.53 years. Severity of the disease was determined using ICMR criteria. Parameters including age, gender, inflammatory markers, calcium levels, and clinical outcomes were assessed. Results: The study showed a prevalence of moderate and severe COVID-19 in 58.1% and 41.9% patients, respectively. Severity was significantly associated with younger age, higher mean inflammatory markers, notably IL-6, procalcitonin, D-Dimer, and lower ionic and total calcium levels, as well as vitamin D levels. Mortality and referral rate were significantly higher in the severe group. Hypocalcemia was prevalent in 39% of the patients and was significantly associated with disease severity, ARDS, and mortality. On multivariate assessment, only age and ionic calcium were significantly associated with COVID-19 severity. Conclusion: Lower serum ionic calcium levels are associated with increased severity and poor outcomes, including higher mortality in COVID-19 patients, underscoring the potential role of calcium as a diagnostic and prognostic marker in COVID-19 pneumonia and may be an important factor in various other forms of pneumonia.

Imaging of pulmonary infections encountered in the emergency department in post-COVID 19 era- common, rare and exotic. Bacterial and viral.

Pulmonary infections contribute substantially to emergency department (ED) visits, posing a considerable health burden. Lower respiratory tract infections are prevalent, particularly among the elderly, constituting a significant percentage of infectious disease-related ED visits. Timely recognition and treatment are crucial to mitigate morbidity and mortality. Imaging studies, primarily chest radiographs and less frequently CT chests, play a pivotal role in diagnosis. This article aims to elucidate the imaging patterns of both common and rare pulmonary infections (bacterial and viral) in the post COVID-19 era, emphasizing the importance of recognizing distinct radiological manifestations. The integration of clinical and microbiological evidence aids in achieving accurate diagnoses, and guiding optimal therapeutic interventions. Despite potential overlapping manifestations, a nuanced understanding of radiological patterns, coupled with comprehensive clinical and microbiological information, enhances diagnostic precision in majority cases.

Immunotherapeutic approaches for Alzheimer's disease: Exploring active and passive vaccine progress.

Alzheimer's disease (AD) is the most common neurodegeneration having non-effective treatments. Vaccines or monoclonal antibodies are two typical immunotherapies for AD. Due to Aß neurotoxicity, most of the treatments target its generation and deposition. However, therapies that specifically target tau protein are also being investigated. UB311 vaccine generates N-terminal anti-Aß antibodies, that neutralize Aß toxicity and promote plaque clearance. It is designed to elicit specific B-cell and wide T-cell responses. ACC001 or PF05236806 vaccine has the same Aß fragment and QS21 as an adjuvant. CAD106 stimulates response against Aß1-6. However, Nasopharyngitis and injection site erythema are its side effects. AN1792, the first-generation vaccine was formulated in proinflammatory QS21 adjuvant. However, T-cell epitopes are omitted from the developed epitope AD vaccine with Aß1-42B-cell epitopes. The first-generation vaccine immune response was immensely successful in clearing Aß, but it was also sufficient to provoke meningoencephalitis. Immunotherapies have been at the forefront of these initiatives in recent years. The review covers the recent updates on active and passive immunotherapy for AD.

Current update on the role of endoanal ultrasound: a primer for radiologists.

Endoanal ultrasound (EAUS) is a valuable imaging modality for the evaluation of anal and perianal pathologies. It provides detailed information about the anatomy and physiology of the anorectal region and has been used in pre-and post-operative settings of anorectal pathologies. EAUS is not only useful in the evaluation of benign pathologies but also in loco-regional staging of anal and rectal tumors. EAUS has several advantages over MRI, including reduced cost, better patient tolerance, and improved scope of application in patients with contraindications to MRI. Despite its benefits, EAUS is not widely performed in many centers across the globe. This article aims to educate radiologists, trainees, and surgeons about the indications, contraindications, patient preparation, imaging technique, and findings of EAUS. We will also highlight the technical difficulties, diagnostic challenges, and procedural complications encountered during EAUS, along with a comparative analysis of EAUS with other imaging approaches.

Regulatory roles of microRNAs in modulating mitochondrial dynamics, amyloid beta fibrillation, microglial activation, and cholinergic signaling: Implications for alzheimer's disease pathogenesis.

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aß) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aß, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease.

Analytical solution of fuzzy heat problem in two-dimensional case under Caputo-type fractional derivative.

This work aims to investigate the analytical solution of a two-dimensional fuzzy fractional-ordered heat equation that includes an external diffusion source factor. We develop the Sawi homotopy perturbation transform scheme (SHPTS) by merging the Sawi transform and the homotopy perturbation scheme. The fractional derivatives are examined in Caputo sense. The novelty and innovation of this study originate from the fact that this technique has never been tested for two-dimensional fuzzy fractional ordered heat problems. We presented two distinguished examples to validate our scheme, and the solutions are in fuzzy form. We also exhibit contour and surface plots for the lower and upper bound solutions of two-dimensional fuzzy fractional-ordered heat problems. The results show that this approach works quite well for resolving fuzzy fractional situations.

Machine learning-based virtual screening and molecular modelling studies for identification of butyrylcholinesterase inhibitors as anti-Alzheimer's agent.

Butyrylcholinesterase (BChE) is a hydrolase involved in the metabolism and detoxification of specific esters in the blood. It is also implicated in the progression of Alzheimer's disease, a type of dementia. As the disease progresses, the level of BChE tends to increase, opting for a major role as an acetylcholine-degrading enzyme and surpassing the role of acetylcholinesterase. Hence, the development of BChE inhibitors could be beneficial for the latter stages of the disease. In the present study, machine learning (ML) models were developed and employed to identify new BChE inhibitors. Further, the identified molecules were subjected to molecular property filters. The filtered ligands were studied through molecular modelling techniques, viz. molecular docking and molecular dynamics (MD). Support vector machine-based ML models resulted in the identification of 3291 compounds that would have predicted IC50 values less than 200 nM. The docking study showed that compounds ART13069594, ART17350769 and LEG19710163 have mean binding energies of -9.62, -9.26 and -8.93 kcal/mol, respectively. The MD study displayed that all the selected ligands showed stable complexes with BChE. The trajectories of all the ligands were stable similar to the standard BChE inhibitors.Communicated by Ramaswamy H. Sarma.

A robust approach for computing solutions of fractional-order two-dimensional Helmholtz equation.

The Helmholtz equation plays a crucial role in the study of wave propagation, underwater acoustics, and the behavior of waves in the ocean environment. The Helmholtz equation is also used to describe propagation through ocean waves, such as sound waves or electromagnetic waves. This paper presents the Elzaki transform residual power series method ([Formula: see text]T-RPSM) for the analytical treatment of fractional-order Helmholtz equation. To develop this scheme, we combine Elzaki transform ([Formula: see text]T) with residual power series method (RPSM). The fractional derivatives are described in Caputo sense. The [Formula: see text]T is capable of handling the fractional order and turning the problem into a recurrence form, which is the novelty of our paper. We implement RPSM in such a way that this recurrence relation generates the results in the form of an iterative series. Two numerical applications are considered to demonstrate the efficiency and authenticity of this scheme. The obtained series are determined very quickly and converge to the exact solution only after a few iterations. Graphical plots and absolute error are shown to observe the authenticity of this suggested approach.

Development of superoxide dismutase based visual and spectrophotometric method for rapid differentiation of fresh and frozen-thawed buffalo meat.

Study aimed to develop biomarker-based assay for rapid detection of fresh and frozen-thawed buffalo meat in the supply chain. The method is based on development of a solvent system and identification of suitable substrate and developer for screening of biomarkers. For the confirmation column chromatography, gel electrophoresis and Western Blotting were carried out. Validation was done by intra- and inter-day validation, storability study, and determination of thermal history. Best results were shown with pH 8.0 Tris-HCl; extraction buffer, 205 µM nicotinamide adenine dinucleotide hydrogen; substrate, 184 µM Nitroblue tetrazolium, and 1.9 µM phenazine methosulfate; developer. The thermal history ranged from 0.14 to 0.17 during storage at -20 °C. The intra- and inter-day assay precision (CV %) ranged from 5.3 to 6.5 %; in chilled and 14.1 - 9.2 % in frozen-thawed samples. The study confirmed SOD as a viable biomarker. Developed method using SOD has significant potential for rapidly differentiating chilled or frozen-thawed meat.

Genetic diversity, population structure analysis and codon substitutions of Indicine Badri cattle using ddRAD sequencing.

The present study was carried out on 96 animals representing three distinct colour variants of Badri cattle to investigate the genetic diversity, population structure and substitution mutations in the genetic codons due to single nucleotide variations. The DNA samples of 96 Badri cows were genotyped using a double digestion restriction associated DNA (ddRAD) sequencing approach. A standardized bioinformatics pipeline was employed to identify single nucleotide polymorphisms (SNPs), initially detecting 7,168,552 SNPs through alignment with the Bos indicus reference genome assembly. Subsequent stringent quality filtration yielded 65,483 high-confidence SNPs for downstream analysis. Genetic diversity analysis of the Badri cattle population resulted in average values of 0.145, 0.088, and 0.091 for Shannon's diversity Index (I), Simpson's Diversity (h), and Simpson's Unbiased Diversity (uh), respectively. Genetic similarities between the black and brown, black and grey, and brown and grey Badri variants were found to be 0.9972, 0.9980 and 0.9970, respectively. Tajima's D diversity value was observed to be significant and positive for 99.29% of high-confidence SNPs (65,483). STRUCTURE analysis showed admixture among the three Badri colour variants, suggesting a lack of genetic differentiation. Annotation of high-confidence SNPs regarding genetic codon changes indicated maximum substitutions in the GGC with GGT (22 occurrences), followed by AAC to AGC (20 occurrences), GAA to TAA (19 occurrences) and CAA to CAG (19 occurrences). The study concludes there are genetic similarities among colour variants, lack of rare alleles, balancing selection, sudden population contraction and genetic codon substitutions within the Badri cattle population. Insights derived from SNP data analysis hold potential significance for conservation initiatives and breed improvement programs for indicine cattle.

Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma.

BACKGROUND: Medulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor prognoses and therapy resistance. However, MYC itself has been one of the most challenging targets for cancer treatment. Here, we identify a novel marinopyrrole natural derivative, MP1, that shows desirable anti-MYC and anti-cancer activities in MB. METHODS: In this study, using MYC-amplified (Group 3) and non-MYC amplified MB cell lines in vitro and in vivo, we evaluated anti-cancer efficacies and molecular mechanism(s) of MP1. RESULTS: MP1 significantly suppressed MB cell growth and sphere counts and induced G2 cell cycle arrest and apoptosis in a MYC-dependent manner. Mechanistically, MP1 strongly downregulated the expression of MYC protein. Our results with RNA-seq revealed that MP1 significantly modulated global gene expression and inhibited MYC-associated transcriptional targets including translation/mTOR targets. In addition, MP1 inhibited MYC-target metabolism, leading to declined energy levels. The combination of MP1 with an FDA-approved mTOR inhibitor temsirolimus synergistically inhibited MB cell growth/survival by downregulating the expression of MYC and mTOR signaling components. Our results further showed that as single agents, both MP1 and temsirolimus, were able to significantly inhibit tumor growth and MYC expression in subcutaneously or orthotopically MYC-amplified MB bearing mice. In combination, there were further anti-MB effects on the tumor growth and MYC expression in mice. CONCLUSION: These preclinical findings highlight the promise of marinopyrrole MP1 as a novel MYC inhibition approach for MYC-amplified MB.

Growth optimization and crossover of transport mechanisms in Bi2Se3thin films.

We report the growth, structural characterization, and transport studies of Bi2Se3thin film on single crystalline silicon (Si), Si/SiO2, quartz, and glass substrates by thermal evaporation method. Our results show that 300 °C is the optimum substrate temperature to obtain thec-axis (001) oriented Bi2Se3films on all the substrates. The film grown on the Si substrate has the minimum crystalline disorder. The energy-dispersive x-ray spectroscopy results show that film on Si substrate is bismuth deficient, the film on Si/SiO2substrate is selenium deficient, and the film on quartz substrate is near perfect stoichiometric providing a way to tune the electronic properties of Bi2Se3films through substrate selection. The film grown on quartz shows the highest mobility (2.7 × 104cm2V-1s-1) which drops to 150 cm2V-1s-1for Si, 60 cm2V-1s-1for Si/SiO2, and 0.9 cm2V-1s-1for glass substrate. Carrier concentration is n-type for Bi2Se3films on Si (∼1018cm-3), quartz (∼1018cm-3) and Si/SiO2(∼1019cm-3) substrate with a clear indication of frozen out effect around 50 K for Si/SiO2and Si substrate. Longitudinal resistivity of Bi2Se3film on Si/SiO2substrate shows different behavior in three different temperature regions: temperature dependent resistivity region due to electron-phonon scattering, a nearly temperature independent resistivity region due to electron-phonon and electron-ion scattering, and a quantum coherent transport region.

Isomeric polythiophene: a promising material for low voltage electronic devices.

In this investigation, we present empirical observations detailing the manifestation of substantial negative capacitance (NC), reaching up to -1 F, within iodine-doped isomeric polythiophene (IPTh-I2). NC observed in our case is not transient but stable enough to be measured for as long as the optimum concentration of the iodine dopant is available. In contrast, undoped isomeric polythiophene (IPTh) manifests a modest positive capacitance ranging from 30 to 60 µF. The concatenation of IPTh-I2 and IPTh in the series results in an augmentation of the total capacitance of the system (∼170 µF), exemplifying a characteristic feature of NC. Conversely, a bilayer configuration consisting of IPTh:IPTh exhibits a reduction in total capacitance by 38%. A notable amplification in the dielectric constant, escalating from 30 in IPTh to approximately 2000 in IPTh-I2, signifies extensive conformational and structural alterations arising from interactions between the doped polymer chain and various iodide species, attributing to the emergence of NC. Furthermore, we document a single-sided p-n junction diode with a low knee voltage (below 0.5 V) as a model device, illustrating the potential of IPTh as a promising material for the design and development of negative capacitance-based field-effect transistors. This research offers avenues for the scientific community to conceive low knee voltage-operating diodes, transistors, supercapacitors, and various other electronic devices based on all-organic semiconductors.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Magnetically Recyclable Nanoscale Zero-Valent Iron-Mediated PhotoRDRP in Ionic Liquid toward Smart, Functional Polymers.

A facile method based on recyclable nanoscale zero-valent iron (nZVI)-mediated photoinduced reversible deactivation radical polymerization in ionic liquid (IL) leads to the synthesis of narrow disperse poly(tert-butyl methacrylate) (PTBMA), amphiphilic PTBMA-block-poly(poly(ethylene glycol)methacrylate) diblock copolymer and double hydrophilic poly(methacrylic acid)-block-poly(poly(ethylene glycol)methacrylate) (PMAA-b-PPEGMA) diblock copolymers thereof. Stimuli response of the synthesized PMAA-b-PPEGMA diblock copolymer against variation in pH and temperature is assessed. Recyclability of the nZVI (catalyst) and IL (solvent) is established. Polymerization may be switched ON or OFF, simply by turning the UVA light irradiation ON or OFF, offering temporal control. The diblock copolymer self-aggregates into spherical nanoaggregates which are employed for encapsulation of coumarin 102 (C102, a typical hydrophobic dye), describing their potential application in drug delivery applications. The facile synthesis strategy may open up new avenues for the preparation of intelligent functional polymers for engineering and biomedical applications.

Biomechanical Response of Head Surrogate With and Without the Helmet.

Measurements of brain deformations under injurious loading scenarios are actively sought. In this work, we report experimentally measured head kinematics and corresponding dynamic, two-dimensional brain simulant deformations in head surrogates under a blunt impact, with and without a helmet. Head surrogates used in this work consisted of skin, skull, dura, falx, tentorium, and brain stimulants. The head surrogate geometry was based on the global human body models consortium's head model. A base head surrogate consisting of skin-skull-brain was considered. In addition, the response of two other head surrogates, skin-skull-dura-brain, and skin-skull-dura-brain-falx-tentorium, was investigated. Head surrogate response was studied for sagittal and coronal plane rotations for impactor velocities of 1 and 3 m/s. Response of head surrogates was compared against strain measurements in PMHS. The strain pattern in the brain simulant was heterogenous, and peak strains were established within ∼30 ms. The choice of head surrogate affect the spatiotemporal evolution of strain. For no helmet case, peak MPS of ∼50-60% and peak MSS of ∼35-50% were seen in brain simulant corresponding to peak rotational accelerations of ∼5000-7000 rad/s2. Peak head kinematics and peak MPS have been reduced by up to 75% and 45%, respectively, with the conventional helmet and by up to 90% and 85%, respectively, with the helmet with antirotational pads. Overall, these results provide important, new data on brain simulant strains under a variety of loading scenarios-with and without the helmets.

PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma.

MYC amplification or overexpression is most common in Group 3 medulloblastomas and is positively associated with poor clinical outcomes. Recently, protein arginine methyltransferase 5 (PRMT5) overexpression has been shown to be associated with tumorigenic MYC functions in cancers, particularly in brain cancers such as glioblastoma and medulloblastoma. PRMT5 regulates oncogenes, including MYC, that are often deregulated in medulloblastomas. However, the role of PRMT5-mediated post-translational modification in the stabilization of these oncoproteins remains poorly understood. The potential impact of PRMT5 inhibition on MYC makes it an attractive target in various cancers. PRMT5 inhibitors are a promising class of anti-cancer drugs demonstrating preclinical and preliminary clinical efficacies. Here, we review the publicly available preclinical and clinical studies on PRMT5 targeting using small molecule inhibitors and discuss the prospects of using them in medulloblastoma therapy.

Unveiling Xanthine Presence in Rohu Fish Using Ag+-Doped MoS2 Nanosheets Through Electrochemical Analysis.

Here, we envisage the development of the rapid, reliable, and facile electrochemical sensor for the primary detection of xanthine (Xn) which is significant for the food quality measurement, based on the silver-doped molybdenum disulfide (Ag@MoS2) nanosheets. The structural and compositional properties of the prepared samples were tested through X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and X-ray photon spectroscopy (XPS). The two-dimensional (2D) MoS2 nanosheets provide the large surface area for the sensing applications and the silver ions help in the enhanced electrochemical response. The fabricated enzymatic biosensor exhibits magnificent cyclic stability with a limit of detection of 27 nM. Also, the sensor was tested for rapid, reproducible, specific, and regenerable up to 10 cycles and has a shelf life of 2 weeks. The outcomes of this study suggest that the proposed matrix could be employed for the fabrication of devices for early detection of xanthine.

Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment.

Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aß) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aß and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC50: 4.16 ± 0.063 µM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aß aggregation at 0.5, 10 and 20 µM doses. Approximately, 50% of AChE-induced Aß aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.

Novel Enzymatic Biosensor Utilizing a MoS2/MoO3 Nanohybrid for the Electrochemical Detection of Xanthine in Fish Meat.

A rapid, reliable, and user-friendly electrochemical sensor was developed for the detection of xanthine (Xn), an important biomarker of food quality. The developed sensor is based on a nanocomposite comprised of molybdenum disulfide-molybdenum trioxide (MoS2/MoO3) and synthesized using a single-pot hydrothermal method. Structural analysis of the MoS2/MoO3 nanocomposite was conducted using X-ray diffraction (XRD) and Raman spectroscopy, while its compositional properties were evaluated through X-ray photoelectron spectroscopy (XPS). Morphological features were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Two-dimensional (2D) MoS2 offers advantages such as a high surface-to-volume ratio, biocompatibility, and strong light-matter interaction, whereas MoO3 serves as an effective electron transfer mediator and exhibits excellent stability in aqueous environments. The enzymatic biosensor derived from this nanocomposite demonstrates remarkable cyclic stability and a low limit of detection of 64 nM. It enables rapid, reproducible, specific, and reproducible detection over 10 cycles while maintaining a shelf life of more than 5 weeks. These findings highlight the potential of our proposed approach for the development of early detection devices for Xn.